Case Studies in Pain Management (Cambridge Medicine) [1 ed.] 1107682894, 9781107682894, 2014006285, 9781316057568, 9781107281950

Edited by internationally recognized pain experts, this unique book describes 73 real life clinical cases, each followed

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Case Studies in Pain Management (Cambridge Medicine) [1 ed.]
 1107682894, 9781107682894, 2014006285, 9781316057568, 9781107281950

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Table of contents :
Cover
Half-title
Title page
Copyright information
Dedication
Table of contents
Contributors
Foreword
Section 1 Neurological Disorders
Chapter 1 Postherpetic neuralgia
Case study
1. What are the basic facts regarding postherpetic neuralgia, varicella-zoster virus, and shingles?
2. What are the basic features of postherpetic neuralgia?
3. Why are there are so many challenges with regard to postherpetic neuralgia treatment options?
4. What are the guidelines for postherpetic neuralgia management?
Criteria for recommendations varies
5. Are there any systematic reviews and meta-analysis data on postherpetic neuralgia treatments?
6. Are there any gaps in the Postherpetic Neuralgia Treatment Guidelines?
7. Are there any new clinical data on postherpetic neuralgia treatments?
High-concentration (8%) topical capsaicin patch
Gastroretentive gabapentin
Gabapentin enacarbil
Pregabalin combination therapeutic approaches
8. What are key considerations in choosing postherpetic neuralgia treatments?
Tolerability
Dosing and onset of analgesia
Are there challenging subsets of patients and guideline gaps in subpopulations of patients with postherpetic neuralgia?
The older patient
Renal/hepatic impairment
Patient with anxiety and depression
The patient with a history of substance abuse
Miscellaneous considerations
9. What are the key summarized points for treatment of postherpetic neuralgia?
References
Chapter 2 Patient with spinal cord injury pain
Case study
1. What is this patient's diagnosis?
2. How many spinal cord injury (SCI) patients are there, and how common is chronic pain in this population?
3. What are commonly experienced types and examples of pain conditions in SCI patients?
4. What types of neuropathic pain are experienced in SCI patients?
5. What form does visceral pain take in SCI patients?
6. What other painful conditions are SCI patients prone to?
7. What other conditions must the pain provider be aware of?
8. What is the relevance of heterotopic ossification?
9. What work-up might be helpful to clarify pain diagnosis in an SCI patient?
10. What are the pharmacologic treatments available for patients with SCI pain?
11. Are there interventional treatments that have been shown to be beneficial for SCI patients?
12. What are the non-pharmacologic treatments effective for SCI pain?
13. Are there particular issues or sensitivities that you need to be aware of when working with SCI patients?
Summary
References
Chapter 3 Patient with poststroke pain
Case study
1. What is the diagnosis explaining this patient's pain?
2. How common is poststroke pain?
3. What is the incidence of CPSP (epidemiology)?
4. What painful conditions are commonly seen in poststroke patients?
5. What area of the brain injury correlates with the development of central poststroke pain?
6. What is the likely mechanism of poststroke pain?
What is the likely mechanism of CPSP?
What is the likely mechanism of shoulder pain?
What is known about spasticity after stroke?
What is known about headache poststroke?
7. What is the work-up of poststroke pain?
Diagnosis of CPSP
Hemiplegic shoulder pain work-up
8. What pharmacologic treatments are available for poststroke pain?
What treatments are available for CPSP?
What are the treatments available for hemiplegic shoulder pain?
9. Are there any interventional treatments that have been tried for the treatment of patients with poststroke pain?
10. What are some special concerns in poststroke pain?
Conclusion/summary
References
Chapter 4 Patient with brachial plexopathy
Case study
1. What is brachial plexopathy?
2. Describe the anatomy of the brachial plexus
3. Clinical classification of brachial plexopathies
4. What is the epidemiology of plexopathies?
5. What are the causes and mechanisms of brachial plexopathies?
6. What happens to nerves in plexopathy?
7. Describe the clinical presentation of brachial plexopathies
8. What is the differential diagnosis?
9. How do you diagnose nerve root avulsion/brachial plexopathies?
10. What other disease processes mimic traumatic nerve root avulsion?
11. How should I treat this patient?
12. Are there any complications to worry about following treatment?
13. What is the prognosis of brachial plexopathies?
14. What are the social considerations in brachial plexopathy patients?
Conclusions
References
Chapter 5 Phantom limb pain
Case study
1. What is postamputation pain?
2. What is phantom limb pain?
3. Demographics/epidemiology of phantom pain?
4. What are the indications for amputation?
5. What are the risk factors for phantom limb pain?
6. What are the clinical symptoms and signs of phantom limb pain?
7. Describe the pathophysiology of phantom limb pain
8. How is PLP diagnosed?
9. How is phantom limb pain managed?
10. How to prevent phantom limb pain
11. How successful are these treatment modalities?
12. How does this impact a person's life?
Conclusions
References
Chapter 6 Patient with post-thoracotomy pain
Case study
1. What is the differential diagnosis?
2. What is a neuroma?
3. Describe the clinical exam and how would one evaluate the differential diagnoses?
4. How do you diagnose the conditions listed in the differential diagnosis?
5. How should one treat this condition?
6. Are there potential complications from injections?
7. What are the outcomes?
References
Chapter 7 Complex regional pain syndrome
Case study
1. What are the differential diagnoses in this case?
2. What is complex regional pain syndrome?
3. What are the classification and diagnostic criteria of CRPS?
4. How does one make the diagnosis of CRPS?
5. What is the treatment approach for CRPS?
6. What interventional methods are available to treat CRPS?
7. What is the course of CRPS?
References
Chapter 8 Diabetic neuropathy
Case study
1. How prevalent is this disease presentation? Could you explain some of the epidemiologic features of this disease? Are there any cost concerns?
2. What are some of the other conditions that could have the same presentation?
3. How would you differentiate diabetic neuropathy from some of these other disorders?
4. What diagnostic studies would you obtain?
5. How would you make a diagnosis of diabetic neuropathy?
6. What are some of the other presentations in diabetic neuropathy?
7. What are the EMG findings in diabetic neuropathy?
8. What is Seddon's and Sunderland's classification for peripheral nerve injuries?
9. What is the pathophysiology of PDPN?
10. What are some treatment modalities you would offer to this patient?
11. Disease-modifying medications
a-Lipoic acid
Protein kinase C inhibitors
Polyol pathway
Advanced glycation end products
12. Symptomatic treatment
Anticonvulsants
Antidepressants
Local anesthetics
Topical agents
Combination therapies
Interventional therapy
Spinal cord stimulation
Intrathecal medication devices
Deep brain stimulation
Surgery
Physical therapy
Psychologic treatment
Complementary and alternative medicine
New developing drugs
13. What are some of the complications from the treatment modalities?
14. The patient has been unable to return to work. How would you improve this?
15. Describe the conclusions you would draw from this case?
References
Chapter 9 Alcohol-induced neuropathy
Case study
1. What are some of the epidemiologic considerations for this disease? What is the financial burden it imposes on society?
2. What is the pathophysiology of the disease?
3. What are some other clinical conditions that may present in a similar way?
4. What are some of the clinical features of alcohol-induced neuropathy?
5. What are other tests including lab tests and imaging that may aid in your diagnostic work-up? How would you make a diagnosis of alcohol neuropathy?
6. Briefly describe the therapeutic options available to treat and manage alcohol neuropathy
Alpha-lipoic acid
Acetyl-L-carnitine
Vitamin E
Anticonvulsants
Antidepressants
Topical agents
Opioids
Physical therapy
Occupational therapy
Psychotherapy
6. Describe any treatment-related complications
7. Patient refuses to stop drinking and using marijuana. Does that impose any ethical issues?
8. What conclusions could you draw from this case?
References
Chapter 10 HIV neuropathy
Case study
1. How prevalent is this disease presentation? Could you explain some of the epidemiologic features of this disease? Are there any cost concerns?
2. What is the differential diagnosis of HIV neuropathy?
3. Describe the clinical presentations of HIV neuropathy
Distal symmetric polyneuropathy (DSP)
ARV-associated neuropathy
Progressive polyradiculopathy
Mononeuropathy multiplex
4. How would you make a diagnosis of HIV neuropathy?
Brief peripheral neuropathy screen
Total neuropathy score
5. Describe some of the laboratory tests that would aid in your diagnosis
Quantitative sensory testing
Nerve conduction studies
EMG
Nerve biopsy
Skin biopsy
Measures of small-fiber neuropathy
Utah Early Neuropathy Scale
Quantitative Sudomotor Axon Reflex Test
Autonomic function testing
6. Are there any imaging tests that would help in the diagnosis?
7. What is the pathophysiology of this disease?
8. What treatment modalities exist currently for this condition?
Pharmacologic treatment
Anticonvulsants
Antidepressants
Topical agents
Opioids
Smoked cannabis
Antiretroviral therapy
Nerve growth factor
Prosapeptide
What conclusions can be made for the treatment of HIV-associated neuropathy?
Complementary and alternative medicine
Psychotherapy/cognitive behavioral therapy
Interventional techniques
9. Are there any special concerns that you might have in the care of patients with HIV neuropathy?
10. What conclusions would you draw from this case?
References
Section 2 Spinal Disorders
Chapter 11 Cervicogenic headache
Case study
1. What is the differential diagnosis?
2. What are the differentiating features of the cervical spine pain syndromes?
3. What are some of the legal ramifications encountered with workplace and motor vehicle injuries?
4. What are the differing roles of clinical assessment between a clinical practitioner and independent medical assessment?
5. How do clinical assessments differ among practitioners in the diagnosis of cervicogenic headache?
6. What symptoms can be associated with cervicogenic headaches?
7. What are some of the different subsets in cervicogenic headache?
8. What are the available treatments for cervicogenic headache and occipital neuralgia?
References
Chapter 12 Cervical stenosis and myelopathy
Case study
1. Cervical x-rays taken 6 weeks earlier reveal
2. Assessment
3. Plan
4. MRI cervical spine following encounter reveals
5. What is the differential diagnosis?
6. What is the definition of cervical spondylotic myelopathy?
7. What is the epidemiology of CSM?
8. What are the clinical manifestations of CSM?
9. What are the physical examination findings in a patient with CSM?
10. What are the imaging studies available to evaluate for CSM?
11. What radiologic criteria are used to diagnose stenosis?
12. What additional studies may be of benefit in the evaluation of CSM?
13. What is the natural history of patients with CSM?
14. What are the risk factors associated with the development of CSM?
15. What is the pathology behind the development of CSM?
16. How is CSM managed non-operatively?
17. What are the surgical options for management of CSM?
18. How does ossification of posterior longitudinal ligament cause CSM?
19. How does rheumatoid arthritis cause CSM?
20. What is the expected neurologic outcome after decompression surgery?
Cited References
References
Chapter 13 Thoracic outlet syndrome (TOS): an enigma in pain medicine
Case study
1. What is thoracic outlet syndrome?
2. What are the types of thoracic outlet syndrome?
3. What is the epidemiology of TOS?
4. What is thoracic outlet?
5. What is the clinical classification of the brachial plexus?
6. Discuss the etiology of TOS
7. Discuss and differentiate clinical presentations by the type of TOS
8. Discuss the differential diagnosis of TOS
9. What is double crush syndrome in TOS?
10. Discuss the relevant physical examination findings in TOS
11. What are the diagnostic modalities of TOS?
12. What are the conservative management strategies of TOS?
13. Discuss surgical management strategies of TOS
14. What are the treatment outcomes for TOS?
15. What could be the impact of TOS on a person's life?
Conclusion
References
Chapter 14 Patient with cervical radiculopathy
Case description
1. Provide a differential diagnosis for the patient´s complaint
2. Who is affected by cervical radiculopathy?
3. Describe the likely anatomical causes of cervical radiculopathy and the pathophysiologic mechanisms for the observed symptoms
4. What factors from the history and physical examination support the diagnosis?
5. What is the value of diagnostic testing and imaging in evaluating a patient with cervical radiculopathy?
6. What is the efficacy of non-surgical treatment strategies?
7. Describe the benefits and risks of interventional strategies to treat cervical radiculopathy
8. Discuss the role for a surgical consultation
9. Compare the anticipated outcomes with conservative, interventional, and surgical approaches
References
Chapter 15 Patient with axial neck pain
Case study
1. What is the differential diagnosis?
2. What is the mechanism of injury in this patient?
3. Why is this condition occasionally misdiagnosed?
4. Describe the anatomy and pathophysiology of the cervical facet (zygopophysial) joints
5. How to diagnose cervical axial pain?
6. What are the treatment options for axial neck pain?
7. Procedural description
8. What are the possible complications from these procedures?
9. What are the outcomes with facet joint procedures?
10. Intradiscal procedures
11. What are the possible complications from a cervical intradiscal procedure?
References
Chapter 16 Patient with thoracic spine pain
Case study
1. What are the anatomical structures that can produce pain in the thoracic region?
2. What are the key features in the differential diagnosis of thoracic pain?
3. What is ankylosing spondylitis?
4. What is Tietze syndrome?
5. What is DISH?
6. What is Scheuermann's kyphosis? Describe the end plate changes of this disease
7. What is posterior rami syndrome (dorsal ramus syndrome, Ma
8. How would you manage patients with thoracic pain?
Conservative approaches
Interventional approaches
References
Chapter 17 Patient with lumbar disc herniation
Case study
1. What is the differential diagnosis?
2. What is a lumbar disc herniation?
3. Describe the pathogenesis of lumbar radiculopathy secondary to an LDH
4. Discuss clinical symptoms, signs, imaging, and diagnostic testing for an LDH
5. Discuss conservative treatment options
6. Discuss surgical approaches to the lumbar disc herniation
References
Chapter 18 Patient with lumbar facet-mediated pain
Case study
1. What is the differential diagnosis?
2. What is the mechanism of pain generation in this patient?
3. What is the difference between the axial back pain and radicular pain?
4. Describe the anatomy and pathophysiology of the lumbar facet (zygapophysial) joint pain?
5. How to diagnose lumbar axial pain?
6. What are the treatment options for axial low back pain due to the facets?
Conservative approaches
Interventional treatments
7. Procedural description
8. What are the possible complications from these procedures?
9. What are the outcomes with facet joint procedures?
References
Chapter 19 Discogenic pain in the setting of lumbar spondylosis
Case study
1. What is the differential diagnosis?
2. What is the anatomy of a healthy intervertebral disc?
3. What risk factors predispose patients to develop degenerative disc disease?
4. What is the pathophysiology of degenerative disc disease?
5. What is the role of radiographic imaging in discogenic pain?
6. Is there a gold standard for the diagnosis of discogenic pain?
7. Does the spread of the contrast on a discogram tell us anything?
8. What are the complications of discography?
9. What treatment modalities are available for discogenic pain?
References
Chapter 20 Unusual pain syndromes: epidural lipomatosis
Case study
1. What is the differential diagnosis?
2. What are the most common symptoms of idiopathic epidural lipomatosis?
3. What is a proper approach to these symptoms?
4. What are the findings during a physical examination in epidural lipomatosis?
5. What is the pathophysiology of idiopathic epidural lipomatosis?
6. What is the most reliable diagnostic modality?
7. How should this patient be treated?
8. What is the long-term outcome after treatment?
Summary
References
Chapter 21 Unusual pain syndromes: Bertolotti´s syndrome
Case study
1. What is Bertolotti's syndrome?
2. Describe the pathophysiology of Bertolotti's syndrome
3. What is Castellvi's classification?
4. How does Bertolotti's syndrome manifest clinically?
5. How do you diagnose a Bertolotti's syndrome?
6. How should I treat this patient?
7. What are the outcomes?
References
Chapter 22 Unusual pain syndromes: Baastrup's disease/interspinous bursitis
Case study
1. What is Baastrup's disease?
2. Describe the epidemiology of Baastrup's disease
3. Describe the anatomy and pathophysiology of Baastrup's disease
4. How to diagnose Baastrup's disease?
5. What are the differential diagnoses of Baastrup's disease?
6. How should you treat a patient with BD/ISB?
References
Chapter 23 Lumbar spinal stenosis and neurogenic claudication
Case study
1. What is spinal stenosis?
2. What is the Verbiest syndrome?
3. What is the natural history of spinal stenosis?
4. What is the anatomical basis of spinal stenosis?
5. How is lumbar spinal stenosis classified radiologically?
6. How is the diagnosis of spinal stenosis made?
7. What are the differential diagnoses of lumbar spinal stenosis?
a. Lumbosacral radicular pain secondary to nerve root impingement
b. Referred pain from adjacent anatomic structures
c. Lumbar vertebral compression fracture
d. Intermittent claudication secondary to peripheral vascular disease
e. Peripheral neuropathy
f. Visceral referred pain
g. Other differential diagnoses
8. Are conservative treatments effective in lumbar spinal stenosis?
9. What is the next step if simple conservative options are not effective?
10. Neuroplasty therapy (adhesiolysis)
11. Minimally invasive lumbar decompression
12. Interspinous spacers
13. How effective is decompression for the treatment of LSS?
14. How would you manage this patient?
References
Chapter 24 Management of the patient with postlaminectomy pain syndrome
Case study
1. What is postlaminectomy pain syndrome?
2. What is the etiology of postlaminectomy pain syndrome?
3. How is postlaminectomy pain syndrome diagnosed?
4. What interventional treatments may be utilized?
Lumbar epidural steroid injections and PLPS
Caudal epidural injection and PLPS
Facet and medial branch interventions
Adhesiolysis
Spinal cord stimulation
Pharmacologic management
Intrathecal drug delivery
Interdisciplinary management
5. Complications/Conclusions
References
Chapter 25 A patient with a lumbar compression fracture
Case study
1. What is the differential diagnosis?
2. What is the difference between a simple vertebral compression fracture and a burst fracture?
3. What is the pathogenesis and pathophysiology of a vertebral compression fracture? Is osteoporosis a factor?
4. How is vertebral compression fracture diagnosed?
5. How are vertebral compression fractures treated? Describe a conservative and an interventional treatment
6. What is the controversy surrounding vertebral augmentation?
References
Chapter 26 Sacroiliac joint pain and arthritis
Case study
1. What are the differential diagnoses in this patient?
2. What are the referred pain patterns that are important in the differential diagnosis?
3. What anatomic considerations help to explain the variable presentation of SI joint pain?
4. What are the physical exam findings that would suggest SI joint pain?
5. Does imaging play a large role in the diagnostic work-up of this patient?
6. How is the diagnosis of SI joint pain made?
7. What are the conservative management options in patients with SI joint pain?
8. When considering SI joint injection, what factors should be kept in mind?
9. Is there a long-term therapeutic solution to SI joint pain?
References
Uncited References
Chapter 27 Sacral insufficiency fracture and treatment options
Case study
1. What is the differential diagnosis?
2. What risk factors predispose patients to develop sacral insufficiency fractures?
3. Why is this condition overlooked?
4. Describe the anatomy and pathophysiology of a SIF
5. How do you diagnose a SIF?
6. Is there any other diagnostic testing that should be done?
7. How should I treat this patient?
Conservative approaches
Procedural
8. Are there any complications to worry about following sacroplasty or sacral kyphoplasty?
9. What are the outcomes?
References
Chapter 28 Skeletal metastases and treatment options
Case study
1. What is the differential diagnosis?
2. What is this?
3. How do you diagnose this?
4. Why is treatment or palliation of this lesion important?
5. The patient presented with skeletal pain shortly after being diagnosed with recurrent bronchial stump cancer. Why is this?
6. How would you treat this pain?
7. Is there a role for targeted therapy in this population?
8. What types of targeted therapy for skeletal metastases are available?
9. What is the mechanism of rapid pain relief?
10. Are there any complications to worry about following vertebroplasty or kyphoplasty?
11. What can one conclude?
References
Chapter 29 Fibromyalgia and opioid-induced hyperalgesia
Case study
1. What is the differential diagnosis?
2. What is fibromyalgia? How do you diagnose it? Are there diagnostic and/or clinical criteria?
3. How do you differentially diagnose fibromyalgia from similar problems?
4. What is the treatment for fibromyalgia? Is it ethical to prescribe opioids in the treatment of fibromyalgia?
Case follow-up
5. Does the worsening of her pain despite opioid therapy make you question your diagnosis? Are there any other diagnoses to consider at this point?
References
Section 3 Musculoskeletal Pain
Chapter 30 Patient with myofascial pain syndrome: focus on functional restoration
Case study
1. What happens when an employee files a claim through workers' compensation?
2. Why do some patients have an attorney?
3. What are the different types of disability benefits and how is candidacy for these benefits determined?
4. What are pharmacologic options for our patient going forward?
Medications
5. Are there interventional options for our patient?
6. What type of physical therapy is best?
7. Is psychologic therapy necessary for this patient?
8. What is a functional restoration program?
References
Chapter 31 Spinal manipulation, osteopathic manipulative treatment, and spasticity
Case study
1. Introduction to spinal manipulation
2. Contraindications to spinal manipulation
3. Current literature considerations
4. Introduction to spasticity
5. Spasticity management
Disclosure
References
Chapter 32 Patient with ankle pain
Case study
1. What is the differential diagnosis?
2. What risk factors predispose patients to have a chronic ankle sprain?
3. Why is this condition overlooked?
4. Describe the anatomy and pathophysiology of a chronic ankle sprain
5. How do you diagnose a chronic ankle sprain?
6. How should I treat this patient?
Conservative approaches
Procedural
Corticosteroid injections
Viscosupplementation/hyaluronic acid injections
Acupuncture
Dry-needling
Radiofrequency ablation/radiofrequency coblation
Regenerative injection procedures
Prolotherapy
Platelet-based procedures
Surgical treatment options
Open surgical repair for chronic ankle instability/hypermobility
Open surgical repair for chronic ankle pain, OA/other causes
References
Chapter 33 Patient with lateral epicondylosis or other focal tendinopathy
Case study
1. What is the differential diagnosis?
2. What risk factors predispose patients to developing sacral insufficiency fractures?
3. Describe the anatomy and pathophysiology of a lateral epicondylosis
4. How do you diagnose a lateral epicondylosis?
5. Is there any other diagnostic testing that should be done?
6. How should I treat this patient?
Conservative approaches
Procedural
References
Chapter 34 Knee osteoarthritis with emphasis on percutaneous regenerative medicine
Case study
1. What are the most common etiologies of chronic knee pain?
2. What is knee osteoarthritis and what is the pathophysiologic basis for its development?
3. What are the common causes of KOA?
4. What other type(s) of arthropathy need to be ruled out and how do they differ from OA?
5. What does a pertinent exam of the knee consist of in a patient that is suspected of having knee osteoarthritis?
6. What imaging is currently used to diagnose KOA and is it adequate?
7. Are there any labs that need to be ordered when working up a patient with knee pain?
8. What are the traditional non-surgical treatment options for early KOA?
Diet and exercise
Physical therapy
Pharmacologic intervention
Orthotics
Psychology therapy
Traditional percutaneous injections
9. What are the innovative non-surgical management options for early KOA?
10. What are the traditional surgical treatment options for early KOA?
11. What are innovative surgical treatment options for KOA?
12. Coalescence of surgery and injections
References
Section 4 Visceral Pain
Chapter 35 Patient with chronic abdominal pain from pancreatitis
Case study
1. What is the difference between acute and chronic pancreatitis?
2. What is the most common cause of chronic pancreatitis and which demographics are usually affected?
3. Describe the typical presentation of pain in chronic pancreatitis
4. What is the pathogenesis of pain in chronic pancreatitis?
5. Which other clinical manifestations may contribute to the overall pain experience of patients?
6. Which diagnostic studies are of value for diagnosis and staging of chronic pancreatitis?
7. What is the first step in treatment of pain in chronic pancreatitis?
8. Which are the initial steps in conservative management of chronic pancreatitis?
9. What are the medical treatment options available for treatment of chronic pancreatitis?
10. Can COX-2 inhibitors be given for long-term pain management in chronic pancreatitis?
11. Which are the most common adjuvants used in medical treatment of chronic pancreatitis?
12. What are the indications for the use of opioids in chronic pancreatitis?
13. What is the reasoning behind the use of antioxidants in the treatment of chronic pancreatitis?
14. When are interventional options indicated and which procedures can be used?
15. What is the evidence behind the use of radiofrequency ablation and spinal cord stimulation for treatment of pain in chronic pancreatitis?
16. What are the endoscopic and surgical treatment options available?
References
Chapter 36 Patient with chronic pelvic pain from endometrial fibrosis
Case study
1. What is chronic pelvic pain?
2. Describe the epidemiology and prevalence of endometriosis
3. What is the pathophysiology of endometriosis?
4. What is the mechanism of pain associated with endometriosis?
5. How is endometriosis presented clinically?
What is the differential diagnosis of chronic pelvic pain in females?[17]
How to establish the diagnosis of CPP due to endometriosis?
How to manage CPP due to endometriosis?
Treatment of endometriosis
Hormonal treatments
Surgical treatment
Managing CPP associated with endometriosis
Medical management
Interventional and surgical management
References
Chapter 37 Patient (male) with chronic pelvic pain from interstitial cystitis
Case study
1. What is the innervation of the male pelvis?
2. What is the differential diagnosis for a male presenting with chronic pelvic pain?
3. How are prostate syndromes classified? What is the epidemiology of chronic prostatitis?
4. How should male CPP be evaluated?
History
Physical exam
Laboratory
Additional studies
5. What non-pharmacologic treatment options are available to patients with CPPS?
6. What pharmacologic agents are used in the treatment of CPPS?
7. What interventional procedures can be performed in the treatment of CPPS?
8. How are the iliohypogastric, ilioinguinal, genitofemoral, and pudendal nerve blocks performed?
Iliohypogastric and ilioinguinal nerve block
Genitofemoral nerve block
Pudendal nerve block
Superior hypogastric plexus block
9. What other treatment options are available if pharmacotherapy and targeted nerve blocks have failed to provide adequate pain relief?
Neuromodulation
Intrathecal drug therapy
10. How do you monitor the progress of treatment in CPPS?
11. What is the treatment course in CPPS?
References
Chapter 38 Chronic rectal pain
Case study
1. What is the differential diagnosis for rectal pain?
2. Describe the neuroanatomy of the pelvic viscera including the rectum
3. What are some unique features of rectal innervation and how do they contribute to rectal pain?
4. What is the typical work-up for rectal pain?
5. What are the pathophysiology and diagnostic criteria of coccygodynia?
6. What are the pathophysiology and diagnostic criteria of proctalgia fugax?
7. What are the pathophysiology and diagnostic criteria of radiation proctitis?
8. What are some treatment modalities of rectal pain?
9. What are some topical medications used to treat rectal pain?
10. When is the ganglion impar block indicated and how is it performed?
11. When is the pudendal nerve block indicated and how is it performed?
12. When is the inferior hypogastric plexus block indicated and how is it performed?
13. How is BOTOX used to treat rectal pain?
14. How can neuromodulation be used to help manage rectal pain?
References
Chapter 39 Pain in pregnancy
Case study
1. What are the common etiologies for pain in the pregnant patient?
Low back pain and disc disease
Pelvic girdle pain
Pubic symphysis separation (pubic diastasis, symphysiolysis, osteitis pubis)
Hip pain and transient osteoporosis of the hip
Knee pain and patellofemoral disorder
Leg cramps
Abdominal wall pain
2. How does the evaluation for low back pain compare from the parturient to the non-parturient?
3. What pharmacotherapy for pain is safe to give in pregnancy?
4. What role do non-pharmacologic therapies have in treatment for pain in pregnancy?
Exercise and physical therapy
Acupuncture
Pelvic belt and pillow
Transcutaneous electronic nerve stimulation
Osteopathic manipulative treatment
5. What role do non-opioid medications have in treating pain in pregnancy?
Acetaminophen
NSAIDs
Benzodiazepines
Antidepressants
Anticonvulsants
Local anesthetics
Skeletal muscle relaxants
Steroids
6. What role do opioids have in treating pain in pregnancy? If started on opioids, what is the risk to the mother and the fetus, both in gestation and the peripartum stage?
7. What interventions are available to the parturient? What are the risks associated with pain procedures for the parturient and the fetus?
8. What would be the suggested overall therapeutic management for the parturient with lower back pain?
References
Chapter 40 Postpartum pain
Case study
1. What are common etiologies of back pain in a postpartum patient?
2. What is the correlation, if any, between neuraxial analgesia and chronic back pain?
3. What other pain syndromes are common or unique to the postpartum female?
Chronic pelvic girdle pain
Meralgia paresthetica
Chronic pelvic pain
Chronic pain after cesarean delivery
Chronic perineal pain
4. What are common risk factors for chronic postpartum pain?
Pre-delivery
During delivery
Post-delivery
5. How should a patient with postpartum pain be evaluated?
Targeted pain history
Targeted physical examination
Imaging and other diagnostic modalities
6. What non-pharmacologic treatment options for postpartum pain are available in a breastfeeding female?
Physical therapy
Pelvic belts
Acupuncture
TENS
Biofeedback and relaxation training
7. What pharmacologic agents are available for treatment of postpartum pain in a breastfeeding female?
Acetaminophen
NSAIDs
Local anesthetics
Steroids
Antidepressants
Benzodiazepines
Opioids
8. What medications should be used with caution in the breastfeeding mother?
Gabapentin
Pregabalin
Antidepressants
Lithium
9. What guidelines can a physician follow in management of postpartum pain in a breastfeeding mother?
References
Section 5 Headaches and Facial Pain
Chapter 41 Patient with migraine headaches
Case study
1. Discuss the epidemiology of migraine
2. Discuss the pathogenesis of migraine
3. Clinical assessment and associated signs
International Headache Society Diagnosis Criteria for Migraine
Migraine without aura (MO) diagnostic criteria[10]
Migraine with aura (MA) diagnostic criteria[10]
4. Counseling on long-term risks of migraine
Stroke
5. Diagnostic evaluation
6. Medications: triptans
7. Medications: other non-opioid abortive treatments
8. Medications: opioids and butalbital-containing combination pills
Beta-blockers (e.g., propranolol, atenolol, nadolol, timolol)
Anticonvulsants (e.g., valproate, topiramate, gabapentin)
Calcium channel blockers (i.e., verapamil, amlodipine)
Tricyclic antidepressants (i.e., amitriptyline, nortriptyline, desipramine)
Selective SNRIs (i.e., duloxetine, milnacipram)
Treatment of chronic migraine
9. Functional measures for outcomes: headache diary
10. Interventional approaches: BOTOX, peripheral nerve blocks, peripheral nerve stimulation (including occipital nerve stimulation and supraorbital nerve stimulation)
11. Preventive measures: physical therapy, modalities, and nutrition
12. Thoughts from an expert, e.g., overlooked areas
References
Chapter 42 Patient with cluster headache
Case study
1. What is the epidemiology and clinical presentation of cluster headache?
2. How is cluster headache diagnosed?
3. What are the diagnostic criteria for cluster headache?
4. What are the diagnostic pitfalls?
5. What is the differential diagnosis?
6. Does the specific diagnosis matter?
7. What risk factors predispose patients to develop cluster headaches?
8. Why is this condition overlooked?
9. What is the anatomy and pathophysiology of a cluster headache?
10. Is there any other diagnostic testing that should be done?
11. How is cluster headache treated?
Pharmacotherapy
Acute treatment
Preventive treatments
Procedural
Occipital nerve block
Neurostimulation
12. How should I treat this patient?
13. Are there any complications to worry about using DHE (dihydroergotamine) or triptans for acute treatment of cluster headache?
14. What are the outcomes of treatment of cluster headache patients?
References
Chapter 43 Patients with tension headaches
Case study
1. What is the differential diagnosis?
2. What is the epidemiology of these headaches?
3. Describe the clinical presentation
4. What is the pathophysiology of tension-type headache?
5. Treatment
6. Conclusion
References
Chapter 44 Pain management in trigeminal neuralgia: clinical case illustrations
Introduction
Clinical cases
1. What are the history, incidence, and epidemiology of trigeminal neuralgia?
2. What are the features of trigeminal neuralgia?
3. What is the etiology and pathophysiology of trigeminal neuralgia?
4. How is a diagnosis of TN made?
5. What are the distinct management categories for trigeminal neuralgia?
6. What is microvascular decompression for trigeminal neuralgia?
7. What are some of the advantages of microvascular decompression for TN?
8. Are there any other alternative techniques for trigeminal neuralgia?
9. What are the key points regarding trigeminal neuralgia for the clinician?
Disclosure
References
Chapter 45 Patient with chronic glossopharyngeal neuralgia/post-tonsillectomy pain
Case study
1. What is glossopharyngeal neuralgia?
2. Describe the signs and symptoms
3. Discuss the etiology and pathophysiology
4. Diagnosis
5. Treatment
References
Chapter 46 Patient with sphenopalatine neuralgia
Case study
1. What is the differential diagnosis?
2. What is Sluder neuralgia or sphenopalatine ganglion neuralgia?
3. What is the anatomy of the sphenopalatine ganglion?
4. What are the major nerve structures involved with the sphenopalatine ganglion?
5. What is the proposed etiology of sphenopalatine neuralgia?
6. What is the clinical presentation of sphenopalatine neuralgia?
7. What is the recommended work-up for suspected sphenopalatine neuralgia?
8. What is the recommended medical management of sphenopalatine neuralgia?
9. What are the interventional therapies for treatment of sphenopalatine neuralgia?
10. What are the complications of the sphenopalatine block?
Summary
References
Chapter 47 Temporomandibular joint disorders
Case study
1. What is temporomandibular joint disorder (TMD) and how does it typically present?
2. What are the relevant anatomical structures related to TMD?
3. What is the cause of pain in TMDs?
4. How common is TMD?
5. What would be included in the differential diagnosis?
6. How is TMD evaluated and diagnosed?
7. What are the potential treatments for TMD?
Conclusion
References
Section 6 Cancer Pain
Chapter 48 Cancer pain
Case study
1. What is the etiology of cancer pain?
2. Could there be other non-cancer causes for the patient's pain?
3. What is the epidemiology of cancer pain?
4. Are there any risk factors for the development of cancer pain?
5. What analgesic treatments are available to relieve this cancer pain?
6. What is the World Health Organization Analgesic Ladder for the treatment of cancer pain?
7. What analgesic medications should I use to treat this cancer pain?
Non-steroidal anti-inflammatory drugs and acetaminophen
Adjuvant analgesics
Opioids
8. What if our patient has intermittent pain in spite of regular opioid therapy?
9. My patient is unable to take oral medications. What should I now do?
10. What opioid side effects are common in the chronic treatment of cancer pain?
11. Are there any non-drug therapies for cancer pain management?
12. Would a "nerve block" be helpful for this patient?
13. What is involved with a celiac plexus neurolytic block?
Conclusions
References
Chapter 49 Patient presents with pancreatic cancer with persistent pain despite all other treatments
Case study
1. What barriers to patient care might an interventional pain physician face in cross-disciplinary care?
2. What are common sources of pain in the pancreatic cancer patient?
3. What interventional techniques may be used?
Blocks
Spinal cord stimulation
Neuraxial drug administration
4. What are the complications/contraindications to neuraxial analgesia?
References
Chapter 50 Pain management in hematological cancer: clinical case illustrations
Case studies
1. Introduction
2. Discussion
Conclusion
References
Chapter 51 Patient with metastatic breast cancer who had a mastectomy complicated by lymphedema
Case study
1. What is the prevalence of upper-body morbidity and lymphedema after breast cancer?
2. What are known risk factors for the development or exacerbation of upper-body morbidity and lymphedema after breast cancer?
3. What is the differential diagnosis for pain syndromes after breast cancer?
4. What are some clinical manifestations of lymphedema after breast cancer?
5. How is lymphedema diagnosed?
6. For patients at risk for lymphedema who do not have the condition, how should they be educated regarding preventive care?
7. What are the components of the "gold standard" treatment regimen for established lymphedema?
8. What other treatments can be considered for lymphedema?
Intermittent external pneumatic compression
Weight loss
Low-level laser therapy
Surgery
9. What rare complications of lymphedema should practitioners be aware of?
10. Conclusions - how would you treat this patient in the vignette?
References
Section 7 Special Topics
Chapter 52 A 57-year-old male with chronic pain syndrome, anxiety disorder, and hypertension is seeking mental health counseling
Why is it important to address the risk of suicide?
The patient doesn't demonstrate any suicidal thoughts, has a good support system at home, and doesn't have any concrete executable plans for self harm. You now feel comfortable discussing more conventional mental health strategies. What do you recommend?
Cognitive behavioral therapy
Relaxation training
Psychoanalysis
Psychiatric approach
During this discussion, the patient presents a newspaper article touting the benefits of biofeedback. He says that one of his friends mentioned hypnosis. Can you explain these modalities to the patient?
What is biofeedback?
What is hypnosis?
Inpatient versus outpatient psychologic therapy?
References
Chapter 53 Pediatric, infant, and fetal pain
Case study 1
1. Would this fetus require analgesia?
2. How can anesthetics/analgesics be delivered to a fetus?
Case study 2
1. How would you assess pain in this patient?
2. How would you treat this infant´s pain?
Case study 3
1. How would you assess this patient´s pain?
2. How would you manage her pain?
Case study 4
1. What is your differential diagnosis?
2. How does complex regional pain type 1 present in children?
3. How would you treat this patient?
Case study 5
1. Is this patient's presentation consistent with functional abdominal pain? Are there any concerning features in this patient's presentation?
2. What diagnostic studies are indicated in this patient?
3. How is FAP treated in children?
References
Chapter 54 Patient with hearing impairment and chronic pain
Case study
1. What should the provider be aware of when communicating with the hearing impaired?
2. Why use sign language?
3. How do you evaluate the deaf pain patient?
References
Chapter 55 Complementary and alternative medicine
Case study
1. How effective are conventional therapies for chronic low back pain?
2. What is complementary and alternative medicine, and who uses it?
3. Discuss the effectiveness of CAM therapies for low back pain
Acupuncture
Massage
Meditation
Autogenic training
Progressive muscle relaxation
Tai chi
Manipulation
Yoga
Biofield therapies
Balneotherapy
Behavioral therapies
Prolotherapy
Neuroreflexotherapy
Herbal therapy
4. What is integrative medicine?
5. What information would you discuss with this patient seeking to use complementary and alternative medicine?
References
Chapter 56 Ethical issues in the substance abusing pain patient
Case study
1. What is the scope of the public health problem related to the use of prescription opioids for pain?
2. What are the differential diagnoses of aberrant opioid-taking behaviors?
3. What are some common terminologies related to drug abuse and addiction?
4. Describe the basic neurobiologic process underlying addiction
5. What are the ethical principles that guide the use of opioids in pain control?
6. How can opioids be safely used for chronic pain?
7. Considering the complexity and risks, why not just avoid offering opioid therapy altogether?
References
Chapter 57 Approach to the patient with abnormal drug screen
Case study 1
1. Clinical assessment
What is the differential diagnosis for a patient with a positive drug screen?
What information exists regarding the epidemiology of drug abuse in the chronic pain population?
What are the clinical implications of drug misuse in this patient population?
2. Overview of drug testing
What modalities and assays are available for clinical drug testing?
What limitations should be considered when interpreting urine drug test results?
What guidelines exist regarding drug testing in the clinical setting?
3. Clinical management
How would the results of this urine drug test affect your future management of this patient?
Case study 2
1. Clinical assessement
What are this patient's risk factors for illicit substance abuse?
What is the differential interpretation of these results?
2. Illicit drug abuse and detection
What are the clinical trends and implications of substance abuse?
What is the time frame for detection of marijuana in urine drug testing? What is the time frame for detection of other drugs with abuse potential?
Would you include marijuana in your routine clinical drug screening? Why or why not?
3. Clinical management
What are the next steps in your management of this patient?
Case study 3
1. Clinical assessment
What is the differential interpretation of these findings?
What steps would you take to determine a diagnosis?
2. Clinical management
What are your next steps in management of this patient?
References
Chapter 58 Physician exposed to excessive radiation
Interventional pain physician has to go to occupational medicine office regarding radiation exposure
1. What is the reason for the state inspection?
2. What are the OSHA standards regarding ionizing radiation?
3. Who sets and enforces the medical radiation dosage standards?
4. What are the penetrating characteristics of various radiation beams?
5. What are the biologic effects of ionizing radiation?
6. What are the maximum permissible doses (MPD) of radiation?
7. What can I do to reduce my exposure to radiation while performing the fluoroscopic procedures?
8. What are the recommendations by US Environmental Protection Agency regarding radiation exposure?
Summary
References
Chapter 59 Patient becomes paralyzed following a lumbar transforaminal epidural steroid injection
Case study
1. What are the possible complications after a transforaminal epidural steroid injection?
2. What is the vascular anatomy of the blood supply to the spinal cord?
3. Where is the location of the arteries in the foramen?
4. What is the pathogenesis and mechanism of injury leading to paraplegia?
5. What changes in technique have been proposed to improve the safety of TFESI?
6. What are the pros and cons of the suggested technique modifications?
7. What is the treatment of paraplegia secondary to infarction?
8. What ethical and legal ramifications are there surrounding this procedure and the possible complications?
References
Chapter 60 Postepidural steroid injection paraplegia
Case study
1. What is the differential diagnosis?
2. Review the anatomy and vasculature of the epidural space
3. If the patient developed lower extremity paralysis immediately following the epidural steroid injection, which diagnosis would be highest on the differential?
4. If the patient underwent a transforaminal epidural steroid injection, describe the most favorable needle placement to minimize the risk of these serious postinjection symptoms?
5. Which of the following symptoms should be the most worrisome for the clinician?
6. What safety measures could the physician have taken to try to prevent such complications secondary to the epidural steroid injection?
7. What is the most reliable way to diagnose an epidural hematoma?
8. How should the clinician interpret the results, depending on when the modality was utilized following symptom onset?
9. What is the treatment for an epidural hematoma?
Acute management
Chronic management
10. What is the role of intravenous steroids in acute spinal cord injury?
References
Chapter 61 Complications: patient with dural puncture following cervical interlaminar epidural steroid injection
Case study
1. What is the differential diagnosis?
2. What are the signs and symptoms of a postdural puncture headache?
3. Describe the anatomy and pathophysiology for postdural puncture headaches
4. How is the diagnosis of a postdural puncture headache made in this patient?
5. What are the non-interventional treatments for a postdural puncture headache?
6. What are the interventional treatments for a postdural headache and how are they performed?
7. What are the factors to avoid a dural puncture?
8. What are the complications from a dural puncture?
References
Chapter 62 Complications: a patient with serotonin syndrome
Case study
What is serotonin syndrome?
Which drugs have been implicated in SS?
How is SS diagnosed?
What is the differential diagnosis?
References
Chapter 63 Office-based buprenorphine to wean patients off opioids
Case study
1. How common is opioid dependence?
2. What is the best approach to address opioid dependence in the USA?
3. What are the risk factors for opioid addiction?
4. How do you diagnose opioid dependence?
5. What are some of the features that make buprenorphine a desirable option for the treatment of opioid addiction?
6. What are the pharmacokinetics and pharmacodynamics of buprenorphine and the best form of administration?
7. Is dose adjustment required for buprenorphine in the presence of hepatic and renal disease?
8. What forms of buprenorphine are available for treatment of opioid dependence?
9. Why is buprenorphine not used via oral route?
10. How can I get certified to prescribe buprenorphine for this indication?
11. How should I start this patient on buprenorphine?
12. What is the standard induction protocol?
13. What is the safety of using buprenorphine in the treatment of opioid dependence?
14. Can you use buprenorphine for pain control?
15. What are the clinical outcomes using buprenorphine?
Summary
References
Chapter 64 Patient on chronic opioids who wants to have anesthesia-assisted detoxification
Case study
1. What are the various terms related to addiction and withdrawal?
2. What are the indications for anesthesia-assisted opiate detoxification (AAOD)?
3. What are the contraindications to anesthesia-assisted opiate detoxification?
Contraindications include:
4. What pre-assessment is needed for anesthesia-assisted detoxification?
Pre-anesthetic testing
4. What is the actual methodology to perform AAOD?
Premedication
Monitoring
Induction and maintenance
4. How do you know when the detoxification is complete?
What post-procedure monitoring is required?
5. What complications can occur in AAOD?
6. How does AAOD compare to traditional methods of detoxification?
7. How can the opiate-dependent patient maintain abstinent state?
8. Does AAOD actually lead to prolonged abstinence?
9. What evidence-based reviews have been conducted of AAOD?
10. Are there potential benefits of AAOD?
11. Should this procedure be conducted at all?
12. What ethical conundrums occur with AAOD?
13. What is the role of clonidine in mitigating withdrawal?
References
Chapter 65 Munchausen syndrome and pain
Case study
What is the origin and history of this condition?
How is this diagnosed?
What are the treatment options?
References
Chapter 66 Insomnia and chronic pain
Case study
1. How common are sleep disorders among chronic pain patients?
2. What type of sleep disorder is this patient struggling with?
3. What information is needed to assist in the diagnosis and treatment of this sleep problem?
Interview
Polysomnography
Sleep diary
Psychometric tools
4. Are there any drugs that may be contributing to his sleep problem?
5. What are some initial recommendations you might make to address sleep difficulties?
6. Are there any medications you might consider to assist with his sleep?
Prescription
Non-prescription
7. What other non-pharmacologic treatments are available?
8. Conclusions
References
Chapter 67 Opioid-induced constipation
Case study
1. What is the differential diagnosis?
2. What is the prevalence of opioid-induced constipation?
3. Describe the relevant anatomy of the bowel as it relates to opioid-induced constipation
4. Describe the opioid receptors in the bowel and its relation to the physiology of the bowel
5. Describe the clinical presentation of opioid-induced constipation
6. What is the role of the patient´s history in determining constipation caused by opioid use?
7. What is the benefit of the physical examination in a patient with opioid-induced constipation?
8. Is there a role for imaging in evaluating opioid-induced constipation?
9. How important is fluid intake for treatment of opioid-induced constipation?
10. What is the roll of diet and fiber?
11. Are fiber-based laxatives safe for patient´s with fecal impaction?
12. Is exercise effective?
13. Why are stimulants effective in opioid-induced constipation?
14. What is the mechanism of action of docusate and is it effective for opiate-induced constipation?
15. What is the mechanism of action of osmotic laxatives such as lactulose and sorbitol?
16. What is the mechanism of action of magnesium sulfate?
17. Should suppositories and enemas be considered as first-line treatment modalities?
18. Is there a role for opioid receptor antagonists in the treatment of opioid-induced constipation?
19. What is opioid rotation?
Conclusion
References
Chapter 68 Complications: vasovagal response during pain procedures
Case study
1. What is the differential diagnosis?
2. What is a vasovagal response?
3. How does a vasovagal response occur?
4. What are the risk factors/causative factors for a vasovagal response during pain procedures?
5. What is the association of vasovagal response with pain procedures?
6. In which type of pain procedures are vasovagal responses more common?
7. How do you diagnose a vasovagal response?
8. How would you treat a patient for a vasovagal response during a pain procedure?
References
Chapter 69 Acute pain management: patient-controlled analgesia
Case study
1. What is patient-controlled analgesia?
2. How does an IV PCA work?
3. Why is an IV PCA beneficial?
4. What are some patient selection criteria for appropriate use of an IV PCA?
5. When would a continuous infusion on an IV PCA be appropriate?
6. What is the ideal opioid for an IV PCA?
7. How do I initially program a PCA in my opioid-naive patients?
8. How do patient characteristics such as age and weight affect IV PCA use?
9. What if the patient continues to have pain while on the PCA?
10. What are the side effects of an IV PCA?
11. How safe is an IV PCA?
12. What are the limitations of an IV PCA?
13. Are there ways to improve the efficacy of IV PCA use?
14. Can a PCA mask postoperative complications?
15. How does the cost of IV PCA compare to conventional dosing?
References
Chapter 70 Acute pain management: PCEA/continuous epidural catheters
Case study
1. What are the indications for placing an epidural catheter for postoperative analgesia?
2. What postoperative pain treatment options are available for patients undergoing thoracotomy?
3. What are the benefits of a thoracic epidural patient-controlled analgesia as an analgesic technique?
4. How should an epidural catheter be placed? What techniques can be used for assistance with a difficult placement?
5. What are some risks of an epidural placement?
6. What are some medications used for epidural analgesia?
7. What are the options for infusion strategies?
8. What special considerations exist for the use of neuraxial analgesia in patients with multiple sclerosis?
9. For what other procedures might epidural analgesia be beneficial?
10. What are the contraindications for placing an epidural catheter?
Reference
Chapter 71 New vistas: continuous peripheral catheters/regional anesthesia in postoperative pain management
Case study
1. What are some of the important epidemiologic considerations in TKA?
2. What is the rationale for standardizing the perioperative pain management pathway for TKA patients?
3. What is a multimodal analgesic protocol?
4. What are potential components of an effective multimodal analgesic protocol?
Local anesthetics
Opioid analgesics
Non-opioid systemic analgesics
5. What are some special considerations for patients with chronic pain and chronic opioid therapy?
6. How does the diagnosis of obstructive sleep apnea (OSA) influence the analgesic protocol?
Conflict of interest
References
Chapter 72 Methadone and treatment of chronic pain
Case study
1. What are the clinical uses of methadone?
2. What about using methadone in the chronically ill patient with HIV?
3. How does her history of substance abuse change methadone prescribing?
4. What is the cost of methadone?
5. How common is accidental overdose in methadone use?
6. What are other risks of methadone use?
7. What are drugdrug interactions of methadone?
8. What is the role of genetic testing?
9. What is the metabolism and mechanism of methadone?
10. What are the advantages of methadone in this patient?
11. What are the risks of methadone in this patient?
12. What are the ethical considerations?
13. What should be the initial approach to this patient?
References
Chapter 73 Drug testing
Case study
1. Why is it important to do drug testing in patients with chronic pain managed with opioids?
2. What methods are available for urine drug testing?
3. How accurate are the urine drug tests?
4. How long will a urine drug test remain positive for opioids, benzodiazepines, and barbiturates?
5. How long will a urine drug test remain positive for drugs of abuse?
6. This patient tells you he ran out of his medication and last took his oxycodone 2 days ago. Would you expect his urine drug test to be positive or negative?
7. Can urine drug testing tell you how much of a given drug the patient is currently taking?
8. What medications and substances can trigger a false positive urine drug test result?
9. How reliable is a physician's history or "gut instinct" in predicting aberrant drug use?
10. What are the most common inappropriate drugs found on a urine drug testing?
11. Is drug testing mandatory or required by law?
12. What would you do if the urine drug test is unexpectedly positive or unexpectedly negative?
References
Index

Citation preview

CAMBRIDGE

Case Studies in Pain Management

Case Studies in Pain Management Edited by

Alan David Kaye, MD, PhD, DABA, DABPM, DABIPP

Professor and Chairman, Department of Anesthesiology, Director of Interventional Pain Services, LSU School of Medicine, New Orleans, LA, USA

Rinoo V. Shah, MD, MBA, DABPMR, DABIPP

Interventional Pain Physician and Minimally Invasive Spine Specialist at Guthrie Clinic, Sayre, PA, USA

University Printing House, Cambridge CB2 8BS, United Kingdom Cambridge University Press is part of the University of Cambridge. It furthers the University’s mission by disseminating knowledge in the pursuit of education, learning and research at the highest international levels of excellence. www.cambridge.org Information on this title: www.cambridge.org/9781107682894 © Cambridge University Press 2015 This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 2015 Printed and bound in the United Kingdom by TJ International Ltd. Padstow, Cornwall A catalog record for this publication is available from the British Library Library of Congress Cataloging in Publication data Case studies in pain management / edited by Alan David Kaye, Rinoo V. Shah. p. ; cm. Includes bibliographical references and index. ISBN 978-1-107-68289-4 (Pbk.) I. Kaye, Alan David, editor. II. Shah, Rinoo V., editor. [DNLM: 1. Pain Management–Case Reports. 2. Analgesics– therapeutic use–Case Reports. 3. Pain–etiology–Case Reports. WL 704.6] RB127 6160 .0472–dc23 2014006285 ISBN 978-1-107-68289-4 Paperback Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. ............................................................................................ Every effort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.

To my parents: my mother Florence Feldman, the former Fania Eichenblat, who despite having a lifetime of chronic pain has never given up in her efforts to make a good life for her children and whose kindness and love I can never adequately repay and my father Joel Kaye, the former Joseph Krakower, for providing me with thousands of enlightening lessons in life and for helping to shape me into the man I am today. To my step parents: Andrea Bennett-Kaye and the late Gideon Feldman, who helped raise me, providing love, support, kindness, and wisdom over the last 30 plus years. To my wife: Dr. Kim Kaye, and my children, Aaron Kaye and Rachel Kaye, for making each day worth living and for giving me balance, support, and inspiration for all that I do in life. Alan D. Kaye, MD, PhD, DABA, DABPM, DABIPP To my parents: my mom, Rajul Shah, and my dad, Vasant Shah, for their unconditional love, patience, dedication, industriousness, kindness, and hard work. They always deserved better, but handled what they had with what gives essence to the meaning to life. I am the luckiest child in all of humanity to have them as my parents. To my wife: Dr. Kejal Shah and my Children, Maaya Shah, Diyaa Shah, and Dev-‘Dehdoo’ for their unconditional love, patience, and for being the source of my eternal happiness and drive. They provide inspiration and keep me focused not only during the good and bad times, but during the ‘meh’ times. They remind me how every second is precious in cosmological time. Rinoo V. Shah, MD, MBA, DABIPP, DABPMR Both Dr. Kaye and Dr. Shah wish to thank Dr. Gabor Racz, Dr. Prithvi Raj, Dr. Miles Day, and Dr. Leland Lou who helped train both of them in the field of pain management at Texas Tech Health Sciences Center in Lubbock, Texas

Contents List of contributors xi Foreword by Laxmaiah Manchikanti

xvi

Section 1 – Neurological Disorders

12. Cervical stenosis and myelopathy 95 Santhosh A. Thomas and Garett J. Helber

1.

Postherpetic neuralgia 1 Alan David Kaye and Charles E. Argoff

2.

Patient with spinal cord injury pain 16 Daniel Krashin, Natalia Murinova, and Alan David Kaye

13. Thoracic outlet syndrome (TOS): an enigma in pain medicine 102 Narendren Narayanasamy and Rahul Rastogi

3.

Patient with poststroke pain 22 Natalia Murinova, Claire Creutzfeldt, Daniel Krashin, and Alan David Kaye

4.

Patient with brachial plexopathy 30 Jonathan Chang and Rahul Rastogi

5.

Phantom limb pain 38 Jonathan Chang and Rahul Rastogi

6.

Patient with post-thoracotomy pain Rinoo V. Shah

7.

Complex regional pain syndrome Gaurav Jain and Nashaat N. Rizk

8.

Diabetic neuropathy 52 Gulshan Doulatram and Tilak Raj

9.

43

46

10. HIV neuropathy 72 Gulshan Doulatram, Tilak Raj, and William Yancey

11. Cervicogenic headache 81 Eric R. Helm and Nashaat N. Rizk

15. Patient with axial neck pain Vikram B. Patel

109

116

16. Patient with thoracic spine pain 123 Ankit Maheshwari and Jianguo Cheng 17. Patient with lumbar disc herniation Julian Sosner

Alcohol-induced neuropathy 64 Gulshan Doulatram, Tilak Raj, and Ankur Khosla

Section 2 – Spinal Disorders

14. Patient with cervical radiculopathy Robert B. Bolash and Jianguo Cheng

131

18. Patient with lumbar facet-mediated pain 137 Vikram B. Patel 19. Discogenic pain in the setting of lumbar spondylosis 144 James Kelly and Jianguo Cheng 20. Unusual pain syndromes: epidural lipomatosis 152 Vikram B. Patel 21. Unusual pain syndromes: Bertolotti’s syndrome 155 Jiang Wu and Jianguo Cheng 22. Unusual pain syndromes: Baastrup’s disease/interspinous bursitis 159 Jijun Xu and Jianguo Cheng 23. Lumbar spinal stenosis and neurogenic claudication 164 Ike Eriator and Zachariah Chambers

vii

Contents

24. Management of the patient with postlaminectomy pain syndrome Jay S. Grider

174

25. A patient with a lumbar compression fracture 182 Nihir Waghela and Magdalena Anitescu 26. Sacroiliac joint pain and arthritis Garrett LaSalle and Jianguo Cheng

195

Section 4 – Visceral Pain 35. Patient with chronic abdominal pain from pancreatitis 253 Rodrigo A. Benavides Corder and Jianguo Cheng 36. Patient with chronic pelvic pain from endometrial fibrosis 261 Maged Guirguis and Jianguo Cheng

27. Sacral insufficiency fracture and treatment options 202 Rinoo V. Shah

37. Patient (male) with chronic pelvic pain from interstitial cystitis 266 John Hau, Michael Truong, Eric S. Hsu, and Irene Wu

28. Skeletal metastases and treatment options 207 Rinoo V. Shah

38. Chronic rectal pain 275 Brandon A. Van Noord, Irene Wu, and Eric S. Hsu

29. Fibromyalgia and opioid-induced hyperalgesia 214 Grace Chen and Elliot Palmer

Section 3 – Musculoskeletal Pain 30. Patient with myofascial pain syndrome: focus on functional restoration 223 Tracy P. Jackson

39. Pain in pregnancy 282 Eugene Garvin, Jakun Ing, Irene Wu, and Eric S. Hsu 40. Postpartum pain 290 Jeffry Chen, Eric S. Hsu, and Irene Wu

Section 5 – Headaches and Facial Pain 41. Patient with migraine headaches 297 Natalia Murinova, Daniel Krashin, and Andrea Trescot

31. Spinal manipulation, osteopathic manipulative treatment, and spasticity 230 Monika A. Krzyzek, John P. McCallin, Justin B. Boge, Dean Hommer, Prasad Lakshminarasimhiah, Rebekah L. Nilson, and Brandon J. Goff

42. Patient with cluster headache 307 Natalia Murinova, Daniel Krashin, and Andrea Trescot

32. Patient with ankle pain 235 Jose E. Barreto and Thomas K. Bond

44. Pain management in trigeminal neuralgia: clinical case illustrations 316 Joaquin Maury, Alan David Kaye, and Harry J. Gould, III

33. Patient with lateral epicondylosis or other focal tendinopathy 240 Jose E. Barreto and Jeff Ericksen 34. Knee osteoarthritis with emphasis on percutaneous regenerative medicine 243 Jason Tucker, Christopher Centeno, and Jeff Ericksen

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43. Patients with tension headaches 312 Natacha Telusca, Chrystina Jeter, and Kingsuk Ganguly

45. Patient with chronic glossopharyngeal neuralgia/post-tonsillectomy pain 325 A. Raj Swain 46. Patient with sphenopalatine neuralgia 329 Mohit Rastogi, Natalia Murinova, and Alan David Kaye

Contents

47. Temporomandibular joint disorders Timothy Furnish

333

Section 6 – Cancer Pain 48. Cancer pain 341 Paul A. Sloan 49. Patient presents with pancreatic cancer with persistent pain despite all other treatments 352 Jay S. Grider 50. Pain management in hematological cancer: clinical case illustrations 358 Quan D. Le, Alan David Kaye, and Harry J. Gould, III 51. Patient with metastatic breast cancer who had a mastectomy complicated by lymphedema 367 Arash Asher and Jack Fu

Section 7 – Special Topics 52. A 57-year-old male with chronic pain syndrome, anxiety disorder, and hypertension is seeking mental health counseling 373 Natacha Telusca and Kingsuk Ganguly 53. Pediatric, infant, and fetal pain 379 Christine Greco and Soorena Khojasteh 54. Patient with hearing impairment and chronic pain 388 Mohit Rastogi 55. Complementary and alternative medicine 390 Ike Eriator and Jinghui Xie 56. Ethical issues in the substance abusing pain patient 399 Ike Eriator, Lori Hill Marshall, and Donald Penzien 57. Approach to the patient with abnormal drug screen 408 Jeffrey Hopcian and Magdalena Anitescu

58. Physician exposed to excessive radiation Vikram B. Patel

417

59. Patient becomes paralyzed following a lumbar transforaminal epidural steroid injection 423 Scott E. Glaser 60. Postepidural steroid injection paraplegia Annemarie E. Gallagher and Devin Peck

429

61. Complications: patient with dural puncture following cervical interlaminar epidural steroid injection 435 Niteesh Bharara and Frank J. E. Falco 62. Complications: a patient with serotonin syndrome 439 Natalia Covarrubias, Amirpasha Ehsan, and Danielle Perret Karimi 63. Office-based buprenorphine to wean patients off opioids 442 Natalia Murinova, Daniel Krashin, Cliff Gevirtz, and Alan David Kaye 64. Patient on chronic opioids who wants to have anesthesia-assisted detoxification 447 Cliff Gevirtz and Alan David Kaye 65. Munchausen syndrome and pain 456 Santhosh A. Thomas and Sachin K. Bansal 66. Insomnia and chronic pain 459 Mark Etscheidt and Paul A. Sloan 67. Opioid-induced constipation 467 John Michels, Hamilton Chen, Danielle Perret Karimi, and Justin Hata 68. Complications: vasovagal response during pain procedures 473 Frank J. E. Falco and Nomen Azeem 69. Acute pain management: patient-controlled analgesia 476 Nyla Azam and Devin Peck 70. Acute pain management: PCEA/continuous epidural catheters 482 Qiao Guo, Minyi Tan, and Devin Peck

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Contents

71. New vistas: continuous peripheral catheters/ regional anesthesia in postoperative pain management 491 Michael R. Rasmussen and Edward R. Mariano 72. Methadone and treatment of chronic pain 498 Daniel Krashin, Natalia Murinova, and Andrea Trescot

x

73. Drug testing 504 Steven Michael Lampert, Richard D. Urman, and Alan David Kaye

Index

508

Contributors

Magdalena Anitescu, MD Associate Professor of Anesthesia and Critical Care, Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA Charles E. Argoff, MD Professor, Department of Neurology, Albany School of Medicine, Albany, NY, USA Arash Asher, MD Assistant Professor at the Cedars-Sinai Medical Center, Los Angeles, CA, USA Nyla Azam, MD New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA Nomen Azeem, MD 22 Chateau Mouton Drive, Kenner, LA, USA; 3439 Prytania Street Suite 501, New Orleans, LA, USA Sachin K. Bansal, MD Interventional Physiatrist, Castle Orthopedics and Sports Medicine, S.C., Aurora, IL, USA Jose E. Barreto, MD, PT TotalCare Health & Wellness Medical Center, Lafayette, LA, USA Rodrigo A. Benavides Corder, MD Clinical Fellow of Pain Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA Niteesh Bharara Physiatrist and Interventional Pain Management Specialist, Virginia Spine Institute, Reston, VA, USA Justin B. Boge, DO Department of Pain Management, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA

Robert B. Bolash, MD Clinical Fellow in Pain Management, Cleveland Clinic, Cleveland, OH, USA Thomas K. Bond, MD, MS Board Certified, Sports Medicine, President/Owner, TotalCare Health & Wellness Medical Center, Lafayette, LA, USA Christopher Centeno Board certified in Physical Medicine and Rehabilitation, Board Certified in Pain Medicine, Centeno-Schultz Clinic, Broomfield, CO, USA Zachariah W. Chambers MD Interventional Pain Physician, Centennial Spine and Pain Center, Las Vegas, NV, USA Jonathan Chang, MD Fellow, Pain Management, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA Grace Chen, MD Division of Pain Management, Oregon Health and Science University, Portland, OR, USA Hamilton Chen, MD UC Irvine Center for Pain Management, University of California, CA, USA Jeffry Chen, MD UCLA Department of Anesthesiology, Santa Monica, CA, USA Jianguo Cheng, MD, PhD Professor of Anesthesiology and Director of Pain Medicine Fellowship Program, Cleveland Clinic Foundation, Cleveland, OH, USA

xi

List of contributors

Natalia Covarrubias Department of Physical Medicine and Rehabilitation, The University of California at Irvine, Irvine, CA, USA Claire J. Creutzfeldt, MD Department of Neurology, University of Washington, Seattle, WA, USA Gulshan Doulatram, MD Department of Anesthesiology, University of Texas, Galveston, TX, USA Amirpasha Ehsan, MD Department of Physical Medicine and Rehabilitation, The University of California at Irvine, Irvine, USA Ike Eriator, MD, MPH Professor of Anesthesiology, University of Mississippi Medical Center, Jackson, MS, USA Jeff Ericksen, MD Division of Regenerative Medicine, Kaplan Center for Integrative Medicine and Department of Physical Medicine and Rehabilitation, Virginia VA Medical Center, McLean, VA, USA Mark Etscheidt, PhD Associate Professor of Anesthesiology, University of Kentucky Medical Center, KY, USA Frank J. E. Falco, MD Mid-Atlantic Spine and Pain Physicians, USA Jack Fu, MD Associate Professor, Department of Palliative Care & Rehabilitation Medicine, Section of Physical Medicine & Rehabilitation, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Timothy Furnish, MD Assistant Clinical Professor of Anesthesiology, UC San Diego Health System, CA, USA Annemarie E. Gallagher, MD New York Presbyterian Hospital and Weill Cornell Medical Center, New York, NY, USA Kingsuk Ganguly, MD Anesthesiology, Pain and Perioperative Medicine, Stanford School of Medicine, Stanford, CA, USA

xii

Eugene Garvin UCLA Department of Anesthesiology, Los Angeles, CA, USA Cliff Gevirtz, MD Department of Anesthesiology at LSU School of Medicine, New Orleans, LA, USA Scott E. Glaser, MD, DABIPP President, Pain Specialists of Greater Chicago, Chicago, IL, USA Lieutenant Colonel Brandon J. Goff, DO Department of Pain Management, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA Harry J. Gould, III, MD, PhD Professor of Neurology and Neuroscience, Louisiana State University Health Sciences Center – New Orleans, New Orleans, LA, USA Christine Greco, MD, FAAP Children’s Hospital Boston and Harvard Medical School, Boston, MA, USA Jay S. Grider, DO, PhD Associate Professor of Anesthesiology, Division Chief, Pain and Regional Anesthesia, and Medical Director, UK HealthCare Pain Services, Lexington, KY, USA Maged Guirguis, MD Clinical Fellow in Pain Management, Cleveland Clinic, Cleveland, OH, USA Qiao Guo, MD New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA Justin Hata, MD Chief, UC Irvine Pain Medicine Division, University of California, CA, USA John Hau UCLA Department of Anesthesiology, Los Angeles, CA, USA Garett J. Helber, DO Staff Physician, Cleveland Clinic – Neurological Institute, Cleveland, OH, USA

List of contributors

Eric R. Helm, MD Division of Pain Medicine, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Soorena Khojasteh, MD Children’s Hospital Boston and Harvard Medical School, Boston, MA, USA

Lori Hill Marshall, MD Medical Director, Premier Pain Care, P. C., Jackson, MS, USA

Ankur Khosla Fellow, Pain Fellowship Program, Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA

Lieutenant Colonel Dean Hommer, MD Physical Medicine & Rehabilitation Service, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA

Daniel Krashin Departments of Psychiatry and Pain & Anesthesia, Harborview Medical Center, University of Washington, Seattle, WA, USA

Jeffrey Hopcian, MD Fellow, Division of Pain Management, Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, IL, USA

Captain Monika A. Krzyzek, DO Department of Pain Management, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA

Eric S. Hsu, MD Clinical Professor, Department of Anesthesiology, David Geffen School of Medicine, University of California Los Angeles, Santa Monica, CA, USA

Major Prasad Lakshminarasimhiah, MD Physical Medicine & Rehabilitation Service, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA

Jakun Ing UCLA Department of Anesthesiology, Los Angeles, CA, USA

Steven Michael Lampert, MD Fellow, International Pain Management, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women’s Hospital/Harvard Medical School, Boston, MA, USA

Tracy P. Jackson, MD Assistant Professor Anesthesiology and Pain Medicine and Program Director, Multidisciplinary Pain Medicine Fellowship, Vanderbilt University, Nashville, TN, USA Gaurav Jain, MD Division of Pain Medicine, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Chrystina Jeter, MD Resident, Anesthesiology, Stanford University Medical Center, Stanford, CA, USA Alan David Kaye, MD, PhD Professor and Chairman, Department of Anesthesiology, Director of Interventional Pain Services, and Professor of Pharmacology, LSU School of Medicine, New Orleans, LA, USA James Kelly, MD Clinical Fellow of Pain Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA

Garrett LaSalle, MD Clinical Fellow in Pain Management, Cleveland Clinic, Cleveland, OH, USA Quan D. Le, MD Departments of Physical Medicine and Rehabilitation and Pain Mastery Center of Louisiana, Louisiana State University Health Sciences Center, New Orleans, LA, USA Ankit Maheshwari, MD Chief Fellow in Pain Management, Cleveland Clinic, Cleveland, OH, USA Edward R. Mariano, MD, MAS Chief, Anesthesiology and Perioperative Care Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, and Associate Professor, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA

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List of contributors

Joaquin Maury, MD Departments of Neurology and Pain Mastery Center of Louisiana, Louisiana State University Health Sciences Center, New Orleans, LA, USA Captain John P. McCallin, MD Physical Medicine & Rehabilitation Service, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA John Michels, MD UCI Center for Pain Management, University of California Irvine, Irvine, CA, USA Natalia Murinova, MD Department of Neurology, University of Washington, Seattle, WA, USA Narendren Narayanasamy, MD Fellow, Pain Management, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA

Tilak Raj Dept of Anesthesiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Michael R. Rasmussen, MD Regional Anesthesiology and Acute Pain Medicine Fellow, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA Mohit Rastogi, MD Clinical Lecturer, Division of Pain Medicine, Department of Anesthesiology, University of Michigan Hospital, Ann Arbor, MI, USA Rahul Rastogi, MD Associate Professor, Program Director Pain Fellowship, Division of Pain, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA

Rebekah L. Nilson, PT Department of Pain Management, San Antonio Military Medical Center, Fort Sam, Houston, TX, USA

Nashaat N. Rizk, MD Associate Professor, Department of Anesthesiology, Fellowship Program Director, Division of Pain Medicine, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Elliot Palmer, MD Pain Medicine Fellow, Oregon Health and Science University, Portland, OR, USA

Rinoo V. Shah, MD, MBA Interventional Pain Physician and Minimally Invasive Spine Specialist at Guthrie Clinic, Sayre, PA, USA

Vikram B. Patel, MD FIPP DABIPP Phoenix Interventional Center for Advanced Learning, Algonquin, IL, USA

Paul A. Sloan, MD Professor of Anesthesiology, University of Kentucky, Lexington, KY, USA

Devin Peck, MD Assistant Professor of Anesthesiology; Director, Tri-Institute Pain Fellowship, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA

Julian Sosner, MD, FIPP Associate Clinical Professor, New York Medical College, Valhalla; Attending Physician, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center and Mount Sinai Medical System, New York; and Director, New York Interventional Pain Medicine Service, PC, New York, NY, USA

Donald B. Penzien, PhD Professor of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA Danielle Perret Karimi, MD Department of Anesthesiology and Perioperative Care and Department of Physical Medicine and Rehabilitation, The University of California at Irvine, Irvine, CA, USA

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A. Raj Swain MD Chief – Pain Management, Berger Hospital and Fayette County Memorial Hospital, OH, USA Minyi Tan, MD New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA

List of contributors

Natacha Telusca, MD, MPH Anesthesia Resident, PGY4, Department of Anesthesiology, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA, USA Santhosh A. Thomas, DO, MBA Staff Physician, Cleveland Clinic – Neurological Institute, Associate Medical Director, Richard E. Jacobs Health Center, and Medical Director – Center for Spine Health at Richard E. Jacobs Health Center, Cleveland, OH, USA Andrea Trescot, MD Pain and Headache Center, Eagle River, AK, USA Michael Truong UCLA Department of Anesthesiology, Los Angeles, CA, USA Jason Tucker Virginia Commonwealth University Department of Physical Medicine and Rehabilitation, Richmond, VA, USA Richard D. Urman, MD, MBA, CPE Assistant Professor of Anesthosia, Director, Procedural Sedation, Management, and Safety, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Brandon A. Van Noord UCLA Department of Anesthesiology, Los Angeles, CA, USA Nihir Waghela, MD Fellow, Division of Pain Management, Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, IL, USA Irene Wu UCLA Department of Anesthesiology, Santa Monica, CA, USA Jiang Wu, MD Clinical Fellow of Pain Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA Jijun Xu, MD, PhD Clinical Fellow of Pain Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA Jinghui Xie, MD, PhD Physician, Careone Pain Management, Advanced Interventional Pain Management, USA William Yancey, MD Fellow, Pain Fellowship Program, Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA

xv

Foreword

Case studies in pain management Pain management is a dynamic and evolving specialty. The diagnosis and treatment of pain-related conditions have changed extensively in recent years. Major changes include not only surgical advances applying minimally invasive techniques and multidisciplinary approaches, but also multiple interventional techniques based on evidence. Numerous publications have described the anatomy, physiology, pathology, and technical aspects of interventional techniques. Other texts have been written describing various non-interventional modalities including pharmacology, psychology, behavioral aspects, and drug therapy. In recent years, pain medicine and interventional pain management have seen a substantial growth in the publication of journals and books. However, there remains a major gap in pain management case studies. This text by Alan Kaye and Rinoo Shah is a monumental accomplishment toward fulfilling this goal. This text extensively describes neurological disorder cases in various categories. However, it does not stop with neuropathic pain cases; this text’s 72 chapters address various spinal disorders, musculoskeletal pain, visceral pain,

xvi

headache and facial pain, cancer pain, and multiple special topics and complications. Our understanding of a multitude of cases has grown over the years based on evolving evidence. The authors of the various cases in this text are of the highest caliber and are drawn from the highest levels of academia, research, and private practice. This text is directed not just to practitioners, but more importantly, to all types of clinicians engaged in managing painful conditions. Once again, the contributing authors are appreciated for undertaking such a monumental task and providing a different perspective in managing painful conditions with the publication of Case Studies in Pain Management. Laxmaiah Manchikanti, MD Chairman of the Board and Chief Executive Officer, ASIPP and SIPMS Medical Director, Pain Management Center of Paducah Clinical Professor Anesthesiology and Perioperative Medicine University of Louisville, Kentucky

Section 1 Chapter

1

Neurological Disorders

Postherpetic neuralgia* Alan David Kaye and Charles E. Argoff

Case study A 78-year-old male with a history of postherpetic neuralgia (PHN) as well as hypertension presents to your office with complaints of moderate to severe pain (intensity 7/10) along the right T8 dermatome. He experienced acute herpes zoster (shingles) in this region 3 years ago and was treated at that time with acyclovir and analgesics. The pain never dissipated and for the past 3 years he has been treated with a variety of medications, including immediate-release gabapentin, nortriptyline, and the 5% lidocaine patch as well as unsuccessful treatment with various nerve blocks and a trial of spinal stimulation.

1. What are the basic facts regarding postherpetic neuralgia, varicella-zoster virus, and shingles? Postherpetic neuralgia is a chronic painful complication of shingles, originating with the varicella-zoster virus (VZV), the same virus that causes chicken pox. Approximately, 98% of adults have been exposed to VZV, mostly as children. Reactivation of VZV can occur decades after initial exposure to the virus. Shingles occurs in approximately 1 million people/ year in the USA alone and thus, it is the neurological disease with the highest incidence in the USA. There is a one out of three lifetime incidence in the general population of developing shingles, with increasing * Some of the material presented in this chapter was previously reviewed and published by the authors in Harden RN, Kaye AD, Kintanar T, Argoff CE. 2013. Evidence-based guidance for the management of postherpetic neuralgia in primary care. Postgrad Med 125(4):191–202. doi: 10.3810/pgm.2013.07.2690.

incidence in the elderly. Between 40% and 50% of the people who develop shingles are older than 60 years of age and between 10% and 20% develop PHN.[1,2] PHN results from damage to sensory neurons caused by reactivation of VZV. In PHN, residual nerve fibers appear to become hyperexcitable, resulting in persistent and unpredictable neural signaling, producing a pain state that is often difficult to manage. PHN is described as the pain that persists 3 months or more beyond the healing of herpes zoster blisters and approximately 15% of people who have had shingles ultimately develop PHN. In the USA, this translates to approximately 150 000 new cases annually.[3]

2. What are the basic features of postherpetic neuralgia? Symptoms of PHN may last indefinitely. Risk factors for PHN include female gender, advanced age, presence of painful VZV prodrome, greater VZV rash severity or significant pain, elevated fever in the acute phase of the VZV episode, and sensory dysfunction in the affected dermatome. As with VZV, PHN disproportionately affects older patients.[4] In one study, the overall incidence of PHN was 18% in all adults, but increased to 33% for those  79 years.[5]

3. Why are there are so many challenges with regard to postherpetic neuralgia treatment options? Numerous pharmacologic options for PHN have been extensively studied in randomized controlled studies, and several guidelines regarding the pharmacologic treatment of PHN itself exist. Treatment success must overcome a series of barriers. First, the PHN patient

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

1

Chapter 1: Postherpetic neuralgia

Table 1.1. Summary of treatment guidelines for PHN*

Alpha-2 delta ligands† ‡

NeuPSIG (2010)

EFNS (2010)

CPS (2007)

AAN (2004)

1st line

1st line

1st line

1st line

TCAs

1st line

1st line

1st line

1st line

Topical lidocaine

1st line

1st line

2nd line

1st line

Opioids (including tramadol)

2nd line

2nd line

3rd line

1st line

Topical capsaicin (0.025–0.075%)

2nd line

3rd line

Not described

Not described



3rd line

Not described

Not described

§

Topical capsaicin (8%)

* Except for the AAN guidelines, all review neuropathic pain in general but make specific mention of PHN within the guidelines. All lines of therapy refer to role in PHN specifically. † Gabapentin immediate release and pregabalin. At the time of publications of these guidelines, gastroretentive gabapentin was not available. ‡ Nortriptyline, amitriptyline, desipramine, imitriptyline. NeuPSIG distinguishes between secondary amine TCAs (nortriptyline and desipramine) and tertiary amine TCAs (amitriptyline, imitriptyline) and recommends the former due to superior tolerability. § Topical capsaicin (high concentration, 8%) was approved on November 16, 2009, shortly before publication of the guidelines.

population is frequently older. As with any older population, medical comorbidities and multidrug regimens may affect the choice of drug therapy. Second, not infrequently, payors may limit treatment options or require a step approach mandating failure with certain generic medications, often used in an offlabel manner (including Medicare Part D providers), before paying for potentially more appropriate, as well as potentially higher cost, options. This often results not only in the use of medications that are not specifically Food and Drug Administration (FDA) approved for the treatment of PHN being used before those that are and for which there may be more data to guide treatment, but also potentially a greater likelihood of failure of treatment and its resulting impact on the patient with PHN. Third, the process required to optimize treatment for most medications used to treat PHN to ameliorate adverse effects may require long titration periods, demanding patience and education on the part of both the physician and the patient. Fourth, assuming the physician can overcome the first three barriers, the patient has, based upon the best available guidelines, literally at best, a 50/50 chance of achieving clinically meaningful pain relief (considered 30% pain intensity reduction) with little chance of predicting who will respond to a particular treatment.

4. What are the guidelines for postherpetic neuralgia management? Over the past decade, several organizations have published guidelines either devoted exclusively to PHN or

2

describing PHN in the context of neuropathic pain conditions in general.[6–9] A summary of their recommendations is found in Table 1.1. Each of the guidelines recognize the alpha-2 delta ligands, tricyclic antidepressants (TCAs), opioids, and tramadol as systemic options and topical lidocaine as a non-systemic approach for the treatment of localized PHN. Alpha-2 delta ligands and TCAs are typically recommended as first- or second-line status in the guidelines, and opioids and tramadol are often relegated to secondor third-line although under certain circumstances, first-line. At the time the Special Interest Group on Neuropathic Pain of the International Association for the Study of Pain (NeuPSIG) guidelines were written, the topical capsaicin (8%) patch was recognized as an emerging therapy with insufficient evidence to make a recommendation. In addition, a gastroretentive form of gabapentin as well as a form of gabapentin which is in fact a prodrug were not addressed. Table 1.2 shows the NeuPSIG guidelines. Additional evidence for the use of these agents is now available. The NeuPSIG[7] and the European Federation of Neurological Societies (EFNS)[8] guidelines are the most recently published. Both review the treatment of neuropathic pain in general, but also include specific mention of PHN. The Canadian Pain Society (CPS), published in 2007, likewise makes specific mention of PHN within the context of overall neuropathic pain. The American Academy of Neurology (AAN), in contrast, published a specific PHN guideline in 2004; however, new published evidence has become available since 2004.

Chapter 1: Postherpetic neuralgia

Table 1.2. Summary of NeuPSIG Guidelines for PHN*



Begin treatment with one or more of the following:    

  

Secondary amine TCA (nortriptyline, desipramine) Alpha-2 delta ligand (gabapentin, pregabalin) Topical lidocaine (for patients with localized PHN) alone or in combination with another therapy Opioids or tramadol for patients with acute exacerbations requiring prompt relief (used alone or in combination with one other firstline therapy)

If pain relief is partial (average pain  4 out of 10), add one of the other first-line therapies If no or inadequate pain relief (< 30% reduction at target dosage) after an adequate trial,† switch to another first-line option If first-line single-agent or combination therapy fails, consider second- or third-line options

* Modified from table 1 in Ref.[7]. † Some drugs such as immediate-release gabapentin and TCAs require long duration of up to 8 weeks.

Criteria for recommendations varies The NeuPSIG guidelines rated a medication first line if it has proven effective in multiple randomized controlled studies (RCTs) and the results are consistent with the authors’ clinical experience; second-line status if efficacy has been established in multiple RCTs but the authors had reservations about the use of the medication relative to first-line options; third-line if efficacy was shown in only one RCT or if the results of two or more RCTs were inconsistent, “but the authors thought that in selected circumstances the medication may be a reasonable treatment option.”[8: p. S4] In contrast, the EFNS rate medications having “established” efficacy based on class I or class II evidence, with class I defined as “an adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations” (Table 1.1).[10] In addition, class I studies must have all of the following: (a) randomization concealment, (b) clearly defined primary outcome(s), (c) clearly defined exclusion/ inclusion criteria, (d) adequate accounting for

dropouts and crossovers with numbers sufficiently low to have minimal potential for bias, and (e) relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for difference. Class II is defined as “prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one of the criteria a–e” (Table 1.1).[10] The CPS published a consensus statement on the management of neuropathic pain in 2007.[9] To be recommended in the guidelines, medications had to show efficacy in at least one methodologically sound RCT (Level 1B or better, as defined by Ref.[11]). The guidelines state that they are based on analgesic efficacy, side effect profiles, ease of use, and cost, but describe no criteria for any of these domains except efficacy. To be recommended as first- or second-line, medications had to have high-quality evidence of efficacy and be considered straightforward to prescribe and to monitor. Medications were relegated to third-line if there was good evidence of efficacy but more specialized follow-up and monitoring were required. The fourth guideline, and the only one to specifically address PHN, is the AAN practice parameter published in 2004. The criteria for a level A recommendation were very similar to the Brainin criteria used by the EFNS and required at least one class I study or at least two consistent, convincing class II studies. For class I and class II, the authors also calculated, if possible, absolute risk reduction, number needed to treat (NNT) for adequate pain relief, 95% confidence interval of the NNT, and number needed to harm. Recommendations were then grouped, with Group 1 medications showing medium to high efficacy, good strength of evidence, and low level of side effects, and Group 2 medications showing lower efficacy than those in Group 1 or limited strength of evidence or side effect concerns. (Three other groups with successively lower strength of evidence are also described in the AAN practice parameter.) The criteria for “medium” versus “high” level of efficacy were not defined, nor were the criteria for what constitute a “side effect concern.” The AAN guidelines are somewhat dated but it is interesting to note that, of the four major drug classes currently recommended today as first-, second-, or third-line

3

Chapter 1: Postherpetic neuralgia

therapy in the NeuPSIG, EFNS, or CPS guidelines, all of them are recommended as Group 1 medications (alpha-2 delta ligands, TCAs, opioids, and lidocaine patch) in the AAN guidelines. All drugs listed as Group 2, 3, and 4 options are now considered ineffective or unproven. More recent guidelines downgrade opioids because of the risk of abuse and the added time needed to assess risk, monitor the patient, monitor for adverse effects, and remove patients from therapy if abuse is suspected. The reader must keep in mind that these guidelines have arrived at similar BUT not identical conclusions.

5. Are there any systematic reviews and meta-analysis data on postherpetic neuralgia treatments? In addition to the above-mentioned guidelines, four separate Cochrane reviews have been published, one each on gabapentin,[12] pregabalin,[13] topical lidocaine,[14] or topical capsaicin,[15] as well as a metaanalysis of a broad range of drugs for PHN.[16] Except for the topical lidocaine Cochrane review, which focused exclusively on PHN, the other Cochrane reviews included a range of neuropathic, and at times non-neuropathic, pain conditions. The Cochrane review on gabapentin[12] included PHN studies of immediate-release and gastroretentive gabapentin. It concluded that gabapentin was effective for chronic neuropathic pain but did not draw any conclusions specifically about efficacy in PHN. The Moore review on pregabalin[13] included 5 PHN studies and concluded that pregabalin at both 300 mg/day and 600 mg/day were effective in PHN, with greater responses seen at 600 mg/day. The Khaliq review[14] on topical lidocaine identified nine published trials but excluded seven of them because they did not meet prespecified inclusion criteria. One additional unpublished trial was identified and data were obtained from the FDA and analyzed. According to this review, these three studies demonstrated modest benefit of topical lidocaine in PHN and the authors concluded that there is insufficient evidence to recommend topical lidocaine as first-line therapy in PHN. The Derry[15] review on topical capsaicin analyzed six studies of low-concentration topical capsaicin (0.075%) cream and two studies utilizing the high-concentration topical capsaicin (8%) patch. The authors concluded that repeated daily applications of

4

the cream and a single application of the patch (applied once every 3 months) provided “some degree of improvement” in patients with PHN.[15: p. 14] The meta-analysis conducted by Edelsberg and colleagues[16] analyzed 12 randomized controlled PHN studies involving eight different agents. This analysis demonstrated that gabapentin immediate release (2 studies), pregabalin (3 studies), the TCAs amitriptyline and nortriptyline (1 study each), morphine (1 study), capsaicin (2 studies), tramadol (1 study), and divalproex (1 study) showed statistically significantly greater reductions in pain compared with placebo. In general, the Cochrane reviews and the meta-analysis are all consistent with the recommendations of current guidelines, with the exception of the topical lidocaine Cochrane review, which did not consider sufficient evidence to exist to recommend topical lidocaine as first-line therapy.

6. Are there any gaps in the Postherpetic Neuralgia Treatment Guidelines? High-quality clinical studies have been the foundation of evidence-based medicine and provide a solid foundation for authoritative guidelines, yet interpreting and applying the guidelines to clinical practice must be done with an awareness of the limitations and blind spots of clinical studies and a full understanding of what evidence-based medicine is and what it is not. Evidence-based medicine includes “hard” data but as defined, also allows for the integration of clinical expertise and patients’ values and preferences.[17] As Sackett has stated, evidence-based medicine is “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. In this definition, the practice of evidence-based medicine means integrating individual clinical expertise with a critical appraisal of the best available external clinical evidence from systematic research.”[18] Regrettably, it is our view that this definition is not addressed in the guidelines described above. Clinical trials often select patient populations to minimize intersubject heterogeneity. Specific comorbidities are often excluded, and concomitant medications that many patients would commonly take are excluded. While this approach minimizes variables that confound interpretation by doing so, it also

Chapter 1: Postherpetic neuralgia

excludes the type of patient that is commonly seen in clinical practice. In addition, differences among formulations of the same drug in terms of efficacy, dosing, adherence, and convenience and patient preferences (which may range from dosing convenience to a specific adverse effect that a patient may find problematic) may not be addressed. Also typically not addressed are differences in tolerability in clinically relevant subpopulations; the efficacy at target doses that typically can be achieved in practice (in contrast to those achieved in clinical studies); differences in the various descriptive components of pain; acute exacerbations of pain; and onset of pain relief. Given that head-to-head studies are often lacking, direct comparisons of various pharmacologic options is difficult, and studies used to develop published guidelines, typically do not assess long-term therapy (> 3 months). Although it would be unfair to say that PHN guidelines don’t address these issues at all, if they are addressed it is often done in the context of neuropathic pain in general and lacking in direction regarding how to integrate numerous clinical variables in practice (the “real” world), particularly in complex patients who have significant medical and other comorbidities and who may be taking numerous medications. PHN guidelines, in particular, are further hampered by a lack of inclusion of more recent clinical data that have emerged since the last guidelines were published in 2010.

7. Are there any new clinical data on postherpetic neuralgia treatments? High-concentration (8%) topical capsaicin patch The high-concentration topical capsaicin patch is administered once every 3 months (in contrast to the low-concentration topical capsaicin creams, which are administered several times daily). Since the publication of the last guidelines, multiple publications including two multicenter, randomized, double-blind PHN studies[19,20] and an integrated analysis of four randomized, double-blind PHN studies[21] have become available. The patch was applied for 60 minutes in all studies although in one study the patch was also applied for 30 and 90 minutes.[20] Subjects in the control arms received a 0.04% capsaicin patch to maintain blinding, as a true placebo

would not induce a local site reaction, which occurs with the 8% patch. The primary endpoint was change from baseline in pain intensity level assessed using a Numerical Pain Rating Scale (NPRS). Change from baseline was calculated by comparing baseline scores with the average of daily NPRS scores from weeks 2–8 and weeks 2–12. Data from Week 1 data were not included because subjects received opioid medication in week 1 to alleviate application site pain caused by the patch. The Irving study[19] showed the highconcentration topical capsaicin patch superior to control in change from baseline in NPRS to weeks 2–8, percentage change from baseline in NPRS from weeks 2–8 and weeks 2–12, percentage of patients with a 30% response, and percentage of patients with a 50% response[19: p. 105] (Table 1.2). In the Webster study,[20] a 60-minute application showed significant improvement in percent change from baseline in average pain score (NPRS) over weeks 2–12, but no significant reduction in mean change from baseline over weeks 2–8 or weeks 2–12 or in percent change from baseline over weeks 2–8. The integrated analysis of over 1000 patients in 4 PHN studies likewise demonstrated statistically significant improvements relative to control in percentage change from baseline in NPRS to weeks 2–12, 30% response rate, and 50% response rate as well as patient global impression of change (PGIC). Based on these data, although published guidelines did not address this treatment for the reasons noted above, it is our opinion that the highconcentration topical capsaicin patch should be considered first-line therapy for patients with localized PHN.

Gastroretentive gabapentin Gastroretentive gabapentin is one of two currently available extended-release formulations of gabapentin. When administered with a meal, this tablet swells and resides in the stomach for up to 15 hours, releasing drug gradually for absorption by the proximal small intestine. The starting dose is 300 mg/day once daily and increased over 2 weeks to a target dose of 1800 mg/day. Three multicenter, randomized, controlled double-blind studies have been reported either shortly before publication of the most recent guidelines or after publication. One study of 452 patients randomized to once daily gastroretentive gabapentin or placebo demonstrated a statistically significant

5

Chapter 1: Postherpetic neuralgia

reduction in mean change in NPRS scores from baseline and in percentage change from baseline to the final week of the treatment period (Week 10).[22] A second study of 407 randomized subjects showed statistically significant improvements in a range of secondary endpoints (average pain on the Neuropathic Pain Score; worst pain, average pain, and current pain on the Brief Pain Inventory). Using last observation carried forward (LOCF) imputation method, which was the imputation method used in the high-concentration topical capsaicin studies, once daily gastroretentive gabapentin also showed a statistically significant improvement in average daily pain score (NPRS) over 10 weeks of treatment. However, on the primary endpoint using the prespecified baseline observation carried forward (BOCF) imputation method, once daily gastroretentive gabapentin (1800 mg/day) was no better than placebo over 10 weeks of treatment.[23] A third study[24] also failed to show a statistically significant difference vs. placebo over 4 weeks of treatment, 2 weeks of which were the titration phase and 2 weeks of which were at full dose. All of these studies used a conservative imputation approach to missing data (BOCF versus the less conservative LOCF). The BOCF method will typically underestimate efficacy compared with LOCF; for patients who don’t complete the study, the baseline scores (pretreatment) are carried forward. With LOCF, the last available score before dropout is carried forward (and thus usually includes scores after some interval of treatment). Based on the available evidence, gastroretentive gabapentin meets the standard of first-line therapy in the EFNS guidelines (one rigorous RCT needed). Whether it meets the standard of first-line therapy in the NeuPSIG guidelines (multiple RCTs needed) is a matter of interpretation. Unlike the highconcentration topical capsaicin studies, each of the three gastroretentive gabapentin studies used a conservative imputation method for each primary efficacy analysis, and one of the failed studies showed clear separation from placebo when data were analyzed using the LOCF imputation method. Based on the available evidence and other features of gastroretentive gabapentin (such as dosing convenience, pharmacokinetics), we believe it can be considered a first-line option for PHN in certain clinical situations. When administered with an evening meal, peak dose occurs in the early morning (approximately 3 AM), when patients are sleeping. This may account for the

6

observed improved tolerability of gastroretentive gabapentin (lower rate of dizziness and sedation) relative to published reports of gabapentin IR and pregabalin.

Gabapentin enacarbil Gabapentin enacarbil is a twice daily extended-release formulation of gabapentin, specifically formulated as a prodrug. It is currently FDA approved for restless leg syndrome and PHN. A randomized, double-blind study of 115 patients with PHN showed superior pain relief with gabapentin enacarbil versus placebo as assessed by mean change from baseline in pain scores and 30% response rate.[25] This study consisted of a 4-day titration phase with gabapentin immediate release, a 7 day run-in phase with gabapentin immediate release 1800 mg, followed by randomization to either gabapentin enacarbil 1200 mg BID or placebo, which subjects received for 2 weeks. Data imputation for subjects who did not complete the double-blind treatment consisted of the mean daily pain scores from the preceding 7 days. The primary efficacy endpoint was change in weekly pain score from baseline to the final week on double-blind treatment. Limited published data are available on this product, and the short duration of this trial precludes any assessment of this product’s long-term efficacy. However, a 12-week efficacy study described in the product label showed efficacy at all doses tested (up to 3600 mg/day), but 2400 mg/day and 3600 mg/day showed no greater efficacy than 1200 mg/day, and adverse effects were more pronounced at higher doses. The starting dose of gabapentin enacarbil is 600 mg in the morning for 3 days; on day 4, dose should be increased to 600 mg twice daily. Though early evidence demonstrates efficacy with an increasing dose-dependent side effect profile, twice daily dosing provides a clear disadvantage versus once daily dosing of gastroretentive gabapentin and titration above 1200 mg/day is not indicated. The lack of a published randomized controlled trial of significant duration is a limitation and precludes a full evaluation of this product’s place in treatment.

Pregabalin combination therapeutic approaches Several recent studies have evaluated the use of pregabalin in combination with lidocaine plaster,[26,27]

Chapter 1: Postherpetic neuralgia

oxycodone,[28] or transcutaneous electrical nerve stimulation (TENS).[29] Rehm and colleagues and Baron and colleagues assessed the combination of topical lidocaine and pregabalin but no data on statistical significance of the findings were reported. Zin and colleagues found that the addition of a fixed-dose of oxycodone 10 mg did not add to the efficacy of pregabalin, but given that opioids are typically titrated to effect, the fixed-dose of oxycodone may have been too low.[28] A study comparing the use of pregabalin with TENS showed that the addition of TENS to pregabalin 300 or 600 mg/day resulted, after 4 weeks of treatment, in a statistically significant improvement in pain assessed using a visual analog scale,[29] compared with pregabalin alone.

8. What are key considerations in choosing postherpetic neuralgia treatments? Efficacy is a critical factor in treatment selection, but several other factors must be considered when selecting a treatment for a person with PHN. These include:

Tolerability Common adverse effects associated with first- and second-line options for PHN are shown in Table 1.3.

A key consideration for therapeutic success is the ability of the patient to tolerate the therapy longterm, a parameter that is specifically required of class I evidence only in the PHN-specific guidelines published.[6] For a study to be rated as class I by AAN, at least 80% of subjects must complete the study.[30] Those options associated with the potential for significant drowsiness and somnolence pose a challenge for patients, in particular the elderly. Alpha-2 delta ligands are associated with dizziness and somnolence in 10%–20% of patients and should therefore be used cautiously in patients with gait or balance problems. CNS effects of gabapentin IR, gastroretentive gabapentin, gabapentin enacarbil, and pregabalin are shown in Table 1.4. Given the fact that dizziness and somnolence are common with all first- and secondline systemic medications (except TCAs) for PHN, even an incremental reduction in these adverse effects may be significant. Picking such an agent is difficult in the absence of head-to-head studies but the reader should review Table 1.4 for guidance. Tramadol is associated with seizure risk if given alone or if given with selective serotonin reuptake inhibitors (SSRIs), TCAs, or other opioids. Although a rare side effect, it is also associated with an increased risk of serotonin syndrome if given with SSRIs, selective norepinephrine reuptake inhibitors (SNRIs), TCAs, or monoamine oxidase inhibitors (MAOIs). Anticholinergic effects are common with TCAs, but may be less

Table 1.3. Common adverse effects

Drug class

Key adverse effects

TCAs*

Cardiac toxicity, postural hypotension, urinary retention, angle-closure glaucoma, dry mouth, constipation, sweating

Gabapentin IR

Dizziness, somnolence, ataxia, fatigue, weight gain, dry mouth, peripheral edema

Gastroretentive gabapentin

Dizziness, somnolence, ataxia, fatigue, weight gain, dry mouth, peripheral edema

Gabapentin enacarbil

Dizziness, somnolence, fatigue/asthenia, peripheral edema

Pregabalin

Dizziness, somnolence, ataxia, fatigue, weight gain, dry mouth, peripheral edema

Opioids

Constipation, nausea, somnolence, dizziness, pruritis

Tramadol

Dizziness, nausea, constipation, somnolence, flushing, pruritis, insomnia, asthenia Seizure risk at high doses and when given with SSRIs, TCAs, opioids Serotonin syndrome risk when given with SSRIs, SNRIs, TCAs, MAOIs, and triptans

* Secondary amines (nortriptyline and desipramine) are considered by the NeuPSIG guidelines as better tolerated than tertiary amines (amitriptyline, imitriptyline). Abbreviations: SSRI, selective serotonin reuptake inhibitor; SNRI, selective norepinephrine reuptake inhibitor; MAOI, monoamine oxidase inhibitor; TCA, tricyclic antidepressant.

7

Chapter 1: Postherpetic neuralgia

Table 1.4. CNS effects of alpha2-delta ligands

% of AE with Alpha-2 Delta Ligands (% of AE with Placebo) Gabapentin IR*

Gastroretentive gabapentin†

Gabapentin enacarbil‡

Pregabalin§

Dizziness

28.0 (7.5)

10.9 (2.2)

17.0 (15.0)

21.0[5]

Somnolence

21.4 (5.3)

4.5 (2.7)

10[8]

12.0[3]

Lethargy

NR

1.1 (0.3)

NR

NR

Fatigue/asthenia

NR

NR

6.0[1]

NR

Ataxia

3.3 (0)

NR

NR

3[1]

Vertigo

NR

NR

NR

3[1]

Confusion

NR

NR

NR

2[1]

Thinking abnormal

2.7 (0)

NR

NR

2 (0)

Abnormal gait

1.5 (0)

NR

NR

1 (0)

Incoordination

1.5 (0)

NR

NR

2 (0)

Amnesia

1.2 (0)

NR

NR

1 (0)

Hypesthesia

1.2 (0)

NR

NR

NR

* Neurontin (gabapentin) Package Insert † Gralise (gabapentin) Package Insert ‡ Horizant (gabapentin) Package Insert. Rates are based on 1200 mg/day. At higher doses, dizziness was 26% with 2400 mg/day and 30% with 3600 mg/day. § Lyrica (pregabalin) Package Insert. Abbreviations: AE, adverse event; NR, not reported.

common with the secondary amines (nortriptyline and desipramine) compared to the tertiary amines (amitriptyline and imitriptyline). Opioids’ adverse effects include dizziness, somnolence, constipation, hypogonadism, and nausea and are associated with the risk of misuse and abuse. Although from an analgesic viewpoint, opioids are generally at least as effective as other drugs for PHN, they are typically not recommended as first line mainly because of their adverse effect profile as well as risk of abuse and the need to screen patients for risk of abuse, monitor potential abuse, and intervene if abuse is suspected. Both topical options (capsaicin and lidocaine) have negligible systemic adverse effects and thus can be very useful for patients on multiple medications or who cannot tolerate systemic medications.

Dosing and onset of analgesia Prescriber knowledge of dosing of available drug therapies is critical for success (Table 1.5). To minimize adverse effects, a slow titration phase is required for TCAs, gabapentin IR, and pregabalin. In contrast, gastroretentive gabapentin can be titrated over 2 weeks

8

up to 1800 mg/day, and gabapentin enacarbil over 1 week up to 1200 mg/day. Onset of efficacy for these agents may be delayed, but if the patient is tolerating these drugs well, the provider and patient should make every effort to complete the titration phase and not terminate early. Frequency of dosing is a major contributor to adherence with chronic use. There is no titration required for the 5% lidocaine patch nor the 8% capsaicin patch. Although few studies have assessed dosing frequency and adherence in chronic pain, in several other therapeutic areas adherence increases with decreasing dosing frequency.[31] Ideally, TID medications should be avoided in favor of medications with BID or QD dosing, especially in patients on multiple medications. In this regard, medications such as topical capsaicin (8%) (applied once every 3 months), the topical lidocaine patch (3 patches applied 12 hours daily), gastroretentive gabapentin (once daily), gabapentin enacarbil (twice daily), the TCAs (once daily or given in two divided doses per day), and some extended-release opioid formulations are more attractive. Gabapentin IR is given three times daily, and pregabalin two to three times daily.

Chapter 1: Postherpetic neuralgia

Table 1.5. Dosing and onset considerations*

Drug class

Dosing

Duration of adequate trial

TCAs

Start at 25 mg at bedtime Increase 25 mg/d every 3–7 days

6–8 weeks with at least 2 weeks at maximum tolerated dosage

Gabapentin IR

Start at 100–300 mg at bedtime or 100–300 mg 3 times daily Increase by 100–300 mg 3 times daily every 1–7 d as tolerated

3–8 weeks for titration plus 2 weeks at maximum dose

Gastroretentive gabapentin

Take with evening meal Start at 300 mg/d Increase dose to 600 mg/d on day 2, 900 mg/d on days 3–6, 1200 mg/d on days 7–10, 1500 mg/d on days 11–14, and 1800 mg/d on day 15

Not defined

Gabapentin enacarbil

Start at 600 mg in the morning for 3 days Increase to 600 mg BID beginning on day 4

Not defined

Pregabalin

Start at 50 mg 3 times daily or 75 mg twice daily as tolerated. Increase to 300 mg/d after 3–7 d, then by 150 mg/d every 3–7 d as tolerated

4 weeks

Topical lidocaine

Maximum of three patches daily for a maximum of 12 hours

3 weeks

Topical capsaicin (8%)

1 patch applied for 60 minutes every 3 months

Not defined

Opioids

Start at 10–15 mg morphine or morphine equivalents every 4 hours as needed After 1–2 weeks, convert total daily dosage to long-acting opioid analgesic and continue short-acting medication as needed

4–6 weeks

Tramadol

Start at 50 mg once or twice daily Increase by 50–100 mg/d in divided doses every 3–7 d as tolerated

4 weeks

* Modified from[7] (Table 2).

Are there challenging subsets of patients and guideline gaps in subpopulations of patients with postherpetic neuralgia? The older patient The PHN patient is typically older, has several comorbidities, and takes multiple medications resulting in special considerations and gaps in treatment considerations (Table 1.6). Approximately 20% of people 65 years of age or older are taking 5 or more drugs.[32] Of the 10 most commonly administered medications given to the elderly, 6 of them (hydrochlorothiazide, lisinopril, metoprolol, atenolol, amlodipine, and furosemide) cause drowsiness, dizziness, or somnolence.[33] Thirty percent of hospitalizations are associated with drug-related problems or adverse effects.[34] This population is particularly sensitive to adverse effects of medications, and it is here where treatment selection becomes complicated.

In addition to a standard pain work-up, special attention should be paid to assessing the older patient’s physical function. Range of motion testing, gait, and balance testing should be considered, and if deficits are found, drugs with a higher risk of dizziness and somnolence should be avoided or used with caution. Because some side effects can be minimized or avoided with slow titration, if the patient with gait or balance problems is a candidate for a drug causing significant sedation or drowsiness, a low starting dose and slow titration schedule may alleviate some of these side effects. Older patients have decreased renal and hepatic function, altered drug distribution, and decreased blood volume, which can affect drug metabolism and tolerability. Glomerular filtration rate decreases by about 0.75 to 0.9 ml/min per year after the age of 30–40 years. By the age of 80, glomerular filtration rate may be two-thirds that of a

9

Chapter 1: Postherpetic neuralgia

Table 1.6. Guideline gaps

Special populations Elderly

Depression Anxiety Renal/ hepatic impairment

Cardiovascular comorbidities

History of substance abuse

NA

NA

Dose reduction required for gabapentin and pregabalin in pts with renal insufficiency

Prescribe TCAs with caution in pts with ischemic heart disease or ventricular conduction abnormalities; limit dosages to 100 mg/d when possible; obtain screening ECG

Risk of abuse of tramadol seems considerably less than that with strong opioids Avoid strong opioids as 1st-line therapy due to risk of abuse/misuse If opioids used, monitor for signs of abuse

EFNS

Topical lidocaine, with its NA excellent tolerability, may be considered 1st-line in the elderly

NA

NA

NA

NA

CPS

Topical lidocaine is a good 2nd-line analgesic for elderly

NA

NA

NA

TCAs are “relatively” contraindicated

NA

AAN

NA

NA

NA

NA

NA

NA

AGS

Start with lower doses of most drugs Older pts rarely tolerate TCA doses > 75–100 mg/d Monitor sedation, ataxia, and edema with alpha-2 delta ligands Opioids can be an effective option in properly selected and monitored patients

NeuPSIG Topical lidocaine’s lack of systemic adverse effects and drug interactions make this product advantageous in older patients

NA ¼ not addressed.

healthy 20- to 30-year-old.[35] Elderly patients are also more sensitive to opioids and benzodiazepines.[36] The American Geriatrics Society (AGS) notes that the elderly and patients with multiple comorbidities are rarely studied in randomized controlled trials, so most recommendations are made based on highly selected and younger populations. The AGS recommends a patient-centered approach, which begins with understanding the patient’s primary

10

concern and treatment goals.[37] AGS also provides the following recommendations:  Pain is underreported in the older patient so clinicians must make an effort to assess it, even in patients with cognitive impairment. Special pain assessments for patients with cognitive impairment exist, a summary of which has been described in an expert consensus statement.[30]  Because of age-related decrements in drug metabolism and clearance, starting doses should

Chapter 1: Postherpetic neuralgia

   

be low and titration slow with frequent reassessment for dosage adjustments. Use of TCAs above 75–100 mg/day are rarely tolerated by the older patient and their use in this population is “often contraindicated.”[37] If prescribed gabapentin or pregabalin, patients must be monitored closely for sedation, ataxia, and edema. Gabapentin and pregabalin are considered to have a more “benign” adverse effect profile than TCAs.[37] Short-acting opioids are useful for acute recurrent, episodic, or breakthrough pain but total daily dose combination products containing acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) should be used carefully to ensure risk of toxic effects of the non-opioid are minimized. Total daily dose of acetaminophen should not exceed more than 4 g/day (less in patients with impaired hepatic function).

The Beers Criteria for Potentially Inappropriate Medications in Older Adults recommends avoiding tertiary TCAs (amitriptyline, imipramine) in the older patient in general, but also notes that tertiary TCAs are particularly problematic for patients with syncope, delirium, dementia, cognitive impairment, and chronic constipation. Tramadol should be avoided in patients with a history of chronic seizures or epilepsy, and anticonvulsants as a class should be avoided in patients with a history of falls or fractures.[37] Based on these considerations, we recommend topical medications for the frail older patient and avoidance of TCAs. Alpha-2 delta ligands have relatively few drug interactions and are a better first choice, but sedation is a significant adverse effect and should be used with caution in patients with gait problems. Of the alpha-2 delta ligands, gastroretentive gabapentin has a lower risk of dizziness and sedation. Data related to gastroretentive gabapentin indicates increased tolerability with a further reduction in the incidence of dizziness and sedation in patients  65 years of age (dizziness, 9.7% versus 12.9%; sedation, 4.0% versus 5.3%, in patients  65 years of age vs. < 65 years of age, respectively).[19] Given the lack of good options for the older patient, the question arises as to the role of opioids in this population. Opioids are second-line options in most guidelines. The long-term risks of these medications cannot and should not be minimized but the AGS

acknowledges that in properly selected and monitored patients, opioid analgesics are “a potentially effective, and in some patients, indispensable treatment as part of a multimodal treatment strategy.”[37: p. 1338] If the clinician chooses opioids, both the clinician and patient must conform to principles of safe opioid prescribing,[38,39] which requires frequent monitoring for efficacy, adverse effects, and abuse. If abuse is confirmed, the clinician must be comfortable exiting the patient off therapy safely, which will require a frank discussion with the patient, a tapering strategy to minimize risk of withdrawal, and a revised care plan to provide pain relief via some other means. Some clinicians may wish to refer such patients to specialists with experience treating patients who have substance abuse or addiction. Although nausea and somnolence with opioids tend to decrease over time, constipation does not and should be anticipated and treated prophylactically.[40] Methadone is not recommended by the AGS as a first-line treatment for pain.[37] Its halflife is variable and conversion to and from other opioids is complicated. Further, many agents can alter methadone levels by inducing or inhibiting the six P450 enzymes involved in its metabolism. Drug accumulation can occur, with potentially fatal consequences. Conversely, drug-drug interactions can reduce methadone levels and precipitate withdrawal.[41] Of the approximately 14 000 deaths attributed to prescription opioids in 2009, over 5000 of them were attributed to methadone.[42] Methadone should only be used by practitioners knowledgeable in its pharmacology and with experience in its use.[37] Opioid-naïve elderly should be started on immediaterelease opioid first, titrated to an effective dose, and then converted, if warranted, to an extended-release formulation.[43] All patients should be instructed to avoid alcohol, benzodiazepines, and barbiturates, as these are CNS depressants and can exacerbate the CNS depressant effects of opioids.[37] Renal/hepatic impairment Pregabalin and gabapentin dose must be reduced in renally impaired patients.[7] Morphine, hydromorphone, and codeine should be used with extreme caution in patients with renal impairment. Morphine and hydromorphone have active metabolites that can accumulate in renally impaired patients and exacerbate the common risks of opioids, and also can result in neuroexcitatory symptoms (in the case of morphine and hydromorphone) and profound

11

Chapter 1: Postherpetic neuralgia

hypotension and narcolepsy (in the case of codeine).[35] Tramadol extended-release is available in limited dosage strengths, so dose adjustments with tramadol are difficult. Fentanyl and methadone appear to be less affected by renal impairment. For reasons stated above, methadone should be avoided, but fentanyl may be a good option if opioid therapy is indicated.[35] In renally impaired patients, dose of opioid should be lower, the interval between doses longer, and creatinine clearance monitored frequently.[44] In patients with significant hepatic impairment, opioid dose should be reduced. Oxymorphone should not be used in patients with moderate to severe hepatic impairment.[35] Dose reductions are required for TCAs but not alpha-2 delta ligands. Patient with anxiety and depression Many patients with anxiety and depression might be receiving medications such as SSRIs and consequently using additional drugs that also raise serotonin (e.g., TCAs) should be used cautiously. Recent evidence suggests that TCAs may be associated with an increased risk of diabetes. In an analysis of three prospective cohort studies (Health Professional Follow-up Study, Nurses’ Health Study I, and Nurses’ Health Study II) totaling over 250 000 subjects, TCAs were associated with a 26% increased risk of diabetes (HR, 1.26: CI, 1.11, 1.42).[45,46] Patients with depression and anxiety also tend to have a higher risk of substance abuse,[35] so any drug with abuse potential should be avoided or used cautiously. Although a history of substance abuse is not an absolute contraindication for opioid therapy, risk of opioid abuse in this type of patient population is significant. A clinician experienced with this subgroup can assess whether opioid therapy is feasible or create a care plan using non-opioid options. The alpha-2 delta ligands are likely a better first choice in these populations. The lack of drug interactions (relative to TCAs) would make them a good choice for the depressed patient being treated with an SSRI or MAOI and their lack of abuse potential make them a better choice over opioids. Furthermore, gabapentin is effective in the treatment of anxiety/social phobia[47,48] and pregabalin has previously demonstrated efficacy in generalized anxiety disorder,[49] making them good choices in patients with anxiety (perhaps providing additive efficacy to other medications while minimizing the potential for increased adverse effects or drug-drug interactions).

12

The patient with a history of substance abuse Any clinician prescribing opioids should be sure to conduct a risk assessment for every patient. A good risk assessment will include current and past history of drug use and family history of drug abuse for each patient. PHN patients with a significant risk of prescription drug abuse generally should not receive opioids, with alpha-2 delta ligands or topicals being a better first choice. In the absence of other options, opioids can be considered, even for patients with a significant risk of abuse, but the prescriber and the patient must establish clear expectations. Furthermore, the prescriber must make a commitment to monitor the patient routinely with urine drug testing and must be comfortable with taking a patient off opioids if evidence of abuse is suspected. This can be achieved in the primary care setting by clinicians who have made a commitment to learn and to apply the principles of safe opioid prescribing. Implementing such principles does take time, which is at a premium in the typical primary care practice. If the clinician cannot make this commitment to safe opioid prescribing, referral to a pain specialist should be considered. Keep in mind, however, that obtaining an appointment to see a pain specialist may take months and a strategy to manage pain in the interim must be in place.

Miscellaneous considerations Patients with cardiomyopathy, valvular disease, or any condition that reduces cardiac output will have reduced renal and hepatic perfusion, which will decrease the rate of elimination of drugs. Starting doses of drugs should be lower, and titration conservative in these patients. Patients with ischemic heart disease or ventricular conduction abnormalities should avoid TCAs, with doses no higher than 100 mg/day.[7] Methadone should not be used in patients with QT prolongation.[35] Patients with cardiovascular or respiratory compromise who are being considered for opioid therapy should be monitored for respiratory depression. Baseline and periodic studies such as oxygen saturation monitoring and/or blood gas analyses, spirometry, ECG, and chest radiographs should be considered.[35] Alpha-2 delta ligands are established antiepileptic agents, providing potential additional advantages; patients with a history of seizures who are on alpha-2 delta ligands but need to be taken off should have their dose of alpha-2 delta ligands titrated downward prior to discontinuation. Very little

Chapter 1: Postherpetic neuralgia

data are available in treating the patient with dementia or cognitive impairment. Amitriptyline should be avoided as it may impair memory.[50] In the context of central neuropathic pain, some experts[50] recommend pregabalin in patients with moderate to severe dementia.

9. What are the key summarized points for treatment of postherpetic neuralgia? Typically, published PHN guidelines are devoid of practical considerations to aid the prescriber in choosing a

References 1.

Gnann JW, Whitley RJ. Clinical practice. Herpes zoster. NEJM. 2002;347:340.

2.

Weaver BA. Herpes zoster overview: natural history and incidence. J Am Osteopath Assoc. 2009;109(6 Suppl 2):S2–6.

3.

Berger A, Dukes EM, Oster G. Clinical characteristics and economic costs of patients with painful neuropathic disorders. J Pain. 2004;5:143–149.

4.

Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008;6(57 RR-5):1–30.

5.

6.

Yawn BP, Itzler RF, Wollan PC, et al. Health care utilization and cost burden of herpes zoster in a community population. Mayo Clin Proc. 2009;84(9):787–794. Dubinsky RM, Kabbani H, ElChami Z, Boutwell C, Ali H. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63(6):959–965. Review. PubMed PMID: 15452284.

7.

particular treatment for an individual patient and thus are not able to truly guide the practitioner. Utilizing key prescribing principles such as considering the efficacy, tolerability, and frequency of administration of a particular PHN treatment can be helpful to the clinician when choosing a treatment option for a given patient. Factors beyond the clinician’s immediate control, including third party reimbursement policies, too often influence the choice of medication prescribed for the treatment of PHN in an individual patient, often exposing the patient to a greater risk of intolerable side effects, subtherapeutic dosing of a particular medication, and treatment failure.

Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85(3 Suppl): S3–14. Review. PubMed PMID: 20194146; PubMed Central PMCID: PMC2844007.

12. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2011;(3): CD007938. Review. PubMed PMID: 21412914.

8.

Attal N, Cruccu G, Baron R, et al. European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113–e88. Epub 2010 Apr 9. Review. PubMed PMID: 20402746.

13. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009;(3):CD007076. Review. PubMed PMID: 19588419. Spring;12(1):13–21. PubMed PMID: 17372630; PubMed Central PMCID: PMC2670721.

9.

Moulin DE, Clark AJ, Gilron I, et al. & Canadian Pain Society. Pharmacological management of chronic neuropathic pain – consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007;12(1):13–21.

14. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of postherpetic neuralgia. Cochrane Database Syst Rev. 2007;(2):CD004846. Review. PubMed PMID: 17443559.

10. Brainin M, Barnes M, Baron JC, et al. Guideline Standards Subcommittee of the EFNS Scientific Committee. Guidance for the preparation of neurological management guidelines by EFNS scientific task forces–revised recommendations 2004. Eur J Neurol. 2004;11(9):577–581. PubMed PMID: 15379736. 11. MacPherson DW. Evidence-based medicine. Can Commun Dis Rep.

1994;20(17):145–147. English, French. PubMed PMID: 7812231.

15. Derry S, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007393. Review. PubMed PMID: 19821411. 16. Edelsberg JS, Lord C, Oster G. Systematic review and metaanalysis of efficacy, safety, and tolerability data from randomized controlled trials of drugs used to treat postherpetic neuralgia. Ann Pharmacother. 2011;45(12):

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Chapter 1: Postherpetic neuralgia

1483–1490. Epub 2011 Nov 15. Review. PubMed PMID: 22085778. 17. Panesar SS, Philippon MJ, Bhandari M. Principles of evidence-based medicine. Orthop Clin North Am. 2010;41(2):131– 138. PubMed PMID: 20399352. 18. Sackett DL. Evidence-based medicine. Semin Perinatol. 1997;21(1):3–5. PubMed PMID: 9190027. 19. Irving GA, Backonja MM, Dunteman E, et al. NGX-4010 C117 Study Group. A multicenter, randomized, double-blind, controlled study of NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Med. 2011;12(1):99–109. doi: 10.1111/ j.1526-4637.2010.01004.x. Epub 2010 Nov 18. PubMed PMID: 21087403. 20. Webster LR, Tark M, Rauck R, Tobias JK, Vanhove GF. Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia. BMC Neurol. 2010 Oct 11;10:92. PubMed PMID: 20937130; PubMed Central PMCID: PMC2958861. 21. Irving G, Backonja M, Rauck R, et al. NGX-4010, a capsaicin 8% dermal patch, administered alone or in combination with systemic neuropathic pain medications, reduces pain in patients with postherpetic neuralgia. Clin J Pain. 2012;28(2):101–107. 22. Sang CN, Sathyanarayana R, Sweeney M; for the DM-1796 Study Investigators. Gastroretentive gabapentin (G-GR) formulation reduces intensity of pain associated with postherpetic neuralgia (PHN). Clin J Pain. 2012 Jul 13. [Epub ahead of print] PubMed PMID: 22801243.

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23. Wallace MS, Irving G, Cowles VE. Gabapentin extended-release tablets for the treatment of patients with postherpetic neuralgia: a randomized, doubleblind, placebo-controlled, multicentre study. Clin Drug Investig. 2010;30(11):765–776. doi: 10.2165/11539520000000000-00000. PubMed PMID: 20818838. 24. Irving G, Sondag E, Sweeney M. Tolerability and safety of oncedaily gabapentin in the treatment of postherpetic neuralgia. Presented at the American Academy of Pain Medicine, 27th Annual Meeting, March 24–27, 2011. National Harbor, MD. Poster #220. 25. Backonja MM, Canafax DM, Cundy KC. Efficacy of gabapentin enacarbil vs placebo in patients with postherpetic neuralgia and a pharmacokinetic comparison with oral gabapentin. Pain Med. 2011;12(7):1098–1108. doi: 10.1111/j.1526-4637.2011.01139.x. Epub 2011 May 31. PubMed PMID: 21627766. 26. Rehm S, Binder A, Baron R. Postherpetic neuralgia: 5% lidocaine medicated plaster, pregabalin, or a combination of both? A randomized, open, clinical effectiveness study. Curr Med Res Opin. 2010;26(7):1607–1619. PubMed PMID: 20429825. 27. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin. 2009;25 (7):1677–1687. PubMed PMID: 19480610. 28. Zin CS, Nissen LM, O’Callaghan JP, Duffull SB, Smith MT, Moore BJ. A randomized, controlled trial of oxycodone versus placebo in patients with postherpetic neuralgia and painful diabetic neuropathy treated with

pregabalin. J Pain. 2010; 11(5):462–471. Epub 2009 Dec 3. PubMed PMID: 19962354. 29. Barbarisi M, Pace MC, Passavanti MB, et al. Pregabalin and transcutaneous electrical nerve stimulation for postherpetic neuralgia treatment. Clin J Pain. 2010;26 (7):567–572. PubMed PMID: 20639738. 30. Hadjistavropoulos T, Herr K, Turk DC, et al. An interdisciplinary expert consensus statement on assessment of pain in older persons. Clin J Pain. 2007 Jan;23(1 Suppl):S1–43. PubMed PMID: 17179836. 31. Ingersoll KS, Cohen J. The impact of medication regimen factors on adherence to chronic treatment: a review of literature. J Behav Med. 2008;31(3):213–224. Epub 2008 Jan 19. Review. PubMed PMID: 18202907; PubMed Central PMCID: PMC2868342. 32. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287(3):337–344. PubMed PMID: 11790213. 33. Qato DM, Alexander GC, Conti RM, et al. Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States. JAMA. 2008;300(24):2867–2878. PubMed PMID: 19109115; PubMed Central PMCID: PMC2702513. 34. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–2724. Erratum in: Arch Intern Med. 2004 Feb 9; 164(3):298. PubMed PMID: 14662625.

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35. Smith H, Bruckenthal P. Implications of opioid analgesia for medically complicated patients. Drugs Aging. 2010; 27(5):417–433. doi: 10.2165/ 11536540-000000000-00000. Review. PubMed PMID: 20450239. 36. Kaye AD, Baluch A, Scott JT. Pain management in the elderly population: a review. Ochsner J. 2010;10(3):179–187. PubMed PMID: 21603375; PubMed Central PMCID: PMC3096211. 37. American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. Pain Med. 2009; 10(6):1062–1083. Epub 2009 Sep 9. Review. PubMed PMID: 19744205. 38. Gourlay D, Heit H. Universal precautions: a matter of mutual trust and responsibility. Pain Med. 2006;7(2):210–211; author reply 212. PubMed PMID: 16634732. 39. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107–112. PubMed PMID: 15773874. 40. van Ojik AL, Jansen PA, Brouwers JR, van Roon EN. Treatment of chronic pain in older people:

evidence-based choice of strongacting opioids. Drugs Aging. 2012;29(8):615–625. doi: 10.2165/ 11632620-000000000-00000. PubMed PMID: 22765848. 41. Ferrari A, Coccia CP, Bertolini A, Sternieri E. Methadone– metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004;50(6):551–559. Review. PubMed PMID: 15501692. 42. Warner M, Chen LH, Makuc DM, Anderson RN, Miniño AM. Drug poisoning deaths in the United States, 1980–2008. NCHS Data Brief. 2011;(81):1–8. PubMed PMID: 22617462. 43. Barber JB, Gibson SJ. Treatment of chronic non-malignant pain in the elderly: safety considerations. Drug Saf. 2009;32(6):457–474. doi: 10.2165/00002018-20093206000003. Review. PubMed PMID: 19459714. 44. Gianni W, Ceci M, Bustacchini S, et al. Opioids for the treatment of chronic non-cancer pain in older people. Drugs Aging. 2009;26 (Suppl 1):63–73. doi: 10.2165/ 11534670-000000000-00000. Review. PubMed PMID: 20136170. 45. Pan A, Sun Q, Okereke OI, et al. Use of antidepressant medication and risk of type 2 diabetes: results from three cohorts of US adults. Diabetologia. 2012;55(1):63–72.

Epub 2011 Aug 3. PubMed PMID: 21811871; PubMed Central PMCID: PMC3229672. 46. Kivimäki M, Batty GD. Antidepressant drug use and future diabetes risk. Diabetologia. 2012;55(1):10–12. Epub 2011 Oct 29. PubMed PMID: 22038524; PubMed Central PMCID: PMC3228947. 47. Chouinard G, Beauclair L, Bélanger MC. Gabapentin: longterm antianxiety and hypnotic effects in psychiatric patients with comorbid anxiety-related disorders. Can J Psychiatry. 1998;43(3):305. PubMed PMID: 9561320. 48. Pande AC, Pollack MH, Crockatt J, et al. Placebo-controlled study of gabapentin treatment of panic disorder. J Clin Psychopharmacol. 2000;20(4):467–471. PubMed PMID: 10917408. 49. Feltner D, Wittchen HU, Kavoussi R, et al. Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol. 2008;23(1): 18–28. PubMed PMID: 18090504 50. Scherder EJ, Plooij B. Assessment and management of pain, with particular emphasis on central neuropathic pain, in moderate to severe dementia. Drugs Aging. 2012;29(9):701–706. PubMed PMID: 23018606.

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Section 1 Chapter

2

Neurological Disorders

Patient with spinal cord injury pain Daniel Krashin, Natalia Murinova, and Alan David Kaye

Case study A 30-year-old high school history teacher is referred to your practice for evaluation of his chest pain and leg pain. He suffered T8 paraplegia in a diving accident a decade ago, while in college. He functions professionally and socially, and is independent in his activities of daily living (ADL), and travels around using a wheelchair. He reports pain in his chest just above the level where he lost sensation. The pain is exacerbated during the day and when he is particularly physically active. He also has burning and aching pain in his legs, which seems to come and go without a pattern, and which is not alleviated by any measures. He is very puzzled by this, since he has no sensation in his legs otherwise, and wonders if this is like the phantom limb pain he has heard about from friends.

1. What is this patient’s diagnosis? This patient is presenting with neuropathic pain related to a spinal cord injury. He has neuropathic pain which is specifically due to nerve root injury and is centrally mediated below the level for neuropathic pain. A broad distinction can be made between musculoskeletal pain, neuropathic pain, and visceral pain in most patients.

2. How many spinal cord injury (SCI) patients are there, and how common is chronic pain in this population? Spinal cord injury is a common medical problem worldwide. In the USA, SCI prevalence is estimated at 721 per million population, or 176 965 persons

alive with SCI.[1] A report in 2005 estimated the number of survivors of traumatic SCI in the USA to be around 273 000.[2] This report also estimated that about 80% of traumatic SCI survivors are male. It has a bimodal distribution; traumatic SCI is more common in younger patients, and non-traumatic is more common in the older population. The most common causes of traumatic SCI are motor vehicle crashes, falls, and gunshot wounds. SCI is associated with significant morbidity and mortality, both directly related to the neurologic deficits and indirect results, such as increased suicides. Higher spinal levels of injury and greater age at time of injury are negative prognostic factors for health and survival. The most common causes of death include pneumonia, sepsis, and cardiovascular disease. Renal disease used to be a major cause of death in SCI but has faded in significance due to improvements in urologic care.[3] One longitudinal study of pain complaints after traumatic SCI showed that 81% of the subjects reported chronic pain. The most common type of pain was musculoskeletal pain at 59%, less likely to be rated as severe. Neuropathic pain at the level of injury was 41% and below the level of the injury was 34%; they were less common and more severe, and visceral pain was found in only 5% of subjects, but was the most likely to be excruciating.[4] This study demonstrated important facts about pain in SCI: it is common and complex, and there are a number of less common pain conditions, which may be extremely severe. In general, about two-thirds of SCI patients report chronic pain, and about one-third report severe pain that interferes with their quality of life and functioning.[5,6]

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 2: Patient with spinal cord injury pain

Table 2.1. Proposed International Spinal Cord Injury Pain (ISCIP) classification

Pain type

Subtype

Examples

Musculoskeletal

Musculoskeletal pain

Shoulder arthritis

Visceral

Visceral pain

Abdominal pain due to impaction

Other

Other nociceptive pain

Postoperative pain

At-level SCI

At-level SCI pain

Nerve root injury, spinal cord compression

Below-level SCI

Below-level SCI pain

Spinal cord compression, thalamic deafferentation pain

Other

Other neuropathic pain

Carpal tunnel syndrome, polyneuropathy

Nociceptive pain

Neuropathic pain

Other pain syndromes

Fibromyalgia, complex regional pain syndrome (CRPS), etc.

Reproduced from TN Bryce. International Spinal Cord Injury Pain Classification: Part I. Background and Description.

3. What are commonly experienced types and examples of pain conditions in SCI patients? In addition to musculoskeletal pain syndromes, which will be detailed separately, the massive nerve injury represented by SCI gives rise to neuropathic pain in many patients, characterized by certain pain qualities such as burning, tingling, stabbing or shocking. This pain can have a clear pattern of a nerve distribution or be diffuse. See Table 2.1 for proposed International Spinal Cord Injury Pain (ISCIP) classification.

4. What types of neuropathic pain are experienced in SCI patients? Neuropathic pain in SCI takes two characteristic forms, at-level and below-level or distal pain. At-level pain is pain is located in the segments associated with the level of the injury. This type of pain is thought to arise from injuries of the local nerve roots and dorsal horn gray matter. This pain may be provoked or exacerbated by activity or changes of position. It can also be a sign of post-traumatic syringomyelia developing near the level of the injury. It should be evaluated with neuroimaging with MRI to rule out syringomyelia, which might further compromise the injured cord.[7] Below-level, or distal, neuropathic pain is pain perceived below the level of spinal cord injury. It can take many forms clinically. This type of pain is attributed to deafferentation due to injury of the

spinothalamic tract and thalamic deafferentation. Without the continuous nerve tract going from the spinal synapses in the dorsal horn to the thalamus, the thalamic nuclei are thought to become hyperexcitable, developing aberrant activity and nerve pain in the distribution of the interrupted tracts. This pain, since it arises from a malfunctioning central nervous system, is generally independent of position or activity. As a central pain, it is often highly resistant to medical management.[8]

5. What form does visceral pain take in SCI patients? Visceral pain is usually described as burning, cramping, fluctuating, or spasmodic. As in other pain patients, the pain is often perceived as “deep” but vaguely localized, and is sometimes referred to other parts of the body. The pain is not always related to abnormal findings on examination.[9]

6. What other painful conditions are SCI patients prone to? Spasticity and contractures are commonly seen in immobile muscles as sequelae of SCI. The prolonged lack of movement and shortening leads to consolidation and tightening of the collagen matrix in muscles, causing them to become increasingly tight and inflexible. This progressive tightening, exacerbated by immobility and physical deconditioning, may predispose patients to pain and loss of function.[10]

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Chapter 2: Patient with spinal cord injury pain

Spasticity is related to the loss of inhibition from upper motor neurons, leading to increased activity and excitability in skeletal muscles. While spasticity has some health benefits, such as facilitating transfers and improving venous tone, it can also be associated with uncomfortable positions and painful muscle cramps. Preventive treatments for spasticity include regular stretching and braces. Oral medications for spasticity include baclofen, tizanidine, and dantrolene, but their effectiveness is limited and side effects are common. Diazepam has previously been used extensively together with tizanidine and baclofen, but it is problematic since it is a controlled substance with high abuse potential and carries risks of sedation and withdrawal.[11] Focal areas of spasticity can be addressed with local injections of chemodenervation agents such as onabotulinum, which are effective for 3–4 months. More permanent denervation can be achieved through neurolytic agents such as alcohol or phenol. All of these treatments inhibit lower motor neuron effects, decreasing spasticity, but can have effects including neuropathy, decreased function, and systemic spread of agents. Intrathecal drug pumps allow direct access to the CNS, bypassing the blood–brain barrier and avoiding the first-pass effect. This route of administration makes baclofen much more effective at much lower overall doses. As with intrathecal medications for pain, patients generally have a trial of intrathecal baclofen as a one-time injection, followed by objective assessments of residual spasticity symptoms, before the decision is made for implantation. With either oral or intrathecal baclofen, abrupt discontinuation (as can occur after pump failure or catheter fracture) can result in a severe and life-threatening discontinuation syndrome. Those body parts that retain innervation and full function, typically the upper extremities and shoulders, are prone to overuse injuries and pain. The complexities of post-SCI rehabilitation go beyond the scope of this book, but some observations are worthwhile. Shoulder injuries are most common, as patients “use their shoulders as replacements for hips” with wheelchairs and transfers. Wrists, elbows, and hands are also common sites of injury. Rotator cuff injuries are common, along with a variety of other overuse-related bursitis conditions and tendinopathies, osteoarthritis of the overused joints, and carpal tunnel syndrome. Musculoskeletal pain tends

18

to be sharp, dull, or aching and is related to movement and use.[12–14] Preventive strategies include education and rehabilitation for safe transfer practices, such as the strengthening and optimal movements for painful shoulders (STOMPS) program.[15] Ergonomic assessments may be helpful by specialized PT or occupational therapy (OT) services. In some cases, the use of powered wheelchairs may be helpful to preserve upper extremity function. The loss of regular exercise resulting from the switch to a powered wheelchair should be made up with other suitable physical activities, as SCI patients are already at high risk for metabolic complications and heart disease.

7. What other conditions must the pain provider be aware of? Painful conditions in SCI may be complicated by autonomic dysreflexia in cases where the level of injury is at or above T6.[16] This phenomenon of disinhibited sympathetic reflexes is due to the interruption of descending control by sympathetic fibers. These fibers balance the sympathetic and parasympathetic tone to meet the current needs for blood pressure, heart rate, and other autonomic nervous system functions. Noxious stimuli below the level of injury have the potential to trigger a sympathetic “storm” which, if unopposed, can cause severe hypertension, sweating, anxiety, nausea, bradycardia, or tachycardia. The noxious stimuli include pressure sores, fractures, bladder distention, fecal impaction, or distention of other hollow organs. This condition exists along a clinical spectrum ranging from mild hypertension and headache to seizures, stroke, and even end organ failure.[17] Autonomic dysreflexia often develops within months of injury.[18] When this condition is recognized, it may be treated immediately by placing the patient in the upright position, treating their blood pressure, and instituting a methodical examination for possible etiologies, including bladder catheterization and rectal exam, examination of integument and extremities, and possibly obtaining x-ray images. This condition may be treated preventively with antihypertensives as well as avoidance of triggers. This condition is of relevance to pain providers since they are likely to see SCI patients with pain complaints, and they may also cause unintentional discomfort to the patient in the

Chapter 2: Patient with spinal cord injury pain

process of their examination and interventional treatment.

8. What is the relevance of heterotopic ossification? A frequent complication of SCI is heterotopic ossification. This is a form of abnormal bone deposition in the soft tissues adjacent to the large joints below the level of injury. Stem cells near the joints that are normally inactive are switched on by changes associated with SCI. They differentiate into osteoblasts, and secrete disorganized bone around the joints. These depositions of bone cause pain and decreased movement due to inflammation and stiffening of tissues. This condition can mimic local infection, tumor, arthritis, and other diagnoses. These bone deposits take a month or more to be visible on radiographs. Serum alkaline phosphatase levels may be elevated. The most sensitive and specific test is a three-phase bone scan. Heterotopic ossification may respond to NSAIDs and range of motion exercises.[19] Medications commonly used for osteoporosis such as etidronate and bisphosphonates have also been reported to be effective.[19] In severe cases, surgery and radiotherapy have been used to halt progression and restore joint function.[20]

9. What work-up might be helpful to clarify pain diagnosis in an SCI patient? All SCI patients should have a thorough evaluation determining their level of injury and deficits due to SCI documented, so that new deficits or problems can be recognized. New deficits or development of at-level pain should prompt MRI scan of the affected area to rule out post-traumatic syrinx. Physical examination of the patient, including observation while sitting in a chair and during transfers, helps with identification of musculoskeletal problems and overuse syndromes. Documentation of the nature and severity of pain complaints and accompanying sensory abnormalities assists in longitudinal observation and identifying gradual improvement. A panel of experts has determined that the standard 10-point rating scale is reasonable for assessing pain severity, and the 7-Point Guy/Farrar Patient Global Impression of Change (PGIC) scale is recommended for global ratings of pain, while pain interference ratings are best used in assessing the functional impact of their pain.[21]

10. What are the pharmacologic treatments available for patients with SCI pain? Tricyclic antidepressants and membrane stabilizers are the most commonly used treatments, but often have limited benefit. Pregabalin may be more effective than other membrane stabilizers.[22] A large systematic review found that gabapentin and pregabalin appeared to have the greatest effectiveness in management of post-SCI pain.[11] Tricyclic antidepressants and SNRI antidepressants such as duloxetine may be beneficial, particularly in patients with comorbid depression. IV analgesics such as ketamine, opioids, and lidocaine had short-term benefits. Opioids have been used with limited success in the management of this type of pain.[23]

11. Are there interventional treatments that have been shown to be beneficial for SCI patients? Chemodenervation and neurolysis have been used for specific neuropathies and spasticity. Neurosurgical procedures of nerve root or spinal cord tract destruction have also been used for SCI-related pain, including rhizotomy, dorsal root entry zone (DREZ), myelotomy, cordotomy, and cordectomy.[24]

12. What are the non-pharmacologic treatments effective for SCI pain? Pharmacotherapy has limited benefits in some patients, who are unable to take the optimal dose of medications due to adverse side effects. Other nonpharmacologic approaches should be tried; these include acupuncture and biofeedback, which have been used for treatment-resistant SCI pain.[17] For specific functional or mechanical issues physical therapy can be especially helpful. Transcutaneous nerve stimulations (TENS) and massage can be effective in some patients. Cannabis has been used as a pain reliever in SCI, but has not been studied well. It is reported to benefit central pain and spasticity in SCI. While there are many anecdotal reports of benefit, it is noted to have a narrow therapeutic window and study results have been mixed and not very impressive.[25]

19

Chapter 2: Patient with spinal cord injury pain

13. Are there particular issues or sensitivities that you need to be aware of when working with SCI patients? Depression is extremely common after SCI with rates of more than 40% within the first few months. Suicide rates for the first 5 years after SCI are dramatically higher compared to age-matched uninjured controls.[26,27] Since depression is a risk factor for suicide and is also associated with worsening outcomes in pain treatment, it is important to screen SCI patients for depression regularly even if that is not the focus of treatment.

Summary Pain significantly amplifies suffering in people with spinal cord injury, and diminishes their quality of life. Pain following SCI is very common, and one of the most difficult problems to manage. The pain is likely maintained by a number of different pathophysiologic mechanisms; this suggests that using therapy

References 1.

2.

3.

4.

5.

20

DeVivo MJ, Chen Y. Trends in new injuries, prevalent cases, and aging with spinal cord injury. Arch Phys Med Rehabil. 2011; 92(3):332–338. National Spinal Cord Injury Statistical Center. The 2005 Annual Statistical Report for the Model Spinal Cord Injury Care Systems. Birmingham, Alabama: National Spinal Cord Injury Statistical Center. 2005. Frankel HL, Coll JR, Charlifue SW, et al. Long-term survival in spinal cord injury: a fifty year investigation. Spinal Cord. 1998;36(4):266–274. Siddall PJ, McClelland JM, Rutkowski SB, Cousins MJ. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain. 2003; 103(3):249–257. Burchiel KJ, Hsu FPK. Pain and spasticity after spinal cord injury: mechanisms and treatment. Spine. 2001;26(24S):S146–S160.

6.

7.

aimed at many different pain-related targets is more advantageous. The rapid progress of neuroscience research yields ever more potential techniques and targets for modulating pain. At the same time, the gap between laboratory bench and clinical application has grown wider, and the rate at which new treatments become available has been dwindling for some time.[28] Clinicians must therefore make the most of the medications that are currently available for treating this form of pain, particularly using neuropathic pain standbys such as tricyclic antidepressants and anticonvulsants.[29] The best available pharmacologic treatments provide only approximately 30% of people with a 50% reduction in their pain and have unacceptable side effects.[30] Combining pharmacological, interventional, and non-pharmacologic approaches is critical in these complicated pain patients, especially when dealing with their central pain. Pain continues to present a major challenge to those with spinal cord injury and their providers, and more research is urgently needed.

Simpson DM, Gracies J-M, Yablon SA, Barbano R, Brashear A. Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study. J Neurol Neurosurg Psychiatry. 2009;80(4):380–385. Wasner G, Lee BB, Engel S, McLachlan E. Residual spinothalamic tract pathways predict development of central pain after spinal cord injury. Brain. 2008;131(9): 2387–2400.

8.

Davidoff G, Roth E, Guarracini M, Sliwa J, Yarkony G. Functionlimiting dysesthetic pain syndrome among traumatic spinal cord injury patients: a crosssectional study. Pain. 1987; 29(1):39–48.

9.

Bockenek WL, Stewart PJ. Pain in patients with spinal cord injury. In Spinal Cord Medicine. Lippincott Williams & Wilkins. 2002: pp. 389–408.

10. Adams MM, Hicks AL. Spasticity after spinal cord injury. Spinal Cord. 2005;43(10):577–586.

11. Teasell RW, Mehta S, Aubut J-AL, et al. A systematic review of pharmacologic treatments of pain after spinal cord injury. Arch Phys Med Rehabil. 2010;91(5):816–831. 12. Gellman H, Sib IEN, Waters RL. Late complications of the weightbearing upper extremity in the paraplegic patient. Clin Orthopaed Rel Res. 1988;233:132–135. 13. Hastings J, Goldstein B. Paraplegia and the shoulder. Phys Med Rehabil Clin North Am. 2004;15(3):699–718. 14. Sinnott KA, Milburn P, McNaughton H. Factors associated with thoracic spinal cord injury, lesion level and rotator cuff disorders. Spinal Cord. 2000;38(12):748. 15. Mulroy SJ, Thompson L, Kemp B, et al. Strengthening and optimal movements for painful shoulders (STOMPS) in chronic spinal cord injury: a randomized controlled trial. Physical Therapy. 2011; 91(3):305–324. 16. Bycroft J, Shergill IS, Choong EAL, Arya N, Shah PJR.

Chapter 2: Patient with spinal cord injury pain

Autonomic dysreflexia: a medical emergency. Postgrad Med J. 2005;81(954):232–235. 17. Kirshblum SC, Priebe MM, Ho CH, et al. Spinal cord injury medicine. 3. Rehabilitation phase after acute spinal cord injury. Arch Phys Med Rehabil. 2007; 88(3):S62–S70. 18. Helkowski WM, Ditunno Jr JF, Boninger M. Autonomic dysreflexia: incidence in persons with neurologically complete and incomplete tetraplegia. J Spinal Cord Med. 2003;26(3):244. 19. Teasell RW, Mehta S, Aubut JL, et al. A systematic review of the therapeutic interventions for heterotopic ossification after spinal cord injury. Spinal Cord. 2010;48(7):512–521. 20. Freebourn TM, Barber DB, Able AC. The treatment of immature heterotopic ossification in spinal cord injury with combination surgery, radiation therapy and NSAID. Spinal Cord. 1999; 37(1):50.

21. Bryce TN, Budh CN, Cardenas DD, et al. Pain after spinal cord injury: an evidence-based review for clinical practice and research: report of the National Institute on Disability and Rehabilitation Research Spinal Cord Injury Measures Meeting. J Spinal Cord Med. 2007;30(5):421. 22. Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK. Pregabalin in central neuropathic pain associated with spinal cord injury: A placebocontrolled trial. Neurology. 2006;67(10):1792–1800. 23. Siddall PJ, Molloy AR, Walker S, et al. The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury. Anesth Analg. 2000;91(6): 1493–1498. 24. Denkers MR, Biagi HL, O’Brien MA, Jadad AR, Gauld ME. Dorsal root entry zone lesioning used to treat central neuropathic pain in patients with traumatic spinal cord injury: a systematic review. Spine. 2002;27(7):E177–E184.

25. Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 2010;70(18): 2409–2438. 26. North NT. The psychological effects of spinal cord injury: a review. Spinal Cord. 1999;37(10): 671. 27. DeVivo MJ, Black KJ, Richards JS, Stover SL. Suicide following spinal cord injury. Spinal Cord. 1991;29(9):620–627. 28. Cuatrecasas P. Drug discovery in jeopardy. Journal of Clinical Investigation. 2006;116(11): 2837–2842. 29. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen Hosp Psychiatry. 2009;31(3): 206–219. 30. Siddall PJ. Management of neuropathic pain following spinal cord injury: now and in the future. Spinal Cord. 2008;47(5): 352–359.

21

Section 1 Chapter

3

Neurological Disorders

Patient with poststroke pain Natalia Murinova, Claire Creutzfeldt, Daniel Krashin, and Alan David Kaye

Case study A 65-year-old woman presents to the emergency room complaining of severe right face and arm pain. She had been recovering from a minor stroke that she had suffered 3 months previously that had caused only numbness in her right side. This numbness had developed into tingling and then pain, especially to touch. Her arm felt “like it was on fire” almost continuously, to the point that she wanted to cut it off. She denied any other focal neurologic deficits. She has history of obesity, diabetes mellitus, and poorly controlled hypertension. She admitted to forgetting to take her amlodipine and aspirin occasionally. A detailed neurologic exam revealed subtle weakness on motor testing on the right side. Assessing the right side with light touch induced pronounced painful response (allodynia). Light pinprick induced an exaggerated amount of pain (e.g., hyperalgesia). Hyperalgesia was limited to right arm and torso and was not present distal to the beltline. Scratching with a pin along the upper arm produced a persistent “pricking” sensation in the hand (hyperpathia). Once the pain was “stirredup” in the right upper body and extremity, it persisted for over a minute. Her blood pressure was 205 mmHg systolic and her head CT showed an old lacunar infarct in the left medial thalamus.

origin is considered one of the most severe pain syndromes, with severe, burning hemibody pain contralateral to the thalamic lesion.[1] The poststroke pain belongs to a group of central pain syndromes. The first introduction to central pain was by Edinger in 1891.[2] The International Association for the Study of Pain (IASP) defines central pain as “pain initiated or caused by a primary lesion or dysfunction of the central nervous system” at levels of spinal cord, brainstem, or cerebral hemispheres.[3] Central poststroke pain (CPSP) is a type of central pain that occurs after a cerebrovascular accident. Patients with CPSP suffer from constant or intermittent pain, and can have changes of thermal sensation. The pain quality has been depicted as burning, freezing, and some people find it difficult to describe. Misdiagnosis and delay are common, especially if patients have cognitive and expression difficulties poststroke. Patients may also display spontaneous abnormal sensations and stimulus-evoked dysesthesia, allodynia, and hyperalgesia. Other painful syndromes such as headache, painful spasms, contractures, hemiplegic shoulder pain, and other musculoskeletal pain can further complicate the clinical presentation of CPSP.[1]

2. How common is poststroke pain? 1. What is the diagnosis explaining this patient’s pain? This patient has Déjerine-Roussy syndrome, a variant of poststroke pain (CPSP) caused by infarction in the thalamus. More than 100 years ago, Déjerine and Roussy characterized thalamic pain as “among the most spectacular, distressing, and intractable pain syndromes”.[1] Central poststroke pain of thalamic

19–74% of stroke patients suffer pain as a complication of stroke.[4] About 795 000 people suffer a stroke annually in the USA, 600 000 of which are first attacks; this means that at least 150 000 people develop stroke-related pain each year. There are more than 7 million stroke survivors alive in the USA today.[5] Stroke is a leading cause of disability and the third leading cause of death in the USA.[5] Central pain is less common in stroke than in spinal cord

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

22

Chapter 3: Patient with poststroke pain

Table 3.1. Number of patients with pain in three different disorders with central pain

Condition

Survivors in USA

Newly diagnosed

All pain

Central pain

Stroke

~7 000 000[5]

795 000[5]

19–74%[4]

1–10%[6]

MS

~211 000[7]

10 400 (estimate)

57.5%[8]

27%[8]

SCI

~273 000[9]

12 000[10]

81%[11]

34–67%[11,12]

~, approximately, as exact numbers are not obtainable.

injury (SCI) or multiple sclerosis (MS); however the incidence of stroke is greater than these disorders, and because of this central pain in stroke is much more commonly encountered than in the other conditions (Table 3.1).

3. What is the incidence of CPSP (epidemiology)? Estimates of the prevalence of CPSP range from 1 to 8%. This fraction of poststroke pain is related directly to the brain area affected by the cerebrovascular accident.[4] It has been estimated that in the USA at least 56 000 cases of CPSP occur each year, if we estimate 700 000 new and recurrent cases of stroke.[6]

Table 3.2. The most common forms of chronic poststroke pain

Poststroke pain type

Percentage of patients with stroke experiencing this kind of pain

Musculoskeletal pain

40%

Shoulder pain

20%

Headache

20%

Central poststroke pain

10%

Spasticity

7%

4. What painful conditions are commonly seen in poststroke patients? See Table 3.2 and Figure 3.1. Shoulder pain is commonly seen in hemiplegia. Studies report the incidence of hemiplegic shoulder pain to be 38% to 84%. The definition of shoulder pain and the time of diagnosis, and period from stroke onset to the development of pain and recognition of pain likely influence the numbers reported.[13–17] When headache types were analyzed poststroke, the most commonly seen types were tension-type headache and migraine; the persistent daily headaches were usually tension-type.[18,19] There is really not much literature to suggest the treatment of headaches in patients poststroke. We recommend using International Headache Society criteria for diagnosing the headache type, and depending on the diagnosis establishing the appropriate treatment.[20] Medication overuse mediated headache, which is commonly seen in headache clinics, especially in people with history of migraine or family history of migraine, was not studied in this population of patients. Further

Figure 3.1. Common types of chronic poststroke pain, showing their relative frequency and overlap in a stroke patient (figure designed by Authors).

research needs to be done if medication overuse mediated headaches are also present in this population of patients, and contribute to their worsening headaches. Some migraine patients, when overusing

23

Chapter 3: Patient with poststroke pain

medications for headaches, develop a cycle of daily or near-daily headaches, which is termed medication overuse headache.[21] Central poststroke pain has a reported incidence of from 2 to 8%; the actual figure is likely to be higher, but it is often misdiagnosed or missed due to difficulty of diagnosis.[22–24] Spino-thalamo-cortical pathway involvement appears to be the major factor in development of CPSP. The lesion level contributes to the associated symptoms and pain features.[22] CPSP can occur after a cerebrovascular accident affecting any level of somatosensory pathways of the brain – this includes medulla, thalamus, and cerebral cortex. The occurrence of CPSP is especially high if the location of the lesion is in the lateral medulla (Wallenberg’s syndrome) or thalamus (ventro-posterior part).[1] When measured 1 year after stroke, painful spasticity is present in 27% to 36% of patients who suffered stroke.[25]

5. What area of the brain injury correlates with the development of central poststroke pain? Sprenger et al tried to identify specific “central painrelated” thalamic nuclei using structural magnetic resonance imaging in poststroke patients. In this study they found that the “ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus” lesions correlate with development of thalamic pain. The implication is that structural imaging might be useful for early detection of patients at risk for CPSP, leading to the development of effective pre-emptive treatment.[26]

6. What is the likely mechanism of poststroke pain? What is the likely mechanism of CPSP? Central poststroke pain is likely influenced by a large number of factors with potentially complex interactions. There have been many suggestions as to the causes of central pain; however, they are not well understood. The central pain evolves very likely as a combination of multiple modulating pathophysiologic processes, which include attenuated central inhibition, imbalance of chemical stimuli, and central sensitization.[27] Central sensitization is thought to

24

be the main mechanism that is responsible for the chronic pain associated with the central nervous system. The associated features of central pain include increased activation of N-methyl-D-aspartate (NMDA) and sodium channels.[28] Evidence suggests that chronic pain can alter brain function. The phenomenon of central sensitization is thought to be a prolonged but reversible augmentation in the excitability and synaptic efficacy of the neurons in the central pain pathway.[29] The changes of the brain are seen in reduced neuronal firing threshold, augmented spontaneous firing, and heightened firing during repetitive stimulation.[30] There are many different areas of the central nervous system that have been associated with central sensitization caused by pain. Increased plasticity of the synapses in the CNS, alterations of receptor function, and acquired channelopathies all appear to play a role in this process of central sensitization. Activation of the microglia can cause an inflammatory response which also contributes to amplification of pain-related activity in the nociceptive networks of the CNS.[31]

What is the likely mechanism of shoulder pain? The prevalence of hemiplegic shoulder pain is proportional to the degree of weakness, therefore it is highest in patients presenting with a plegic shoulder.[32] The proposed mechanism underlying hemiplegic shoulder pain (HSP) is a subluxation of the shoulder joint in the setting of both sensory and motor deficits as well as limited passive range of motion. Adhesive capsulitis may be contributory,[33] as is spastic shoulder pain, which shows a pattern of adduction and internal rotation of the shoulder. Although HSP is often thought of as a musculoskeletal pain, a neuropathic component is suggested by the common association with chronic pain throughout the affected side as well as the location of infarction in areas responsible for pain perception and processing.[34]

What is known about spasticity after stroke? Hemihypesthesia is more frequently found in patients with spasticity of the upper and lower limb and is more frequent than in patients without sensory deficits (P ≤ 0.001).[35] In a study by Urban et al spasticity was reported in 42.6% of patients with initial central paresis.[35]

Chapter 3: Patient with poststroke pain

What is known about headache poststroke? There are not many studies addressing headache poststroke. About 10% of patients develop headache poststroke, many of them daily and persistent. Headache poststroke diagnosed using International Headache Society criteria[20] are most commonly tension-type headache and migraine. The mechanism specific to stroke is not addressed in the literature.

7. What is the work-up of poststroke pain? The first step in working up poststroke pain is a high clinical suspicion in patients with stroke. Many stroke survivors are unable to express their pain due to language or cognitive impairment. This group of patients is also less likely to receive adequate pain treatment.[36]

Diagnosis of CPSP Key to the diagnosis of CPSP is (1) the neuroimaging association (CT or MRI) of the pain with an infarct in the corresponding area of the brain and (2) the exclusion of any other causes of neuropathic pain.[1] A careful history and physical exam should be done to look for signs of peripheral nerve or tissue damage, focal neurologic deficits not consistent with the area of the infarction, and other common pain syndromes as discussed below. A depression screen should be considered as depression can exacerbate pain and vice versa, and this information may aid in the choice of pharmacologic treatment (below).

Hemiplegic shoulder pain work-up While shoulder MRI may reveal adhesive capsulitis,[33] or soft tissue injury, a shoulder x-ray will suffice to rule out causes such as fractures or dislocation.

8. What pharmacologic treatments are available for poststroke pain? What treatments are available for CPSP? Our rudimentary understanding of the pathophysiology and neurobiology underlying CPSP makes it challenging to develop novel treatment targets. Large controlled trials to guide the management of CPSP are lacking, in part due to the heterogeneity of the underlying strokes, and the variability in pain quality

and intensity as well as the individual response rate of affected patients.[37] The current drug of choice is the tricyclic antidepressant amitriptyline or the metabolite nortriptyline.[38] This recommendation is based on small studies, and side effects such as dry mouth, drowsiness, and constipation are common. Recommendations for other antidepressants such as venlafaxine and some selective serotonergic receptor inhibitors are based on good evidence supporting their effect on neuropathic pain.[39] Antidepressants should be considered in patients with concurrent depression. Other first-line agents include the antiepileptic drug lamotrigine[40] and gabapentin, whereby the evidence for the latter is extrapolated from its effectiveness in treating neuropathic pain syndromes.[41] There is no conclusive evidence for phenytoin, zonisamide, and topiramate effectiveness in CPSP.[42–44] The effect of opioids on CPSP is questionable (Table 3.3).[45]

What are the treatments available for hemiplegic shoulder pain? Whereas the neuropathic component of HSP may respond to pharmacologic treatment as described above (amitriptyline, lamotrigine, or gabapentin), non-pharmacologic treatments such as ice, heat, and soft tissue massage are commonly recommended. Strengthening of the shoulder girdle with physical therapy may reduce dislocation of the joint, while passive range of motion may reduce the risk of adhesive capsulitis. Many patients wear a shoulder sling at night and/or during ambulation to support the arm and to prevent upper extremity trauma. Overhead movement is best avoided to reduce the risk of subluxation. Non-steroidal anti-inflammatory agents have temporizing pain relief and can be used prior to physical therapy. Intramuscular BOTOX injections and neuromuscular electric stimulation may be helpful.[48] The prognosis for HSP is generally good, with most patients improved at 6 months.[49]

9. Are there any interventional treatments that have been tried for the treatment of patients with poststroke pain? Spinal cord and deep brain stimulation are not effective for CPSP.[50] Motor cortex stimulation fares

25

Chapter 3: Patient with poststroke pain

Table 3.3. Medications studied in central poststroke pain

Medication

Dosage

Number of patients; response to treatment

Notes

Amitriptyline[22]

75 mg[22]

15 patients; 10/15 patients responded[22]

Very effective

Carbamazepine[22]

750 mg[22]

15 patients; 5 of the 14 patients who completed the study responded No statistical significance[22]

Lamotrigine[40]

200 mg[40]

30 patients; 12/30 partial response[40]

Moderately effective

Gabapentin[46]

Up to 2400 mg

23 patients; only two had poststroke pain – not clear if it had effect on these patients

Moderate relief

Phenytoin[42]

150 mg[42]

2 case reports[42]

Significant toxicity

Topiramate[44]

50–200 mg 3 times daily[44]

3 patients; no patient showed CPSP relief[44]

Zonisamide[43]

200 mg[43]

2 case reports[43]

Pregabalin[47]

150–600 mg/day[47]

219 patients, placebo-controlled; no significant pain relief[47]

much better as a treatment for refractory CPSP, a stimulation electrode being placed contralateral to the side of the pain. Cortical stimulation via corticocortical and maybe cortico-thalamic pathways inhibits the perception of pain.[50,51]

10. What are some special concerns in poststroke pain? Chronic poststroke pain is one of the most devastating outcomes of stroke according to patients; however, research into the quality of life (QOL) of these patients is limited. Small studies have shown decreases in health-related QOL.[52] Poststroke shoulder pain in particular is associated with decreased QOL, although this finding is not related to actual functional impairment.[53] A Korean study of patients 6 months or more following stroke found that 42% complained of chronic pain, but their QOL did not differ significantly from that of other patients in the sample.[54] The population of stroke survivors is changing demographically. About half of stroke patients are now under 65 years of age, with a significant number of patients younger than 55, still in economically productive years. Traditionally stroke patients have been discharged to a variety of settings depending on their functional limitations, but expectations are relatively modest. Younger patients with longer life expectancies and milder strokes have greater

26

Well tolerated

expectations regarding restoration of function and quality of life. They have a variety of complex psychosocial needs in addition to the traditional rehabilitation issues, including concerns about independent living, social and occupational fun, functioning, and the ability to fill family roles.[55] It has been shown that the families of stroke survivors also suffer significantly.[56] Comorbid conditions such as poststroke pain and poststroke depression have a large impact on a patient’s ability to face these challenges, but these issues are often neglected, particularly in those patients who do not require extensive rehabilitation and supportive living environments. Many of these patients flounder when they return home and are not able to resume active lives or employment.[57] This is a great loss for the patients, who frequently perceive this as an important marker of recovery and suffer greatly from its absence.[58,59] It is also a large cost to the economy: it has been estimated that of the $65 billion annual cost of stroke in the USA, a third is accounted for by indirect costs related to lost productivity.[60] In the EU, indirect stroke costs make up a similar 31% of the 27 billion euro annual cost of stroke. Despite these large economic and personal impacts, polls of stroke patients suggest that they feel little attention is paid to their concerns about fatigue, employability, and function.[61] Stroke patients also feel significant losses of autonomy after stroke, and appear to benefit from increased support for independence during and after rehabilitation.[62]

Chapter 3: Patient with poststroke pain

Conclusion/summary Stroke is, as we have discussed, an increasingly common condition associated with very significant rates of disability, morbidity, and death among adults. In addition to the obvious neurologic deficits that many are left with, such as aphasia, loss of coordination or function in a limb, and difficulties with activities of daily living, many stroke patients also develop chronic pain conditions.[54] Along with depression, chronic pain is a very common complication of stroke that can have a large impact on a patient’s quality of life. Recognition of poststroke pain can be extremely challenging. Musculoskeletal pain conditions may not be recognized as being related to the stroke by the physician or the patient. Pain quality and distribution can vary among patients, and stroke patients frequently have more than one type of pain.[22] The highest diagnostic yield is probably obtained by careful assessment of the nature of the pain complaints, examination of sensory response, and correlation with neuroimaging data.[1] This should help determine the cause of pain and rule out other causes, but it should be noted that not every encountered CPSP is due to thalamic stroke.[22] Given the large proportion of stroke patients who develop chronic poststroke pain, pain symptoms should be routinely assessed by clinicians. Risk factors for developing poststroke pain are not fully

References 1.

Klit H, Finnerup NB, Jensen TS. Central post-stroke pain: clinical characteristics, pathophysiology, and management. Lancet Neurol. 2009;8(9):857–868.

2.

Edinger L. Giebt es central entstehende Schmerzen? Dtsch Z Nervenheilkd. 1891;1:262–282.

3.

Merskey H, Bogduk N. International Association for the Study of Pain. Task Force on Taxonomy. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. Seattle: IASP Press; 1994.

4.

Kim JS. Post-stroke pain. Expert Rev Neurother. 2009;9(5): 711–721.

5.

6.

7.

8.

understood, although it appears to be associated with paresis and sensory changes, and with comorbid depression.[63] It is not known whether CPSP shares any mechanisms or risk factors with other pain conditions attributed to central sensitization. The clinical usefulness of anticonvulsants in both types of pain disorders provides a suggestion that there is some common pathophysiology that is being addressed, possibly increased sensitization and excitability in the nociceptive nerve pathway. If this hypothesis proves correct, it may be possible to identify patients at increased risk for developing chronic pain early, and to institute preventive measures.[29] Since there are no gold-standard diagnostic criteria or treatments for chronic poststroke pain, treatment must be empirical, driven by the diagnosis and guided by patient response. Since an estimated 795 000 people each year in the USA have a new or recurrent stroke, this is a highly significant pain condition.[64] It is important to remember that poststroke pain patients may be affected simultaneously with many other sequelae, including fatigue, motor and sensory abnormalities, emotional lability, strained relationships, disability, and depression.[65] Many of these problems can respond to treatment; the challenge is to address them comprehensively. Improving the evidence base for treating complications and sequelae of stroke is imperative.

Center IS. Stroke Center Statistics. 2006; Statistics about strokes. Available at: http://www. strokecenter.org/patients/stats. htm (accessed 10/08/2013, 2013). Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics – 2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2006;113(6):e85–e151. Noonan CW, Kathman SJ, White MC. Prevalence estimates for MS in the United States and evidence of an increasing trend for women. Neurology. 2002;58(1):136–138. Österberg A, Boivie J, Thuomas KÅ. Central pain in multiple sclerosis: prevalence and clinical

9.

characteristics. Eur J Pain. 2005; 9(5):531–542. National Spinal Cord Injury Statistical Center. The 2005 Annual Statistical Report for the Model Spinal Cord Injury Care Systems. Birmingham, Alabama: National Spinal Cord Injury Statistical Center. 2005.

10. DeVivo MJ. Epidemiology of spinal cord injury. In Lin VW, Bono CM, Cardenas DC, eds. Spinal Cord Medicine Principles and Practice. New York, NY: Demos Medical Publishing. 2010: pp. 78–84. 11. Siddall PJ, McClelland JM, Rutkowski SB, Cousins MJ. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following

27

Chapter 3: Patient with poststroke pain

spinal cord injury. Pain. 2003; 103(3):249–257. 12. Finnerup NB, Johannesen IL, Sindrup SH, Bach FW, Jensen TS. Pain and dysesthesia in patients with spinal cord injury: a postal survey. Spinal Cord. 2001;39(5): 256–262. 13. Griffin JW. Hemiplegic shoulder pain. Physical Therapy. 1986; 66(12):1884–1893. 14. Wanklyn P, Forster A, Young J. Hemiplegic shoulder pain (HSP): natural history and investigation of associated features. Disabil Rehabil. 1996; 18(10):497–501.

24. Bowsher D. The management of central post-stroke pain. Postgrad Med J. 1995;71(840):598–604. 25. Watkins CL, Leathley MJ, Gregson JM, et al. Prevalence of spasticity post stroke. Clin Rehabil. 2002;16(5):515–522. 26. Sprenger T, Seifert CL, Valet M, et al. Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping. Brain. 2012;135(8):2536–2545.

15. Roy CW, Sands MR, Hill LD. Shoulder pain in acutely admitted hemiplegics. Clin Rehabil. 1994; 8(4):334–340.

27. Kumar B, Kalita J, Kumar G, Misra UK. Central poststroke pain: a review of pathophysiology and treatment. Anesth & Analg. 2009;108(5):1645–1657.

16. Bohannon RW, Larkin PA, Smith MB, Horton MG. Shoulder pain in hemiplegia: statistical relationship with five variables. Arch Phys Med Rehabil. 1986; 67(8):514–516.

28. Wiesenfeld-Hallin Z, Aldskogius H, Grant G, et al. Central inhibitory dysfunctions: mechanisms and clinical implications. Behav Brain Sci. 1997;20(3):420–425.

17. Teasell RW, McRae M. The painful hemiplegic shoulder. Phys Med Rehabil. 1998;12:489–500.

29. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011; 152(3):S2–S15.

18. Vestergaard K, Andersen G, Nielsen MI, Jensen TS. Headache in stroke. Stroke. 1993;24(11): 1621–1624. 19. Ferro JM, Melo TP, Guerreiro M. Headaches in intracerebral hemorrhage survivors. Neurology. 1998;50(1):203–207. 20. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629–808. 21. Tepper SJ, Tepper DE. Breaking the cycle of medication overuse headache. Cleveland Clin J Med. 2010;77(4):236–242. 22. Leijon G, Boivie J. Central poststroke pain: a controlled trial of amitriptyline and carbamazepine. Pain. 1989;36(1):27–36.

28

23. Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke pain. Pain. 1995;61(2):187–193.

30. McMahon SB, Lewin GR, Wall PD. Central hyperexcitability triggered by noxious inputs. Curr Opin Neurobiol. 1993;3(4): 602–610. 31. Saab CY. Pain-related changes in the brain: diagnostic and therapeutic potentials. Trends Neurosci. 2012;35(10):629-637. 32. Lindgren I, Jönsson A-C, Norrving B, Lindgren A. Shoulder pain after stroke: A prospective population-based study. Stroke. 2007;38(2):343–348. 33. Távora DGF, Gama RL, Bomfim RC, Nakayama M, Silva CEP. MRI findings in the painful hemiplegic shoulder. Clin Radiol. 2010; 65(10):789–794. 34. Zeilig G, Rivel M, Weingarden H, Gaidoukov E, Defrin R. Evidence of a neuropathic origin in

hemiplegic shoulder pain. Pain. 2013;154(2):263–271. 35. Urban PP, Wolf T, Uebele M, et al. Occurence and clinical predictors of spasticity after ischemic stroke. Stroke. 2010; 41(9):2016–2020. 36. Kehayia E, Korner-Bitensky N, Singer F, et al. Differences in pain medication use in stroke patients with aphasia and without aphasia. Stroke. 1997;28(10):1867–1870. 37. Gordon A. Best Practice Guidelines for Treatment of Central Pain after Stroke. Central Neuropathic Pain: Focus on Poststroke Pain. Seattle: IASP Press. 2007. 38. Creutzfeldt CJ, Holloway RG, Walker M. Symptomatic and palliative care for stroke survivors. J Gen Intern Med. 2012;27(7): 853–860. 39. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007;4(4). 40. Vestergaard K, Andersen G, Gottrup H, Kristensen BT, Jensen TS. Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology. 2001;56(2):184–190. 41. Serpell MG. Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial. Pain. 2002;99(3):557–566. 42. Cantor FK. Phenytoin treatment of thalamic pain. Br Med J. 1972; 4(5840):590. 43. Takahashi Y, Hashimoto K, Tsuji S. Successful use of zonisamide for central poststroke pain. J Pain. 2004;5(3):192–194. 44. Canavero S, Bonicalzi V, Paolotti R. Lack of effect of topiramate for central pain. Neurology. 2002; 58(5):831–832. 45. Frese A, Husstedt IW, Ringelstein EB, Evers S. Pharmacologic treatment of central post-stroke pain. Clin J Pain. 2006;22(3): 252–260.

Chapter 3: Patient with poststroke pain

46. Attal N, Brasseur L, Parker F, Chauvin M, Bouhassira D. Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study. Eur Neurol. 1998;40 (4):191–200. 47. Kim JS, Bashford G, Murphy TK, et al. Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain. 2011;152 (5):1018–1023. 48. Singh JA, Fitzgerald PM. Botulinum toxin for shoulder pain. Cochrane Database Syst Rev. 2010;9. 49. Gamble GE, Barberan E, Laasch HU, et al. Poststroke shoulder pain: a prospective study of the association and risk factors in 152 patients from a consecutive cohort of 205 patients presenting with stroke. Eur J Pain. 2002; 6(6):467–474. 50. Katayama Y, Yamamoto T, Kobayashi K, et al. Motor cortex stimulation for post-stroke pain: comparison of spinal cord and thalamic stimulation. Stereotact Funct Neurosurg. 2002;77(1–4): 183–186. 51. Rasche D, Ruppolt M, Stippich C, Unterberg A, Tronnier VM. Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain. 2006;121(1): 43–52. 52. Widar M, Ahlström G, Ek AC. Health-related quality of life in persons with long-term pain after

a stroke. J Clin Nurs. 2004;13(4): 497–505. 53. Chae J, Mascarenhas D, Yu DT, et al. Poststroke shoulder pain: its relationship to motor impairment, activity limitation, and quality of life. Arch Phys Med Rehabil. 2007;88(3):298–301. 54. Kong K-H, Woon V-C, Yang S-Y. Prevalence of chronic pain and its impact on health-related quality of life in stroke survivors. Arch Phys Med Rehabil. 2004;85(1): 35–40. 55. Wolf TJ, Baum C, Connor LT. Changing face of stroke: Implications for occupational therapy practice. Am J Occup Ther. 2009;63(5):621–625. 56. Visser-Meily A, Post M, Schepers V, Lindeman E. Spouses’ quality of life 1 year after stroke: prediction at the start of clinical rehabilitation. Cerebrovasc Dis. 2005;20(6):443–448. 57. Banks P, Pearson C. Improving Services for Younger Stroke Survivors and their Families. Edinburgh: Chest Heart and Stroke Scotland. 2003. 58. Alaszewski A, Alaszewski H, Potter J, Penhale B. Working after a stroke: survivors’ experiences and perceptions of barriers to and facilitators of the return to paid employment. Disabil Rehabil. 2007;29(24):1858–1869. 59. Vestling M, Tufvesson B, Iwarsson S. Indicators for return to work after stroke and the importance of work for subjective well-being and life

satisfaction. J Rehabil Med. 2003; 35(3):127–131. 60. Di Carlo A. Human and economic burden of stroke. Age Ageing. 2009;38(1):4–5. 61. Bendz M. The first year of rehabilitation after a stroke: from two perspectives. Scand J Caring Sci. 2003;17(3):215–222. 62. Proot IM, Abu-Saad HH, de Esch-Janssen WP, Crebolder HFJM, ter Meulen RHJ. Patient autonomy during rehabilitation: the experiences of stroke patients in nursing homes. Int J Nurs Stud. 2000;37(3): 267–276. 63. Lundström E, Smits A, Terént A, Borg J. Risk factors for strokerelated pain 1 year after first-ever stroke. Eur J Neurol. 2009;16(2): 188–193. 64. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart Disease and Stroke Statistics – 2012 Update: A Report From the American Heart Association. Circulation. 2012;125(1):e2–e220. 65. Jönsson A-C, Lindgren I, Hallström B, Norrving B, Lindgren A. Prevalence and intensity of pain after stroke: a population based study focusing on patients’ perspectives. J Neurol Neurosurg Psychiatry. 2006;77(5): 590–595. 66. Siniscalchi A, Gallelli L, De Sarro G, Malferrari G, Santangelo E. Antiepileptic drugs for central post-stroke pain management. Pharmacol Res. 2012;65(2): 171–175.

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Section 1 Chapter

4

Neurological Disorders

Patient with brachial plexopathy Jonathan Chang and Rahul Rastogi

Case study A 25-year-old male football player complains of new right upper extremity numbness and weakness. Symptoms are such that he is unable to catch an American football; however he is able to loosely hold a can of soda. He states the symptoms started after a motorcycle accident 1 week ago and have got worse. The pain from the accident has improved, but the numbness and weakness are unchanged and a little worse. The patient rates his pain at a 3/10 with radiation down his arm from his shoulder to his fingers. Physical exam is remarkable for a well-developed male with prominent upper-body musculature. There is no noted edema, cyanosis, or clubbing of the upper extremity. There are equal strong bilateral radial pulses, 2+ biceps reflexes on the left, 5/5 strength of the left upper extremity, 1+ biceps reflex on the right, 3/5 shoulder abduction, 3/5 biceps flexion, 3/5 wrist extension, and 4/5 strength to the intrinsic muscles of the hand. Tinel’s sign is negative, bilaterally.

The spinal nerve roots C5 to T1 merge to form 3 trunks: the upper trunk from C5 and C6, the middle trunk from C7, and the lower trunk from C8 and T1. Each trunk further divides into anterior and posterior divisions. The anterior divisions of upper and middle trunk form the lateral cord while the anterior division of the lower trunk becomes the medial cord. All three posterior divisions merge to form the posterior cord. The cords are named medial, lateral, and posterior because of their anatomic relationship to the axillary artery. The cords form 5 terminal nerves: the medial cord forms the ulnar nerve, the lateral cord forms the musculo-cutaneous nerve, the medial and lateral cord together form the median nerve, and the posterior cord forms the axillary and radial nerves.

3. Clinical classification of brachial plexopathies

The brachial plexus is a complex web of anterior rami of spinal nerves arising from cervical spine and situated in the neck and shoulder. It provides both sensory and motor nerve supply to the ipsilateral shoulder and upper extremity. Anatomically, the brachial plexus is vulnerable to injury resulting in abnormal function and/or sensation of the ipsilateral shoulder and upper extremity. This constellation of symptoms is termed “brachial plexopathy.”

Brachial plexus lesions are classified into three broad categories in relation to the clavicle: (1) supraclavicular – constitutes mainly roots and trunk; (2) retroclavicular – mainly divisions; and (3) infraclavicular – comprising cords and terminal nerves of the brachial plexus. Supraclavicular plexopathies are the most common type, while retroclavicular plexopathies remain rare. On the basis of trunk involvement, supraclavicular plexopathies are divided into: upper (C5 and 6 root and upper trunk), middle (C7 root and middle trunk), and lower (C8 and T1 root and lower trunk).

2. Describe the anatomy of the brachial plexus

4. What is the epidemiology of plexopathies?

The brachial plexus is composed of 5 nerve roots, 3 trunks, 6 divisions, 3 cords, and 5 terminal nerves.

Brachial plexus injuries occur in ~1% of trauma patients. Young males (average age in 20s) are at higher

1. What is brachial plexopathy?

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 4: Patient with brachial plexopathy

risk for this type of injury. Motor vehicle accidents lead to traumatic etiology, while other types of accidents, e.g., sports injuries, work injuries, and recreational activity injuries, are less common in brachial plexus injuries. Traction/traumatic injuries to the brachial plexus can also result from poor surgical positioning. Supraclavicular injuries are predominant and account for ~60% of injuries. Infraclavicular injuries account for the remaining ~40%. Supraclavicular injuries also tend to be more severe than infraclavicular injuries.

5. What are the causes and mechanisms of brachial plexopathies? Traction, compression, laceration, contusion, ischemia, and inflammation are the predominant mechanisms involved in brachial plexopathies (Table 4.1). Table 4.1. Causes and mechanism of brachial plexopathies

Mechanisms

Causes

Traction

Trauma, iatrogenic, obstetric, surgical positioning, avulsion, sports injuries

Compression

Trauma, metastatic tumor, thoracic outlet syndrome, Pancoast syndrome, use of crutches

Laceration

Trauma, open brachial plexus injury

Contusion

Trauma

Ischemia

Trauma, vascular

Inflammation

Trauma, radiation neuritis

Intraneural factors

Primary nerve neoplasm, i.e., neurofibromatosis

6. What happens to nerves in plexopathy? Injury to nerves was classified by Seddon (1943) (Table 4.2).These injuries are progressively worse: ischemia > demyelination > axonotmesis > neurotmesis.

7. Describe the clinical presentation of brachial plexopathies Brachial plexopathies present with muscle weakness and atrophy, sensory loss or paresthesias, and pain. Clinical presentation varies with the level of the lesion or the type of plexopathy. Careful history and physical examination help make the diagnosis by elucidating the mechanism and possible anatomic level of injury (Table 4.3). Supraclavicular plexopathies present in a segmental distribution. Supraclavicular upper trunk plexopathies are most common and often result from trauma and traction. These plexopathies have the best prognosis. Supraclavicular root plexopathies, i.e., nerve root avulsions, are uncommon and carry a poor prognosis. Tumor spread and compression are a common source of supraclavicular lower trunk plexopathies and may be associated with Horner’s syndrome. In contrast, infraclavicular plexopathies lack segmental distinction, but symptoms present in specific terminal nerve distributions

8. What is the differential diagnosis? a. Nerve root avulsion b. Acute brachial plexus neuritis (Parsonage–Turner syndrome)

Table 4.2. Types of nerve injury

Nerve injury

Neural structural damage

Prognosis

Affects myelin

Incomplete axonal damage

Present

No

AXONOTMESIS (axon damage with preservation of connective tissues)

Yes

Yes

NEUROTMESIS (complete transection of axon including connective tissues)

Yes

Yes

NEUROPRAXIA Ischemic Demyelination

Complete transection of axon

No Conduction block across nerve injury Days to months to recover

Good

No Distal axonal degeneration Recovery depends upon extent of nerve damage

Fair

Yes Distal axonal degeneration Regeneration if axons in aberrant path and forms neuroma

Poor

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Chapter 4: Patient with brachial plexopathy

Table 4.3. Clinical presentation of brachial plexopathy

Type of plexopathy

Motor

Sensory

Reflexes

Supra/infraspinatus (arm external rotation), deltoid (arm abduction), biceps, and brachioradialis (elbow flexion) Partial weakness in forearm pronation, wrist flexion, and elbow extension Weakness of elbow, wrist, and finger extension, wrist flexion, forearm pronation All ulnar and median innervated muscle + C8 radial innervated muscles Weakness of hand grip, inability to full flexion of fingers, partial weakness of finger & wrist extension

Decreased sensation lateral upper arm (axillary n.), lateral forearm (lateral ante-brachial cutaneous n), and lateral hand and 1–3 digits (post. cutaneous n.) Decreased sensation to posterior forearm, hand over middle finger

Biceps Brachioradialis

Altered sensation in medial arm, medial forearm, medial hand, and 4&5 digits

None

Lateral forearm and digits 1–3 Lateral arm (axillary n.), posterior arm and forearm (posterior cutaneous n.), radial dorsum of hand (superficial radial n.) Altered sensation in medial arm, medial forearm, medial hand, and 4&5 digits

Biceps reflex Triceps Brachioradialis

Widespread sensory loss

All reflexes absent

S U P R A C L A V I C U L A R

Upper trunk (C5, C6) (most common)

I N F R A C L A V I C U L A R

Lateral cord Posterior cord

Wrist flexion, elbow flexion Weakness in finger, arm, wrist extension (wrist drop), weak shoulder ab/ adduction

Medial cord (same as lower trunk except preservation of C8 fibers)

Weakness of grip, weak hand muscles

Middle trunk (C7) (rare) Lower trunk (C8, T1)

PAN PLEXOPATHY

c. d. e. f. g. h. i. j.

Deficit

Weakness of all upper extremities, except rhomboids and serratus anterior function

Thoracic outlet syndrome Cervical radiculopathy Carpel tunnel syndrome Radial neuropathy Ulnar neuropathy Myelopathies Pancoast tumor, syringomyelia, schwannomas Complex regional pain syndrome

Our patient suffers from traumatic nerve root avulsion.

32

Triceps reflex

None

9. How do you diagnose nerve root avulsion/brachial plexopathies? As mentioned previously, a detailed history and physical exam is central to making the correct diagnosis. In particular, the history of upper-body trauma with associated motor deficits (weakness, loss of function, and atrophy of muscles), sensory deficits (paresthesias and numbness), and/or diminished reflexes in the targeted limb strongly suggest nerve root avulsion.

Chapter 4: Patient with brachial plexopathy

Several other diagnostic tools are helpful in making the diagnosis. a. Electromyography/nerve conduction studies. EMG is a complex diagnostic test in the evaluation of brachial plexopathy in the presence of several nerves, roots, trunks, and divisions. Usually this examination includes: i. sensory and motor evaluation of ulnar, median, and radial nerve ii. Needle examination of targeted muscles Sensory exam helps differentiate preganglionic lesions from postganglionic peripheral nerve lesions, because the sensory exam is normal with lesions proximal to dorsal root ganglion. Electroneuromyography (EMGNCV) also helps in differentiation of neuropraxia and axonotmesis/neurotmesis. b. Imaging of cervical spine and shoulder – MRI/CT scan/x-rays. Imaging of cervical spine helps in ruling out any traumatic avulsion, degenerative cervical spine, shoulder, or spinal pathology. It also diagnoses any compressive etiology, i.e., tumor, hematoma, accessory muscles/bands, or ribs. c. Chest and neck x-ray to check for spine, rib cage, or collarbone abnormalities d. Imaging of brachial plexus – MRI/ultrasound. Direct evaluation of brachial plexus rules out any obvious damage and compression causing plexopathy. e. Complete blood count, basic metabolic profile, erythrocyte sedimentation rate, antinuclear antibody assay, biopsy.

10. What other disease processes mimic traumatic nerve root avulsion? There are several disease entities that mimic traumatic nerve root avulsion. Some common diseases are Parsonage–Turner syndrome, cervical radiculopathy, thoracic outlet syndrome (TOS), and complex regional pain syndrome (CRPS) of upper limb (Table 4.4). A detailed history and physical exam is key to differentiating among these entities.

11. How should I treat this patient? Pain and abnormal physical exam findings are common in nerve root avulsion. Depending upon

the level of injury, different care paths should be considered. In a patient with an open injury and neural loss immediate surgical evaluation is recommended. If appropriate, surgical repair should be attempted. In contrast, a patient with a closed injury should initially undergo conservative treatment. Treatment goals include: a. Improving pain relief. Patient should be prescribed analgesics, ranging from OTC to prescription medications, i.e., acetaminophen, NSAIDs, muscle relaxants, opioids, etc. For the neuropathic component of pain, antiepileptics (i.e., gabapentin, pregabalin, etc.) and antidepressants (amitriptyline, nortriptyline, duloxetine, etc.) may be used (Table 4.5). TENS may also be helpful. A spinal cord stimulator should be tried if conservative medical treatments fail to control the pain. b. Improving function. Physical therapy should be routinely utilized to maintain and improve muscle function and strength. Sometimes assist devices, i.e., braces, splints, can help increase upper extremity function. Ergonomics, vocational rehabilitation, and occupational therapy are also helpful in improving function. c. Correcting the underlying etiologies. Nerve damage and/or nerve compression is sometimes amenable to surgical repair and/or surgical decompression. These types of surgery in addition to tendon transfer surgery can be very helpful in regaining a patient’s function. d. Intractable refractory pain (after the failure of the above therapies). Radiofrequency/surgical destruction of brachial plexus roots, i.e., DREZ lesions, amputation of brachial plexus/upper extremity may be an option.

12. Are there any complications to worry about following treatment? Persistent intractable pain, profound numbness, muscle atrophies, development of contractures, and joint deformities are extremely disabling outcomes of brachial plexopathies. Diminishing or loss of mobility results in osteopenia, skin breakdown/infection, depression, and anxiety. These complications often worsen a patient’s pain and slow recovery.

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34

Table 4.4. Differential diagnosis of brachial plexopathy

Nerve root avulsion

Idiopathic brachial neuritis (Parsonage–Turner syndrome, neuralgic amyotrophy)

Thoracic outlet syndrome (Cervical rib syndrome, scalenus anticus syndrome)

Cervical radiculopathy

Complex regional pain syndrome (CRPS) (Causalgia, reflex sympathetic dystrophy)

Onset

Acute

Acute

Sudden to gradual

Gradual to sudden

Varies

Location

Unilateral shoulder and UE

Unilateral shoulder >> bilateral and UE

Unilateral > bilateral neck, shoulder and UE

Most common roots involved C7 > C6

Unilateral, regional distribution

Etiology

Trauma

Surgery, infection, vaccination

Repetitive UE lifting

Disc herniation or DJD, tumors, infection

Trauma, tumor, stroke, idiopathic

Pain

Immediate sharp, severe pain and numbness in dermatome distribution

Sharp, severe pain usually resolves in a few weeks

Varied pain presentation along with paresthesias and numbness in UE

Varied pain with dermatome distribution

Varied pain with hyperalgesia and allodynia

Weakness

Immediate weakness in myotome distribution, atrophy of denervated muscles over time

As pain resolving, weakness ensues in proximal UE muscles

Varies

+/–

+/–

Motor: sensory deficit

Motor ¼ sensory

Motor >> sensory

Sensory >> motor Usually C8, T1 involvement

+/– Sensory > motor

Sensory > sudo/ vasomotor > motor Motor in late stages

Type of nerve involvement

Variable–complete

Incomplete

Variable–incomplete

Variable

Variable

Epidemiology

♂:♀ 2:1 Age: 20–60 years

♂:♀: 2:1 Age: 30–70 years

nTOS (85–90%)- ♂:♀ 1:3 vTOS (10–12%) – ♂:♀ 1:1 aTOS (2–4%) – ♂:♀ 1:1

Incidence 85:100 000 population

Incidence 1–5% ♂:♀ 1:3 Age: 10–70 years

Pathology

Avulsion

Immunemediated – inflammatory?

Compression of neurovascular bundle in thoracic outlet (brachial plexus (nTOS), subclavian vein (vTOS), subclavian artery (aTOS))

Inflamed nerve root/ compression

Includes: peripheral inflammation, peripheral sensitization, sympathetic– afferent coupling, immune dysfunction, central sensitization & cortical reorganization

Clinical presentation

Variable, in severe cases – numbness and immediate weakness followed by severe pain. Atrophy of affected muscles over time

Intense pain followed by proximal muscle weakness and atrophy of shoulder and UE

nTOS ¼ pain, paresthesias, "" on UE elevation nTOS ¼ swelling & cyanosis of UE, heaviness and pain aTOS ¼ claudicating cramping UE pain

Pain in affected nerve root dermatome with +/– sensory or/and motor deficit, precipitated by cervical spine movements

Regional presentation of pain, allodynia, weakness, atrophy, intermittent color changes, swelling, temperature differences

Risk factors

Age, gender, athlete, trauma

Preceding stress, illness

Age Repetitive heavy use of upper extremity

Heavy manual labor, smoking, operating vibrating equipment

Trauma

Diagnostics

EMG, MRI

EMG, spine imaging

MRI Scalene diagnostic blocks EMG-NCV

Spine imaging shows Cspine abnormalities, SNR diagnostic blocks

No specific diagnostic test

Management

Variable

Symptomatic Conservative – PT +/– OT, analgesics, oral prednisone Late surgical repair

Conservative – PT, medications Surgical repair

Prevention – PT, Conservative – analgesics, PT, cervical epidural steroid Surgical interventions

Symptomatic – analgesics Functional – PT, OT, GMI, psychotherapy Interventional – sympathetic blocks, SCS, sympathectomy, amputation

Outcome

Variable

Usually good prognosis Resolve in 6–18 months

Fair prognosis

Usually good

Varied, usually children have better prognosis

aTOS, arterial thoracic outlet syndrome; C-spine, cervical spine; DJD, degenerative joint disease of spine; EMG-NCV, electroneuromyography; GMI, graded motor imagery; MRI, magnetic resonance imaging; nTOS, neurogenic thoracic outlet syndrome; OT, occupational therapy; PT, physical therapy; SCS, spinal cord stimulation; SNR, selective nerve root; sTOS, symptomatic disputed thoracic outlet syndrome; UE, upper extremities; vTOS, venous thoracic outlet syndrome.

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Chapter 4: Patient with brachial plexopathy

Table 4.5. Common medications utilized for chronic pain management

Drugs/class

Mechanism

Concern

Dosages

ANALGESICS Unknown

Liver damage

325–4000 mg/d

Non-steroidal antiinflammatory drugs

Ibuprofen Naproxen Meloxicam Celecoxib

Decrease prostaglandins by inhibiting cyclo-oxygenase

GI irritation, renal effects, bleeding

200–2400 mg/d 250–1500 mg/d 7.5–15 mg/d 100–400 mg/d

Opioids

Hydrocodone Fentanyl Morphine Oxycodone Methadone Tramadol Tapentadol

Agonist to opioid receptors Tramadol – additional SSRI and NRI effect Tapentadol – additional NRI action

Nausea/ vomiting, constipation, drowsiness, respiratory depression Methadone-variable t1/2 Tramadol/tapentadol – caution with antidepressants

Variable Variable Variable Variable Variable 50–400 mg/d 50–600 mg/d

Tricyclics (amitriptyline, nortriptyline, desipramine) SNRI (duloxetine)

Modulation of neurotransmission of serotonin and norepinephrine

Sedation, tachycardia, urinary hesitancy, weight gain

Gabapentin Pregabalin

α2δ subunit of voltage-gated N-type Ca2+ channel modulation Na+ channel blockade Na+ channel blockade

Drowsiness, confusion, weight gain, rash LFT monitoring for carbamazepine

GABA-b agonist

Confusion, drowsiness, dizziness

Acetaminophen

ADJUVANT ANALGESICS Antidepressants

Antiepileptics

Lamotrigine Carbamazepine Muscle relaxants

Baclofen Cyclobenzaprine Methocarbamol

Unknown action on CNS

25–150 mg HS

20–90 mg/d 300–3600 mg/d 75–600 mg/d 100–600 mg/d 200–1200 mg/d 10–80 mg/d 10–60 mg/d 500–2000 mg/d

Alpha-2 adrenergics

Clonidine Tizanidine

α2 adrenergic agonism

Drowsiness, #BP, #HR LFT caution – tizanidine

01–0.3 TD patch 2–32 mg/d

Local anesthetic

Mexelitine

Na+ channel blockade

Liver toxicity, #BP

150–900 mg/d

Corticosteroids

Methyl prednisone Dexamethasone

Hyperglycemia, weight gain, edema, agitation

Variable 4–96 mg/d

BP, blood pressure; Ca2+, calcium; CNS, central nervous system; GABA, gamma aminobutyric acid; GI, gastrointestinal; HS, bedtime; HR, heart rate; LFT, liver function test; mg/d, milligram per day; Na+, sodium; NRI, norepinephrine reuptake inhibition; SNRI, serotonin– norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibition; t1/2, half-life; TD, transdermal.

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Chapter 4: Patient with brachial plexopathy

13. What is the prognosis of brachial plexopathies? Prognosis is highly variable with spontaneous and surgical recovery within days to months. Recovery may be complete or incomplete dependent on each patient’s particular type and degree of injury.

14. What are the social considerations in brachial plexopathy patients? Patients will need comprehensive support in all aspects of life. Patients will also need to adjust to new limitations in performance of their activities of

References 1.

http://www.aafp.org/afp/2000/ 1101/p2067.html (acute brachial plexus neuritis)

2.

Thompson RW. Challenges in the treatment of thoracic outlet syndrome. Tex Heart Inst J. 2012;39(6):842–843.

3.

4.

https://www.clinicalkey.com/ topics/anesthesiology/thoracicoutlet-syndrome.html Smania N, Berto G, La Marchina E, et al. Rehabilitation of brachial

5. 6.

daily living. Many of these patients are very physically active and are accustomed to independence. They may require psychologic counseling as they adjust to coping with these changes in their physical ability and occupational limitations.

Conclusions Brachial plexopathy is a very distressing syndrome for patients. These patients are often highfunctioning individuals who have a dramatic and rapid change in their functional abilities. There are very limited treatment options with highly variable efficacy.

plexus injuries in adults and children. Eur J Phys Rehabil Med 2012;48;483–506. http://www. minervamedica.it/en/getfreepdf/ qCwJ4qBn6KYLZ0kPMOr ZIH41iynTZ4WNlHUnn WtgkmaWYBozHilflyIK% 252FDlzLlS%252FmB5lTjX% 252BXSUdV43JbSRZAA%253D% 253D/R33Y2012N03A0483.pdf http://emedicine.medscape.com/ article/316888-followup#a2651

population. Neurosurgery. 1997; 40(6):182–188. 7.

Dubuisson AS, Kline DG. Brachial plexus injury: a survey of 100 consecutive cases from a single service. Neurosurgery. 2002; 51(3):673–683.

8.

Thompson RW. Challenges in the treatment of thoracic outlet syndrome. Tex Heart Inst J. 2012; 39(6):842–843.

Midha R. Epidemiology of brachial plexus injuries in a multitrauma

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Section 1 Chapter

5

Neurological Disorders

Phantom limb pain Jonathan Chang and Rahul Rastogi

Case study

2. What is phantom limb pain?

A 36-year-old male fractured his distal tibia following a motor vehicle accident 5 years prior to presentation and developed foot pain. Surgical fixation did not alleviate the pain which worsened and spread to his leg (below the knee). Treatments including analgesics, physical therapy, sympathetic blocks, and spinal cord stimulation were unsuccessful. Due to persistent pain, an above the knee amputation was performed 4 years following the initial injury. The pain abated for 2 weeks, but painful symptoms developed in the missing left leg and gradually worsened. The pain symptoms were continuous and described as “aching, tightening, and burning,” mainly localized to the distal third of the lower leg and foot. He also reports intermittent twitching and spasms at the stump. He currently takes methadone 20 mg twice a day, cymbalta 60 mg at bedtime, and baclofen 20 mg three times a day with partial benefit.

A range of unpleasant sensations from tingling to pain in the absent postamputation limb; it is a neuropathic type of pain.

1. What is postamputation pain? A variety of unpleasant sensations are experienced after limb amputation, also known as “postamputation pain” (PAP). This was first formally described as a medical problem by Paré in 1551. In 1871 Weir Mitchell described it in Civil War soldiers and termed it “phantom limb pain” (PLP). There are three different sensory experiences described after amputation: (1) non-noxious phantom sensation, (2) residual limb pain (stump pain) (RLP), and (3) phantom pain. Phantom pain commonly involves the limbs, but it can present as “phantom breast,” “phantom tooth,” “phantom testes,” or “phantom (body part)” surgical amputation pain.

3. Demographics/epidemiology of phantom pain? The incidence of PAP is as high as 90%. The phantom sensation occurs in almost all patients undergoing amputation, but the precise incidence of PLP or RLP is difficult to assess due to the overlap of different types of PAP. The incidence of PLP ranges from 45 to 78%. However, 75% of PLP patients report experiencing pain on the first day of amputation and the remaining 25% develop pain within 1–2 weeks. The prevalence of PLP decreases with time. PLP affects upper limbs (≈80%) more often than lower limbs (≈54%). Age, laterality, level of amputation, and gender do not affect prevalence.

4. What are the indications for amputation? Trauma, vascular abnormalities, ischemia, cancer, and intractable pain are common indications for limb amputation. PLP not only follows physical removal of a limb, but can affect a congenitally absent body part or neurologically deficient limb, i.e., palsy, stroke.

5. What are the risk factors for phantom limb pain? Several studies suggest risk of developing PLP after amputation is increased in:

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 5: Phantom limb pain

a. b. c. d. e.

Females Upper limb amputation Presence of pre-amputation pain Persistent residual limb pain Closer to the time since amputation

Table 5.1. Proposed mechanisms of phantom limb pain

Level

Mechanism

Peripheral

Peripheral sensitization: Up-regulation of voltage-gated sodium channel at peripheral neuroma and dorsal root ganglion Sympathetic–afferent coupling Both result in ectopic discharges, and hyperexcitability

Spinal

Lamina reorganization: Peripheral afferent non-noxious neurons (Lamina 3 & 4) forming new crosslinks with other afferent noxious neurons of different lamina (1 & 2) Central sensitization: Barrage of peripheral noxious input results in hyperexcitability and expansion of neuronal receptive field causes “wind-up” (up-regulation) of NMDA receptors

Supraspinal

Cortical reorganization: Amputated limb area taken over by adjacent body area on somatosensory and motor cortex Cortical motor-sensory dissociation Psychogenic

Stress, anxiety, depression, and other emotional factors contribute to triggering, exacerbation, or persistence of PLP.

6. What are the clinical symptoms and signs of phantom limb pain? PLP is a neuropathic pain that presents with a range of descriptors, e.g., tingling, burning, aching, shooting, gripping, knife-like, electrical shock, pricking, and numbing. It presents with a variable intensity on the affected side. Usually pain starts in the distal portion of missing limb and presents intermittently. PLP may be continuously present. Pain develops within the first few weeks. Rarely, it is precipitated in the amputated limb following a spinal or epidural anesthetic block later in life. Usually with time PLP dissipates, but persistence beyond 6 months indicates a poor prognosis. Some PLP patients experience shortening of missing limb (especially shortening of middle portion of missing limb, without affecting size of distal portion), thus the distal portion of limb, i.e., hands or feet feel very close to stump. This phenomenon is called “telescoping.” Telescoping is associated with relatively poor prognosis. RLP may coexist with PLP. RLP affects 5–10% of amputated limbs. It can present with stabbing, throbbing, and/ or aching pain associated with hyperalgesia and/or allodynia of affected stump. RLP can be spontaneous or as a result of a poorly fitted prosthesis. There may be focal neuromata accounting for RLP.

7. Describe the pathophysiology of phantom limb pain The exact mechanism of PLP pain is essentially unclear, but various theories are proposed. Broadly the postulated mechanisms are divided into peripheral, spinal, and supraspinal mechanisms (Table 5.1).

8. How is PLP diagnosed? PLP is diagnosed on the basis of history and examination. No specific diagnostic test is recommended.

9. Howisphantomlimbpainmanaged? PLP is sometimes debilitating and refractory to management. There is a distinct lack of specific treatment modality. A multidisciplinary, multimodal approach should be utilized. Treatment categories include: A. Pharmacological: i. Prevention of PLP: Pre- and perioperative pain control has some advantages in management of PLP and has shown decrease in PLP incidence. This can be effectively achieved by perioperative epidural/perineural analgesia or patient-controlled analgesia. ii. Management of PLP: Pain can be managed with analgesics, i.e., acetaminophen, nonsteroid anti-inflammatory (NSAID) agents. Opioids (tramadol, oxycodone, morphine, methadone, etc.) can be used in intractable pain. Use of adjuvants, i.e., antidepressants (nortriptyline, amitriptyline, mirtazapine, duloxetine, etc.), anticonvulsants (gabapentin, carbamazepine, pregabalin, etc.), NMDA antagonist (i.e., ketamine), and calcitonin have shown some benefit in management of PLP (Table 5.2).

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Chapter 5: Phantom limb pain

Table 5.2. Common medications utilized for chronic pain management

Drugs/class

Mechanism

Concern

Dosages

ANALGESICS Unknown

Liver damage

325–4000 mg /d

Non-steroidal antiinflammatory drugs

Acetaminophen Ibuprofen Naproxen Meloxicam Celecoxib

Decrease prostaglandins by inhibiting cyclooxygenase

GI irritation Renal effects Bleeding

200–2400 mg/d 250–1500 mg/d 7.5–15 mg/d 100–400 mg/d

Opioids

Hydrocodone Fentanyl Morphine Oxycodone Methadone Tramadol Tapentadol

Agonist to opioid receptors Tramadol – additional SSRI and NRI effect Tapentadol – additional NRI action

Nausea/vomiting, constipation, drowsiness, respiratory depression Methadone – variable long t1/2 Tramadol/tapentadol – caution with antidepressants

Variable Variable Variable Variable Variable 50–400 mg/d 50–600 mg/d

Tricyclics (amitriptyline, nortriptyline, desipramine) SNRI (Duloxetine)

Modulation of neurotransmission of serotonin and norepinephrine

Sedation, tachycardia, urinary hesitancy, weight gain

25–150 mg HS

Gabapentin Pregabalin

α2δ subunit of voltagegated N-type Ca2+ channel modulation Na+ channel blocker Na+ channel blockade

Drowsiness, confusion, weight gain, rash LFT monitoring for carbamazepine

Selective GABA-b agonist Unknown action on CNS

Confusion, drowsiness, dizziness

ADJUVANT ANALGESICS Antidepressants

Antiepileptics

Lamotrigine Carbamazepine Muscle relaxants

Baclofen Cyclobenzaprine Methocarbamol

20–90 mg/d 300–3600 mg/d 75–600 mg/d 100–600 mg/d 200–1200 mg/d 10–80 mg/d 2–32 mg/d 10–60 mg/d 500–2000 mg/d

Alpha-2 adrenergics

Clonidine Tizanidine

α2 adrenergic agonism

Drowsiness, #BP, #HR LFT caution – tizanidine

01–0.3 TD patch 2–32 mg/d

NMDA blockers

Ketamine

NMDA blockade

Delerium, "BP, "HR, cognition, hepatotoxicity, vesicopathy

10–240 mg/d PO 50–600 mg/d SC

Local anesthetic

Mexelitine

Na+ channel blocker

Liver toxicity, #BP

150–900 mg/d

Corticosteroids

Methyl prednisone Dexamethasone

Hyperglycemia, weight gain, edema, agitation

Variable 4–96 mg/d

2+

BP, blood pressure; Ca , calcium; CNS, central nervous system; GABA, gamma aminobutyric acid; GI, gastrointestinal; HS, bedtime; HR, heart rate; LFT, liver function test; mg/d, milligram per day; Na+, sodium; NMDA, N-methyl D-aspartate; NRI, norepinephrine reuptake inhibition; SSRI, selective serotonin reuptake inhibition; t1/2, half-life; TD, transdermal.

A. Non-pharmacological: Various non-pharmacologic modalities have shown mild to moderate benefit in PLP patients. These include:

40

i. Prosthesis: A properly fitted prosthesis has been shown to decrease the intensity of PLP.

Chapter 5: Phantom limb pain

ii. TENS: Use of TENs has shown some efficacy in PLP and RLP pain control. iii. Mirror therapy: Mirror therapy alone or as part of graded motor imagery (GMI) has shown significant benefit in management of PLP. The patient places the normal and amputated limbs into a box with a vertical mirror. The mirror reflects the normal limb and its motion. The patient cannot see the amputated limb since they are looking at the mirror reflection of the normal limb. Due to visuo-proprioceptive dissociation, via activation of mirror neurons in the brain, the PLP symptoms are reduced. iv. Biofeedback/behavioral therapies v. Acupuncture/external heat/cold and massages: Anecdotal evidence of some help. B. Injection therapies: Studies have shown variable benefit from perineural or regional nerve block in RLP, but benefit from injection therapies in PLP is limited. Various injectates including local anesthetics, botulinum toxin, corticosteroids, etc. are used in management of RLP with short-lasting benefit. C. Surgical therapies: Surgical modalities for pain management have variable outcomes; they are reserved for intractable and refractory PLP. Some efficacious modalities include: i. Neuromodulation: a. Peripheral nerve stimulation: It is useful in pain restricted to 1 or 2 peripheral nerve distributions, thus useful in RLP. b. Spinal cord stimulation: Modulation of painful signals at spinal level by use of spinal cord stimulator can provide significant relief and has proven successful in several neuropathic pain conditions. Extrapolation to PLP has proven to be less efficacious. c. Deep brain/motor cortex stimulation: Results for deep brain stimulation for PLP in various studies are suggesting a positive trend. Efficacy is unclear. ii. Dorsal root entry zone lesioning: Surgical lesion at dorsal root entry zone has been successful in management of PAP from brachial plexus avulsions, but studies are limited for lower extremity PAP.

iii. Stump revision: Selective RLP patients with specific neuroma benefit from stump revision or neuroma resection surgery. Outcomes are variable.

10. How to prevent phantom limb pain Not many things have been proven to decrease the risk of PLP. Studies have suggested that effective perioperative pain control decreases the risk of PLP after amputation. Studies recommend achieving effective pain control perioperatively by utilizing local, epidural, and perineural blocks and infusions with local anesthetics or intravenous patient-controlled analgesia 48 hours prior to amputation. These treatments should be continued for 48 hours after surgery.

11. How successful are these treatment modalities? Management of PLP is a challenging proposition, thus various treatment modalities are used for achieving pain control. Studies show limited benefit from pharmacologic agents. Ketamine and opioids (methadone, oxycodone, etc.) trials were statistically beneficial, while results of gabapentin, calcitonin, amitriptyline, and mexiletine are limited and conflicting. Graded motor imagery and mirror box consistently show significant relief in PLP patients. Studies show positive benefit especially for RLP and PLP with the use of prosthesis. In small series, neuromodulation, i.e., spinal cord stimulation and peripheral nerve stimulation, provides significant analgesia. Surgical modality studies are not shown to have any statistically significant benefit, and thus use of this modality is limited to refractory PLP patients.

12. How does this impact a person’s life? Refractory phantom pain is extremely debilitating to a patient’s physical, social, and emotional well being. The pain and loss of limb requires them to limit and/or adjust their activities. This feeling of handicap and dependency on others or aids is sometimes emotionally challenging resulting in anxiety and depression. If unchecked it can lead to suicidal thoughts. The patient

41

Chapter 5: Phantom limb pain

should be encouraged to seek psychotherapy and vocational rehabilitation early.

Conclusions PLP is a challenging life-changing health problem and its exact mechanisms are still unknown and treatments have variable and often poor outcomes. It also affects

References 1.

2.

42

Hsu E, Cohen SP. Postamputation pain: epidemiology, mechanisms, and treatment. J Pain Res. 2013;6:121–136. Knotkova H, Cruciani RA, Tronnier VM, Rasche D. Current and future options for the management of

3.

4.

patients’ physical, emotional, and socioeconomic status negatively. Current management strategies directed toward postulated mechanisms have at best provided limited efficacy. A multimodal approach should be utilized to address multifaceted effects of PLP. Further research on understanding of PLP mechanisms and development of treatments is needed to effectively manage this challenging health problem.

phantom-limb pain. J Pain Res. 2012;5:39–49. Lamont K, Chin M, Kogan M. Mirror Box Therapy – Seeing is believing. Explore. 2011;7:369–372. Weeks SR, Anderson-Barnes VC, Tsao JW. Phantom limb pain: theories and therapies. The Neurologist. 2010;16:277–286.

5.

Subedi B, Grossberg GT. Phantom limb pain: Mechanisms and treatment approaches. Pain Res Treat 2011;2011:864605.

6.

Vishwanathan A, Phan PC, Burton W. Use of spinal cord stimulation in the treatment of phantom limb pain: Case series and review of the literature. Pain Practice. 2010;10:479–484.

Section 1 Chapter

6

Neurological Disorders

Patient with post-thoracotomy pain Rinoo V. Shah

Case study A 44-year-old roofer fell and sustained a T7 burst fracture. He underwent emergent surgical repair requiring an anterolateral approach via a thoracotomy and underwent an anterior surgical stabilization. Two months postoperatively, he is referred for persistent surgical site pain.

1. What is the differential diagnosis? a. b. c. d.

Intercostal neuralgia Thoracic radiculopathy Pleuritis Scar neuromata

2. What is a neuroma? Neuromas are considered “tumors” of neural structures. In this instance, they are non-neoplastic. Neuromas typically form following surgical transection, trauma, or entrapment. Neuromas are considered to be discrete enlargements. If superficial, they may be palpable. If deeper, they may be visualized with noninvasive imaging tools (MRI, ultrasound).

3. Describe the clinical exam and how would one evaluate the differential diagnoses? Neuroma can be stimulated with normal palpation (allodynia). Painful stimuli over a neuroma may lead to an excessive or prolonged pain response, i.e., hyperalgesia and hyperpathia. Due to dysfunction of this neural tissue, there may be impairment in conduction. Motor function and sensory processing may

be dysfunctional. Autonomous and maladaptive reflexes may be present. In this patient’s case, the scar may be well healed. Although spontaneous and evoked pain may spill outside of the zone of the healed scar, neuroma are confined to the location of traumatic injury. Physical examination findings include a palpable and tender swelling. This is painful with light touch (allodynia). Deeper pressure leads to a more protracted (hyperpathic) and heightened (hyperalgesic) pain response. The scar should be healed. Poorly healing scars or ulcers should be addressed, before considering neuroma injections. Some healed surgical scars may demonstrate dystrophic or color changes. There may be a significant amount of allodynia, distributed around the scar. In this situation, there may be a heightened sympathetic response in addition to the presence of neuromas. Passive stretching of the scar or focal neuroma compression should elicit pain. This pain should be eliminated following a neuroma injection. Arguably, a pressure algometer may be useful: “an increase in the pressure pain threshold by 2–3 kg, immediately after the NI will indicate an effective injection.” Trigger points are commonly present in patients who have undergone surgery. This is especially true when the surgical scar injured a peripheral nerve, e.g., limb amputation or rib resection or retraction. Neuromas may be found in the surgical bed, in areas exposed to repetitive trauma, or in areas exposed to overuse. Neuromas may be confused with tender points, as is usually found in patients with fibromyalgia. Unlike fibromyalgia, neuromas are typically isolated and develop secondary to a specific event. Intercostal neuralgia is a peripheral nerve injury and is fairly discrete in its location when associated

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

43

Chapter 6: Patient with post-thoracotomy pain

with a stretch injury. Transection or traumatic injury (surgical blade as opposed to surgical retraction for exposure) is a more significant injury. Central and peripheral sensitization is more significant with this type of injury as compared to a stretch. Intercostal neuralgia may overlap with neuroma. The terminal branches that were injured may regrow eccentrically, given the damage to the axonal conduit. These nerves sprout and become enmeshed in scar tissue. Given the peripheral and central sensitization, clinical symptoms may be evoked with breathing, light touch, and palpation. There may be a widened receptor field, so the patient may feel pain outside the surgical site, at one-two dermatomes above and below. There may be altered sensibility, e.g., reduction in light touch but a heightened pain response with a low sensory threshold. Thoracic radiculopathy is plausible. This may occur from the initial burst fracture injury or during internal fixation with hardware and bone graft material. A delayed presentation of pain could be attributed to heterotopic bone growth that encroaches the nerve. Pleuritis may be local and somatic pain due to violation of the parietal pleura; visceral or deeper nagging and suffocating (feeling “stuck” in the chest) may be due to violation of the visceral pleura. Rib fractures may be a consideration, but at 8 weeks they should heal – healing bone pain should improve at this juncture. A cardiopulmonary and abdominal exam is important to distinguish other more urgent findings, specifically viscerally mediated pain. These could include intra-abdominal pathology, cardiac disease, and pulmonary dysfunction. These latter phenomena may be associated with other associated symptoms: dyspnea, palpitations, nausea, vomiting, and referred limb pain. Adjunct diagnostic tests may be necessary: electrocardiogram, upper gastrointestinal endoscopy, chest x-ray, pulmonary function tests, and exercise stress tests.

4. How do you diagnose the conditions listed in the differential diagnosis? Imaging studies would be helpful to evaluate other visceral pathology that is urgent or life threatening as outlined above. However, for the conditions listed in the differential diagnosis, imaging studies except diagnostic ultrasound are generally not as helpful as the physical exam and clinical history.

44

Diagnostic injections may be helpful. Thoracic radiculopathy could be treated with a nerve block or an interlaminar epidural injection with a catheter. The risks of a thoracic spinal nerve block in a patient with prior surgery is discussed in Chapters 59 and 60. A targeted thoracic interlaminar epidural injection with a catheter and administration of local anesthetic may be useful. Intercostal nerve blocks with local anesthetic may be helpful to diagnose intercostal neuralgia. Viscerosomatic pain from pleuritis may be diagnosed with an intrapleural injection which would block visceral pain (thoracic sympathetic chain) and somatic pain (thoracic spinal nerves).

5. How should one treat this condition? Conservative treatment methods are discussed in Chapters 5, 8, and 10. Briefly, they involve multimodal treatment. Physical therapy with alternating passive temperature modalities using hot and cold packs can be used. Iontophoresis of steroids or local anesthetics or transcutaneous electrical stimulation may be used. Acupuncture and massage are useful holistic methods. Cognitive behavioral methods to minimize fear avoidance and anxiety associated with movement, spontaneous pain, and breathing should be advised. Analgesics from different drug classes, such as antineuropathic, antiseizure, antidepressant, antiinflammatory, and anti-spasmodic, should be considered. Opioids are usually a last resort, but severe neuropathic pain may not be controlled with nonopioid adjuvant medications. The “diagnostic” methods described above may serve a dual treatment role. An intercostal nerve block may be performed blindly, with ultrasound, or fluoroscopic guidance. In the case of a thoracic spine surgery, a catheter directed thoracic epidural steroid injection may be the best option for thoracic radiculitis. In this author’s experience, a thoracic transforaminal epidural steroid injection should be attempted in this patient if all other options are not feasible – given the legitimate concern about paraplegia. An intrapleural injection or thoracic sympathetic block may be an option to evaluate thoracic visceral pain. A consultation with an interventional pain specialist is advised for these procedures. In a practical sense, however, a neuroma injection should be the first consideration. Neuroma injections are commonly used as a treatment option in patients

Chapter 6: Patient with post-thoracotomy pain

with acute and chronic pain. The primary goal is to inactivate the neuromas by anesthetizing the primary area of pain through needling and infiltration with an injectable solution. Perineural infiltration of neuroma by direct feel and palpation or with ultrasound guidance is useful to diagnose neuroma pain. One should avoid direct intraneural injections since permanent nerve damage could result and paradoxically lead to a deafferentation pain syndrome. These should be conducted in a sterile fashion with the use of betadine, chlorhexidine, or an ethyl chloride spray. A local anesthetic solution (1% lidocaine and/or 0.25% or 0.5% marcaine) mixed with or without a steroid (40 mg depo-medrol, 3–6 mg betamethasone, or 2–4 mg dexamethasone) may be used. Small gauge needles with variable lengths should be used: 1. 25 G 1½ inch needle for superficial neuromas; and 2. 22 or 25 G 3½ inch needle for deeper neuromas. The patient is positioned in the prone or side lying position unless the neuroma is located on the anterior aspect of the body (chest wall, abdomen, inguinal region, limbs). One must make sure that the patient is comfortable and breathing appropriately. Noninvasive monitors may be advised for higher risk patient due to the risk of vasovagal reaction. Area to be injected is cleaned with an antiseptic solution of choice or ethyl chloride used until there is a slight frost point over the skin. The needle should be advanced past skin, subcutaneous tissue, and normal

References 1:

2:

Atluri S, Glaser SE, Shah RV, Sudarshan G. Needle position analysis in cases of paralysis from transforaminal epidurals: consider alternative approaches to traditional technique. Pain Physician. 2013;16(4):321–334. Shah RV. Paraplegia following thoracic and lumbar

muscle until it contacts the neuroma or fibrotic tissue. Pain should be elicited. The needle trajectory should be at a 45 degree angle to the skin. This is especially important near the chest wall. After negative aspiration of blood, fluid, or air a total of 1–5 ml of solution per neuroma location should be injected.

6. Are there potential complications from injections? Infection, bleeding, reaction to the medications used (keep total lidocaine used to no more than 20 ml), vasovagal reaction, injection site pain (temporary flare up), or more serious complications such as pneumothorax are possible complications. If using steroid be aware of potential skin depigmentation changes and possible skin atrophy particularly in thin patients and with superficial muscles.

7. What are the outcomes? Unfortunately, many of these patients will continue to have pain. They may require maintenance analgesic therapy for the rest of their lives. Physical therapy, psychologic counseling, and injections may have to be used periodically to help with pain. In this author’s estimation, patients that comply with multimodal treatment are likely to have better functional outcomes as opposed to those just seeking a passive route: analgesics and staying at home.

transforaminal epidural steroid injections: how relevant are particulate steroids? Pain Pract. 2013 Oct 24. doi: 10.1111/ papr.12110 [Epub ahead of print]. 3:

Shah RV. Paraplegia following thoracic and lumbar transforaminal epidural steroid injections: how relevant is physician negligence?

J Neurointerv Surg. 2013 Aug 28. doi: 10.1136/neurintsurg-2013010903 [Epub ahead of print]. 4:

Shah RV. The problem with diagnostic selective nerve root blocks. Spine (Phila Pa 1976). 2012;37(24):1991–1993.

5:

Shah RV. Spine pain classification: the problem. Spine (Phila Pa 1976). 2012;37(22):1853–1855.

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Section 1 Chapter

7

Neurological Disorders

Complex regional pain syndrome Gaurav Jain and Nashaat N. Rizk

Case study A 50-year-old woman sustained an injury to her right wrist after a computer fell on it. A few weeks later she had pain and swelling in her right wrist. All wrist movements were painful. Due to the possibility of tendon injury, a plastic surgeon operated on her wrist and found no abnormalities. After surgery, her hand was swollen and pain worsened. It was mostly aching and burning, but sometimes sharp in nature. Gradually, she was unable to use her right hand due to pain, swelling, discomfort, tightness, and weakness. Gradually, she started to notice that the right hand felt colder and looked paler than the other hand. She had poor nail growth and the skin on her affected hand became dry. She was crippled in her personal and occupational life due to the above condition.

1. What are the differential diagnoses in this case?  Cellulitis  Lymphedema  Soft tissue or bone injury, including occult or stress fracture  Compartment syndrome  Arthritis or arthrosis  Tenosynovitis  Upper or lower limb venous thrombosis  Arterial insufficiency such as thromboangiitis obliterans or severe atherosclerosis  Scleroderma  Plexitis, peripheral neuropathy  Erythromelalgia

2. What is complex regional pain syndrome? Complex regional pain syndrome (CRPS) is a chronic regional (not in a specific nerve territory or dermatome) pain syndrome that occurs most often in an extremity in association with abnormal autonomic nervous system activity and trophic changes. The pain is seemingly disproportionate in time or degree to the usual course of any known trauma or other lesion. The disorder has both nociceptive and neuropathic features and is characterized by disabling persistent pain, hyperalgesia or allodynia, swelling, vasomotor instability, sudomotor abnormality, and impairment of motor function. In many cases, the syndrome is preceded by an inciting noxious event, surgery, trauma, or immobilization, while in some cases (9%) there is no precipitating trauma at all. However, the condition is not related to trauma severity. The syndrome shows variable progression over time. Transient features of CRPS are much more common than most clinicians realize, occurring in up to 25% of minor limb injuries. Approximately 15% of sufferers will have unrelenting pain and physical impairment up to 5 years after CRPS onset, although more patients will have a lesser degree of ongoing pain and dysfunction impacting their ability to work and function normally. The incidence per person-years at risk of CRPS based on the results of two epidemiologic studies ranged from 5.46 to 26.6/100000 personyears at risk. It is commoner in females than males, at a ratio of 2–3:1, and frequently occurs in the 5th– 7th decade of life.

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 7: Complex regional pain syndrome

Table 7.1. The 2007 Budapest Consensus Dignostic Criteria for CRPS*

Category

Symptom

Sign (evidence needed on exam)

Sensory

Hyperesthesia and/or allodynia

Hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement)

Vasomotor

Temperature asymmetry and/or skin color changes and/or skin color asymmetry

Temperature asymmetry (> 1°C) and/or skin color changes and/or asymmetry

Sudomotor/ edema

Edema and/or sweating changes and/or sweating asymmetry

Edema and/or sweating changes and/or sweating asymmetry

Motor/ trophic

Decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

Decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)

* One symptom in at least three categories and one sign in at least two categories are required for diagnosis.

3. What are the classification and diagnostic criteria of CRPS? CRPS is classified into two types based on the absence (type I) or presence (type II) of a definable nerve injury. In 1998, the International Association for the Study of Pain (IASP) established the following four criteria that must be present for a clinical diagnosis of CRPS to be made: 1. Preceding noxious event without (CRPS I) or with obvious nerve lesion (CRPS II). 2. Spontaneous pain or hyperalgesia-hyperesthesia not limited to a single nerve territory and disproportionate to the inciting event. 3. Edema, skin blood flow (temperature), or sudomotor abnormalities, motor symptoms, or trophic changes present in the affected limb, in particular at distal sites. 4. Other diagnoses are excluded. Although the IASP diagnostic criteria had a high sensitivity, their specificity was only around 40%. In 2007, the Budapest Consensus refined the diagnostic criteria to include stricter conditions for clinical diagnosis, which increased the specificity to about 70% while maintaining high sensitivity. The criteria were as follows: 1. Continuing pain disproportionate to any inciting event 2. Must report at least one symptom in three of the four categories listed in Table 7.1

3. Must display at least one sign at time of evaluation in two or more of the categories listed in Table 7.1 4. No other diagnosis better explains the signs and symptoms (see Table 7.1) Schwartzman et al divided CRPS into three clinical stages, which are useful descriptively. The syndrome may not always follow this stepwise evolution. The stages of CRPS are described as follows: i. Stage 1: severe pain; pitting edema; redness; warmth; increased hair and nail growth; hyperhidrosis may begin; osteoporosis may begin. ii. Stage 2: continued pain; brawny edema; periarticular thickening; cyanosis or pallor; livedo reticularis; coolness; hyperhidrosis; increased osteoporosis; ridged nails. iii. Stage 3: pallor; dry, cool skin; atrophic soft tissue (dystrophy); contracture; extensive osteoporosis.

4. How does one make the diagnosis of CRPS? CPRS is primarily a clinical diagnosis The pathophysiology of CRPS is poorly understood. Based on current literature, several hypothesized mechanisms appear to play roles: autonomic dysfunction, neurogenic inflammation, and neuroplastic changes within the central nervous system (central/peripheral sensitization and progressive small-fiber degeneration).

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Chapter 7: Complex regional pain syndrome

Currently no diagnostic test is considered a gold standard and no objective test is specific for CRPS. However, several diagnostic studies may be helpful in its evaluation and to rule out other pathologic processes. Autonomic function can be assessed by following tests: infrared thermometry and thermography, quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat test (TST), and laser Doppler flowmetry. The skin temperature can be measured by Doppler flowmeter and infrared thermography; cutaneous blood flow can be measured by vital capillaroscopy (the affected extremity may demonstrate higher perfusion); sweat output can be assessed by quantitative sudomotor axon reflex testing; and coexisting nerve injury and muscle fiber loss can be quantified by electromyography and nerve conduction studies. The limitations of these tests are non-specific to this condition and most require special equipment and setup that make clinical applications less viable. Imaging is useful to exclude other diagnoses. Plain films are usually normal except in extreme cases, in which demineralization can occur (Sudeck’s atrophy). Trophic changes can be assessed by threephase bone scintigraphy, which detects pathologic delayed uptake in the distal bones such as the metacarpophalangeal or metacarpal bones. The sensitivity and specificity of three-phase bone scintigraphy are variable. Although an abnormal bone scan finding can confirm the clinical diagnosis of CRPS, the condition cannot be ruled out by a normal study. Magnetic resonance imaging may demonstrate marrow edema, soft tissue swelling, and joint effusion. Although clinically unavailable, central nervous system functional imaging studies may provide clues to reorganization in central somatosensory and motor networks, which lead to an altered central processing of tactile and nociceptive stimuli, as well as to an altered cerebral organization of movement.

5. What is the treatment approach for CRPS? Prompt diagnosis and early treatment is the cornerstone in management. It helps to avoid secondary physical problems associated with disuse of the affected limb and the psychologic consequences of living with undiagnosed chronic pain. Early referral to physiotherapy and encouraging gentle movement as

48

early as possible may potentially prevent progression of symptoms. Except in mild cases, patients with CRPS are generally best managed in specialist pain management or rehabilitation programs. An integrated and interdisciplinary pain rehabilitation treatment approach that includes the following four components is required: a. Patient information and education b. Pain relief with medications and procedures c. Physical and vocational rehabilitation d. Psychologic interventions (pain-coping skills, biofeedback, relaxation training, and cognitive behavior therapy) Treatment with medications and procedures can be individualized according to the symptoms, signs, and degree of severity. Tricyclic antidepressants are traditional choices in neuropathic pain disorders with good evidence to support their use for neuropathic pain. Antiepileptic agents are some of the best-studied agents for neuropathic pain, and strong evidence demonstrates their effectiveness. Non-steroidal antiinflammatory drugs may be effective in the acute phase with symptoms of swelling, erythema, or warmth. Oral corticosteroid agents can be particularly effective early in the disease when significant inflammation is present, and their use is substantially supported by randomized controlled clinical trials. A short course of steroids in the acute stage of the disease may be indicated. The lidocaine patch is used topically to deliver medication locally to the area of allodynia. Because of the suspected role of increased sympathetic nervous system activity in CRPS, alphaadrenergic antagonists such as phenoxybenzamine and phentolamine have also been used and may be beneficial in cases of sympathetically maintained pain. Opioids may be useful in the acute stages of CRPS for pain control. However, their use in chronic pain conditions and conditions with neuropathic features remains controversial. Methadone may be a choice in cases of severe neuropathic pain because of its NMDA receptor antagonist activity. Bisphosphonates have been tested in randomized controlled trials with some demonstrated efficacy, with the assumption that antinociceptive effect is primarily due to their capacity to inactivate osteoclasts and inhibit prostaglandin E2, proteolytic enzymes, and lactic acid. Calcitonin is another recent addition to the CRPS drug therapy armamentarium. However, results of randomized trials have been equivocal.

Chapter 7: Complex regional pain syndrome

6. What interventional methods are available to treat CRPS? Local anesthetic sympathetic blockade is the conventional and most common early intervention. However, patients can be divided by those with sympathetically maintained pain and those with sympathetically independent pain based on positive or negative response to selective sympathetic blockade or blockade of the alpha-adrenergic receptors. Stellate ganglion blocks for upper limb and lumbar chain blocks for lower limb symptoms can be offered. Alternatively, intrapleural infusion of local anesthetic can be used to block the sympathetic chain from T1 to L2.

Bier block procedures, involving the intravenous infusion of pharmacologic substances into a limb after gravitational drainage of the venous bed, may also be used. Depending on the substance infused, this can accomplish regional sympathetic blockade with guanethidine, sensorimotor blockade with lidocaine, or a combination of the two. For those patients with sympathetically independent pain, regional sensorimotor blockade with lidocaine should be the early intervention of choice. Such procedures have the possibility of achieving rapid and effective pain relief, allowing more timely progression in rehabilitation. In addition to interventional pain control procedures, which should be used aggressively early in the Figure 7.1. Lumbar sympathetic block. From personal files of Rinoo V. Shah, MD, MBA.

Figure 7.2. Stellate ganglion block. From personal files of Rinoo V. Shah, MD, MBA.

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Chapter 7: Complex regional pain syndrome

Figure 7.3. Spinal cord stimulation. From personal files of Rinoo V. Shah, MD, MBA.

Figure 7.5. Same patient as Figure 7.4: cervical spinal cord stimulation midline (dorsal columns) and dorsal root/entry zone stimulation. From personal files of Rinoo V. Shah, MD, MBA.

50

Figure 7.4. Cervical spinal cord stimulation midline/dorsal columns. From personal files of Rinoo V. Shah, MD, MBA.

disease course, spinal cord stimulation (SCS) can be a beneficial treatment modality for those who do not have a satisfactory response to the above treatment in 12–16 weeks. SCS has been shown to be effective for treatment of both CRPS I and CRPS II when other less invasive treatment strategies have failed. Neuromodulation may act to restore normal gamma-aminobutyric acid levels in the dorsal horn and affect release of adenosine, thus reducing neuropathic pain. SCS has proven effective in supporting functional restoration in the affected limb. Peripheral nerve stimulation uses a similar technique to SCS. However, due to a new modality, available data is limited. A spinal cord stimulator lead can sometimes be placed in the dorsolateral epidural space to target the dorsal roots or dorsal root entry zone. Patients who have a good response to sympathetic blocks can be offered sympathetic denervation through radiofrequency ablation or surgical sympathectomy. However, the quality of evidence for these treatments is poor and several complications can occur, which include postsympathectomy sympathalgia, compensatory hyperhidrosis, Horner’s syndrome, infection, and spinal cord injury.

Chapter 7: Complex regional pain syndrome

Sometimes CRPS may spread to the contralateral limb or to involve a different region of the body. Surgeons operating on patients with resolved or dormant CRPS must be aware of reactivation and spread of this disease, even if the surgery is remote to the original CRPS involved limb. If recurrence and spread occur, blocks and infusions targeting the sympathetically independent and maintained pain generators should be pursued, according to Shah and Day.[15]

7. What is the course of CRPS? The outcome of CRPS varies from person to person. Younger patients, especially children and teenagers, tend to have good recovery. Occasionally patients are left with unremitting pain and crippling, irreversible

References 1.

2.

3.

4.

5.

Janig W, Stanton-Hicks M (eds). Reflex sympathetic dystrophy: a reappraisal. In Progress In Pain Research and Management, vol. 6. Seattle, Washington: IASP Press; 1996. Harden RN, Bruehl S, StantonHicks M et al. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med. 2007;8:326–331. de Mos M, de Bruijn AGJ, Huygen FJPM, et al. The incidence of complex regional pain syndrome: a populationbased study. Pain. 2007; 129:12–20. Raja SN, Grabow TS. Complex regional pain syndrome I (reflex sympathetic dystrophy). Anesthesiology. 2002; 96:1254–1260. Veldman PHJM, Reynen HM, Arntz IE, et al. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet. 1993;342:1012–1016.

6.

7.

8.

changes despite treatment. There is some evidence to suggest early treatment, particularly rehabilitation, is helfpul in limiting the disorder, but this benefit has not yet been proven in large randomized clinical studies. More research is needed to understand the causes of CRPS, how it progresses, and the role of early treatment. In a sub-group of patients with unremitting chronic pain, it may give rise to physical deconditioning, anxiety, depression, weight gain, and sleep disturbance. Also, with inadequate treatment, all aspects of the patient’s life can be affected, often with negative social, vocational, financial, and recreational consequences. In addition, limb contracture and loss of strength may lead to difficulty in ambulation and activities of daily living.

Schwartzman RJ, McLellan TL. Reflex sympathetic dystrophy: a review. Arch Neurol. 1987;44:555–561. Atkins RM, Duckworth T, Kanis JA. Features of algodystrophy after Colles’ fracture. J Bone Joint Surg. 1990;72:105–110.

Schasfoort FC, Bussmann JB, Stam HJ. Impairments and activity limitations in subjects with chronic upper-limb complex regional pain syndrome type I. Arch Phys Med Rehabil. 2004;85:557–566. 9. Janig W, Baron R. Complex regional pain syndrome: mystery explained? Lancet Neurol. 2003;2:687–697. 10. Cepeda MS, Carr DB, Lau J. Local anesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev. 2005;4:CD004598. 11. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and costeffectiveness literature and

assessment of prognostic factors. Eur J Pain. 2006;10:91–101. 12. Turner-Stokes L, Goebel A. Complex regional pain syndrome in adults: concise guidance. Clin Med. 2011; 11: 596–600. 13. Albazaz R, Wong Y, HomerVanniasinkam S. Complex regional pain syndrome: a review. Ann Vasc Surg. 2008;22: 297–306. 14. Sharma A, Williams K, Raja S. Advances in treatment of complex regional pain syndrome: recent insights on a perplexing disease. Curr Opin Anaesthesiol, 2006;19:566–572. 15. Shah RV, Day MR. Recurrence and spread of complex regional pain syndrome caused by remotesite surgery: a case report. Am J Orthop (Belle Mead NJ). 2006;35 (11):523–526. 16. Bailey A, Auclette JF. Complex regional pain syndrome. In Frontera WR, Silver JK, Rizzo TD, (eds). Essentials of Physical Medicine and Rehabilitation, 2nd edn. Philadelphia, PA: Saunders/ Elsevier. 2008: pp. 511–517.

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Section 1 Chapter

8

Neurological Disorders

Diabetic neuropathy Gulshan Doulatram and Tilak Raj

Case study A 55-year-old female presents to your clinic with pain in the back and associated tingling, numbness, and pain in both her legs for the past year. The symptoms are worse at night. She has an antalgic broad-based gait and has been using a walker to get around. She was working as a school teacher, but has been on short-term disability for the last 4 months. She is depressed about her prognosis and is asking you to fix her so she can return to work.

1. How prevalent is this disease presentation?Couldyouexplainsomeof the epidemiologic features of this disease? Are there any cost concerns? The 2011 Diabetes fact sheet published by the Centers for Disease Control confirmed that 25 million Americans have diabetes, a disease now affecting one in every four patients. Five percent of these individuals have type 1 diabetes mellitus (DM) and 95% have type 2 DM. Diabetic patients have a life time prevalence of 60% of developing diabetic neuropathy.[1] There are currently 8 million people in the USA who have symptomatic diabetic polyneuropathy. Diabetic polyneuropathy is a length-dependent disorder of peripheral nerve fibers, characterized by a distal-to-proximal loss of peripheral nerve axons and function. The progression of disease from painful neuropathy to loss of sensation and development of foot ulcers and amputations causes a significant burden to society both in social and financial ways. The cost of diabetic neuropathy was estimated to be $50 billion in 2007, which is 25% of total costs related to DM. This number is expected to rise exponentially.[2] Patients with painful diabetic peripheral neuropathy (PDPN) are more likely

to have foot ulcers and amputations, further increasing the burden of the disease and decreasing quality of life for those affected. The prevalence of diabetic polyneuropathy (DPN) and PDPN increases with age, duration of diabetes, and worsening of glucose tolerance. The overall prevalence of PDPN in the diabetic population is 15%.[3]

2. What are some of the other conditions that could have the same presentation? In up to 25% of diabetic patients with neuropathy, the neuropathy could have another cause. Hence the diagnosis of diabetic neuropathy requires careful evaluation.[4,5] Other conditions with a similar presentation include:  Posterior disc protrusion  Spinal cord tumors  Malignant nerve root infiltrations  Inflammatory neuropathies  Pernicious anemia  Vitamin B6 intoxication  Alcoholism  Uremia  Chemical toxins  Nerve entrapment and compression of benign etiology  Hepatitis  Idiopathic  Congenital (various hereditary sensory motor neuropathies)  Paraneoplastic syndrome  Syphilis  HIV/AIDS

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 8: Diabetic neuropathy

 Medication (e.g., chemotherapy, isoniazid, radiation induced)  Spine disease (e.g., radiculopathy, stenosis)  Vitamin B12 deficiency  Hypothyroidism

3. How would you differentiate diabetic neuropathy from some of these other disorders? Diabetic neuropathy is usually diagnosed presumptively by the presentation including the symptoms, medical history, and physical exam. Fasting plasma glucose and hemoglobin A1c are important laboratory screening tests for diabetic neuropathy. While imaging of the spine rarely helps diagnose or manage diabetic neuropathy, it may exclude other causes mimicking diabetic neuropathy. A subset of patients may have abnormal glucose tolerance (AGT) and still have severe neuropathic symptoms.

4. What diagnostic studies would you obtain?  Fasting plasma glucose and hemoglobin A1c – screening tests for diabetes.  Urine analysis to screen for nephropathy and proteinuria.  Complete blood cell count and complete metabolic panel (electrolytes, renal function, and liver function panel).  Vitamin B12 and folate levels.  Thyroid function tests.  Erythrocyte sedimentation rate and C-reactive protein.  Serum protein electrophoresis with immunofixation electrophoresis.  Antinuclear antibody, Anti-SSA and SSB antibodies, rheumatoid factor.  Paraneoplastic antibodies.  Rapid plasma regain.  Genetic screens.  Hematology screen to check for anemia.  Nerve conduction studies (NCS) and electromyography (EMG).  Imaging of the spine to exclude other causes.  Quantitative sensory testing (QST) – QST[6] measures sensory thresholds for pain, touch,

vibration, and hot and cold temperature sensation. It is increasingly used, especially in clinical therapeutic trials. A number of devices are commercially available and range from handheld tools to sophisticated computerized equipment with complicated testing algorithms. Specific fiber functions can be assessed: Aδ-fibers with cold and cold-pain detection thresholds, C-fibers with heat and heat-pain detection thresholds, and large fiber (Aαβ-) functions with vibration detection thresholds. Elevated sensory thresholds correlate with sensory loss and lowered thresholds occur in allodynia and hyperalgesia. In asymptomatic patients, abnormal QST thresholds suggest subclinical nerve damage. QST is a psychophysical test and therefore is dependent upon patient motivation, alertness, and concentration.  Autonomic function testing. Autonomic testing is valuable in patients with neuropathic pain disorder in which patients had normal or mildly abnormal electrophysiologic (NCV/EMG) findings (27% of patients). The most useful tests are the QSART, thermoregulatory sweat test, heart rate responses to deep breathing, Valsalva ratio, and surface skin temperature. In a recent study of patients with diabetic polyneuropathy, discordance was noted between efferent C-fiber responses in sudomotor tests (QSART and sweat imprint), and primary afferent (nociceptor) C-fiber axon reflex flare responses. These findings indicate that these two C-fiber subclasses can be differentially affected in diabetic small-fiber polyneuropathy. Autonomic functions can also be abnormal in peripheral neuropathies not associated with pain.  Skin biopsy. Epidermal nerve fiber density and morphology, e.g., tortuosity, complex ramifications, clustering, and axon swellings, can be quantified and compared with control values with a 3-cm skin biopsy and immunohistochemistry. A reduced density of epidermal nerve fibers is seen in small-fiber neuropathies, diabetic neuropathy, and impaired glucose tolerance neuropathy, each of which is associated with neuropathic pain. In a subgroup analysis of one such study, the skin biopsy was found to be a more sensitive measure than QSART or QST in diagnosing neuropathy in patients with burning feet and normal NCVs.

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 Functional brain imaging. Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) may not be practically used but are currently useful in study outcomes and have potential in the future.  Microneurography. This looks at individual nerve fibers and is very sensitive in detecting early neuropathy, but can be too cumbersome to be used routinely in clinical practice.

5. How would you make a diagnosis of diabetic neuropathy? Screening test for DPN. The Center for Medicare and Medicaid Services, the International Diabetes Federation, and the World Health Organization recommend that this testing on the feet should be done by The Semmes Weinstein monofilament examination (SWME). The optimal method is to use the 5.07/10 g monofilament to test the plantar aspects of the great toe, third, and fifth metatarsal heads. Patients unable to detect one or more sites should be classified as at risk in order to maximize sensitivity.[7] Neuropathic Pain Scale (NPS). This is the first scale developed specifically to assess neuropathic pain. The NPS includes characteristics of pain intensity and unpleasantness that assess the global dimensions of pain. The NPS also includes eight classifications of pain that assess specific qualities of neuropathic pain: sharp (like a knife), hot (on fire), dull (aching), cold (freezing), sensitive (raw skin), itchy (like poison oak), deep, and surface. Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS). This consists of a 7-item pain scale, including both sensory descriptors and items for sensory examination. Neuropathic Pain Questionnaire (NPQ). This instrument provides a general assessment of neuropathic pain symptoms and is useful in discriminating between neuropathic and non-neuropathic pain. Neuropathic Pain Symptom Inventory (NPSI). NPSI includes 10 descriptors that allow discrimination and quantification of five distinct clinically relevant dimensions of neuropathic pain syndromes. The psychometric properties of the NPSI make it extremely useful in assessing and quantifying the response to various pharmacologic and non-pharmacologic interventions. All of these scales are extremely useful in studies to assess outcomes of specific modalities but are not commonly used in clinical practice.

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Table 8.1. Defining citeria for diabetic polyneuropathy according to The Toronto Expert Panel on Diabetic Neuropathy[5]

Classification

Characteristics

Possible clinical DN

Symptoms or signs of DN. Symptoms can be positive (pain) or negative (loss of sensation) in the feet Signs can include symmetrical decreased sensory loss in the feet or decreased or absent ankle reflexes

Probable clinical DN

A combination of symptoms and signs of DN, as described above, with any two or more of the following: neuropathic symptoms, decreased sensation, or decreased or absent ankle reflexes

Confirmed clinical DN

An abnormal nerve conduction study and a symptom or sign of DN, as described above

Subclinical DN (stage 1a)

An abnormal nerve conduction study with no signs or symptoms of DN

Diagnostic criteria for diabetic polyneuropathy were developed 25 years ago by a panel of neurologists and diabetologists but proved too costly and time-consuming. A second group of experts (Toronto Expert Panel on Diabetic Neuropathy) published revised criteria in 2011. These criteria are presented in Table 8.1.[1]

6. What are some of the other presentations in diabetic neuropathy? Diabetic neuropathies are heterogeneous diseases and can have diverse clinical manifestations. They can be classified as follows:[8]  Generalized or symmetrical neuropathies: 

Sensory neuropathies  



Acute sensorimotor neuropathy Chronic sensorimotor distal polyneuropathy

Autonomic neuropathies   

Cardiovascular Gastrointestinal Genitourinary

Chapter 8: Diabetic neuropathy

 Focal and multifocal or asymmetrical neuropathies:     

Cranial Truncal Focal limb Proximal motor (amyotropy) Chronic inflammatory demyelinating polyneuropathies (CIDP)

Generalized, symmetrical polyneuropathy is the most common type and may have sensory, motor, and autonomic manifestations. It typically has a chronic presentation with features of small-fiber dysfunction, i.e., pain with loss of pain, temperature and vibration sensory perception, absent ankle reflexes, and formation of foot ulcers. Symptoms start in the toes and feet and ascend in the lower limb; upper limb involvement is rare and occurs in long-standing disease. Some neuropathic features include:  Paresthesias – abnormal sensations that are not painful; some examples include tingling and burning  Dysesthesia – abnormal sensations that are painful  Mechanical allodynia – abnormal perception of pain from usually non-painful mechanical stimulation  Thermal allodynia – abnormal sensation of pain from usually non-painful thermal stimulation such as cold or warmth  Summation – abnormally increasing painful sensation to a repeated stimulus although the actual stimulus remains constant  Hyperalgesia – exaggerated pain response from a usually painful stimulation  Hyperpathia – abnormally painful and exaggerated reaction to a stimulus, especially to repetitive stimuli  Aftersensation – abnormal persistence of a sensory perception provoked by a stimulus even though the stimulus has ceased Autonomic neuropathy is common and underreported and may affect many organ systems but most commonly involves cardiovascular, gastrointestinal, and genitourinary systems. Features include resting tachycardia, orthostatic hypotension, distal anhidrosis, sexual dysfunction, and gastrointestinal features including severe constipation and diarrhea. Among the multifocal neuropathies, the mononeuropathies commonly involve median, ulnar, and

common peroneal nerves. Cranial neuropathies involving the oculomotor and abducens nerve are rare. Diabetic amyotropy generally occurs in type 2 diabetes, and is subacute with pain, asymmetric weakness, and atrophy of proximal limb muscles. Rarely distal lower limb and upper limb muscles may be involved. Sensory deficit is minimal but pain is usually severe with loss of patellar reflex. Other subacute presentations include:  Development of acute sensory neuropathy when blood sugar levels are high  Development of acute sensory neuropathy when treated with insulin  Acute painful neuropathy associated with weight loss (diabetic neuropathic cachexia)

7. What are the EMG findings in diabetic neuropathy? In patients with diabetes, abnormalities may be found on nerve conduction study, even in the absence of clinical symptoms of polyneuropathy. Nerve conduction studies and electromyography (EMG) can provide objective evidence of dysfunction of large myelinated (Aβ) nerves, characterize the neuropathy (e.g., axonal, demyelinating), localize it (e.g., mononeuropathy versus radiculopathy or distal neuropathy), and possibly assess the severity and even prognosis. Findings on nerve conduction studies depend on the pattern of nerve damage.[9] Axon loss results in loss of amplitude of nerve action potentials, and evidence of denervation is found on needle examination of affected muscles. Myelin loss results in slowed conduction velocities, prolonged distal latencies, conduction block, temporal dispersion, and prolonged minimum F-wave latencies. NCS/EMG does not provide information about the function of small myelinated (Aδ) or unmyelinated (C) fibers which is a major limitation. Polyneuropathies with only small-fiber involvement can have normal NCVs and EMG despite significant nerve damage and neuropathic pain. The most common presentation is distal symmetric sensorimotor neuropathy, which is associated with predominant axonal loss and causes reduced or absent sensory nerve action potentials. The lower limbs are affected first and more severely. With progression of the neuropathy, compound motor action potential amplitudes may also be reduced and abnormalities may then be observed in the hands.[10] These changes

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Chapter 8: Diabetic neuropathy

reflect length-dependent degeneration of large-diameter myelinated nerve fibers. Conduction velocities are generally within the normal range (or only mildly slowed) in distal symmetrical polyneuropathy. Conduction velocities less than 70% or a conduction block may suggest demyelination, and, if generalized, should prompt further evaluation for CIDP. EMG may be normal in mild or asymptomatic subjects, but demonstrates denervation in more severe cases. Denervation changes include positive sharp waves and fibrillation potentials (spontaneous discharges). Chronicity is indicated by reinnervation changes such as large-amplitude, long-duration, and polyphasic motor unit potentials. Focal slowing of conduction velocity at common entrapment sites may indicate one of the mononeuropathies. Paraspinal muscle abnormalities indicate spinal nerve root disease.

8. What is Seddon’s and Sunderland’s classification for peripheral nerve injuries? The most widely accepted classifications of peripheral nerve injuries are those by Seddon (neuropraxia, axonotmesis, and neurotmesis) and Sunderland (Grade 1–5 nerve injury)[10] (see Table 8.2).

Table 8.2. Classification of peripheral nerve injuries

Seddon

Sunderland

Pathophysiology

Neuropraxia (compression)

Type 1

Local myelin damage with the nerve still intact

Axonotmesis (crush)

Type 2

The continuity of axons is lost. The endoneurium, perineurium, and epineurium remain intact. Loss of continuity of axons with wallerian degeneration due to disruption of axoplasmic flow Type 2 with endoneurial injury Type 2 with endoneurial and perineurial injury but an intact epineurium

Type 3 Type 4

Neurotmesis (transection)

Type 5

Complete physiologic disruption of the entire nerve trunk. Early surgical intervention necessary. Prognosis guarded

9. What is the pathophysiology of PDPN? The pathophysiology of PDPN is multifactorial and involves both the toxic effect of glucose on nerve cells and ischemia of peripheral nerves.[11] High blood glucose activates the polyol pathway, generates reactive oxygen species (ROS), and causes accumulation of advanced glycation end products (AGE). Accumulation of sorbitol produced by activation of the polyol pathway causes reduction in nerve myo-inositol and disruption of Na+/K+-ATPase membrane activity, leading to intracellular sodium accumulation, impaired axonal transport, and finally structural damage to the nerves. Hyperglycemia causes glycation of the free amino group on proteins, lipids, and nucleic acids with alteration in their molecular structure and function. The basement membrane of endothelial cells becomes glycosylated which causes vasoconstriction and contributes further to ischemia. AGEs bind to receptors of AGE on macrophages, causing the release of a cascade of proinflammatory cytokines (interleukin-1,

56

tumor necrosis factor-α), growth factors (insulin-like growth factor, platelet-derived growth factor, tissue growth factor-β), and adhesion molecules (vascular cell adhesion molecules-1) (VCAM-1). Elevated intracellular glucose causes activation of protein kinase C (PKC), which produces direct neuronal damage by affecting endothelial function. Several treatment modalities have targeted these pathophysiologic pathways with varying success in PDPN.

10. What are some treatment modalities you would offer to this patient? The treatment of the PDPN is multi-pronged to achieve optimal results. The treatment modalities include a vast array of options, including physical therapy, psychology, injections, implantable devices

Chapter 8: Diabetic neuropathy

Figure 8.1. Diabetic neuropathy.

DIABETIC NEUROPATHY

HISTORY / EXAM

BLOOD GLUCOSE, HgA1C

RULE OUT OTHER CAUSES

POSSIBLE QST, EMG, NCV, SKIN BIOPSY IF DIAGNOSIS IS IN DOUBT

MEDICAL MANAGEMENT

TRICYCLIC ANTIDEPRESSANT

SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS

VOLTAGE-GATED CALCIUM CHANNEL BLOCKERS

COMBINATION OF THREE

NO RELIEF

OPIOIDS

TRAMADOL

NO RELIEF

SPINAL CORD STIMULATION

or neuromodulation, surgery, medications, holistic treatments, and herbal medications. Overall, strict blood sugar control is necessary to prevent some of the diabetic complications. A definite correlation has been found between the degree of blood sugar control and development of painful neuropathy. Lifestyle modification with diet, exercise, and correction of metabolic derangements and associated morbidities are essential for optimal outcomes. Most of the treatment modalities available to a diabetic patient are often only symptomatic and do not change the course of the disease. Treatment can often be frustrating, both for the patient and pain practitioner, especially when medications fail to provide the desired relief;

however a stepwise logical approach must be utilized in all patients with PDPN. The treatment algorithm presented here is a modification from guidelines formulated by the Toronto Expert Panel on Diabetic Neuropathy.[12] (Figure 8.1)

11. Disease-modifying medications α-Lipoic acid D-L-α-lipoic acid (ALA), a potent antioxidant, has been extensively evaluated in prospective, placebocontrolled studies in subjects with PDPN. Several large-scale trials have shown an improvement in both

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Chapter 8: Diabetic neuropathy

the neuropathic pain scores and electrophysiologic parameters.[11] A dose of 600 mg/day appears to offer the best balance between efficacy and side effect profile.

Protein kinase C inhibitors Activation of PKC is thought to play an important role in the microvascular complications of diabetes. A multinational, randomized, Phase II double-blind placebo-controlled trial using ruboxistaurin (a PKC-β inhibitor) showed improvement in neuropathy and vibration detection thresholds (VDT).

Polyol pathway Aldose reductase inhibitors (ARIs) reduce the flux of glucose through the polyol or sorbitol pathway, hence decreasing the levels of intracellular sorbitol and fructose. Fidarestat was associated with significant improvement in electrophysiologic and symptomatic measures in patients with type 1 and 2 diabetes. The ARI epalrestat, approved in Japan for clinical use, also showed an improvement in patients’ symptoms and prevented the deterioration of median motor nerve conduction velocity. Another ARI that has been evaluated in a Phase III study is ranirestat, which has been shown to slow the progression of neuropathy.

Advanced glycation end products The accumulation of AGEs causes release of inflammatory mediators and leads to microvascular damage. However, the identification and testing of a safe AGE inhibitor has proved problematic. Amino-guanidine was discontinued because of toxicity in humans. Benfotiamine, a derivative of thiamine (vitamin B1), has been shown to reduce tissue AGEs. Studies with benfotiamine have been reported to show some effectiveness compared to placebo. Benfotiamine has also been studied in combination with pyridoxamine (vitamin B6) and cyanocobalamin (vitamin B12). These studies reported a significant improvement in vibration perception threshold, motor function, and symptom scores.

12. Symptomatic treatment Anticonvulsants These include the traditional agents, such as carbamazepine and valproate, and newer agents, such as gabapentin and pregabalin.

58

Carbamazepine, phenytoin (Dilantin), and valproate are some of the older anticonvulsants that have been used to treat neuropathic pain. There are not too many studies specifically testing these drugs for PDPN. Patients should have detailed laboratory tests prior to initiation of therapy, including: blood urea nitrogen, creatinine, transaminase, iron levels, a complete blood count (including platelets), reticulocyte count, and liver function test. Carbamazepine can also cause dermatologic reactions, such as toxic epidermal necrolysis and Stevens–Johnson syndrome. In light of the array of adverse effects, newer anticonvulsants are preferred.[12,13] Gabapentin is used in the treatment of neuropathic pain and PDPN. The major side effects reported from gabapentin include sedation and dizziness. The major drawbacks are the requirement of high doses and poor bioavailability.[12] Pregabalin, an analog of the neurotransmitter gamma-aminobutyric acid (GABA), binds the alpha2delta (a2-d) unit of the calcium channels, reducing calcium influx at nerve terminals. This reduces the release of several neurotransmitters, including glutamate, noradrenaline, and substance P. Pregabalin does not bind GABA-A and GABA-B receptors, and it is not converted metabolically into GABA.[13] A 2008 metaanalysis of seven trials showed pregabalin was effective in treating diabetic peripheral neuropathic pain in 1510 patients.[14] Pregabalin is one of the only two drugs approved by the FDA in the treatment of PDPN. Pregabalin is usually well tolerated, and has a good safety profile. Common side effects include somnolence, dizziness, weight gain, and peripheral edema, which rarely require stopping the medication. Rare but serious adverse events include rhabdomyolysis, acute renal failure, hyperthermia, and secondary acute-angle glaucoma. The dose of pregabalin requires careful titration in patients with chronic kidney disease. Pregabalin has the advantage of improving mood and sleep, and thus addresses the interaction of chronic pain, sleep loss, and mood disturbance in diabetic neuropathy.

Antidepressants TCA antidepressants, such as amitryptiline and nortryptiline, are effective in the treatment of diabetic neuropathy because of their central modulation of inhibitory pathways.[15] They are not tolerated well by patients due to their effects on alpha-adrenergic,

Chapter 8: Diabetic neuropathy

H1-histamine, muscarinic cholinergic, and N-methylD-aspartate receptors. Some of the adverse effects reported with TCAs include orthostatic hypotension, cardiac arrhythmias, dizziness, and sedation. TCAs are contraindicated in the presence of heart failure, arrhythmias, or recent myocardial infarction. Because of the anticholinergic effects of TCAs, physicians should be cautious when prescribing them for patients with narrow-angle glaucoma, benign prostatic hypertrophy, orthostasis, urinary retention, impaired liver function, or thyroid disease. QTc interval should be assessed because of the risk of torsades de pointes. Serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine (Effexor) and duloxetine (Cymbalta), are also used in the treatment of diabetic peripheral neuropathic pain.[2,16] They are better tolerated and have fewer drug interactions than TCAs. Several trials have shown promising results with venlafaxine. Duloxetine hydrochloride is a dual-reuptake inhibitor of both 5-HT and NE (SNRI) transporters, and is the only other agent (apart from pregabalin) that has been approved by the FDA in the treatment of diabetic neuropathy.[17] Duloxetine has been shown to be both effective and well tolerated. Some of the side effects include somnolence, nausea, dizziness, decreased appetite, and constipation. When compared to TCA, duloxetine can be safely prescribed to diabetic patients with concomitant cardiovascular problems. It has also been shown that if either pregabalin or duloxetine is not effective, combination therapy can be tried in the treatment of diabetic neuropathy. Duloxetine was found to be more cost-effective than pregabalin. All three classes of drugs are found to be fairly effective in the treatment of PDPN. Pregabalin has been shown to improve sleep function as an added advantage compared to duloxetine and tricyclic antidepressants.[18,19]

Local anesthetics Intravenous lidocaine has been shown to be effective in diabetic neuropathy; however, the duration and need for monitoring do not make this practical in a long-term setting. Oral mexilitine is used if there is a positive response to lidocaine. However, its use is extremely limited by its side effects.

Topical agents 5% lidocaine, a sodium channel blocker, is used for patients with painful sensory neuropathy, and is a useful adjunct to the use of antidepressants and anticonvulsants.[20] A multicenter randomized, openlabel, parallel-group study of lidocaine patch versus pregabalin with a drug washout phase of up to 2 weeks and a comparative phase of 4-week treatment period showed that lidocaine was as effective as pregabalin in reducing pain and was free of side effects. Capsaicin (0.075%) is a topically applied alkaloid that acts peripherally by depleting the neurotransmitter substance P from sensory nerves. The most common adverse effects are stinging and burning related to the brief release of substance P. Recently, an 8% capsaicin patch has shown to provide long-lasting relief in twothirds of the study population.[20] Topical clonidine gel has also shown promise in a few patients with minimal side effects. Several compounding creams containing a mixture of different medications including gabapentin, non-steroidal anti-inflammatory drugs (NSAIDs), and clonidine are now available. The effectiveness of these creams has not yet been established. Tramadol acts at both the opioid receptor and serotonin/norepinephrine receptor, and has been shown to be effective in treating pain, quality of life, and physical functioning in diabetic patients.[16] However, tramadol should be used as a second-line drug only after firstline treatments either alone or in combination have been found to be ineffective. The side effects of tramadol are related to both its opioid and serotonergic effects. Constipation, respiratory depression, lowered seizure threshold, somnolence, and serotonin syndrome (especially in patients taking concomitant antidepressants) can occur. Opioids, including short-acting and long-acting opioids, are used as the last line of medications if all other medications have failed and the pain is associated with other musculoskeletal abnormalities.[2] In that case, opioids should be used along with other neuropathic medications. Monotherapy with opiates should be reserved for patients who do not achieve pain relief goals with other therapies. Relying on opioids as sole agents in the treatment carries the risk of tolerance and opioid-induced hyperalgesia. A 2006 Cochrane review evaluated the use of opiates including methadone, levorphanol, morphine, and controlled-release oxycodone (Oxycontin) and demonstrated the superiority of opiates over placebo.

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Chapter 8: Diabetic neuropathy

Combination therapies

Intrathecal medication devices

Traditionally, single agents are tried prior to starting combination therapies. Some limited evidence exists to support combination therapies including adding opioids to gabapentin. Similarly, a combination of TCA and gabapentin has been shown to be effective. Current consensus guidelines specify that the treatment of DN should include first-line drugs including antidepressants such as tricyclics, venlafaxine, duloxetine, and pregabalin. If these medications are not successful, then second-line drugs such as tramadol and opioids can be used in conjunction with the first-line drugs.[12] However, the concomitant use of tramadol and SSRIs carries the risk of serotonin syndrome, a potentially serious condition.

There are no clinical trials supporting intrathecal medication devices (IMD) in the treatment of PDPN. The use of ziconitide has been found to be promising in other neuropathic conditions, but no studies have been done to demonstrate its efficacy in PDPN.

Interventional therapy Spinal cord stimulation SCS can be an option if the patient has failed conventional treatment or if such treatment is limited due to side effects. There are four studies which look at the efficacy of SCS in PDPN.[21,22] These studies showed long-term clinically relevant pain relief ranging from 2 to 5 years (SCS). The mechanism of pain relief with SCS for diabetic neuropathy is by a direct effect on spinothalamic tracts, segmental inhibition via coarse fiber activation, effects on the central sympathetic system, and brain stem loops to thalamocortical mechanisms. Patients who have severe autonomic neuropathy did not seem to get long-term benefit from pain and ischemia with SCS. Improvement in transcutaneous oxygen tension (TCPO2) in the trial period was a good prognostic sign for long-term benefits from SCS.[23,24] Diabetic patients with peripheral arterial occlusive disease and severe autonomic neuropathy, and those without an increase of TCPO2 in the test period should be excluded from permanent device implantation on the basis of poor long-term results and cost. One must keep in mind that all the trials supporting the use of SCS for PDPN are small and in the absence of RCTs, a blanket recommendation for the use of SCS cannot be made. Decision to use SCS must be made on an individual basis after all other modalities have failed. Further studies should also be able to predict if a certain subgroup of PDPN will respond to SCS, or if SCS should be used early or late in the disease process.

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Deep brain stimulation A review by the European Federation of Neurologic Societies found weak but positive results for deep brain stimulation (DBS) in peripheral neuropathic pain, with 70% of the small number of patients showing long-term benefit.

Surgery A review of 11 case series has shown improvement in pain scores in patients undergoing surgical decompression. Good outcomes were predicted by the presence of a positive Tinel sign preoperatively in both diabetic and non-diabetic patients.[25] However, surgery is reserved only for those patients where there is both clinical and diagnostic evidence (NCV) of nerve compression.

Physical therapy Patients with PDPN have increased risks of falls, pressure ulcers, and limited mobility due to pain, foot deformities, and sensory neuropathy. Weight-bearing exercise has the advantage of improving several parameters, including glucose levels, deconditioning, and overall quality of life, but must be balanced against constant plantar pressure and predisposition to developing ulcers in insensate feet.[26] In an independent study, Tai Chi improved glucose control, balance, neuropathic symptoms, and some dimensions of quality of life in diabetic patients with neuropathy.[27]

Psychologic treatment Diabetic patients suffer from a significantly higher rate of depressive symptoms due to the chronicity of the disease, pain, limited mobility, and complications caused either by the disease itself or its treatments. Psychotherapy treatments in diabetes mellitus can have a positive influence on anxiety and depressive symptoms, but more importantly also improve somatic complaints and blood glucose levels.[28,29] Specifically, biofeedback can reduce foot pressure to a safe level in patients with PDPN.[28]

Chapter 8: Diabetic neuropathy

Complementary and alternative medicine Complementary and alternative medicine (CAM) modalities can be used as adjuncts along with traditional therapies. Some of the CAM modalities found to be effective include biofeedback, hypnosis, and progressive muscle relaxation. A study also showed that thermal biofeedback improved healing of foot ulcers by increasing nutritive blood flow. In addition, biofeedback decreases blood pressure, probably by reducing sympathetic outflow and by enhancing the descending inhibitory systems. L-carnitine, alphalipoic acid, and primrose oil, all of which are available over-the-counter, have shown positive results, but more long-term data are needed. TENS therapy has shown good results and can be used as an alternative non-pharmacologic therapy. TENS works by the production of endogenous opioids and gate control mechanisms.[30] It has been initially postulated that low-frequency TENS works by the release of endogenous opioids, and high-frequency TENS works by stimulation of large-diameter afferent fibers, inhibiting second-order neurons in the dorsal horn and preventing impulses carried by smalldiameter C and A delta fibers from being transmitted (Gate Control theory). Low-frequency TENS activates μ opioid receptors and high-frequency TENS activates delta opioid receptors. Frequency-modulated electromagnet neural stimulation therapy includes the use of pulsed electromagnetic fields, static magnetic field therapy, lowfrequency pulsed magnetic field, high-frequency external muscle stimulation (HF), frequency-modulated electromagnetic neural stimulation (FREMS), and percutaneous electrical nerve stimulation (PENS). Each of these modalities has been shown to be effective in individual studies, but a comparative meta-analysis did not confirm this. In the absence of this data, a recommendation for or against use of these modalities cannot be made and must be made at the individual level.

New developing drugs Several new and emerging drugs are currently in the testing phase for the treatment of PDPN. These drugs target specific receptors known to be upregulated in neuropathic pain.[31] Transient receptor potential channels–vanilloid receptors (TRP V1): These agents are promising

in the treatment of diabetic neuropathy. The only agent that is approved currently is capsaicin, TRPV1 agonist, used both in lower concentrations and the higher (8%) patch. Studies are currently underway evaluating the long-term effects of capsaicin for diabetic neuropathy. Some concerns about the patch reflect its ability to cause small-fiber sensory and autonomic denervation, both of which are concerning in patients who may already have peripheral denervation. Oral TRP antagonists are still at experimental stages, but are showing some promise in Phase 1 and 2 trials for neuropathic pain. Selective sodium channel blockers (Na (v) 1.3–1.9) are also currently in the planning phase for the treatment of diabetic neuropathic pain. Opioid agonist/norepinephrine reuptake inhibitor tapentadol. This is a novel, centrally acting analgesic which acts at the μ receptor and noradrenaline receptor and has been approved for the treatment of painful diabetic neuropathy. Several studies have suggested that the drug has an efficacy comparable to other opioids but a lower incidence of constipation. Gene therapy: Currently, the only open label uncontrolled study that has been shown to be effective is intramuscular injection of plasmid DNA containing hepatocyte growth factor (HGF) given 2 weeks apart in three doses. A randomized double-blinded placebo-controlled trial is underway to objectively assess the role of HGF in diabetic neuropathy. Tanezumab, an antibody that inhibits nerve growth factor, has been studied in patients with diabetic neuropathy and shown to have a positive response, although there was a higher incidence of joint-related complications.

13. What are some of the complications from the treatment modalities? Complications associated with SCS[32] include lead migration (14%), lead breakage (7%), implanted pulse generator migration (1%), loss of therapeutic effect/ paresthesia, infection or wound breakdown (10%), pain at pulse generator implantation site (12%), and fluid collection at pulse generator implantation site (5%). Overall, diabetic patients are at higher risks from SCS complications due to their underlying disease and poor wound healing.

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14. The patient has been unable to return to work. How would you improve this? Diabetic neuropathy has a negative impact on all areas of a patient’s life, including activities of daily living, mood, sleep, self-worth, independence, ability to work, and enjoyment of life. A careful assessment at this time by a psychologist may help differentiate the cause of disability. Pain, motor weakness, low tolerance to activity (including walking), complications related to medications or any interventions, and poor healing foot ulcers may all contribute to disability. At this time, we would utilize all the modalities, including pharmacologic and interventional, physical therapy, and psychotherapy to address the somatic and psychologic derangements common in this disease.

15. Describe the conclusions you would draw from this case? This patient is suffering from PDNP that is possibly associated with motor abnormalities. This confirms both small and large fiber involvement as is seen in the more chronic form of the disease.[11,33] After a complete assessment including detailed history, physical examination, metabolic profile, and panel of neuropathic diagnostic studies, treatment should promptly address pain, physical impairment, and psychosocial issues. Good communication between the patient and provider is essential for both early

References 1.

2.

3.

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Callaghan BC, Hur J, Feldman EL. Diabetic neuropathy: one disease or two? Curr Opin Neurol. 2012; 25(5):536–541. Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521–534. Centers for Disease Control and Prevention. National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States.

diagnosis and therapeutic decisions. Efficacy, side effects, and cost of different treatment modalities need to be discussed, as well as realistic expectations. She should be reassured that strict glucose control and compliance with therapy will increase the chance of successfully managing this chronic condition. Painful DPN is a significant clinical problem affecting up to a quarter of all diabetic patients and resulting in loss of quality of life. The minimum requirements for diagnosis of painful DPN are assessment of symptoms and a comprehensive neurologic examination. Other diagnostic tests are helpful in confirming the diagnosis and assessing the severity of nerve damage. Other reversible causes of neuropathy should be considered and ruled out. Current treatment guidelines recommend first-line therapies be considered. These include TCA, the SNRI duloxetine, and anticonvulsants such as pregabalin or gabapentin. Monotherapy should be instituted before combining them. The choice will depend on costs, sleep patterns, and presence of other coexisting diseases. If these are ineffective, medications such as opioids, lidocaine patches, and/or capsaicin patches can be used. Glucose levels should be optimized. There is emerging evidence that several nonpharmacologic therapies are also effective in treating both pain and disability associated with diabetic neuropathy. Invasive therapies such as SCS and IMD can be considered, but we still lack extensive data to support the routine use of these modalities. Finally, there is a promise of newer drugs, including gene therapy, that are currently being developed.

Atlanta, GA: Centers for Disease Control and Prevention. 2011. 4.

Rutkove SB. A 52-year-old woman with disabling peripheral neuropathy: review of diabetic polyneuropathy. JAMA. 2009; 302(13):1451–1458.

5.

Waldman SD. Diabetic neuropathy: diagnosis and treatment for the pain management specialist. Curr Rev Pain. 2000;4(5):383–387.

6.

Horowitz SH. The diagnostic workup of patients with neuropathic pain. Med Clin North Am. 2007;91(1):21–30.

7.

Feng Y, Schlosser FJ, Sumpio BE. The Semmes Weinstein monofilament examination as a screening tool for diabetic peripheral neuropathy. J Vasc Surg. 2009;50(3):675–682.

8.

Williams KA, Hurley RW, Lin EA, Wu CL. Neuropathic pain syndromes. In Benzon H, Rathmell JP, Wu CL, Turk DC, Argoff CE, eds. Raj’s Practical Management of Pain, 4th ed. Philadelphia: Mosby Elsevier. 2013: pp. 427–444.

9.

Bril V. Electrophysiologic testing. In Gries FA, Cameron NE, Low

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PA, Ziegler D, eds. Diabetic Neuropathy. New York: Thieme. 2003: pp. 177–184. 10. Lalkhen AG, Bhatia K. Perioperative peripheral nerve injuries. Cont Edu Anaesth Crit Care Pain. 2012;12(1):38–42. 11. Shakher J, Stevens MJ. Update on the management of diabetic polyneuropathies. Diabetes Metab Syndr Obes. 2011;4:289–305. 12. Tesfaye S, Vileikyte L, Rayman G, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011; Jun 21. 13. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev. 2011;(1):CD005451. 14. Freeman R, Durso-Decruz E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses. Diabetes Care. 2008; 31(7):1448–1454. 15. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev. 2007;(4):CD005454. 16. Ziegler D. Painful diabetic neuropathy: advantage of novel drugs over old drugs? Diabetes Care. 2009;32(Suppl 2): S414–S419. 17. Wernicke JF, Pritchett YL, D’Souza DN, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology. 2006;67(8): 1411–1420. 18. Boyle J, Eriksson ME, Gribble L, et al. Randomized, placebocontrolled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral

neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care. 2012;35(12): 2451–2458. 19. Tanenberg RJ, Irving GA, Risser RC, et al. Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an openlabel, randomized, noninferiority comparison. Mayo Clin Proc. 2011;86(7):615–626. 20. Martini C, Yassen A, Olofsen E, et al. Pharmacodynamic analysis of the analgesic effect of capsaicin 8% patch (Qutenza) in diabetic neuropathic pain patients: detection of distinct response groups. J Pain Res. 2012;5:51–59. 21. de Vos CC, Rajan V, Steenbergen W, van der Aa HE, Buschman HP. Effect and safety of spinal cord stimulation for treatment of chronic pain caused by diabetic neuropathy. J Diabetes Complications. 2009;23(1):40–45. 22. Dworkin RH, O’Connor AB, Kent J, et al. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. 2013;154(11):2249–2261. 23. Petrakis IE, Sciacca V. Does autonomic neuropathy influence spinal cord stimulation therapy success in diabetic patients with critical lower limb ischemia? Surg Neurol. 2000;53(2):182–188. 24. Petrakis IE, Sciacca V. Spinal cord stimulation in diabetic lower limb critical ischaemia: transcutaneous oxygen measurement as predictor for treatment success. Eur J Vasc Endovasc Surg. 2000;19(6): 587–592. 25. Tesfaye S, Vileikyte L, Rayman G, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Metab

Res Rev. 2011 Jun 21 [Epub ahead of print]. 26. Mueller MJ, Tuttle LJ, Lemaster JW, et al. Weight-bearing versus nonweight-bearing exercise for persons with diabetes and peripheral neuropathy: a randomized controlled trial. Arch Phys Med Rehabil. 2013; 94(5):829–838. 27. Ahn S, Song R. Effects of Tai Chi Exercise on glucose control, neuropathy scores, balance, and quality of life in patients with type 2 diabetes and neuropathy. J Altern Complement Med. 2012;18(12):1172–1178. 28. De Leon Rodriguez D, Allet L, Golay A, et al. Biofeedback can reduce foot pressure to a safe level and without causing new at-risk zones in patients with diabetes and peripheral neuropathy. Diabetes Metab Res Rev. 2013;29(2):139–144. 29. Simson U, Nawarotzky U, Friese G, et al. Psychotherapy intervention to reduce depressive symptoms in patients with diabetic foot syndrome. Diabet Med. 2008;25(2):206–212. 30. Stein C, Eibel B, Sbruzzi G, Lago PD, Plentz RD. Electrical stimulation and electromagnetic field use in patients with diabetic neuropathy: systematic review and meta-analysis. Braz J Phys Ther. 2013;17(2):93–104. 31. Freeman R. New and developing drugs for the treatment of neuropathic pain in diabetes. Curr Diab Rep. 2013;13(4):500–508. 32. Pluijms W, Huygen F, Cheng J, et al. Evidence-based interventional pain medicine according to clinical diagnoses. 18. Painful diabetic polyneuropathy. Pain Pract. 2011;11(2):191–198. 33. Khalil H. Painful diabetic neuropathy management. Int J Evid Based Healthcare. 2013; 11(1):77–79.

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Section 1 Chapter

9

Neurological Disorders

Alcohol-induced neuropathy Gulshan Doulatram, Tilak Raj, and Ankur Khosla

Case study A 60-year-old man presents with pain characterized as pins and needles on his soles extending up to his knees. He also complains of weakness, and has had two falls in the last 2 months. The symptoms have been gradually getting worse over the last 6 months. He appears very cachectic and reports a very heavy alcohol use for the last 30 years.

1. What are some of the epidemiologic considerations for this disease? What is the financial burden it imposes on society? Alcohol is one of the most commonly used substances in the world, and the abuse of this toxin closely mirrors in incidence. Consequently, the myriad detrimental effects to the body result in significant morbidity and mortality. From the notable increase in fat deposition, to pains of alcohol-induced gout, alcoholinduced neuropathy (AIN) is the most common. The true incidence of this condition is difficult to ascertain due to the varying definitions employed for AIN in the different studies. Definitions set forth by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) estimate that neuropathy is present in 25–66% of defined “chronic alcoholics” when using clinical and electrodiagnostic criteria.[1] When evaluating the risk factors for this condition, there appears to be some form of genetic component. Pessione et al demonstrated an increased risk in people with a parental history of alcoholism.[2] AIN is more common in women compared to men.[3] Data investigating this phenomenon suggests that peripheral nerves among females are

at increased sensitivity to the toxic effects of this chemical.[4] Given that the risk of developing alcoholic neuropathy is associated with the duration and extent of total lifetime consumption of alcohol, it is not surprising that it is more prevalent in elderly patients. Most people present with symptoms of the disease between the ages of 40–60. There is a dearth of information on the economic toll imposed upon society with specific regards to alcoholic neuropathy. Hence, the economic constraints of diabetic neuropathy can be used as a surrogate measure. It is reported that in the USA, the total annual cost of DPN and its complications was estimated to be between $4.6 and $13.7 billion, of which up to 27% of the costs of diabetes may be attributed to DPN.[5] It is evident that the burden carried by the individual and by society is of serious consideration during this era of chronic healthcare.

2. What is the pathophysiology of the disease? Alcoholic neuropathy is a primary axonal neuropathy characterized by wallerian degeneration of the axons and secondary demyelination of sensory and small motor fibers. Acetaldehyde, a metabolite of alcohol, has a direct neurotoxic effect by impairing axonal transport. The pathophysiology of alcohol-related nerve damage is complex and multifactorial, and includes: activation of spinal cord microglia, oxidative stress leading to free radical damage to nerves, activation of metabotropic glutamate receptors (mGlu5) in the spinal cord, and activation of the sympathoadrenal and hypothalamo– pituitary–adrenal (HPA) axis.[6] Ethanol promotes oxidative stress by decreasing the concentration of endogenous antioxidants, by generating reactive oxygen species, and increasing lipid peroxidation.

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Thiamine, an essential vitamin in the metabolism of pyruvate, has a role in the health of the peripheral nervous system. Thiamine deficiency is commonly found in alcoholic patients due to decreased absorption and hepatic depletion. Other studies have linked the direct toxic effects of alcohol on peripheral nerves with development of neuropathy. A combination of nutritional deficiency and direct toxicity is likely involved in the pathogenesis of alcoholic neuropathy, and these effects may be additive. Thiamine affects the larger motor fibers, compared to alcoholic neuropathy which affects small sensory fibers primarily by causing axonal damage.[7]

3. What are some other clinical conditions that may present in a similar way? Signs and symptoms of alcoholic neuropathy are not specific to this disorder. The range of neuropathic symptoms (including allodynia and paresthesia) are shared among a few other comorbidities. A detailed history and physical exam is important in helping to navigate through the possibilities. A non-exhaustive list includes:  Nutritional causes: Beriberi (thiamine deficiency) Folate deficiency Vitamin B12 deficiency Infectious causes:  Lyme disease Postpolio syndrome HIV-1-associated acute/chronic inflammatory demyelinating polyneuropathy HIV-1-associated distal painful sensorimotor polyneuropathy HIV-1-associated neuromuscular complications HIV-1-associated vacuolar myelopathy Leptomeningeal carcinomatosis Neuropathy of leprosy Tropical myeloneuropathies  Toxic/metabolic causes: Diabetic neuropathy Diabetic lumbosacral plexopathy Hypothyroid Disulfiram-induced polyneuropathy

Organophosphates Chemotherapeutical agents Radiation therapy  Immune system causes: Amyotrophic lateral sclerosis Charcot–Marie–Tooth disease Mononeuritis multiplex Chronic inflammatory demyelinating polyradiculoneuropathy Lambert–Eaton myasthenic syndrome Paraneoplastic autonomic neuropathy Paraneoplastic encephalomyelitis Primary lateral sclerosis Sarcoidosis Syringomyelia Compressive causes:  Femoral mononeuropathy Meralgia paresthetica Peroneal mononeuropathy

4. What are some of the clinical features of alcohol-induced neuropathy? Given that alcohol abuse comes with comorbid conditions such as vitamin deficiencies, the presentation of alcoholic neuropathy can be concurrent with a vitamin B1 deficiency-induced neuropathy. The former is a progressive sensory-dominant symptomatology, and the latter has an inconsistent presentation. In alcohol-induced neuropathy, paresthesias of the feet and toes are commonly reported. With disease progression, the paresthesias migrate in a proximal and symmetric distribution. Consequently, difficulty walking with propensity for falls secondary to decreased afferent neuronal input may be reported. The paresthesias follow a “stocking” distribution, and objectively will demonstrate diminished vibratory/pinprick sensation, as well as thermal/ proprioceptive sensation. In advanced cases, reflex arches can be disrupted. The clinician should examine the patellar, Achilles, and gastrocnemius– soleus muscle complex reflexes. This will help evaluate progression of symptoms. Visual inspection with palpation for muscle body definition/ tone of the lower leg and foot will provide useful information.

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5. What are other tests including lab tests and imaging that may aid in your diagnostic work-up? How would you make a diagnosis of alcohol neuropathy?  Complete metabolic panel (electrolytes, renal function, and liver function panel – chronic alcohol consumption causes an increase in liver enzymes, e.g., gamma glutamyltransferase, aspartate aminotransferase, alanine aminotransferase).  Thiamine, vitamin B12, and folate levels – these vitamins are essential for the proper functioning of the nervous system and should be checked early in a patient with polyneuropathy. Alcoholics may have nutritional deficiencies which may contribute to the development of neuropathy.[8] Other vitamin levels that need checking include pyridoxine (B6), pantothenic acid and biotin, niacin, and vitamin A.  Hematology screen to check for anemia.  Diabetes testing – plasma glucose and HbA1c – peripheral neuropathy may be the presenting symptom in diabetes; however diabetic polyneuropathy usually occurs in patients who have had diabetes for several years.  Urine analysis and serum creatinine to screen for renal insufficiency.  Thyroid function tests.  Erythrocyte sedimentation rate and C-reactive protein.  Serum protein electrophoresis with immunofixation electrophoresis.  Antinuclear antibody, Anti-SSA and SSB antibodies, rheumatoid factor.  Paraneoplastic antibodies.  Rapid plasma regain.  Esophagogastroduodenoscopy and lower GI series may be considered only if symptoms are present. After the more common diagnoses have been excluded then the following are required:  Screening for heavy metal toxicity, e.g., lead.  Tests for HIV and venereal disease – Distal symmetrical polyneuropathy can be a common and early manifestation of HIV infection.[9] HIV-

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infected patients who use illicit substances like alcohol are at a higher risk for developing distal symmetrical polyneuropathy.[10] Imaging studies – There may be radiographic evidence of distal neuropathic arthropathy from long-standing sensory deficits. Nerve conduction studies – Although not specific for alcoholic neuropathy, NCS can help with the diagnosis of neuropathy and quantify the extent. NCS may be normal if only small fibers are involved, although more typically they show a pattern of sensory axon loss with abnormal sural sensory action potentials and conduction velocity as the most sensitive markers.[11] Tibial H-reflex – There may be absent response or symmetrically reduced amplitude or increased latency. This is thought to be the most sensitive test to measure nerve conduction velocity in alcoholic polyneuropathy with some studies quoting rates as high as 60%.[1] T-wave – Like the H-reflex the T-wave response is also a sensitive test for latent alcoholic neuropathy[12] showing a delay in 60% of patients with subclinical alcoholic neuropathy. It is simple and painless to perform. The T-wave is elicited by a tap from the reflex hammer. The smallest latency as well as the maximum reflex amplitude is recorded from eight taps in succession. Needle electromyography (EMG) – A typical neuropathy screen will involve a proximal and a distal muscle in the upper and lower extremity. Significant abnormalities seen in patients with ETOH neuropathy include the presence of positive sharp waves and/or fibrillation potentials indicating denervation. Complex, repetitive discharges also may be observed. Quantitative sensory testing (QST) – This measures sensory thresholds for pain, touch, vibration, and hot and cold temperature sensation. Skin biopsy – Epidermal nerve fiber density and morphology, e.g., tortuosity, complex ramifications, clustering, and axon swellings, can be quantified and compared with control values with a 3-cm skin biopsy and immunohistochemistry. Sural nerve biopsy – Small-fiber-predominant axonal loss is characteristic of alcoholic neuropathy. Myelin irregularities and segmental demyelination due to widening of consecutive

Chapter 9: Alcohol-induced neuropathy

nodes of Ranvier most likely caused by axonal atrophy were conspicuous.[13]  Diagnosis is based on establishing the presence of a slowly progressive sensory-dominant neuropathy and chronic alcohol abuse, and ruling out other causes of neuropathy. Unhealthy drinking is defined as more than three or four drinks per day or more than 10 g of alcohol per day.

6. Briefly describe the therapeutic options available to treat and manage alcohol neuropathy The treatment of AIN starts by preventing any further damage to the nerves. This includes complete abstinence from alcohol by rehabilitation and correction of any coexisting nutritional deficiencies. Although nutritional deficiencies often coexist with alcoholism and contribute toward the overall symptoms and pathophysiology, correcting them alone does not cause significant improvement. Hence, a comprehensive approach aimed toward correction of all associated nutritional deficiencies (especially vitamin B1 and B12) and cessation of alcohol provides the most realistic chances of partial recovery from nerve damage and the associated neuropathy. After achieving these two primary goals, a wide array of neuropathic medications can be utilized to treat the symptoms of alcoholic neuropathy.[6] Unfortunately, there are no randomized controlled trials assessing the effectiveness of the different neuropathic medications in AIN. Hence, the medications described below can be tried, keeping in mind that the evidence for their use has been extrapolated from other known, well-studied neuropathic conditions such as painful diabetic peripheral neuropathy.

Alpha-lipoic acid Alpha-lipoic acid is a nutrient that has been shown to increase glucose uptake, glutathione concentrations, and blood flow in neurons. Though most studies have established the effectiveness of alpha-lipoic acid in the treatment of diabetic neuropathy, this medication has not been studied in alcohol-induced neuropathy.[14]

Acetyl-L-carnitine Acetyl-L-carnitine (ALC) is a molecule derived from acetylation of carnitine in the mitochondria. ALC

supplementation can potentially induce neuroprotective and analgesic effects in the peripheral nervous system. Several studies (including double-blind, placebo-controlled, parallel-group studies and few open studies) have shown an effect of ALC in various neuropathies, such as diabetic neuropathy, HIV and antiretroviral therapy-induced neuropathies, and neuropathies due to compression and chemotherapeutic agents. ALC is known to work even after neuropathic pain has been established.[15] ALC can also improve the function of peripheral nerves by increasing nerve conduction velocity, reducing sensory neuronal loss, and promoting nerve regeneration. ALC regulates processes in energy metabolism, as well as activation of muscarinic cholinergic receptors in the forebrain. Though this drug has never been studied in alcoholic neuropathy, it shows potential primarily due to its mechanisms of actions.

Vitamin E Studies with vitamin E have shown that both alphatocopherol and tocotrienol are effective in rat models of alcohol-induced neuropathy by virtue of their antioxidant properties.[16] Studies in humans, unfortunately, do not exist to confirm this. In another recent study, curcumin, an alkaloid isolated from Curcuma longa, was shown to improve motor nerve conduction velocity and decrease pain in rats.[17] This protective effect of curcumin may be accounted for by a reduction in oxidative stress, inhibition of cytokines, and a decrease in DNA fragmentation.

Anticonvulsants These include the traditional agents, such as carbamazepine and valproate, and newer agents, such as gabapentin and pregabalin. Carbamazepine, phenytoin (Dilantin), and valproate are some of the older anticonvulsants that have been used to treat neuropathic pain.[18] Patients should have detailed laboratory tests, including blood urea nitrogen, creatinine, transaminase, iron levels, a complete blood count (including platelets), reticulocyte count, and liver function test prior to initiation of therapy. Carbamazepine also can cause dermatologic reactions such as toxic epidermal necrolysis and Stevens–Johnson syndrome. In light of the array of adverse effects, newer anticonvulsants are preferred. Gabapentin is used widely in the treatment of neuropathic pain. The major side effects reported from

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gabapentin include sedation and dizziness. The major drawback is the poor bioavailability of the drug requiring high doses.[19] Pregabalin, an analog of the neurotransmitter GABA, binds the alpha2-delta (a2-d) unit of the calcium channels reducing calcium influx at nerve terminals. This reduces the release of several neurotransmitters, including glutamate, noradrenaline, and substance P. Pregabalin does not bind GABA-A and GABA-B receptors and it is not converted metabolically into GABA.[2] Pregabalin is usually well tolerated, and has a good safety profile. Common side effects include somnolence, dizziness, weight gain, and peripheral edema, which rarely require discontinuation of therapy. Rare but serious adverse events include rhabdomyolysis, acute renal failure, hyperthermia, and secondary acute-angle glaucoma. The dose of pregabalin requires careful titration in patients with chronic kidney disease.

Antidepressants TCA antidepressants, such as amitryptiline and nortryptiline, are effective in treatment of various neuropathies by their central modulation of inhibitory pathways.[20] They are not tolerated well by patients due to their effects on alpha-adrenergic, H1-histamine, muscarinic, cholinergic, and N-methyl-D-aspartate receptors. Some of the adverse effects reported with TCAs include orthostatic hypotension, cardiac arrhythmias, dizziness, and sedation. TCA are contraindicated in the presence of heart failure, arrhythmias, or recent myocardial infarction. Anticholinergic effects of TCAs warrant caution in patients with narrow-angle glaucoma, benign prostatic hypertrophy, orthostatic hypotension, urinary retention, impaired liver function, or thyroid disease. QTc interval should be assessed because of the risk of torsades de pointes. SNRIs, including venlafaxine (Effexor) and duloxetine (Cymbalta) are used in the treatment of neuropathic pain. They are better tolerated and have fewer drug interactions than TCAs. Duloxetine hydrochloride, a dual-reuptake inhibitor of 5-HT and NE (SNRI), is both effective and well tolerated by patients with neuropathic pain. Some of the side effects include somnolence, nausea, dizziness, decreased appetite, and constipation.

Topical agents 5% lidocaine, a sodium channel blocker, is a useful adjunct to antidepressants and anticonvulsants in patients with painful sensory neuropathy.

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Capsaicin (0.075%) is a topically applied alkaloid that acts peripherally by depleting the neurotransmitter substance P from sensory nerves. The most common adverse effects are stinging and burning related to the brief release of substance P. In a large, multicenter, double-blinded placebo-controlled trial, it was shown that patients who received 0.075% capsaicin had reduced intensity and improved pain relief.[19] However, this study was done in patients with diabetic neuropathy and the results can be extended to alcoholic patients with similar neuropathic symptoms. It can be speculated that the higher concentration 8% capsaicin patch, an agonist at transient receptor potential channels–vanilloid receptors (TRP V1) could also be effective in these patients. Topical clonidine gel has also shown promise in a few patients with minimal side effects. Several compounding creams containing a mixture of different medications including gabapentin, NSAIDs, and clonidine are now available. The effectiveness of these creams has not yet been established.

Opioids Tramadol acts at both the opioid and serotonin/norepinephrine receptors, and is effective in treating pain and improving quality of life and physical functioning, specifically in patients with neuropathic pain.[21] However, tramadol should be used only as a secondline drug after first-line treatments either alone or in combination are found to be ineffective. The side effects of tramadol are related to both its opioid and serotonergic effects. Constipation, respiratory depression, lowered seizure threshold, somnolence, and serotonin syndrome, especially in patients taking concomitant antidepressants, can occur. Opioids, including short-acting and long-acting opioids are used in combination with other neuropathic medications as a last resort if all other medications have failed. Relying solely on opioids in the treatment of AIN carries the risk of tolerance and opioid-induced hyperalgesia. This is especially true in patients who may have a potential for opioid abuse in addition to primary alcohol dependence. Opioid therapy should be implemented very cautiously, titrating doses slowly and instituting objective measures of compliance, including regular urinary drug screening modalities. Methylcobalamin: Patients with clinical vitamin B12 deficiency can be tested for serum levels of metabolites

Chapter 9: Alcohol-induced neuropathy

such as methylmalonic acid and homocysteine. Hypomethylation at the myelin sheath contributes to neuropathy associated with this deficiency.[22] Supplementation with methylcobalamin may improve these clinical symptoms. Further studies are required to see if correction of these changes will improve the clinical course in patients with alcoholic neuropathy. Benfotiamine: S-benzoylthiamine O-monophosphate, a synthetic derivative of thiamine has been shown to reverse neuropathic symptoms and electrophysiologic changes in some small studies.[23] Deficiency of vitamin B6 has been shown to occur commonly in alcoholics due to inadequate dietary intake, and decreased absorption and depletion of thiamine diphosphate (the active coenzyme of thiamine). Myo-inositol: Myo-inositol is an important constituent of the phospholipids that make up nerve cell membranes. Supplementation with myo-inositol completely prevented a reduction in nerve conduction velocity in diabetic rats.[24] Further studies are required with myo-inositol to determine its effectiveness in alleviating symptoms associated with alcoholic neuropathy. N-acetylcysteine: N-acetylcysteine, an amino acid, is a potent antioxidant, and helps to enhance glutathione concentrations.[25] It has been used in animal models of diabetic and cisplatin-induced neuropathy. Further preclinical and clinical studies are required to assess this molecule in alcoholic neuropathy.

Physical therapy Patients with alcoholic neuropathy need a comprehensive physical therapy plan to improve gait and balance, which are frequently affected in these patients. These include strengthening of weakened lower extremity muscles, range of motion (ROM) exercises, and stretching to prevent contracture and maintain normal gait mechanics. An ankle-foot orthosis (AFO) may be needed to assist patients with weak ankle dorsiflexion, eversion, and/or plantar flexion. This device can also help with ankle proprioception and improve gait and prevent ankle sprains. Vigilant foot care and the use of shoes with an enlarged toe box are useful in preventing foot ulcers.

Occupational therapy Occupational therapy is also a key component of the rehabilitation process in patients with alcoholic neuropathy. The occupational therapist can (1) assist

with several aspects to improve function including ADL, with adaptive equipment, and (2) focus on compensatory mechanics to overcome both gait and strength abnormalities.

Psychotherapy Consultation with a psychologist may be indicated to help patients with chronic alcoholism recover from the physical and emotional withdrawal associated with cessation of alcohol consumption. Consultation with a nutritionist may help formulate strategies for replacement of essential nutrients in malnourished alcoholic patients. Referral to a substance abuse support group, such as Alcoholics Anonymous (AA), may help patients cope with alcohol cessation. Complete cessation of alcohol consumption is necessary to improve or reverse the symptoms associated with alcoholic neuropathy.

6. Describe any treatment-related complications The complications related to treatment of alcoholic neuropathy are primarily from the medications commonly used for alcoholism or neuropathic pain. One specific mention is disulfiram associated neuropathy. In fact, 1 in 15 000 patients taking disulfiram develops peripheral neuropathy every year due to disulfiram toxicity. These patients are often misdiagnosed as having alcoholic neuropathy and pose a challenge to patients attempting to abstain from alcohol.

7. Patient refuses to stop drinking and using marijuana. Does that impose any ethical issues? The presence of ongoing neuropathic pain in a patient with alcoholic neuropathy who refuses to stop drinking poses a unique dilemma to the treating physician. The physician will need to counsel the patient about the effects of alcohol on the nervous system, while offering a comprehensive treatment plan. The patient should also be provided complete support from a psychologist, social services, and rehabilitation services. Potential conflicts with opioid therapy may arise in patients with continued alcohol or drug use. A decision to withdraw opioid therapy must be made at an individual level, and after extensive counseling has been offered to the patient. The patient may still, however, require extensive

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and sustained psychologic support to avoid relapses. Close communication with the primary care physician and regular follow-up care for the patient is essential to monitor the effectiveness of therapy.

8. What conclusions could you draw from this case? Alcohol neuropathy is associated with increased morbidity and a definite decrease in the quality of life. These patients are often not diagnosed early, and usually present to pain consultants after the involvement of sensory and long motor fibers. The disease is commonly associated with several nutritional deficiencies (especially thiamine and folate) which worsen the neuropathy. Initially, neuropathy from alcohol was thought to be only due to thiamine deficiency. More recent studies have elucidated the direct toxic

References 1.

2.

3.

4.

5.

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Laker SR. Alcoholic neuropathy. Medscape com 2013 June 1. Available from: URL: http:// emedicine.medscape.com/article/ 315159-overview (cited Aug 23, 2013).

6.

7.

effect of alcohol and its metabolites on nerves. The treatment involves abstinence of alcohol to halt the progressive nature of nerve damage, correction of nutritional deficiencies, and an array of medications. Consultation with a nutritionist may help formulate strategies for replacement of essential nutrients in malnourished alcoholic patients. None of the medications have been studied extensively in humans. Of the medications, benfotiamine, alpha-lipoic acid, ALC, and methylcobalamin are among the well-researched options for the treatment of peripheral neuropathy. Other potential nutrient or botanical therapies include vitamin E, myo-inositol, N-acetylcysteine, and topical capsaicin. Understanding the basic pathophysiologic mechanisms involved in alcohol-induced neuropathic pain will pave the way in the development of new therapeutic modalities which can target disrupted cellular signaling machinery.

Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012; 73(3):348–362. Koike H, Iijima M, Sugiura M, et al. Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann Neurol. 2003;54(1):19–29.

subjects. J Peripher Nerv Syst. 2005;10(4):375–381. 12. Schott K, Schafer G, Gunthner A, Bartels M, Mann K. T-wave response: a sensitive test for latent alcoholic polyneuropathy. Addict Biol. 2002;7(3):315–319. 13. Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. 2006;19(5):481–486.

Pessione F, Gerchstein JL, Rueff B. Parental history of alcoholism: a risk factor for alcohol-related peripheral neuropathies. Alcohol Alcohol. 1995;30(6):749–754.

8.

Monforte R, Estruch R, Valls-Sole J, et al. Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose-related toxic effect of alcohol. Arch Neurol. 1995;52(1):45–51.

Peters TJ, Kotowicz J, Nyka W, et al. Treatment of alcoholic polyneuropathy with vitamin B complex: a randomised controlled trial. Alcohol Alcohol. 2006;41(6):636–642.

14. Kishi Y, Schmelzer JD, Yao JK, et al. Alpha-lipoic acid: effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy. Diabetes. 1999;48(10):2045–2051.

9.

Fama R, Eisen JC, Rosenbloom MJ, et al. Upper and lower limb motor impairments in alcoholism, HIV infection, and their comorbidity. Alcohol Clin Exp Res. 2007;31(6): 1038–1044.

15. Pisano C, Pratesi G, Laccabue D, et al. Paclitaxel and Cisplatininduced neurotoxicity: a protective role of acetyl-Lcarnitine. Clin Cancer Res. 2003; 9(V):5756–5767.

Ammendola A, Gemini D, Iannaccone S, et al. Gender and peripheral neuropathy in chronic alcoholism: a clinicalelectroneurographic study. Alcohol Alcohol. 2000;35 (4):368–371. Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care. 2003;26(6): 1790–1795.

10. Robinson-Papp J, Gelman BB, Grant I, et al. Substance abuse increases the risk of neuropathy in an HIV-infected cohort. Muscle Nerve. 2012;45(4):471–476. 11. Zambelis T, Karandreas N, Tzavellas E, Kokotis P, Liappas J. Large and small fiber neuropathy in chronic alcohol-dependent

16. Tutuncu NB, Bayraktar M, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. Diabetes Care. 1998;21(11): 1915–1918. 17. Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Therapeutic role of curcumin

Chapter 9: Alcohol-induced neuropathy

in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals. Neurosci Lett. 2012;511(1):18–22. 18. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289–305. 19. Rains C, Bryson HM. Topical capsaicin. A review of its pharmacological properties and therapeutic potential in postherpetic neuralgia, diabetic neuropathy and osteoarthritis. Drugs Aging. 1995;7(4):317–328. 20. Sandercock D, Cramer M, Wu J, et al. Gabapentin extended release for the treatment of painful

diabetic peripheral neuropathy: efficacy and tolerability in a double-blind, randomized, controlled clinical trial. Diabetes Care. 2009;32(2):e20. 21. Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11(6):521–534. 22. Saperstein DS, Barohn RJ. Peripheral neuropathy due to cobalamin deficiency. Curr Treat Options Neurol. 2002; 4(3):197–201. 23. Woelk H, Lehrl S, Bitsch R, Kopcke W. Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week

randomized controlled study (BAP I Study). Alcohol Alcohol. 1998;33(6):631–638. 24. Sundkvist G, Dahlin LB, Nilsson H, et al. Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance. Diabet Med. 2000; 17(4):259–268. 25. Love A, Cotter MA, Cameron NE. Effects of the sulphydryl donor N-acetyl-L-cysteine on nerve conduction, perfusion, maturation and regeneration following freeze damage in diabetic rats. Eur J Clin Invest. 1996;26(8):698–706.

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Section 1 Chapter

10

Neurological Disorders

HIV neuropathy Gulshan Doulatram, Tilak Raj, and William Yancey

Case study A 44-year-old male presents with burning in both legs for the past 8 months which has become severe in the last 2 months. He has been diagnosed with HIV for the past 3 years. His current CD4+ cell count is 250 cells/µl and viral load 50 copies/ml. He was started on highly active antiretroviral therapy (HAART) about 3 months ago. He smokes marijuana and insists that it helps with his pain.

1. How prevalent is this disease presentation?Couldyouexplainsomeof the epidemiologic features of this disease? Are there any cost concerns? In its 2012 HIV Surveillance Supplemental Report, the Centers for Disease Control estimates that over 1.1 million persons in the USA are infected with HIV, and predicts an additional 50000 new infections each year.[1,2] The global prevalence of HIV is 33 million. These individuals are at risk for multiple neurologic complications due to their disease. The most common of these complications is distal symmetric polyneuropathy (DSP).[3,4] Its high prevalence ranks it as one of the more frequently encountered etiologies of neuropathic pain in the general population. As such, DSP is a substantial contributor to the healthcare cost of neuropathic pain as a whole. Berger et al examined this and demonstrated an average yearly healthcare cost of $17355 for a patient with a painful neuropathic disorder versus $5715 for a matched control patient.[5] The prevalence of DSP among HIV-infected individuals has been reported to be between 34 and 63%.[6–8] Data is limited for pediatric populations, but DSP appears to be similarly common in children with HIV with a prevalence of 34%.[9] Differences

among these estimates can be attributed in part to the evolution of HIV into a chronic disease with the advent of effective antiretroviral therapy (ART).[10] ART has resulted in a decrease in the incidence of DSP as well as a shift in its associated risk factors.[7,10,11] Prior to effective ART, the risk of DSP had been linked to decreased CD4 lymphocyte counts and increased HIV viral loads.[12,13] More recent studies have not confirmed these risk factors[7,11] and have, instead, identified factors such as substance abuse,[14] diabetes, nutritional deficiencies,[15] and aging.[11]

2. What is the differential diagnosis of HIV neuropathy? The patient with HIV is susceptible to multiple painful neurologic complications, including those most commonly associated with HIV infection and those of the general population. A complete differential should include both categories and allow for the coexistence of two or more diagnoses to explain a patient’s pain. HIV neuropathy is often difficult to differentiate from antiretroviral neuropathy.[16,17] Differentiating the two requires identification of a potentially offending agent, such as a dideoxynucleoside, among the patient’s medications and determining whether onset of therapy with this drug was associated with the onset of neuropathy (usually 1 week to 6 months later).[16] Additional painful neuropathies associated with HIV infection include mononeuropathy multiplex (MM) and progressive polyradiculopathy (PP). These conditions may be most easily differentiated from DSP based on their clinical presentations. For example, in contrast to the classic stocking-glove distribution and primarily sensory effects of DSP, MM presents with asymmetric, multifocal findings that may involve both peripheral and cranial nerves. Further,

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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MM is more likely to result in motor deficits.[17] PP can similarly be discerned by its motor effects, which may include a rapidly progressive flaccid paraparesis.[18] Additionally, PP is associated with lumbosacral pain and radicular symptoms.[16] Lastly, a complete differential should include diagnoses not necessarily related to HIV infection. Depending on clinical suspicion, these could include the following:  Nutritional causes: Beriberi (thiamine deficiency) Folate deficiency Vitamin B12 deficiency  Infectious causes: Lyme disease Postpolio syndrome Leptomeningeal carcinomatosis Neuropathy of leprosy Tropical myeloneuropathies Syphilis  Toxic/metabolic: Diabetic neuropathy Diabetic lumbosacral plexopathy Hypothyroid Disulfiram-induced polyneuropathy Organophosphates Chemotherapeutical agents Radiation therapy Alcohol Uremic neuropathy  Immune: Amyotrophic lateral sclerosis Charcot–Marie–Tooth disease Mononeuritis multiplex Chronic inflammatory demyelinating polyradiculoneuropathy Lambert–Eaton myasthenic syndrome Paraneoplastic autonomic neuropathy Paraneoplastic encephalomyelitis Primary lateral sclerosis Sarcoidosis Syringomyelia  Compressive: Femoral mononeuropathy Meralgia paresthetica Peroneal mononeuropathy

Most of these diagnoses can be evaluated by simple laboratory studies.

3. Describe the clinical presentations of HIV neuropathy Distal symmetric polyneuropathy (DSP) This is the most common form of neuropathy and usually affects the lower extremities in the toes and soles similar to diabetic neuropathy. The upper extremities usually are involved much later. Sensory symptoms are the hallmarks of DSP.[17] Significant muscle weakness and loss of proprioception are usually not seen and should prompt an evaluation for other causes of neuropathy or a different presentation. Visual analog scale (VAS) and Gracely (a 20 point scale with verbal descriptors of pain) pain scales are commonly used in DSP. Some of the signs and symptoms include:  Paresthesia  Dysesthesia  Numbness  Diminished ankle reflexes  Reduction of pinprick  Reduction of temperature  Antalgic gait  Loss of vibration

ARV-associated neuropathy This painful neuropathy is triggered by the antiretroviral therapy including HAART. Thirty-six percent of HIV patients treated with HAART will develop this neuropathy.[17,20] Risk factors include age, severe immunosuppression, and combined use of dideoxynucleoside analogs stavudine (D4T), zalcitabine (ddC), and didanosine (ddI). These drugs inhibit mitochondrial DNA synthesis which leads to mitochondrial dysfunction and reduced energy availability. There is predominantly small-fiber involvement with prominent pain and paresthesias very similar to DSP.

Progressive polyradiculopathy PP involving the lumbar nerve roots is fortunately rare and only seen in the very advanced forms of the disease. Opportunistic infection of the lumbar nerve roots is usually caused by cytomegalovirus (CMV), varicella-zoster, herpes simplex, syphilis, tuberculosis, and lymphoma. Clinically, patients present with

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radicular pain, profound weakness, and bladder and bowel incontinence. Signs include flaccid paralysis and absent reflexes and sensation.[16] Treatment includes early detection and aggressive treatment of the infectious causes, which in most cases is CMV related. This can potentially prevent advanced and permanent motor and sensory sequelae.

Mononeuropathy multiplex Mononeuropathy multiplex involves cranial and peripheral nerves and is associated with pain and paresthesias in the affected dermatomes with motor deficits.[17] Steroids, plasmapheresis and intravenous immunoglobulin can be used in severe cases.

4. How would you make a diagnosis of HIV neuropathy? Apart from a history of HIV infection, clinical evaluation, and laboratory testing to rule out other potential causes for neuropathy, there are a few screening measures which can diagnose and quantify the severity of neuropathy.[17]

Brief peripheral neuropathy screen A brief peripheral neuropathy screen (BPNS) is a simple way to assess neuropathic pain symptoms in HIV patients and has the advantage that it relies only on the history and physical exam. The test involves three questions in the history and two examination measures. BPNS has a high specificity and low sensitivity and has the advantage that it can be used clinically and does not rely on other tests. The signs and symptoms include: 1. Pain, aching, or burning in the feet 2. Pins and needles in feet/legs 3. Numbness in legs 4. Lower extremity vibration 5. Lower extremity reflexes

Total neuropathy score Total neuropathy score (TNS) is based on clinical tests and functional nerve studies. These include sensory and motor symptoms, sensation to pin and vibration, tendon reflexes, motor function, QST, and NCS. All these components are summed up to give a TNS which can highlight the severity of the disease and assess response to various treatment regimes.

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5. Describesomeofthelaboratorytests that would aid in your diagnosis Quantitative sensory testing QST measures sensory thresholds for pain, touch, vibration, and hot and cold temperature sensation. It is increasingly used, especially in clinical therapeutic trials. A number of devices are commercially available and range from handheld tools to sophisticated computerized equipment with complicated testing algorithms. Specific fiber functions can be assessed: Aδ fibers with cold and cold-pain detection thresholds, C-fibers with heat and heat-pain detection thresholds, and large fiber (Aαβ-) functions with vibration detection thresholds. Elevated sensory thresholds correlate with sensory loss and lowered thresholds occur in allodynia and hyperalgesia. In asymptomatic patients, abnormal QST thresholds suggest subclinical nerve damage. QST is a psychophysical test and therefore is dependent upon patient motivation, alertness, and concentration.

Nerve conduction studies Sural nerve amplitude is absent or reduced in DSP with occasional involvement of median and ulnar nerves. In MM, there is a dramatic decrease in compound motor and sensory action potentials.

EMG EMG shows signs of chronic denervation with reinnervation in distal muscles of lower extremities. In a patient with PP, EMG findings include severe and widespread axonal pathology of the lumbar nerve roots.

Nerve biopsy Sural nerve biopsy shows degeneration of myelinated and unmyelinated axons of the sural nerve with associated moderate inflammatory infiltrates. These changes are more marked in MM with detection of CMV inclusions in peripheral nerves.

Skin biopsy Decrease in distal epidermal nerve fiber density (ENFD) is associated with worsening of distal sensory polyneuropathy and is a very sensitive test to detect early disease.

Chapter 10: HIV neuropathy

Measures of small-fiber neuropathy Most of the tests mentioned above measure large fiber involvement. ART therapy for HIV is usually associated with small-fiber neuropathy and hence may go undetected with the standard tests.[18] Utah Early Neuropathy Scale (UENS) and QSART can be used in this subset of population to detect neuropathy in the early stages of therapy.

Utah Early Neuropathy Scale The Utah Early Neuropathy Scale (UENS) has a sensitivity of 92% for early sensory loss. UENS emphasizes severity and spatial distribution of pin (sharp) sensation loss in the foot and leg and focuses less on motor weakness.

Quantitative Sudomotor Axon Reflex Test QSART is sensitive (80% sensitivity) and non-invasive and has been studied in other well-known neuropathies including diabetes. It is generally shown to correlate very well with fiber loss as measured by intraepidermal nerve fiber density (IENFD). The test assesses autonomic C-fibers by measuring sweat volume, and is a measure of autonomic mediated cutaneous sweat production in response to iontophoresed acetylcholine.

Autonomic function testing Autonomic testing is valuable in patients with neuropathic pain disorder who have normal or mildly abnormal electrophysiologic (NCV/EMG) findings. The most useful tests are the QSART, thermoregulatory sweat test, heart rate responses to deep breathing, Valsalva ratio, and surface skin temperature. It has been clearly shown that DSP is closely associated with autonomic neuropathy in HIV patients.[19]

6. Are there any imaging tests that would help in the diagnosis? Imaging modalities are rarely required to diagnose distal sensory neuropathy. However, MRI with contrast may be useful in PP because it typically shows enhancement of spinal nerve roots.

7. What is the pathophysiology of this disease? The envelope glycoprotein of HIV, gp-120, is primarily responsible for the development of DSP.[20] The

interaction between gp120 and chemokine receptors CXCR4 and CXCR5 on the spinal cord microglia promotes DSP in HIV patients. This interaction is further potentiated by nitric oxide (NO) by causing the release of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukins. Nitric oxide inhibitors and TNF and interleukin antagonists have been shown to reduce allodynia in animal models. Proinflammatory cytokines such as TNF, IL-1, and IL-6 released by the microglia and dorsal root ganglia are nociceptor mediators and play an important role in the development and maintenance of HIV-associated neuropathy. Mitochondrial dysfunction and energy failure in the distal axon are also thought to be responsible in the pathophysiology of DSP.

8. What treatment modalities exist currently for this condition? As with other neuropathies, once the diagnosis is established, treatment should promptly begin utilizing a stepwise approach. Patients with HIV-related neuropathy are usually undertreated. This is due to inadequate evidence for the effectiveness of therapeutic options and resistance on the part of physicians due to fear of addiction in patients with concomitant substance abuse. There are no FDA-approved medications for the use of HIV-associated neuropathy. The main goals of therapy include effective analgesia and improvement in the quality of life. Mild analgesics such as acetaminophen, aspirin, and other non-steroidal agents could be effective initially.[20] Anticonvulsants, antidepressants, lidocaine patch, and opioids have also been used. If DSP is related to antiretroviral therapy, then a careful consideration needs to be made to stop therapy if ineffective or to continue therapy with concomitant analgesics. In addition to pharmacologic options, non-pharmacologic remedies such as biofeedback, meditation, acupuncture, and physical therapy have been shown to be equally effective in the treatment of distal sensory polyneuropathy.

Pharmacologic treatment Anticonvulsants Most of the data that support the use of anticonvulsants stem from studies in other well-known neuropathic pain states. However, according to existing guidelines in the treatment of neuropathic pain, all first-line agents, including anticonvulsants, have been found to be

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ineffective in DSP.[20] Some of the anticonvulsants commonly used in other neuropathic pain states include gabapentin, carbamazepine, lamotrigine, phenytoin, topiramate, and clonazepam. Several multicenter double-blinded randomized trials showed no improvement in the VAS scores despite using high doses of gabapentin and pregabalin. There is also some evidence for lamotrigine in the treatment of DSP. Apart from a modest effect in HAART-associated neuropathy, lamotrigine was also found to be ineffective and hence does not have a significant place in the analgesic therapy.

Antidepressants Two trials that have looked at the efficacy of amitryptiline and mexilitine in HIV-associated neuropathy have shown no benefits compared to placebo treatment. In the absence of evidence, and in light of anticholinergic side effects such as arrhythmias, orthostatic hypotension, dry mouth, and sedation, it may be prudent not to consider this class of medications as a first choice in the treatment of DSP.

Topical agents Topical preparations are useful adjuncts to oral agents since they are generally well tolerated and safe. 5% lidocaine and 0.75% clonidine can be used in patients exhibiting classic neuropathic symptoms. Four trials have examined the role of 0.075% capsaicin and found it to be ineffective.[21] The 8% capsaicin patch, however, has shown promise in patients with distal sensory neuropathy.[22] Capsaicin binds to vanilloid receptors causing depolarization of C-fiber nociceptors, increased permeability to sodium and calcium ions, and release of Substance P. This explains the transient burning seen with the application of capsaicin. Subsequently, depletion of Substance P contributes toward its analgesic effect with eventual loss of C-fiber neurons causing degeneration of epidermal nerve fibers. This effect is controversial in HIV neuropathy where there is already loss of epidermal nerve fibers.

Opioids In 2007, recommendations from the Neuropathic Pain Special Interest Group moved opioids to second-line therapy in the treatment of neuropathic pain.[23] Exceptions to this rule include acute severe pain, neuropathic cancer pain, and pain not controlled with usual first-line medications. Opioids are not routinely recommended for long-term use because their long-term safety has not been established. Other reasons include

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potential for immunosuppression, hypogonadism, opioid-induced hyperalgesia, and addiction. Longacting opioids are preferred due to consistent plasma levels. Potential interactions of opioids and other HIV medications need to be considered. Antiretrovirals such as ritonavir increase plasma concentrations of oxycodone. Compliance to therapy should be monitored very carefully, especially if there are other risk factors such as prior substance abuse. More recent evidence has shown that opioid therapy may actually be nociceptive by upregulating specific chemokine receptors that promote pain in HIV patients. μ-Opioids can increase toxicity either by their direct action on neurons or by potentiating HIV replication in infected cells of the CNS, which, in turn, increases the production of neurotoxic proteins, cytokines, glutamate, reactive oxygen species, and nitric oxide.

Smoked cannabis Smoked cannabis has been shown to be statistically superior to placebo in two separate studies by causing a greater than 30% improvement in VAS scores.[24] Cannabis exerts its effects by binding to cannabinoid receptors in the central and peripheral nervous system, which interact with noradrenergic and kappa-opioid receptors to promote attenuation of pain.

Antiretroviral therapy The effects of antiretroviral therapy on DSP are usually positive, with studies demonstrating that patients improved both symptomatically as well as scored well in quantitative thermal testing. However, in one study of a small group of patients, the neurotoxic dideoxynucleoside may have worsened or caused neuropathic pain.[25] The diagnosis is usually made by decreasing or stopping the medication for 4 weeks to see if symptoms improve. Often, the therapy can be switched to non-toxic antiretroviral agents, but, if that is not possible, then a consideration should be made to continue therapy and manage symptoms of neuropathy with other medications. One must keep in mind that DSP is clinically indistinguishable from ART associated neuropathy, except for the temporal association. Hence, stopping therapy and worsening the outcome of HIV or continuing therapy and managing the side effects is often a therapeutic dilemma for the patient and practitioner.

Nerve growth factor One study has looked at recombinant human nerve growth factor (rhNGF) in the treatment of

Chapter 10: HIV neuropathy

HIV-associated neuropathy.[24] Patients who were given two doses for 18 weeks demonstrated improvement in the Gracely Pain Scores, but there was no evidence of nerve regeneration.

Prosapeptide Prosapeptide is a peptide known to reverse nerve regeneration and can improve allodynia and hyperalgesia in a rat model. A very small study showed promising results in humans, and the drug is currently being evaluated on a larger scale.

What conclusions can be made for the treatment of HIV-associated neuropathy? The evidence for the treatment of HIV-associated neuropathy is not conclusive. In fact, most studies showed a negative effect for gabapentin, pregabalin, amitryptiline, mexilitine, peptide-T, acetyl-carnitine, and lamotrigine. Evidence for efficacy currently exists only for rhNGF (which is clinically unavailable) and smoked cannabis, which cannot be recommended for routine therapy.[24]

Complementary and alternative medicine CAM has been used and studied well in HIV neuropathy, and may improve quality of life for those living with HIV/AIDS.[26] Some of these include:  Acupuncture: Acupuncture stimulates the release of endogenous opioids, thereby altering pain perception. Acupuncture has been used to treat HIV-related symptoms such as peripheral neuropathy, diarrhea, nausea, vomiting, insomnia, and muscle pains.[26] It has shown a modest decrease in symptoms of DSP, especially in ARTinduced neuropathy. It also demonstrated an improvement in sleep quality, an indirect measure of quality of life. However, the studies with acupuncture are small, hence some large-scale studies are needed to see if these positive effects can be replicated.  Massage therapy: HIV patients use manual healing techniques including massage therapy, Shiatsu, Reiki, therapeutic touch, acupressure, and chiropractic manipulation. Touch can increase blood flow, decrease pain, cause relaxation, and stimulate the immune system and release of endorphins. Massage therapy has

been shown to decrease stress and anxiety in HIV patients.  Nutritional support: Patients with HIV are often nutritionally compromised and would benefit from vitamin and nutritional supplementation. No studies exist to support or disprove this theory. A small study using L-glutamine antioxidant showed weight gain in these patients.  Herbal remedies: Marijuana plant-based therapy has been shown to be effective in HIV neuropathy. Cannabinoid-based drugs, such as dronabinol (Marinol), have been reported to stimulate appetite, weight gain, and provide relief from nausea, especially in anorexic HIV patients.[26] Alternatively, other plant-based therapies, such as St John’s Wort and garlic, interact with antiretroviral medications and can cause resistance to treatment. The psychologic benefits of various CAM modalities should not be underestimated. There is evidence suggesting that decreasing depression can decrease HIV-related somatic complaints. Currently, many patients do not self-report the use of CAM, and physicians are unlikely to recommend these modalities. This will likely change as CAM becomes more widely recognized as a legitimate medical intervention. Larger studies are needed to accurately assess the safety of such interventions.

Psychotherapy/cognitive behavioral therapy Cognitive behavior intervention can reduce pain and suffering in some patients with HIV neuropathic pain.[27] Cognitive behavioral therapy (CBT) was compared to supportive psychotherapy in reducing pain, pain-related interference with functioning, and distress. The cognitive behavior group improved in most domains of functional activity and distress compared to the supportive psychotherapy group. The high dropout rate suggests that psychotherapeutic treatments for HIV-related pain, though important, may not be practically feasible.

Interventional techniques Currently, there are no studies that have looked at spinal cord stimulation, deep brain stimulation, and implantable medication devices in HIV neuropathy. A careful assessment should be done before any of these modalities are considered. Rationale behind the use of these

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interventions has to be made from their use in other known neuropathic conditions, such as diabetic neuropathy and complex regional pain syndrome.

9. Are there any special concerns that you might have in the care of patients with HIV neuropathy? Patients with HIV neuropathy often have other sequelae of the disease, including AIDS. These patients often have poor support systems and nutritional status, which further compound the pain associated with neuropathy. Patients may not be compliant with therapy and have other concomitant issues with illicit drugs and alcohol. Smoked cannabis, which can cause cognitive and motor dysfunction, has been shown to be effective in the treatment of DSP. This causes a therapeutic dilemma for the pain physician, especially if the patient is also using chronic opioids.

10. What conclusions would you draw from this case? HIV neuropathy is commonly seen in patients with HIV, and causes a distal involvement of sensory fibers

References 1.

2.

3.

4.

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Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data – United States and 6 U.S. dependent areas – 2010. HIV Surveillance Supplemental Report. 2012;17(Number 3 Part A). Centers for Disease Control and Prevention. Estimated HIV incidence among adults and adolescents in the United States, 2007–2010. HIV Surveillance Supplemental Report. 2012;17 (No. 4).

especially of the lower extremity. Its clinical presentation is often very similar to other causes of neuropathy. Diagnosis can be confirmed by a battery of tests to look for small sensory and autonomic fiber abnormalities. These tests can be pivotal in the early diagnosis of HIV neuropathy. The treatment of neuropathic pain usually relies on known modalities such as antidepressants and anticonvulsants initially. However, these modalities have not been shown to work in HIV neuropathy. Opioid therapy is also very controversial in this subset of patients but may become necessary in advanced disease. Antiretroviral therapy must be continued unless there is a suspicion of HAART-induced neuropathy.[23,28] There are currently an estimated 33 million people living with HIV, and this number is expected to rise with the use of highly effective antiretroviral therapy. Furthermore, treatment of this chronic condition does not follow the algorithmic approach used to treat other neuropathic conditions. Of all therapies, only recombinant nerve growth factor, smoked cannabis, and high-concentration capsaicin patch have shown positive results. Evidence-based treatment approaches will be required in the future to effectively treat this chronic disease. neuropathy associated with acquired immunodeficiency syndrome: Prevalence and clinical features from a population-based survey. Arch Neurol. 1988;45(9): 945–948.

virus-associated distal sensory polyneuropathy: still common after many successes. Arch Neurol. 2010;67(5):534–535. 5.

6.

Bacellar H, Munoz A, Miller EN, et al. Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985–1992. Neurology. 1994;44(10):1892–1900.

7.

Kolson DL, Gonzalez-Scarano F. Human immunodeficiency

8.

Berger A, Dukes EM, Oster G. Clinical characteristics and economic costs of patients with painful neuropathic disorders. J Pain. 2004;5(3):143–149. Hall CD, Snyder CR, Messenheimer JA, et al. Peripheral neuropathy in a cohort of human immunodeficiency virus-infected patients: Incidence and relationship to other nervous system dysfunction. Arch Neurol. 1991;48(12):1273–1274. Simpson DM, Kitch D, Evans SR, et al. HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology. 2006;66(11): 1679–1687. So YT, Holtzman DM, Abrams DI, Olney RK. Peripheral

9.

Araujo AP, Nascimento OJ, Garcia OS. Distal sensory polyneuropathy in a cohort of HIV-infected children over five years of age. Pediatrics. 2000; 106(3):E35.

10. Lichtenstein KA, Armon C, Baron A, et al. Modification of the incidence of drugassociated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis. 2005;40(1): 148–157. 11. Evans SR, Ellis RJ, Chen H, et al. Peripheral neuropathy in HIV: prevalence and risk factors. AIDS 2011;25(7):919–928.

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12. Childs EA, Lyles RH, Selnes OA, et al. Plasma viral load and CD4 lymphocytes predict HIV associated dementia and sensory neuropathy. Neurology. 1999; 52(3):607–613. 13. Tagliati M, Grinnell J, Godbold J, Simpson DM. Peripheral nerve function in HIV infection: clinical, electrophysiologic, and laboratory findings. Arch Neurol. 1999;56(1): 84–89. 14. Robinson-Papp J, Gelman BB, Grant I, et al. Substance abuse increases the risk of neuropathy in an HIV-infected cohort. Muscle Nerve. 2012;45(4):471–476. 15. Kieburtz KD, Giang DW, Schiffer RB, Vakil N. Abnormal vitamin B12 metabolism in human immunodeficiency virus infection: Association with neurological dysfunction. Arch Neurol. 1991; 48(3):312–314. 16. Keswani SC, Pardo CA, Cherry CL, Hoke A, McArthur JC. HIV-associated sensory neuropathies. AIDS. 2002; 16(16):2105–2117. 17. Verma S, Estanislao L, Simpson D. HIV-associated neuropathic pain: epidemiology, pathophysiology and

management. CNS Drugs. 2005; 19(4):325–334. 18. Boger MS, Hulgan T, Haas DW, et al. Measures of small-fiber neuropathy in HIV infection. Auton Neurosci. 2012;169(1): 56–61. 19. Robinson-Papp J, Sharma S, Simpson DM, Morgello S. Autonomic dysfunction is common in HIV and associated with distal symmetric polyneuropathy. J Neurovirol. 2013;19(2):172–180. 20. Smith HS. Treatment considerations in painful HIVrelated neuropathy. Pain Physician. 2011;14(6):E505–E524. 21. Paice JA, Ferrans CE, Lashley FR, et al. Topical capsaicin in the management of HIV-associated peripheral neuropathy. J Pain Symptom Manage. 2000;19(1): 45–52. 22. Simpson DM, Estanislao L, Brown SJ, Sampson J. An open-label pilot study of high-concentration capsaicin patch in painful HIV neuropathy. J Pain Symptom Manage. 2008;35(3):299–306. 23. Dorsey SG, Morton PG. HIV peripheral neuropathy:

pathophysiology and clinical implications. AACN Clin Issues. 2006;17(1):30–36. 24. Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS. Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials. PLoS One. 2010; 5(12):e14433. 25. Capers KN, Turnacioglu S, Leshner RT, Crawford JR. Antiretroviral therapy-associated acute motor and sensory axonal neuropathy. Case Rep Neurol. 2011;3(1):1–6. 26. Power R, Gore-Felton C, Vosvick M, Israelski DM, Spiegel D. HIV: effectiveness of complementary and alternative medicine. Prim Care. 2002;29(2):361–378. 27. Evans S, Fishman B, Spielman L, Haley A. Randomized trial of cognitive behavior therapy versus supportive psychotherapy for HIV-related peripheral neuropathic pain. Psychosomatics. 2003;44(1):44–50. 28. Wiebe LA, Phillips TJ, Li JM, Allen JA, Shetty K. Pain in HIV: an evolving epidemic. J Pain. 2011;12(6):619–624.

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Section 2 Chapter

11

Spinal Disorders

Cervicogenic headache Eric R. Helm and Nashaat N. Rizk

Case study A 30-year-old male presents to your clinic with a 2month history of base of neck and posterior scalp pain after a motor vehicle accident. He complains of headaches, poor sleep duration, and depressed mood. He has returned to work as an attorney, but poor concentration and cognitive fatigue is affecting his performance.

1. What is the differential diagnosis? a. b. c. d. e. f.

Cervicogenic headache Cervical facet arthropathy Occipital neuralgia Concussion with post-concussive symptoms Occipital-atlantoaxial joint instability Cervical myofascial pain syndrome

Cervicogenic headache is a relatively common secondary source of headache that is seen in 4–6% of the population. It is defined as pain referred to the head from a source in the cervical spine. There is a strong correlation between motor vehicle collision and development of cervicogenic headache. Cervical “whiplash” is a common injury sustained in rear-end motor vehicle collisions. Injury typically occurs in the lower cervical spine components, including zygoapophyseal joint capsular ligament tears, annular disruption, and ligamentum flavum stretch. The suboccipital muscle group can be involved as well. These consist of the rectus capitus posterior major and minor and the superior and inferior oblique. Elliott et al[1] found significantly greater fatty infiltration in the cervical extensors, especially in the deeper muscles of the upper cervical spine, in patients with whiplash-associated disorders compared to healthy controls. The deep suboccipital muscle group produces functional movement

and provides proprioception and stabilization to the craniocervical junction. The pathophysiology behind cervical “whiplash” injuries involves the generation of peak horizontal extension forces transmitted to the cervical spine. During the course of rear-ended impact, the neck is subjected to shear forces parallel to the direction of impact, as well as compression, tension, flexion, and extension at different cervical levels and at different stages of the event.[2] The initial impact results in forward acceleration of both truck and shoulders, forcing the lower cervical spine into extension, as the head moves posterior to the T1 vertebral body. The head is then thrust into extension, followed by forward acceleration, which forces the entire neck into flexion. The discrepancy between the upper and lower cervical spinal segments in flexion and extension, respectively, in combination with the velocity of the impacting vehicle, result in horizontal force transmission. The proposed threshold for a cervical strain is approximately 4–5 g, which is seen with velocities of 6–8 km/hour.[3] At velocities as low as 8 km/hour, 38% of subjects exposed to controlled rear-end collisions experienced cervical “whiplash” symptoms.[4] Whiplash is a multifaceted clinical syndrome that includes neck pain and stiffness, upper limb pain and paresthesias, headaches, visual disturbances, memory and concentration problems, and emotional disturbances. The annual incidence of neck pain associated with whiplash varies greatly. More importantly, although 50% of whiplash victims recover in 3 to 6 months, 30% to 40% have persisting mild to moderate pain and 10% to 20% retain more severe pain.[5] Controversy exists regarding the role psychologic factors play in the injured patient. These patients may also be experiencing neuropsychologic disturbances from an acquired traumatic

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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brain injury. The most common problems seen in brain injuries of this magnitude are inattention, working memory difficulties, and cognitive fatigue. Currently, there is not a lot of strong data to support the incidence of cervical discogenic disease, cervical radiculopathy, and temporomandibular joint dysfunction associated with cervical whiplash. However there is considerable overlap between whiplash-associated disorders and the cervical anatomic abnormalities that are discussed below.

2. What are the differentiating features of the cervical spine pain syndromes? Cervicogenic headache is pain perceived in the head referred from a primary source in the cervical spine. When clinical criteria have been used, the prevalence of cervicogenic headache has been estimated to be up to 4.1% in the general population and as high as 17.5% among patients with severe headaches.[6] The most reliable features are: pain that starts in the neck and radiates to the fronto-temporal region; pain that radiates to the ipsilateral shoulder and arm; and provocation of pain by neck movement.[7] Sometimes it is tough to distinguish cervicogenic headache from migraine. Clinical features that point more toward cervicogenic headache are the absence of an aura, history of neck trauma, fluctuating non-throbbing pain quality, and exacerbation with provocative neck maneuvers (e.g., supine cervical facet glide examination). Given the mechanism discussed above for cervical “whiplash,” the cervical zygapophysial joints (Z-joints, facet joints) are at a substantial risk for overload and injury. The prevalence of cervical facet joint-mediated pain in patients with complaints of neck pain ranges from 36% to 60%.[8] Cervical zygapophysial joints extend from C2-C3 to C7-T1. The distribution of axial cervical pain associated with these joints can encompass the suboccipital to mid-scapular regions, depending on the joint involved. Upper cervical zygapophysial joint pain (e.g., C2-C3, C3-C4) may present as neck pain with associated headaches, whereas lower cervical joint involvement (e.g., C5-C6, C6-C7) may present as neck pain with associated shoulder or mid-scapular pain.[9] The majority of patients with cervical facet joint pain has only one symptomatic joint; however traumatic etiologies are more likely to have multiple joint involvements. Traumatically induced lower cervical pain attributable

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to a facet joint most commonly involves the C5-C6 level.[10] Non-traumatic involvement is likely caused by either improper biomechanics or cervical spondylosis. Key features of cervical facet joint-mediated pain include: axial neck pain with potential radiation into the periscapular region, focal tenderness to palpation posterolaterally over symptomatic joint, and increased focal suboccipital pain exacerbated with 45 degrees of cervical flexion followed by axial rotation.[11] Myofascial pain syndrome is a local and regional pain disorder characterized by the presence of trigger points, which can be active or latent. Active trigger points convey painful information in the absence of palpation and are more likely present in patients with regional conditions. Latent trigger points require palpation to produce local and referred pain. These trigger points are discrete areas of deep muscle tenderness located in a taut band in the muscle. Palpation results in distant zones of perceived pain, local “twitch response,” or muscle contraction. Trigger points are a distinct entity from the tender points that comprise the clinical diagnosis of fibromyalgia. Myofascial pain syndrome is more common in certain patient populations, such as female sex, whiplash-associated disorders, mood disorders (e.g., depression, anxiety), and tension-type headaches. Cervical joint subluxation is a serious injury that can be sustained during a motor vehicle accident. Abrupt deceleration typically results in a flexiontype injury, while abrupt acceleration results in an extension-type injury. The mechanism of injury for cervical joint subluxation or dislocations is the application of an axial load in conjunction with excessive cervical flexion or extension. The most common affected level is C5-C6 because of the increased movement in this area. Excessive flexion in the cervical spine, especially C3-C7 levels, can cause an anterior subluxation or unilateral or bilateral facet subluxations. The most devastating complication of bilateral cervical facet joint subluxations is when they result in “jumped locked” facets. This typically results in a neurologically complete spinal cord injury.

3. What are some of the legal ramifications encountered with workplace and motor vehicle injuries? The most expensive source of injuries is work and transportation-related musculoskeletal disorders. A National Academy of Sciences study found that

Chapter 11: Cervicogenic headache

musculoskeletal disorders of the neck and arm cause more than 1 million workers to miss time from their job each year, at an annual cost of more than $50 billion.[12] Workers’ compensation involves interaction between medical and legal systems, and physicians that treat spine-related conditions need to understand some basics of the legal system. When a medico-legal case is contested, the treating physician can be required to give sworn testimony regarding their patient. This can be in the form of a courtroom testimony or deposition. Prior to this deposition, it is prudent to review all available medical records. Law professionals always stress the five Ps: “Proper preparation prevents poor performance.” The typical issues in question during deposition involve the mechanism of injury, pre-existing conditions, contributing factors, and whether the resulting impairments or disability is consistent with the injury.[13] In dealing with medico-legal cases, important terms to understand are malingering, causation, and Daubert. Malingering is the intentional misrepresentation of signs or symptoms with the intent to receive secondary gain.[13] It should not be confused with symptom exaggeration or magnification. Workplace and traffic camera use of surveillance to document potential malingering is becoming more commonplace in today’s society. Hospital-based outpatient practices can use video evidence, especially in determining functional ability and return to work status. In a medico-legal case, causation provides a connection between the mechanism of injury and the resultant functional ability. A physician’s opinion during a deposition must be within a “reasonable degree of medical certainty.” This reasonable certainty means that, based on available evidence, the truth of the statements is more likely than not.[14] The principle of Daubert is important to understand if you are asked to give expert testimony in a lawsuit. It states that expert testimony must be generally well accepted in the medical community, published in peer-reviewed literature, have a scientific basis, and have a known error rate.[13] These four criteria must be met for an expert witness to appropriately testify.

4. What are the differing roles of clinical assessment between a clinical practitioner and independent medical assessment? The in-depth clinical assessment of a patient with neck pain and headache involves an extensive history and

physical examination with provocative testing, radiologic viewing, medical record review, diagnosis, treatment plan, and follow-up care. A patient-physician relationship has been established and the treatment plan is consistently being updated and reviewed at subsequent office visits. Based on response to treatment and return to work goals, formal rehabilitation programs such as work hardening can be utilized. Functional capacity evaluations (FCE) can also be beneficial in return to work status. This is an extensive evaluation with formalized physical and occupational testing. They are performed by physical and occupational therapists. The FCE often can guide or clarify what category job the injured worker can perform and is helpful in documenting inconsistencies, decreased effort, and lack of validity on repeat testing.[13] Vocational rehabilitation is helpful when a patient is unable to return to their previous employment. A clinical assessment differs from an independent medical assessment. An independent medical assessment (IME) involves an independent review of a medical case. An IME can help to clarify controversies regarding causation, maximal medical improvement, work restrictions, impairments, and disability.[13] This encounter does not establish a doctor-patient relationship and no treatments are ordered by the examining physician. The physician performing the IME thoroughly reviews all available medical records, radiologic imaging, laboratory testing, and performs an extensive history of physical examination. Similar to a clinical assessment, diagnoses are stated and recommendations are given. A commendable IME involves a thorough assessment, unbiased thought process, clear recommendations, and is legally defensible in court. Important definitions to understand when conducting an IME are maximal medical improvement, impairment, and disability. Maximal medical improvement is attained once the medical condition has resolved or has become fixed and stable. At this point, further diagnostic testing and intervention are not recommended. At maximum medical improvement (MMI), the injured worker is not expected to significantly change in pain level or functional ability in the near future.[14] The American Medical Association (AMA) defines impairment as a significant deviation, loss, or loss of use of any body structure or body function in an individual with a health condition, disorder, or disease.[15] The impairment rating scales are used to calculate the range of

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whole-person impairment in certain disease states. Disability is the inability to engage in any substantial gainful activity, by reason of any medically determinable physical or mental impairment, that can be expected to result in death or that has lasted or can be expected to last for a continuous period of not less than 12 months.[16]

5. How do clinical assessments differ among practitioners in the diagnosis of cervicogenic headache? The clinical assessment of cervicogenic headache starts with an in-depth history of physical examination. It is important to determine the mechanism of injury, chronicity of symptoms, radiologic studies, pre-morbid diagnosis that may confer increased risk, completed treatments, previous and current functional abilities, and return to work status. Then there is the formulation of a “working” differential diagnosis. This is followed by a formal physical examination with emphasis on the upper and lower cervical spine. Clinical evaluation of the upper cervical spine is the most important part of the examination. This evaluation is focused on the assessment of dynamic movements that occur in the craniocervical junction. Hypermobility of the craniocervical junction can lead to mechanical instability. Severe instability can lead to spinal cord compression, resulting in bowel and bladder incontinence, gait ataxia, hemiparesis, and paresthesias. Clinicians need to consider the possibility of craniocervical junction hypermobility and instability when evaluating a patient with axial neck pain and headaches. Physical therapists, chiropractors, and interventionalists each have their own specialty training and approach to the assessment and treatment of cervicogenic headache. Physical therapists are trained to assess body position and functional movements. Their overall goals are to functionally assess, stretch, stabilize, strengthen, and return patient to sport. Appropriate modifications in manual therapy, such as cervical facet mobilization and manipulation, should be made in underlying craniocervical junction hypermobility. Two specific physical examination procedures can be used diagnostically to test hypermobility at these joints: the Sharp-Purser and lateral shear test. The Sharp-Purser test evaluates flexion of the atlas while the lateral shear test evaluates lateral translation of the atlas. The Sharp-Purser test is

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performed by placing one hand over the patient’s forehead, while the thumb of the opposite hand is placed over the C2 spinous process for stabilization.[17] The patient is asked to flex the head on the neck, while you apply a posteriorly directed force on the forehead. A positive test is indicated if there is backward movement of the head, which may be accompanied by a “clunk.” The backward movement indicates that the subluxation of C1, produced by forward flexion of the neck, has been reduced.[18] The associated sensitivity is 0.69, and specificity is 0.96, when compared with a radiographic reference standard in patients with rheumatoid arthritis.[19] The lateral shear test is performed with the patient lying supine. The metacarpophalangeal (MCP) joint of digit 2 is placed against the transverse process of the atlas on one side and the MCP of digit 2 from the contralateral hand is placed on the transverse process of axis on the opposite side. The two MCP joints are pushed toward one another, creating a shear force of C1 on C2. The test is considered positive if you feel an increased transitory “shift” between the two bones or patient symptoms are provoked by the maneuver.[18] Chiropractors also perform a clinical functional assessment. However, more time is spent in determining specific areas that have restricted motion and evaluating for frank instability. The chiropractor’s emphasis is on treatment, not diagnostic work-up, which differs significantly from both physical therapy and physicians. Both chiropractors and physical therapists employ techniques such as high velocity low amplitude (HVLA) manipulation, cervical facet mobilization, myofascial release techniques, and cervical spine traction. However, typically physical therapists also focus on postural mechanics, vestibular therapy exercises, and return to work/sport, all of which are important in treating cervicogenic headache in active individuals. Clinicians should consider interventional treatment when patients have not improved with noninterventional strategies, including physical therapy with manual techniques, chiropractor care, medication trials, and activity modification. At this point an interventionalist will perform diagnostic cervical medial branch blocks, therapeutic intra-articular facet joint injections, and radiofrequency neurotomy. It is important to remember that the success of all radiofrequency neurotomy procedures for managing cervicogenic headache depends on the patient’s previous response to diagnostic challenge with cervical medial

Chapter 11: Cervicogenic headache

Table 11.1. Criteria for cervicogenic headache per the International Headache Society

Criteria

Description

A

Pain, referred from a source in the neck and perceived in one or more regions of the head and/or face, fulfilling criteria C and D

B

Clinical, laboratory, and/or imaging evidence of a disorder or lesion within the cervical spine or soft tissues of the neck known to be or generally accepted as a valid cause of headache

C

Evidence that the pain can be attributed to the neck disorder or lesion based on at least one of the following:  Demonstrations of clinical signs that implicate a source of pain in the neck; or  Abolition of headache after diagnostic blockade of a cervical structure or its nerve supply by the use of placebo or other adequate controls

D

Pain resolves within 3 months after successful treatment of the causative disorder or lesion

branch block.[20] The most recent criteria of the International Headache Society (see Table 11.1) list diagnostic blockade of a cervical structure or of its nerve supply as mandatory for the diagnosis of cervicogenic headache.[21] Despite discussions and controversy among many practitioners about the diagnosis of cervicogenic headache or for that matter, most benign spinal pain syndromes, these discussions have focused on a structural basis for pain. There has been a gap, unfortunately, between the scientific understanding of chronic pain and our clinical methods to assess pain. Neurobiologists increasingly view chronic pain as a disease of the nervous system and less of a structural problem, per se. Clinicians, likewise, should begin embracing these concepts rather than sticking to an oversimplified structural approach. In fact the opposite is true, wherein ad hoc classification systems and treatment approaches abound. Does the patient have cervicogenic headache, muscle spasms, Qi blood stagnation syndrome, subluxed joints, entrapped/ inflammed upper cervical and occipital nerves, or facet synovitis? Several articles have raised concern that these disparate classification systems are integral

to how practitioners treat pain and how these treatments are not coordinated. This is unique to chronic pain. One would not use multiple classification systems and disparate treatments for cardiac disease, diabetes mellitus, or cancer – but we do for chronic pain syndromes. The use of ad hoc classification systems in chronic pain, such as cervicogenic headache, highlights our lack of understanding of this disease. Consequences include patient and practitioner frustration with treatment, rising expenditures, payor denial of care, and societal costs.[22–25]

6. What symptoms can be associated with cervicogenic headaches? Cervicogenic headache is a multifaceted clinical syndrome that includes neck pain and stiffness, upper limb pain and paresthesias, headaches, tinnitus, visual disturbances, memory and concentration problems, and emotional disturbances. The most commonly seen cognitive problems are cognitive fatigue, poor concentration, and inattention, especially divided attention. Functional MRI studies have shown the frontal and parieto-occipital lobes as common areas of hypoperfusion in cervicogenic headache patients. Memory loss can also be seen, especially anterograde memory loss. The Galveston Orientation and Amnesia Test (GOAT) and the Orientation Log (O-Log) are clinical tests that can be used in assessment and to track progress of memory loss associated with posttraumatic amnesia. Deficits in working memory can be seen in higher functioning individuals. Mood disorders, such as depression and anxiety, are typically seen late in the disease course. These are seen more commonly in “chronic” pain states. Cortical neurotransmitter reorganization, with deficits in serotonin and norepinephrine, has been seen in basic science research. Patients may warrant psychologic assessment and the addition of a SSRI or SNRI as part of the treatment plan. The diagnosis of cervicogenic headache relies on establishing that the pain generator lies in the neck, using reliable and validated diagnostic techniques. Nikolai Bogduk’s convergence trigeminocervical nucleus convergence theory (Figure 11.1) is the most commonly accepted model. In this theory, nociceptive afferents from the C1, C2, and C3 spinal nerves converge onto second-order neurons that also receive afferents from adjacent cervical nerves and from the first division of the trigeminal nerve, via the

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Figure 11.1. Convergence between cervical and trigeminal afferents in trigeminocervical nucleus.[35]

Midbrain

Pons

Trigeminal nerve (V)

Trigeminothalamic tract Spinal tract of trigeminal nerve

C1 spinal nerve

C2 spinal nerve Trigeminocervical nucleus C3 spinal nerve

trigeminal nerve spinal tract.[26] This convergence results in referral of upper cervical pain to the head, specifically the occipital and auricular region and parietal, frontal, and orbital area. The cervical spine has multiple possible pain generators and referral patterns (Table 11.2) that must be considered in the work-up of a patient with cervicogenic headache. Common areas of pain referral are toward the vertex of the scalp, ipsilateral anterolateral temple, forehead, midface, or ipsilateral shoulder girdle. Cyriax[27] showed that stimulation of the suboccipital muscles with injections of hypertonic saline could produce referred pain in the head. The more cephalad the site of stimulation, the closer to the forehead the pain projected. Stimulation of upper cervical spine structures elicits pain in the occipital, frontal, and orbital regions, while more caudal stimulation elicits pain in the base of the neck and periscapular region. The referred pain from cervical facet

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joints, especially the C2-C3 zygapophysial joint, is a common cause of secondary headache. Among patients with neck pain and headache in which headache was the dominant symptom, the prevalence of C2-C3 zygapophysial joint pain was 50%.[28] Lord et al[29] performed 44 double-blind, placebocontrolled blocks of the third occipital nerve; 53% of patients whose major complaint was headache obtained relief from the block that was of appropriate length based on whether a short- or longer-acting anesthetic was used.

7. What are some of the different subsets in cervicogenic headache? We will discuss the common subsets that encompass cervicogenic headache. These are the occipitalatlantoaxial joint complex and greater, lesser, and least occipital neuralgia. The occipital-atlantoaxial

Chapter 11: Cervicogenic headache

Table 11.2. Cervicogenic headache pain generators and their referral patterns[30]

Pain generator

Innervation

Referral pattern

Atlanto-occipital joint

Ventral ramus of C1

Occiput, subocciput

Atlantoaxial joint

Medial AA joint: recurrent meningeal branch (ventral ramus) of C1, C2, C3 Lateral AA joint: ventral ramus of C2

Occiput, subocciput, vertex, orbit, and ear

C2-C3 zygapophysial joint

Third occipital nerve (superficial medial branch of C3 dorsal primary ramus)

Head, upper, and lateral cervical region

C3-C4 zygapophysial joint

C3 and C4 medial branch of dorsal primary ramus

Head, upper, and lower cervical region

C2-C3 disc

Sinuvertebral branch of superficial medial branch of C3 dorsal ramus

Occiput

Greater occipital nerve

C2 medial branch of dorsal primary ramus

Occiput, C2 dermatome

Lesser occipital nerve

C3 dorsal primary ramus

Occiput (lateral to GON)

Greater auricular nerve

C2 and C3 dorsal ramus contributions

Posterior scalp behind the ear, posterior auricular region, and skin overlying the parotid gland

joint is the most complex joint in the craniocervical junction. These are two distinct joint complexes: occipital-atlanto (C0-C1) and atlantoaxial (C1-C2) joint complexes. The C0-C1 joint is responsible for flexion, extension, and lateral flexion. The C1-C2 joint is designed for rotation, with 50% of the total cervical rotation taking place at this level.[31] Previously discussed above, the suboccipital muscle group provides both active movement and proprioception to these joints. The C1-C2 articulation has two primary ligamentous stabilizers: the cruciform ligament and the paired alar ligaments. The cruciform ligament’s horizontally oriented fibers are the primary passive restraint of C1 displacement in the sagittal plane.[32] The alar ligaments are important passive restraints to axial rotation of the atlas on the axis.[33] The alar ligaments restrain contralateral axial rotation (e.g., the left alar ligament restrains right axial rotation) and lateral flexion. Patients with mild to moderate instability of these joint complexes present with symptoms of suboccipital pain, dizziness, unilateral headache, and upper limb paresthesia.[34] Severe instability can lead to catastrophic consequences, including disturbances of bowel/bladder control, impaired gait, motor incoordination, sensory loss, and the extreme instance of death from spinal cord compression.[36] Clinicians must be cautious in the application of a manual force to the craniocervical

junction and prior diagnostic work-up should include anterior-to-posterior open mouth radiographs, with the head in neutral, right, and left lateral flexion positions (Figures 11.2 and 11.3). The typical radiology order for these views are: three open mouth AP views of C1-C2 (one as a straight AP, one maximally laterally flexed to the right, one maximally laterally flexed to the left) to assess for lateral deviation of the C1–2 joint. The International Classification of Headache Disorders II has three diagnostic criteria for the classification of occipital neuralgia[21]: A. Paroxysmal stabbing pain, with or without persistent ache between paroxysms, in the distribution(s) of the greater, lesser, and/or third occipital nerves. B. Tenderness over the affected nerve. C. Pain eased temporarily by local anesthetic block of the nerve. Occipital neuralgia must be distinguished from occipital referral of pain from the atlantoaxial joints, upper cervical zygapophysial joints, or active trigger points in neck muscles or their insertions.[37] Each peripheral occipital nerve has a different distinct level of innervation. The greater occipital nerve is a continuation of the C2 medial branch of dorsal primary ramus, while the lesser occipital nerve is a

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L

R

Figure 11.2. Abnormal right translation of the right lateral mass over the body of C2, due to the failure of the left alar ligament. The right alar ligament appears intact.

3 mm

A

B

C

Figure 11.3. Normal C1-C2 joint translation in right lateral flexion, straight AP, and left lateral flexion (A–C).

continuation of the C3 dorsal primary ramus. The 3rd occipital nerve (also known as the least occipital nerve) originates from the superficial medial branch of C3 dorsal primary ramus. There is considerable

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overlap in the referral pattern of these pain generators (Table 11.2). The 3rd occipital nerve is most commonly implicated in the interventional treatment of cervicogenic headache. However, it is

Chapter 11: Cervicogenic headache

important to recognize the more peripherally located pain generators.

8. What are the available treatments for cervicogenic headache and occipital neuralgia? Cervicogenic headache treatment options are based on detailed history and physical examination findings, radiologic studies, and formal clinical assessment. In the evaluation of a patient with cervicogenic headache, the clinician must determine if there is any sign of hypermobility in the craniocervical junction and rule out abnormal neurologic signs. In the presence of either hyper- or hypo-mobility of the C0-C1, C1-C2, or C2-C3 zygapophysial joints, an initial treatment plan should include referral to physical therapy. The manual treatment plan must include cervical stabilization exercises, and proprioceptive training with eye and head coordination exercises in dynamic positions. Postural exercises focusing on cervicoscapular stabilizers, scapular mechanics, and upper-body ergometry are important to emphasize.[38] Examples of these include prone scapular depression and elevation, upright rows, and seated pull-downs. Dynamic strengthening exercises are incorporated later on in the plan of care. At the completion of the outpatient physical therapy program, a home exercise program of trunk stabilization is provided, consisting of bridging, prone planks, and side planks.[17] In the presence of hypomobility of the cervical and thoracic spine, both the physical therapist and chiropractor should employ a manual therapy protocol. This should include: mobilization of the occiput, cervical and thoracic facet, and costo-transverse joints, traction manipulation of the occiput, and occipital glide mobilization.[39] The primary rational for these components is to inhibit increased activity in the suboccipital and levator scapulae muscles and relieve stiffness in the upper thoracic region.[40] Thoracic mobilization is important in this patient population because restoring normal scapulothoracic movement will assist with reducing postural stiffness. The C2-C3 zygapophysial joint is believed to be responsible for 70% of cervicogenic headaches, while the atlantoaxial joint is thought to be the 2nd most common source.[41] Interventional procedures targeting the 3rd occipital nerve, craniocervical junction, cervical medial branch dorsal primary ramus

anesthetic blocks, and upper cervical intra-articular facet joints are common treatments after poor symptom relief with less invasive modalities. All diagnostic and therapeutic cervical spine procedures require imaging guidance with live and static fluoroscopy to ensure correct placement of the needle/probe and injectate at the targeted structure. The use of nonionic contrast media should also be used for target localization and exclude intravascular uptake. Current literature supports the role for diagnostic medial branch blocks and not intra-articular injections as the criterion standard for diagnosis of pain emanating from or mediated by the cervical zygapophysial joint.[42] The 3rd occipital nerve is thicker than the cervical medial branches of the dorsal primary ramus and usually embedded in the periscapular fascia of the C2-C3 joint. Three target points have been defined by Bogduk and Dreyfuss to ensure correct needle placement for 3rd occipital nerve blocks. The target points lie on a vertical line that bisects the C2-C3 joint. The cranial target point lies opposite the level of the apex of the C3 superior articular process. The caudal target point lies opposite the inferior aspect of C2-C3 intervertebral foramen. The middle point lies midway between these two points, typically on the subchondral plate of the C3 superior articular process. See Figure 11.4. Positive comparative blocks with two different local anesthetics will generally allow the operator to be 81% certain that a confirmatory response represents a “true” positive. This statistic is true regardless of whether the result is “concordant” positive or “discordant” positive, in which the duration of pain relief correlates or does not correlate with the local anesthetic used.[42] The International Headache Society criteria for cervicogenic pain accept  90% reduction in pain to a level of < 5 on a 100-point visual analog scale.[21] The most researched interventional treatment for cervicogenic headache is percutaneous radiofrequency neurotomy (radiofrequency ablation). The goal of this procedure is destruction of the afferent nerve supply from the 3rd occipital nerve and C2 and C3 medial branches. The target radiofrequency temperatures range from 80 to 90°C and duration from 80 to 90 seconds. It is important to remember that the coagulation occurs in a radial direction, perpendicular to the long axis of the electrode,[43] so the active radiofrequency needle tip must be placed parallel to the targeted nerve. Data shows that 3rd occipital

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A

B

C

Figure 11.4. Lateral views of the upper cervical spine showing the target points for third occipital nerve blocks (A–C).

nerve radiofrequency neurotomy is effective in 88% of patients that have confirmatory controlled diagnostic blocks with a 297-day median duration of relief.[44] Pulsed radiofrequency neurotomy is a technique in which energy is applied intermittently in short bursts, allowing dispersion of heat between each cycle and temperature is held at a non-neuronal destruction level. One study evaluated its use for cervicogenic headache and was performed at the lateral atlantoaxial joint. Fifty percent of patients had > 50% pain relief at 2 and 6 months, and 44% at 1 year.[45] Intra-articular corticosteroid injections, especially targeting the lateral atlantoaxial joint, have been

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described as effective treatment for cervicogenic headache. Narouze et al investigated 32 patients that received lateral atlantoaxial joint injections for C1-C2 pain. More than 80% of patients had 50% pain relief immediately after the injection. However at the 6th month time-point, they were no longer experiencing any significant symptom improvement.[46] Slipman et al retrospectively evaluated C2-C3 facet joint injections for cervicogenic headache after a whiplash event. Residual improvement was demonstrated at an average of 12 months.[47] Patients with whiplash-associated cervicogenic headache typically suffer from headaches, and ultimately may develop chronic daily headaches. A greater

Chapter 11: Cervicogenic headache

A

B

C

Figure 11.5. Lateral and AP views of the upper cervical spine showing the target points for third occipital nerve radiofrequency neurotomy (A–C).

occipital nerve block can be a beneficial treatment for both the suboccipital pain and headaches. The injection site is localized 1/3 of the distance from the greater occipital protuberance to the mastoid process. A newer, more novel treatment for chronic daily headaches that have a cervicogenic component is Botulinum toxin. The FDA has approved Botulinum

toxin for treatment of chronic migraine headaches, with 15 or more headache days a month, each lasting 4 hours or more. Botulinum toxin (BOTOX) is not specifically indicated for treatment of cervical spine pain generators, but may prove beneficial for these patients suffering from chronic daily headaches. Botulinum toxin is a neurotoxin and biologic product

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Chapter 11: Cervicogenic headache

A

B

Figure 11.6. AP and lateral views of the upper cervical spine showing the target points for lateral atlantoaxial joint injection (A–B).

of bacteria, Clostridium botulinum. All seven serotypes (A–G) act at the presynaptic neuromuscular junction to inhibit the release of acetylcholine. The mechanism of action involves uptake by the synaptic vesicle, followed by cleavage of one or more of the SNAPE proteins. This destruction results in the inability of the vesicle to bind and release the acetylcholine into the synaptic cleft, resulting in transient motor weakness. It is also FDA approved for the treatment of conditions such as strabismus, blepharospasm, upper limb spasticity, and cervical dystonia. The recommended dose for treating chronic migraine is 155 Units administered intramuscularly using a sterile 30-gauge, 0.5-inch needle. Two industry-sponsored randomized, multicenter, placebo-controlled doubleblind studies have shown that treated patients had a greater decrease in headache frequency, especially after 4 weeks. Line et al[48] analyzed the response to Onabotulinum toxin A in 28 cervicogenic headache patients. The randomized, placebo-controlled, crossover study found no significant difference between Onabotulinum toxin A and placebo in the reduction of days with moderate to severe headache. Peripheral nerve stimulation does offer a novel approach in the treatment of occipital neuralgia. Peripheral nerve stimulation is an important treatment

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algorithm for neuropathic pain. Peripheral nerve stimulation is defined as the direct electrical stimulation of named peripheral nerves that lie outside the neuroaxis. Peripheral nerve field stimulation is the stimulation of unnamed nerves that lie in the vicinity of painful, subcutaneous structures. FDA defines both uses as “off-label” in the treatment of neuropathic pain syndromes. Percutaneous occipital nerve stimulation involves a trial placement of subcutaneous electrodes placed superficial to the cervical muscular fascia in the suboccipital area.[37] If the patient has an effective trial, a permanent implant may be carried out using the same percutaneous electrode lead or paddle-type surgical lead, which is attached to a pulse generator implanted in the infraclavicular area, flank, upper buttock, or abdomen.[37] Indications for occipital stimulation include patients diagnosed with cervicogenic headache and occipital neuralgia. There is clinical discrepancy regarding diagnostic confirmation of symptom improvement to occipital nerve blocks and/or interventional treatment in the upper cervical spine. Contraindications to the procedure include untreated psychiatric disorder, bleeding disorder, and systemic or local infections. Several small, uncontrolled studies have investigated the use in occipital neuralgia. Johnstone and Sunderaj found that 70% of patients

Chapter 11: Cervicogenic headache

that underwent permanent implantation had at least > 50% reduction in VAS pain score.[49] Slavin et al. performed occipital nerve stimulation on 14 patients with occipital neuralgia. This was a retrospective study

References 1.

2.

3.

4.

5.

6.

7.

8.

Elliott J, Jull G, Noteboom JT, et al. Fatty infiltration in the cervical extensor muscles in persistent whiplash-associated disorders: a magnetic resonance imaging analysis. Spine (Phila Pa 1976). 2006;31:E847–855. Tencer AF, Mirza S, Bensel K. Internal loads in the cervical spine during motor vehicle rear-end impacts: the effect of acceleration and head-to-head restraint proximity. Spine. 2002;27: 34–42. Allen ME, Weir-Jones I, Motiuk DR, et al. Acceleration perturbations of daily living: a comparison to “whiplash.” Spine. 1994;19:1285–1290. Brault JR, Wheeler JB, Siegmund GP, Brault EJ. Clinical response of human subjects to rear-end automobile collisions. Arch Phys Med Rehabil. 1998;79:72–80. Carroll LJ, Holm, LW, HoggJohnson S, et al. Course and prognostic factors for neck pain in whiplash-associated disorders (WAD): results of the Bone and Joint Decade 2000–2010 task force on Neck Pain and Its Associated Disorders. J Manip Physiol Therapeut. 2009;32(Suppl 2): S97–S107. Evers S. Comparison of cervicogenic headache with migraine. Cephalalgia. 2008; 28(Suppl 1):16–17. Van Suijlekom JA, de Vet HCW, van den Berg SGM, Weber WEJ. Interobserver reliability of diagnostic criteria for cervicogenic headache. Cephalalgia. 1999;19:817–823. Barnsley L, Lord SM, Wallis BJ, et al. The prevalence of chronic cervical

9.

with a mean follow-up of 22 months. Seventy percent of the patients had a successful trial and underwent permanent implantation, with reduction in VAS pain scores that ranged between 60 and 90%.[50]

zygapophyseal joint pain after whiplash. Spine. 1995;20:20–26.

PA: WB Saunders Company. 2008.

Cooper G, Baily B, Bogduk N. Cervical zygapophysial joint pan maps. Pain Med. 2007; 8(4):344–353.

19. Utivlugt G, Indenbaum S. Clinical assessment of atlantoaxial instability using Sharp-Purser test. Arthritis Rheum. 1988;31:321–329.

10. Bogduk N, Aprill C. On the nature of neck pain, discography and cervical zygapophysial joint blocks. Pain. 1993;54:213–217.

20. Blume HG. Cervicogenic headaches: radiofrequency neurotomy and the cervical disc and fusion. Clin Exp Rheumatol. 2000;18(Suppl 19):S53–S58.

11. Dreyfuss P, Michaelsen M, Fletcher D. Atlanto-occipital and lateral atlanto-axial joint pain patterns. Spine. 1994;19:1125–1131.

21. International Headache Society. International Headache Society Classification (ICHD-II). 2001, Nov 2.

12. National Academy of Sciences. Musculoskeletal Disorders and the Workplace: Low Back and Upper Extremities. Washington, DC, National Academy of Sciences. 2001. 13. Braddom L. Physical Medicine & Rehabilitation. Philadelphia: Saunders Elsevier. 2012. 14. Melhorn JM. Impairment and disability evaluations: understanding the process. J Bone Joint Surg Am. 2001;83(12): 1905–1911. 15. Cocchiarella L, Andersson GBJ, eds. Guides to the Evaluation of Permanent Impairment, 5th ed. Chicago: American Medical Association Press. 2001. 16. SSA. Disability Evaluation Under Social Security. Washington, DC: US Government Printing Office. 1994. 17. Mathers SK, Schneider M, Timko M. Occult hypermobility of the craniocervical junction: a case report and review. J Orthop Sports Phys Ther 2011;41(6):444–457. 18. Magee DJ. Orthopedic Physical Assessment, 5th edn. Philadelphia,

22. Shah RV. Spine pain classification: a solution. Pain Physician. 2013;16 (2):E51–59. PubMed PMID: 23511691. 23. Shah RV. The problem with diagnostic selective nerve root blocks. Spine (Phil Pa 1976). 2012;37(24):1991–1993. doi: 10.1097/BRS.0b013e318270a7ba. PubMed PMID: 22941096. 24. Shah RV. Spine pain classification: the problem. Spine (Phila Pa 1976). 2012;37(22):1853–1855. doi: 10.1097/BRS.0b013e3 182652a86. PubMed PMID: 22732822. 25. Shah RV, Kaye AD. Evolving concepts in the understanding of cervical facet joint pain. Pain Physician. 2004;7(3):295–299. PubMed PMID: 16858465. 26. Bogduk N. Cervicogenic headache: anatomic basis and pathophysiologic mechanisms. Curr Pain Headache Rep. 2001;5: 382–386. 27. Cyriax J. Rheumatic headache. BMJ. 1938;2:1367–1368. 28. Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygoapophyseal joint pain after

93

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whiplash: a placebo-controlled prevalence study. Spine. 1996; 21:1737–1744. 29. Lord SM, Barnsley L, Wallis BJ, Bogduk N. Third occipital nerve headache: a prevalence study. J Neurol Neurosurg Psychiatry. 1994;57:1187–1190. 30. Mehnert MJ, Freedman MK. Update on the role of Z-joint injection and radiofrequency neurotomy for cervicogenic headache. PM R. 2013;5:221–227. 31. Vernon H, Minor S. The Neck Disability Index: a study of reliability and validity. J Manipulative Physiol Ther. 1991;14:409–415. 32. Dvorak J, Panjabi MM. Functional anatomy of the alar ligaments. Spine. 1987;12:183–189. 33. Haldeman S, Kohlbeck FJ, McGregor M. Unpredictability of cerebral vascular ischemia associated with cervical spine manipulation therapy: a review of sixty-four cases after cervical spine manipulation. Spine. 2002;27:49–55. 34. Bitterling H, Stabler A, Bruckmann H. [Mystery of alar ligament rupture: value of MRI in whiplash injuries – biomechanical, anatomical and clinical studies]. Rofo. 2007;179:1127–1136. 35. Bogduk N. The neck and headaches. Neurol Clin N Am. 2004;22:151–171. 36. Aspinall W. Clinical testing for the craniovertebral hypermobility

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syndrome. J Orthop Sports Phys Ther. 1990;12:47–54. 37. Narouze S. Cervicogenic headache. In Benzon HT, ed. Essentials of Pain Medicine. Philadelphia, PA: Elsevier/ Saunders. 2011: pp. 278-283. 38. O’Leary S, Falla D, Elliott JM, Jull G. Muscle dysfunction in cervical spine pain: implications for assessment and management. J Orthop Sports Phys Ther. 2009;39:324–333. 39. Grieve G. Modern Manual Therapy of the Vertebral Column. London, UK: Churchill Livingstone. 1986. 40. Erhard R. The Spinal Exercise Handbook. A Home Exercise Manual for a Managed Care Environment. Pittsburgh, PA: Laurel Concepts. 1998. 41. Dwyer A, Aprill C, Bogduk N. Cervical zygapophyseal joint pain patterns I: A study in normal volunteers. Spine. 1990;15:453–457. 42. Bogduk N. On the rationale use of diagnostic blocks for spinal pain. Neurosurg Q. 2009;19:88–100. 43. Lord SM, McDonald GJ, Bogduk N. Percutaneous radiofrequency neurotomy of the cervical medial branches: a validated treatment for cervical zygapophyseal joint pain. Neurosurg Q. 1998;8:288–308. 44. Govind J, King W, Bailey B, Bogduk N. Radiofrequency neurotomy for the treatment of third occipital headache. J Neurol

Neurosurg Psychiatry. 2003;74:88–93. 45. Halim W, Chua NHL, Vissers KC. Long-term pain relief in patients with cervicogenic headaches after pulsed radiofrequency application into the lateral atlantoaxial (C1–2) joint using an anterolateral approach. Pain Practice. 2010;10:267–271. 46. Narouze SN, Casanova J, Mekhail N. The longitudinal effectiveness of lateral atlantoaxial intraarticular steroid injection in the treatment of cervicogenic headache. Pain Med. 2007;8:184–188. 47. Slipman CW, Lipetz JS, Plastaras CT, et al. Therapeutic zygapophyseal joint injections for headaches emanating from the C2–3 joint. Am J Phys Med Rehabil. 2001;80:182–188. 48. Linde M, Hagen K. Onabotulinum toxin A treatment of cervicogenic headache: a randomized, double-blind, placebo-controlled crossover study. Cephalalgia. 2011;31(7): 797–807. 49. Johnstone CS, Sunderaj R. Occipital nerve stimulation for the treatment of occipital neuralgia: eight case studies. Neuromodulation. 2006;9:41–47. 50. Slavin KV, Nersesyan H, Wess C. Peripheral neurostimulation for treatment of intractable occipital neuralgia. Neurosurgery. 2006;58:112–119.

Section 2 Chapter

12

Spinal Disorders

Cervical stenosis and myelopathy Santhosh A. Thomas and Garett J. Helber

Case study

2. Assessment

A 68-year-old right-hand dominant female presents with resolving neck and left upper extremity pain. She reports pain developed 8 weeks ago following exercise. She reports her neck pain was constant, sharp, and achy in quality with stabbing pain radiating down her left arm. She noted associated left hand numbness which has resolved. She denies any weakness of her upper or lower extremities. Pain was made worse with nothing specific and improved with stretching. She underwent a course of physical therapy and steroid taper with resulting resolution of all symptoms. On physical examination her tandem gait is impaired with preserved ability to toe and heel walk. Cervical range of motion is full and without pain. Sensation is preserved to light touch in the bilateral upper and lower limb dermatomes. Muscle stretch reflexes noted to be 3+/4 in the right triceps and biceps, bilateral patella, and bilateral Achilles. Sustained clonus is present at the right ankle and Hoffmann’s sign is grossly positive on the left hand. Muscle strength is preserved in all muscles tested of the bilateral upper and lower extremities.

A 68-year-old female with resolved left cervical radiculopathy with concern for cervical myelopathy.

1. Cervical x-rays taken 6 weeks earlier reveal A grade 1 anterior subluxation of C3, minimal posterior subluxation of C5, and grade 1 anterior subluxation of C7. The C3–4 through C6–7 interspaces are severely narrowed with opposing endplate sclerosis, anteroposterior spurring, and uncovertebral joint osteophytes.

3. Plan 1. MRI cervical spine. 2. Call after results obtained to review and formulate treatment plan which may include surgical consultation. 3. Continue home exercise program and activity as tolerated.

4. MRI cervical spine following encounter reveals C2–C3: Canal and foramina are patent. C3–C4: The interspace is severely narrowed and appears fused. Uncovertebral change moderately narrows the neural foramina. The central osseous canal is patent. C4–C5: The interspace is severely narrowed. Disc/ osteophyte changes result in moderate right and severe left foraminal encroachment. There is cord contact with mild ventral cord compression. C5–C6: The interspace is severely narrowed. Disk osteophyte change results in mild ventral cord compression with mild right and severe left foraminal encroachment. C6–C7: The interspace is severely narrowed. Uncovertebral change mildly narrows the neural foramina. Central canal is patent.

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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C7–T1: Canal and foramina are patent. Mild facet hypertrophic changes are present bilaterally.

5. What is the differential diagnosis? The differential diagnosis to consider is quite broad and includes:  Cervical spondylotic myelopathy (CSM)  Cervical plexopathy/radiculopathy and/or peripheral neuropathy  Polyradiculitis (Guillain-Barré syndrome)  Multiple sclerosis  Spinal cord injury (central cord syndrome)  Cerebrovascular disease  Syringomyelia  Tabes dorsalis  Atrophic lateral sclerosis  Rheumatoid arthritis  Subacute combined degeneration (vitamin B12)  Intraspinal or intracranial tumor  Spinal arteriovenous malformation  Epidural abscess or hemorrhage  Chiari malformation or other congenital malformation of the brain stem  Ossification of the posterior longitudinal ligament  Normal pressure hydrocephalus  Hereditary spastic paraplegia  Vascular ischemia of the spinal cord

6. What is the definition of cervical spondylotic myelopathy? Cervical myelopathy is present when there is clinically symptomatic dysfunction affecting the cervical spinal cord. When this dysfunction is due to cord compromise resulting from degenerative changes (spondylosis) of the cervical spine it is referred to as CSM. It is important that cervical myelopathy be distinguished from other disorders including cervical radiculopathy and axial neck pain as these conditions may coexist.

7. What is the epidemiology of CSM? CSM is the leading cause of spinal cord dysfunction in older patients and predominantly affects men in their seventh decade of life. Due to its subtle presentation that often involves elderly patients, the diagnosis can be overlooked and thus may still be under-recognized.

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In one study 23.6% of 585 patients admitted with tetraparesis or paraparesis to a UK regional neuroscience center were diagnosed with CSM.

8. What are the clinical manifestations of CSM? Clinical presentations vary from patient to patient. The presenting symptoms depend on the stage of myelopathy and impaired signals from the spinal cord based on intrinsic or extrinsic neural conditions which include:  Difficulty walking with a wide-based, sometimes jerky or spastic gait is the most common presentation.  Balance difficulties with unsteadiness while on their feet.  Weakness of the upper extremities often with loss of fine motor coordination involving the hands.  Associated numbness and paresthesias of the upper extremities may be present.  Positive Lhermitte sign: neck flexion results in an electrical shock sensation that extends throughout the body (thought to be due to stimulation of the dorsal columns).  Lower extremity dysfunction, including sensory and motor changes, typically occurs after the upper extremities are involved.  Dysfunction of bladder and/or bowel is noted infrequently and is often a late finding. Most common finding in early CSM is urinary frequency and urgency. Urinary retention is mostly associated in patients with CSM over the age of 65.

9. What are the physical examination findings in a patient with CSM?  Hyperreflexia below level of compression.  Inverted radial reflex.  Decreased sensation of any or all sensory modalities depending on the anatomic location of the lesion, but pain and temperature sensation are most commonly affected (due to compression of the spinothalamic tracts).  Weakness due to upper motor neuron damage may be present at the level of the lesion.  Increased muscle tone and spasticity may be found below the level of the lesion.

Chapter 12: Cervical stenosis and myelopathy

 Clonus, Babinski, and Hoffmann’s sign.  Hands may demonstrate intrinsic muscle atrophy.  Evaluation of gait typically reveals a broad-based, hesitant, stiff or spastic gait, secondary to upper motor neuron disease and proprioceptive loss.

10. What are the imaging studies available to evaluate for CSM? A diagnosis of CSM requires a patient who is both symptomatic and has radiographic evidence of spinal cord impingement or compression, thus making radiographic assessment essential. Magnetic resonance imaging is the gold standard as it provides the best view of spinal cord, exiting nerve roots, and CSF signal. CT myelography however may be useful in instances of previous surgery in viewing residual bony anatomy while minimizing artifact from residual hardware. It is important to remember that the appearance of cord compression does not indicate the presence of myelopathy. Further, the correlation between radiographic spondylotic cord damage and clinically significant CSM is not well established. Xray studies, including anteroposterior, oblique, and lateral views with or without flexion and extension of the spine, may reveal narrowing of the disc space, osteophyte formation, spondylolisthesis, and/or instability. These factors have all been identified and implicated in the development of CSM.

11. What radiologic criteria are used to diagnose stenosis? Many investigations have been made in an attempt to diagnose cervical stenosis and correlate it to the development of CSM. Of paramount importance is the fact that a congenitally narrowed canal will lower the threshold at which the cumulative effects of these various structures encroaching on the spinal cord will result in signs and symptoms of myelopathy. The normal cervical canal diameter from C3 to C7 is 17–18 mm in White and 15–17 mm in Japanese individuals. It has been shown that an absolute AP diameter of the canal that is less than 11 mm correlates with a high risk of CSM and that a Pavlov ratio (anteroposterior (AP) diameter of the spinal canal to the anteroposterior diameter of vertebral body at the same level) of 0.8 or less also places a patient at greater risk for development. (A Torg ratio is the

same as a Pavlov ratio.) A normal ratio is 1.0. Symptoms are also believed to develop when the spinal cord has been reduced by at least 30%. Despite numerous studies no definitive criteria currently exist to quantify stenosis, as substantial stenosis has been reported in association with mid-sagittal diameters of < 10 mm,[1] < 12 mm,[2] and < 14 mm.[3]

12. What additional studies may be of benefit in the evaluation of CSM? Bednarik et al found that electromyography and sensory-evoked potential abnormalities, in association with clinical radiculopathy, when present initially predicted the development of CSM.[4]

13. What is the natural history of patients with CSM? The natural history of CSM is mixed and variable and therefore it is very difficult to predict the course of disease in any given patient. Some patients will remain neurologically stable, some will even improve (though significant improvement is rare), while others may experience additional neurologic deficits. A 2002 Cochrane review concluded there is no clear evidence to support the idea that CSM patients experience inevitable neurologic deterioration. Numerous studies demonstrate that longer symptom duration (12–24 months) portends worse neurologic recovery. Subtle progression is characteristic of the disease process, with findings of urinary urgency or incontinence, difficulties with balance and gait, and loss of fine motor control concerning for disease progression.

14. What are the risk factors associated with the development of CSM?  Underlying structural kyphosis.  Abnormal or excessive cervical motion.  Almost all patients with CSM from strictly degenerative changes, excluding those with ossification of posterior longitudinal ligament (OPLL), have congenital stenosis.  Risk factors for the development of spondylosis include advanced age, heavy labor, posture, and genetic predisposition.

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15. What is the pathology behind the development of CSM? Any disease leading to loss of space available for the spinal cord, with resulting compromise and dysfunction, may be implicated in the development of CSM. Despite involvement of the spinal cord, this condition begins extrinsic to it with involvement of surrounding osseous and soft tissue structures. The initial lesion is the deterioration of the intervertebral disc, which is often insidious and without symptoms. Repeated stress and aging leads to several changes including disc collapse or deterioration, loss of elasticity, and unequal distribution of hydrostatic pressure on the annulus with compressive forces. As the disc loses its strength and integrity surrounding structures are required to bear a greater burden of the applied load. As these structures continue to bear more weight they undergo secondary changes. End plates, uncovertebral joints, and facet joints remodel and form osteophytes to increase the weight-bearing surface area. Reactive hyperostosis occurs, thus increasing the diameter of the vertebral body at the level. As a result the spondylotic bars/osteophytes can project posteriorly into the spinal canal and reduce the space available for both the spinal cord and its blood supply. Osteophytes that arise from the joints of Luschka and facet joints further compromise the areas of both the spinal canal and neuroforamina. In addition the ligamentum flavum may invaginate into the canal as the disc collapses and additionally compresses the spinal cord. Involvement is most commonly seen at C5–6, followed by C6–7, where most of flexion and extension in the subaxial spine occurs, creating greater reactive changes. Symptoms may be worsened owing to the fact that C5–7 is a watershed area of the cervical cord, thus increasing the risk for spinal cord ischemia at these levels. The resulting neurologic deficit is thus likely due to a combination of neuronal compression and alterations of local neuronal blood flow resulting in ischemia.

16. How is CSM managed nonoperatively? In mild CSM a conservative course appears appropriate but those with significant or progressive neurologic deficits should be considered candidates for surgical intervention. All treatments should attempt

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to decrease pain and restore function with consideration given for patient safety and if needed home alterations. Patients should first be instructed to avoid those activities which precipitate their symptoms. Immobilization in a firm cervicothoracic orthosis serves to decrease the motion of the vertebral bodies although there is little evidence for efficacy. Those with significant pain may be managed with nonsteroidal anti-inflammatory agents as with other degenerative diseases, with analgesics reserved for more acute and intense periods of pain. The use of epidural steroids has not been shown to result in any lasting benefit.

17. What are the surgical options for management of CSM? Decompression is indicated for significant or progressive neurologic deterioration. The goal of treatment is to relieve the compression on the cord while maintaining spinal stability. The best results may be obtained when decompression is achieved early (6–12 months) after the onset of symptoms and in those who develop early, mild myelopathic findings. Numerous techniques exist to achieve decompression which can be completed via an anterior or posterior approach. Anterior techniques include anterior discectomy with or without fusion and anterior corpectomy with fusion which may also include plate fixation for more extensive disease. Posterior techniques include laminectomy with or without fusion and canal expansive laminoplasty. Anterior cervical discectomy and fusion remains the standard in cases of CSM arising from a single level disc herniation. The procedure allows relief of spinal cord compression with a low rate of postoperative axial neck pain. Multiple discectomies are not favored for multilevel disease as there exists an increased likelihood of symptomatic pseudoarthrosis formation due to the increased number of surfaces across which fusion is expected to occur. Anterior corpectomy and strut grafting is reserved for those cases of multilevel disease where there exists compression of the cord across more than just the disc space or in a patient with pronounced kyphosis. This procedure allows for complete decompression of the cord and the restoration of a more normal cervical alignment. Posterior decompression via laminectomy has historically been the mainstay of treatment in relieving

Chapter 12: Cervical stenosis and myelopathy

compression and restoring neurologic function in patients with neutral or lordotic alignment. However, in those with some degree of kyphosis there is a significant risk of progressive postoperative kyphotic deformity with recurrence of CSM. Long-term studies after isolated laminectomy range from 14% to 47% for postoperative kyphosis. As a result of the potential for kyphotic deformity fusion may be recommended. While accompanying fusion is effective in preventing deformity it often results in loss of a significant degree of motion and thus the risks and benefits of its use must be carefully weighed. Posterior decompression via laminoplasty allows for decompression of the cord without leading to increasing kyphotic deformity. However, the procedure does not ensure that the spinal canal will be completely open for the cord when the posterior elements are hinged open while the lamina remains preserved. However, as there is no fusion less loss of cervical motion occurs and lessens the need for postoperative immobilization. Despite these general indications there is currently no class I or II evidence to suggest superiority among laminoplasty, laminectomy with arthrodesis, anterior cervical corpectomy and fusion (ACCF), or anterior cervical discectomy and fusion (ACDF) with plate fixation.

18. How does ossification of posterior longitudinal ligament cause CSM? The spinal ligamentous tissue is replaced by ectopic new bone formation, leading to narrowing of the spinal canal. The etiologies of OPLL remain ambiguous; nevertheless, genetic background is a contributing factor. This disease is more prevalent among Japanese and other Asians compared to Whites. OPLL progression has been noted in long-term follow-up after cervical laminoplasty and should be given consideration as a cause of recurrent myelopathy.

Cited References 1.

Adams CBT, Logue V. Studies in cervical spondylotic myelopathy. II. The movement and contour of the spine in relation to the neural complications of cervical spondylosis. Brain. 1971;94: 569–586.

19. How does rheumatoid arthritis cause CSM? Cervical spine involvement is well established in patients with rheumatoid arthritis (RA). Upper cervical lesions recognized as atlantoaxial subluxation are well known in patients with RA. Synovial pannus formation is also well recognized in patients with RA. Indirect compression of the spinal cord by cervical subluxation and/or direct compression of the spinal cord by the synovial pannus can present as CSM. The atlas dental interval (ADI) is a useful marker for evaluating atlantoaxial subluxation. It is generally accepted that patients with ADI exceeding 5 mm have a greater risk of CSM but this can be unreliable. Cranial settling can also be seen in about 5–8% of patients with RA where C1 settles on top of C2 leading to dens of C2 to move upwards. Depending on severity of compression, patients may present with neck pain or CSM.

20. What is the expected neurologic outcome after decompression surgery? Numerous studies reveal that the majority of patients either improve or remain neurologically stable following surgical decompression. A study by Lesoin reports only 10% with continued deterioration who were managed operatively and followed for 20 years.[5] Poorer neurologic recovery has been demonstrated in those with greater radiographic canal stenosis (canal area of 30 to 45 mm2). It has also been concluded that age (> 60) and abnormal cervical curvature (lack of normal cervical lordosis) predict less postoperative neurologic improvement. The presence of preoperative high signal intensity within the spinal cord may also reflect less neurologic improvement (T2 hyperintensity at multiple levels or T2 hyperintensity in combination with T1 hypointensity).

2.

Epstein BS, Epstein JA, Jones MD. Cervical spinal stenosis. Radiol Clin North Am. 1977;15:215–226.

3.

Countee RW, Vijayanathan T. Congenital stenosis of the cervical spine: diagnosis and management. J Nat Med Assn. 1979;71:257–264.

4.

Bednarik J, Kadanka Z, Dusek L, et al. Presymptomatic spondylotic cervical cord compression. Spine (Phila Pa 1976). 2004;29(20): 2260–2269.

5.

Lesoin F, Bouasakao N, Clarisse J, Rousseaux M, Jomin M. Results of surgical treatment of

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radiculomyelopathy caused by cervical arthrosis based on 1000 operations. Surg Neurol. 1985;23: 350–355.

References 1.

2.

3.

4.

Alexander JT. Natural history and nonoperative management of cervical spondylosis. In Menezes AH, Sonntag VK, eds. Principles of Spinal Surgery. New York: McGraw-Hill Companies, Health Professions Division. 1996: pp. 547–557. Al-Mefty O, Harkey LH, Middleton TH, et al. Myelopathic cervical spondylotic lesions demonstrated by magnetic resonance imaging. J Neurosurg. 1988;68(2):217–222. Arnold JG, Jr. The clinical manifestations of spondylochondrosis (spondylosis) of the cervical spine. Ann Surg. 1955;141:872–889. Baron EM, Young WF. Cervical spondylotic myelopathy: a brief review of its pathophysiology, clinical course, and diagnosis. Neurosurgery. 2007;60(1 Supp1 1): S35–S41.

5.

Bohlman HH. Cervical spondylosis and myelopathy. Instr Course Lect. 1995;44:81–98.

6.

Bohlman HH, Emery SE. The pathophysiology of cervical spondylosis and myelopathy. Spine (Phila Pa 1976). 1988;13(7): 843–846.

7.

Chiles 3rd BW, Leonard MA, Choudhri HF, Cooper PR. Cervical spondylotic myelopathy: patterns of neurological deficit and recovery after anterior cervical decompression. Neurosurgery. 1999;44(4): 762–769.discussion 769–770.

8.

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Clark C. Degenerative conditions of the cervical spine: differential diagnosis and nonoperative management. In Frymoyer JW, ed. The Adult Spine: Principles and Practice, 2nd edn. Philadelphia:

Lippincott-Raven. 1997: pp. 1323–1348. 9.

Clark CR. Cervical spondylotic myelopathy: history and physical findings. Spine. 1988;13:847–849.

10. Collins DN, Barnes CL, FitzRandolph RL. Cervical spine instability in rheumatoid patients having total hip or knee arthroplasty. Clin Orthop. 1991;272:127–135. 11. Connell MD, Wiesel SW. Natural history and pathogenesis of cervical disk disease. Orthop Clin North Am. 1992;23(3):369–380. 12. El-Khoury GY, Wener MH, Menezes AH, Dolan KD. Cranial settling in rheumatoid arthritis. Radiology. 1980;137(3):637–642. 13. Emery SE. Cervical spondylotic myelopathy: diagnosis and treatment. J Am Acad Orthop Surg. 2001;9(6):376–388. 14. Emery SE, Bohlman HH, Bolesta MJ, Jones PK. Anterior cervical decompression and arthrodesis for the treatment of cervical spondylotic myelopathy: two to seventeen-year follow-up. J Bone Joint Surg [Am]. 1998;80(7): 941–951. 15. Epstein JA, Epstein NA. The surgical management of cervical spinal stenosis, spondylosis, and myeloradiculopathy by means of the posterior approach. In The Cervical Spine Research Society Editorial Committee, ed. The Cervical Spine, 2nd edn. Philadelphia, J.B. Lippincott. 1989: pp. 625–643. 16. Epstein N, Epstein J, Carras R. Cervical spondylostenosis and related disorders in patients over 65: current management and diagnostic techniques. Orthotransactions. 1987;11:15. 17. Fouyas IP, Statham PF, Sandercock PA. Cochrane review on the role of surgery in cervical spondylotic radiculomyelopathy. Spine (Phila Pa 1976). 2002; 27(7):736–747.

18. Fujiwara K, Yonenobu K, Ebara S, et al. The prognosis of surgery for cervical compression myelopathy: an analysis of the factors involved. J Bone Joint Surg [Br]. 1989;71(3): 393–398. 19. Hayashi H, Okada K, Hamada M, et al. Etiologic factors of myelopathy. A radiographic evaluation of the aging changes in the cervical spine. Clin Orthop. 1987;214:200–209. 20. Heller JG, Edwards 2nd CC, Murakami H., Rodts GE. Laminoplasty versus laminectomy and fusion for multilevel cervical myelopathy: an independent matched cohort analysis. Spine (Phila Pa 1976). 2001; 26(12):1330–1336. 21. Herkowitz HN. The surgical management of cervical spondylotic radiculopathy and myelopathy. Clin Orthop. 1989;239:94–108. 22. Hirabayashi K, Satomi K. Operative procedure and results of expansive open-door laminoplasty. Spine. 1988;13: 870–876. 23. Hirabyashi K, Bohlman HH. Multilevel cervical spondylosis: Laminoplasty versus anterior decompression. Spine. 1995;20:1732–1734. 24. Hiroshima K, Ono K, Fujiwara K. Pathology of cervical spondylosis, spondylotic myelopathy, and similar disorders: is clinicopathological correlation verified? In Ono K, Dvorak J, Dunn E, eds. Cervical Spondylosis and Similar Disorders. Singapore, New Jersey, London, Hong Kong: World Scientific. 1998: pp. 89–139. 25. Hududa S, Ogata M, Katsura A. Experimental study on acute aggravating factors of cervical spondylotic myelopathy. Spine. 1988;13:15–20. 26. Kaptain GJ, Simmons NE, Replogle RE, Pobereskin L. Incidence and outcome of

Chapter 12: Cervical stenosis and myelopathy

kyphotic deformity following laminectomy for cervical spondylotic myelopathy. J Neurosurg. 2000;93(Suppl 2): 199–204. 27. Kasai Y, Uchida A. New evaluation method using preoperative magnetic resonance imaging for cervical spondylotic myelopathy. Arch Orthop Trauma Surg. 2001;121(9):508–510. 28. Kawaguchi Y, Kanamori M, Ishihara H, et al. Progression of ossification of the posterior longitudinal ligament following en bloc laminoplasty. J Bone Joint Surg. 2001;83A:1798–1802. 29. Law M, Bernhardt M, White AA. Evaluation and management of cervical spondylotic myelopathy. Inst Course Lect. 1995;44:99–110. 30. Lestini WF, Wiesel SW. The pathogenesis of cervical spondylosis. Clin Orthop. 1989;239:69–93. 31. Lipson SJ. Rheumatoid arthritis in the cervical spine. Clin Orthop. 1989;239:121–127. 32. Macdonald RL, Rehlings MG, Tator CH, et al. Multilevel anterior cervical corpectomy and fibular allograft fusion for cervical myelopathy. J Neurosurg. 1997;86:990–997. 33. Matsunaga S, Sakou T. Epidemiology of ossification of the posterior longitudinal ligament. In Yonenobu K, Sakou T, Ono K, eds. Ossification of the Posterior Longitudinal Ligament. Tokyo, Berlin, Heidelberg, New York: Springer. 1997: pp. 11–17. 34. Moore AP, Blumhardt LD. A prospective survey of the causes of non-traumatic spastic paraparesis and tetraparesis in 585

patients. Spinal Cord. 1997;35(6): 361–367. 35. Morio Y, Teshima R, Nagashima H, et al. Correlation between operative outcomes of cervical compression myelopathy and MRI of the spinal cord. Spine (Phila Pa 1976). 2001;26(11): 1238–1245. 36. Morio Y, Yamamoto K, Kuranobu K, et al. Does increased signal intensity of the spinal cord on MR images due to cervical myelopathy predict prognosis? Arch Orthop Trauma Surg 1994;113(5): 254–259. 37. Northover JR, Wild JB, Braybrooke J, Blanco J. The epidemiology of cervical spondylotic myelopathy. Skeletal Radiol. 2012;41:1543–1546 38. Ono K, Ebara S, Fuji T, et al. Myelopathy hand: new clinical signs of cervical cord damage. J Bone Joint Surg [Br]. 1987;69(2): 215–219. 39. Orr RD, Zdeblick TA. Cervical spondylotic myelopathy: approaches to surgical treatment. Clin Ortho Relat Res. 1999;359: 58–66. 40. Ota K, Ikata T, Katoh, S et al. Implications of signal intensity on T1 weighted MR Image on the prognosis of cervical spondylotic myelopathy. Orthop Trans. 1996;20:443. 41. Parke WW. Correlative anatomy of cervical spondylotic myelopathy. Spine. 1988;13: 831–837. 42. Pavlov H, Torg JS, Robie B, Jahre C. Cervical spinal stenosis: determination with vertebral body ratio method. Radiology, 1987;164:771–1775.

43. Penning L, Wilmink JT, van Woerden HH, Knole E. CT myelographic findings in degenerative disorders of the cervical spine: clinical significance. AJR Am J Roentgenol. 1986;146:793–801. 44. Penning L. Some aspects of plain radiography of the cervical spine in chronic myelopathy. Neurology. 1962;12:513–519. 45. Roberts A. Myelopathy due to cervical spondylosis treated by collar immobilization. Neurology. 1966;16:951–954. 46. Sadasivan KK, Reddy RP, Albright JA. The natural history of cervical spondylotic myelopathy. Yale J Biol Med. 1993;66(3):235–242. 47. Satomi K, Hirabayahi K. Ossification of posterior longitudinal ligament. In Herkowitz HN, Eismont FJ, Garvin SR, et al., eds. RothmanSimeone, The spine, 4th edn. Philadelphia: WB Saunders. 1999: pp. 565–580. 48. Snow RB, Weiner H. Cervical laminectomy and foraminotomy as surgical treatment of cervical spondylosis: a follow-up study with analysis of failures. J Spinal Disord. 1993;6:245–251. 49. Uchida K, Nakajima H, Sato R, et al Cervical spondylotic myelopathy associated with kyphosis or sagittal sigmoid alignment: clinical article. J Neurosurg Spine 2009;11(5): 521–528. 50. Yonezawa T, Tsuji H, Matsui H, et al. Subaxial lesions in rheumatoid arthritis: radiological factors suggestive of lower cervical myelopathy. Spine. 1995;20: 208–215.

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Spinal Disorders

Thoracic outlet syndrome (TOS): an enigma in pain medicine Narendren Narayanasamy and Rahul Rastogi

Case study A 26-year-old female started having strange tingling and dull ache in her left arm. Her symptoms started at 17 years of age during her training to become a beauty therapist. She also noticed numbness in her upper extremities with elevation of arms above the shoulders. She put off these symptoms for a long time attributing them to physical exertion. Upon evaluation, her primary care physician incidentally found significant wasting of the hand muscles with prominent tendons, and decreased sensation of the arm and hand to pin prick.

1. What is thoracic outlet syndrome? Over the last few decades, a constellation of symptoms comprising pain, numbness/tingling, and weakness in the shoulder and upper extremity were addressed with different names such as cervical rib syndrome, scalenus anticus syndrome, costoclavicular syndrome, arm hyperabduction syndrome, etc. It was in 1956 that Pette et al collectively called all these different clinical entities “thoracic outlet syndrome” (TOS). TOS is a myriad of symptoms secondary to compression of the neurovascular bundle consisting of the subclavian vein, subclavian artery, and/or brachial plexus, during their course through the cervicothoracobrachial region into the axilla.

2. What are the types of thoracic outlet syndrome? Due to lack of specific diagnostic criteria, thoracic outlet syndrome remains a controversial and complex clinical diagnosis. It is broadly divided into three categories on the basis of the presence of predominant symptoms from compression of neurovascular bundle in the thoracic outlet; namely arterial (aTOS),

venous (vTOS), and neurogenic (nTOS) TOS. Isolated pure TOS of any type is rare. Most of them are mixed presentation of the above types. There is a group of patients who do not fall under any of the above categories. They are currently classified as disputed or symptomatic TOS (sTOS) with predominant neurogenic symptoms.

3. What is the epidemiology of TOS? Incidence of TOS is essentially unknown, although nTOS is the common (95%) type followed by venous vTOS (2–4%) and aTOS (1–2%) types. TOS usually affects middle aged adults (20–60 years), with the exception of aTOS, which affects both the young and older adults. Gender ratio favors females in nTOS (3:1), and males in vTOS (2:1), while aTOS is gender neutral.

4. What is thoracic outlet? Anatomically the “thoracic outlet” is a narrow passage in the neck, which extends up to axilla that house muscles, subclavian vessels, and the brachial plexus. It is divided into three narrow passages/spaces, namely scalene triangle, costoclavicular space, and subcoracoid/subpectoral space (see Table 13.1, Figure 13.1). Besides functional and traumatic causes, anomalous anatomy of the components of thoracic outlet can exert compressive effects on neurovascular bundle along these tight passages to produce TOS symptoms.

5. What is the clinical classification of the brachial plexus? The brachial plexus is classified on the basis of its relationship to the clavicle: supraclavicular plexus constitutes roots and trunks;

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 13: Thoracic outlet syndrome (TOS): an enigma in pain medicine

Table 13.1. Thoracic outlet spaces

Spaces

Boundaries

Structures

Interscalene triangle

Anterior, middle scalene muscles, and first rib

Subclavian vein runs anterior to anterior scalene muscle Subclavian artery and supraclavicular upper brachial plexus run between 2 scalene muscles

Costoclavicular space

Subcoracoid space

Between clavicle and first rib

Below coracoid process and pectoralis minor tendon

Vessels and supraclavicular upper plexus then runs under subclavius muscle and costoclavicular ligament, and finally under clavicle to enter subcoracoid space Neurovascular bundle passes under tendon of pectoralis minor through this tight space to enter axilla

retroclavicular plexus constitutes divisions; and infraclavicuar plexus constitutes cords and terminal nerve plexi. The supraclavicular plexus is further subdivided into: (a) upper plexus that includes the upper trunk and C5 and C6 nerve root; (b) middle plexus that includes the middle trunk and C7 nerve root; and (c) lower plexus that includes the lower trunk and C8 and T1 nerve roots.

6. Discuss the etiology of TOS There are several causes that lead to the development of TOS symptoms. They can be divided into four categories: 1. Congenital: This includes the presence of accessory cervical rib, prolonged C7 transverse process, muscular anomalies of scalene muscles, anomalous fibrous bands, altered course of neurovascular bundle, etc. 2. Post-traumatic: Bone overgrowth/callus in clavicle or first rib, fibrosis of scalene muscle

C4

C5 MS

C6 AS C7

1 2

T1

3 T2

M

C

V

A

R1 PM R2

Figure 13.1. Thoracic outlet spaces: 1 ¼ scalene triangle, 2 ¼ costoclavicular space, 3 ¼ subpectoral space. A – subclavian artery, AS – anterior scalene, C – clavicle, C4 to C7 – cervical vertebrae, M – manubrium, MS – middle scalene muscle, PM – pectoralis minor, R1 to R2 – first and second ribs, T1 to T2 – thoracic vertebrae, V – subclavian vein.

following soft tissue trauma, whiplash injury, etc. 3. Functional acquired: This is a common cause resulting from hypertrophied muscles due to repetitive movements of outstretched hands and elevation of arm above the shoulder, drooping shoulders from poor posture, prolonged downward shoulder girdle pressure, etc. The patient in this case indulged in repetetive movements with outstretched hands as a beauty therapist that predisposes her to the development of TOS. 4. Other acquired: Pancoast tumor, atherosclerotic plaques formation, inflammatory, and infective fibrosis. Trauma remains the most common cause of TOS.

7. Discuss and differentiate clinical presentations by the type of TOS Isolated TOS with symptoms pertaining to neural, venous, or arterial etiology is rare. True nTOS is

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Chapter 13: Thoracic outlet syndrome (TOS): an enigma in pain medicine

Table 13.2. Clinical presentation of thoracic outlet syndrome

nTOS

sTOS

aTOS

vTOS

Etiology/compression

Brachial plexus lower trunk, T1 > C8 nerve root

Unknown

Subclavian artery

Subclavian vein

Pain (neck, shoulder, upper extremity, chest, periscapular)

+ Late Early minimal pain

+ Early and late Predominant pain symptoms

Intermittent claudication of shoulder and upper extremity

Fullness of upper extremity Cramping of UE

Sensory – numbness, paresthesia, in medial aspect of arm, forearm, and ulnar distribution of finger

+

+, Along other segmental distribution

–/+

–/+

Motor deficit (lower trunk), thenar weakness, intrinsic hand muscle weakness

+, Presents with chronic progressive UE weakness

+/–

Weakness in UE upon elevation and resolution upon dependency of UE

+/–

Radial artery pulse

+

+



+

UE color changes





Pale

Cyanotic

Swelling







++

Supraclavicular tenderness and Tinel’s sign

+

+

+/–

+/–

Elevation of UE precipitating symptoms

+

+





Occipital headache, vison/hearing changes, facial/ jaw pain

Supraclavicular pulsatile swelling, limb ischemia

Cyanotic shoulder, venous HTN

Other

aTOS, arterial thoracic outlet syndrome; HTN, hypertension; nTOS, neurogenic thoracic outlet syndrome; sTOS, symptomatic disputed thoracic outlet syndrome; UE, upper extremities; vTOS, venous thoracic outlet syndrome.

relatively uncommon (4–5%). Disputed sTOS constitutes the majority of the nTOS (95–96%). In these cases, pain and clinical presentation mimics the established TOS presentation, but lacks a specific identifiable cause for the pain. Lower brachial plexus trunk (C8 and T1) is affected in the majority of TOS patients. However, T2 is rarely involved and presents as retrosternal pain. Upper trunk involvement presents only as shoulder and periscapular symptoms. See Table 13.2 for clinical presentations of TOS.

8. Discuss the differential diagnosis of TOS There are no defined diagnostic criteria for TOS. Due to its variable presentation, other clinical entities

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could mimic TOS presentation. Hence, it is advisable to be cautious in reaching a diagnosis. Syndromes that present as TOS: 1. Brachial plexopathies (BPs): Usually involve upper plexus C5-C6, which can usually be ruled out with EMG study. 2. Cervical radiculopathies: These arise as a result of cervical spondylosis, metastatic spine disease, or nerve tumors. The symptoms follow specific root distribution. These can be differentiated from TOS using provocation tests, EMG, and imaging of cervical spine. 3. Complex regional pain syndrome of limb: History of injury and presence of sudomotor and vasomotor symptoms with normal spine imaging helps in distinguishing this entity from TOS.

Chapter 13: Thoracic outlet syndrome (TOS): an enigma in pain medicine

Table 13.3. Provocative diagnostic tests for thoracic outlet syndrome

Test

Maneuver

Result

VASCULAR TESTS (positive in 50% of the general population) Adson test

Upon deep breath, ipsilateral upper extremity is extended & supinated with lateral rotation of neck toward test side

Decrease or absence of radial pulse

Allen test

Upon lateral rotation of neck toward opposite side with test side shoulder abducted at 90° with 90° flexion of elbow

Decrease or absence of radial pulse

NON-VASCULAR TESTS Elevated arm stress test of Roos (EAST)

In 90° flexion of elbow and abduction of shoulder (surrender position), patient is asked to repetitively close and open the fist

Precipitates paresthesia and symptoms within 3 minutes

Upper limb tension test of Elvey (ULTT)

In sitting position, abduction and external rotation of shoulder and extended elbow Position 1: then active dorsiflexion of wrist Position 2: then further lateral flexion of neck

Triggering symptoms on ipsilateral upper extremity with position 1 and on contralateral upper extremity with position 2

Halstead test

Elevation of chin with pulling the shoulder joint behind in an extreme “attention” position (military position)

Precipitates symptoms

Morley test

Asymmetrical suprascapular tenderness on palpation

Triggers radiating symptoms in UE

4. Peripheral nerve etiology (nerve lesion and/or entrapment syndromes – cubital/carpal tunnel, neuropathy): Location of pain and neural symptoms, provocative tests, and EMG helps in reaching a precise diagnosis. 5. Apical lung etiology: Infection, pancoast tumor, etc.

9. What is double crush syndrome in TOS? Upton et al suggested that proximal nerve lesion makes the distal nerve more vulnerable to compression, resulting in coexistent proximal and distal nerve symptoms called “double crush syndrome” (DCS). This results in a complex clinical presentation with the development of carpal tunnel syndrome in the presence of pre-existing TOS. Double crush syndrome has poor outcomes from isolated peripheral nerve release surgery like carpal/cubital tunnel release. Thus, simultaneous surgical release of both the compressive etiology of thoracic outlet and peripheral nerve compartments are required to achieve an optimal outcome. In DCS there is a sudden decompensation of TOS symptomatology, and/or rapid occurrence of symptoms

of peripheral nerve entrapment neuropathies. DCS is thought to affect mainly C8 fibers; however the median nerve sensory fibers (in carpal tunnel syndrome) do not follow this path. Therefore other possible etiologies should be evaluated to explain DCS, i.e., central mechanisms or more proximal compression of these fibers as in scalene syndrome.

10. Discuss the relevant physical examination findings in TOS The general physical exam findings in patients with TOS include decreased function of upper extremity, lowered and protracted position of the shoulder, contracted scalene and scapular muscles, and wasting and weakness of the intrinsic muscles of the hand with prominent tendons. Additionally, these signs could accompany supraclavicular fullness due to cervical rib and/or aneurismal pulsations. Vascular TOS in particular may also present with cyanosis, edema, and collaterals of the upper extremity. Several provocative tests were suggested for TOS, and are broadly divided into vascular and non-vascular tests (Table 13.3). Vascular tests lack specificity. Among

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Chapter 13: Thoracic outlet syndrome (TOS): an enigma in pain medicine

non-vascular provocative tests, the upper limb tension test (ULTT) of Elvey is pathognomic for TOS.

11. What are the diagnostic modalities of TOS? There is no specific diagnostic test used for diagnosis of symptomatic TOS. These tests are mainly used to rule out differential diagnosis, and to evaluate anatomical variations for possible surgery. Thus, comprehensive history and physical exam are the basis of diagnosis of TOS. Tests commonly in use are: A. Chest, shoulder, and cervical spine imaging (plain radiographs, CT scan, and/or MRI): These imaging techniques help to identify anatomical defects and variations, i.e., hypertrophic callus from old fracture, accessory ribs, fibrous scalene bands, compressive tumors, spinal disc, or canal pathologies, etc. B. Vascular imaging (CT or MR angiography, duplex ultrasound): These imaging techniques are helpful in the presence of vascular clinical signs and symptoms to delineate vascular pathologies and their differential. These diagnostic tests are sometimes essential in surgical decision making. C. Neural imaging (MR neurography): Direct visualization of neural structures under MRI including anatomical relationship of nerves, nerve injury, and inflammation aid in diagnosis of TOS. D. Nerve conduction and electromyographic study (EMG): sTOS, the commonest form of TOS, comprises more than 90% of total TOS. In these patients EMG findings are normal or non-specific, but presence of partial denervation of intrinsic muscles of hand and absent or decreased amplitude of action potential in the ulnar and medial antebrachial cutaneous sensory nerve and decreased amplitude of the median nerve compound motor action potential suggest neurogenic TOS. The above findings along with normal sensory median nerve action potential essentially rules out cervical radiculopathy and myelopathy, and are highly suggestive of lower trunk (C8-T1) compression of the brachial plexus. E. Anterior scalene muscle (ASM) block: In patients with suspected nTOS caused by ASM pathology, a local anesthetic injected into the ASM produces temporary relaxation of the muscle relieving

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tension on the involved nerve resulting in improvement of symptoms. Ninety-four percent of patients who have a positive block and who subsequently undergo surgery were shown to have a positive outcome compared to only 50% who underwent surgical correction following a failed block.

12. What are the conservative management strategies of TOS? Vascular TOS usually needs a surgical intervention. Symptom monitoring is rarely suitable in lieu of active surgical options in vascular TOS. However, neurogenic TOS treatment strategies remain controversial. A multimodal treatment approach should be incorporated in a patient’s regimen. These include: A. Physiotherapeutic and occupational rehabilitation. Rehabilitative approach should be recommended to all neurogenic TOS patients with the goal to improve function, ergonomical changes at workplace, and correction of cervicobrachial structural musculoskeletal imbalance resulting in dysfunction. Modalities include physical therapy (active stretching exercises, mobilization techniques, muscular tapping and postural correction exercises, etc.), weight loss, life style changes, and improving work place ergonomics. B. Pharmacologic therapies. Medical management is essentially directed toward symptom management. Neuropathic pain is the primary and debilitating symptom, which is managed by use of analgesics (non-steroidal anti-inflammatory agents and/ or opioids). Use of adjuvants to manage pain is routinely utilized like muscle relaxants (i.e., methocarbamol, baclofen, tizanidine) and/or anticonvulsants (i.e., gabapentin, pregabalin, etc.), and/or antidepressants (i.e., amitriptyline, nortriptyline, cymbalta, etc.). In vascular TOS anticoagulant medications, i.e., warfarin, clopidogrel, etc., are part of the treatment regimen to prevent clot formation and patency of vessels. See Table 13.4. C. Injection therapies. Use of early thromboembolic therapy is considered in vascular TOS when thrombi are considered an etiology. For relieving painful myofascial symptoms in TOS patients,

Chapter 13: Thoracic outlet syndrome (TOS): an enigma in pain medicine

Table 13.4. Common medications utilized for chronic pain management

Drugs/class

Mechanism

Concern

Dosages

ANALGESICS Acetaminophen

Unknown

Liver damage

325–4000 mg/d

Non-steroidal antiinflammatory drugs

Ibuprofen Naproxen Meloxicam Celecoxib

Decrease prostaglandins by inhibiting cyclooxygenase

GI irritation Renal effects Bleeding

200–2400 mg/d 250–1500 mg/d 7.5–15 mg/d 100–400 mg/d

Opioids

Hydrocodone Fentanyl Morphine Oxycodone Methadone Tramadol Tapentadol

Agonist to opioid receptors Tramadol – additional SSRI and NRI effect Tapentadol – additional NRI action

Nausea/vomiting, constipation, drowsiness, respiratory depression Methadone – variable long t1/2 Tramadol/tapentadol – caution with antidepressants

Variable Variable Variable Variable Variable 50–400 mg/d 50–600 mg/d

Tricyclics (amitriptyline, nortriptyline, desipramine) SNRI (duloxetine)

Modulation of neurotransmission of serotonin and norepinephrine

Sedation, tachycardia, urinary hesitancy Weight gain

25–150 mg HS

Gabapentin Pregabalin Lamotrigine Carbamazepine

α2δ subunit of voltagegated N-type Ca2+ channel modulation Na+ channel blocker Na+ channel blockade

Drowsiness, confusion, weight gain, rash LFT monitoring for carbamazepine

Baclofen

Selective GABA-b agonist

Confusion, drowsiness, dizziness

ADJUVANT ANALGESICS Antidepressants

Antiepileptics

Muscle relaxants

Cyclobenzaprine Methocarbamol

20–90 mg/d

Unknown action on CNS

300–3600 mg/d 75–600 mg/d 100–600 mg/d 200–1200 mg/d 10–80 mg/d 2–32 mg/d 10–60 mg/d 500–2000 mg/d

Alpha-2 adrenergics

Clonidine Tizanidine

α2 adrenergic agonism

Drowsiness, #BP, #HR LFT caution – tizanidine

01–0.3 TD patch 2–32 mg/d

Local anesthetic

Mexelitine

Na+ channel blocker

Liver toxicity, #BP

150–900 mg/d

Corticosteroids

Methyl prednisone Dexamethasone

Hyperglycemia, weight gain, edema, agitation

Variable 4–96 mg/d

BP, blood pressure; Ca2+, calcium; CNS, central nervous system; GABA, gamma aminobutyric acid; GI, gastrointestinal; HS, bedtime; HR, heart rate; LFT, liver function test; mg/d, milligram per day; Na+, sodium; NRI, norepinephrine reuptake inhibition; SSRI, selective serotonin reuptake inhibition; t1/2, half-life; TD, transdermal.

injection of local anesthetic and/or botulinum toxin into anterior scalene and/or pectoralis muscle can produce the desired relief, although it is only short lasting. Trigger point injections to the surrounding musculature involved are utilized for breakthrough pain control.

13. Discuss surgical management strategies of TOS Patients with a definitive etiology and who have failed conservative management are ideal candidates for surgical correction. The three surgical approaches

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Chapter 13: Thoracic outlet syndrome (TOS): an enigma in pain medicine

include a supraclavicular, transaxillary, and posterior surgical approach. A supraclavicular approach is preferred for resection of a cervical rib along with scalenectomy, while some surgeons choose a transaxillary approach for first rib and scalene muscle resection. The posterior approach is technically challenging and utilized when the above two methods have failed to relieve symptoms. A dorsal sympathectomy is also considered in these patients. A vascular surgeon is usually involved to surgically correct vascular deformities and/or compromise to restore circulation to the affected extremity. Regardless of the surgical technique used, a major factor that is shown to prevent patients from going back to work is a pre-existing poor psychosocial working condition.

14. What are the treatment outcomes for TOS? Vascular TOS operated early has been shown to produce excellent results. By the disability of the shoulder, arm, and hand (DASH) questionnaire, 80% of patients reported minimal disability for up to 10 years. nTOS is challenging to diagnose and treat. Patient selection, comorbidities, baseline functional status, and surgical expertise and the type of surgical approach seem to play a role in the outcome of this pathology. Generally, demonstrating a definitive etiology during surgery is correlated with 80% success

References

15. What could be the impact of TOS on a person’s life? TOS can be a life-altering debilitating disease upon failure of standard treatment strategies. Many of the patients with TOS are physically active prior to the onset of symptoms, and are accustomed to an independent life style. Because of the decline in their functional status, they frequently need comprehensive support in all aspects of life. They may require psychologic counseling and vocational rehabilitation as they adjust to cope with the changes that result from their physical inability and occupational limitation.

Conclusion This case serves to emphasize that thorough clinical examination and appropriate clinical testing is critical in identifying TOS. More importantly, raising awareness about this entity could help practitioners consider this pathology in their differential diagnosis for shoulder and upper extremity pain and/or paresthesia symptoms so that their patients are directed appropriately to get timely interventions. documentation of brachial plexus/ thoracic outlet compression during elevated arm stress testing. Hand, American Association of Hand Surgery, online version published 4 May 2013.

definition, aetiological factors, diagnosis, management and occupational impact. J Occup Rehabil. 2011;21(3): 366–373.

1.

Klaassen Z, Sorenson E, Tubbs RS, et al. Thoracic outlet syndrome: a neurological and vascular disorder. Clin Anat. 2014;27(5):724–732.

2.

Ozoa G, Alves D, Fish DE. Thoracic outlet syndrome. Phy Med Rehabil Clin N Am. 2011;22(3):473–483.

4.

3.

Laulan J, Fouquet B, Rodaix C, et al. Thoracic outlet syndrome:

5.

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rate. However, recurrence due to scar tissue is commonly seen within 6 months of surgery. Further, late recurrence due to a different pathology makes this type of TOS extremely difficult to manage and treat.

Thompson JF. Thoracic outlet syndrome (Review). Surgery, 2013;31(5):256–260. Fried S, Nazarian LN. Dynamic neuromusculoskeletal ultrasound

6.

Winterton R, Farnell R. Peripheral nerve entrapment syndromes of the upper limb. Surgery. 2013; 31(4):172–176.

Section 2 Chapter

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Spinal Disorders

Patient with cervical radiculopathy Robert B. Bolash and Jianguo Cheng

Case description A 52-year-old male presented with neck, peri-scapular, and left upper extremity shooting pain associated with paresthesias in the forearm, hand, and third-fifth fingers without any clear provocative event. His complaints were associated with subjective weakness in the wrist flexors.

1. Provide a differential diagnosis for the patient’s complaint      

Cervical radiculopathy Zygapophysial (facet) joint syndrome Brachial plexopathy Thoracic outlet syndrome Pancoast tumor Shoulder pathology including tendonitis, impingement syndromes, rotator cuff tears, adhesive capsulitis, gleno-humeral arthritis  Peripheral nerve entrapment  Sympathetically mediated pain syndromes

2. Who is affected by cervical radiculopathy? Cervical radiculopathy refers to a set of conditions in which one or more nerve roots in the cervical region are affected and do not function properly. The emphasis is on the nerve root involvement that results in pain (radicular pain), weakness, and numbness in specific areas of the arms and hands. It has an approximate annual incidence of 0.1% and affects men nearly twice as often as women. The peak age of onset is in the fifth decade of life. While patients often cite a motor vehicle accident as the cause of their cervical radicular symptoms, this association is

not supported by large epidemiologic studies. Trauma is present in only 15% of patients suffering from radiculopathy, and the absence of an inciting event is consistent with the pathophysiologic mechanism; namely that radicular symptoms are caused by progressive degenerative changes more often than an acute disc herniation.

3. Describe the likely anatomical causes of cervical radiculopathy and the pathophysiologic mechanisms for the observed symptoms There are seven cervical vertebrae and eight pairs of cervical spinal nerves. The cervical nerve roots are numbered to correspond with the vertebral body caudal to the level where the nerve exits the foramen. The C1 nerve root exits above the vertebral body of C1 while the C8 nerve root exits the foramen created by the posterior elements of the vertebral body of C7 and T1. Most cases of cervical radiculopathy are caused by encroachment upon the intervertebral foramen by hypertrophic zygapophysial and uncovertebral joints. Stress on these posterior joints can be accelerated by progressive loss of disc height, though disc herniation is not thought to be the predominant pathophysiologic entity. In contrast to the proposed mechanisms for the development of lumbar radiculopathy, only 22% of the cases of radiculopathies in the cervical region result from herniation of the cervical disc. Hypertrophy of the facet (zygapophysial) joints narrow the intervertebral foramen and cause compressive and inflammatory changes of the nerve root. These changes have a propensity to involve the lower cervical spine with the C7 nerve root most often affected (70% of cases), followed by the C6 (20%) nerve root.

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Deficits on clinical examination can assist in predicting the affected cervical nerve root (Table 14.1). Compression of the nerve root by the overgrowth of the bony elements is thought to cause compression and hypoxia of both the nerve root and dorsal root Table 14.1. Deficits on clinical examination can assist in predicting the affected cervical nerve root

Effected root

Motor group deficit

Sensory deficit

Reflex decrement

C5

Shoulder abductors

Lateral upper arm

Supinator reflex

C6

Elbow flexion

Thumb

Biceps reflex

C7

Wrist flexion

Third digit

Triceps reflex

C8

Thumb flexors

Fifth digit

None

Hypertrophy of uncovertebral joint

Spinal ganglion

Hypertrophy of zygapophysial joint

Herniation of nucleus pulposus

Spinal nerve

Superior articular process

Spinal cord

Cervical vertebra

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ganglion which can result in pain in the corresponding dermatome. Because the cervical nerve roots emerging from the foramen are mixed, both sensory symptoms such as pain or paresthesia, as well as motor symptoms such as hyporeflexia or weakness can occur. Herniation of the nucleus pulposus, if present, occurs when the tough outer disc annulus fractures resulting in protrusion or extrusion of the gelatinous contents of the nucleus pulposus through the annular defect. The posterior longitudinal ligament does not extend very far laterally in the cervical region providing a path of low resistance for the nuclear contents to travel posterolateral toward the neural structures. Radicular symptoms develop if the disc contents mechanically compress or chemically irritate the nerve root, resulting in inflammatory changes in and around the nerve roots. Inflammatory mediators including interleukins and prostaglandins result in Figure 14.1. Cervical vertebrae and associated neural elements. Cervical radiculopathy can develop when the nerve root is compressed by the development of an osteophyte at the uncovertebral or zygapophysial joint, or when a disc hernation compresses the nerve as it exits the intervertebral foramen. From Carette S, Fehlings MG. N Engl J Med. 2005;353:392–399, with permission.

Chapter 14: Patient with cervical radiculopathy

edema and worsen the local compression. In the presence of inflammatory mediators, the nerves of nociception are more easily activated due to peripheral sensitization. As a general rule, a history consistent with acute worsening of symptoms is more consistent with disc herniation, while a gradual progression suggests a bony overgrowth as the etiology. A minority of cervical radiculopathies are attributable to noncompressive causes such as infection, granulomatous infiltrate, or demyelinating disorders. These etiologies tend not to be confined to a single nerve root, instead presenting with symptoms involving multiple levels. The natural history of non-compressive etiologies tends to be dictated by the response to treatment of the underlying condition.

4. What factors from the history and physical examination support the diagnosis? Cervical radiculopathy presents as neck and arm pain described as burning or tingling and distributed in a myotomal or dermatomal pattern. The radicular syndrome is sometimes associated with the loss of stretch reflexes in the distribution of the affected nerve root. Subjective weakness is seen in the minority of cases. At times, clinically isolating the affected nerve root by history or physical exam maneuvers is often difficult because of overlap of the cervical dermatomes. Myotomal deficits may have greater diagnostic value than sensory dermatomes. Clinical diagnosis can be further complicated by the observation that there is some anatomic variation in the innervation of the upper extremity. Frame shift variants of the cervical innervation by one vertebral level can be present in some individuals complicating the clinical exam. Physical exam maneuvers for the diagnosis of cervical radiculopathy are centered on assessing the response to either provoking or alleviating tension on the neural elements at the level of the nerve root, or opening or narrowing the neural foramen. At least four tests have been described and have some evidence to support their use: (1) Spurling’s maneuver, (2) shoulder abduction, (3) Valsalva maneuver, and (4) traction/neck distraction. The Spurling’s maneuver is performed in the sitting position. The patient extends the neck and rotates and laterally bends the head toward the symptomatic

side; an axial compression force of approximately 7 kg is then applied by the examiner through the top of the patient’s head; the test is considered positive when the maneuver elicits the typical radicular arm pain. Pain in the neck without radicular symptoms is a negative result. Rotation narrows the intervertebral foramen while neck extension worsens disc bulge. To perform the shoulder abduction relief test, the practitioner asks the patient to place the hand of the affected side atop their head in the seated position and assess whether there is any change in the radicular symptoms. A positive test results in decrease or elimination of the radicular symptoms with the maneuver. Some patients may have discovered this on their own and assume a hand-atop-head position when reclining and provide this information on history. The Valsalva maneuver requires that the patient take a deep breath and exhale forcefully against a closed upper airway. The resultant increase in intrathecal pressure worsens nerve root compression when space-occupying lesions such as an osteophyte or herniated disc are present. The traction/neck distraction test is performed with the patient in a comfortable supine position. The physician then grasps the head by placing one hand under the occiput and another beneath the chin and applying 15 kg of axial traction force. A positive test will result in a decrease or elimination of the radicular symptoms. The Spurling’s, Valsalva, and traction/neck distraction tests all demonstrated high specificity and low sensitivity when reviewed with objective testing. Overall, a positive test is helpful in establishing the diagnosis of cervical radiculopathy, but a negative test has low utility in narrowing the differential diagnosis.

5. What is the value of diagnostic testing and imaging in evaluating a patient with cervical radiculopathy? Given that cervical radiculopathy is a clinical diagnosis, a careful history and physical exam is the most important diagnostic tool. The ability to make the diagnosis based on history alone has been reported as high as 75%. The prevalence of asymptomatic disc bulge can be seen in over half of all patients without complaints of neck pain undergoing imaging studies for other indications. Therefore, radiographic imaging

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is a poor screening test. Despite these observations, imaging or electrodiagnostic modalities can support the clinical diagnosis and remains useful in differentiating cervical radiculopathy from other disorders and in planning a surgical approach. Plain radiographs are of limited utility in the assessment of cervical radiculopathy. The inability to detect tumor, infection, disc herniation, or cord compression limits the utility of plain radiographs. They are reserved for patients with traumatic injury and are often obtained as part of a flexion/extension series to evaluate patients with spondylolisthesis. Cervical radiculopathy due to compressive etiologies is best evaluated with non-contrast MRI. Though soft tissue structures are well visualized, bony abnormalities may be underestimated when compared to CT. In the presence of clinical concern for non-compressive etiologies, MRI with gadolinium contrast is also indicated. There are no well-established guidelines dictating when to order an MRI, but most would agree that clinical suspicion for tumor or infection, as well as progressive symptoms are indicators for obtaining imaging. Neuroimaging is recommended when persistent symptoms do not resolve after 6 weeks of conservative treatment or when significant neurologic symptoms such as weakness or myelopathy are present. CT can be useful in detecting osteophytes or assessing the bony architecture in clinical situations where an MRI is not easily obtainable. While easily able to visualize bony structures, CT alone has limited ability to visualize soft tissue structures. CT myelography combines traditional CT with the administration of intrathecal contrast. Myelography provides assessments similar in quality to those obtained with MRI, but requires a dural puncture and carries the risks associated with interventional procedures. For these reasons, it has fallen out of favor as an initial imaging modality and is instead reserved for those individuals who are unable to undergo MRI. CT myelography may also offer better sensitivity for foraminal and bony abnormalities when clinical signs are discordant with MRI findings. Non-contrast cervical MRI can be normal in noncompressive etiologies of cervical radiculopathy and may prompt investigation with electrodiagnostic studies. Upper extremity electrodiagnostic studies can also be performed when differentiating cervical radiculopathy from other neurologic conditions is difficult. Estimated sensitivity of electrodiagnostic testing is thought to be as high as 50–71%.

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Nerve conduction studies (NCS) are accompanied by needle electromyography (EMG) in both the muscles of the arm and posterior neck. NCS are most useful to rule out peripheral nerve entrapment syndromes or diffuse peripheral neuropathies while EMG is useful to characterize abnormalities that occur in a myotomal distribution. Spontaneous single muscle fiber action potentials are seen in the presence of ongoing axonal loss of motor neurons. Fibrillation potentials and positive sharp wave potentials develop subacutely after muscle denervation occurs, and are considered to be most sensitive for establishing the diagnosis of cervical radiculopathy. Nerve fibers innervating the unaffected muscles slowly sprout to supply the denervated muscle groups and demonstrate longer and larger motor units on needle EMG. In order to capture this phenomenon, EMG is therefore often delayed until the symptoms are present for more than 3 weeks. Laboratory testing is non-specific for mechanical causes of radicular pain. C-reactive protein and erythrocyte sedimentation rate can be obtained when considering infectious and neoplastic processes, though these tests are non-specific and nearly universally followed by imaging modalities.

6. What is the efficacy of non-surgical treatment strategies? Analgesics, traction, manipulation, physical therapy, cervical collars, and massage are among the most commonly employed conservative strategies despite variable evidence supporting their superiority over a wait-and-see approach. Oral analgesics including non-steroidal anti-inflammatories, membrane stabilizers, muscle relaxants, corticosteroid tapers, and opioids have all been utilized without consistent evidence supporting one agent over another. Despite the lack of a significant body of supportive evidence, these agents are typically well accepted by patients and are often employed as the first-line treatment approach. Cervical traction applies a distracting force to the neck to relieve the pressure on the cervical nerve roots by increasing the joint spaces and relaxing the cervical paraspinous musculature. Despite its widespread use, several studies and a systematic review have failed to consistently demonstrate efficacy of this modality, and some have shown the therapy may actually worsen symptoms.

Chapter 14: Patient with cervical radiculopathy

Both low velocity low amplitude and high velocity low amplitude manipulation have been shown to reduce radicular symptoms and improve pain scores in cervical radiculopathy patients. MRI obtained after a course of chiropractic therapy demonstrated a reduction in disc herniation in 63% of treated patients, the majority of whom were able to return to work. Risks with chiropractic manipulation include worsening of neurologic symptoms and rare catastrophic vascular events. In considering patients to exclude from chiropractic therapy, pre-manipulation imaging can be obtained to exclude those at increased risk. In a randomized control trial, both a short-term semi-hard cervical collar and physical therapy program have been shown to be more effective than a wait-and-see approach at 6-week follow-up. This leads the clinician to question whether it is best to counsel patients to increase activity or decrease mobility. In another study, manual therapy combined with exercise physical therapy (PT) is superior to either modality alone. The effectiveness of PT is seen at 6 weeks but is no better than a wait-and-see intervention at 6 months follow-up. Similarly the outcomes with a cervical collar are no better at 6-month follow-up than those that employed a strategy promoting mobility. Despite the conflicting evidence, it is typically recommended that patients with cervical radiculopathy commence a formal physical therapy program shortly after presentation given the minimal risk, though a cervical collar seems to be equally effective and is likely less costly.

7. Describe the benefits and risks of interventional strategies to treat cervical radiculopathy Prospective studies have demonstrated the effectiveness of epidural steroid injections for the treatment of cervical radiculopathy resulting in resolution of upper extremity complaints in 40–75% of patients. Intramuscular placement was compared to epidural injection and the effectiveness of the corticosteroid was site specific. Both interlaminar and transforaminal approaches have been employed, but there has been no head-to-head study of the superiority of one approach over the other in the cervical region. However, cervical transforaminal injection of particulate steroids has particularly been linked to catastrophic

complications and is therefore generally not recommended. Although the effects of epidural steroid injection are usually short lived, complete or near complete pain relief can be sustained for more than 3 years at long-term follow-up in some cases. Diagnostic selective nerve root blocks can be performed to isolate a single nerve root when clinical and radiographic diagnosis remains uncertain. Using fluoroscopy and radiographic contrast material, 0.5 ml of local anesthetic is injected along the suspected nerve root and pain is assessed postprocedurally. If pain persists, the intervention can be carried out at another level until the affected nerve root is identified. This strategy will offer only shortterm relief, but may be useful in planning a surgical intervention, especially when multilevel or discordant pathology is present on neuroimaging. Reported complications of cervical epidural injections include brainstem or spinal cord ischemia due to vasospasm, infarction due to the inadvertent intravascular injection of particulate steroid, and unrecognized intrathecal injection of local anesthetic. At least 15 fatal case reports with a transforaminal approach have been noted. To mitigate these risks, the following are generally recommended: the use of skilled practitioners, fluoroscopic guidance, an interlaminar approach, and the avoidance of general anesthesia. Though not in widespread use, pulsed radiofrequency neurotomy of the dorsal root ganglion has been shown to result in a sustained decrease in pain scores at 3-month follow-up. Neuritis, paresthesia, and motor weakness have all been reported following radiofrequency ablation. Despite its clinical application, spinal cord stimulation has not been well studied for cervical radiculopathy.

8. Discuss the role for a surgical consultation Symptoms of gait disturbances, lower extremity symptoms, sphincter incontinence, hyperreflexia, hypertonia, clonus, spasticity, and clumsiness suggest myelopathy and should prompt a surgical referral. Myelopathy can often be progressive and irreversible and therefore warrants early consideration for surgical decompression. Fever, chills, or weight loss suggest non-compressive etiologies including neoplastic or infectious causes and require prompt evaluation and treatment of the underlying etiology.

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Surgical consult is recommended if the patients with MRI evidence of nerve root compression fail to respond to multiple conservative and interventional approaches in 3 months. Three-quarters of patients typically obtain significant relief of their radicular symptoms following surgical decompression and this is sustained at 2-year follow-up. The presence of preoperative EMG abnormalities correlates with a higher likelihood of a successful surgical outcome. Discectomy and corpectomy can be performed via an anterior approach and can employ insertion of a synthetic disc spacer or bone graft. The anterior approach minimizes manipulation of the spinal cord and permits removal of both disc material and osteophytes. Laminectomy, foraminotomy or laminoplasty require posterior surgical approaches and are typically employed when a single paramedian disc herniation is present. Intervertebral fusion can be performed via either anterior or posterior approaches. Specific surgical complications include non-union, dysphagia, nerve root or spinal cord injury, and increased symptoms including worsening pain.

9. Compare the anticipated outcomes with conservative, interventional, and surgical approaches Between 40 and 90% of patients will experience resolution of cervical radicular symptoms with conservative

References 1.

2.

3.

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Arnasson O, Carlsson CA, Pellettieri L. Surgical and conservative treatment of cervical spondylotic radiculopathy and myelopathy. Acta Neurochir (Wien). 1987;84:48–53. BenEliyahu DJ. Magnetic resonance imaging and clinical follow-up: study of 27 patients receiving chiropractic care for cervical and lumbar disc herniations. J Manipulative Physiol Ther. 1996;19: 597–606. Boden SD, McCowin PR, Davis DO, et al. Abnormal magneticresonance scans of the cervical spine in asymptomatic subjects: a prospective investigation. J Bone Joint Surg Am. 1990;72(8): 1178–1184.

4.

5.

6.

7.

measures alone advocating the importance of patient counseling and reassurance. Larger and more lateral disc herniations, when they occur, tend to exhibit a greater degree of regression. Five predictors of poor outcome have been defined: (1) multiple episodes of radicular symptoms for more than 5 years, (2) more than three episodes of radiculopathy, (3) bilateral symptoms, (4) women over age 50, and (5) symptoms which are worsening at the time of presentation. There are few head-to-head trials comparing outcomes with various treatment modalities. When randomized to treatments with a hard collar, physical therapy, or surgical intervention, the surgical group obtained the most significant improvement in pain reduction at 3-month follow-up. When again assessed at 1-year or 2-year follow-up, there were no differences between the surgery group and the conservative treatment groups. Conservative treatment strategies are preferred since most patients will be asymptomatic or only suffer minor limitations at long-term follow-up. It is reasonable to anticipate that one-third of patients will suffer a reoccurrence of radicular symptoms following initial resolution. We counsel patients to again follow a conservative stepwise approach and employ those strategies they found useful in the past if their symptoms return.

CM Bono CM, Ghiselli G, Gilbert TJ, et al. An evidence-based clinical guideline for the diagnosis and treatment of cervical radiculopathy from degenerative disorders. Spine J. 2011;11:64–72. British Association of Physical Medicine. Pain in the neck and arm: a multicentre trial of the effects of physiotherapy, arranged by the British Association of Physical Medicine. Br Med J. 1966;1:253–258. Bush K, Hillier S. Outcome of cervical radiculopathy treated with periradicular/epidural corticosteroid injections: a prospective study with independent clinical review. Eur Spine J. 1996;5:319–325. Carette S, Fehlings MG. Clinical practice: Cervical radiculopathy. N Engl J Med. 2005;353:392–399.

8.

Cicala RS, Thoni K, Angel JJ. Long-term results of cervical epidural steroid injections. Clin J Pain. 1989;5:143–145.

9.

De Hertogh WJ, Vaes PH, Vijverman V, et al. The clinical examination of neck pain patients: the validity of a group of tests. Man Ther. 2007;12:50–55.

10. Graham N, Gross AR, Goldsmith C. Mechanical traction for mechanical neck disorders: a systematic review. J Rehabil Med. 2006;38:145–152. 11. Kuijper B, Tans JT, Beelen A, et al. Cervical collar or physiotherapy versus wait and see policy for recent onset cervical radiculopathy: randomised trial. BMJ. 2009;339:b3883. 12. Martin GM, Corbin KB. An evaluation of conservative

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treatment for patients with cervical disk syndrome. Arch Phys Med Rehabil. 1954;35:87–92. 13. Persson L, Karlberg M, Magnusson M. Effects of different treatments on postural performance in patients with cervical root compression: A randomized prospective study assessing the importance of the neck in postural control. J Vestib Res. 1996;6:439–453. 14. Persson LC, Carlsson CA, Carlsson JY. Long-lasting cervical radicular pain managed with surgery, physiotherapy, or a cervical collar: A prospective, randomized study. Spine. 1997;22:751–758. 15. Radhakrishnan K, Litchy WJ, O’Fallon WM, et al. Epidemiology of cervical radiculopathy: A population-based study from Rochester, Minnesota, 1976 through 1990. Brain. 1994;117:325–335. 16. Rodine RJ, Vernon H. Cervical radiculopathy: a systematic review

on treatment by spinal manipulation and measurement with the Neck Disability Index. J Can Chiropr Assoc. 2012;56: 18–28.

21. Valtonen EJ, Kiuru E. Cervical traction as a therapeutic tool: A clinical analysis based on 212 patients. Scand J Rehabil Med. 1970;2:29–36.

17. Rubinstein SM, Pool JJ, van Tulder MW, et al. Systematic review of the diagnostic accuracy of provocative tests of the neck for diagnosing cervical radiculopathy. Eur Spine J. 2007;16:307–319.

22. van der Heijden GJ, Beurskens AJ, Koes BW, et al. The efficacy of traction for back and neck pain: a systematic, blinded review of randomized clinical trial methods. Phys Ther. 1995;75:93–104.

18. Shabat S, Leitner Y, David R, et al. The correlation between Spurling test and imaging studies in detecting cervical radiculopathy. J Neuroimaging. 2012;22:375–378.

23. van Kleef M, Liem L, Lousberg R. Radiofrequency lesion adjacent to the dorsal root ganglion for cervicobrachial pain: a prospective double blind randomized study. Neurosurgery. 1996;38:1127–1131.

19. Tong HC, Haig AJ, Yamakawa K. The Spurling test and cervical radiculopathy. Spine. 2002;27:156–159. 20. Vallée JN, Feydy A, Carlier RY, et al. Chronic cervical radiculopathy: lateral-approach periradicular corticosteroid injection. Radiology. 2001;218:886–892.

24. Van Zundert J, Huntoon M, Patijn J, et al. Cervical radicular pain. Pain Pract. 2010;10:1–17. 25. Young IA, Michener LA, Cleland JA, et al. Manual therapy, exercise, and traction for patients with cervical radiculopathy: a randomized clinical trial. Phys Ther. 2009;89(7):632–642.

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Section 2 Chapter

15

Spinal Disorders

Patient with axial neck pain Vikram B. Patel

Case study A 38-year-old healthy female was in a car accident. She was behind another car at a stop light when a pick-up truck rear-ended her vehicle at about 20 mph. She was taken to an emergency room and a cervical fracture was ruled out with a plain x-ray. She continued to have neck pain radiating to the left shoulder and also had severe muscle spasms. Pain does not radiate beyond the shoulder on the left side and she does not have any tingling or numbness in the arm or hand. MRI of the cervical spine after 1 month shows a bulging disc at C5–6 with no neural compromise and no spinal cord compression.

1. What is the differential diagnosis? a. Cervical facet joint injury causing cervical facet syndrome secondary to whiplash type of injury b. Cervical discogenic pain due to annular disruption of the disc secondary to flexion injury c. Myofascial pain syndrome Cervical pain after a whiplash type of injury is a very common symptom, and was initially defined by the Quebec Task Force (QTF) in 1995.[1] Transition to chronicity is also prevalent. About 50% of patients reported neck pain after a 1-year follow-up.[2] As this woman was rear-ended, the impact has likely caused an extension type of injury leading to the facet joints being inflamed and generating pain. Cervical spine undergoes a sigmoid deformation very early after impact. During this deformation, lower cervical segments undergo posterior rotation around an abnormally high axis of rotation, resulting in abnormal separation of the anterior elements of the cervical spine, and impaction of the facet joints. The demonstration of a mechanism for injury of the facet joints complements postmortem studies that reveal lesions

in these joints, and clinical studies that have demonstrated that facet joint pain is the single most common basis for chronic neck pain after injury.[3] As she was behind another car, she would also have suffered a frontal collision causing somewhat milder flexion type of injury. Flexion injuries are the main cause of cervical disc damage and hence a disc bulge or even a rupture is very common based on the speed and severity of the impact. Disc strains are highest in the C4-C5-C6 disc segments, and ligament strains are greatest in these ligaments.[4]

2. What is the mechanism of injury in this patient? a. Whiplash type of cervical spine injury b. Extension type of injury during a rear-ended impact c. Flexion type of injury due to a frontal collision d. Spinal pain leading to secondary myofascial pain e. Shoulder joint may be involved during the initial injury f. Joint mobility may be reduced due to muscle pain, immobility, and dysfunction i. This can lead to secondary joint pain because of decreased range of motion ii. Shoulder adhesions may cause additional reduced range of motion and pain

3. Why is this condition occasionally misdiagnosed? Cervical axial pain is often misdiagnosed as radicular pain or shoulder pain (because of the radiation pattern). This may be secondary to an incidental finding of a

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Figure 15.2. Anteroposterior x-ray of the cervical spine with “0pen mouth” view showing the joints at the upper level of the cervical spine. Figure 15.1. Cervical facet joint pain radiation pattern.

damaged intervertebral disc or the radiation pattern of the pain. Nerve root compression leading to radicular pain usually presents with paresthesiae in the distribution of that particular nerve root and may be accompanied by pain, numbness, and/or weakness. Axial pain is more commonly presented without any neuropathic symptoms. It is localized in case of discogenic pain and has a specific radiation pattern if the facet joints are the pain generators (Figure 15.1). The facet joint radiation pattern from adjacent joints often overlap but it rarely radiates beyond the mid-upper arm.

4. Describe the anatomy and pathophysiology of the cervical facet (zygopophysial) joints The cervical spine consists of seven cervical vertebral bodies and intervertebral discs between them. The first vertebra is a ring-shaped structure called the atlas and articulates with the skull at the atlanto-occipital joint and with the second vertebral body at the atlantoaxial joint. The second vertebra has a vertical process called the odontoid process which provides rotational movement with its articulation along the anterior aspect of the 1st cervical vertebra (Figure 15.2). The cervical spine may be arbitrarily divided into anterior, middle, and posterior segments (Figure 15.3).

The anterior segment is made up of the vertebral body, intervertebral disc, and the anterior longitudinal ligament. The middle segment contains the intervertebral foramen, the posterior longitudinal ligament, the intervertebral foramen, the exiting nerve roots plus the blood vessels to and from the spinal cord. The posterior segment is made up of the articular elements and in the cervical spine these elements are labeled articular pillars. Each vertebra articulates with the superior as well as inferior vertebral body. These articular joints are called the facet or zygopophysial joints (Figures 15.3 and 15.4). In the cervical spine, these segments overlap and the middle + posterior segments present in the same plane (Figure 15.3). The anterior segment containing the disc is subjected to excessive pressure during a forceful forward flexion as well as rotational movements and may rupture. Subluxation of the cervical vertebral bodies is also likely and may cause damage to the vertebral arteries.

5. How to diagnose cervical axial pain? Diagnosis of axial neck pain is based on the imaging studies (e.g., MRI of the neck, plain x-ray) as well as the history and physical examination. a. MRI findings: i. A bulging disc in the cervical spine often denotes an internally disrupted disc. A visibly

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Figure 15.3. Cervical spine cross-section at C7.

Figure 15.4. Articular pillars and the facet joints in the cervical spine.

herniated disc may cause axial pain as well as radicular pain if a nerve root is compressed and also be due to the inflammatory response from the herniated disc. Narrowing of the cervical spinal canal is usually present and may compress the spinal cord itself. ii. The facet joints may show narrowing, inflammation, and swelling. b. Plain x-ray of the cervical spine may show any anatomical displacement in the form of subluxation or a fracture. It may also reveal reduction of cervical lordosis and reduction in the disc height. c. History of injury or accident and the nature of the injury would help determine the pain generator: i. Facet joint pain is usually increased with extension and rotation on the ipsilateral side of

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the cervical spine and may also radiate in a specific pattern but rarely extends beyond the mid-humeral level. This is an extension type of injury. ii. Increased pain with flexion with or without any paresthesiae may indicate a disc as the pain generator, and is usually the result of a flexion type of injury. iii. Superimposed myofascial pain is usually secondary to the spine pain and may exacerbate overall pain during flexion as well as extension and cause stiffness of the neck, restricting the movements. iv. Complaints of radiating pain vs. non-radiating (axial) pain would help in differentiating the facet vs. nerve root related pain.

Chapter 15: Patient with axial neck pain

Figure 15.5. Cervical medial branches AP and lateral views. The centroid of the lateral masses represents on a lateral view represents the target point for a diagnostic cervical medial branch block.

6. What are the treatment options for axial neck pain? a. Conservative approaches. Conservative treatment for axial neck pain due to the disc or the facets is largely based on the intensity of pain, radiologic findings, and the patient’s ability to perform dayto-day activities. In most patients, cervical discs heal without any interventions if further damage is prevented. PT, anti-inflammatory agents, and mild oral analgesics are the mainstay of the conservative treatment options. b. Interventional treatments: i. Minimally invasive treatment options are reserved for patients who fail to improve despite adequate trials of physical therapy, inability to perform physical therapy due to increased pain, inadequate response to medications, or inability to tolerate medications due to side effects. ii. Facet joint procedures: (1) Intra-articular facet joint injections of steroid have recently lost their appeal after several studies revealed poor evidence for the efficacy of such injections.[5] (2) Facet joints are supplied by the medial branches of the cervical nerve roots. Each joint is supplied by two medial branches, one from the same level and one from the

Figure 15.6. Cervical medial branch block needle placement.

level below, thus C3–4 facet joint is supplied by the C3 as well as C4 medial branches (Figure 15.5). Hence to denervate these joints one has to lyse two medial branches per level. (3) A carefully performed diagnostic medial branch block (Figure 15.6) on two different occasions using two different local anesthetics provides the most reliable diagnostic criteria to identify the facets

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Figure 15.7. Radiofrequency ablation of the cervical medial branch in a patient with post laminectomy syndrome. Note the needle tip at the “waist” of the cervical articular pillar in AP view.

as the pain generators.[5] Radiofrequency ablation is then performed to denervate these joints for the long term (Figure 15.7). iii. Disc procedures: (1) Minimally invasive intradiscal procedures are aimed at reducing the bulk of the intervertebral disc by removing part of the nucleus percutaneously. A properly performed discogram may help determine if the disc has an intact annulus and the herniation is contained.

7. Procedural description a. Facet joint medial branch block: i. The block is ideally performed under fluoroscopic guidance, although recently it has been performed by some practitioners with the use of ultrasound guidance. ii. Lateral or posterior approaches have been described. The needle tip is fluoroscopically positioned at the midpoint of the articular pillar at the given level. A small amount of local anesthetic is then injected (usually < 0.25 ml) at each level (Figure 15.6).

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iii. The level of pain relief is assessed soon after the block and the duration of the block depends on the type of local anesthetic injected. At least 75% of pain reduction lasting for the duration of the injected local anesthetic is a reliable indicator of facet joint mediated pain,[6] and the evidence for this procedure is a level II-1.[7] However, the patient may report longer duration of pain relief as the blocked facets may also relieve the superimposed muscular spasm and pain. b. Medial branch radiofrequency ablation: i. After a successful diagnostic set of medial branch blocks, radiofrequency ablation of the same medial branches is performed for longer pain relief. ii. The needles (22-G, 5 cm needle with 4 or 5 mm active tip) may be placed via posterior or lateral approach. Lateral approach may be preferable in patients who cannot tolerate prone position due to other comorbidities. Mild sedation may be provided for this procedure. iii. Once the needle tip is at the right placement, i.e., at the midpoint of the articular pillar on lateral view and at the “waist” of the articular pillar in anteroposterior view, sensory as well as motor stimulation is carried out. Sensory

Chapter 15: Patient with axial neck pain

stimulation may reveal pressure-like sensation in the neck and motor stimulation would elicit paraspinal muscle stimulation. These stimuli should not radiate to the arm. iv. After satisfactory stimulation pattern is established, local anesthetic with or without a minute amount of corticosteroid is injected (not to exceed 0.25 ml) and radiofrequency ablation is carried out. v. Preferences for the duration as well as temperature vary among practitioners. The author prefers a 60-second lesion set at 70°C.

8. What are the possible complications from these procedures? Risk of infection, bleeding, no pain relief, or nerve damage is similar to any cervical spine procedure but perhaps less with the medial branch block as it only involves local anesthetic injection. The radiofrequency lesioning may cause nerve damage if proper protocols are not observed and the needle tip is too close to the nerve roots. Sedation may also lead to complications if the patient is heavily sedated and cannot respond in an appropriate manner. A short period of increased pain may be due to muscular spasms and myofascial pain.

9. What are the outcomes with facet joint procedures? a. Radiofrequency ablation provides sustained longterm pain relief and may also help reduce the muscular pain which is secondary to the facet joint pain. Combined with proper physical therapy, it may provide 6–9 months of good pain relief. b. The evidence for diagnosis of cervical facet joint pain with controlled comparative local anesthetic blocks is Level I or II-1. The indicated evidence for therapeutic facet joint interventions is Level II-1 for medial branch blocks, and Level II-1 or II-2 for radiofrequency neurotomy.[7],[5]

10. Intradiscal procedures a. Diagnostic discogram i. Indications: disc bulge on an MRI ii. Increased pain with flexion of the neck iii. Failed conservative treatments

iv. It is a diagnostic tool rather than a prognostic tool and should be interpreted as such. However, a combination of diagnostic discogram and a pathologic disc pattern on imaging studies can essentially confirm the diagnosis of discogenic pain.[8] b. Procedure i. The procedure is performed under fluoroscopic guidance with strict aseptic precautions in supine position. Patient receives preoperative IV antibiotics and may also have antibiotics in the discography injectate. ii. A small caliber needle is placed within the nucleus of the target disc via right anterolateral approach.[9] This approach is preferable to mainly avoid penetration of the esophagus which can lead to a higher chance of infection (discitis). iii. A small amount of contrast material is injected (not to exceed 0.5 ml) and subsequent imaging is obtained to evaluate the disc morphology. A post-discogram CT scan provides the best diagnostic value. Reproduction of concordant pain is another important parameter that should be noted.

11. What are the possible complications from a cervical intradiscal procedure? a. Bleeding, nerve root damage, intraspinal penetration with possible spinal cord trauma. b. Infection is a very real risk[9] with subsequent discitis and possible epidural abscess, especially due to the possibility of the needle accidently traversing the esophagus on its way to the nucleus. Appropriate precautions such as strict aseptic technique and preoperative IV antibiotics as well as intradiscal antibiotics are required to lower such a risk. c. Excessive pressurization during a discogram may lead to the rupture of an already weakened annulus. Soft bulge of the disc with possible cord compression has also been reported. d. Damage to the endplates from the percutaneous discectomy procedures are likely if the probe is in contact with the endplate of the vertebral body.

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References 1.

2.

122

Spitzer WO, Skovron ML, Salmi LR, et al. Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining “whiplash” and its management. Soine. 1995; 20(8 Suppl):1S–73S. Carroll LJ, Holm LW, HoggJohnson S, et al. Course and prognostic factors for neck pain in whiplash-associated disorders (WAD): results of the Bone and Joint Decade 2000–2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33(4 Suppl): S83–92.

3.

Bogduk N, Yoganandan N. Biomechanics of the cervical spine Part 3: minor injuries. Clin Biomech (Bristol, Avon). 2001; 16(4):267–275.

joint injections. Pain Physician. 2012;15(6):E807–838. 7.

Falco FJ, Erhart S, Wargo BW, et al. Systematic review of diagnostic utility and therapeutic effectiveness of cervical facet joint interventions. Pain Physician. 2009;12(2):323–344.

4.

Panzer MB, Fice JB, Cronin DS. Cervical spine response in frontal crash. Med Eng Phys. 2011;33(9): 1147–1159.

8.

5.

Falco FJ, Manchikanti L, Datta S, et al. Systematic review of the therapeutic effectiveness of cervical facet joint interventions: an update. Pain Physician. 2012;15 (6):E839–868.

Siebenrock KA, Aebi M. The value of diskography in disk-related pain syndrome of the cervical spine for evaluation of indications for spondylodesis. Z Orthop Ihre Grenzgeb. 1993;131(3):220–224.

9.

6.

Falco FJ, Datta S, Manchikanti L, et al. An updated review of the diagnostic utility of cervical facet

Singh, V. The role of cervical discography in interventional pain management. Pain Physician. 2004;7(2):249–255.

Section 2 Chapter

16

Spinal Disorders

Patient with thoracic spine pain Ankit Maheshwari and Jianguo Cheng

Case study

Table 16.1. Differential diagnosis of a patient with thoracic pain

A 27-year-old male presents with pain in the back between the shoulder blades for 10 years. The pain is described as aching, heavy, and continuous. It is worse in the morning and improves as the day progresses. It has progressively deteriorated over the last 10 years. On physical exam, the patient has poor posture, reduced range of motion of the spine, paraspinal muscle spasm, and bilateral sacroiliac pain as well.

Nociceptive pain Compression fracture of the vertebrae Rib fracture/malignancy Facet arthropathy Axial Spondyloarthropathies: costochondritis, costoclavicular joint pain, costosternal joint pain Teitze’s syndrome DISH Myofascial pain syndrome

1. What are the anatomical structures that can produce pain in the thoracic region? Thoracic pain is not an uncommon presentation in the pain clinic affecting about 5% to 15% of patients.[1,2] The chest wall is made up of the vertebrae posteriorly, the sternum anteriorly, and the ribs laterally. The musculature of the chest wall may also be a source of pain. In addition, the chest viscera may produce pain in the thoracic region.[3] The differential diagnosis of thoracic pain is listed in Table 16.1. A thorough history and physical exam are essential to diagnosis. Interventional pain procedures have diagnostic and therapeutic value. We will focus on chest pain of spinal and musculoskeletal origin here. However, it is imperative not to overlook visceral pain when evaluating a patient because these conditions may be life threatening (cardiovascular and pulmonary diseases). Pain from abdominal viscera and the diaphragm can also be referred to the thoracic region.

Neuropathic pain Spinal cord disease: multiple sclerosis, tumor, syringomyelia Epidural cord compression: vertebral pathology, abscess, hematoma, facet hypertrophy Disc prolapse with cord/root compression Intercostal neuralgia - Infectious: herpes zoster and postherpetic neuralgia, syphilis - Traumatic: rib fracture, post-thoracotomy, postmastectomy - Tumor: schwannoma, neurofibroma

2. What are the key features in the differential diagnosis of thoracic pain? Thoracic pain can be nociceptive, neuropathic, mixed, or idiopathic. It could originate from the bony structures (rib fracture, sternum fracture, and compression fracture of the vertebral body), the intervertebral discs, the facet joints, the costovertebral joints, and the muscles and fascia. It can also be neuropathic, affecting the peripheral nervous system in such conditions as nerve root compression, herpes zoster and

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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postherpetic neuralgia, painful diabetic neuropathy, post-thoracotomy syndrome, postmastectomy syndrome, postradiation neuritis, and Maigne’s disease (posterior rami syndrome). Less frequently, neuropathic pain can originate from pathologies of the central nervous system such as syringomyelia, multiple sclerosis, and lesions compressing the spinal cord. Neuropathic pain is often described as burning, tingling, lancinating, and “electric like” while nociceptive pain is usually described as aching, heavy, tight, stiff, and sometimes sharp. Acute pain can typically be linked to specific inciting events and pathology

while chronic pain can be challenging to determine the cause and pathology. The key differential factors on history and physical exam are listed in Table 16.2. Conditions that must be kept in the differential are ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis (DISH), Scheuermann’s kyphosis, rheumatoid arthritis, osteoarthritis (compression fractures), costochondritis, Tietze syndrome, apophyseal facet syndrome, and primary cancer or metastatic disease of the spine. In addition, muscular pain with discrete trigger points is suggestive of myofascial pain syndrome.

Table 16.2. Key findings of various clinical syndromes affecting the thoracic spine

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Disease

History

Physical and investigation

1. Ankylosing spondylitis

Adolescent to young adult Morning stiffness Pain improves with exercise Shifting low back (SI joint) pain

Restricted range of motion SI joint involvement Anterior chest wall involvement Lab: High ESR, C-reactive protein (CRP) HLA B-27 may be positive Imaging: sacroiliitis, spinal fusion “bamboo spine”

2. Vertebral compression

Elderly person History of osteoarthritis/trauma Initially sharp and localized pain but can later become radiating (neuropathic) due to compression of nerve roots/spinal cord

Vertebral and paravertebral tenderness Imaging: x-ray shows compression fracture MRI needed of planning vertebroplasty

3. DISH

Middle aged or older patient Back and spinal stiffness causing aching pain

Spinal immobility Tenderness to palpation spread across affected vertebrae Reduced ROM Imaging is necessary to make the diagnosis, findings as listed in Table 3

4. Costovertebral joint arthritis

Patient with history of manual labor or known history of inflammatory arthritis Localized aching pain of mild to moderate intensity

Tenderness to deep palpation of affected joints Diagnostic local anesthetic injection of the joint relieves pain

5. Facet arthropathy

Patient with history of deep aching pain, sometimes sharp and worse with extension of the spine. Leaning forward makes the pain better

Tenderness of deep palpation of the affected joints Facet loading elicits pain Paraspinal muscle spasm is commonly associated Diagnostic medial branch block of the affected levels relieves the pain

6. Costochondritis

More common in younger people Focal area of pain in the lower anterior rib cage Exacerbation of pain with coughing, sneezing, and deep breathing

Focal tenderness to palpation over the costochondral joints Horizontal flexion test positive Diagnostic local anesthetic injection of the joint relieves pain

Chapter 16: Patient with thoracic spine pain

Table 16.2. (cont.)

Disease

History

Physical and investigation

7. Tietze syndrome

Commoner in people older than 50 years of age which confuses this with a coronary event Localized pain and swelling of the upper anterior chest wall Aggravating factors same as costochondritis

Tenderness to palpation and localized swelling over the 2nd and 3rd costochondral joints Imaging is normal

8. Myofascial pain

Patient will usually give a history of heavy lifting, repeated and heavy use of the affected musculature Mild to moderate aching pain on pressing and deep breathing

Discrete trigger points present Injection of local anesthetic in trigger points relieves pain

9. Dercum’s disease (adiposis dolorosa)

Patient may be an obese woman Presence of subcutaneous nodules, most commonly in the chest and arm area causing shooting/stabbing pain

Painful subcutaneous nodules with shooting pain on palpation

10. Spinal cord disease (tumor, syrinx, MS)

Diffuse and poorly localized pain, which is burning or tingling in nature Sensory or motor loss of varying degrees

Diffuse pain, no focal areas of tenderness Detailed neurologic examination reveals abnormal findings based on the location and extent of disease Imaging: MRI of the spine

11. Epidural lesion causing spinal compression (hematoma, abscess, tumor)

History of infectious/traumatic/iatrogenic event Localized back pain Associated neurologic impairment

Tenderness to deep palpation or fist thumping on the affected segment Detailed neurologic examination reveals abnormal findings based on the location and extent of disease Imaging: MRI of the spine with contrast

12. Disc herniation causing spinal compression

Generally older patient Localized moderate to severe pain in a segmental nerve distribution Described as shooting or throbbing aggravated by coughing, sneezing, straining

Discogenic pain is infrequent in the thoracic region. Pain is primarily radicular due to compression of the spine/nerve roots from disc herniation Imaging: MRI spine

13. Intercostal neuralgia (herpes zoster, PHN, tabes dorsalis)

History of herpes or syphilis Severe burning or lancinating pain in a segmental/dermatomal distribution

Hyperalgesia, Hyperesthesia in the affected dermatome Rash +/ Lab confirmation for herpes or syphilis Imaging of spine/thorax normal

14. Maigne’s syndrome (posterior rami syndrome)

Lower thoracic, upper lumbar back pain preceded by sudden twisting of the spine Concomitant pain in the gluteal or groin region

Tenderness over the thoracolumbar facets with possible limitation of range of motion and positive facet loading with pain reproduction on the ipsilateral side Low back pain that has not responded to treatments aimed at the lumbosacral levels

3. What is ankylosing spondylitis? Ankylosing spondylitis (AS) is a form of spondyloarthropathy which refers to any joint disease of the vertebral column. AS results in stiff spine due to

arthritic changes in the intervertebral joints including the costovertebral, costotransverse, and apophyseal facet joints.[4] History of morning stiffness, waking up in the second half of the night, and improvement of pain with movement and sacroiliitis is highly

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predictive of AS. This history associated with key radiologic and laboratory findings are highly sensitive for the diagnosis of AS.[5] Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein are elevated. The HLA-B27 antigen system is commonly positive although negative HLA-B27 does not rule out the diagnosis of AS. Pain from costovertebral joints is common in AS (Bechterew’s disease). The 1st, 11th, and 12th ribs (ribs with just one facet plane) and the 6th through 8th ribs (longest) are the most frequently affected.[6] The prevalence of thoracic facet joint pain in patients with localized thoracic pain is about 42%.[7] Pain in the anterior chest wall (ACW) is often due to involvement of the costochondral and costosternal joints. The presentation and subsequent tests in this case are consistent with the diagnosis of AS. The general approach to treatment of thoracic pain is discussed later.

4. What is Tietze syndrome? Tietze syndrome is a benign but painful swelling of the 2nd or 3rd costal cartilage.[8] Straining, severe cough, heavy manual work, and arthritic conditions have been implicated as the causes. There is localized swelling and tenderness over the involved cartilage.[9] The condition is usually self-limited with occasional exacerbations and remissions of unclear cause. Tietze syndrome is not the same as costochondritis and involves swelling of the costal cartilages, which does not appear in costochondritis. Costochondritis is the most common cause of anterior chest wall syndrome.[10] The pain is described as aching to sharp. Unlike Teitze syndrome, it involves multiple sites, typically the 3rd to 6th costal cartilages. There is no swelling but tenderness to palpation over the involved cartilage is present. The horizontal flexion test is indicative of costochondritis. It consists of flexing the arm at the shoulder and crossing across the anterior chest wall while applying steady traction in a horizontal direction. Rotating the patient’s head on the ipsilateral side produces pain by pressuring the costochondral joints.

5. What is DISH? DISH is a common disease with prevalence as high as 15% in women and 25% in men over age 50, and 26% in women and 28% in men over age 80.[11,12] The usual presentation is a middle aged or older patient with chronic middle to lower back pain and spinal stiffness. The diagnosis is predominantly radiologic as described

126

Table 16.3. Radiologic features of DISH

1. Flowing ossification along the anterolateral aspect of at least four contiguous vertebrae 2. Preservation of disc height in the involved vertebral segment; the relative absence of significant degenerative changes, such as marginal sclerosis in vertebral bodies or vacuum phenomenon 3. Absence of facet joint ankylosis; absence of sacroiliac erosion, sclerosis, or intra-articular osseous fusion Figure 16.1. Radiograph of the thoracic spine shows flowing new bone formation along the anterior aspects of at least four vertebral bodies. The disc spaces are maintained.

by Resnick et al (Table 16.3, Figure 16.1).[13] The disease may be associated with extra-articular manifestations which are usually bilateral and symmetric. The absence of sacroiliitis, true syndesmophytes, and ankylosing apophyseal joints distinguish this syndrome from AS.[14]

6. What is Scheuermann’s kyphosis? Describe the end plate changes of this disease Scheuermann’s kyphosis is the most common cause of angular, progressive, structural thoracic, or

Chapter 16: Patient with thoracic spine pain

neurologic complications secondary to degenerative spondylosis and disc herniation.[17] The treatment depends on the severity of the deformity and development of neurologic and cosmetic symptoms. Physiotherapy includes hamstrings stretching and strengthening of the core and trunk extensors. PT does not correct the progression of the deformity. Bracing may be a solution for patients with flexibility of the spine at the levels with kyphosis, kyphosis < 65 degrees, and skeletal immaturity.[18] Surgical correction may be needed for severe deformity and neurologic and pulmonary complications and after failure of conservative therapy.[19]

7. What is posterior rami syndrome (dorsal ramus syndrome, Maigne’s syndrome)?

Figure 16.2. Characteristic radiographic findings in a patient with Scheuermann’s disease showing irregular vertebral endplates with Schmorl’s nodes narrowing of the intervening intervertebral disc space.

thoracolumbar hyperkyphosis with associated back pain in adolescence. It has an incidence of 4–8% with no gender predominance.[15] Patients complain of a dull non-radiating pain at the apex of the “gibbus.” This is associated with a compensatory lumbar hyperlordosis, tightness in the hamstrings and iliopsoas, and stiffness of the anterior shoulder girdle.[15] The radiologic diagnosis can be established in the presence of kyphosis > 45 degrees with anterior wedging of three or more consecutive vertebrae by 5 degrees, the presence of irregular vertebral endplates with Schmorl’s nodes narrowing of the intervening intervertebral disc space (Figure 16.2). The angle of kyphosis is measured using the Cobb method.[16] The classic definition of involvement of three or more continuous vertebrae has been challenged by some authors and practically the presence of the above findings even in one vertebra has been used to make this diagnosis earlier. The condition is expected to have a benign course after completion of spinal growth. However, a patient with severe curves can develop progressive deformities with potential for

Posterior ramus syndrome, also referred to as thoracolumbar junction syndrome, is caused by the unexplained activation of the primary division of a dorsal ramus of spinal nerve. This causes neuropathic pain distributed in a tri-branched pattern. One branch sets off anteriorly to the groin or pubic region; a second branch remains posterior, innervating the lower back and upper gluteal region; and a third branch passes down the anterolateral thigh or trochanter region. While any (or all) of these branches may be involved, their constancy of location is what allows this to be defined as a distinct syndrome. Although the pain is distributed in areas of the lumbosacral region, the facet joints in the thoracic spine are implicated in the pathophysiology of this syndrome. The orientation of the thoracic facet joints between T9 and T12 vertebrae may change abruptly to that of the lumbar area.[20] The stress of this transition can produce facet arthropathy over time and result in irritation of the dorsal rami, causing dorsal ramus syndrome.[21] This pain is conducted through the lateral branches of the posterior primary rami of the lower thoracic and upper lumbar nerve roots, specifically the cluneal nerves from T12, L1, and L2.[22] The diagnosis of thoracolumbar syndrome is clinical with the variable presence of four criteria. First, the patient usually relates the onset of pain to a rotational twisting movement. The affected posterior ramus ends cutaneously causing trophic changes of the skin. Neuropathic pain in three well-described

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Chapter 16: Patient with thoracic spine pain

regions serves as the principal clinical component of the syndrome. Typical neuropathic skin changes are a thickening or nodularity of the skin, hair loss, or even a swollen puffy appearance. Second, the patients usually do not have spontaneous pain at the offending spinal level. Pain can be provoked by palpation of the facet joints and spinous processes which may help to determine the level of origin. Additional key physical findings include: (a) pain and deep tenderness to palpation over the iliac crest at the point where the distal cluneal nerve branches cross the iliac crest, (b) hypersensitivity of the skin and subcutaneous tissues of the gluteal and iliac crest areas, noted when a fold of skin is rolled between the fingers, (c) localized tenderness over the affected thoracolumbar segment when posterior-to-anterior or lateral pressure is applied to the spinous process at the affected level, and (d) tenderness and restricted motion. Pressure at these points will reproduce local discomfort and the patient’s referred pain.[23] Typically, patients do not have pain radiating below the knee, which is more typical of anterior ramus involvement. Third, radiographic evidence is non-contributory. Fourth, the diagnosis is confirmed by injection of local anesthetic into the correct facet joint that results in pain relief. This diagnostic procedure can also be therapeutic; the steroid injection or radiofrequency ablation of the medial branch can be applied for longer pain relief. Other treatment includes anti-inflammatory medications, spinal manipulation, and physical therapy.

8. How would you manage patients with thoracic pain? In the last decades, significant progress has been made in the management of patients with immunemediated diseases such as AS.[24] Early diagnosis can prevent or delay future anatomical abnormalities and painful spinal immobility. Generally, the strategy to treat patients with thoracic pain should include the following.

Conservative approaches Inflammatory arthritis and small joint arthritic pain such as costochondritis usually respond well to NSAIDs. Disease-modifying anti-rheumatologic drugs (DMARDs) and TNF-alpha inhibitors are the treatment of choice for most axial spondyloarthopathies and AS, typically in conjunction with NSAIDs,

128

physical therapy, and interventional treatments as needed. For neuropathic pain, the use of gabapentin or pregabalin has been shown to be effective for postherpetic neuralgia.[21–23] Antidepressants, such as TCAs, may also be effective.[25] Opioid medications should be reserved as a last resort in the treatment of these patients and used only for a short period of time with clear goals and close monitoring. TENS units have been shown to improve pain of myofascial origin as well as neuropathic pain. This may be a useful adjunct to medications and physical therapy in the treatment of thoracic spinal pain. Physical therapy for mobilization and strengthening and occupational therapy for posture correction is beneficial for somatic pain conditions of the thoracic spine. Braces may be indicated for spinal deformities.[18]

Interventional approaches Epidural or paravertebral injection of local anesthetics with steroid, with or without additives such as clonidine, has been shown to provide pain relief for thoracic radiculopathy, zoster and postherpetic neuralgia, intercostal neuralgia, and post-thoracotomy syndrome. Epidural injections for managing chronic thoracic pain showed fair evidence with one randomized controlled trial in patients with various causes whereas the evidence for post-thoracotomy syndrome was poor.[26] Chest wall pain from rib fractures after trauma is amenable to treatment with continuous epidural infusion through a catheter placed in the epidural space. This reduces splinting due to pain and improves ventilation.[27,28] Intercostal neuralgia may be treated with intercostal nerve block and paravertebral block.[29] Facet medial branch block can be diagnostic and therapeutic. There is strong evidence for diagnostic facet joint block for the diagnosis of facet joint pain. Studies have shown sustained pain relief of 1 year with repeated thoracic facet medial branch block.[30] Radiofrequency ablation of the medial branches after two successful medial branch blocks may be considered in patients with good but transient pain relief. Facet joint intra-articular injections can be done but have not been extensively studied for the thoracic spine.[31] Costochondral and costovertebral joint injections may have both diagnostic and therapeutic values.

Chapter 16: Patient with thoracic spine pain

These injections may facilitate participation in physical therapy. Trigger point injections with local anesthetic with or without steroid are indicated for myofascial pain where discrete trigger points can be identified. Spinal cord stimulation may be considered for neuropathic chest wall pain in refractory cases.[32,33] Vertebroplasty or kyphoplasty may be indicated for the treatment of compression fractures. The best time to treat patients with this modality is

References 1.

Linton SJ, Hallden K. Can we screen for problematic back pain? A screening questionnaire for predicting outcome in acute and subacute back pain. Clin J Pain. 1998;14(3):209–215.

2.

Lou L, Gauci CA. Radiofrequency treatment in thoracic pain. Pain Pract. 2002;2(3):224–225.

3.

Snell RS. Clinical Anatomy by Regions, 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2007.

4.

Reuler JB, Girard DE, Nardone DA. Sternoclavicular joint involvement in ankylosing spondylitis. South Med J. 1978; 71(12):1480–1481.

5.

Walker BF, Williamson OD. Mechanical or inflammatory low back pain: what are the potential signs and symptoms? Man Ther. 2009;14(3):314–320.

6.

Sidiropoulos PI, Hatemi G, Song IH, et al. Evidence-based recommendations for the management of ankylosing spondylitis: systematic literature search of the 3E Initiative in Rheumatology involving a broad panel of experts and practising rheumatologists. Rheumatology (Oxford). 2008;47(3):355–361.

7.

8.

Manchikanti L, Boswell MV, Singh V, et al. Prevalence of facet joint pain in chronic spinal pain of cervical, thoracic, and lumbar regions. BMC Musculoskelet Disord. 2004;5:15. Motulsky A, Rohn RJ. Tietze’s syndrome; cause of chest pain and

within 6 weeks after the fracture.[34,35] Alternative therapies such as acupuncture and chiropractic manipulation may have a role in facet arthropathy, costovertebral joint pain, costochondritis, and myofascial pain syndrome. Surgical interventions, such as discectomy and spine deformity correction or fusion, may be required in advanced stages of disease or advanced anatomical abnormalities that are not amenable to conservative treatment.

chest wall swelling. J Am Med Assoc. 1953;152(6):504–506. 9.

Gill G. Epidemic of Teitze’s Syndrome. BMJ. 1977;(2):499.

10. Scobie BA. Costochondral pain in gastroenterologic practice. N Engl J Med. 1976;295(22):1261. 11. Meyer PR Jr. Diffuse idiopathic skeletal hyperostosis in the cervical spine. Clin Orthop Relat Res. 1999;(359):49–57. 12. Weinfeld RM, Olson PN, Maki DD, Griffiths HJ. The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in two large American Midwest metropolitan hospital populations. Skeletal Radiol. 1997;26(4):222–225. 13. Resnick D, Shapiro RF, Wiesner KB, et al. Diffuse idiopathic skeletal hyperostosis (DISH) [ankylosing hyperostosis of Forestier and Rotes-Querol]. Semin Arthritis Rheum. 1978; 7(3):153–187. 14. Resnick D, Niwayama G. Radiographic and pathologic features of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). Radiology. 1976;119(3):559–568. 15. Ali RM, Green DW, Patel TC. Scheuermann’s kyphosis. Curr Opin Pediatr. 1999;11(1):70–75. 16. Voutsinas SA, MacEwen GD. Sagittal profiles of the spine. Clin Orthop Relat Res. 1986;210:235–242. 17. Tsirikos AI, Jain AK. Scheuermann’s kyphosis: current controversies. J Bone Joint Surg Br. 2011;93(7):857–864.

18. Weiss HR, Turnbull D, Bohr S. Brace treatment for patients with Scheuermann’s disease: a review of the literature and first experiences with a new brace design. Scoliosis. 2009;4:22. 19. Arlet V, Schlenzka D. Scheuermann’s kyphosis: surgical management. Eur Spine J. 2005; 14(9):817–827. 20. White AA, Panjabi MM. Clinical Biomechanics of the Spine. Philadelphia: JB Lippincott. 1978. 21. Grieve GP. Common Vertebral Joint Problems. New York: Churchill Livingstone. 1981. 22. Maigne R. Low back pain of thoracolumbar origin. Arch Phys Med Rehabil. 1980;61(9):389–395. 23. Maigne R. [The thoraco-lumbar junction syndrome. Low back pain, pseudo-visceral pain, pseudo-hip pain and pseudopubic pain (author’s transl)]. Sem Hop. 1981;57(11–12):545–554. 24. Haroon N, Inman RD, Learch TJ, et al. The impact of TNFinhibitors on radiographic progression in Ankylosing Spondylitis. Arthritis Rheum. 2013;65(10):2645–2654. 25. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010;81(12):1372–1373. 26. Benyamin RM, Wang VC, Vallejo R, Singh V, Helm Ii S. A systematic evaluation of thoracic interlaminar epidural injections. Pain Physician. 2012;15(4):E497–514.

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27. Mackersie RC, Karagianes TG, Hoyt DB, Davis JW. Prospective evaluation of epidural and intravenous administration of fentanyl for pain control and restoration of ventilatory function following multiple rib fractures. J Trauma. 1991;31(4):443–449; discussion 9–51. 28. Ullman DA, Fortune JB, Greenhouse BB, Wimpy RE, Kennedy TM. The treatment of patients with multiple rib fractures using continuous thoracic epidural narcotic infusion. Reg Anesth. 1989; 14(1):43–47. 29. Cheng J, Cata J. Interpleural analgesia. In Smith H, ed. Current Therapy in Pain. Philadelphia,

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PA: Elsevier (Saunders). 2008: pp. 92–94. 30. Manchikanti KN, Atluri S, Singh V, et al. An update of evaluation of therapeutic thoracic facet joint interventions. Pain Physician. 2012;15(4):E463–481. 31. Pope J, Cheng J. Facet joint injections: cervical, lumbar and thoracic. In Benzon H, Huntoon M, Narouze S, eds. Spinal Injections and Peripheral Nerve Blocks, 1st edn. Philadelphia, PA: Elsevier. 2010: pp. 129–135. 32. Wininger KL, Bester ML, Deshpande KK. Spinal cord stimulation to treat postthoracotomy neuralgia: nonsmall-cell lung cancer: a case

report. Pain Manag Nurs. 2012; 13(1):52–59. 33. Yakovlev AE, Resch BE, Karasev SA. Treatment of chronic chest wall pain in a patient with LoeysDietz syndrome using spinal cord stimulation. Neuromodulation. 2011;14(1):27–29; discussion 9. 34. Barr JD, Barr MS, Lemley TJ, McCann RM. Percutaneous vertebroplasty for pain relief and spinal stabilization. Spine (Phila Pa 1976). 2000;25(8):923–928. 35. Mathis JM, Barr JD, Belkoff SM, et al. Percutaneous vertebroplasty: a developing standard of care for vertebral compression fractures. AJNR Am J Neuroradiol. 2001; 22(2):373–381.

Section 2 Chapter

17

Spinal Disorders

Patient with lumbar disc herniation Julian Sosner

Case study A 23-year-old, medical student presents with a 3-day history of severe posterolateral leg pain that was preceded by 2 weeks of ipsilateral back and buttock pain. The character of the pain changed during this interval from a dull and spasmodic back ache to a sharp, lancinating pain going down the leg to the calf. He has difficulty with push off during normal ambulation and sprints. Sitting and squatting worsen pain. Pain is severe in the morning but never lasts more than half an hour. Physical exam demonstrates weakness with ipsilateral plantar flexion, reduced ankle jerk (muscle stretch reflex – or the misnomer, deep tendon reflex), reduced light touch in S1 dermatome, hypersensitivity to pinprick in S1 dermatome, and ipsilateral straight leg raise test positive.

1. What is the differential diagnosis? The patient’s age and presentation with no past medical history suggests a benign condition: 1. Lumbar facet pain 2. Lumbar discogenic pain 3. Lumbar synovial cyst 4. Lumbar spinal stenosis – congenital 5. Muscle spasm 6. Acute inflammatory demyelinating polyneuropathy 7. Mononeuritis multiplex 8. Traumatic spinal cord syrinx 9. Lumbar disc herniation The most likely etiology based on the history (age, acuity, progression from back to leg, weakness with

push off, pain worse with sitting) and physical exam (myotomal weakness, dermatomal radiation, reduced muscle stretch reflex, dural tension signs) suggests a lumbar radiculopathy. The most common etiology for this patient would be a lumbar disc herniation (LDH).

2. What is a lumbar disc herniation? There are multiple ways to classify an LDH: (1) radiologic (MRI or CT); and (2) anatomical (for surgical planning and surgical outcomes). A widely used classification, as recommended by the combined task forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology, is based on CT or MRI imaging. A herniation is defined as a localized displacement of disc material beyond the limits of the intervertebral disc space contour. It can be “focal” or “broad based” depending on the size of the base of this displacement relative to the disc circumference: (1) Focal is < 25%; and (2) broad based is 25–50%. If the broad based is > 50%, this is considered to be a “bulging” disc and not an LDH. The second set of criteria for an LDH refers to the size of the displaced material relative to the base. If the base is larger in terms of width as compared to the width of the displaced material, this is a disc protrusion. If the base is smaller in terms of width as compared to the width of the displaced material, this is a disc extrusion. If the displaced disc material is detached from the rest of the disc then it is called a “sequestered” disc herniation. If there is a layer of annulus around the herniation it is called “contained” and if not, it is called

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 17: Patient with lumbar disc herniation

Figure 17.1. Lumbar disc herniation classification on vertebral model.

“uncontained.” Dye injected into the disc will leak out of the disc. A displacement into the vertebral endplate is called “intravertebral herniation” or a “Schmorl’s node.” A “migrated” herniated disc is disc material displaced beyond the opening in the annulus. It can be continuous or detached from the disc. With respect to the posterior longitudinal ligament (PLL), a herniation may be “subligamentous,” “extraligamentous,” “transligamentous,” or “perforated.” Based on the location within the spinal canal, an LDH may also be classified as central, paracentral, lateral (foraminal), or far lateral (extraforaminal) (Figure 17.1). The bony landmarks are the medial borders of the facets and the medial and lateral border of the pedicles. The central canal zone is the area between the medial borders of the facets. The subarticular zone is the lateral recess area. The pedicle area is the foraminal zone. The area beyond the lateral pedicle border is the extraforaminal or far lateral zone. This obviously has clinical significance in the clinical presentation and surgical treatment of an LDH. A central or paracentral herniation will affect nerve roots that exit at lower levels, while a foraminal or extraforaminal herniation will affect the nerve root at the same numerical level as the disc level affected. There is more “space” in the central portion of the vertebral canal, i.e., the central and paracentral herniation zone is larger than the lateral or far lateral zone. So, a larger volume of herniated disc can be tolerated centrally or paracentrally and be less

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symptomatic as compared to a similar sized herniation in the lateral or far lateral zone. The location of the disc herniation can be further described in the caudocranial direction based on its relationship to the pedicle and disc: supra-pedicular, pedicular, infrapedicular, and discal.

3. Describe the pathogenesis of lumbar radiculopathy secondary to an LDH There are many other causes of radiculopathy besides that from an LDH, which are beyond the scope of this chapter. The radiculopathy from a herniated disc can be caused by direct and indirect mechanical compression, by an inflammatory reaction, or by a combination of the two. Direct mechanical compression or vascular compromise (venous) can block nerve transmission (neuropraxia) or cause axonal damage (axonotmesis). True neurotmesis is rare and will occur only in prolonged, severe compression of the nerve. A multitude of clinical scenarios may present depending on the degree of sensory, motor, and sympathetic nerve fiber compromise. Differentional nerve fiber damage occurs due to size and location – the larger the diameter of the nerve fiber, the worse the damage. A profound inflammatory reaction occurs when the nucleus pulposus extrudes beyond the annulus and onto the nerve. This is mediated by phospholipase A2, nitric oxide, prostaglandin E, tumor necrosis factor alpha (TNF-α), and various cytokines.

Chapter 17: Patient with lumbar disc herniation

4. Discuss clinical symptoms, signs, imaging, and diagnostic testing for an LDH Clinical symptoms and signs of lumbar radiculopathy can be thought as being grouped in positive and negative signs groups. The positive (irritation) signs are: (1) presence of pain in a dermatomal distribution; (2) areas of hypesthesia; (3) presence of lumbar paraspinal spasm; (4) signs of peripheral nerve irritation such as sciatic or Valeix tender points (tenderness to deep localized pressure in the gluteal sciatic notch and posterior thigh, respectively); and (5) signs of nerve root irritation with dural tension testing. Dural tension tests involve passively stretching the limb, and hence, the nerve, against an LDH. These tests have been validated in cadavers. The straight leg sign is positive if pain is evoked by straightening of the knee and flexion of the hip while the patient is seated or supine. The Lasegue sign is positive if pain is evoked in the posterior thigh and leg upon passive extension of the flexed knee while raising the lower limb with the patient supine. Lazarevic sign is evoked pain in the posterior thigh and leg when bending toward one foot or the other. The femoral stretch sign is evoked pain in the anterior thigh upon passive flexion of the knee and extension of the hip. The negative (deficit) signs are motor and sensory deficits in corresponding myotomes and dermatomes. There may be decreased or absent muscle stretch reflexes (deep tendon reflexes). The knee reflex (quadriceps) involves the L2, L3, and L4 spinal nerves. The hamstring reflex involves L5 and S1. The ankle reflex involves S1. This patient had evidence of an S1 radiculopathy.

Imaging of the LDH includes computerized tomography (CT), MRI, myelograpy, and discography. The “gold standard” is the MRI of the lumbar spine (Figure 17.2). It shows the relevant soft tissues: disc, ligaments, epidural space, nerves, and bone marrow. Intravenous contrast can help differentiate between a herniated disc and scar tissue (prior back surgery), infection, or neoplastic processes. Synovial (usually facet joint) or discal cysts (another etiology of radiculopathy) and their origin can be well visualized. The advantage of MRI is the richness of information it can provide and the absence of ionizing radiation to the body. The disadvantages are: (1) cost; (2) length of time for scanning; (3) claustrophobic patients; and (4) contraindication in patients with metallic implants or shrapnel. A CT of the lumbar spine is valuable in diagnosing the disc herniation location, but is less accurate in detailing the configuration of the herniated fragments or extrusion. CT is useful in delineating bony details. CT is particularly useful in combination with myelography or discography – these modalities provide detailed information about the relationships between the disc herniation, the nerve root, the dural sleeve, and the vertebral and foraminal canals. The advantages of CT are: (1) relatively short scan times; (2) reduced risk of claustrophobia; and (3) lower costs. The main disadvantages are the high dose of ionizing radiation that the patient receives and a less detailed image of the soft tissues as compared to an MRI. Myelography details the contour of the dural sac and dural sleeves. CT myelography can identify neural compromise by the LDH and relative stenosis of the vertebral and foraminal canals. The disadvantages are high costs and risk of dural puncture complications:

Figure 17.2. Left L5-S1 disc herniation T2 axial, T1 axial, T2 sagittal (left to right).

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Chapter 17: Patient with lumbar disc herniation

infection; hematoma; positional headache; intracranial hypotension; seizures; and allergic reactions. A discography test gives detailed information about the disc architecture and the pathologies involved in producing LDHs. Annular tears, endplate herniations, multi-directional herniations, contained herniations, and internal disc disruption may be identified. In addition to anatomic detail, physiologic information may be identified with discography. Intradiscal pressures can be measured. The degree of “sensitization” of the disc depends on the evoked pain pressure threshold also known as discogenic pain. A postdiscogram CT can better delineate the LDH or internal disc disruption. Disadvantages of the discogram are high cost and the potential for complications (infection, hematoma, and nerve damage). There is some discussion in the literature that performing a discogram can accelerate the disc degeneration. The relevant diagnostic tests in case of radiculopathy are mainly nerve conduction and electromyography testing. The test is performed on the muscles and nerves of both the lower extremities and lumbar spine. In a positive test for radiculopathy there are usually normal nerve conduction findings (latency times, conduction velocities, and muscle action potentials). Needle electromyography demonstrates abnormal findings such as “denervation potentials” (positive sharp waves and fibrillations) in the paraspinal and peripheral muscles that are innervated by the compromised nerve roots. These findings become positive about 3 weeks after the occurrence of the acute radicular compression. During the first 3 weeks there might be only increased “needle insertional activity” which means an initial muscle membrane instability that can lead later to the denervation potentials mentioned above. This means that often the test is normal in the first 3 weeks.

5. Discuss conservative treatment options The pain is unbearable. Hence, analgesia is paramount before addressing rehabilitation. Oral steroids, muscle relaxants, antiseizure medication, NSAIDs, and opioids may be considered. Modified, active rest within the first 2 days may be advised. Patients may need an assistive device, back brace, ankle-foot orthotic, or knee brace given the type of myotomal weakness. Eventually, physical therapy may be commenced. Usually, spinal extension, core strengthening, and neural flossing exercises

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are used. Passive modalities include heat, cold packs, transcutaneous electrical stimulation. Non-traditional therapies such as acupuncture may be beneficial for pain control, but the reality is that this pain is extremely severe. Interventional procedures include epidural steroid injections, via the interlaminar, transforaminal, or caudal routes. Conservative measures have demonstrated comparable long term success to surgery, but for more immediate relief, surgery has been successful.

6. Discuss surgical approaches to the lumbar disc herniation The surgical approaches to the LDH can be grossly divided into discectomies that are percutaneous, minimally invasive endoscopic, minimally dissecting using a surgical microscope, and conventional discectomies. Percutaneous disc procedures are usually performed with the aid of fluoroscopy and rarely with CT. A conventional discogram approach is performed with a needle (14 to 18 Gauge) introduced percutaneously into the disc. Then a “device” is introduced through the needle to decompress the nucleus polposus. There are several such devices: DeKompressor (Stryker), enSpire (Spine View), and Nucleotome (Clarus). Most use a mechanical or heating element to decompress the disc centrally; the hope is that intradiscal volume reduction, even by a small amount, will allow the LDH to shrink inwards and take pressure off the nerve root. The principal indication for these procedures is broad-based, contained protrusions of the disc. The advantages of these procedures are that they are the least invasive, relatively simple to perform, require minimal specialized equipment, and may be done with local anesthesia or mild sedation. The disadvantages are that the amount of disc material removed is small and the decompression is expected to indirectly relieve pressure on the herniated part. There is no direct removal of the herniated disc material. Minimally invasive endoscopic discectomy allows endoscopic visualization of the anatomic structures and a controlled direct discectomy. It can be performed via a modified “discogram approach” entering the disc first and then the herniation from inside the disc (“inside–out”) (Figure 17.3). It can also be performed via a transforaminal approach – first approaching the herniation and then the disc (“outside–in”). In both techniques the approach to the disc occurs through the Kambin’s triangle at the foramen (see Chapter 59). The

Chapter 17: Patient with lumbar disc herniation

Figure 17.3. Lumbar endoscopic discectomy In-Out approach.

confines of this virtual “triangle” are delimited ventrally by the exiting root, caudally by the pedicle and the posterior vertebral wall, dorsally by the traversing root and the articular processes, and the floor by the intervertebral disc. Some of the instruments mentioned below permit a partial facetectomy to enlarge the bony foramen (foraminotomy/foraminoplasty) in addition to a discectomy. In these procedures a needle is introduced percutaneously and advanced to the desired target point in the Kambin’s triangle. A guide wire is passed through the needle and kept in place while the needle is removed. Progressively larger dilators are passed over the guide wire to form a channel of 6 to 9 millimeters through which a cannula is introduced. The cannula serves as a conduit and working channel for the scope, the circulating fluid, and the working instruments. A discogram is then performed with a mixture of contrast, Carmine blue, and antibiotics. This allows visualizing the disc and the herniated part with both the fluoroscopy and the scope. Hemostasis and a partial discectomy can be performed utilizing specialized bipolar cautery. Discectomy is done with a range of different endoscopic grasping instruments. In the “inside–out” technique, contained disc herniations can be targeted. With the “outside–in” technique, both contained and extruded herniations as well as some migrated fragments can be removed. There are several endoscopic spinal discectomy systems including the JoiMax TESSYS (Transforaminal Endoscopic System) (Joimax Inc.), MaxMore (MaxMore spine), the EnSpire MIS (Spine View Inc.), Disc-Fx (Elliquence), YESS (Yeung Endoscopic Spine Surgery), and Vertebris (Richard Wolf). These systems are very versatile and can treat most of the types of herniated discs independently of their location. Indeed, a recent study showed that the surgical outcomes are similar to conventional microdiscectomy. For very large herniated discs a bilateral approach is sometimes necessary. The principal

advantages of these surgical modalities are that there is no muscle, fascia, or ligament cutting and no periosteal detachment of muscles which allows for the patient’s quick recovery; he or she can return home on the day of surgery. There is a reduced infection rate due to the continuous irrigation during the procedure. Neural injury may be reduced due to the use of local anesthetics and mild sedation, which allows patient feedback. The disadvantages are that there is a steeper learning curve for the pain specialist or surgeon to use these techniques and instruments and to master the fluoroscopic views and endoscopic images. Minimal dissection microscopic discectomy is performed via a dorsal lumbar approach using only a small incision of 2 to 5 cm. The surgical technique mimics the traditional discectomy. There is dissection of the paravertebral muscles down to the lamina and incision of the fascia and ligaments. Than a partial laminectomy and ligamentum flavum removal is performed to gain access to the dorsal epidural space. A surgical microscope is used to visualize the deep structures. The dural sac and traversing nerve roots have to be manipulated and moved in order to gain access to the disc and to the herniated part in the anterior epidural space. The procedure is usually done with sedation or general anesthesia. A traditional discectomy is done similarly to the microscopic discectomy but the incision, the disruption of tissue, and also the size of the laminectomy are larger than in all of the procedures discussed above. The disadvantages are that the surgery is usually done with general anesthesia and the patient frequently stays in the hospital for a few days postsurgically. The larger tissue dissection leads to slower recovery. Most importantly, the manipulation of the dura and nerves combined with the laminectomy and flavectomy discussed above, can cause formation of scar tissue and neuropathic pain. This is true also for the microscopic

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Chapter 17: Patient with lumbar disc herniation

discectomy discussed above. The advantages are that the epidural space can be easily inspected and extruded and uncontained fragments can be removed even if they are lodged in multiple locations. Also, a large or complete laminectomy can be done to decompress the canal in case of concomitant canal stenosis.

References

Clearly, a less invasive procedure with less tissue and muscle disruption and manipulation leads to less complications, less postoperative pain, faster patient mobilization, and return to normal daily activities and less expensive global surgical and rehabilitation treatment.

1.

Tarulli AW, Raynor EM. Lumbosacral radiculopathy. Neurol Clin. 2007;25(2):387–405.

5.

2.

Parke WW, Whalen JL., The vascular pattern of the dorsal root ganglion and its probable bearing on a compartment syndrome. Spine. 2002;27:347–352.

Kambin P. Arthroscopic and Endoscopic Spinal Surgery: Text and Atlas. New Jersey: Humana Press. 2005.

6.

McMahon SB, Koltzenburg M. Wall and Melzack’s Textbook of Pain, 5th edn. Elsevier Churchill Livingstone. 2006.

3.

4.

136

Fardon DF, Milette PC: Nomenclature and classification of lumbar disc pathology. Recommendations of the Combined task forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine. 2001;26(5). Lewandrowski K-U, Lee S-H, Iprenburg M. Endoscopic Spine

Award Winner: lumbosacral nerve root displacement and strain: part 1. A novel measurement technique during straight leg raise in unembalmed cadavers. Spine (Phila Pa 1976). 2007;32(14):1513–1520. PubMed PMID: 17572621.

Surgery. JP Medical Publishers. 2013.

7.

8.

Gilbert KK, Brismée JM, Collins DL, et al. Young Investigator Award Winner: lumbosacral nerve root displacement and strain: part 2. A comparison of 2 straight leg raise conditions in unembalmed cadavers. Spine (Phila Pa 1976). 2007;32(14):1521– 1525. PubMed PMID: 17572622. Gilbert KK, Brismée JM, Collins DL, et al. 2006 Young Investigator

9.

Shah RV, Lutz GE. Lumbar intraspinal synovial cysts: conservative management and review of the world’s literature. Spine J. 2003;3(6):479–488. Review. PubMed PMID: 14609693.

10. Shah RV, Everett CR, McKenzieBrown AM, Sehgal N. Discography as a diagnostic test for spinal pain: a systematic and narrative review. Pain Physician. 2005;8(2):187–209. PubMed PMID: 16850074

Section 2 Chapter

18

Spinal Disorders

Patient with lumbar facet-mediated pain Vikram B. Patel

Case study A 72-year-old male was suffering from low back pain for the last 5 years. He worked as a baggage handler at JFK airport in New York. He had retired when he was 65 years old and had no medical problems until then. Lately, he had been having low back pain which has gradually increased in severity. He had seen his primary care physician who had prescribed an anti-inflammatory agent for pain. However, his recent cardiac stent placement mandated clopidogrel which he has to take every day and hence he is unable to take the anti-inflammatory medicine. He was referred to a pain specialist who obtained an MRI of his lumbar spine. The findings suggested hypertrophy of the lumbar facets at multiple levels, more severe on the left side. His intervertebral discs were also degenerated at almost all the lumbar levels with significant disc space narrowing. There was mild spinal canal central stenosis but no foraminal compromise and no nerve root compression. He has occasional tingling in the left leg but no numbness or weakness. He feels pressure-like sensation in both thighs after walking for about 10 min and has to sit down leaning forward to relieve his symptoms. On physical examination he had increased pain with extension of his lumbar spine and tended to walk and sit leaning forward. He had no sensory motor deficits in the legs and the straight leg raising test was negative in both legs. There was moderate tenderness on palpation in the lower back on both sides. There were no other positive findings.

1. What is the differential diagnosis? a. Lumbar facet joint mediated pain causing low back pain b. Lumbar spinal stenosis with possible neurogenic claudication

c. Myofascial pain syndrome secondary to the spinal pain d. Referred pain from abdominal organs e. Lumbar discogenic pain Lumbar facet joint pain is common in older age due to degeneration of the discs, especially combined with a life style that constantly creates loading of the lumbar spine. The most frequent causes of LS facet syndrome are functional disorders (functional blockade or dysfunction of facet joint¼reversible restriction of facet joint movements caused by meniscoid entrapment) and degenerative changes of facet joints while the others, such as spondyloarthropathies, infection, tuberculosis, synovial cyst, and injury, are less frequent.[1] Most of these patients have a gradual onset of pain with increasing severity. They complain of primarily lower back pain which increases with upright position and is partially relieved after sitting down and flexing the spine. Patients also have increased pain while descending stairs with extended back, walking, sitting straight for prolonged periods, etc. They tend to lean forward or take support while walking. Neurogenic claudication is a symptom of spinal stenosis caused by multiple factors. The increased narrowing of the spinal canal secondary to ligamentum flavum hypertrophy as well as facet joint hypertrophy leads to spinal canal stenosis, which is symptomatic after a variable length of spinal extension such as while walking. The buckling of the ligamentum flavum is partially reduced after sitting down with a flexed spine, thus relieving the symptoms of neurogenic claudication. The facet joint syndromes are also common after lumbar spine surgery, especially a fusion where the facet joints above and below the fusion suffer accelerated degeneration causing facet joint syndrome. Some of the precipitating factors for patients to develop such pain are advanced

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Chapter 18: Patient with lumbar facet-mediated pain

age, long operative time, intraoperative complications, history of recurrent disc prolapse, discectomy, and lack of rehabilitation.[2]

2. What is the mechanism of pain generation in this patient? a. Inflammation of the lumbar facet joints secondary to degeneration and arthritis b. Facet joint loading during extension of the lumbar spine c. Spinal stenosis causing neurogenic claudication d. Spinal pain leading to secondary myofascial pain e. Forward flexion leading to increased pressure on the already degenerated discs i. Further narrowing of the facet joint space ii. Increased degeneration of the facet joints

3. What is the difference between the axial back pain and radicular pain? a. Spinal axial pain is basically secondary to the musculo-skeletal elements of the spine. b. Discogenic pain is also axial in nature. c. There is no nerve root compromise; hence there is no radicular pain secondary to radiculopathy. d. Pain is usually localized but may radiate in a certain pattern in the lower extremities if

e.

f.

g. h. i.

the facet joints are the pain generators (Figure 18.1). The radiation pattern significantly overlaps between the involved joints. There is also anterior thigh and groin radiation from the L3–S1 facets. The pain usually does not radiate beyond the posterior thigh but may occasionally radiate up to the calf from the L5–S1 facet joint. Pain does not radiate to the foot as opposed to a radicular pattern of pain radiation. There are no paresthesiae associated with axial spine pain. Pain is usually felt as a deep dull ache, which can sometimes be described as sharp, especially if the muscular pain is also present.

4. Describe the anatomy and pathophysiology of the lumbar facet (zygapophysial) joint pain? The lumbar spine consists of: a. Five and sometimes six lumbar vertebral bodies and intervertebral discs between them. b. The L5 vertebral body articulates with the sacrum to form the L5–S1 facet joints. i. Each vertebra consists of (Figure 18.2): (1) Body (2) Transverse process (TP) (3) Laminar arches – joining in the middle to form the spinous process (4) Superior articular process (SAP) (5) Inferior articular process (IAP) (6) The pedicles join the body with the articular arches c. The intervertebral discs (IVD) join the vertebrae above and below and provide the articulation and cushioning to the spine (Figure 18.3):

Figure 18.1. Lumbar facet joint pain radiation pattern.

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i. The IVD has two distinct parts: the tough fibrous outer rim called the annulus fibrosus and a softer inner core called the nucleus pulposus. ii. Disc herniation is a result of the nucleus bulging out or extruding through partial or complete tear of the annulus. iii. The disc derives its blood supply from the vertebral end plates above and below.

Chapter 18: Patient with lumbar facet-mediated pain

L1 Transverse process Superior articular process Lamina

Inferior articular process

L5 Sacrum

Figure 18.2. Lumbar spine anatomy.

Figure 18.4. Lumbar spine zones.

the posterior longitudinal ligament, the intervertebral foramen, the exiting nerve roots, plus the blood vessels to and from the spinal cord. The posterior segment is made up of the articular elements comprising the superior and inferior articular processes. Each vertebra articulates with the superior as well as inferior vertebral body. These articular joints are called the facet or zygapophysial joints (Figure 18.4).

5. How to diagnose lumbar axial pain? Diagnosis of axial lower back pain is based on the imaging studies (e.g., MRI of the lumbar spine, plain x-ray) as well as the history and physical examination. There are no unique identifying features in the history, physical examination, and radiologic imaging of patients with pain of lumbar zygapophysial (facet) joint origin.[3,4,5] a. MRI findings:

Figure 18.3. The intervertebral disc (IVD). NP – nucleus pulposus, AF – annulus fibrosus, SC – spinal cord, NR – nerve root, G.R. – gray ramus, SV.N. – sinuvertebral nerve, S.C. – sympathetic chain.

iv. Only the outer third of the annulus possesses the nerve endings responsible for pain generation. Clinically, the lumbar spine elements may be divided into three separate zones. The anterior segment is made up of the vertebral body, intervertebral disc, and the anterior longitudinal ligament. The middle segment contains the intervertebral foramen,

i. MRI of the lumbar spine may reveal disc degeneration, facet joint hypertrophy, and osteophyte formations which are the signs of lumbar spondylosis. ii. The facet joints may show narrowing, inflammation, and swelling. iii. CT scan is not a reliable test for facet joint syndrome.[6] b. Plain x-ray of the lumbar spine may show any anatomical displacement in the form of anterior or posterior displacement of the vertebral body (spondylolisthesis) or a fracture. It may also reveal any congenital defects such as a pars articularis defect. c. Work history is important in a chronically worsening low back pain. Any history of injury with an extension type of impact may lead to facet joint pain and dysfunction.

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Chapter 18: Patient with lumbar facet-mediated pain

i. Facet joint pain is usually increased with extension and rotation on the ipsilateral side of the lumbar spine and may also radiate in a specific pattern but rarely extends beyond thigh or calf level. It is usually not felt when rising from a sitting position as opposed to SI joint pain.[7] ii. Increased pain with flexion with or without any paresthesiae may indicate a disc as the pain generator. iii. Superimposed myofascial pain is usually secondary to the spine pain and may exacerbate overall pain during flexion as well as extension and cause stiffness of the lower back, restricting all the movements. iv. Complaints of radiating pain vs. non-radiating (axial) pain with paresthesiae and/or numbness and weakness would help in differentiating the facet vs. nerve root related pain. d. Diagnostic block of the medial branches is the only reliable diagnostic approach for this pain syndrome.[8]

6. What are the treatment options for axial low back pain due to the facets? Conservative approaches Conservative treatment for axial low back due to the facets is largely based on the intensity of pain,

radiologic findings, and the patient’s ability to perform day-to-day activities. Physical therapy, antiinflammatory agents, and mild oral analgesics are the mainstay of the conservative treatment options. TENS unit may also be helpful particularly if the myofascial pain is the main source of a patient’s pain.

Interventional treatments i. Minimally invasive treatment options are required for patients who fail to improve despite adequate trials of physical therapy, inability to perform physical therapy due to increased pain, inadequate response to medications, or inability to tolerate medications due to side effects. Certain degenerative states do not respond adequately to conservative measures and require interventional treatment options. ii. Facet joint procedures: (1) Intra-articular steroid injection for the facet joints has moderate evidence for efficacy for lumbar facet joints.[9,10] Patients who do not respond to the intra-articular injections or who have advanced degenerative changes, require ablation of the facet joint nerves. (2) Facet joints are supplied by the medial branches of the lumbar nerve roots. Each joint is supplied by two medial branches, one from the same level and one from the level above, thus L3–4 facet joint is supplied by the L3 and L2 medial branches (Figure 18.5). Hence to

Figure 18.5. Lumbar facet joint intra-articular injection under oblique fluoroscopic view.

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Chapter 18: Patient with lumbar facet-mediated pain

B

A

Figure 18.6. (A,B) Lumbar facet medial branch blocks. Images demonstrate a left sided L4 medial branch which lies over the left L5 transverse process and a right sided L5 medial branch block which lies in the groove between the right sacral superior articular process and the ala of the sacrum.

denervate these joints one has to lyse two medial branches per level. The evidence for radiofrequency ablation of the lumbar medial branches is moderate to strong.[10] (3) A carefully performed diagnostic medial branch block (Figure 18.6) on two different occasions using two different local anesthetics provides the most reliable diagnostic criteria to identify the facets as the pain generators.[11,12] The evidence for diagnosis of lumbar facet joint pain with controlled local anesthetic blocks is Level I or II-1. False-positive rate for a single diagnostic block is 27–47%.[12] Radiofrequency ablation is then performed to denervate these joints for long term (Figure 18.7). Level II-2 or II-3 evidence for radiofrequency neurotomy.[12]

7. Procedural description a. The approach for intra-articular facet joint injection is from a postero-lateral approach under fluoroscopic guidance (Figure 18.5). More recently, ultrasound-guided injections have also

been published and found to be as effective as fluoroscopically guided injection.[13] i. During an oblique view it is important to obtain a proper angle as the joint is most visible on fluoroscopy at its middle portion rather than the posterior joint border and hence the fluoroscopic view should be halted just as the joint becomes visible while going from an AP to oblique view. ii. A small amount of radiologic contrast medium to confirm intra-articular placement followed by a small amount of injectate consisting of local anesthetic and steroid is preformed. The total amount should not exceed 1 ml as the normal joint space is limited in a degenerate joint. b. Facet joint medial branch block: i. The block is ideally performed under fluoroscopic guidance, although recently it has been performed by some practitioners with the use of ultrasound guidance. ii. Posterolateral (oblique) view (Figures 18.5 and 18.6) is ideal for performing this block. However, the angle depends on the level to be injected to almost AP at higher levels.

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Chapter 18: Patient with lumbar facet-mediated pain

B

A

Figure 18.7. (A,B) Note the tangential approach to the left L4 medial branch on an oblique view and the corresponding image demonstrating the needle position in a lateral view.

A

B

Figure 18.8. (A,B) Radiofrequency ablation of the right L5 medial branch at the junction of the ala of the sacrum and its corresponding superior articular process on AP and lateral fluoroscopic views.

c. Radiofrequency ablation: i. After a successful double diagnostic block of the related medial branches to diagnose the pain generator, radiofrequency ablation can be performed. ii. The approach is slightly different than an intra-articular injection in that the needle should be placed parallel to the medial branch

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with a tangential approach from one level below to obtain an optimal lesion (Figures 18.7 and 18.8). iii. An AP and a lateral view is a must to confirm the needle tip posterior to the neural foramen. iv. A 10 or 15 cm radiofrequency needle with a 10 or 15 mm active tip is preferred. Needle gauge of 20 or 22 is commonly utilized.

Chapter 18: Patient with lumbar facet-mediated pain

v. The sensory and motor stimulation is then carried out to assure proper proximity to the medial branch and also to confirm its distance from the exiting nerve root. vi. After a successful placement, local anesthetic (and sometimes combined with a small amount of steroid) is injected to prevent pain from the lesion generation. Usually about 0.5 ml is injected. A radiofrequency lesion is generated at 80°C for 90 seconds.

8. What are the possible complications from these procedures? Risk of infection, bleeding, failure to relieve pain, or nerve damage is similar to any lumbar spine procedure but perhaps less with the medial branch block as it only involves local anesthetic injection and is much more posterior to the neural foramen. The radiofrequency lesioning may cause nerve damage if proper protocols are not observed and the

References 1.

2.

3.

4.

5.

Grgić V. Lumbosacral facet syndrome: functional and organic disorders of lumbosacral facet joints. Lijec Vjesn. 2011; 133(9–10):330–336. Steib K, Proescholdt M, Brawanski A, et al. Predictors of facet joint syndrome after lumbar disc surgery. J Clin Neurosci. 2012;19(3):418–422. Dreyer SJ, Dreyfuss PH. Low back pain and the zygapophysial (facet) joints. Arch Phys Med Rehabil. 1996;77(3):290–300. Schwarzer AC, Aprill CN, Derby R, et al. Clinical features of patients with pain stemming from the lumbar zygapophysial joints: is the lumbar facet syndrome a clinical entity? Spine. 1994; 19(10):1132–1137. Schwarzer AC, Wang SC, Bogduk N, et al. Prevalence and clinical features of lumbar zygapophysial

needle tip is too close to the nerve roots. Sedation may also lead to complication if the patient is heavily sedated and cannot respond in an appropriate manner. A short period of increased pain may be due to muscular spasms and myofascial pain. The majority of complications are short lived.

9. What are the outcomes with facet joint procedures? a. Diagnostic lumbar facet joint blocks are safe and reliable modalities to diagnose the facet joint related pain. A double block technique is preferred to minimize false-positive rates. The strength of evidence for this procedure is Level I or II-1 based on multiple controlled trials.[12] b. The level of evidence for radiofrequency ablation of the medial branches to treat the facet joint related pain is Level II to II-3 based on studies with a recommendation of 1B or 1C for this procedure.[12]

joint pain: a study in an Australian population with chronic low back pain. Ann Rheum Dis. 1995;54(2):100–106. 6.

7.

8.

9.

Schwarzer AC, Wang SC, O’Driscoll D, et al. The ability of computed tomography to identify a painful zygapophysial joint in patients with chronic low back pain. Spine. 1995;20(8): 907–912. Young S, Aprill C, Laslett M. Correlation of clinical examination characteristics with three sources of chronic low back pain. Spine. 2003;3(6): 460–465. Cohen SP, Huang JH, Brummett C. Facet joint pain: advances in patient selection and treatment. Nat Rev Rheumatol. 2013; 9(2):101–116. Boswell MV, Colson JD, Sehgal N, et al. A systematic review of therapeutic facet joint interventions in chronic spinal

pain. Pain Physician. 2007;10(1): 229–253. 10. Boswell MV, Colson JD, Spillane WF. Therapeutic facet joint interventions in chronic spinal pain: a systematic review of effectiveness and complications. Pain Physician. 2005;8(1):101–114. 11. Atluri S, Datta S, Falco FJ, et al. Systematic review of diagnostic utility and therapeutic effectiveness of thoracic facet joint interventions. Pain Physician. 2008;11(5):611–629. 12. Datta S, Lee M, Falco FJ, et al. Systematic assessment of diagnostic accuracy and therapeutic utility of lumbar facet joint interventions. Pain Physician. 2009;12(2):437–460. 13. Yun DH, Kim HS, Yoo SD, et al. Efficacy of ultrasonographyguided injections in patients with facet syndrome of the low lumbar spine. Ann Rehabil Med. 2012;36(1):66–71.

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Discogenic pain in the setting of lumbar spondylosis James Kelly and Jianguo Cheng

Case study A 45-year-old construction worker presents complaining of low back pain with radiation into the buttock and posterior thigh. He is otherwise healthy and his work consists of jack hammering and shoveling. He notes a gradual onset of his pain over the last 2 to 3 months and describes it as aching in nature. It is worsened by sitting or standing for long periods of time and also by transitioning from sitting to standing. He is unsure whether his pain is worsened by sneezing and denies numbness in his lower extremities or the loss of bowel or bladder control. He has taken over-thecounter naproxen sodium for the last week with little relief. He feels that the only thing that helps to alleviate his pain is lying down.

1. What is the differential diagnosis? a. b. c. d. e. f. g.

Muscle strain or sprain Lumbar facet disease Sacro-iliac joint pain Discogenic pain Vertebral compression fracture Spinal stenosis Aceto-femoral osteoarthritis

Lumbar degenerative disc disease is a leading cause of low back pain. It often occurs in younger, relatively healthy individuals. The onset is gradual in nature. It is often described as a deep pressure or ache that becomes intolerant upon activities that load the axial spine such as prolonged sitting or standing or transitioning from sitting to standing. Pain is also often worsened with maneuvers that raise intradiscal pressure (coughing, sneezing, bearing down, etc.). Positions that unload the spine, such as lying down,

often reduce or eliminate pain. The pain experienced is normally axial but may radiate/refer into the buttock or posterior thigh in a non-dermatomal fashion. Discogenic pain alone should not cause overt weakness or radiate below the knee. Straight leg raise testing is often negative and deep palpation over the spinous process of the affected disc may reproduce pain. Normal lumbar range of motion may be limited and symptoms are often worsened upon flexion. Reflexes and sensation are within normal limits and gait is most often normal. The diagnosis is usually established after excluding the other conditions listed above. It is noteworthy though that discogenic pain may coexist with one or more of these listed conditions.

2. What is the anatomy of a healthy intervertebral disc? A normal intervertebral disc consists of an inner nucleus pulposus and an outer annular fibrosus. The nucleus pulposus is sparsely populated with chondrocyte-like cells while cells in the annular fibrosus have fibrocyte-like features. The nucleus pulposus is primarily made up of water and proteoglycans, giving it a gelatin-like consistency. It is contained within the annulus fibrosis’ layered collagen, forming a high-pressured cushion that is well suited to withstand repetitive, constant stress. The intervertebral disc is the largest avascular structure in the body: its nerves are mostly mechanoreceptors and the blood vessels are typically found only in the outer third of the annulus fibrosus. This relatively anaerobic environment predisposes the disc, especially the inner nucleus pulposus, to degeneration in the face of injury or metabolic derangement. For

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this same reason, discs are also prone to spontaneous or iatrogenic infection. Intervertebral discs derive their innervation from plexuses along the anterior and posterior intervertebral ligaments. The anterior and posterior plexuses both receive their input from the gray rami communicans. The posterior plexus also receives contributions from the sinuvertebral nerve that arises from each spinal level.

3. What risk factors predispose patients to develop degenerative disc disease? a. b. c. d. e. f. g.

Advanced age Trauma Certain athletic activity Obesity Vascular disease Family history Increased mechanical stress

4. What is the pathophysiology of degenerative disc disease? The intervertebral disc was first presumed to be a pain generator in 1947 by Inman. Mechanically, KirkaldyWillis in 1978 described a three phased cascade of degeneration marked by dysfunction, instability, and finally, stabilization. The cascade involves the progression of an acute injury to a chronic disarrangement due to poor body mechanics, immobility, and lack of activity with resultant ligamentous alterations (“my back gives out”) and eventual spondylytic changes (“my back is always stiff”). Biologically, dysfunction and decline in the viable cells of the nucleus pulposus, coupled with an increase in cytokines and proinflammatory mediators within the disc, start a vicious cycle that results in the reduction of the proteoglycan content. This change in matrix content increases the compressibility of the nucleus pulposus and, in turn, increases the pressure applied to the annulus fibrosus. Buckling of the annular lamellae results in microfractures and fissures. This serves as a substrate for neovascularity and migration of annular nociceptors inward toward the nucleus pulposus. In the setting of increased proinflammatory mediators, the nociceptors are most likely sensitized and prone to hyperesthesia and hyperalgesia.

5. What is the role of radiographic imaging in discogenic pain? Plain radiographs are of limited value for discogenic pain evaluation. Because loss of disc height and sclerotic bone changes are late findings, plain films lack in sensitivity for diagnosing degenerative disc disease. Computed tomography provides better bony detail and inferences as to the soft tissue than radiographs but MRI has quickly become the modality of choice for disc investigation. MRI protocols consist of T1- and T2-weighted sagittal and axial imaging. Contrast-enhanced studies are reserved for imaging of postoperative changes or in patients who are suspected of having an infection or tumor. Many practitioners find T2-weighted sagittal images to be most useful in analyzing the intervertebral discs as the overall shape, its hydration, and inferences as to the neural elements in the spinal canal and foramen are best appreciated. A grading system of five grades was developed by Pfirrmann in 2001 to assess and standardize disc degeneration as appreciated on MRI. Grade I discs, as seen in normal adolescents, have signal equal to that of the cerebrospinal fluid, a homogeneous contour, no loss of height, and a clear distinction between the annulus fibrosus and the nucleus pulposus. Grade II discs, as seen in normal adults, are similar to Grade I discs but may contain an inhomogeneous contour and gray horizontal bands. Grade III discs, classified as being mildly degenerated, show a gray signal, decreased body height, and an indistinct border between the nucleus pulposus and the annulus fibrosus. Grade IV discs, classified as being moderately degenerated, are gray or black, show normal to moderate loss of height, and have complete loss of the border between the nucleus pulposus and annulus fibrosus. Grade V discs, severely degenerated, are black with a collapsed disc space. These disc variations are often compared to the three types of endplate and subchondral bone marrow changes classified by Modic in 1988 (Figure 19.1). Modic Type 1 involves disruption and fissuring of the endplate with regions of degeneration, regeneration, reactive bone formation, endplate edema, and infiltrative vascular granulation tissue. This is reflected on MRI as an edema pattern of hypointense T1-weighted imaging and hyperintense T2-weighted imaging. Modic Type 2 changes are hyperintense on T1-weighted imagine and isointense or slightly hyperintense on

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A

B

C

Figure 19.1. Type 1(A), type 2(B), and type 3(C) modic endplate changes. With permission from reference[9].

T2-weighted imaging and are associated with conversion of normal red hemopoietic bone marrow into yellow fatty marrow as a result of marrow ischemia. Modic Type 3 changes are described as hypointense on both T1- and T2-weighted imaging and are thought to

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represent subchondral bone sclerosis. Mixed-type 1/2 and 2/3 Modic changes have also been reported, suggesting that these changes can convert from one type to another and that they all present different stages of the same pathologic process. The absence of Modic changes, a normal anatomic appearance, has often been designated Modic type 0. Modic Type 1 changes intuitively represent inflammation and are believed to best correlate to segmental instability and discogenic low back pain. Most recently, Modic Type 1 change has been closely linked to bacterial infection of the herniated disc in several studies. The most commonly isolated pathogen from disc tissues obtained from spine surgeries is Proprionibacterium acnes. These studies convincingly linked chronic low back pain to bacterial infection of the herniated discs and the subsequent changes of subchondral bone marrow changes. A recent doubleblind randomized, placebo-controlled clinical trial clearly demonstrated the efficacy and safety of antibiotic treatment in patients with chronic low back pain and Modic Type 1 changes. Taken together, this line of studies signifies a new era of etiologic treatment of certain types of chronic low back pain. There has been an increased interest in highintensity zones (HIZ) on MRI. HIZ are best viewed on T1-weighted images and represent a tear in the posterior annulus. They have been found to correlate closely with the pain of discography and represent yet another tool to diagnose discogenic pain. However, it remains controversial on the correlation between HIZ and discogenic pain and some authors argue that psychologic components are better predictors. Lumbar imaging is not without its drawbacks. It is not only that grading of lesions varies greatly between observers, but more importantly, disc abnormalities are appreciated in 64% of asymptomatic patients. Thus, the high sensitivity and low specificity of the imaging studies emphasize the need that the imaging results must be carefully correlated to findings from the history and physical examinations.

6. Is there a gold standard for the diagnosis of discogenic pain? Provocative discography has long been considered the gold standard for the diagnosis of discogenic pain. It was first introduced by Schmorl and Junghanns and was first performed in the US at the Cleveland Clinic by Wise and Weiford in 1951. The key diagnostic

Chapter 19: Discogenic pain in the setting of lumbar spondylosis

feature is the reproduction of the patient’s low back pain and this process requires the cooperation of the patient. It is important to note that discogenic pain is a different diagnosis from disc herniation. The North American Spine Society Diagnostic and Therapeutic Committee suggest that discography should only be used when a patient has failed an adequate course of non-operative treatment and non-interventional tests such as MRI have failed to provide sufficient diagnostic information. Further, the group asserts that discography should not be performed in the setting of mild to moderate, acute low back pain. Accordingly, many physicians feel that, given the invasive nature of discography, patients should be trialed with less invasive procedures such as medial branch blocks and trigger point injections prior to the procedure. The American Association of Neurologic Surgeons/Congress of Neurologic Surgeons asserts that positive discography in the setting of normal MRI findings should be considered a contraindication to surgical or other invasive interventions. Discography involves accessing the disc that is the suspected pain generator and two to three control discs. The patient is placed in the prone position and the lower back prepped and draped. Anterior– posterior fluoroscopic images with alignment of the end plates of the adjacent vertebral bodies are first obtained to provide good visualization of the disc. The C-arm is then oblique until the superior articular process reaches the midline of the corresponding vertebral endplate. The entry point is marked just lateral to the superior articular process and local anesthetic infiltrated. A two-needle technique has been shown to reduce the rate of discitis to 0.7%, thus an 18-gauge needle is advanced roughly two inches. A 6-inch, 22gauge needle is inserted through the 18-gauge needle. Care is taken not to touch the tip of the 22-gauge needle. The disc is found to have a rubbery texture when encountered. At this point, AP and lateral images should be obtained to assure that the needle is in the center of the disc. After placement of the needles in the control discs, the opening pressure is noted and non-ionic contrast administered into the disc. Concordant pain is sought with an increase of less than 30 psi above the opening pressure. Concordant is most often defined as significant pain in the distribution of the patient’s normal pain. Most practitioners start with a control disc and

pressure should not be raised above 90 psi to avoid false-positive results. Many practitioners consider pain in two or more control discs to suggest that the study is invalid. Furthermore, the subjective nature of the test adds an additional confounding factor. Moreover, patients with elevated scores on the hysteria and hypochondriasis scale of the Minnesota Multiphasic Personality Inventory were significantly more likely to report pain during injection than controls. See Figure 19.2.

7. Does the spread of the contrast on a discogram tell us anything? Efforts were made to standardize visual results obtained from discograms. In 1986 Adams et al described fluoroscopic classification of discs on cadavers. He reported 87% reproduction of his results by repeating the procedure 6 months after the initial discogram. Following the procedure, the morphology can be further evaluated by CT imaging. The Adams classification for discogram morphology describes five types of results. Type I is described as a cotton ball. The dye is well contained within the nucleus and the density is uniform. Type II, termed lobular, results when the dye is distributed within the nucleus pulposus in two distinct lobes. Type III is an irregular dye pattern with evidence of penetration of the dye into the inner annulus fibrosus. This is appreciated by a speckled dye pattern. Type IV morphology shows evidence of fissures. The contrast reaches the outer annulus fibrosus and may even extend beyond the edge of the vertebral body if the disc is herniated. A Type V contrast pattern shows rupture of the disc with spread of the dye into the epidural space. Adams and colleagues’ initial study suggested that discogram morphologic results were reproducible. Later studies have looked at the interobserver and intraobserver agreement and the reliability of the scale. In the clinical setting the absolute interobserver and intraobserver agreement occurred in 82 levels or 62%, regardless of level of experience (Agorastides et al 2002).

8. What are the complications of discography? Potential complications of discography include pain at the entry site, increased disc pain, discitis, epidural

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B

Figure 19.2. (A) Anteroposterior view of lumbar discogram L2–3, L3–4, L4–5, L5-S1; with left L5-S1 contrast extravasation through high-grade annular tear. (B) Post discogram CT scan with thin cross-sectional slices. From personal files of Rinoo V. Shah, MD, MBA.

hematoma, transient radiculopathy, spinal headache, arachnoiditis, and pulmonary embolism. Lumbar discography is associated with complications in 0% to 2.7% of patients. There is no evidence to support that lumbar discography causes damage or causes lumbar discs to herniate. The most common complication of discography is increased pain. This occurs in up to 81% of individuals undergoing the procedure. There is a correlation between patients who had significant back pain 1-year post discography and significant emotional, psychologic, and chronic pain problems. Discitis remains the most common serious complication. Aside from standard prep, drape, and scrub, many practitioners employ a broad spectrum, parenteral antibiotic prior to discography. A one-time dose of cafazolin roughly 30 minutes prior to the procedure is often the choice. However, Willem found the infections rate to be 0.25% in 4891 patients and 0.094% in 12 770 discs in which preprocedural antibiotics were not used. A twoneedle technique, as described earlier, has been touted as a more effective means by which to reduce infection.

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9. What treatment modalities are available for discogenic pain? As difficult a disease as it is to diagnose, discogenic pain is an even more difficult entity to treat. As is the case when targeting other pain generators, it is recommended for practitioners to start with the least invasive options and mold the treatment protocol based on response. As with other chronic pain syndromes, psychiatric illness remains a barrier to substantial symptoms reduction. A recent exciting development is the isolation of Proprionibacterium acnes bacteria as a cause of low back pain. The results of the recent randomized controlled trial (RCT), based on the infected herniated disc hypothesis, have provided strong evidence that antibiotic therapy can lead to dramatic reduction in disability and pain in patients with Modic Type 1 change. It is quite hopeful that etiologic treatment for certain types of chronic discogenic pain may be within reach in the near future if confirmatory studies reproduce the reported results. Conservative measures such as alternating ice and heat and oral anti-inflammatories, neuromodulators, and analgesics provide only modest relief of symptoms.

Chapter 19: Discogenic pain in the setting of lumbar spondylosis

A

B

Figure 19.3 Lateral (A) and anteroposterior (B) fluoroscopic view of L4–5 IDET (intradiscal electrothermal therapy). From personal files of Rinoo V. Shah, MD, MBA.

Exercise and physical therapy remains a mainstay of treatment with a focus on core strengthening, traction, and flexibility. Many patients suffer from worsening deconditioning due to their fear that exercise will worsen their symptoms. In fact, exercise was related to increased flexibility and strength, reduced pain, and decreased negative behavior and beliefs about pain. When such a workout program was coupled with cognitive therapy results were even more significant in terms of reduced healthcare visits, work absenteeism, and taking long-term sick leave disability. Minimally invasive treatments have aimed to denature sensitized nociceptors. One such agent, methylene blue, has been postulated to denervate the small fibers that grow into the annulus fibrosus. One study reported a success rate of 89% following one treatment with intradiscal methylene blue. However, confirmatory studies remain to be seen to reproduce the reported stellar results. Intradiscal steroids and ozone have shown equally equivocal results.

Figure 19.4. IDET L3–4 and L4–5. From personal files of Rinoo V. Shah, MD, MBA.

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Patients with discogenic pain of duration greater than 6 months may be candidates for thermal ablation. Procedures such as intradiscal electrothermal therapy (IDET) and, more recently, biacuplasty, aim to not only ablate the sensitized nociceptors but also thermally modify collagen fibers located in the annulus. It is of note that thermal lesioning of the disc of a prone patient renders the nerve roots in a more vulnerable, anterior position. IDET was shown to be effective in select patients but the procedure has fallen out of favor due to a lack of consistency in terms of outcomes from randomized controlled trials. Biaculoplasty creates a lesion using bipolar electrodes that are easily placed as compared to IDET. Initial studies

References 1.

Buckwalter JA, Mow VC, Boden SD, et al. Intervertebral disk structure, composition and mechanical function. In Buckwalter JA, Einhorn TA, Simon SR, eds. Orthopaedic Basic Science: Biology and Biomechanics of the Musculoskeletal System. Rosemont, IL: American Academy of Orthopaedics Surgeons. 2000: pp. 548–555.

2.

Bogduk N, Tynan W, Wilson AS. The nerve supply to the human lumbar intervertebral discs. J Anat. 1981;132:39–56.

3.

Kirkaldy-Willis WH, Wedge JH, Yong-Hing K, Reilly J. Pathology and pathogenesis of lumbar spondylosis and stenosis. Spine. 1978;3:319–328.

4.

Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine. 1995;20:1307–1314.

5.

Kang JD, Georgescu HI, McIntyre-Larkin L. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6 and prostaglandin E2. Spine. 1996;21:271–277.

6.

Ledermann HP, Schweitzer ME, Morrison WB, Carrino JA. MR imaging findings in spinal infections: rules or myths? Radiology. 2003;228(2):506–514.

150

7.

8.

9.

involving few patients show improvements in functional capacity, pain scores, and opiate use at 1 and 6 months of observation. However, a recent RCT did not provide convincing evidence of efficacy. Theoretically removal of the diseased disc and stabilization through fusion should relieve the discogenic pain. Artificial disc replacement has also been trialed. However, results have been mixed at best. In fact, despite advances in surgical technology, the rates of failed back surgery syndrome have not declined. This speaks to the multifactorial nature of lumbar discogenic pain and the need for future research and innovation. See Figures 19.3 and 19.4.

Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. 2001;26(17): 1873–1878. Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology. 1988; 166:193–199. Rahme R, Moussa R. The Modic vertebral endplate and marrow changes: pathologic significance and relation to low back pain and segmental instability of the lumbar spine. Am J Neuroradiol. 2008;29(5):838–842.

10. Jensen MC, Brant-Zawadzki MN, Obuchowski N, et al. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med. 1994;331(2): 69–73. 11. Peng B, Hou S, Wu W, et al. The pathogenesis and clinical significance of a high-intensity zone (HIZ) of lumbar intervertebral disc on MR imaging in the patients with discogenic low back pain. Eur Spine J. 2006;15: 583–587. 12. Carragee EJ, Paragioudakis SJ, Khurana S. Volvo award winner in clinical studies. Lumbar highintensity zone and discography in

subjects without low back problems. Spine. 2000;25(23): 2987–2992. 13. Wise RE, Weiford EC. X-ray visualization of the intervertebral disk: report of a case. Cleve Clin Q. 1951;18:127–130. 14. Willems PC, Jacobs W, Duinkerke ES, De Kleuver M. Lumbar discography: should we use prophylactic antibiotics? A study of 435 consecutive discograms and a systematic review of the literature. J Spinal Disord Tech. 2004;17:243–247. 15. Block AR, Vanharanta H, Ohnmeiss DD, Guyer RD. Discographic pain report: influence of psychological factors. Spine. 1996;21:334–338. 16. Adams MA, Dolan P, Hutton WC. The stages of disc degeneration as revealed by discograms. J Bone Joint Surgn Br. 1986;68-B:36–41. 17. Agorastides ID, Lam KS, Freeman BJ, Mulholland RC. The Adams classification for cadaveric discograms: inter- and intraobserver error in the clinical setting. Eur Spine J. 2002;11: 76–79. 18. Schreck RI, Manion WL, Kambin P, et al. Nucleus pulposus pulmonary embolism: a case report. Spine. 1995;22: 2463–2466

Chapter 19: Discogenic pain in the setting of lumbar spondylosis

19. Walker J, Omar EA, Zacharia I, Stefan M. Discography in practice: a clinical and historical review. Curr Rev Musculoskelet Med. 2008;1(2):69–83. 20. Johnson RG. Does discography injure normal discs? An analysis of repeat discograms. Spine. 1989;14(4):424–426 21. Kahanovitz N, Arnoczky SP, Sissons HA, Steiner GC, Schwarez P. The effect of discography on the canine intervertebral disc. Spine. 1986;11(1):26–27. 22. Tallroth K, Soini J, Antti-Poika I, et al. Premedication and short term complications in iohexol discography. Ann Chir Gynaecol. 1991;80:49–53. 23. Carragee EJ, Chen Y, Tanner C, Hayward C, Rossi M, Hagle C. Can discography cause long term back symptoms in previously asymptomatic subjects? Spine. 2000;25(14):1803–1808. 24. Buenaventura RM, Shah RV, Patel V, Benyamin R, Singh V. Systematic review of discography as a diagnostic test for spinal pain: an update. Pain Physician. 2007;10(1):147–64. Review. PubMed PMID: 17256028. 25. Shah RV, Everett CR, McKenzieBrown AM, Sehgal N. Discography as a diagnostic test for spinal pain: a systematic and narrative review. Pain Physician. 2005;8(2):187–209.

26. Rainville J, Hartigan C, Martinez E, et al. Exercise as a treatment for chronic low back pain. Spine J. 2004;4:106–115.

electrothermal therapy: a preliminary histologic study. Arch Phys Med Rehabil. 2001;82 (9):1230–1237.

27. Linton SJ, Boersma K, Jansson M, Svard L, Botvalde M. The effects of cognitive-behavioral and physical therapy preventive interventions on pain-related sick leave: a randomized controlled trial. Clin J Pain. 2005;21:109–119.

34. Kapural L, Ng A, Dalton J, Mascha E, et al. Intervertebral disc biacuplasty for the treatment of lumbar discogenic pain: results of a six-month follow-up. Pain Med. 2008;9(1):60–67.

28. Peng B, Zhang Y, Hou S, Wu W, Fu X. Intradiscal methylene blue injection for the treatment of chronic discogenic low back pain. Eur Spine J. 2007;16:33–38. 29. Gupta G, Radhakrishna M, Chankowsky J, Francisco Asenjo J. Methylene blue in the treatment of discogenic low back pain. Pain Physician. 2012;15:333–338. 30. Simmons JW, McMillin JN, Emery SF, Kimmich SJ. Intradiscal steroids: a prospective double-blind clinical trial. Spine. 1992;17:S172–S175. 31. Muto M, Ambrosanio G, Guarnieri G, et al. Low back pain and sciatica: treatment with intradiscal-intraforaminal O(2)O(3) injection. Our experience. Radiol Med. 2008;113:695–706. 32. Mekhail N, Kapural L. Intradiscal thermal annuloplasty for discogenic pain: an outcome study. Pain Pract. 2004;4(2):84–90. 33. Shah RV, Lutz GE, Lee J, Doty SB, Rodeo S. Intradiskal

35. Gibson JN, Waddell G, Grant IC. Surgery for degenerative lumbar spondylosis. Cochrane Database Syst Rev. 2000;2:CD001352. 36. Chan CW, Peng P. Failed back surgery syndrome. Pain Med. 2011;12(4):577–606. 37. Rahme R, Moussa R. The Modic vertebral endplate and marrow changes: pathologic significance and relation to low back pain and segmental instability of the lumbar spine AJNR Am J Neuroradiol. 2008;29: 838–842. 38. Kapural L. Vrooman B, Sarwar S, et al. A randomized, placebocontrolled trial of transdiscal radiofrequency, biacuplasty for treatment of discogenic lower back pain. Pain Med. 2013;14; 362–373. 32. Agorastides ID, Lam KS, Freeman BJ, Mulholland RC. The Adams classification for cadaveric discograms: inter- and intraobserver error in the clinical setting. Eur Spine J. 2002;11(1): 76–79.

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Unusual pain syndromes: epidural lipomatosis Vikram B. Patel

Case study A 58-year-old male with chronic low back pain had been receiving epidural steroids on a regular basis for several years for his symptoms. He has concurrent diagnoses of obesity, hypertension, and type 2 diabetes mellitus. He recently had a repeat epidural injection as the symptoms had gradually worsened over the last few months with increased low back pain which was now accompanied by tingling and deep ache in both legs as well as poor gait and balance.

1. What is the differential diagnosis? a. Worsening spinal degeneration b. Increasing lumbar spinal stenosis with possible neurogenic claudication c. Centrally herniated intervertebral disc causing compression of the nerve roots d. Cauda equine syndrome i. Loss of bowel control, urinary retention, bilateral. Lower extremity weakness and numbness, low back pain e. Thoracic or cervical disc herniation causing spinal cord compression

f. g. h. i.

i. May have accompanying cervical and upper extremity symptoms Epidural abscess Epidural hematoma Idiopathic spinal epidural lipomatosis secondary to corticosteroid administrations Other rare conditions such as multiple sclerosis, syringomyelia, transverse myelitis, etc.

Lumbar spine degeneration is a common occurrence and is frequently treated with epidural steroid injections. These injections are sometimes performed

on a regular basis for chronic conditions that do not respond to short-term treatments. Worsening of symptoms following an epidural injection should prompt a practitioner to evaluate the possible etiology. Although worsening symptoms may just be a progression of the patient’s usual pathology, additional symptoms such as lower extremity weakness, neurogenic claudication, paresthesiae, fever, etc. should be properly evaluated to rule out any serious condition.

2. What are the most common symptoms of idiopathic epidural lipomatosis? a. b. c. d. e. f.

Low back pain Radicular pain Sensory loss Burning dysesthesiae Motor weakness Bladder dysfunction

3. What is a proper approach to these symptoms? a. A thorough history and physical examination: i. History of injury, infections, fever, duration of symptoms, bowel and bladder dysfunction ii. Physical examination of the neurologic system is a must and should include gait and balance assessment b. Vital signs including temperature to rule out any infectious process c. Blood tests including WBC count, erythrocyte sedimentation rate, and C-reactive protein d. MRI of the lumbar spine

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Diagnosis of the condition requires an MRI of the lumbar spine. Several conditions causing these symptoms can be either confirmed or ruled out based on this study. Soft tissue and fluid (blood, pus, seroma) can only be properly assessed with an MRI. A bone scan may be required in some patients. In patients who cannot have an MRI (e.g., pace maker, spinal cord stimulator), a CT scan may be performed along with a myelogram to properly evaluate the spinal canal.

4. What are the findings during a physical examination in epidural lipomatosis?[1,2] a. On observation, one can sometimes observe unsteady and unbalanced gait b. Patient may complain of neurogenic claudication after walking only a short distance c. Sensory deficit can be elicited in the lumbar dermatomes (or higher dermatomes depending on the level of lipomatosis) d. Motor weakness in the lower extremities e. Decreased deep tendon reflexes f. Positive straight leg raising test

5. What is the pathophysiology of idiopathic epidural lipomatosis? a. Excessive deposits of adipose tissue in the epidural space b. It may be caused by endogenous elevation of steroids c. It is also known to occur in exogenous steroid therapy such as in immunosuppressive therapy after organ transplantation, steroid therapy for asthma, steroid therapy for rheumatoid arthritis, etc.[1–5] d. In most cases, the etiology is idiopathic e. Majority of these cases have been reported in morbidly obese patients, receiving steroid therapy or suffering from endocrinopathies such as Cushing’s syndrome, hypothyroidism, etc.[2–6]

6. What is the most reliable diagnostic modality? a. Magnetic resonance imaging is the most reliable imaging study[6]

7. How should this patient be treated? a. Patients with minimal or no spinal cord compression symptoms may be treated with conservative modalities such as reduction of steroid dosage, weight reduction, correction of underlying causes such as hypothyroidism b. Aggressive treatment is recommended in patients representing cord compression symptomatology to avoid long term and irreversible damage to the spinal cord and the nerve roots c. Surgical decompression is the most effective therapy d. Extensive laminectomies and subsequent fusion may be required for effective debulking of the epidural adipose tissue

8. What is the long-term outcome after treatment? a. In most cases recurrence is not seen after 2 years follow-up.[2] b. Early intervention can help prevent permanent spinal cord or nerve root injury

Summary Epidural lipomatosis is a rare condition that requires aggressive treatments especially if the spinal cord or the nerve roots are compressed. It may affect any age group but is more common in middle aged patients. Exogenous steroid therapy is the most common cause for this condition. The condition arises when there is excessive deposition of adipose tissue in the epidural space which is in most cases circumferential. Likely risk factors such as morbid obesity, hypothyroidism, Cushing’s syndrome, and immunosuppressive therapy should be considered in patients receiving steroid therapy on a chronic basis. Magnetic resonance imaging is the gold standard for evaluating such symptoms due to its higher reliability to differentiate the soft tissues. Aggressive therapy with extensive laminectomies and fusion are required in patients exhibiting signs and symptoms of spinal cord or nerve root compression. Milder symptoms may be managed conservatively.

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References 1.

Fessler R, Johnson D, Brown F, et al. Epidural lipomatosis in steroid-treated patients. Spine. 1992;17(2):183–188.

2.

Lisai P, Doria C, Crissantu L, et al. Cauda equina syndrome secondary to idiopathic spinal epidural lipomatosis. Spine. 2001;26(3):307–309.

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3.

Chapman PH, Martuza RI, Poletti CE, et al. Symptomatic spinal epidural lipomatosis associated with Cushing’s syndrome. Neurosurgery. 1981;8: 724–727.

4.

Kumar K, Nath RK, Nair CPV, et al. Symptomatic epidural lipomatosis secondary to obesity. J Neurosurg. 1996;85: 348–350.

5.

Russell NA, Belanger G, Benoit BG, et al. Spinal epidural lipomatosis: a complication of glucocorticoid therapy. Can J Neurol Sci. 1984;11:383–386.

6.

Toshniwal PK, Glic RP. Spinal epidural lipomatosis: Report of a case secondary to Hypothyroidism and review of literature. J Neurol. 1987;234(3): 172–176.

Section 2 Chapter

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Spinal Disorders

Unusual pain syndromes: Bertolotti’s syndrome Jiang Wu and Jianguo Cheng

Case study A 34-year-old woman presents with a chief complaint of left low back pain for 1 year. She describes the pain as deep aching, and progressively getting worse in the last few months. The pain radiates into her left hip and posterior thigh above the knee. It is better with rest and worse with physical activity particularly with extension or e.g. bending to the left side. The use of NSAIDs and core strengthening exercise failed to relieve the pain. She has tenderness over the low back left to the lumbar spine. She was suspected to have spondylosis and facet arthropathy. On the day of a scheduled diagnostic facet medial branch block, she was found under fluoroscopy to have a lumbosacral transitional vertebra that articulated with the left ilium through an enlarged transverse process. A diagnosis of Bertolotti’s syndrome was thus established.

1. What is Bertolotti’s syndrome? Lumbosacral transitional vertebra is an anatomical variation of the most caudal lumbar vertebra in which an enlarged transverse process can articulate or fuse with the sacrum or ilium. The association of this congenital variant with chronic low back pain and the change in the biomechanical properties of the lumbar spine is called Bertolotti’s syndrome.[1] Although Bertolotti’s syndrome is a congenital abnormality, it is often clinically manifested only after the second decade of life.[2] It is estimated this syndrome accounts for 4.6%[2] to 7%[1] of cases of low back pain in adults, and for more than 11% of patients with low back pain who are under 30 years old.[2] The differential diagnosis of Bertolotti’s syndrome includes sacroiliac joint pain, myofascial pain, lumbar disc herniation (DDD), lumbar facet pain, and stress fracture.

2. Describe the pathophysiology of Bertolotti’s syndrome The incidence of lumbosacral transitional vertebra is 4–8% in the general population.[1] Although it was stated as early as in 1917 that these abnormal vertebrae may produce low back pain[3] and an association has been found between lumbosacral transitional vertebra and disc herniation as well as facet joint degeneration,[4,5] little is yet known about the biomechanical and pathophysiologic effects of such abnormal vertebra. It has been hypothesized that the primary effect of lumbosacral transitional vertebra is the reduced and asymmetrical motion between the transitional vertebra and the sacrum. This asymmetry can result in early arthritic changes occurring at “pseudoarticulation,” which is similar in mechanism to a surgical pseudarthrosis in which repeated motion over an unstable bony bridge of fibrous mass results in local limitation and inflammation.[6] The impingement of enlarged transverse process on the nerve root extra-foraminally could result in sciatica.[7] The secondary effects of such abnormal vertebra are the progressively compensatory modifications in the biomechanics of the mobile vertebral segments superior to the transitional vertebra due to the restriction of rotation and bending motion at the lumbosacral articulation.[8] The disc above a transitional vertebra appears to predispose to degenerative changes, whereas the disc below appears to be protected.[5,9–11] Secondary degeneration and strain of the supra-adjacent disc cause discogenic pain or inflame the adjacent lumber nerve root resulting in “sciatic” or radicular pain patterns.[5] Generating abnormal weight overload in the opposite articular facets results in ongoing lumbar facet pain.[12]

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In addition to the progressive modifications, the instability above the transitional vertebrae because of a weak iliolumbar ligament also leads to dysfunctional motion and muscle strain pain.[9,13–15]

3. What is Castellvi’s classification? The Castellvi classification was proposed to morphologically characterize four types of lumbosacral transitional vertebrae:[4] Type I – dysplastic transverse process with height > 19 mm Type II – incomplete lumbarization/sacralization (diarthrosis) Type III – complete lumbarization/sacralization with complete fusion with the neighboring sacral basis Type IV – mixed The type II transitional vertebra has been associated with an increased number of disc prolapses, and related to discogenic and/or contralateral facetogenic low back pain.[4,16]

4. How does Bertolotti’s syndrome manifest clinically? Patients with Bertolotti’s syndrome usually present with chronic, progressive midline, or paramedian low back pain that is deep, sharp, or dull in nature or a sensation of pulled muscle or unilateral upper buttock pain. The severity of pain is moderate to severe, worse with physical exertion, and better with rest. The provocative factors of pain include heavy lifting, forward flexion, excessive extension or lateralization of the back to the same side of the megaapophysis. It may be accompanied with sciatica, medial thigh cramping, leg radicular pain, weakness, or numbness. Patients may have significant ambulatory and functional limitations. Physical examination demonstrates focal tenderness along the base of the lumbosacral spine and near the posterior-superior iliac spine, provoked by superficial and deep palpation. Patients may have normal and symmetric muscle bulk and tone in their paraspinal muscles and in all extremities. Laséque’s sign, or straight leg raise test, may be positive; range of motion may be impaired. Pronator drift, Romberg signs, patellar and Achilles deep tendon reflexes, and sensation test usually are intact.

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5. How do you diagnose a Bertolotti’s syndrome? Because of unapproved association of this congenital variant with chronic low back pain and poor understanding of the biomechanics of such abnormal vertebrae, Bertolotti’s syndrome is very difficult to recognize. The correct diagnosis is made based on imaging studies which included lumbosacral CT scans, plain x-rays, and MRI scans in the context of typical history of low back pain and physical exam. The extension-flexion lumbosacral radiographs in anteroposterior, lateral, and oblique views demonstrate lumbosacral transitional vertebra, with an enlarged unilateral or bilateral transverse processes of the most distal lumbar vertebra, abnormally articulating with the ala of the sacrum and degenerative changes of the pseudarthrosis. In addition, plain radiographs can reveal lumbar lordosis and/or disc space narrowing. In addition to showing sacralization of the most distal lumbar vertebra with pseudoarticulation of the enlarged transverse process and the ala, CT scan of the lumbosacral spine may help identify associated stenosis, osteophytes, and areas of sclerosis surrounding the pseudoarticulation. MRI provides detailed anatomic information regarding degenerative disc disease and possibly associated disc herniation. It shows degeneration and desiccation of disc spaces, any central canal or foraminal stenosis, and the degree of compression of the dural sac or spinal nerves. A selective radiculogram of the spinal nerve may demonstrate entrapment of the spinal nerve in the extra-foraminal zone. Bone scintigraphy may reveal an inflammatory process within the articular facets, specifically at the level of the mega-apophysis. Singlephoton emission CT may be useful in the identification of possible candidates for local anesthetic infiltration and future radiofrequency ablation.[17]

6. How should I treat this patient? A course of conservative management including activity modification, medication management with NSAIDs, muscle relaxants, opioids, and rehabilitative physical therapy should be offered initially, with the recognition that these therapies are less likely to result in satisfactory pain control.

Chapter 21: Unusual pain syndromes: Bertolotti’s syndrome

Due to the multifactorial etiology of low back pain in patients with Bertolotti’s syndrome, the identification of the primary and secondary origin of the pain become paramount to choose the most appropriate treatment for each case. If the primary origin of the pain is at the pseudoarticulation between the transverse process and ilium due to the arthritic changes, a local anesthetic and corticosteroid can be injected into this pseudoarticulation after contrast dye confirmation of correct spread in or around the pseudoarticulation under fluoroscopic guidance.[6,15,18] These blocks should be performed with a minimal amount of anesthetic delivered precisely to the point of interest to achieve temporary pain relief. If rapid pain relief doesn’t occur almost instantaneously, alternative pain generators should be sought. The anesthetic block can be repeated if in doubt. If the patient experiences temporary pain relief and the pain is truly localized in the transitional joint without evidence of disc pathology, a minimally invasive approach may be taken to resect the anomalous transverse process with the accompanying pseudoarticulation.[12] If still unsuccessful, based on the hypothesis that the rigidity of the L5–S1 portion of the spine puts extra stress on the L4–5 level, further surgical intervention either to free the rigid level or to further stabilize the spine by resection or fusion of the anomalous transverse process to protect L4–5 could be considered.[3] Due to progressively compensative modifications in the biomechanics of the mobile vertebral segments superior to the transitional vertebra, multiple secondary origins of pain may exist. If the degenerative changes occur at the contralateral facet joints as a possible source of pain, then diagnostic medial branch blocks should be performed and, if positive, followed by radiofrequency sensory ablation of these

References 1.

2.

Elster AD. Bertolotti’s syndrome revisited: transitional vertebrae of the lumbar spine. Spine. 1989; 14(12):1373–1377. Quinlan JF, Duke D, Eustace, S. Bertolotti’s syndrome: a cause of back pain in young people. J Bone Joint Surg Br. 2006; 88(9):1183–1186.

3.

4.

joints.[18] If the disc above the transitional vertebra is thought to be the source of pain, then discography may be useful in diagnosis. The therapeutic armamentarium for degenerative disc disease includes surgical microdiscectomy, nucleolysis, and arthrodesis.[2] The latter involves pedicular screws, transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF) and, more recently, anterior lumbar interbody fusion (ALIF).[8] If a spinal nerve is impinged in the extraforaminal zone by disc herniation or transverse process, surgical options including fenestration, posterolateral fusion, and transforaminal interbody fusion may be considered.[7] Microendoscopic decompression may be particularly useful in this location.[19]

7. What are the outcomes? There is a paucity of literature regarding interventional outcomes. Conventional radiofrequency neurolysis may be used for facetogenic pain, providing significant pain relief and aiding future physical rehabilitation programs.[20] However, the relief may be temporary and repeated procedures may be necessary.[8] Minimally invasive techniques have been developed to limit iatrogenic soft tissue injury during exposures for spine surgery. These techniques provide adequate exposure of the involved spinal segment with limited tissue destruction and retraction. It has been hypothesized that limiting iatrogenic tissue injury may reduce chronic back pain years after surgery.[21–24] Surgical treatment of Bertolotti’s syndrome was only slightly better than conservative treatment and should only be used in very selective patients with disc pathology.[15] In order to achieve long-term improvement by any therapeutic options, a continuing physical rehabilitation program is often needed.

Bertolotti M. Contributo alia conoscenza dei vizi di differenzazione regionale del rachide con speciale riguardo all assimilazione sacrale della V. lombare. Radiologique Medica 1917;4:113–144. Castellvi AE, Goldstein LA, Chan DPK. Lumbosacral transitional vertebra and their relationship

with lumbar extadural defects. Spine. 1983;9:493–495. 5.

Vergauwen S, Parizel PM, Van Breusegem L, et al. Distribution and incidence of degenerative spine changes in patients with a lumbosacral transitional vertebra. Eur Spine J. 1997;6:168–172.

6.

Ugokwe KT, Chen TL, Klineberg E, Steinmetz MP. Minimally

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7.

8.

9.

invasive surgical treatment of Bertolotti’s Syndrome: case report. Neurosurgery. 2008;62(5 Suppl 2): ONSE454–5; discussion ONSE456.

12. Brault JS, Smith J, Currier BL. Partial lumbosacral transitional vertebra resection for contralateral facetogenic pain. Spine. 2001;26(2):226–229.

Shibayama M, Ito F, Miura,Y, et al. Unsuspected reason for sciatica in Bertolotti’s syndrome. J Bone Joint Surg Br. 2011;93(5): 705–707.

13. Jonsson B, Stromqvist B, Egund N. Anomalous lumbosacral articulations and low back pain: evaluation and treatment. Spine. 1989;14:831–834.

Almeida DB, Mattei TA, Soria MG, et al. Transitional lumbosacral vertebrae and low back pain: diagnostic pitfalls and management of Bertolotti’s syndrome. Arquivos de NeuroPsiquiatria. 2009;67(2A): 268–272.

14. Magora A, Schwartz A. Relationship between the low back pain syndrome and x-ray findings. 2. Transitional vertebra (mainly sacralization). Scan J Rehabil Med. 1978;10:135–145.

Aihara T, Takahashi K, Ogasawara A, et al. Intervertebral disc degeneration associated with lumbosacral transitional vertebrae: a clinical and anatomical study. J Bone Joint Surg Br. 2005;87:687–691.

10. Luoma K, Vehmas T, Raininko R, Luukkonen R, Riihimaki H. Lumbosacral transitional vertebra: relation to disc degeneration and low back pain. Spine. 2004;29:200–205. 11. Brown MF, Rockall AG, Hallam P, Hall-Craggs MA, Edgar MA. Transitional lumbosacral vertebra: incidence of disc degeneration above and below. J Bone Joint Surg Br 82-B 2000;(Suppl II):180.

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15. Santavirta S, Tallroth K, Ylinen P, Suoranta H. Surgical treatment of Bertolotti’s syndrome: follow-up of 16 patients. Arch Orthopaed Trauma Surg. 1993;112(2):82–87. 16. Dai L. Lumbosacral transitional vertebrae and low back pain. Bull Hosp Jt Dis. 1999;58:191–193. 17. Scharf S. SPECT/CT imaging in general orthopedic practice. Sem Nuclear Med. 2009;39(5):293–307. 18. Burnham R. Radiofrequency sensory ablation as a treatment for symptomatic unilateral lumbosacral junction pseudarticulation (Bertolotti’s syndrome): a case report. Pain Med. 2010;11(6):853–855. 19. Matsumoto M, Chiba K, Ishii K, et al. Microendoscopic partial

resection of the sacral ala to relieve extraforaminal entrapment of the L5 spinal nerve at the lumbosacral tunnel: technical note. J Neurosurg Spine. 2006;4:342–346. 20. Endo K, Ito K, Ichimaru K, et al. A case of severe low back pain associated with Richard disease (lumbosacral transitional vertebra). Minim Invasive Neurosurg. 2004;47:253–255. 21. Airaksinen O, Herno A, Kaukanen E, et al. Density of lumbar muscles 4 years after decompressive spinal surgery. Eur Spine J. 1996;5:193–197. 22. Kawaguchi Y, Yabuki S, Styf J, et al. Back muscle injury after posterior lumbar spine surgery: topographic evaluation of intramuscular pressure and blood flow in the porcine back muscle during surgery. Spine. 1996;21:2683–2688. 23. Sihvonen T, Paljarvi L. Point of view: preventive measures of back muscle injury after posterior lumbar spine surgery in rats. Spine. 1998;23:2288. 24. Styf JR, Willén J. The effects of external compression by three different retractors on pressure in the erector spine muscles during and after posterior lumbar spine surgery in humans. Spine. 1998;23:354–358.

Section 2 Chapter

22

Spinal Disorders

Unusual pain syndromes: Baastrup’s disease/interspinous bursitis Jijun Xu and Jianguo Cheng

Case study A 70-year-old male presents with chronic low back pain for more than 10 years. He reports tenderness to deep palpation along the midline at the lumbar region and over the facet joints. The pain is worse with back extension and is better with forward flexion. Plain radiographs on lateral view show enlarged L3–5 posterior spinous processes that are closely approximated and appear to be in direct contact. On computed tomography (CT) image, small bone geodes are present between the spinous processes of L3–5 that are in close proximity (“kissing”). The sagittal contrastenhanced T1-weighted fat-saturated MRI shows that the L3 and L4 spinous processes are “touching” each other and the residual interspinous space is filled with enhanced tissue with surrounding edema and inflammatory changes in the interspinous ligaments. The intervertebral disc height and neuroforamen are unremarkable.

1. What is Baastrup’s disease? Baastrup’s disease (BD), a back pain syndrome named after Danish radiologist Christian Ingerslev Baastrup, is characterized by several pathologic changes in adjacent spinous processes and the soft tissues between them. BD is also known as “kissing spine” because of the close approximation and contact of adjacent spinous processes on sagittal plane; and “interspinous bursitis (ISB)” because the interspinous region can form an adventitious bursa with the creation of a synovial articulation.[1] For this reason, BD and ISB are used interchangeably in this chapter.

2. Describe the epidemiology of Baastrup’s disease BD was reported in many patients with heavy work such as miners and in athletes. It is now generally accepted that it is an age-related disease and tends to be more common in elderly patients.[2] Kissing spine was diagnosed clinically in 6.3% of college athletes, most commonly gymnasts.[3] In a cross-sectional retrospective review of 539 patients with lumbar spine MRI, lumbar interspinous bursitis was present in 8.2% of patients.[4] The majority (47.7%) of lumbar interspinous bursitis was seen at multiple levels, most commonly at the L4–L5 level. There was a statistically significant association between the presence of lumbar ISB and age, disc bulging, central canal stenosis, and anterolisthesis. On the other hand, gender, disc degeneration, disc herniation, endplate marrow signal alteration, facet osteoarthritis, retrolisthesis, lordosis, or scoliosis was not significantly associated with lumber ISB. In another large cohort study of 1008 patients,[5] evidence of BD (close contact between adjacent spinous processes and the opposing ends were sclerotic) was found in 413 patients (41.0%). The frequency increases in elderly patient populations with a peak of 81.3% among patients older than 80 years. Again, BD occurred most commonly at the L4–L5 level but as many as five levels could be affected. Associated degenerative changes were found at almost all affected levels (899/901).

3. Describe the anatomy and pathophysiology of Baastrup’s disease The space between adjacent lumbar spinous processes is occupied by interspinous ligament, bilateral

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paraligamentous bursae, and bilateral paired interspinous lumborum muscles. The etiology of BD is not precisely known, but has been attributed to translational movement or abutting of the posterior spinous processes resulting from substantial disc space loss or excessive lordosis. BD may also develop secondary to chronic inflammatory facet arthropathy. Conversely, facet synovitis may occur secondary to active interspinous bursitis.[6] Chronic inflammation of the interspinous ligaments may gradually lead to abutting of the spinous processes, and eventually BD characterized by small cystic erosions or geodes occurring where the spinous processes contact (Figure 22.1). This process may lead to interspinous adventitial bursa formation and eventually formation of a synovial-lined articulation between the spinous processes. Calcium pyrophosphate dehydrate (CPPD) and hydroxyapatite crystal deposition may be present in the bursa. The adjacent posterior paraspinal musculature and nearby facet capsules may also be inflamed. A communication between the interspinous bursa and the facet joint has been demonstrated in some patients by injecting the interspinous bursa. As the interspinous structures degenerate, the “kissing spines” may rub against each other. This process of agitation may gradually lead to an overgrowth of the hard bone tissue, resulting in interspinous osteophytes which may subsequently cause considerable back pain particularly on spine extension. BD may cause neurogenic claudication according to a case report.[7]

4. How to diagnose Baastrup’s disease? The prominent feature of BD is the extravagant osteophytosis and approximation of the adjacent spinous processes. Often the condition is asymptomatic but it may present with reduced mobility of the spine associated with back pain. The midline localized spine tenderness and back pain can be aggravated on back extension and relieved on flexion. In some patients, increase in lordosis may bring the spinous processes into contact, leading to reactive sclerosis. These patients have axial low back pain on assuming a lordotic posture. Kwong et al[5] suggested that, because of the nearly universal association with other degenerative changes, caution should be taken before diagnosing BD as the cause of back pain. On the other hand, many clinicians fail to consider spinous process as a possible cause of back pain and many radiologists do not routinely use fat suppression MRI sequences to

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Figure 22.1. Baastrup disease. Lateral radiograph of the lumbar spine shows enlarged spinous processes that are flattened and sclerotic in their inferior and superior portions (arrow). http://flylib. com/books/en/4.48.1.15/1/

uncover the edematous/inflammatory changes of the spinous process and interspinous ligament. Lamer et al[8] suggested that BD should be considered in the differential diagnosis and work-up of back pain when the following clinical and radiographic criteria are present: 1. Midline back pain reproduced with palpation of the spinous process and exacerbated by extension

Chapter 22: Unusual pain syndromes: Baastrup’s disease/interspinous bursitis

the bursitis as well as surrounding edema and inflammation as mentioned above (Figure 22.2). Increased fluorodeoxyglucose (FDG) uptake may also be observed in inflamed interspinous ligaments using positron emission tomography-computed tomography (PET-CT imaging) in patients with BD[10–12] whereas CT alone may fail to identify the definite abnormality.[12]

5. What are the differential diagnoses of Baastrup’s disease?

Figure 22.2. Baastrup disease. Contrast-enhanced T1-weighted fat-saturated sagittal image showed narrowing and enhancing of the interspinous associated with small erosion of the adjacent spinous process (arrows). Adapted from Czervionke[6] with permission.

of the spine. Pain relief with local anesthetic injection around the affected spinous processes. 2. Lateral view x-ray reveals spinous processes that appear to be in direct contact (Figure 22.1). MRI is more sensitive in detecting interspinous inflammation, bursa, and new bone formation.[9] BD may precede the changes on x-rays. MRI demonstrates edema and/or inflammation in and surrounding the spinous process. Regional inflammation evidenced by contrast-enhanced, fat-saturated, T1-weighted sequences, and edema by non-enhancing increased fat-suppressed T2 signal intensity (Figure 22.2). MRI is useful to provide insight into the soft tissue with regards to depicting interspinous fluid representing

The differential diagnosis of BD includes: 1. Proliferative hyperostosis of the lumbar spinous processes: Usually seen in diffuse idiopathic skeletal hyperostosis (DISH) with formation of pseudoarthrosis between the bases of spinous processes. DISH is a non-inflammatory disease, with the principal manifestation being calcification and ossification of spinal ligaments in regions where tendons and ligaments attach to bone. The most common and characteristic radiographic findings involve the thoracic spine, but abnormalities may also be present in the cervical and lumbosacral spine. There may be extraspinal involvement with hyperostosis in the olecranon, patella, calcaneus, shoulder, and acetabulum. 2. Degenerative disease of the spine: Degeneration of the intervertebral disc and/or facet joints can present with joint space narrowing, bone eburnation, and osteophytosis. These disorders may present along with BD. Radiographic evidence of degenerative changes is nearly ubiquitous in patients over 65 year of age. BD is often identified with close approximation of spinous process along with degenerative changes of the spine in the differential diagnosis and workup of back pain. 3. Sclerotic bone metastases to spine: Can arise from a number of different primary malignancies and lesions are often located in vertebra. Knowledge of increased FDG uptake in the interspinous space on PET-CT scan is important to differentiate BD from a spinous process metastatic lesion. 4. Ankylosing spondylosis: May cause erosion of the spinous processes and the interspinous ligament may calcify and eventually ossify, resulting in fusion of the spinous processes.[1] In ankylosing

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spondylitis, however, the bony bridges are slender, vertical bony bridges that involve the outer margin of the annulus fibrosis; erosions and bony ankylosis of the sacroiliac and apophyseal joints are not seen in BD. 5. Ossification of the posterior longitudinal ligament: It occurs more commonly in East Asian patients and predominantly in the cervical spine. Most symptomatic patients present with neurologic deficits such as myelopathy or radiculopathy, and surgery is frequently required. 6. Cysts: a. Aneurysmal bone cyst (ABC) of the spine: ABC mainly affects children and young adults and is commonly located at the metaphysis of long bones.[13] Vertebral lesions tend to start posteriorly and may spread through the pedicle into the vertebral body and epidural space.[14] b. Posterior epidural cysts: Chen et al reported that BD can be associated with posterior intraspinal epidural cysts leading to compression of the thecal sac and, in some cases, central canal stenosis.[15]

Figure 22.3. Left fluoroscopic oblique view, left intra-articular L4–5 facet injection demonstrates communication with interspinous bursa and contralateral L4–5 facet joint. From personal files of Rinoo V. Shah, MD, MBA.

6. How should you treat a patient with BD/ISB? Both conservative and surgical options are available for the treatment of BD/ISB. However, there is a lack of evidence from controlled clinical trials largely because this condition appears to have a low prevalence rate. The current therapeutic approaches are, therefore, mainly empirical. 1. Traditional management: a. Pharmacologic therapy: Non-steroidal antiinflammatory drugs (NSAIDs) are typically prescribed although they may or may not be effective. Short-term steroid dose pack may be effective in treating patients with BD. b. Physical therapy: Manual mobilization can be tried once the local tenderness is improving. Contrast heat and hot fomentation can also be effective. Ergonomic corrective methods and postural awareness are of great importance. 2. Interventional management: Targeted injections can be tried if traditional management is not

162

Figure 22.4. Anteroposterior view, left L4–5 intra-articular facet injection demonstrates communication with interspinous bursa and contralateral L4–5 facet joint. From personal files of Rinoo V. Shah, MD, MBA.

effective. Lamer et al[8] reported effectiveness of fluoroscopically guided injection to treat BD in a 3-case series. A 22-gauge needle is advanced approximately midway along the dorsal-ventral axis of the affected spinous processes. Two to three milliliters of 0.25% bupivacaine and 3 mg of betamethasone was injected after confirmed contrast spread between the targeted spinous

Chapter 22: Unusual pain syndromes: Baastrup’s disease/interspinous bursitis

processes. Two patients had a long-term response to the injection while the third one, who had more prominent degenerative changes, responded only temporarily to the injection. They concluded that, if BD has not responded to traditional treatments, local anesthetic injection of the inflamed spinous process and associated interspinous ligaments may be diagnostic and local anesthetic/ corticosteroid injection may be therapeutic. Others reported that interspinous ligament injections with 0.5 ml of 1% lidocaine and 0.5 ml of 40 mg/ml of triamcinolone acetate achieved pain free for 3 months after the injection.[16] In patients with associated inflammatory facet arthropathy, the facet joints should be injected initially because the interspinous bursae may fill during facet injection.[6] See Figures 22.3 and 22.4.

References 1.

2.

3.

4.

5.

Sartoris DJ, Resnick D, Tyson R, Haghighi P. Age-related alterations in the vertebral spinous processes and intervening soft tissues: radiologic-pathologic correlation. AJR Am J Roentgenol. 1985;145(5): 1025–1030. Epub 1985/11/01.

6.

Czervionke LF. Interspinous Bursitis (Baastrup’s Disease). In Czervionke LF, Fenton DS, eds. Imaging Painful Spine Disorders, 1st ed. Saunders. 2011: pp. 302–131.

7.

Rajasekaran S, Pithwa YK. Baastrup’s disease as a cause of neurogenic claudication: a case report. Spine. 2003;28(14): E273–275. Epub 2003/07/17.

Bywaters EG, Evans S. The lumbar interspinous bursae and Baastrup’s syndrome: an autopsy study. Rheumatol Int. 1982;2(2): 87–96. Epub 1982/01/01.

8.

Keene JS, Albert MJ, Springer SL, Drummond DS, Clancy WG, Jr. Back injuries in college athletes. J Spinal Disord. 1989;2(3): 190–195. Epub 1989/09/01.

9.

Maes R, Morrison WB, Parker L, Schweitzer ME, Carrino JA. Lumbar interspinous bursitis (Baastrup disease) in a symptomatic population: prevalence on magnetic resonance imaging. Spine. 2008;33(7): E211–215. Epub 2008/04/02. Kwong Y, Rao N, Latief K. MDCT findings in Baastrup disease: disease or normal feature of the aging spine? AJR Am J Roentgenol. 2011;196(5):1156–1159. Epub 2011/04/23.

3. Surgical management: Surgery is reserved for refractory BD patients who fail to respond to the above therapies. Surgical options include interspinous process decompression devices (e.g., Wallis system, X-STOP) and excision of the affected spinous processes.[8] If there is associated vertebral instability, surgical fusion procedure may also be considered.[6] The outcome of surgical excision varied. Franck reported improvement of pain and symptoms in 10 patients[17] whereas Beks demonstrated that only 11 out of 64 patients were free of complaints after the operation and stayed asymptomatic. The pain remained or returned in the other 53 patients, in whom other spine pathologies were found to be more evident.[18]

Lamer TJ, Tiede JM, Fenton DS. Fluoroscopically-guided injections to treat “kissing spine” disease. Pain Physician. 2008;11(4): 549–554. Epub 2008/08/12. Clifford PD. Baastrup disease. Am J Orthop (Belle Mead NJ). 2007;36 (10):560–561. Epub 2007/11/23.

10. Gorospe L, Jover R, Vicente-Bartulos A, et al. FDG-PET/CT demonstration of Baastrup disease (“Kissing” Spine). Clin Nucl Med. 2008;33(2):133–134. Epub 2008/01/23. 11. Lin E. Baastrup’s disease (kissing spine) demonstrated by FDG PET/CT. Skeletal Radiol. 2008;37 (2):173–175. Epub 2007/12/19. 12. Ho L, Wassef H, Seto J, Henderson R. Multi-level lumbar Baastrup disease on F-18 FDG PET-CT. Clin Nucl Med. 2009; 34(12):896–897. Epub 2010/02/09.

13. Vergel De Dios AM, Bond JR, Shives TC, McLeod RA, Unni KK. Aneurysmal bone cyst: a clinicopathologic study of 238 cases. Cancer. 1992;69(12): 2921–2931. Epub 1992/06/15. 14. Hay MC, Paterson D, Taylor TK. Aneurysmal bone cysts of the spine. J Bone Joint Surg Br. 1978;60-B(3):406–411. Epub 1978/08/01. 15. Chen CK, Yeh L, Resnick D, et al. Intraspinal posterior epidural cysts associated with Baastrup’s disease: report of 10 patients. AJR American J Roentgenol. 2004;182 (1):191–194. Epub 2003/12/20. 16. Mitra R, Ghazi U, Kirpalani D, Cheng I. Interspinous ligament steroid injections for the management of Baastrup’s disease: a case report. Arch Phys Med Rehabil. 2007;88(10): 1353–1356. Epub 2007/10/03. 17. Franck S. Surgical treatment of intraspinal osteoarthrosis (kissing spine). Acta Orthop Scand. 1944;14:127–152. 18. Beks JW. Kissing spines: fact or fancy? Acta Neurochirurgica. 1989;100(3–4):134–135. Epub 1989/01/01.

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Section 2 Chapter

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Spinal Disorders

Lumbar spinal stenosis and neurogenic claudication Ike Eriator and Zachariah Chambers

Case study A 72-year-old female reports pain in the low back during periods of standing or ambulation for the past 2 years. This is associated with numbness and tingling in the posterior thighs after walking for about half a block. The symptoms are relieved with leaning forward or sitting. Physical examination revealed a broadbased gait, negative sensory, motor, reflex testing or provocative maneuvers.

1. What is spinal stenosis? Lumbar spinal stenosis (LSS) is defined as buttock or lower extremity pain which may occur with or without low back pain, associated with diminished space available for neural and vascular elements in the lumbar spine. Neurogenic claudication refers to pain or discomfort that radiates to the lower extremity which occurs with walking or prolonged standing, and is relieved by rest or bending forward. Today, there are more treatment options for spinal stenosis than any other spinal pathology. It is the commonest indication for spine surgery in people over the age of 65 years.[1] About 75% of the cases of spinal stenosis occur in the lumbar spine. In 2007, about 38 000 operations were performed on patients with a primary diagnosis of lumbar spinal stenosis at a cost of $1.7 billion.[2]

2. What is the Verbiest syndrome? Spinal stenosis started appearing in the medical literature in the early 19th century. In 1893 a laminectomy was successfully performed to relieve a woman of the symptoms of cauda equina syndrome caused by spinal stenosis.[3] A description of lumbar spinal

stenosis was published by Sachs and Frankel[4] in 1900, but it is the classic description by the Dutch neurosurgeon, Henk Verbiest[5] in 1954 in a paper titled “A radicular syndrome from developmental narrowing of the lumbar vertebral canal” that is widely accepted as the initial description of the clinical syndrome of lumbar spinal stenosis. Neurogenic claudication or intermittent spinal claudication is called the Verbiest syndrome. Verbiest defined the clinical syndrome of lumbar stenosis in seven middle aged and older men who had back pain, bilateral radicular pain, and motor and sensory disturbances in the legs caused by standing, walking, and hyperextension. He described a myelographic block in the lumbar spine in every case, and at surgery a shallow canal with a compressed dural sac was observed. He postulated that the encroachment upon the canal by an enlarged articular process was a possible cause. Until the description, intermittent claudication was usually attributed to peripheral vascular disease of the aorto-iliac system. In the next two decades, the syndrome began to be more recognized and diagnosed. Kirkaldy-Willis and colleagues in 1978 described the pathology and pathogenesis of lumbar spondylosis and stenosis and described the three-joint complex composed of the facet joints and the intervertebral disc. They postulated that rotation and compression injuries led to degenerative changes of the three-joint complex. Subsequent to such injuries, the intervertebral discs can develop circumferential or radial annular tears, internal disruption, loss of disc height, and protrusion. The facet joints can then undergo synovitis, cartilage destruction, osteophyte formation, capsular laxity, ligamentum hypertrophy or buckling, and joint

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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instability or subluxation. The results of these changes to the three-joint complex create degenerative spondylolisthesis, retrolisthesis, degenerative scoliosis, and rotational deformities.[3]

3. What is the natural history of spinal stenosis? With age, progressive changes occur in the composition of the intervertebral disc similar to changes in other aging tissues in the body. This change affects the mechanical properties of the disc leading to decreased stiffness and strength, as well as accumulation of degraded matrix material. Some of these changes may be seen on MRI as “dark disc disease.” However, there is no direct relationship between such age-related changes and back pain.[6] Loss of disc integrity often leads to anterior instability, causing ligaments to buckle and hypertrophy from exposure to excessive forces, including new torsion forces. This may further lead to facet degeneration and hypertrophy. Bony encroachment into foramen of the exiting nerve root may lead to radicular features. If the anterior structures including the discs and ligaments fail at the same rate as the posterior structures, anterior subluxation (partial dislocation) of one vertebra on another may occur, leading to spondylolisthesis (anterior or posterior displacement). This may lead to a decrease in canal or foraminal space and spinal stenosis. Spondylosis refers to the agerelated changes with disc collapse and bony spur formation seen on radiologic investigations. The chronic compression of the nerve roots of the cauda equina contributes to the pain. The mechanical deformation of the cauda equina leads to increase in the intraspinal pressure, venous congestion, dilatation of the epidural veins, ischemia, and axonal injury.[7] The onset of pain is usually insidious; the natural history is characterized by fluctuations in the severity of symptoms and a tendency toward modest improvement in patients who choose not to have surgery. Degenerative lumbar stenosis is 3–5 times more common in women than men, and more commonly affects the L4–5 segment, followed by L3–4. L5–S1 segments rarely have degenerative slips because their facet joints have a coronal orientation, unlike the sagittal orientation in that of L4–5. Although lumbar spinal stenosis is typically degenerative in etiology, it is not necessarily progressive. Over time, the spine could undergo physiologic

arthrodesis, leading to long-term relief. In a prospective randomized trial (conservative versus surgical) that included 100 patients who were followed up for 10 years, it was noted that after 3 months, pain relief had occurred in most patients. After 4 years, 50% of patients in the conservative group had excellent or fair results compared to 80% in the surgically managed group. Delaying surgery did not appear to worsen the outcome.

4. What is the anatomical basis of spinal stenosis? The vertebral canal is formed with the combination of each successive vertebral foramen. The anterior boundary of the canal is made up of the posterior longitudinal ligament, the posterior surface of the vertebral body, and the intervertebral discs. The lateral border of the canal is formed by the superior and inferior pedicles of each vertebral segment. The posterior canal is bound by the vertebral lamina and the ligamentum flavum. The exiting nerve roots follow a course running laterally through the neural foramen which is an opening just inferior to each pedicle. The amount of room that is available for nerves in the vertebral canal is determined by the shape as well as the size of the vertebral canal. Spinal stenosis or canal stenosis occurs when the space is decreased due to encroachment of the boundaries of the canal. In congenital or developmental spinal stenosis, the shape and size of the canal is abnormally small due to abnormal development of the neural arch. For instance, the articular process may be too large or the pedicle too thick in relation to the size of the canal. This renders the canal relatively small for the contained neural elements.[8] It predisposes the patient to compression should minor changes occur in the boundaries of the canal. However, age-related degeneration associated with the upright position required for bipedal motion is the most common cause of spinal stenosis. Lumbar spinal stenosis occurs due to changes in the three-joint complex formed by the disc and the two facet joints. These three-joint complexes define the spine as a tripod with the disc as one leg and the facet joints as the other two legs forming the posterior support.[7] Dysfunction in any of these joints causes abnormal biomechanical stresses leading to abnormal degeneration in the other joints, thus creating a cycle of degenerative changes. Acquired

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Table 23.1. Etiologic classification of lumbar spinal stenosis

Acquired

Congenital

Degenerative Spondylolisthesis/ spondylosis Scoliosis Intervertebral disc bulge/herniation Facet hypertrophy Ligamentum flavum hypertrophy Synovial cysts

Idiopathic Dwarfism Achondroplasia Mucopolysaccharidosis

Degenerative/congenital Spondylolysis Iatrogenic Postlaminectomy Postfusion Post-traumatic Vertebral body compression fracture Osteoporosis Trauma Metastatic disease Tumors Metabolic Paget’s disease Fluorosis Miscellaneous Diffuse idiopathic skeletal hyperostosis Epidural hematoma Epidural abscess

spinal stenosis occurs when the structural boundaries of the canal are affected by diseases or degeneration leading to enlargement of the structure and encroachment into the canal. Spinal stenosis usually has a gradual onset and progresses as a person ages; as the intervertebral discs desiccate, degenerate, and bulge, the ligamentum flavum begins to buckle inwards. Hypertrophic osteophytes form at the facet joints. Such changes may affect one or multiple vertebral levels. Acquired spinal stenosis is the most common type of anatomic lumbar spinal stenosis and involves a combination of these factors: disc bulge or herniation, facet joint hypertrophy, and ligamentum hypertrophy/buckling. Spinal stenosis may also be caused by bone diseases, such as Paget’s

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disease, achondroplasia, tumors, or intrinsic bone pathology that encroaches on the nerve roots or the spinal cord (Table 23.1). Spinal canal stenosis is often multifactorial in origin.

5. How is lumbar spinal stenosis classified radiologically? Radiologic classification of lumbar stenosis refers to spinal canal narrowing on cross-sectional imaging. Stenosis may be: (1) central; (2) subarticular; or (3) foraminal. Central stenosis refers to the space between the medial edges of the two facet joints. Lateral recess (subarticular) stenosis refers to the area between the medial edge of the facet joint and the medial border of the pedicle. Neuroforaminal stenosis refers to the zone underneath the pedicle, i.e., between the medial and lateral borders of the pedicle. Anatomical lumbar canal stenosis refers to the intraoperative finding of a narrow spinal canal. The anteroposterior diameter of the lumbar spinal canal varies with race and gender. In general, a midsagittal diameter greater than 12 mm is considered normal. Relative stenosis exists when the diameter is between 10 and 12 mm. LSS can be defined as a spinal canal with an anterior-posterior diameter of less than 12 mm, while absolute LSS is 10 mm or less.[9] In a review that included 25 studies and four systematic reviews, Steurer and his colleagues noted that in general, in radiologic quantification of lumbar canal stenosis, an anteroposterior diameter of less than 10 mm and a cross-sectional area of the canal that is less than 70 mm2 were the criteria most often used for central canal stenosis.[10] For lateral stenosis, height and depth of the lateral recess was typically used and the foraminal diameter was used for foraminal stenosis. A lateral recess height of 5 mm or more is normal. A height of 3–4 mm suggests lateral stenosis, while a height of 2 mm or less is pathologic. The lumbar intervertebral foramen is shaped like an inverted tear drop. The normal width is 8–10 mm. A foramen height that is less than 5 mm and a width less than 4 mm has been found to be associated with nerve root compression 80% of the time. These measures are only guidelines. The patient’s symptoms are more important than the canal diameter.

Chapter 23: Lumbar spinal stenosis & neurogenic claudication

6. How is the diagnosis of spinal stenosis made? There are no widely accepted set of diagnostic criteria. The gold standard for the diagnosis is still the impression of an expert clinician, confirmed with radiologic or anatomical finding of the narrowed spinal canal. Spinal stenosis is characterized by non-specific limb symptoms that interfere with the duration of comfortable standing or walking (neuroclaudication or pseudoclaudication). Lumbar spinal stenosis causes numbness and pain in the legs with the patient walking or/and standing up for a moderate amount of time. The distress usually subsides when the patient bends forward or sits, and recurs when standing up and walking. One typical example of this disorder in daily life is the patient feeling pain and leg numbness while shopping at the supermarket. When the patient leans against the shopping cart (shopping cart sign) slightly bending forward, the symptoms are alleviated and the patient manages to finish the shopping. The patients often find that the symptoms improve when walking upstairs, and get worse when walking down. Sleeping postures result in lumbar extension and the patient finds that the symptom is worse in the middle of the night or early in the morning. This type of pain is characteristic of spinal stenosis, as opposed to intermittent claudication of vascular etiology that does not subside with sitting and bending forward. The symptoms of vascular insufficiency can be relieved by simply standing still. Neurogenic claudication may present with more subtle symptoms including a feeling of weakness, abnormal sensations, and fatigue affecting the lower extremity. Physical examination may reveal weakness, sensory loss, or gait changes.[11] However, symptoms are rarely associated with strong focal findings on examination. Often, symptoms will get worse slowly over time. Most often, symptoms will be on one side of the body or the other, but may involve both legs. Most people with spinal stenosis cannot walk for a long period of time. More serious symptoms include: difficulty or poor balance when walking and problems controlling urine or bowel movements. In severe cases of spinal stenosis, the patient is not able to take even one step and has urinary or defecation problems, due to intense pressure on the cauda equina, which may ultimately lead to incontinence.

The findings that most strongly suggest lumbar spinal stenosis are symptoms that improve with bending forward and absence of pain when seated.[11] Other strongly suggestive features include unexplained urinary disturbance (retention or incontinence), intermittent claudication, and presence of bilateral buttock or leg pain. The finding of a widebased gait is also important in ruling in the diagnosis. The absence of neurogenic claudication decreases the likelihood of lumbar spinal stenosis. In patients with history and physical examination findings consistent with degenerative lumbar spinal stenosis, MRI is the most appropriate, non-invasive test to confirm the presence of anatomic narrowing of the spinal canal or the presence of nerve root impingement. Where MRI is contraindicated or inconclusive, CT myelography is recommended. MRI or CT with axial loading is useful as an adjunct to routine imaging. Electrodiagnostic studies can help to rule out other causes that mimic the symptoms of LSS. LSS requires the presence of characteristic clinical findings (intermittent claudication, radicular pain, or their combination) and radiographic or anatomic confirmation. Many individuals with radiographic or anatomic lumbar spinal canal stenosis may not demonstrate the symptoms and signs of LSS. Radiographic or anatomic stenosis by themselves are not sufficient to diagnose this clinical syndrome.

7. What are the differential diagnoses of lumbar spinal stenosis? a. Lumbosacral radicular pain secondary to nerve root impingement This is pain induced by irritation, inflammation, pressure, or ectopic activation of nociceptive afferent fibers in a lumbar spinal nerve or its roots. The pain is perceived as being located in the ipsilateral lower extremity and is often characterized as a sharp, stabbing, electric shock sensation.

b. Referred pain from adjacent anatomic structures The facet or zygapophysial joints are paired diarthrodial articulations between adjacent vertebrae that are innervated by the medial branches of the dorsal rami. The referral pain patterns from the facet joint include the lumbar spinal and gluteal areas as well as the

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trochanter, lateral thigh, posterior thigh, and groin regions. Although not typical, the referral pain may also extend below the knee. The intervertebral disc is composed of the nucleus pulposus, the annulus fibrosis, and the vertebral endplates. Chemical and mechanical factors can explain pain emanating from the discs. The patterns of intervertebral disc pain include a sharp bilateral pain located at the posterior belt line which is usually preceded by multiple episodes of less severe low back pain. The pain is localized to the lower back and gluteal area and increases with flexion, rotation, or prolonged sitting or standing. Pain can be relieved in a recumbent position. Buttock pain is the most common pain referral area from a symptomatic hip joint. Groin and thigh referral areas can also occur but are less common. Hip joint pain can occasionally refer distally to the foot. Lower lumbar spine referral does not usually occur. Symptoms of greater trochanteric bursitis consist of persistent pain in the lateral hip radiating along the lateral aspect of the thigh to the knee and occasionally below the knee and/or buttock. Physical examination reveals point tenderness in the posterolateral area of the greater trochanter.

c. Lumbar vertebral compression fracture The osteoporotic vertebral fracture can cause a sudden, acute, intense pain that is aggravated even with the slightest movement and is located at the center of the spine, approximately at the level of the fracture, potentially radiating along the sides of the body.

d. Intermittent claudication secondary to peripheral vascular disease This is an intermittent cramping pain which is severe and usually arises after fixed and consistent amounts of exercise. Pain is usually relieved with rest or placing the limb in a dependent position. Low back pain is usually absent in vascular claudication. Vascular pain begins in the calves and progresses proximally, unlike neurogenic claudication which begins proximally and progresses distally. The stationary bicycle test can help with diagnosis. Patients with neurogenic claudication are able to tolerate the exercise since the lumbar is flexed, unlike the vascular claudication patients who should become symptomatic. This diagnosis can generally be ruled out if the ankle brachial indices are

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normal, unlike vascular claudication where the indices are typically closer to 0.7. Sometimes, these two conditions can coexist!

e. Peripheral neuropathy Peripheral neuropathy is a type of neuropathic pain attributed to dysfunction of peripheral nerves. It is manifested with functional nerve decline affecting various sensations such as touch, pain, vibration leading to numbness and dysesthesia. Longer nerves are more susceptible and, as a result, peripheral neuropathy symptoms initially occur in hands and feet, following the so-called “glove and stocking” distribution. Peripheral neuropathy usually affects both sides of the body symmetrically.

f. Visceral referred pain Visceral structures are highly sensitive to distention, ischemia, and inflammation while they are relatively insensate to cutting or burning. They present with vague pain symptoms with poor localization due to a low density of sensory innervation of the viscera and extensive divergence of the visceral input within the central nervous system. Multiple visceral structures including the kidneys, prostate, urethra, bowel, bladder, and pancreas can refer pain to the low back, buttocks, and upper legs.

g. Other differential diagnoses These include pain related to the sacroiliac joint, piriformis syndrome, myofascial pain, and compartment syndrome of the leg. In pathology due to the sacroiliac joint, the pain is in the lower back, overlying the posterior-superior iliac spine and may radiate to the buttocks and lower extremity. In piriformis syndrome, the pain is localized over the piriformis muscle in the buttocks, and may radiate down to the posterior buttock and lower extremity. In myofascial pain, trigger points can be felt over the muscle. In compartment syndrome, patients have tightness in the calf induced by strenuous exercise and are relieved slowly with elevation of the limb.[11]

8. Are conservative treatments effective in lumbar spinal stenosis? Conservative management is geared toward reducing inflammation, decreasing pain, strengthening the

Chapter 23: Lumbar spinal stenosis & neurogenic claudication

paravertebral muscles, and increasing the range of motion. Surgery is not devoid of complications and therefore many physicians will begin treatment with a conservative management regimen including physical therapy, pharmacotherapy, manipulation, bracing, traction, CBT, psychologic counseling, and electrical stimulation. Cold packs and heat therapy may also help with pain flare-ups. Although physical therapy is a popular treatment option, passive physical therapy shows only minimal benefits in the patient with LSS when used as sole therapy.[12] There has been no optimal regimen designed for active physiotherapy in patients with LSS. However, a regime that combines manual therapy/exercise and body weight supported ambulation has shown higher rates of perceived recovery in the short term.[13] Other modalities often used in physical therapy including transcutaneous electrical nerve stimulation and ultrasonography also have limited benefit in the treatment of back pain. Although back braces have been a popular method of treating back pain there has been no evidence that braces correct the cause of the pain generator. Braces may, however, be a physical reminder that the patient needs to use correct bending and lifting techniques while at work or home. A number of different medications have been trialed for pain secondary to lumbar spinal stenosis including gabapentin, limaprost, and methylcobalamin. Non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and opioid analgesics are often used to treat low back pain based on their mechanism of action. Calcitonin has analgesic properties and can decrease the blood supply to bones by decreasing the metabolic activity. Parenteral calcitonin (but not intranasal administration) can transiently decrease pain.[12] Gabapentin by binding to the alpha 2 subunit of the calcium channel, modulates neural transmission and provides analgesia. In lumbar spinal stenosis trials, patients on gabapentin had a greater walking distance, significantly lower pain score at 3–4 months, and decreased sensory deficits.[14] Limaprost (alprostadil) is an oral prostaglandin E1 analog with vasodilatory and antiplatelet properties. In a shortterm RCT, patients with LSS who were on limaprost in comparison to those on etodolac, had better pain scores, walking distance, improvement in leg numbness, and satisfaction after 8 weeks.[15] NSAIDs are effective for both anti-inflammatory and analgesic effects; however they should be used

with caution in patients due to the risk of gastritis, gastrointestinal bleeding, and renal dysfunction. NSAIDs should be used at the lowest dose for the desired effect and should not be used long-term. Their cardiovascular risk profile calls for care in this group of patients who are usually elderly. Acetaminophen is an effective medication for mild to moderate pain but has no effect on inflammation or muscle relaxation. Opioids can help in moderate to severe pain in general, but their use in chronic non-cancer pain remains controversial.

9. What is the next step if simple conservative options are not effective? Epidural corticosteroid injections have been shown to be effective in the short-term treatment of acute and subacute lumbar radicular pain. The transforaminal epidural injection may be more effective than the classical interlaminar approach since the infusion of the theraupeutic drug solution is selectively targeted to the affected nerve root.[16] Interlaminar epidural steroid injections can also provide short-term (weeks) improvement in function. The addition of steroid to the local anesthetic may not significantly increase the duration of relief.[12] A multiple injection regimen of radiographically guided transforaminal epidural steroid injection or caudal injections can provide medium-term (3–36 months) relief of pain.

10. Neuroplasty therapy (adhesiolysis) There is strong evidence supporting the efficacy of neuroplasty with corticosteroids in the short and long-term control of pain in refractory radiculopathy and neuropathic spinal pain. Such epidural adhesiolysis can produce reduction in pain and improvement in disability index over 12 months.[17] In this procedure, the sacral hiatus is located after sterile cleaning and draping. Lidocaine is infiltrated through the skin and subcutaneous tissue. An epidural/introducer needle is inserted until the tip of the needle is positioned within the sacral hiatus and well below a horizontal line connecting the inferior border of the S3 foramina (to avoid the dural sac). Contrast is used to confirm placement. The epidurogram typically shows a Christmas tree pattern. A radiopaque, styletted, and steerable catheter is inserted through the needle and guided until the tip is below the stenotic

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level. Contrast is used to confirm placement and to ensure absence of subarachnoid, subdural or vascular spread and to ensure adequate run off (no loculation). Local anesthetic and steroid are then injected. The needle is retracted with the catheter left in place. Fluoroscopy is used to confirm that the catheter is still in position. The catheter is then secured to the back. After confirming that the catheter is not in the intrathecal space, hypertonic saline is injected in aliquots. Hypertonic saline solution has historically been 10%. Hyaluronidase may be used prior to the hypertonic saline. The catheter is removed with the tip intact. Sedation (and analgesia) is tailored to the patient’s comfort during the procedure.

11. Minimally invasive lumbar decompression Minimally invasive lumbar decompression (MILD) is focused on debulking the ligamentum flavum, thereby widening the spinal canal without disruption of the biomechanical support. It can be performed in an ambulatory setting and may be an option for patients who are not suitable candidates for surgical decompression due to comorbidity or other reasons. It is usually done under local anesthetic with sedation. In this procedure, contrast material is injected in the epidural space under fluoroscopic guidance. A cannula is inserted about one and a half vertebral bodies below the level of the epidural needle and slightly medial to the pedicle and clamped in place. The edges of the lamina and the thickened ligamentum flavum are resected using special tools under fluoroscopic guidance.[18] The process is repeated on the opposite side for bilateral decompression of the canal stenosis. In a randomized trial that compared the effectiveness of MILD with that of epidural steroid injection, LSS patients in the MILD group showed statistically significant greater pain reduction and improvement in mobility at 12 weeks follow-up.[19] Complications including nerve transection and dural tear and high failure rates have been reported. Practitioner’s training and careful patient selection are very important for success. Patients who are chosen for the MILD procedure must be differentiated from those with pure radicular pain. Patients who have ligamentum flavum hypertrophy may also have co-factors that worsen LSS symptoms, including facet hypertrophy, spondylolisthesis,

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disc protrusion, epidural lipomatosis, and foraminal stenosis. Although patients may have multiple comorbidities related to the LSS it is not necessary to treat all of the causes of LSS to see symptom relief.[20] Studies have indicated that most patients show significant early improvement following treatment and have considerable stability and durability 2 years after the MILD procedure.[21]

12. Interspinous spacers In some patients with lumbar spinal stenosis in whom conservative approaches have not been successful, interspinous spacers are surgical alternatives that can be performed under local anesthetic with sedation in an outpatient setting. It is a less invasive procedure compared to a decompressive laminectomy. A titanium implant is fixated to the interspinous ligament between the two symptomatic vertebrae, thus decreasing extension of the spine at that level. Flexion can still occur. Considering that lumbar spinal stenosis occurs in the latter decades of life when patients have multiple medical problems, some of which may be debilitating, the risk profile associated with the interspinous spacers makes them a viable alternative to traditional laminectomy with or without fusion. The X-STOP Interspinous Process Decompression (IPD) System was approved by the FDA in 2005 for implantation at one or two lumbar levels. The X-STOP consists of two titanium flanking “wings” connected by a central bar. During the procedure the surgeon removes one of the wings, inserts the bar between two adjacent spinous processes, and then locks the second wing down. The contraindications include allergy to titanium, significant lumbar spine instability, ankylosis at the levels to be treated, significant scoliosis, acute fracture of the spinous process or pars interarticularis, severe osteoporosis, cauda equina syndrome, or systemic or local infections. Patients can still have surgical decompression in the future if their symptoms persist or recur. The X-STOP PEEK (polyetherketone) is a modified version of the X-STOP and was approved in 2006. It includes a PEEK spacer and additional 16 mm spacer size. The Coflex Interspinous Spacer is a U-shaped titanium alloy with pairs of wings that surround the superior and inferior spinous processes and is designed to improve the cross-sectional diameter of the spinal canal. It was approved by the FDA in 2012.

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In a retrospective cohort analysis of medicare claims for 2006–2009, Dayo et al (2013)[22] compared the complications and repeat operations in patients who had surgical decompression or fusion to those who had interspinous spacers for lumbar spinal stenosis. Patients who had placement of spacers were older (though there was little evidence of greater comorbidity). Patients who received the spacer alone had fewer complications than those who had decompression or fusion (1.2% vs. 1.8% vs. 3.3%). However, at the 2-year line, patients who were treated with the spacers had higher rates of further inpatient lumbar surgery (16.7% vs. 8.5% for decompression and 9.8% for fusion). Hospital payments for spacer surgery were higher than those for decompression alone, but less than that for fusion.

13. How effective is decompression for the treatment of LSS? The purpose or goal of surgical intervention is to correct the underlying process that is causing the symptoms of lumbar spinal stenosis. It is usually performed for the relief of pain in the lower extremity, not low back pain. Surgical treatment can provide longterm improvement in patients with degenerative lumbar spinal stenosis and has been shown to improve outcomes in a large percentage of patients.[23] Elderly patients with spinal stenosis who tolerate their daily activities well usually do not need surgery unless they develop new signs of bowel and bladder dysfunction. Patient’s preferences, the presence of other medical conditions, and the risks of surgery should be considered. Surgery for spinal stenosis is rarely considered in the first 3 months of symptoms. Surgery is beneficial in appropriately selected patients, and it may be done through several options. Decompressive laminectomies are the most common surgeries performed on the lumbar spine and involve removal of the laminae (roof) of the vertebrae to create more space for the neural elements. However, conventional decompressive laminectomy disrupts several supportive elements including the spinous process, lamina, and inter-spinal ligaments and leads to potential instability and increased stress on the adjacent discs and facets. Decompression alone is suggested for patients with leg predominant symptoms without instability. It involves removal of ligamentum and lamina. The dural sac is then retracted to access the disc material causing the neural

compression. Due to variations in the skills, knowledge, and experience of the surgeon, the outcome also varies.[6] Foraminotomy takes the pressure off the nerve root and allows the spine to move more easily. Laminectomy with or without fusion has been the surgical treatment favored by most surgeons for patients with lumbar spinal stenosis and associated poor quality of life. Complications include worsening pain, disability, neurologic deficit, poor wound healing, and even death. About 30% to 70% of patients report significant improvement in symptoms. Gross total laminectomies are rarely done nowadays due to the complicating post laminectomy kyphosis. Rather, midline sparing procedures like laminotomies or hemilaminectomies are preferable, and these can be done through minimally invasive approaches. Microdiscectomy by any method is now the operation of choice, as it is less invasive and is associated with decreased postoperative pain, hospital costs, and the number of missed work days. The prevalence of recurrent disc herniation varies and it may relate more to the surgical skill rather than to the choice of microdiscectomy or open discectomy. Minimal access procedures like percutaneous discectomy, microscopic discectomy, or energy-assisted discectomy minimizes surgical exposure, but they require greater knowledge of spinal anatomy, as separating the nerves from bony structures can be difficult with such minimally invasive exposures.[6] In certain conditions like spondylolisthesis, spinal fusion is the standard procedure to ensure spinal stabilization and this provides a better outcome.

14. How would you manage this patient? The diagnosis of lumbar spinal stenosis should be considered in older patients presenting with a history of gluteal or lower extremity symptoms exacerbated by walking or standing, which improves or resolves with sitting or bending forward. Patients whose pain is not made worse with walking have a low likelihood of stenosis. The most common symptom associated with lumbar spinal stenosis is neurogenic claudication. The likelihood of clinical lumbar spinal stenosis increases with age, especially in individuals above 70 years of age. A diagnosis of spinal stenosis is made by history and physical examination and confirmed by diagnostic testing.

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The history and physical examination findings in this patient are suggestive of lumbar spinal stenosis. The bicycle test can help to differentiate neurogenic and vascular claudication. An MRI would be helpful for radiologic confirmation and quantification. Plain x-rays (with flexion/extension) can provide an estimate of the degree of instability. It can show fractures, osteophytes spinous process settling (kissing spine), and metastatic disease. Depending on comorbidities, other special tests like ankle brachial indices and EMG may be needed to rule out the differential diagnoses. If the MRI confirms the spinal stenosis, it will also help with planning in terms of the location and classification of the stenosis. The treatment options, associated side effects, and expected outcomes should be discussed. The symptoms may not deteriorate if she chooses palliative relief and simple follow-up. But about 15% of patients with lumbar spinal stenosis will deteriorate,

References 1.

2.

7.

Lurie JD, Tosteson AN, Tosteson, TD, et al. Reliability of reading of magnetic resonance imaging features of lumbar spinal stenosis. Spine (Phila Pa 1976), 2008; 33(14):1605–1610.

Storm PB, Chou D, Tamargo RJ. Lumbar spinal stenosis, cauda equine syndrome and multiple lumbo-sacral radiculopathies. Phys Med Rehabil Clin N Am. 2002;13:713–733.

8.

Deyo RA, Mirza SK, Martin BI, et al. Trends, major medical complications, and charges associated with surgery for lumbar spinal stenosis in older adults. JAMA. 2010;303:1259–1265.

Bogduk N. The lumbar lordosis and vertebral canal. In Clinical Anatomy of the Lumbar Spine and Sacrum, 3rd ed. London, UK: Churchill Livingstone. 1997: chapter 5, pp. 55–62.

9.

Kalichman L, Cole R, Kim DH, et al. Spinal stenosis prevalence and association with symptoms: The Framingham study. Spine J. 2009;9(7): 545–550.

3.

Botwin K, Gruber R. Lumbar spinal stenosis: anatomy and pathogenesis. Phys Med Rehabil Clin N Am. 2003;14:1–15.

4.

Sachs B, Frankel V. Progressive and kyphotic rigidity of the spine. J Nerv Ment Dis. 1900;27:1–15.

5.

Verbiest H. A radicular syndrome from developmental narrowing of the lumbar vertebral canal. J Bone Joint Surg Br. 1954;36B(2): 230–237.

6.

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and about 15% will have improvement. Nonconservative approaches with analgesics, coanalgesics, and physical therapy (manual with body weight support) may help. But considering the limited ambulation and the gait disturbance, our advice will be to consider further treatment options. Lumbar epidural injection, the technical approach of which can be tailored to the MRI findings of the location of stenosis, can help in the short term. Epidurolysis may also be helpful in this case. If no long-term relief is obtained, and the patient chooses to have something more done, the options of MILD, inter spinous spacer, microdiscectomy, and lumbar laminectomy with or without fusion should be discussed guided by the MRI findings. The most efficacious treatment for patients with lumbar stenosis remains elusive. A multidisciplinary approach to treatment is the recommended course at this time.

Lavelle W, Carl A, Lavelle ED. Invasive and minimally invasive surgical techniques for back pain conditions. Med Clin N Am. 2007;91:287–298.

10. Steurer J, Roner S, Gnannt R, Hodler J. Quantitative radiologic criteria for the diagnosis of lumbar spinal stenosis: a systematic literature review. BMC Musculoskeletal Disorders. 2011;12:175. 11. Suri P, Rainville J, Kalichman L, Katz J. Does this older adult with lower extremity pain have the clinical syndrome of lumbar spinal stenosis? JAMA. 2010; 304(23):2628–2636.

12. Tran DQH, Doung S, Finlayson RJ. Lumbar spinal stenosis: a brief review of the nonsurgical management. Can J Anesth. 2010;57:694–703. 13. Whitman JM, Flynn TW, Childs JD, et al. A comparison between two physical therapy treatment programs for patients with lumbar spinal stenosis: a randomized clinical trial. Spine (Phila Pa 1976). 2006;31: 2541–2549. 14. Yaksi A, Ozgonenel L, Ozgonenel B. The efficiency of gabapentin therapy in patients with lumbar spinal stenosis. Spine. 2007;32:939–942. 15. Matsudaira K, Seichi A, Kunogi J, et al. The efficacy of prostaglandin E1 derivative in patients with lumbar spinal stenosis. Spine (Phila Pa 1976). 2009;34:115–120. 16. Lee JH, An JH, Lee SH. Comparison of the effectiveness of interlaminar and bilateral transforaminal epidural steroid injections in treatment of patients with lumbosacral disc herniation and spinal stenosis. Clin J Pain. 2009;25(3):206–210.

Chapter 23: Lumbar spinal stenosis & neurogenic claudication

17. Manchikanti L, Cash KA, McManus C, et al. The preliminary results of a comparative effectiveness evaluation of adhesiolysis and caudal epidural injections in managing chronic low back pain secondary to spinal stenosis: a randomized equivalence control trial. Pain Physician. 2009;34:E342–351. 18. Vallejo R, Benyamin R. Novel options for patients with lumbar spinal stenosis: minimally invasive lumbar decompression and other strategies. Tech Reg Anesth Pain Manag. 2013;16:84–88.

19. Brown L. A double blind, randomized prospective study of epidural steroid injection vs the MILD procedure in patients with symptomatic lumbar spinal stenosis. Pain Pract. 2012;12: 333–341. 20. Mekhai N, Costandi S, Abraham B, Samuel S. Functional and patient-reported outcomes in symptomatic lumbar spinal stenosis following percutaneous decompression. Pain Practice. 2012;12(6):417–425. 21. Chopko B. Long-term results of percutaneous lumbar

decompression of LSS: two-year outcomes. Clin J Pain. 2013; 29(11):939–943. 22. Dayo RA, Martin, BI, Ching A, et al. Interspinous spacers compared with decompression or fusion for lumbar stenosis: complications and repeat operations in the medicare population. Spine (Phila Pa 1976). 2013;38(10):1865–1872. 23. Airaksinen O, Herno A, Turunen V, et al. Surgical outcome of 438 patients treated surgically for lumbar spinal stenosis. Spine. 1997;22:2278–2282.

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Spinal Disorders

Management of the patient with postlaminectomy pain syndrome Jay S. Grider

Case study The patient is a 64-year-old male who underwent microdiscectomy 10 years prior. Eighteen months ago the same spine surgeon diagnosed spinal stenosis and performed a two level, decompressive laminectomy. This was successful in relieving his pain for approximately 1 year; however the patient reports that pain has worsened over the last 6 months and is now intolerable with conservative measures such as physical therapy, NSAIDs, and opioids having been tried. He describes low back pain across the center of his lumbar region with a dull ache to the posterior aspect of both hips and thighs. Additionally, he reports pain down the left leg to the top of his left foot. He presents to the Pain Center today inquiring about treatment options as the oxycodone 7.5/325 tablets he was taking 3 times per day as prescribed by his primary care physician have become less efficacious with time.

1. What is postlaminectomy pain syndrome? There are several conditions which fall under the heading of postlaminectomy pain syndrome (PLPS). While the name implies an etiology that is confined to patients who have had laminectomy, the syndrome may be more accurately defined as postlumbar surgery syndrome. This “catch all” term as used in clinical vernacular also often includes patients who have had discectomy or fusion. The term failed back surgery syndrome (FBSS) is also used, but for obvious reasons carries connotations that are distasteful to the spine surgeon. The concept of pain persisting despite appropriate execution of the surgical intervention and anatomical correction (to the degree possible) is the

principle which underpins the concept of PLPS regardless of nomenclature.[1,2] It has been estimated that as many as 30% of patients will have ongoing pain after decompression.[2] Likewise approximately 75% of patients have persistent low back pain 10–20 years following discectomy. While the surgical procedures mentioned can be performed at any spinal level, the concept of postlaminectomy pain syndrome as a clinical entity is usually confined to the lumbar spine.[1–3]

2. What is the etiology of postlaminectomy pain syndrome? There are established sources of PLPS that can be attributed to the pre-, intra- and postoperative period. Table 24.1 outlines these etiologies. Though beyond the control of the interventional pain physician, the preoperative selection process and the psychosocial aspects around patient selection for initial surgery are often overlooked. It stands to reason that the outcome of spinal surgery in an individual with major tendencies toward somatization will frequently yield mixed results. It is clear that patients with preoperative legal or workers’ compensation issues surrounding their care have inferior outcomes;[2,4] the reasons for this are multifactorial. Intraoperative issues include surgical intervention on an anatomically aberrant structure that, despite the poor appearance on imaging (and occasionally corroborated with neurodiagnostic studies), is not the primary pain generator.[4] An example of this concept would be the patient with disc herniation and dermatomal radicular pain in which the leg pain improves after surgery while the low back pain persists into the postoperative period. If low back pain

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Table 24.1. Factors associated with postlaminectomy pain syndrome

Preoperative factors

Intraoperative factors

Postoperative factors

Ignoring psychologic factors complicating symptoms

Inaccessible pathology

Restenosis/ herniation

Litigation

Misdiagnosis

Fibrosis

Poor surgeonpatient communication

Wrong level/ inadequate decompression

Continued deterioration of lumbar spine

Unrealistic expectation (patient)

Fusion instability

was the primary presenting complaint to the surgeon while the radicular lower extremity pain was secondary, the patient may be dissatisfied with the outcome when radicular pain improves and back pain persists. Anecdotally, This appears to be relatively common anecdotally. Common postoperative causes of persistent pain include residual anatomic pathology that is not accessible via the employed surgical approach, reoccurrence of the pathology, internal disc disruption, and fibrosis of the surgical site.[3] Recent studies have suggested a link between the severity of pain after lumbar spine surgery and the degree of fibrosis that occurs.[5] These concepts have led to several studies designed to limit fibrosis and concomitant adhesions after spine surgery.[5] While beyond the scope of the current discussion it is important to note that these intraoperative/postoperative applications of lidocaine, primecrolimus, heparin extracts, and allantoin have had variable success in preventing fibrosis.[3]

3. How is postlaminectomy pain syndrome diagnosed? Diagnosis often begins with imaging. Standing flexion/extension x-rays give basic clues to alignment and stability of the lumbar spine. MRI imaging without contrast enhancement can evaluate the disc and the diameter of the central and lateral spinal canal with regard to stenosis.[6,7] Reevaluation for patients who have had discectomy may require contrast

enhancement to determine the presence of discrelated pathology. The presence of pedicle screws may cause artifact on MRI that may obscure the desired view. In these cases CT-myelogram may be a superior imaging choice to evaluate stenosis; however this modality has the downside of requiring intrathecal access. If postdural puncture headache occurs in the laminectomy/fusion patient, treatment with an epidural blood patch may be difficult.[7–9] While the formal designation of what constitutes critical canal stenosis has not been established it has been suggested that a canal diameter in the 10–12 mm range may become symptomatic.[9] Anecdotally the development of moderate-severe canal stenosis above or below the level of previous decompression or fusion must be considered. Discogram is a method to identify symptomatic intradiscal pathology. The usefulness of this modality in diagnosing the source of discogenic pain has many advocates and detractors. The interested reader is directed to several excellent references on this topic.[10,11] While useful in the diagnosis of discogenic pain and disrupted disc morphology, the risks (disc infection, false-positive) and benefits must be carefully considered. The systematic use of injective therapy as a diagnostic tool is often underappreciated as these modalities are primarily thought of as therapeutic interventions. As the clinician uses image-guided injections to identify the pain generator a more precise treatment plan may be formulated. Diagnostic image-guided injections of the sacroiliac joint, facet joints, at the neuroforamen/pedicle screw interface, and myofascial structures surrounding hardware are often sources of pain that can be evaluated. The use of selective nerve root/transforaminal injections can identify the level of pathology.[12] The use of ultrasound as a modality to evaluate musculoskeletal issues and to guide diagnostic intervention is currently a rapidly evolving area of interest. It is important to underscore to the patient who may have been prescribed injective therapy prior to their surgery that the use of diagnostic blocks is to determine if there is new or treatable pathology. Underscoring the diagnostic application of these blocks ensures that the patient understands that there may not be long-term therapeutic benefit to the procedure they are undergoing. The inability to identify a pain generator may provide important information for the clinician. The treatment paradigm may change

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Chapter 24: Management of the patient with postlaminectomy pain syndrome

from an interventional or rehabilitative model to a more palliative model that assists with coping and support mechanisms for the patient with pain that may not be easily treated.

4. What interventional treatments may be utilized? The modalities available to treat PLPS include the following: 1. Epidural steroid injection – interlaminar and transforaminal 2. Lumbar facet interventions – steroid facet injections and radiofrequency ablation 3. Adhesiolysis 4. Spinal cord stimulation 5. Intrathecal drug delivery 6. Medication management a. Adjunctive medications b. Opioid analgesics

Figure 24.1. Lumbar transforaminal. Note extensive lumbar laminectomy and prior removal of hardware at L4, L5, and S1 pedicles. From personal files of Rinoo V. Shah, MD, MBA.

Lumbar epidural steroid injections and PLPS There is evidence to suggest that lumbar epidural steroid injections certainly provide short-term (less than 3 months) and possibly long-term (greater than 6 months) decrease in pain-related symptoms and dysfunction. This point is however controversial as recent studies have called the long-term efficacy of interlaminar injections into question.[13–15] It is possible that transforaminal epidural injections may provide greater long-term efficacy as at least one report has suggested that this approach may provide enough pain relief to prevent consideration of reoperation.[14] It is imperative that these injections be image-guided rather than blind in nature as the transforaminal data would suggest that specific anatomic localization improves outcome.[14] Since many of the lumbar epidural steroid articles range over several years (with a wide variety of techniques and approaches used) conclusions on efficacy are somewhat difficult with many of the recent studies suggesting less benefit than previously thought from midline transforaminal lumbar epidural steroid injections. Recently an interlaminar approach to the lateral recess has been described and may hold promise as a therapeutic approach.[15] Clinically epidural steroid injections can be uncomfortable for the patient if increasing volumes are used. This could be due to

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the volume of injectate breaking down scar tissue in a rudimentary lysis of adhesions fashion.[3] See Figure 24.1.

Caudal epidural injection and PLPS Special consideration to caudal epidural injections is warranted as there is evidence to support this approach in long-term treatment of pain associated with patients who have had spine surgery with residual pain.[16] At least one well-designed randomized controlled trial has shown benefit superior to the caudal approach vs. the traditional lumbar interlaminar treatment approach.[17] While not limited to laminectomy, this study demonstrated that benefit was obtained with either lidocaine alone or with steroid. Use of other medications such as hyaluronidase have had mixed results when utilized in the lumbar/ caudal epidural space.[15,17,18]

Facet and medial branch interventions The contribution of facetogenic pain to PLPS is currently unknown but diagnosis and treatment follows the same algorithms as non-PLPS facet-mediated pain.[16] There is evidence to suggest that patients

Chapter 24: Management of the patient with postlaminectomy pain syndrome

Figure 24.2. Lumbar epidural adhesiolysis, note epidural scar impedance of contrast cephalad to L5–S1. From personal files of Rinoo V. Shah, MD, MBA.

with axial back pain of facet origin respond similarly despite previous surgical intervention.[19,20]

Adhesiolysis When lumbar/caudal injections do not prove effective in treating PLPS pain, adhesiolysis has been shown to be effective in improving pain and increasing function.[16] Lidocaine, hypertonic saline, and nonparticulate betamethasone solutions have been used and shown to provide greater benefit than epidural steroid injections.[16] Adjuvant drugs such as hyaluronidase may be utilized as well. Conversely, adhesiolysis may be more uncomfortable for the patient than epidural steroid injection. Evidence concerning the safety and efficacy of the procedure in patients with PLPS has been supported by several clinical trials.[16,21–24] See Figures 24.2 and 24.3.

Spinal cord stimulation The use of spinal neuromodulation in the treatment of PLPS has been studied in one of the better interventional pain studies to date: the PROCESS trial (Prospective Randomized Controlled Trial of Effectiveness of Spinal Cord Stimulation).[25–27] In this study and two other related studies, 100 patients were randomized to both spinal neuromodulation and conventional medical management versus medical management. The results suggest that spinal cord

Figure 24.3. Lumbar transforaminal-far lateral approach given posterolateral bone graft on transverse processes.[36] From personal files of Rinoo V. Shah, MD, MBA.

stimulation coupled with conventional medical management significantly improves analgesia over medical management alone in patients with PLPS. Similarly North and colleagues[28] found that spinal cord stimulation provides better outcomes with regard to function and analgesia than a second spinal surgery. These studies have led many thought leaders to suggest that spinal neuromodulation should be considered earlier in the treatment algorithm of lumbar radicular pain and certainly before reoperation unless there is a clear anatomic cause for surgical intervention. As neuromodulation techniques have matured, the use of stimulation in the periphery for PLPS has been reported with success. While in the early stages of description several reports suggest that true peripheral nerve stimulation and peripheral field stimulation, both with and without epidural lead placement, may have benefit in this patient population.[29] These concepts require further investigation but appear to have a very favorable risk–benefit profile.[16] See Figures 24.4 and 24.5.

Pharmacologic management There is reasonable evidence for analgesic efficacy with NSAIDs; however this class of medications has side effect profiles that limit their usefulness in several patient populations. Anticonvulsant and selected

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Figure 24.5. Lateral view cervical spinal cord stimulation in patient with cervical postlaminectomy syndrome; left lead cannot pass further cephalad due to epidural scarring-whereas right lead can pass. From personal files of Rinoo V. Shah, MD, MBA.

Figure 24.4. Anteroposterior view cervical spinal cord stimulation in patient with cervical postlaminectomy syndrome; left lead cannot pass further cephalad due to epidural scarring-whereas right lead can pass. From personal files of Rinoo V. Shah, MD, MBA.

antidepressant medications have also been utilized with success for neuropathic pain associated with PLPS but have proven less effective for isolated chronic low back pain.[3] The use of opioids in the treatment of patients with previous spine surgery, while common, has limited evidence of success in the literature and as such is a topic of much debate currently.[30,31] The significant risks to be considered from an opioid habituation and aberrancy standpoint must be carefully weighed in an assessment of improved function.[30]

Intrathecal drug delivery Patients who have not received benefit from less invasive interventional treatment options, such as injections, medications and even spinal cord stimulation, may be candidates for intrathecal drug delivery (IDD). In many cases patients become tolerant to

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the oral opioid effects and/or have side effects of oral opioids that preclude their continued use. It has been estimated that oral opioid therapy is discontinued in over 50% of subjects in whom it is started because of poor efficacy or side effects.[32,33] Patients with PLPS are often excellent candidates for IDD because they often have axial spine pain that is a greater symptomatic issue than radicular lower extremity pain. For patients with predominantly low back pain, IDD has been suggested as an excellent source of analgesia without systemic side effects.[32] Currently only preservative-free morphine, baclofen, and ziconotide are approved by the FDA for intrathecal use; the Polyanalgesic Consensus Guidelines prepared by the North American Neuromodulation Society lists other commonly accepted agents for which there is reasonable safety data for intrathecal use.[32] These medications include the opioids hydromorphone and fentanyl as well as the local anesthetic bupivacaine and antihypertensive medication clonidine.[31] The opioids are often used for axial spinal pain while the other adjunctive medications and ziconotide are considered useful for neuropathic pain.[32] The balance between clinical experience (which for many of these medications is vast) and regulatory approval via FDA has created a dilemma for clinicians as they attempt to treat patients with IDD.[33] Aggressive use of medications not approved for intrathecal use has

Chapter 24: Management of the patient with postlaminectomy pain syndrome

drawn stern warnings from many professional societies; however the Polyanalgesic Guidelines represent evidence-based, reasonable pharmacologic applications of drugs with long histories of safety and efficacy some of which would represent an off-label usage.[33] A recent patient alert bulletin by the Medtronic Corporation suggests that changing between medications (morphine to hydromorphone, for example) may result in a short-term aberration in drug delivery (hours) that may result in slightly higher or lower doses of medication than intended and as such careful attention to the medication bridge-bolus with patient education as to possible effects is important.[33] Additionally, recent bulletins concerning improper filling of the devices (known as “pocket fills”) has led to renewed emphasis on safety during all phases of care with IDD.[33,34] The trialing and dosing regimens used by clinicians for IDD have been based largely on anecdotal and expert opinion for over the past three decades. Recently there have been attempts by several major pain societies to examine the evidence surrounding IDD patient selection and maintenance dosing.[31] While the 1990s saw aggressive dosing of IDD, recently there have been calls for reexamination of higher doses of medications delivered intrathecally with the concomitant risk of granuloma formation from these more aggressive dosing regimens. Recent studies have suggested the dose-response relationship in humans may be toward the lower end of the currently used dose spectrum for humans and as such aggressive dose titration may be, at the least, ineffective and at the most, harmful.[35]

Interdisciplinary management The role of physical therapy and behavioral therapy in treatment of PLPS cannot be discounted. Many patients suggest that physical therapy has not benefitted them in the past. The reasons for this are multiple but often include (1) a therapist with strong bent toward aggressive rehabilitation which is difficult for the deconditioned PLPS patient or (2) the deconditioning itself concomitant with the PLPS discourages many patients giving a sense of hopelessness with regards to rehabilitation. A trusted therapist who understands that the PLPS patient did not become dysfunctional suddenly and that it

will take time and patience to regain function is key to improvement. The services of an experienced behavioral therapist with pain management experience helps the patient to understand that their plight is not unusual and that the mental approach to chronic disease management often is a major determinant in return to function.[3] This is especially true for the patient who may have become opioid habituated along the way but is now deriving less benefit from this therapy. Soberly addressing the true reasons behind usage of medications commonly prescribed by practitioners such as opioids and benzodiazepines is of vital importance. Determining on a consistent basis that aberrant usage patterns are not developing is also vital to ensuring that the PLPS patient is moving from a less functional state to improved function.

5. Complications/Conclusions Postlaminectomy pain syndrome is a very common clinical entity encountered in contemporary pain medicine due to the explosion in spinal surgery with its estimated 20–40% failure rate with regard to pain relief.[2] The complications of PLPS are the summation of the risks of all the treatment modalities discussed and therefore are difficult to estimate.[3] One common refrain heard anecdotally from patients is that pain is worsening while repeat imaging shows little disease progression. Perhaps the biggest complication in PLPS is the tendency for diligence in clinical work-up to fatigue after years of treating a patient with marginal improvement in symptoms or satisfaction. This diligence fatigue on the part of the clinician could prevent detection of new pathologies, which must always be in the differential diagnosis. Continuously monitoring the patient in a cost-efficient manner (i.e., not ordering expensive imaging routinely) while maintaining a watchful eye for new or clinically worsening pathology is a clinical challenge. The constellation of symptoms with PLPS usually requires a multimodal and multidisciplinary approach to management. Providing the patient with a stable clinical environment often is key to (1) limiting unnecessary expenditures to the health system in the form of emergency department visits and (2) providing reassurance that easily accessible medical attention for this chronic ongoing problem is available.

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References 1.

Vleggeert-Lankamp C, Arts M, Jacobs W, Peul W. Failed back (surgery) syndrome: time for a paradigm shift. J Pain. 2013;7:48–55.

2.

Deyo R, Gray D, Kreuter W, Mirza S, Martin B. United States trends in lumbar fusion surgery for degenerative conditions. Spine. 2005;30:141–145.

3.

Hussain A, Erdek M. Interventional pain management for failed back surgery syndrome. Pain Pract. 2013;3. doi: 10.1111/ papr.12035.

4.

5.

Slipman CW, Shin CH, Patel RK, et al. Etiologies of failed back surgery syndrome. Pain Med. 2002;3:200–214; discussion 214–217. Ross J, Frederickson R, et al. Association between peridural scar and recurrent radicular pain after lumber discectomy: magnetic resonance evaluation. ADCONL European study group. Neurosurgery. 1996:38:855–861.

6.

Herzog RJ, Marcotte PJ. Assessment of spinal fusion. Critical evaluation of imaging techniques. Spine (Phila Pa 1976). 1996;21:1114–1118.

7.

Bokov A, Isrelov A, Skorodumov A, et al. An analysis of reasons for failed back surgery syndrome and partial results after different types of surgical lumbar nerve root decompression. Pain Physician. 2011;14:545–557.

8.

9.

Guyer RD, Patterson M, Ohnmeiss DD. Failed back surgery syndrome: diagnostic evaluation. J Am Acad Orthop Surg. 2006;14:534–543. Marnish N, Brumann, M, Hodler J, et al. Radiologic criteria for the diagnosis of spinal stenosis: results of the Delphi survey. Radiology. 2012;264(1):174–179.

10. Buenaventura RM, Shah RV, Patel V, Benyamin R, Singh V. Systematic review of discography as a diagnostic test for spinal pain:

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an update. Pain Physician. 2007; 10(1):147–164. Review. PubMed PMID: 17256028. 11. Shah RV, Everett CR, McKenzieBrown AM, Sehgal N. Discography as a diagnostic test for spinal pain: a systematic and narrative review. Pain Physician. 2005;8(2):187–209. PubMed PMID: 16850074. 12. Shah RV, Merritt W, Collins D, Racz GB. Targeting the spinal nerve via a double-needle, transforaminal approach in failed back surgery syndrome: demonstration of a technique. Pain Physician. 2004;7(1):93–97. PubMed PMID:16868618. 13. Gharibo CG, Varlotta GP, Rhame EE, et al. Interlaminar versus transforaminal epidural steroids for the treatment of subacute lumbar radicular pain: a randomized, blinded, prospective outcome study. Pain Physician. 2011;14:499–511. 14. Deer T. An update on the medical pain management of the multiply operate lumbar spine including neuroablative and other minimally invasive techniques. Semin Spine Surg. 2008; 20:248–256. 15. Candido K, Raghawendra M, Chinthagada M, et al. A prospective evaluation of iodinated contrast flow patterns with fluoroscopically guided lumbar epidural steroid injections: the lateral parasagittal interlaminar epidural approach versus the transforaminal epidural approach. Anesth Anal. 2008;106 (2);638–644. 16. Manchikanti L, Abdi S, Alturi S, et al. An update of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. Part II: Guidance and recommendations. Pain Physician. 2013;16:S49–S283. 17. Manchikanti L, Singh V, Cash KA, Pampati V, Datta S. Management of pain of post lumbar surgery

syndrome: one-year results of a randomized, double-blind, active controlled trial of fluoroscopic caudal epidural injections. Pain Physician. 2010;13:509–521. 18. Yousef AA, EL-Deen AS, Al-Deeb AE. The role of adding hyaluronidase to fluoroscopically guided caudal steroid and hypertonic saline injection in patients with failed back surgery syndrome: a prospective, doubleblinded, randomized study. Pain Pract. 2010;10:548–553. 19. Cohen SP, Hurley RW, Christo PJ, et al. Clinical predictors of success and failure for lumbar facet radiofrequency denervation. Clin J Pain. 2007;23:45–52. 20. Leclaire R, Fortin L, Lambert R, Bergeron YM, Rossignol M. Radiofrequency facet joint denervation in the treatment of low back pain: a placebocontrolled clinical trial to assess efficacy. Spine (Phila Pa 1976). 2001;26:1411–1416; discussion 1417. 21. Manchikanti L, Pampati V, Bakhit CE, Pakanati RR. Non-endoscopic and endoscopic adhesiolysis in post-lumbar laminectomy syndrome: a one-year outcome study and cost effectiveness analysis. Pain Physician. 1999;2:52–58. 22. Manchikanti L, Pampati V, Fellows B, et al. Role of one day epidural adhesiolysis in management of chronic low back pain: a randomized clinical trial. Pain Physician. 2001;4:153–166. 23. Manchikanti L, Rivera JJ, Pampati V, et al. Spinal endoscopic adhesiolysis in the management of chronic low back pain: a preliminary report of a randomized, double-blind trial. Pain Physician. 2003;6:259–267. 24. Manchikanti L, Singh V, Cash KA, Pampati V, Datta S. A comparative effectiveness evaluation of percutaneous adhesiolysis and epidural steroid

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injections in managing lumbar post-surgery syndrome: a randomized, equivalence controlled trial. Pain Physician. 2009;12:E355–E368. 25. Kumar K, Taylor RS, Jacques L, et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicenter randomized controlled trial in patients with failed back surgery syndrome. Pain. 2007;132:179–188. 26. Kumar K, Taylor RS, Jacques L, et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month followup of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery. 2008;63:762–770; discussion 770. 27. Manca A, Kumar K, Taylor RS, et al. Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial). Eur J Pain. 2008;12:1047–1058.

28. North RB, Kidd D, Shipley J, Taylor RS. Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial. Neurosurgery. 2007;61:361–368; discussion 368–369.

Conference 2012: Recommendations for management of pain by Intrathecal (intraspinal) drug delivery: Report of an interdisciplinary expert panel. Neuromodulation. 2012;15: 436–466.

29. Reverberi C, Dario A, Barolat G. Spinal cord stimulation (SCS) in conjunction with peripheral nerve field stimulation (PNFS) for the treatment of complex failed back surgery syndrome. Neuromodulation. 2013;16:78–83.

33. Falco F, Patel V, Hayek S et al. Intrathecal infusion systems for long-term management for chronic non-cancer pain: an update of the evidence. Pain Physician. 2013;16: SE185–216.

30. White AP, Arnold PM, Norvell DC, Ecker E, Fehlings MG. Pharmacologic management of chronic low back pain: synthesis of the evidence. Spine (Phila Pa 1976). 2011;36(21 Suppl): S131–S143.

34. Medtronic pump refill safety bulletin June 2013. http:// professional.medtronic.com.

31. Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85(3 Suppl): S3–S14. 32. Deer T, Prager J, Levy R, Rathmell J, et al. Polyanalgesic Consensus

35. Grider J, Harned M, Etscheidt M. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician. 2011;14:1533–1559. 36. Shah RV, Merritt W, Collins D, Racz GB. Targeting the spinal nerve via a double-needle, transforaminal approach in failed back surgery syndrome: demonstration of a technique. Pain Physician. 2004;7(1):93–97.

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Spinal Disorders

A patient with a lumbar compression fracture Nihir Waghela and Magdalena Anitescu

Case study A 73-year-old woman with a long history of osteoporosis had sudden onset of unrelenting and severe mid-back pain after a strong sneeze. Her pain was unresponsive to a 6-week course of conservative therapy with NSAIDs and opiates. She has been bed bound since her symptoms started and was being referred for consultation to a pain specialist for her treatment.

1. What is the differential diagnosis? a. b. c. d. e.

Vertebral compression fracture Acute intervertebral disc herniation Degenerative disc disease Muscle spasm of the paravertebral muscles Degenerative joint disease and facet arthropathy

In a patient with severe osteoporosis vertebral compression fracture is suspected especially after sudden increased axial pressure from a forceful cough. The main symptom of a compression fracture is unrelenting pain even with small movements, similar to that described in the case above. In a compressed vertebral body, tapping over the mid-thoracic area elicits pain. In most cases, the pain does not radiate from the localized area of discomfort, thus the practitioner must differentiate between radicular pain from disc herniation or back pain from facet arthropathy and a newly developing compression fracture. Vertebral compression fractures can occur spontaneously in osteoporosis or after minimal pro-dromal injury. Postmenopausal women with osteoporosis are most likely to be affected. Depending on the magnitude of force applied to the osteoporotic bone, the fracture can be a simple or a burst compression fracture.

2. What is the difference between a simple vertebral compression fracture and a burst fracture? In 1983 Denis described a three column model for the spine: anterior, middle, and posterior. The anterior column consists of the anterior longitudinal ligament, anterior half of the vertebral body, and its adjacent intervertebral disc and annulus. The middle column consists of the posterior half of the vertebral body, disc, the posterior annulus, and the posterior longitudinal ligament. The posterior column consists of the facet joints, transverse process, spinous process, pedicles, ligamentum flavum, and inter- and supraspinous ligaments.[1–3]

Figure 25.1. The anterior, middle, and posterior column as described by Denis.[1]

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Chapter 25: A patient with a lumbar compression fracture

The middle column is in the neutral axis of the spine during flexion and extension. It provides the greatest mechanical stability and bears the greatest axial load of the spine. A compression fracture affects only the anterior column; a burst fracture, both the anterior and the middle columns.[1–3] In a compression fracture the anterior column fails under compression while the middle and posterior columns remain intact. The intact middle column acts as a hinge. The fracture is usually stable and rarely associated with neurologic compromise because bone fragments are not retropulsed into the vertebral canal. The column becomes unstable if the ligamentous complex in the posterior column is disrupted.[1–3] A burst fracture results from failure of the vertebral body under an axial load. The anterior and middle columns fail under compression; the posterior column remains intact. Posterior fragments may be driven into the spinal cord or cauda equina, making this injury more dangerous than a simple compression fracture. A burst fracture can be stable or unstable depending on the integrity of the posterior ligamentous complex.[1–3]

Figure 25.2. Forces acting from above and below will increase flexion. Most thoracolumbar injuries are hyperflexion injuries.[1,2,7]

3. What is the pathogenesis and pathophysiology of a vertebral compression fracture? Is osteoporosis a factor? Each year about 700 000 vertebral compression fractures occur in the USA, with a prevalence of up to 25% in women over the age of 50. Only about onethird of those fractures are symptomatic but almost all increase in morbidity and mortality from functional and psychologic impairment.[4,5] The most common site of injury to the spine is the thoracolumbar junction where the spine transitions from the more rigid thoracic spine to the more mobile lumbar spine.[6] Injuries to the vertebral bodies tend to occur from compression, flexion, or twisting forces. The posterior elements are usually damaged by direct trauma. Most injuries occur as a consequence of hyperflexion since the predominant natural force of the spine is that of flexion.[1,2,7] Osteoporosis is a skeletal disease characterized by compromise in bone strength predisposing an individual to fracture. Two types of osteoporosis have

been described (Table 25.1).[9] Osteoporosis is the main cause of vertebral compression fractures. Secondary causes of osteoporosis must be excluded before diagnosing a patient with primary, idiopathic, or iatrogenic osteoporosis. Secondary causes of osteoporosis include Paget’s disease, malabsorption syndrome, hyperparathyroidism, multiple myeloma, hyperthyroidism, prolonged corticosteroid therapy, and osteomalacia hypogonadism.[10] Osteoporosis is manifested by reduction in bone mass per unit volume. Normal individuals have a bone mineral density (BMD) of one standard deviation (SD) from the mean of young adults.

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Chapter 25: A patient with a lumbar compression fracture

In osteopenia BMD is between 1 and 2.5 SDs below the mean of the young adult population. In osteoporosis BMD is more than 2.5 SDs from the young adult mean.[11] There is a direct association between each Table 25.1 Osteoporosis clinical manifestation

Type 1

Type 2

Age

51–75

> 70

Sex ratio (F:M)

6:1

2:1

Type of bone loss

Trabecular

Cortical

Rate of bone loss

Accelerated

Not accelerated

Fracture site

Vertebrae (crush) and Colles’ fractures

Vertebral (multiple wedge), pelvic, proximal tibia, and proximal humerus

PTH function

Decreased

Increased

Calcium deficiency

Absent

Present

Metabolism of 25-OH-D to 1, 25(OH)2D

Secondary decrease

Primary decrease

Main causes

Estrogen deficiency, low calcium intake, low weight-bearing routine, cigarette smoking, excessive alcohol intake

Low calcium intake, no estrogen deficiency

SD decrease in bone mineral density and rate of bone turnover and the risk of fracture. Bone strength is based on bone density, turnover, size, area, microarchitecture, and degree of mineralization. The vertebral body is composed of hard cortical bone on the outside and less dense, cancellous trabecular bone inside. The inner, trabecular bone is sensitive to high bone turnover. Trabecular bone is largely responsible for axial and extra-axial stress. With osteoporosis, as trabecular bone density decreases structural strength is lost. Rapid bone turnover leads to an imbalance in bone renewal and to loss of connectivity within the trabeculae to irreversibly weaken the structural integrity of the bone.[12–15]

4. How is vertebral compression fracture diagnosed? The mainstay of diagnosis of vertebral compression fracture is a thorough history and physical examination. Only about one-third of vertebral fractures are diagnosed because patients do not report back pain serious enough to warrant imaging studies.[16–19] Patients often have acute or subacute back pain with no associated provoking event. If the supine position alleviates the pain and standing or walking exacerbates it deep and midline, the pain usually improves with rest even though patients have difficulty sleeping with pain exacerbation on movement.[20–22] A physical examination reveals point tenderness over the area of acute fracture. It may also reveal an increased degree of kyphosis.[23] Kyphosis is an important sign of vertebral compression fracture in the elderly. Figure 25.3. Construction crane analogy as described by Whiteside. The crane falls forward after the cable holding it vertical breaks. Injuries to the spine which compromise the PLC produce this type of motion.[8]

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Chapter 25: A patient with a lumbar compression fracture

Figure 25.4. Lateral plain film of thoracic spine showing severe wedge fracture of T7 body.[28]

A height loss of > 4 cm is associated with kyphosis of 15 degrees.[24] Gait is usually normal. The simplest and the most cost-effective way to confirm diagnosis is a plain radiograph. Vertebral fractures are commonly observed on radiographs obtained for other reasons in patients who may not show signs or symptoms of fracture. Loss of vertebral height (> 4 mm or > 20% compared to baseline), disruption of alignment along anterior and posterior vertebral body lines, facet dislocation, and an increase in interpedicular and interspinous distance (> 7 mm) are indicators of vertebral column disorder on a plain radiograph.[25,26] Plain film does not detect ligamentous injury.[27] MRI is indicated if there is suspicion of vertebral compression fracture. MRI helps detect the age of the

fracture, spinal column compromise, or tumor presence. Acute injuries are identified by a T2 signal because of increased signal intensity from vertebral body edema.[25] A hypointense T1 image also suggests edema.[29] Short tau inversion recovery (STIR) is an MRI image that causes loss of fat signal (bone marrow) from the relaxation properties of fat protons. STIR imaging is the most sensitive modality for visualization of edema and thus of acute fractures.[29,30] Lack of edema on MRI or lack of radiopharmaceutical uptake on a bone scan suggests chronic fracture.[28] MRI is also useful for differentiating osteoporotic fractures from pathologic fractures by showing bone marrow and contrast enhancement in adjacent tissue for pathologic fractures.[28] The “fluid sign” (presence of a fat-fluid level, or lipohemarthrosis) on MRI can be useful to distinguish osteoporosis from malignancy as the cause for pathologic fracture.[31] A CT scan is used if an MRI is contraindicated. CT can be helpful for identifying a fracture not well visualized on plain films. CT can reveal complex fractures, spinal canal narrowing, and compression or a burst fracture. It can also reveal whether the fracture line has extended through the posterior wall of a vertebral body. It cannot detect horizontal fractures of the vertebral body or the pedicles.[20] A nuclear bone scan is also useful. Acute or unhealed fractures will take up the injected 99mTcMDP tracer in higher concentration than does normal bone. It is particularly helpful in a variation of vertebral compression fracture, the sacral insufficiency fractures, which are difficult to identify on plain films. Sacral injury usually appears as an “H” or “butterfly” pattern across the sacrum.[20,28,32]

5. How are vertebral compression fractures treated? Describe a conservative and an interventional treatment The mainstay and gold standard of treatment for vertebral compression fractures is conservative medical management with or without immobility.[33,34] Conservative management includes a short period of bed rest followed by gradual mobilization with external orthoses.[35] A cruciform anterior spinal hyperextension brace is used since these injuries are usually flexion injuries. Older patients require longer bed rest than younger patients since they do not tolerate

185

Chapter 25: A patient with a lumbar compression fracture

Figure 25.5. Sagittal STIR image shows compression deformity of L2 vertebral body.[29]

braces well.[36] Non-steroidal and opiate medications are prescribed with bed rest and orthoses. Most of these medications have unwanted adverse effects including GI ulcers, hemorrhage, somnolence, physical dependence, tolerance, nausea, vomiting, and constipation. Calcitonin when administered subcutaneously, rectally, or intranasally has analgesic properties from increased endorphin levels.[37–40] Most patients have spontaneous resolution of pain even without medications within 4–6 weeks of initial fracture.[34,41,42] Interventional management is the second line of treatment if conservative management has failed. If pain is refractory to oral medications over a 6- to 12-week period or if oral medications or hospital admission for parenteral narcotics is contraindicated,

186

Figure 25.6. T1-weighted image showing acutely fractured T12 and L1 body with hypointense signal compared to chronically fractured L2 body.[28]

intervention is considered.[33,43–46] Given the possible benefit of effective restoration of vertebral height, vertebral augmentation (VBA) procedures may be indicated in fractures < 3 months old.[47,48] Although fractures can heal spontaneously in 4–6 months, they can also cause symptoms beyond this time frame from chronic non-union or avascular necrosis of the vertebral body (Kummel’s disease).[49] In those instances, vertebral augmentation procedures may help the elderly who are completely disabled by severe back pain.

Chapter 25: A patient with a lumbar compression fracture

Figure 25.7. Lack of tracer uptake on bone scan (A) indicating old fracture. Corresponding plain film (B) showing L2 fracture.[28]

Figure 25.8. Bone scan (A) shows tracer uptake at L2. Corresponding plain film (B) shows burst fracture at L2.[28]

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Chapter 25: A patient with a lumbar compression fracture

Not all symptomatic patients are suitable for VBA. Common criteria for consideration are as follows: a. Severe incidental pain with movement, reproducible with vigorous tapping over the affected area b. MRI showing edema visible in T2 and STIR images c. Absence of neurologic compromise The best candidates for VBA are patients with fractures of < 50% collapse. Burst fractures with > 60% loss of height may be difficult to access. They may be treated better medically because of the risk of cement leak, embolus, or nerve injury. If medical treatment is ineffective or quality of life rapidly deteriorates, VBA may be considered only after detailed explanation of risks and benefits to the patient and the family.[50–52] There are several surgical options for the management of painful osteoporotic fractures. VBA through minimally invasive techniques such as kyphoplasty and percutaneous vertebroplasty (VP) are among the most popular. Percutaneous vertebroplasty has been performed in the USA since the 1990s. Polymethylmethacrylate (PMMA) is injected into the fractured vertebral body with unipedical or bipedical needles. Most patients report reduced pain and pain-related morbidity with this procedure. Almost half of patients have complete resolution of symptoms.[53–55] Women and patients < 75 years appear to experience the most benefit. The best results have been obtained in fractures < 6 months old. The main objective of VP is not height restoration but stabilization of the fracture and prevention of any further collapse.[26,55,56] The advantages of VP include low cost, a short procedure, and stabilization of the vertebral body. Disadvantages include cement extravasation in more than one-third of patients, limited correction of lost vertebral body height and failure to correct sagittal imbalance.[57] Balloon kyphoplasty, introduced in 1998, is another option for treatment of stable compression fracture. In this procedure a needle with an inflatable vertebral balloon is inserted into the fractured vertebra. The inflated balloon creates a cavity and reexpands the compressed vertebra which is then filled with a thick PMMA mixture under low pressure with a unipedical or bipedical needle.[58] Kyphoplasty may restore height and improve kyphosis.[53,54,59]

188

Kyphoplasty usually works best with acute fractures of < 3 months.[26,47,48] The advantages of kyphoplasty are low cement extravasation, restored vertebral body height, corrected sagittal imbalance, and low complication rate. Disadvantages include increased cost and procedure time, the need for general anesthesia, and an overnight hospital stay.[57] Complications of all VBA procedures include cement leak (41% for vertebroplasty vs. 9% for kyphoplasty), radiculopathy, infection, cord compression, cement embolism, bleeding, hematoma, and neurologic deficit. Cement can leak into the epidural space, blood stream, and surrounding muscles producing a toxic reaction. Delayed complications include fracture at other vertebral levels.[26,54,57,60,61] VBA procedures are contraindicated with active site infection, uncorrectable coagulopathy, young age, pain unrelated to fracture, solid tissue or osteoblastic tumor, spinal instability, pregnancy, myelopathy, burst fractures, fractured pedicles, bone fragment retropulsion, or allergy to PMMA cement or contrast agent.[57] The most common injectable bone cement used in all VBA procedures is PMMA. It reinforces and hardens the fractured vertebral body. In VP a fluid PMMA with a longer liquid phase is injected under high pressure. In balloon kyphoplasty partially cured, “doughy” cement with a shorter liquid phase is injected under lower pressure to fill the cavity left in place by the “tamp” balloon. Cement can be ready for injection in as little as 5 minutes (in partially cured products) to 20 minutes. The polymerization time is increased by refrigerating the product or placing the syringe in a surgical glove filled with ice. All the cement injectable materials contain barium sulfate in various concentrations for direct visualization of the product during injection.[62–65] PMMA is a bioinert material considered ideal for reinforcing frail bone. It does not, however, remodel or biologically integrate into the surrounding bone. It results in a high polymerization temperature of up to 70°C in the center of the vertebrae during cement setting producing discomfort for patients and potential monomer toxicity. PMMA within the fractured bone may increase stiffness of the vertebrae to 174% of baseline, thus predisposing adjacent vertebrae to early post-procedure fractures within 3 months to 1 year. In osteoporotic fractures treated with VBA procedures, other vertebrae fractured in up to 28% of

Chapter 25: A patient with a lumbar compression fracture

patients after VP and up to 33% after balloon kyphoplasty, higher than the 19% incidence reported in the general osteoporotic population. Since 66% of the new fractures after VBA were adjacent to cemented vertebrae, special attention should be paid to the amount of the cement placed within the vertebrae. It is recommended that no more than 4–6 cc per vertebral body and no more than six vertebrae be treated per session (or a maximum of 25 cc cement injected). The most feared complication of PMMA injection is leakage of the material into the nearby structures, entrapping nerve roots and compressing of the spinal cord. Liquid PMMA can cause pulmonary emboli. Cement leakage after VP was 41% and after balloon kyphoplasty, 9%. PMMA can be highly arrythmogenic and cardiotoxic if taken up in the systemic circulation with an estimate of a fatality risk of 1 in 3000–5000 hip arthroplasty surgeries. Assuming similar risk with the VBA procedures, cement use limits should apply. In view of increased morbidity or mortality risk with PMMA vascular uptake, it is currently advisable to limit the amount of cement placed in the vertebral body to a maximum of 6 ml per vertebrae with a maximum of two vertebrae (or 12 ml cement total) treated per surgical intervention.[66,67] Patients undergoing VBA procedures are usually frail. Care is taken in positioning the patient for the procedure, and neurologic status is evaluated immediately after the procedure.[68–71] There is no consensus on the type of anesthesia to be used for the VBA procedures. The number of vertebrae to be treated and the associated patient comorbidities affect the decision. Active distention with the balloon in kyphoplasty can be painful, and general anesthesia may be an option; however, if the number of vertebrae treated exceeds 3, a long operating time in an uncomfortable position may make general anesthesia preferable. Patient comorbidities and age favor local anesthesia and conscious sedation. In patients with advanced COPD and CO2 retention, a deep sedation can aggravate respiratory depression, worsen oxygenation, and increase the right ventricular afterload because of hypercapnia and pulmonary vasoconstriction. Therefore, regional anesthesia can be used for these cases. Using neuraxial short-acting local anesthetic agents and small doses of neuraxial opioids, the VBA can be performed with light systemic sedation and maximum patient comfort.[72–75] Two fluoroscopic image intensifiers are used for anteroposterior and lateral monitoring. If one

fluoroscopic machine is used, it must be adjusted between the two views, lengthening the operative time. Perfect alignment and squared vertebral body in both anteroposterior and lateral positions is ideal for easy pass of working cannulas within the vertebral pedicles. Cement is injected under a direct lateral view and injection is stopped at the least sign of extravasations. “Paste-like” cement has less chance of leakage. Nonetheless, expansion of cement close to the posterior wall can be associated with complications. To prevent PMMA placement close to the posterior wall, introducers are pushed as far forward in the vertebral body as safely possible. Two working cannulas are placed in each vertebral body. Once the desired amount of cement is deposited in the first one, the filler is removed and the original stylet is placed within the working cannula to prevent tracking the cement toward the posterior vertebral wall or in the pedicle. Evaluation of the effect of the VBA takes place within 30 min–1 hour after cementing. Patients report significant pain relief immediately upon hardening of the cement. This procedure is performed in an ambulatory care center, and the patients are routinely discharged home on the same day.[76–78] Response to treatment of osteoporotic fracture is better than to treatment of metastatic disease (75–95% improvement in osteoporosis vs. 56–85% in neoplastic vertebral collapse). With meticulous technique, careful selection of patients, a controlled OR procedure, and frequent post-procedure followup excellent patient outcomes are possible.

6. What is the controversy surrounding vertebral augmentation? Vertebral augmentation is a common procedure now given the rapidity of clinical response and low procedural risk. Yet there has been debate about its utility and societal cost-effectiveness. Some clinicians have described prophylactic vertebroplasty.[61] There is no consensus about when to use VP or balloon kyphoplasty. When 69 peer-reviewed reports of clinical trials of VP and balloon kyphoplasty were studied, pain relief was similar (87% and 92% for VP and balloon kyphoplasty, respectively), and pain scores were comparable (8.2 to 3 for VP and 7.2 to 3.4 for balloon kyphoplasty).[79] Two multicenter, randomized, double-blind placebo-controlled trials have assessed the effectiveness

189

Chapter 25: A patient with a lumbar compression fracture

Figure 25.9. Lumbar kyphoplasty-balloon insufflations – lateral fluoroscopy view. From personal files of Rinoo V. Shah, MD, MBA.

Figure 25.11. Lumbar kyphoplasty-PMMA cement – anteroposterior view. From personal files of Rinoo V. Shah, MD, MBA.

of VP in the treatment of painful osteoporotic compression fractures.[41,80] Both studies had a similar number of patients in both arms, and pain was lessened after VP. Both studies concluded that the VP groups did not show a statistical advantage over

190

Figure 25.10. Lumbar kyphoplasty-PMMA cement – lateral fluoroscopy view; note small cement tail in pedicle-not a complication. From personal files of Rinoo V. Shah, MD, MBA.

Figure 25.12. Vertebroplasty–primary bone tumor. From personal files of Rinoo V. Shah, MD, MBA. 70f with recurrent chondrosarcoma. Bone scan increased activity T8, T9 and CT scan increased radiopacity with some trabecular infiltration of T8 and T9.

the placebo group. These results have stimulated a debate in the medical community. Criticism was mainly about the scientific validity of the trials, possible placebo effect, the high crossover rate between the two arms, and the small sample size.

Chapter 25: A patient with a lumbar compression fracture

Figure 25.13. Staxx kyphoplasty with PEEK wafers. From personal files of Rinoo V. Shah, MD, MBA. Figure 25.14. Staxx kyphoplasty with PEEK wafers and PMMA cement. From personal files of Rinoo V. Shah, MD, MBA.

A randomized controlled trial demonstrated efficacy and safety of kyphoplasty over conventional non-surgical care with improvement in pain and function.[76] Overall, kyphoplasty and vertebroplasty

References 1.

2.

Denis F. The three column spine and its significance in the classification of acute thoracolumbar spinal injuries. Spine. 1983;8(8):817–831. Magerl F, Aebi M, Gertzbein SD, Harms J, Nazarian S. A comprehensive classification of thoracic and lumbar injuries. Eur Spine J. 1994;3(4):184–201.

have a good safety profile with multiple series demonstrating improvement in quality of life, function, and pain control.

osteoporosis: insights afforded by epidemiology. Bone. 1995;17(5): S505–S511. 6.

Patel U, Skingle S, Campbell GA, Crisp AJ, Boyle IT. Clinical profile of acute vertebral compression fractures in osteoporosis. Rheumatology. 1991;30(6): 418–421.

7.

Dennis HH, Tak HH. A review of thoracolumbar spine fracture classifications. J Orthos Trauma. 2011:1–5.

Bohlman HH, Freehafer A, Dejak J. The results of treatment of acute injuries of the upper thoracic spine with paralysis. J Bone Joint Surg Am. 1985;67(3):360–369.

8.

4.

Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359(9319):1761–1767.

Whitesides TE Jr. Traumatic kyphosis of the thoracolumbar spine. Clin Orthop. 1977;128: 78–92.

9.

5.

Riggs BL, Melton LJ III. The worldwide problem of

Riggs BL, Melton LJ III. Involutional osteoporosis. N Engl J Med. 1986;314(26):1676.

3.

10. Kenny AM, Prestwood KM. Osteoporosis: pathogenesis, diagnosis, and treatment in older adults. Rheum Dis Clin N Am 2000;26(3):569–591. 11. WHO Study Group on Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis. Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis (No. 843). Geneva: World Health Organization. 1994. 12. Snyder BD, Piazza S, Edwards WT, Hayes WC. Role of trabecular morphology in the etiology of age-related vertebral fractures. Calcif Tissue Int. 1993;53(1):S14–S22. 13. Preteux F, Bergot C, LavalJeantet AM. Automatic quantification of

191

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vertebral cancellous bone remodeling during aging. Anat Clin. 1985;7(3):203–208. 14. Riggs BL, Melton LJ III, O’Fallon WM. Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone. 1996;18(3):S197–S201. 15. Mosekilde L. Age-related changes in vertebral trabecular bone architecture: assessed by a new method. Bone. 1988;9(4):247–250. 16. Riggs BL, Melton LJ III. The prevention and treatment of osteoporosis. N Engl J Med. 1992;327(9):620–627. 17. Cooper C, Melton LJ III. Vertebral fractures, how large is the silent epidemic? BMJ. 1992;304:793–794. 18. Ross PD. Clinical consequences of vertebral fractures. Am J Med. 1997;103(2):S30–S43. 19. Cooper C, Atkinson EJ, O’Fallon WM, Melton JL. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res. 1992;7(2):221–227. 20. Old JL, Calvert M. Vertebral compression fractures in the elderly. Am Fam Phys. 2004; 69(1):111. 21. Asenjo JF, Rossel F. Vertebroplasty and kyphoplasty: new evidence adds heat to the debate. Curr Opin Anaesthesiol. 2012;25(5):577–583. 22. Hulme PA, Krebs J, Ferguson SJ, Berlemann U. Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine 2006;31(17):1983–2001. 23. Bratton RL. Assessment and management of acute low back pain. Am Fam Phys. 1999; 60(8):2299–2308. 24. Papaioannou A, Watts NB, Kendler DL, et al. Diagnosis and management of vertebral fractures

192

in elderly adults. Am J Med. 2002;113(3):220–228. 25. Alexandru D, So W (2012). Evaluation and management of vertebral compression fractures. The Permanente Journal. 16(4):46. 26. Nevitt MC, Ettinger B, Black DM, et al. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med. 1998;128 (10):793–800. 27. Epstein O, Ludwig S, Gelb D, Poelstra K, O’Brien J. Comparison of computed tomography and plain radiography in assessing traumatic spinal deformity. J Spinal Disord Tech. 2009; 22(3):197–201. 28. Lenchik L, Rogers LF, Delmas PD, Genant H K. Diagnosis of osteoporotic vertebral fractures: importance of recognition and description by radiologists. Am J Roentgen. 2004;183(4):949–958. 29. Long SS, Yablon CM, Eisenberg RL. Bone marrow signal alteration in the spine and sacrum. Am J Roentgen. 2010;195(3):W178– W200. 30. Gelderen WF, Al-Hindawi M, Gale RS, Steward AH, Archibald CG. Significance of short tau inversion recovery magnetic resonance sequence in the management of skeletal injuries. Australas Radiol. 1997;41(1): 13–15. 31. Baur A, Stäbler A, Arbogast S, et al. Acute osteoporotic and neoplastic vertebral compression fractures: fluid sign at MR imaging. Radiology. 2012; 225(3):730–735.

Vertebral Compression Fractures. Reston, Virginia: American College of Radiology. 2010. 34. Rousing R, Andersen MO, Jespersen SM, Thomsen K, Lauritsen J. Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures: three-months follow-up in a clinical randomized study. Spine. 2009;34(13):1349–1354. 35. Gardner MJ, Demetrakopoulos D, Shindle MK, Griffith MH, Lane JM. Osteoporosis and skeletal fractures. HSS. 2006; 2(1):62–69. 36. Truumees E, Hilibrand A, Vaccaro AR. Percutaneous vertebral augmentation. Spine. 2004;4(2):218–229. 37. Lyritis GP, Tsakalakos N, Magiasis B, et al. Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study. Calcif Tissue Int. 1991;49(6):369–372. 38. Pun KK, Chan LW. Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. Clin Ther. 1988;11(2):205–209. 39. Lyritis GP, Ioannidis GV, Karachalios T, Roidis N, Kataxaki E. Analgesic effect of salmon calcitonin suppositories in patients with acute pain due to recent osteoporotic vertebral crush fractures: a prospective double-blind, randomized, placebo-controlled clinical study. Clin J Pain. 1999;15(4):284–289.

32. Gates GF. SPECT bone scanning of the spine. Semin Nucl Med. 1998;28(1):78–94.

40. Laurian L, Oberman Z, Graf E, et al. Calcitonin-induced increase in ACTH, β-endorphin and cortisol secretion. Horm Metab Res. 1986;18(04):268–271.

33. Saad WE, Funaki BS, Ray CE Jr, et al. Expert Panel on Interventional Radiology: ACR Appropriateness Criteria. Radiologic Management of

41. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009;361(6):569–579.

Chapter 25: A patient with a lumbar compression fracture

42. Silverman SL. The clinical consequences of vertebral compression fracture. Bone. 1992;13:S27–S31. 43. Cortet B, Cotton A, Boutry N, et al. Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: osteoporotic vertebral compression fractures. An open prospective study. J Rheumatol. 1999;26(10):2222–2228. 44. Cotten A, Boutry N, Cortet B, et al. Percutaneous vertebroplasty: state of the art. Radiographics. 1998;18(2):311–320. 45. Jensen ME, Dion JE. Percutaneous vertebroplasty in the treatment of osteoporotic compression fractures. Neuroimaging Clin N Am. 2000; 10(3):547–568. 46. Jensen ME, Evans AJ, Mathis JM, et al. Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body compression fractures: technical aspects. Am J Neuroradiol. 1997;18(10):1897–1904. 47. Shen MS, Kim YH. Vertebroplasty and kyphoplasty: treatment techniques for managing osteoporotic vertebral compression fractures. Bulletin NYU Hospital Joint Diseases. 2006;64(3–4):106. 48. Garfin SR, Buckley RA, Ledlie J. Balloon Kyphoplasty Outcomes Group: Balloon kyphoplasty for symptomatic vertebral body compression fractures results in rapid, significant, and sustained improvements in back pain, function, and quality of life for elderly patients. Spine. 2006; 31(19):2213–2220. 49. Van Eenenaam DP, Georges Y. Delayed post-traumatic vertebral collapse (Kummell’s disease): case report with serial radiographs, computed tomographic scans, and bone scans. Spine. 1993; 18(9):1236–1241.

50. Heini PF, Wälchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. Eur Spine J. 2000; 9(5):445–450. 51. Mathis JM, Deramond H, Belkoff SM, eds. Percutaneous Vertebroplasty. New York: Springer. 2002. 52. Lieberman IH, Togawa D, Kayanja MM. Vertebroplasty and kyphoplasty: filler materials. Spine. 2005;5(6):S305–S316. 53. Blattert TR, Jestaedt L, Weckbach A. Suitability of calcium phosphate cement in osteoporotic vertebral body fracture augmentation: a controlled, randomized, clinical trial of balloon kyphoplasty comparing calcium phosphate versus polymethylmethacrylate. Spine. 2009;34(2):108–114. 54. Muto M, Perrotta V, Guarnieri G, et al. Vertebroplasty and kyphoplasty: friends or foes? Radiol Med (Torino). 2008; 113(8):1171–1184. 55. Masala S, Mammucari M, Angelopoulos G, et al. Percutaneous vertebroplasty in the management of vertebral osteoporotic fractures. Shortterm, mid-term and long-term follow-up of 285 patients. Skeletal Radiol. 2009;38(9):863–869. 56. Jha RM, Yoo AJ, Hirsch AE, Growney M, Hirsch JA. Predictors of successful palliation of compression fractures with vertebral augmentation: singlecenter experience of 525 cases. J Vasc Interv Radiol. 2009; 20(6):760–768. 57. Halpin RJ, Bendok BR, Liu JC. Minimally invasive treatments for spinal metastases: vertebroplasty, kyphoplasty, and radiofrequency ablation. J Support Oncol. 2004; 2(4):339–351. 58. Papadopoulos EC, Edobor-Osula F, Gardner MJ, Shindle MK, Lane JM. Unipedicular balloon

kyphoplasty for the treatment of osteoporotic vertebral compression fractures: early results. J Spinal Disord Tech. 2008;21(8):589–596. 59. Carbognin G, Sandri A, Girardi V, et al. Treatment of type-A3 amyelic thoracolumbar fractures (burst fractures) with kyphoplasty: initial experience. Radiol Med. 2009;114(1):133–140. 60. Eskey CJ, Hirsch JA, Manchikanti L. Vertebroplasty and kyphoplasty. In Manchikanti L, Singh V, eds. Interventional Techniques in Chronic Spinal Pain. Paducah, KY: ASIPP Publishing. 2007: pp. 633–652. 61. Kobayashi N, Numaguchi Y, Fuwa S, et al. Prophylactic vertebroplasty: cement injection into non-fractured vertebral bodies during percutaneous vertebroplasty. Acad Radiol. 2009;16(2):136–143. 62. Deramond H, Wright NT, Belkoff SM. Temperature elevation caused by bone cement polymerization during vertebroplasty. Bone. 1999; 25(2):17S–21S. 63. Belkoff SM, Molloy S. Temperature measurement during polymerization of polymethylmethacrylate cement used for vertebroplasty. Spine. 2003;28(14):1555–1559. 64. Webb JCJ, Spencer RF. The role of polymethylmethacrylate bone cement in modern orthopaedic surgery. J Bone Joint Surg Br. 2007;89(7):851–857. 65. Jaeblon T. Polymethylmethacrylate: properties and contemporary uses in orthopaedics. J Am Acad Orthop Surg. 2010;18(5): 297–305. 66. Coventry MB, Beckenbaugh RD, Nolan DR, Ilstrup DM. 2,012 total hip arthroplasties: a study of postoperative course and early complications. J Bone Joint Surg. 1974;56(2):273–284.

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67. Charnley J. Systemic Effects of Monomer. Acrylic Cement in Orthopaedic Surgery. Baltimore: Williams and Wilkins Livingstone. 1970: pp. 72–78. 68. Kasperk C, Grafe IA, Schmitt S, et al. Three-year outcomes after kyphoplasty in patients with osteoporosis with painful vertebral fractures. J Vasc Interv Radiol. 2010;21(5): 701–709. 69. McGirt MJ, Parker SL, Wolinsky JP, et al. Vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: an evidenced-based review of the literature. Spin. 2009;9(6): 501–508. 70. Liu JT, Liao WJ, Tan WC, et al. Balloon kyphoplasty versus vertebroplasty for treatment of osteoporotic vertebral compression fracture: a prospective, comparative, and randomized clinical study. Osteoporos Int. 2010;21(2): 359–364. 71. Pflugmacher R, Taylor R, Agarwal A, et al. Balloon kyphoplasty in the treatment of metastatic disease of the spine: a 2-year prospective

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evaluation. Eur Spine J. 2008; 17(8):1042–1048.

trial. Lancet. 2009;373 (9668):1016–1024.

72. Krueger A, Bliemel C, Zettl R, Ruchholtz S. Management of pulmonary cement embolism after percutaneous vertebroplasty and kyphoplasty: a systematic review of the literature. Eur Spine J. 2009;18(9):1257–1265.

77. Yang HL, Wang GL, Niu GQ, et al. Using MRI to determine painful vertebrae to be treated by kyphoplasty in multiple-level vertebral compression fractures: a prospective study. J Int Med Res. 2008;36(5):1056–1063.

73. Elshaug AG, Garber AM. How CER could pay for itself: insights from vertebral fracture treatments. N Engl J Med. 2011;364(15):1390–1393.

78. Berenson J, Pflugmacher R, Jarzem P, et al. Cancer Patient Fracture Evaluation (CAFE) Investigators. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicenter, randomised controlled trial. Lancet Oncol. 2011;12(3): 225–235.

74. Burton AW, Hamid B. Kyphoplasty and vertebroplasty. Curr Pain Headache Repr. 2008; 12(1):22–27. 75. Schofer MD, Efe T, Timmesfeld N, Kortmann HR, Quante M. Comparison of kyphoplasty and vertebroplasty in the treatment of fresh vertebral compression fractures. Arch Orthop Trauma Surger. 2009;129(10):1391–1399. 76. Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled

79. Hulme PA, Krebs J, Ferguson SJ, Berlemann U. Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine. 2006;31(17):1983–2001. 80. Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med. 2009;361(6): 557–568.

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Sacroiliac joint pain and arthritis Garrett LaSalle and Jianguo Cheng

Case study A 45-year-old female presents with persistent low back and right buttock pain for 13 months. The pain started after a motor vehicle accident, in which her automobile was struck from behind while the patient was stepping on the brake pedal of her car with her right foot. The pain is described as sharp and aching, with the most intense pain being located in the right buttock, and radiation of the pain down the posterolateral aspect of the right lower extremity to the ankle. Straight leg raising test is negative. A trial of oral NSAIDs, duloxetine, and physical therapy for 3 months failed to provide significant improvement. MRI of the lumbosacral spine demonstrated mild multilevel degenerative disc and facet arthropathy without any significant neuroforaminal or central canal stenosis. She has undergone two separate transforaminal epidural steroid injections by a local pain physician (at L5 and subsequently at S1) without significant improvement.

1. What are the differential diagnoses in this patient? The differential diagnosis of this patient includes:  Discogenic pain  Lumbosacral radiculitis  Myofascial pain/trigger points of gluteal musculature  Piriformis syndrome  Sacroiliac joint (SIJ) pathology  Lumbar facet arthropathy SI joint pain accounts for approximately 15–30% patients complaining of axial low back pain.[1] The

clinical history of patients presenting with SI joint pain can be quite diverse. Pain in the SI joint is commonly associated with an inciting event. The inciting events can be classified as a single traumatic event (44%), repetitive injury (21%), or idiopathic (35%).[2] The most common single traumatic events include motor vehicle accidents, falls onto the buttock, pregnancy/parturition, and pelvic fracture. Repetitive injury can be secondary to repeated lifting, running, and altered gait secondary to disorders of the lower extremities. The association of SI joint pain with altered gait deserves special attention. Unbeknownst to the patient, a minor leg length discrepancy, prior lower extremity injury resulting in altered gait, or even a slight lower extremity asymmetry that may be introduced by lower extremity total joint arthroplasties (hip or knee) can lead to altered biomechanics that may ultimately manifest as SI joint arthritis and pain. Low back pain is a very common complaint among pregnant women. One study[3] that followed 855 pregnant women starting at 12 weeks gestation found the 9-month prevalence of all types of back pain to be 49%, with pain localized in the SI joint region in approximately 50% of the patients. In addition, of the three distinct patterns of back pain reported (high back pain above the lumbar region, low back pain, and SI pain), the SI pain pattern was the only pattern associated with increasing intensity as the pregnancy progressed. A major limitation of this study is that the diagnosis of SI joint pain was made solely on the basis of pain location, and not on the basis of provocative physical exam testing or the gold-standard diagnostic test (fluoroscopically guided local anesthetic injection into the SI joint).

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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A class of rheumatologic conditions known as the seronegative spondyloarthropathies is associated with increased risk of SI joint pain. There are usually five distinct entities in this group: ankylosing spondylitis, enteropathic arthritis (arthritis associated with inflammatory bowel disease), psoriatic arthritis, reactive arthritis, and idiopathic/undifferentiated spondyloarthropathy. A key feature of SI joint pain in this population is the inflammatory nature of the pain. This is often manifested as a dull pain with prominent morning stiffness and pain that lasts at least 30 minutes, but often several hours, with gradual improvement as the day progresses. This is in contrast with degenerative SI joint pain, which is often worse at the end of a day of activity. The classic description of inflammatory back pain is: “worse with rest, improved with light activity.” The pain may initially present in the buttocks, but as the systemic inflammatory process progresses the lower lumbar and other areas of the spine may become symptomatic. Additionally, SI joint pain in the spondyloarthropathies usually has an earlier age of onset (usually adolescence or early adulthood). Other features that can signal SI joint pain related to a systemic inflammatory condition include the following: positive family history of SI joint pain, HLA B27 positivity, and loss of spinal and chest wall mobility (evaluated with the modified Schober test and chest wall expansion evaluation).[4] If any of these features are present in the history of a patient with SI joint pain, further evaluation may need to be done. These features may indicate an underlying inflammatory systemic condition that requires, not simply pain management, but also prompt rheumatologic evaluation and systemic treatment.

Another group of patients at increased risk for SI joint pathology/pain include those with prior lumbar or lumbosacral fusion. Studies have shown increased rates of degenerative disease that occur following spinal fusion in those spinal segments adjacent to the fused segments. This likely results, at least partially, from altered biomechanics at those segments above and below the fusion mass. The SI joint constitutes an essential articulation within the spine axis and, thus can functionally be classified as a spinal segment, subject to the same biomechanical and degenerative processes that affect other spinal segments after fusion.[5]

2. What are the referred pain patterns that are important in the differential diagnosis? Patients with SI joint pain tend to present with variable pain distribution patterns that are not confined to the anatomic region of the SI joint (Figure 26.1). A retrospective study[6] evaluated the pain referral patterns of 50 patients with injection-confirmed SI joint pain. The vast majority of patients (> 90%) reported buttock pain, with a large majority (72%) reporting lower lumbar pain. Half of all patients had some form of lower extremity pain, with more than 50% reporting pain radiating distal to the knee and 12% reporting pain as far distal as the foot. This finding suggests that not all low back pain with radiation to the lower extremity (even as far distally as the foot) is secondary to lumbosacral radiculitis. The SI joint innervation is very complex and variable between patients, resulting in multiple, complex referral zones. In addition, there are a large number of structures intimately associated with the SI joint that Figure 26.1 Sacroiliac joint injection. From personal files of Rinoo V. Shah, MD, MBA.

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can be affected by inflammatory or structural pathology, including the piriformis muscle, sciatic nerve, and lumbosacral spinal nerves. Even though the SI joint is a paramedian structure, axial lower lumbar pain is common. It often responds to unilateral SI joint injection. While the majority of pain referral patterns included the low back, buttocks, and lower extremities (as would be expected), atypical pain referral patterns do occur, such as referred pain in the groin and abdomen.

3. What anatomic considerations help to explain the variable presentation of SI joint pain? The sacroiliac joint is the articulating surface between the sacrum and the iliac bones, thus providing the functional unit connecting the spine to the lower extremities. The SI joint is classified as a true diarthroidial joint–with opposing articular surfaces separated by a synovial fluid-filled space and covered by a fibrous capsule. Despite this general characteristic, the SI joint has several unique features. It has a large surface area covered with both hyaline cartilage and fibrocartilage and it has much less mobility among its surfaces (most of the motion at this joint is not perceived during the majority of physiologic activities). Unlike most joints that have smooth articulating surfaces such as the knee or hip, the lateral surface of the sacrum is characterized by multiple elevations and depressions that articulate with complementary depressions and elevations on the medial surface of the iliac bones, thus providing a loose, multiplyrepeated interlocking contact surface which serves to significantly reduce the mobility of the joint.[7] The innervation of the sacroiliac joint is complex and variable. The posterior innervation of the SI joint most commonly arises from the dorsal ramus of L5 and the lateral branches of the dorsal rami of S1-S3, with contributions in some patients from the L4 medial branch and S4 lateral branch.[1] The ventral innervation of the joint appears to arise from the ventral rami of L5-S2 with some potential contributions from L4. The clinical finding that the SI joint is a source of pain in many patients is supported by histologic examination of joint structures and surrounding tissues. Positive immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P has been identified

in both iliac and sacral cartilage and adjacent ligamentous structures.[8]

4. What are the physical exam findings that would suggest SI joint pain? In addition to history, physical examination findings may suggest the SI joint as a pain generator. However, no historical or physical examination findings are either sufficiently sensitive or specific for SI joint pain. As a result, a combination of several tests have commonly been used to increase sensitivity and specificity. The majority of the tests are used to reproduce the pain complaints in patients suffering from SI joint pathology (provocation tests). Five of the most commonly used tests are listed below. How these tests are performed is demonstrated in one of several education videos[9] (the authors have no financial connection to this video). A provocation test is considered positive if the test reproduces the patient’s original pain complaint. 1. Thigh thrust test: The patient lies supine with the hip and knee of the affected side both flexed to approximately 90°. The unaffected hemipelvis is stabilized as dorsal pressure is applied along the axis of the femur of the affected side. 2. Compression test: The patient is placed in a lateral decubitus position with the affected side up, the hips flexed at approximately 45°, the knees flexed at approximately 90°, and a pillow placed between the knees. The examiner exerts medial (downward) pressure over the anterior portion of the iliac crest on the affected side. 3. Distraction test: The patient lies supine with a pillow under the knees and one arm placed under their lumbar spine. The examiner stands at the patient’s side and uses a crossed arm technique to apply dorso-lateral pressure in a sustained manner to the bilateral anterior superior iliac spines. 4. Gaenslen test: The patient lies supine at the edge of the examination table in a position such that the lower extremity of the affected side is allowed to drop toward the floor in an extension motion past the horizontal plane of the examination table. The contralateral (unaffected) hip is flexed maximally with the patient actively pulling that knee toward the chest. The examiner exerts downward/dorsal pressure on the anterior aspects of bilateral knees in an attempt to facilitate a rotation motion.

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5. Patrick test (FABER test): The patient lies supine. The femur on the affected side is flexed, abducted, and externally rotated (FABER) so as to place the lateral malleolus on the anterior aspect of the contralateral knee. The unaffected hemipelvis is stabilized at the anterior superior iliac spine and dorsal (downward) pressure is applied to the knee of the affected side. Each of these tests in isolation has very poor sensitivity and specificity for diagnosing SI joint pain. However, when several of these tests are positive in the same patient, sensitivity and specificity increase significantly.[10] A combination of three or more positive tests was found to have high sensitivity and specificity (85% and 79%, respectively) as well as high positive and negative predictive values (77% and 87%, respectively) for injection-confirmed SI joint pain. Therefore, multiple provocation tests need to be positive in a single patient in order to have a high suspicion of pain emanating from the SI joint complex. In addition, unilateral pain and worsening symptoms when arising from a sitting position are also contributory.

5. Does imaging play a large role in the diagnostic work-up of this patient? The specificity of imaging findings has traditionally been poor for SI joint pain. Imaging is typically used in an attempt to rule out other types of pathology when the diagnosis is in question.[11] CT imaging of painful SI joints was found to be only 57.5% sensitive and 69% specific.[12] Radionuclide bone scan with Tc-99m only has 12.9% specificity and 100% sensitivity for SI joint pain.[13] MRI appears to be more beneficial in evaluating patients with SI joint pain and concurrent spondyloarthropathy, but does not have good test characteristics for degenerative conditions. Thus, imaging has limited value in the diagnosis of SI joint pathology and pain.

6. How is the diagnosis of SI joint pain made? While the history and physical examination may suggest the SI joint as a primary pain generator, a diagnosis should not be based solely on these findings. The currently accepted gold standard for diagnosis of SI joint pain is a positive response to local anesthetic

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instillation within the SI joint.[2] Many practitioners advocate a double block paradigm (improvement of pain after each of two separate blocks) because a single intra-articular SI joint injection has a high false-positive rate, which is arbitrarily defined as > 50% pain relief following the first injection but with lack of pain relief following a second (confirmatory) SI joint injection.[1] However, a false-negative SI joint “confirmatory” block is also possible secondary to technical or patient factors. The response to SI joint injections is often used to predict success with sacral lateral branch radiofrequency ablation (RFA). The reliability of this approach is an area of active research.[14]

7. What are the conservative management options in patients with SI joint pain? A trial of conservative management is usually appropriate in most patients. Topical therapy such as lidocaine or NSAIDs can be attempted. Some patients may respond to a TENS unit applied to the painful region. Oral non-opioid analgesics such as NSAIDs and other adjuvant therapies, such as duloxetine and pregabalin, can be considered, as in other chronic musculoskeletal complaints. Physical therapy and manipulative therapy can have significant positive impact with low risk. Attempts to restore proper body mechanics with gluteal, abdominal, and lower extremity strengthening/therapy are often employed. SI joint belts can be used in patients with muscle weakness and pain in order to provide compression, which can improve proprioceptive feedback to gluteal musculature.[15] In those with mild or moderate pain, the belt can be worn only with activity; however, those with severe pain/weakness frequently note improvement with more regular use, even during sedentary activities. Orthotics and shoe modifications such as shoe lifts can be used in an attempt to compensate for lower extremity pathology resulting in altered biomechanics.

8. When considering SI joint injection, what factors should be kept in mind? Many practitioners have advocated the use of contrast injection into the SI joint prior to local

Chapter 26: Sacroiliac joint pain and arthritis

anesthetic injection, in order to obtain an arthrogram under fluoroscopy and verify needle placement into the SI joint. However, considering the fact that both the intra-articular and extra-articular structures of the SI joint such as the capsules and ligaments are innervated by nociceptive fibers, it is conceivable that blocking all these structures would lead to better pain reduction. Elderly patients tend to have pain originating from bilateral SI joints within the SI joint itself (intra-articular pathology such as degenerative arthritic changes). In contrast, young people often have unilateral SI joint pain arising from the periarticular structures such as the muscles, fascia, and ligaments.[1] It is conceivable that the entity “sacroiliac joint pain” is, in reality, a spectrum of disorders: including (at one end of the spectrum) those pain states arising from within the SI joint, those arising from structures outside the joint proper, and those arising from both of these structures. All states result in pain complaints that localize to the SI joint region but likely respond differently to interventional therapies. The differential response of structures within the SI complex was elegantly demonstrated in a double-blind, randomized, placebo-controlled fashion.[16] In this study, 70% of normal subjects were found to have anesthesia of posterior extraarticular structures (interosseous ligament and dorsal sacroiliac ligament) upon L5 dorsal ramus and sacral lateral branch (S1-S3) local anesthetic infiltration in a multi-site and multi-depth technique. However, it was found that 86% of these patients (with excellent posterior SI complex/ extra-articular anesthesia) did not have anesthesia to capsular distention. This finding seems to indicate that extra-articular/posterior SI complex anesthesia is not synonymous with intra-articular anesthesia and that the SI joint is not solely innervated by the sacral dorsal rami. It appears that intra-articular pathology is well-addressed with intra-articular injections, but is not well-addressed with sacral lateral branch blockade. These two diagnostic procedures may be complementary and be used in conjunction with each other to diagnose pain arising from the two separate regions of the SI joint complex. The optimal volume of intraarticular injection is unknown. Rupture of the capsule due to injection of a large volume is a concern. A total volume of 2–4 ml is commonly used in clinical practice.[7,15]

9. Is there a long-term therapeutic solution to SI joint pain? A patient is usually diagnosed as having SI joint pain based on history, physical exam, and one or more diagnostic intra-articular SI joint injections. Once a diagnosis of SI joint pain is made, a more long-term treatment is usually sought. For those who do not have long-lasting pain relief after SI joint steroid injection, RFA is usually employed. The current RFA treatment of chronic SI joint pain targets only the lateral branches of the S1–3 sacral dorsal rami and L4 medial branch/L5 dorsal ramus. This approach is not able to access ventral neural structures, and thus leaves some intra-articular structures untreated. In traditional thermal RFA (tRFA), the region of significant heating surrounding the active tip of a traditional RFA needle is confined to a small area around the active tip of the probe. Because of the complexity and wide variability of the lateral branches, this approach may lead to partial denervation of the SI joint. In an attempt to increase the size of the lesion and modify the geometry of the lesions, two other forms of RFA have been developed, cooled RFA (cRFA) and bipolar RFA (bRFA). Cooled RFA is introduced to create larger lesions lateral to the sacral foramen in hope to denervate as many sub-branches of the lateral branches to overcome the anatomical variations. This technique uses an RF probe that is internally cooled with water/ saline. This cooling prevents tissues surrounding the RF probe from reaching temperatures sufficient to result in tissue charring that may impede further heat conductance from the RF probe tip. When this is avoided, greater energy is transmitted to tissue sites distant to the RF probe tip and larger lesion is created. cRFA is theoretically more amenable to neural ablation. More recently, a bipolar RFA approach has been introduced. It is a modification of the tRFA method.[18] Instead of using a grounding electrode the electric circuitry is completed between two adjacent RFA probes. The probes are placed in close proximity to each other at about 1 cm intervals. Using this method, a “strip lesion” can be created between two such bipolar RFA needles. In a chain of such “strip lesions” barricading the neural foramen and the SI joint, the neural tissue is ablated and a more complete denervation of the SI joint may be achieved.

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Pulsed RF treatment is a further modification and the electrical current is delivered over very short time frames, with intervening periods of no energy delivery. This pulsed delivery of energy allows for tissues to dissipate heat in between the delivery periods, thus leading to lower maximum temperatures.[17] In fact the temperatures are low enough that neuronal destruction is prevented. The exact mechanisms by which pulsed RF treatment appears to exert its effects are unclear, but may involve the alteration of nociceptive transmission without the destruction of the neural structure.[1] Pulsed RF treatment has been evaluated in a small prospective case series.[17] This study demonstrated a statistically significant improvement in VAS scores in 73% of patients who underwent pulsed RF of the medial branch of L4, dorsal ramus of L5, and S1 and S2 lateral branches. The mean duration of pain relief was 20 weeks which is comparable to the outcomes of tRFA and cRFA. Comparative outcomes of these various modalities of treatment is an active area of research.

 SI joint pain is likely to result from either a single inciting event (motor vehicle accident, fall onto the buttock, parturition, etc.) or repetitive inciting events (running, repetitive lifting, lower extremity pathology altering the biomechanics of ambulation, etc.).  Pain emanating from the SI joint can have variable radiation patterns, with a large

1.

2.

3.

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Cohen SP, Chen Y, Neufeld NJ. Sacroiliac joint pain: a comprehensive review of epidemiology, diagnosis and treatment. Expert Rev Neurother. 2013;13(1):99–116. Chou LH, Slipman CW, Bhagia SM, et al. Inciting events initiating injection-proven sacroiliac joint syndrome. Pain Med. 2004; 5(1):26–32. Ostgaard HC, Andersson GBJ, Karlsson K. Prevalence of back pain in pregnancy. Spine. 1991; 16(5):549–552.





Key points

References





proportion of patients experiencing pain in the lower extremities, as far distal as the foot. Not all low back pain that radiates to the distal lower extremities is related to lumbosacral radiculitis. Single physical examination/provocation tests for SI joint pain are unreliable, but when three or more of these tests are positive in the same patient, probability of SI joint pathology is greatly increased. Multiple structures of the SI joint complex can result in clinical symptoms of pain. These include intra-articular structures (degenerative arthritis, and inflammatory conditions) as well as extra-articular structures (ligaments, muscles, etc.). It appears that intra-articular injections address intra-articular pathology while targeting the sacral lateral branches, in addition to L5 dorsal ramus and maybe L4 medial branch, addresses a broader pathology of the SI joint. There is no universally accepted method of long-term pain control in chronic SI joint pain. Radiofrequency denervation of the SI joint has emerged as one of the best options. There are multiple types of RF treatment. Comparative outcomes of these modalities remain to be determined. The optimal treatment for chronic SI joint pain involves a multidisciplinary, personalized approach.

4.

Lianne G. Clinical features of ankylosing spondylitis. In Hochberg M, Silman A, Smolen J, Weinblatt M, Weismann M, eds. Rheumatology. Philadelphia, PA: Elsevier. 2011: pp. 1129–1133.

5.

Kee-Yong H, Jun-Seok L, Ki-Won K. Degeneration of sacroiliac joint after instrumented lumbar or lumbosacral fusion. Spine. 2008;33(11):1192–1198.

6.

Slipman CW, Jackson HB, Lipetz JS, et al. Sacroiliac joint pain referral zones. Arch Phys Med Rehabil. 2000;81:334–338.

7.

Forst SL, Wheeler MT, Fortin JD, Vilensky JA. The sacroiliac joint: anatomy, physiology and clinical significance. Pain Physician. 2006;9:61–68.

8.

Szadek KM, Hoogland PVJM, Zuurmond WWA, De Lange JJ, Perez RSGM. Possible nociceptive structures in the sacroiliac joint cartilage: an immunohistochemical study. Clin Anat. 2010;23(2): 192–198.

9.

Mazza, B. Diagnosing SI joint disorders: provocative testing. YouTube® video 2011;6:50.

Chapter 26: Sacroiliac joint pain and arthritis

http://www.youtube.com/watch? v=ukDJ_OxOuBY. 10. van der Wurff P, Buijs EJ, Groen GJ. A multitest regimen of pain provocation tests as an aid to reduce unnecessary minimally invasive sacroiliac joint procedures. Arch Phys Med Rehabil. 2006;87:10–14. 11. Vanelderen P, Szadek K, Cohen SP, et al. Sacroiliac joint pain. Pain Practice. 2010;10(5): 470–478. 12. Elgafy H, Semaan HB, Ebraheim NA, Coombs RJ. Computed tomography findings in patients with sacroiliac pain. Clin Orthop Relat Res. 2001;382:112–118. 13. Slipman CW, Sterenfeld EB, Chou LH, Herzog R, Vresilovic E. The value of radionuclide imaging in the diagnosis of sacroiliac joint syndrome. Spine. 1996;21 (19):2251–2254. 14. Cohen SP, Strassels SA, Kurihara C, et al. Outcome predictors for

sacroiliac joint (lateral branch) radiofrequency denervation. Reg Anesth Pain Med. 2009;34: 206–214.

Uncited References 1.

15. Prather H, Hunt D. Conservative management of low back pain, part I. Sacroiliac joint pain. Dis Mon. 2004;50(12):670–683.

Fortin, JD, Washington WJ, Falco FJE. Three pathways between the sacroiliac joint and neural structures. Am J Neuroradiol. 1999;20:1429–1434.

2.

16. Dreyfuss P, Henning T, Malladi N, Goldstein B, Bogduk N. The ability of multi-site, multi-depth sacral lateral branch blocks to anesthetize the sacroiliac joint complex. Pain Med. 2009; 10(4):679–688.

Cheng J, Pope JE, Dalton JE, Cheng O, Bensitel A. Comparative outcomes of cooled versus traditional radiofrequency ablation of the lateral branches for sacroiliac joint pain. Clin J Pain. 2013;29:132–137.

3

Hagiwara S, Iwasaka H, Takeshima N, Noguchi T. Mechanisms of analgesic action of pulsed radiofrequency on the adjuvant-induced pain in the rat: roles of descending adrenergic and serotonergic systems. Eur J Pain. 2009;13(3):249–252.

4.

Srejic U, Calvillo O, Kabakibou K. Viscosupplementation: a new concept in the treatment of sacroiliac joint syndrome: a preliminary report of four cases. Reg Anesth Pain Med. 1999;24(1):84–88.

17. Vallejo R, Benyamin RM, Kramer J, Stanton G, Joseph NJ. Pulsed radiofrequency denervation for the treatment of sacroiliac joint syndrome. Pain Med. 2006; 7(5):429–434. 18. Cosman ER Jr, Gonzalez CD. Bipolar radiofrequency lesion geometry: implications for palisade treatment of sacroiliac joint pain. Pain Pract. 2011; 11(1):3–22.

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Spinal Disorders

Sacral insufficiency fracture and treatment options Rinoo V. Shah

Case study A 83-year-old lady slipped on black ice and fell. She developed severe pain in the buttock area and could not get up. She was transferred to the hospital for treatment.

1. What is the differential diagnosis? a. b. c. d. e. f.

Vertebral compression fracture Sacroiliac joint pain Inflammatory sacroiliitis Sacral insufficiency fracture Stress fracture Hip fracture

Sacral insufficiency fracture (SIF) was described by Lourie as “spontaneous osteoporotic fracture of the sacrum.” This is essentially a “stress fracture” of the sacrum in patients with osteoporosis. Postmenopausal women with osteoporosis are the most likely to be affected. Although this can develop with trauma, many patients report a negligible pro-dromal injury or no injury whatsoever. The mean age afflicted is 71–81 years old. In a meta-analysis conducted by Finiels et al the typical patient was over 60 years old and twothirds reported no trauma.

2. What risk factors predispose patients to develop sacral insufficiency fractures? a. b. c. d.

Osteoporosis to osteopenia continuum Rheumatoid arthritis Local pelvic irradiation Corticosteroid use

e. Less common conditions: i. ii. iii. iv.

Hyperparathyroidism Lumbar fusion Paget’s disease Pregnancy (stress fracture versus sacral insufficiency fracture) v. Eating disorders (stress fracture versus sacral insufficiency fracture)

3. Why is this condition overlooked? SIFs are overlooked. There is a low background incidence ranging from 0.14% to 2%. The higher rates were reported in a spine specialty clinic that is dedicated to the diagnostic evaluation of spinal pathology. With advanced imaging options and increased awareness of SIFs, reporting has increased over the past few decades. In Finland, the prevalence of SIFs increased between 1970 and 2012 in patients over 60. Nonetheless, SIFs are still missed due to a lack of knowledge by practitioners, prevalence of other spinal pathologies in the elderly, and the low fidelity of radiographs for detecting SIFs.

4. Describe the anatomy and pathophysiology of a SIF The sacrum looks like a curved spade. It is convex posteriorly and concave anteriorly. The sacrum is composed of a body, sacral ala, rudimentary fused articular processes, superior sacral facets (articulates with inferior articular processes of L5), central spinal canal, sacral foramina (dorsal and ventral), median sacral crest (roof of sacral canal), lateral auricular surface (articulates with ilium to create sacroiliac joint), sacral cornua, and sacral hiatus.

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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The Denis classification for traumatic sacral fractures is useful for sacral insufficiency fractures. There are three vertical zones separated by imaginary lines. Zone 1 is lateral to the sacral foramina and extends to the lateral auricular surface. This zone is roughly parallel to the sacroiliac joint. Neurologic symptoms are rare when traumatic fractures occur in this zone. SIFs most commonly occur in Zone 1. Zone 2 is the foraminal zone. Traumatic injuries typically cause radiculopathy. SIFs however primarily affect the bone margins and spare the exiting nerve roots. Zone 3 is defined by the median sacral crest, the sacral canal, and body. Zone 3 traumatic injuries are typically horizontal and may cause cauda equina syndrome. However, SIFs in this region rarely cause cauda equina syndrome. SIFs occur because of normal daily stress and forces transmitted toward weakened bone. Normal axial stresses are transferred from the spine. These pass through the sacrum en route through the lower limbs. The sacrum however has reduced mineralization, reduced elastic resistance, and reduced trabecular bone density. Since compressive strength is proportional to density squared, osteoporosis significantly reduces compressive strength. The ventral corpus or sacral body is better able to withstand forces, as compared to the ala. Furthermore, degenerative disc disease reduces the capacity of the spine to withstand axial forces and transfers forces to the sacrum. Pelvic ring failure results in increased instability and stress across the sacroiliac joints. Repetitive cyclical loading leads to a fracture and regular movement contributes to a persistent nonunion.

5. How do you diagnose a SIF? The pain could be acute as in the above described patient. Other patients may present with insidious, intractable pain radiating to the lower back, buttocks, and pelvis. Pain could refer to the legs and groin. Patients may have significant ambulatory and functional limitations. Sometimes, they are confined to the bed. Pain worsens with weight bearing and improves with rest. There may be tenderness to palpation at the SIJ. SIJ provocation tests may be positive (see Chapter 26), e.g., Patrick test: the hip is flexed, abducted, and externally rotated. Gait is antalgic and apprehensive. Patients may feel they need to hang onto the walls or a walker to move. Neurologic assessment may

be normal. The straight leg raise may be negative for radicular pain but passive movement of the limb may reproduce pain. Laboratory studies are usually not helpful. The alkaline phosphatase may be slightly elevated. However, laboratory studies may be helpful in assessing the etiology of secondary causes of osteoporosis. Radiographs have low fidelity for SIFs. Chronic SIFs may show sclerotic bands. Advanced imaging studies play an important role in diagnosing SIFs. Bone scintigraphy with technetium 99 is very sensitive for acute fractures. An SIF could be diagnosed within 48–72 hours of an injury. The classic H or “Honda” sign may be present in 43% of patients. False-negatives may appear because of uptake in the SIJ due to sacroiliitis or osteoarthritis. False positives occur in the presence of sacral metastases. Hence, false positives are still useful. Magnetic resonance imaging provides detailed anatomic and physiologic information. This test is very sensitive but, again, not specific, i.e., low falsenegative rate but high false-positive rate. Again, false positives may be sacral metastases. The SIF appears as low signal on T1-weighted images, high on T2-weighting, and high on STIR sequences. The latter is particularly useful for detecting bone edema or fractures. The CT scan may be used in patients with contraindications to MRI, e.g., pacemaker implants. The CT scan is also useful for percutaneous cement augmentation procedures, such as sacral kyphoplasty. Bone detail is excellent with sclerotic healing indicating a healing fracture. Fracture lines indicate a recent fracture. Multiplanar reformatting enables 3-dimensional rendering of the fracture. This level of detail is important for percutaneous sacral kyphoplasty.

6. Is there any other diagnostic testing that should be done? A sacral insufficiency fracture, along with vertebral compression fractures, is a fragility fracture. Some consider these pathognomonic for osteoporosis. Low energy compression fractures were rarely referred by orthopedic surgeons for additional diagnostic testing. Only 60% of orthopedic surgeons checked a DEXA (dual energy x-ray absorptiometry) scan. Thirty-nine percent checked serum chemistries. Among those specialists that did not order the above tests, only 63% referred the patient to the primary care physician

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or endocrinologist for further management. Pain specialists may be consulted and should ensure appropriate referral for medical management of osteoporosis. DEXA scans evaluate bone density and compare patient results to a nomogram. A patient’s bone density is compared to the mean density of young, healthy adult men or women (T-score). This population represents healthy patients at the peak of bone density. If the T-score is more than 2.5 standard deviations less than this mean, the patient has osteoporosis. A T-score between 1 and 2.5 standard deviations is osteopenia. A T-score less than one standard deviation is considered normal. The Z-score is the mean bone density for agematched controls, not young adult healthy controls. If the patient’s bone density is between 1 and 2.5 standard deviations from the Z-score, this patient has primary or senile osteoporosis. If the bone density is more than 2.5 standard deviations from the Z-score, the patient has a secondary cause of osteoporosis. This requires the input of an endocrinologist.

7. How should I treat this patient? Conservative approaches This is a controversial topic. Patients improve within 2 weeks and then slowly improve over the next 6–12 months. Early rehabilitation is imperative. Patients should avoid immobility and associated deconditioning. Patients should be reminded of the deleterious effects of immobilization: venous thromboembolic disease, urinary retention and infection, reduced cardiac output, postural hypotension, pressure ulcers, depression, catabolic state, and pneumonia. In the USA, some of these complications will not be compensated by insurance carriers. Prevention of these complications necessitates more intensive nursing and rehabilitation care. So, an active approach to conservative care is needed with appropriate use of analgesics and physical therapy. Typical analgesic therapy consists of non-steroidal anti-inflammatories or opioids. These analgesics carry greater risks in the elderly. If a procedure is not planned, venous thromboprophylaxis is advised. A sacroiliac joint belt may help reduce pain and reduce apprehension with standing or transfers. Osteoporosis treatment includes calcium and vitamin D supplementation, antiresorptive agents to slow bone loss, teriparitide (recombinant parathyroid

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hormone), and selective estrogen receptor modulators. Teriparitide increases bone density, trabecular bone, and cortical thickness, while reducing osteocyte apoptosis.

Procedural Given limitations of conservative care, percutaneous cement augmentation of sacral insufficiency fractures has gained popularity: sacroplasty or sacral kyphoplasty. Open surgical approaches or radiotherapy, although feasible for sacral metastases, are not utilized for SIFs. Surgical fixation with pedicle screws, pins, or similar devices is not used given the osteoporosis and potential migration risks. Sacral kyphoplasty or sacroplasty are minimally invasive procedures with low morbidity and good efficacy rates. Preoperative planning is essential. Medical clearance is advised since the patient may need monitored anesthetic care or general anesthesia. Patients are placed in a prone position so eye, peripheral joint, and skin assessments are useful, to ensure adequate pressure relief. Preoperative antibiotics should be administered within 30–60 minutes of the incision. Review the CT scan preoperatively. Imaging software permits making distance measurements from the median sacral crest to the lateral margin of the foramen. An indelible pen is used to mark the midline on the skin surface. The triangulation tool on the CT scan allows one to trace the sacroplasty trajectory from the skin to the sacral ala; one can then plan the correct trajectory in the patient. Depth, cephalocaudad angulation, and medio-lateral distance may be estimated. Fracture lines can be identified to help predict cement spread. A short axis approach, which is roughly perpendicular to the sacroiliac joint, is commonly used. Lidocaine 1% with 1:100 000 epinephrine is used to anesthetize the skin. Stab incisions are made along a vertical line connecting the 9 o’clock or 3 o’clock positions of the S1-S3 sacral foramina, on the left and right respectively. In the horizontal plane, the incisions are made between the foramina, which are remnants of “fused articular processes”: between the superior articular process of the sacrum and above the S1 foramen; between S1-S2 foramen; and between the S2-S3 foramen. The styletted cannula is directed in a medio-lateral direction, about 45 degrees to the skin surface. Bony

Chapter 27: Sacral insufficiency fracture and treatment options

Figure 27.2. Anteroposterior fluoroscopic view; sacral kyphoplasty post cement delivery. From personal files of Rinoo V. Shah, MD, MBA. Figure 27.1. Sagittal fluoroscopic view; sacral kyphoplasty post cement delivery. From personal files of Rinoo V. Shah, MD, MBA.

contact should ideally be made lateral to the aforementioned vertical line, well within Denis Zone 1. The cannulas are advanced to the auricular surface of the sacrum. The sacroiliac joint and ventral cortex of the sacrum should not be violated. Fluoroscopy confirms final cannula placement. Stylets are removed and a balloon may or may not be inserted. The balloon is insufflated to a volume of 2–4 ml. The balloon creates a cavity, which delimits the space available for cement delivery. Polymethylmethacrylate is mixed with barium powder (for radiopacity). After sufficient viscosity is reached, 1–3 ml of cement is delivered through each cannula. Fluoroscopy is essential to monitor cement spread. Typically, four cannulas (two per side) are sufficient. After the cannulas are removed, steri-strips are applied to the stab incisions and a pressure dressing is applied. Patients report rapid pain relief within hours of the procedure. If relief doesn’t occur almost instantaneously, alternative pain generators should be sought.

8. Are there any complications to worry about following sacroplasty or sacral kyphoplasty? The major risks are infection, bleeding, no pain relief, or nerve damage. A cement leak onto the

sacral foramina or sacral canal can cause permanent damage. Cement can also leak into the soft tissues. This is often asymptomatic; however, the cement hardens and causes an exothermic reaction which could cause soft tissue necrosis and severe pain. The cannulas similarly could violate the cortical bone and cause nerve or soft tissue damage, which is one reason why the cannulas are placed lateral to the fused articular pillars. Cement extravasation into these structures typically will not cause pain or nerve damage. The cement leak is siphoned off, so to speak, by these fused articular pillars.

9. What are the outcomes? According to Frey et al, mean visual analog scores dropped from 8.2 to 3.4 in the immediate postoperative period, in a prospective observational cohort study.[1] The mean visual analog score continued to drop to 0.8 at 52 weeks. Shah confirmed similar findings in a retrospective study of sacral kyphoplasty.[2] There is an ethical dilemma when extrapolating observational and retrospective studies to clinical practice; on the other hand, randomized clinical trials are more difficult to conduct and may have negative outcomes. Practitioners must exercise due diligence, sound judgment, and provide informed consent.

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Chapter 27: Sacral insufficiency fracture and treatment options

Figure 27.3. Coronal oblique CT scan; sacral kyphoplasty post cement delivery. From personal files of Rinoo V. Shah, MD, MBA.

References 1.

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Frey ME, Depalma MJ, Cifu DX, et al. Percutaneous sacroplasty for osteoporotic sacral insufficiency fractures: a prospective,

Figure 27.4. Coronal CT scan; sacral kyphoplasty post cement delivery. From personal files of Rinoo V. Shah, MD, MBA.

12(2):113–120. doi: 10.1016/j. spinee.2012.01.019.

multicenter, observational pilot study. Spine J. 2008;8(2):367–373. 2.

Shah RV. Sacral kyphoplasty for the treatment of painful sacral insufficiency fractures and metastases. Spine J. 2012;

3.

Depalma MJ, Ketchum JM, Saullo T. What is the source of chronic low back pain and does age play a role? Pain Med. 2011;12:224–233.

Section 2 Chapter

28

Spinal Disorders

Skeletal metastases and treatment options Rinoo V. Shah

Case study A 58-year-old man underwent a right lower lobectomy, for squamous cell carcinoma. He received adjuvant chemotherapy, but could not complete the entire course due to side effects. Nonetheless, he remained disease free as evidenced by negative postoperative CT scans. During a routine referral for smoking cessation and obstructive airway disease - the patient continued to smoke postoperatively for almost 2 years - the pulmonologist advised bronchoscopy. Cancer recurrence was identified at the bronchial stump. PET scanning demonstrated multicentric disease and the patient was not a candidate for pneumonectomy. Over the next few months, the patient was frequently hospitalized for pulmonary and pain complaints. One painful area was localized over the anterior sternum.

1. What is the differential diagnosis? a. b. c. d. e. f. g.

Costochondritis or Tietze’s syndrome Myofascial pain Pleuritis Visceral pain (angina) Mediastinis Aortic dissection Metastasis

A sternal CT demonstrates a circumscribed osteolytic and cavitating lesion.

2. What is this? This is a skeletal metastasis. Bone lesions are common in advanced cancer, particularly lung, prostate, breast, and multiple myeloma. Metastatic non-small cell lung cancer is the leading cause of cancer death among men and women in the USA and worldwide. Among

patients with metastatic breast and prostate cancer, 65–75% will have bone metastases. Bone metastases in breast cancer have a high predilection for causing skeletal-related events (SRE): pathologic fractures, spinal cord compression, severe bone pain, structural impairment requiring prophylactic stabilization, and hypercalcemia. Life expectancy in patients with metastatic bone disease is significantly shortened. Patients with metastatic non-small cell lung cancer have a median survival of 8.9 months and with palliative care, this increases to 11.6 months. Breast cancer patients with bone metastases have a survival of about 2 years, but are at risk for SREs. Typically, survival is less than 1 year for metastatic lung cancer and a few years for metastatic breast and prostate cancer. Quality of life is poor, however, due to the risk of 3–4 SREs per year.[1–6]

3. How do you diagnose this? Typically, the history suggests an acute presentation. Patients may have other systemic signs, such as weight loss, cachexia, progressive debilitation, and fevers. The metastasis may cause additional SREs. Patients may report neurologic loss, weakness, and non-focal pain that radiates to the limbs. Other non-skeletal metastases may cause visceral/organ dysfunction or cognitive impairment. Patients may have significant ambulatory and functional limitations. Sometimes, they are confined to bed. Pain worsens with weight bearing, but only slightly improves with rest. Patients may have night pain and poor sleep. There may be tenderness to palpation over the bony prominences, e.g., spine, hips, knees, shoulders, arms, and skull. Laboratory studies are usually not helpful. The alkaline phosphatase and calcium may be elevated. Radiographs may demonstrate osteolytic lesions, but

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Chapter 28: Skeletal metastases and treatment options

may be missed in patients with osteoporosis. Advanced imaging studies are important in diagnosing skeletal metastases. Bone scintigraphy with technetium 99 is very sensitive for acute osteolytic lesions but may be confused with fractures. A sacral metastases for instance may not present with the classic “Honda” sign since lesions could be unilateral. Magnetic resonance imaging provides detailed anatomic and physiologic information. This test has high diagnostic accuracy. Lesions appear high on T2-weighting and high on STIR (fat suppression) sequences, due to bone edema. Due to tumor vascularity, contrast preferentially enhances tumor and advanced imaging, such as an MRI or CT, should be ordered with this modality, as long as there are no contraindications such as renal insufficiency or allergies. The CT scan may be used in patients with contraindications to MRI, e.g., pacemaker implants. The CT scan is also useful for percutaneous cement augmentation procedures, such as sacral kyphoplasty (Figure 28.1). Bone detail is excellent and multiplanar reformatting enables 3-dimensional rendering of the metastasis.[1,2]

4. Why is treatment or palliation of this lesion important? Early palliative care of skeletal metastases, within 8 weeks of diagnosis, will lead to improvements in quality of life and mood.[1–6]

5. The patient presented with skeletal pain shortly after being diagnosed with recurrent bronchial stump cancer. Why is this? Early stage metastatic bone disease may remain undetected. Patients often present with pain with latestage metastases. Skeletal-related events (SREs), such as spinal cord compression or vertebral fractures, are devastating.[3] Metastases alone, however, can be painful and disabling due to direct invasion and osteolysis. This patient’s pain was due to osteolysis.[1–6]

6. How would you treat this pain? Multimodal care is imperative. This includes analgesics, bracing (for support), protected weight bearing if the metastasis involves the lower limbs, activity modification balanced with mobilization, and counseling given

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the prevalence of fear and apprehension. Antiresorptive agents may be necessary given the risk of hypercalcemia. Polymodal analgesic care may include nonsteroidal anti-inflammatory agents, muscle relaxants, antiepileptic drugs, anxiolytics, and opioids. Fear, anxiety, and apprehension are common in this population. Not only is fear of pain paramount, but so is apprehension about additional procedures and mobility given the severity of pain. An extensive discussion of these approaches is covered in Chapters 48, 49, and 50.

7. Is there a role for targeted therapy in this population? These lesions are very focal, painful, and disabling. The doses of opioids necessary may be very high; these doses carry attendant risks of opioid hyperalgesia (Chapter 29) and respiratory sedation. Furthermore, at the end of life, comfort afforded by high-dose opioids may impair cognition, alertness, and sleep-wake cycles. This interferes with the patient’s ability to coordinate end of life plans and communication with family members. So, targeted palliative care is an important consideration and should be broached with the oncologist, oncology team, and palliative care team. These specialists may have the perception that treatment of these lesions is invasive, disruptive to patient care, and expensive. So, targeted therapy plays a role in this population.

8. What types of targeted therapy for skeletal metastases are available? Historically, radiation therapy and open surgical excision were the most common treatments. Open surgical approaches or radiotherapy carry high morbidity. Radiotherapy may damage soft tissues around the tumor bed. Surgery carries intraoperative and perioperative risks. Increasingly, percutaneous ablative procedures are used to target painful soft tissue tumors. These techniques are being used, with increasing frequency, in primary and metastatic bone tumors.[4] These procedures offer a lower risk of morbidity compared to radiotherapy and surgery. These methods utilize imaging and specialized access devices. Tumor destruction is afforded by chemical agents (ethyl alcohol or acetic acid) or thermal energy (laser, microwave, ultrasound, cryotherapy, radiofrequency).[4] Radiofrequency ablation produces a discrete thermal lesion and has been efficacious in painful skeletal metastases.[5] Bipolar

Chapter 28: Skeletal metastases and treatment options

A

Figure 28.1. (A) CT reconstruction, focal lytic sternal lesion. (B) Sternal kyphoplasty, cannula and balloon displacing anterior and posterior cortical walls of sternum note cavitation. (C) PMMA cement in sternal metastasis; some anterior extravasation, but none posterior into mediastinum. From personal files of Rinoo V. Shah, MD, MBA.

B

C

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Chapter 28: Skeletal metastases and treatment options

radiofrequency or monopolar radiofrequency lesioning affords tumor necrosis and involution to improve focal pain. Discrete vertebral column metastases have been successfully treated with percutaneous spine stabilization.[6] Pain relief following vertebroplasty and kyphoplasty, in pathologic and non-pathologic vertebral fractures, has been attributed to spinal stabilization.[6,7] Radiofrequency ablation, osteoplasty, and kyphoplasty are relatively safe, target specific, and efficacious. Most can be conducted with monitored anesthetic care or conscious sedation. In those patients requiring general anesthesia, the procedure time is short, blood loss is minimal, and surgical stimulation is mild. Preoperative planning is essential. Medical clearance is advised. Patients are placed in a prone position with attention to eye, peripheral joint, and skin protection. Preoperative antibiotics should be administered within 30–60 minutes of the incision. Review the CT scan preoperatively. Imaging software permits making distance measurements from the skin to bone metastasis and trajectory planning. A transpedicular or extrapedicular approach is used for spinal metastases in the thoracic and lumbar spine. An anterolateral approach to the vertebral body is used for cervical spine tumors. A short axis or modified short axis approach is advised for sacral metastases. Other flat bones may be targeted under fluoroscopic or CT guidance. A recent novel approach using fluoroscopy and sonography, coupled with pre-op CT imaging software was used to treat a sternal metastasis. Under fluoroscopy, a styletted cannula is advanced using the aforementioned approaches into the metastasis. For kyphoplasty or radiofrequency ablation of thoracolumbar metastases, the technique is modified. The cannula is advanced to the posterior third of the vertebral body. The stylet is removed from the cannula and replaced with a curette. This curette advances past the tip of the cannula toward the anterior vertebral body wall. A bone biopsy may then be obtained. Fluoroscopy is used to confirm placement. The curette is removed and replaced by a balloon. The balloon is inflated and the margins should be within the confines of the vertebral body. The pressure rating is typically less than 250 pounds per square inch. Some vendors of kyphoplasty equipment have developed higher balloon pressure ratings for very dense, compact, and sclerotic bone tumors. Bone density or tumor density will affect balloon pressure and volume. In the case of vertebroplasty,

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the cannula is advanced to the anterior third and no balloon is used. Adjunctive equipment is available to create a cavity, if the balloon doesn’t suffice. Polymethylmethacrylate (PMMA) is mixed with barium powder (for radiopacity). High viscosity PMMA with a thickened consistency is delivered in small aliquots under low pressure. Fluoroscopy is imperative to ensure no leak occurs. PMMA may sometimes be obscured by the cannulas and due to patient habitus. Working time is 10–20 minutes allowing one enough time for slow controlled delivery. In the case of spinal tumors, cement may leak unpredictably and rapidly. For instance, a midline and anterior cannula may access the vertebrobasilar venous system. The veins are low resistance as compared to bone or tumor. PMMA could then rapidly extravasate into the epidural space. Another issue is target specificity. Bone tumors may be well circumscribed and careful placement under fluoroscopy is necessary: in some cases, CT guidance may be necessary. Older versions of PMMA had to be delivered in a liquid form – which increased the risk of extravasation and leakage: working times were shorter and PMMA was not deliverable once hardened (see Chapter 25 for additional details). Current versions of PMMA have a thicker consistency and longer working times, which enhances safety and allows more complete fills. PMMA is preferable to newer biointegrative cements in metastatic disease; adjacent segment fractures are less of a concern as compared to effective palliation of metastases. PMMA causes tumor necrosis and neurolysis via an exothermic reaction, while providing structural stabilization. Polyetheretherketone (PEEK) wafers may provide additional fracture reduction/tumor stabilization while minimizing cement volume requirements (Figure 28.2). In patients with complex metastases that pose a high risk/contraindication to vertebroplasty/ kyphoplasty, e.g., retropulsion of the vertebral body, radiofrequency thermocoagulation may be considered. A bipolar radiofrequency needle connected to a radiofrequency generator, while cooled by continuous saline irrigation, is a recent advance for this patient population. Saline irrigation permits needle tip temperature stabilization while augmenting lesion size. Radiofrequency ablation technology has been discussed in Chapters 15, 16, and 26. In essence, a high-frequency electrical current is sent to the uninsulated portion of the needle. This causes oscillation of surrounding molecules and places them at a higher energy state.

Chapter 28: Skeletal metastases and treatment options

A B

C

D

Figure 28.2. (A–D) Peek wafer lumbar kyphoplasty (Staxx FX Kyphoplasty Spine Wave, Shelton, Connecticut); sequential placement of PEEK wafers (A, B, C) and PMMA instillation (D). From personal files of Rinoo V. Shah, MD, MBA.

As these molecules return to their baseline energy state, heat is generated. RF energy causes protein denaturation in a very circumscribed spheroid configuration allowing it to be very target specific. The bone metastasis and surrounding edema have lower impedance compared to surrounding intact bone. Ablation preferentially occurs within the metastasis as opposed to bone. This is opposed to electrocautery or an open flame which can char intact bone in an uncontrolled manner. Bipolar versus monopolar refer to the location of the electric sink or ground. In bipolar RF, the grounding pad/electrical sink is contained within the

needle itself and is proximal to the active tip. Lesion size is larger in an axial/radial dimension as compared to monopolar lesions. Continuous saline irrigation further enables a larger radial lesion; it promotes temperature stabilization and a rapid temperature drop off to protect surrounding tissues. Patients report rapid pain relief within hours of the procedure. Recently, clinical trials have demonstrated the success of combining kyphoplasty with radiopharmaceutical agents: 125-I seeds and samarium-153. These target-specific options are being explored as options to external beam radiotherapy and intravenous radiopharmaceutical agents.[1–2,7–25]

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9. What is the mechanism of rapid pain relief? Cementoplasty of metastases in non-weight-bearing bones suggests a mechanism of pain relief, unrelated to bone stabilization.[8] Polymethylmethacrylate cement causes an exothermic reaction, with curing and solidification. Temperatures ranging from 50 to 57°C have been reported at the bone-cement interface, during polymerization. Average peak temperatures ranging from 45 to 100°C, depending on the cement, have been reported.[9] Neurolysis occurs at 45°C;[10] these temperatures result in destruction of tumor cells and vascular supply.[8] So, pain relief may occur due to several mechanisms: (1) bone stabilization; (2) direct tissue toxicity; (3) neurolysis; and (4) thermal injury. There have been several reports of successful cementoplasty of skeletal metastases.[1–2,7–25]

10. Are there any complications to worry about following vertebroplasty or kyphoplasty? The major risks are infection, bleeding, no pain relief, or nerve damage. A cement leak into the spinal canal or neuroforamina can cause permanent neurologic damage; a cement leak into the soft tissues is often asymptomatic. Sometimes, the cement hardens and

References 1.

Shah RV. Sacral kyphoplasty for the treatment of painful sacral insufficiency fractures and metastases. Spine J. 2012;12(2): 113–120. doi: 10.1016/j. spinee.2012.01.019.

2.

Shah RV. Sternal kyphoplasty for metastatic lung cancer: imageguided palliative care, utilizing fluoroscopy and sonography. Pain Med. 2012;13(2):198–203. doi: 10.1111/j.1526-4637.2011.01299.x. Epub 2012 Jan 13. PubMed PMID: 22239702.

3.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300. Epub 2010 Jul 7. PubMed PMID: 20610543.

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causes an exothermic reaction that leads to soft tissue necrosis and severe pain. However, leaks into the pleural cavity or vascular supply can be catastrophic. Cement emboli into the lungs may cause rapid patient demise. The cannulas similarly could violate the cortical bone and cause nerve or soft tissue damage.[1,2]

11. What can one conclude? These patients require multimodal therapy. Unfortunately, focal tumor metastases are difficult to treat with systemic methods. Often high doses of opioids are required with associated complications of sedation, respiratory depression, and opioid hyperalgesia. Patients may become nauseated, constipated, or pruritic, which further complicates management. Radiotherapy and surgery may lead to morbidity. Focal treatment with kyphoplasty, radiofrequency ablation, and targeted radiopharmaceuticals promote the principles of tumor debulking and necrosis for pain control. They enhance safety by minimizing collateral tissue damage. Shah et al demonstrated effective palliation of a non-weightbearing bone (sternum - metastasis) with kyphoplasty.[2] There is an ethical dilemma in extrapolating observational and retrospective studies to clinical practice. Practitioners must exercise due diligence, sound judgment, and provide informed consent, while cognizant of the desperate nature of spinal metastatic disease.

4.

Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic nonsmall-cell lung cancer. N Engl J Med. 2010;363(8):733–742.

5.

Major PP, Cook RJ, Lipton A, et al. Natural history of malignant bone disease in breast cancer and the use of cumulative mean functions to measure skeletal morbidity. BMC Cancer. 2009;9:272. doi: 10.1186/14712407-9-272. PubMed PMID: 19660124; PubMed Central PMCID: PMC2739221.

6.

Hirsh V. Skeletal disease contributes substantially to morbidity and mortality in patients with lung cancer. Clin Lung Cancer. 2009;10(4):223–229 [Review].

7.

Kurup AN, Callstrom MR. Ablation of skeletal metastases: current status. J Vasc Interv Radiol. 2010;21(8 Suppl): S242–250. 8. Thanos L, Mylona S, Galani P, et al. Radiofrequency ablation of osseous metastases for the palliation of pain. Skeletal Radiol. 2008;37(3):189–194. Epub 2007 Nov 21. 9. Yang Z, Yang D, Xie L, et al. Treatment of metastatic spinal tumors by percutaneous vertebroplasty versus percutaneous vertebroplasty combined with interstitial implantation of 125I seeds. Acta Radiol. 2009;50(10):1142–1148. 10. Dalbayrak S, Onen MR, Yilmaz M, Naderi S. Clinical and

Chapter 28: Skeletal metastases and treatment options

radiographic results of balloon kyphoplasty for treatment of vertebral body metastases and multiple myelomas. J Clin Neurosci. 2010 Feb;17(2):219–224. 11. Choi HR, Lee PB, Kim KH. Scapuloplasty alleviates scapular pain resulting from lung cancer metastasis. Pain Physician. 2010;13(5):485–491. 12. Anselmetti GC, Manca A, Kanika K, et al. Temperature measurement during polymerization of bone cement in percutaneous vertebroplasty: an in vivo study in humans. Cardiovasc Intervent Radiol. 2009;32(3):491– 498. 13. Shah RV, Lutz GE, Lee J, Doty SB, Rodeo S. Intradiskal electrothermal therapy: a preliminary histologic study. Arch Phys Med Rehabil. 2001;82(9): 1230–1237. 14. Zhou B, Wu CG, Li MH, Gu YF, Cheng YD. Percutaneous osteoplasty for painful sternal lesion from multiple myeloma. Skeletal Radiol. 2009;38(3): 281–285. 15. Masala S, Manenti G, Roselli M, et al. Percutaneous combined therapy for painful sternal metastases: a radiofrequency thermal ablation (RFTA) and cementoplasty protocol.

Anticancer Res. 2007;27(6C): 4259–4262. 16. Gianfelice D, Gupta C, Kucharczyk W, et al. Palliative treatment of painful bone metastases with MR imaging– guided focused ultrasound. Radiology. 2008;249(1):355–363. 17. Tang D, Peng EW, Giri D, Chowdhary M, Sarkar P. Mediastinal irradiation and its effect on the cardiovascular system. Br J Hosp Med (Lond). 2009;70(4):222–224. 18. Adams MJ, Hardenbergh PH, Constine LS, Lipshultz SE. Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol. 2003;45(1):55–75. 19. Dalbayrak S, Onen MR, Yilmaz M, Naderi S. Clinical and radiographic results of balloon kyphoplasty for treatment of vertebral body metastases and multiple myelomas. J Clin Neurosci. 2010;17(2): 219–224. 20. Mendel E, Bourekas E, Gerszten P, Golan JD. Percutaneous techniques in the treatment of spine tumors: what are the diagnostic and therapeutic indications and outcomes. Spine (Phila Pa 1976). 2009;34(22 Suppl):S93–100.

21. Belfiore G, Tedeschi E, Ronza FM, et al. Radiofrequency ablation of bone metastases induces longlasting palliation in patients with untreatable cancer. Singapore Med J. 2008;49(7):565–570. 22. Lane MD, Le HB, Lee S, et al. Combination radiofrequency ablation and cementoplasty for palliative treatment of painful neoplastic bone metastasis: experience with 53 treated lesions in 36 patients. Skeletal Radiol. 2011;40(1):25–32. 23. Amdur RJ, Bennett J, Olivier K, et al. A prospective, phase II study demonstrating the potential value and limitation of radiosurgery for spine metastases. Am J Clin Oncol. 2009;32(5):515–520. 24. Cardoso ER, Ashamalla H, Weng L, et al. Percutaneous tumor curettage and interstitial delivery of samarium-153 coupled with kyphoplasty for treatment of vertebral metastases. J Neurosurg Spine. 2009;10(4):336–342. 25. Yang Z, Yang D, Xie L, et al. Treatment of metastatic spinal tumors by percutaneous vertebroplasty versus percutaneous vertebroplasty combined with interstitial implantation of 125I seeds. Acta Radiol. 2009;50(10):1142–1148.

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Spinal Disorders

Fibromyalgia and opioid-induced hyperalgesia Grace Chen and Elliot Palmer

Case study A 45-year-old woman was referred to a pain management center from her primary care doctor’s office for evaluation and treatment of her fibromyalgia. Per history, patient complains of worsening fatigue, headache, and widespread and migrating pain all over her body. She relates that the pain is most bothersome in her shoulders and lower back but is also present in her thoracic spine, neck, right elbow, and bilaterally in her knees. She remembers having diffuse body pain since age 25 when she got into a motor vehicle accident in which her car was wrecked even though she did not have any fractures or hospitalization from that accident. On further evaluation, she has also been dealing with depression and insomnia. She does not think that she has fibromyalgia and she would like to have a different diagnosis and be cured of her pain. She also would like to increase her opioid dosage as her pain has worsened since her son had gone to college.

1. What is the differential diagnosis? Some differential diagnoses for widespread body pain include: a. Fibromyalgia b. Polymyalgia rheumatica c. Myositis/myopathies d. Myofascial pain syndrome e. Rheumatoid arthritis f. Systemic lupus erythematosis g. Sjogren’s syndrome h. Ankylosing spondylitis i. Hypothyroidism j. Somatoform disorder

k. Cervical spinal stenosis l. Systemic vasculitis

2. What is fibromyalgia? How do you diagnose it? Are there diagnostic and/or clinical criteria? According to the 2010 American College of Rheumatology preliminary revised diagnostic criteria, fibromyalgia is characterized by widespread body pain, cognitive symptoms, unrefreshed sleep, fatigue, and a number of somatic symptoms.[1] These relatively new diagnostic criteria mark a change from the 1990 diagnostic criteria espoused by the ACR that included physical exam findings of 11/18 manual tender points. For 20 years, practitioners used American College of Rheumatology’s “Manual Tender Point Survey” along with history and physical exam as mainstays in the diagnosis of fibromyalgia (Figure 29.1). This survey involves palpation of 18 specified muscle insertion sites throughout the body with approximately 10 pounds of weight and a simple “yes” or “no” answer from the patient regarding the presence or absence of tenderness. There are three control points built in to the survey, and the diagnosis requires that 11/18 noncontrol points be scored as positive.[2] However, this survey was originally developed as a research tool and was not intended for use in clinical practice. Additionally, many clinicians thought that the criteria were too restrictive and failed to account for the heterogeneity in the population thought to have fibromyalgia. Born from this and other factors, the ACR has more recently published a set of not yet validated preliminary diagnostic criteria for fibromyalgia that does not include the tender point exam. These

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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Table 29.1 2010 ACR fibromyalgia diagnostic criteria

A patient satisfies diagnostic criteria for fibromyalgia if the following three conditions are met: 1. Widespread Pain Index (WPI)  7 and Symptom Severity (SS) Scale Score  5 OR WPI 3–6 and SS  9 2. Symptoms have been present at a similar level for at least 3 months 3. The patient does not have a disorder that would otherwise explain the pain WPI: Answer the question, “in how many areas has the patient had pain over the last week?” The score will be from 0–19. Areas: 1. Shoulder girdle, left 2. Shoulder girdle, right 3. Upper arm, left 4. Upper arm, right 5. Lower arm, left 6. Lower arm, right 7. Hip (buttock/trochanter), right 8. Hip (buttock/trochanter), left 9. Upper leg, left 10. Upper leg, right 11. Lower leg, left 12. Lower leg, right 13. Jaw, left 14. Jaw, right 15. Chest 16. Abdomen 17. Upper back 18. Lower back 19. Neck SS Scale Score: The sum of the severity of three specified symptoms + the severity of somatic symptoms in general 1. For each of the 3 (i, ii, iii) symptoms below, indicate the level of severity over the past week (0 ¼ no problem, 1 ¼ slight or mild problems/intermittent, 2 ¼ moderate problems/often present, 3 ¼ severe, pervasive, continuous problems): i. Fatigue ii. Waking unrefreshed iii. Cognitive symptoms 2. Considering somatic symptoms in general*, indicate whether the patient has: 0 ¼ no symptoms 1 ¼ few symptoms 2 ¼ a moderate number of symptoms 3 ¼ a great deal of symptoms * Somatic symptoms might include: muscle pain, irritable bowel syndrome (IBS), fatigue, cognitive problems, weakness, headache, abdominal pain/cramps, numbness, tingling, dizziness, insomnia, depression, constipation, chest pain, blurred vision, dry mouth, itching, tinnitus, nausea, vomiting, etc.

1 3

2

5

10

4 6

12

7

11 13

14 9

15

8 16 17

19

18

20

21

Figure 29.1 Manual Tender Point Survey.

criteria are proposed as a parallel method of diagnosis and represent the most current thinking (Table 29.1). The foremost feature of fibromyalgia is chronic, widespread pain that is not explained by an injury or another rheumatic or systemic disorder. There are a number of other salient features, aside from pain, that are present in many patients with fibromyalgia – common among them are fatigue, mood disturbance, and insomnia. There is a strong association between fibromyalgia and other autoimmune disorders. Also, it is clear that many patients with fibromyalgia demonstrate similar neuroendocrine changes, patterns of central nervous system response to pain, and even distinct features on functional neuroimaging. Fibromyalgia was far more common in 1st degree relatives of others with the diagnosis than in matched controls with rheumatoid arthritis.[3] It also commonly coexists with other systemic disorders like temporomandibular joint disorders, headaches, and irritable bowel syndrome.[4]

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Stressors from the environment also seem to play a role. The development of fibromyalgia has been associated with certain infections[5] as well as with physical abuse and trauma.[6] Furthermore, patients with fibromyalgia show alterations in CSF levels of endogenous opioids,[7] norepinephrine, dopamine, and serotonin[8] and show abnormal patterns of cerebral blood flow and neural activity when compared to controls.[9,10] Fibromyalgia was once thought of as an unknown entity or a label for patients without any identifiable cause for their pain. However, it is now clear that fybromyalgia is a complex condition with multiple objective identifying features. Patients present clinically with signs of central sensitization such as allodynia, hyperpathia, and hyperalgesia. One clinical hypothesis for fibromyalgia pathophysiology is a combination of spinal cord amplification of pain that may be triggered by multiple causes, combined with autonomic arousal such as the fight-or-flight response, leading to loss of slow-wave sleep. Autonomic arousal can be due to psychiatric causes such as post-traumatic stress, anxiety, or even to sleep apnea and/or cervical cord impingement. Loss of slow-wave sleep correlates with the loss of pain inhibition. Peripheral pain generators, such as conditions like osteoarthritis, are amplified in the dorsal horn of the spinal cord. Pain signals travel to the brain, causing another set of disturbances, including neuro-hormonal dysfunction, especially of the hypothalamic–pituitary– adrenal axis that adversely affect cortisol and growth hormone release. Fibromyalgia patients have blunted morning cortisol release, contributing to their intense morning fatigue. Growth hormone release is poor in these patients and is needed for a sense of well-being and for repair of muscle microtrauma. This may explain the post-exertion pain and fatigue seen in these patients. It is also clear that dopaminergic neurotransmission is impaired to areas of the brain related to pain inhibition. Restless leg syndrome, a manifestation of dopamine depletion, can occur in severe fibromyalgia. It reflects poor dopamine activity in the somatosensory cortex. It also disrupts sleep. Small hippocampi are seen in patients with posttraumatic stress disorder (PTSD) and severe depression. The hippocampus is needed for short-term memory storage and moderates autonomic arousal. Mood issues, such as anxiety, depression, and cognitive dysfunction, are often comorbidities with fibromyalgia and share neurotransmitter pathways in the brain, possibly contributing to the “fibrofog,” a complaint

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voiced by many patients. Poor cognition in fibromyalgia patients may be aggravated by compromised BDNF (brain derived neurotrophic factor) activity which is needed to make new synapses. Interestingly, aerobic exercise increases BDNF and may improve cognition. Changes in corticotrophin-releasing factor (CRF) receptor sensitivity also increase anxiety and high CRF activity causes hippocampal atrophy. Thus, fibromyalgia is a constellation of pain, fatigue, and poor sleep. Fibromyalgia may have a genetic predisposition and may be triggered by life events. The use of manual tender points in the previous diagnosis of fibromyalgia highlights one of the most prominent features of this condition. In addition to widespread pain, patients with fibromyalgia are very sensitive to painful stimuli. They also demonstrate both allodynia and hyperalgesia. These aspects are thought to be due to neurochemical changes as well as increased wind-up and diminished descending inhibitory pathways. Patients with fibromyalgia also have a high incidence of sleep disorders[11] and psychiatric illness.[12] However fibromyalgia is defined, it is clear that it is a relatively common disorder with clear ramifications for the quality of a patient’s life. The estimated prevalence of fibromyalgia is 2–4% of the population, thus affecting over 6 million people in the USA alone, with a clear female predominance.[13–15] In addition, fibromyalgia imposes significant financial burdens on both the patients and medical system, and these increase with the severity of the disease.[16]

3. How do you differentially diagnose fibromyalgia from similar problems? According to the 2010 preliminary criteria, fibromyalgia is a diagnosis of exclusion. Thus, all other diagnoses causing widespread pain and fatigue must be excluded before giving the diagnosis of fibromyalgia. According to the 1990 criteria, fibromyalgia diagnosis is an independent one that may coexist with other diagnoses caused by similar symptoms, as long as the patient has chronic pain and more than 11 of 18 manual tender points. The following are some features of other rheumatologic diagnoses that may also cause widespread pain and fatigue.  Polymyalgia rheumatica (PMR)

:

Pain and fatigue are common to both PMR and fibromyalgia; however, the pain in PMR is

Chapter 29: Fibromyalgia and opioid-induced hyperalgesia

typically limited to the neck, shoulders, and hips whereas the pain in fibromyalgia is classically described as affecting all four quadrants of the body (left and right sides, above and below the waist). Additionally, PMR typically affects adults over the age of 60 whereas fibromyalgia is most commonly seen between the ages of 20 and 50.  Myositis/myopathies

:

Myositis, a general term for inflammation of muscles, encompasses a wide variety of conditions including myositis ossificans, dermatomyositis, polymyositis, pyomyositis, and drug-induced (i.e., statins) myositis, among others. Myopathy, or muscle disease, is a similarly broad term with many variations. It is beyond the scope of this chapter to delineate these, but the etiologies range from inflammatory to infectious to metabolic, and diagnostic criteria vary widely as well. Fibromyalgia has been described as a disorder of “central sensitization,” whereas a myositis or myopathy is most often a clearly peripheral phenomenon.  Myofascial pain syndrome (MPS)

:

Myofascial pain syndrome and fibromyalgia share some features and may even coexist, but they are often distinguishable. Myofascial pain involves irritable foci of pain termed “trigger points.” The pain is often described as a deep aching sensation, and muscle stiffness is typically present.[17]

Additionally, trigger points in MPS are most commonly found in the erector spinae, gluteal fascia, and presacral fascia as opposed to the generalized and widespread tenderness seen in the majority of fibromyalgia patients.  Somatoform disorders

:

There are different varieties of somatoform disorders, though the one commonly confused with fibromyalgia is somatization disorder. The DSM IV-TR defines somatization disorder as a history of many physical complaints beginning before age 30 that occur over several years and result in treatment being sought or significant functional impairment. Each of the following criteria must be met, with individual symptoms

occurring at any time during the course of the disturbance: – 4 pain symptoms: a history of pain related to at least four different sites or functions; – 2 gastrointestinal symptoms: a history of at least two gastrointestinal symptoms other than pain; – 1 sexual symptom: a history of at least one sexual or reproductive symptom other than pain; – 1 pseudoneurologic symptom: a history of at least one symptom or deficit that suggests a neurologic condition not limited to pain. Additionally, either each of the symptoms cannot be fully explained by a known general medical condition or the direct effects of a substance after appropriate investigation, or when there is a related general medical condition, the physical complaints or resulting social or occupational impairment are in excess of what would be expected from the history, physical examination, or laboratory findings. Importantly, the symptoms in this disorder are not intentionally produced or feigned.[18]

4. What is the treatment for fibromyalgia? Is it ethical to prescribe opioids in the treatment of fibromyalgia? Pharmacologic treatment is the primary approach to management for the majority of patients. However, most physicians recognize that patients with fibromyalgia benefit from a multidisciplinary approach including physical therapy, CBT, and pain psychology.[19] Many medications have been used to treat fibromyalgia with varying degrees of success. For a long time, none of the commonly used medications were recognized or approved. However, in 2007 Lyrica (pregabalin) became the first FDA-approved drug for specifically treating fibromyalgia. One year later, Cymbalta (duloxetine hydrochloride) became the second approved drug. In 2009, the FDA approved a third drug, milnacipran. Several classes of drugs have been used to treat fibromyalgia: tricyclic antidepressants (TCAs), SSRIs, selective serotonin/norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase

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inhibitors (MAOI), 5-HT3 receptor antagonists, anticonvulsive or antiseizure medications (AEDs), muscle relaxants, NMDA receptor antagonists, dopamine agonists, NSAIDs, and opioids.[20] There are altered levels of norepinephrine and serotonin in fibromyalgia. Drugs that augment these neurotransmitter levels within the central nervous system (TCAs, SNRIs, tramadol) are thus useful in the treatment of fibromyalgia.  Tricyclic antidepressants

:

These are the most well-studied medications for fibromyalgia, in part because they have been around the longest. These medications work by blocking reuptake and thus increasing the concentrations of serotonin and norepinephrine. They appear to effectively improve sleep, stiffness, and tenderness associated with fibromyalgia.[21]  Selective serotonin reuptake inhibitors

:

SSRIs have also been used in the treatment of fibromyalgia, largely due to their superior side effect profile when compared to TCAs. Trials of efficacy have had conflicting results, but in one trial, when compared head-to-head, SSRIs were found to be effective but not quite as efficacious as TCAs.[22]  Selective serotonin and norepinephrine reuptake inhibitors

:

Fibromyalgia, similar to other chronic pain states, seems to respond better to serotonergic–noradrenergic antidepressants than to purely serotonergic antidepressants.[23] The similarity of these drugs to TCAs makes their efficacy not surprising. As mentioned above, both duloxetine and milnacipran have now been FDA approved for the treatment of fibromyalgia.  Other drugs

:

218

Pregabalin is an anticonvulsant drug also used for chronic pain, designed as a more potent successor of gabapentin. Pregabalin works by binding to the alpha-2 delta subunit of voltage gated calcium channels in the central nervous system and reducing their activity. Thus, it decreases neurotransmitter release, such as glutamate, norepinephrine, and substance P. In a randomized controlled trial, beneficial effects on pain, sleep disturbance, and fatigue

were shown.[24] Until recently, pregabalin was the only pharmacologic agent approved for the treatment of fibromyalgia. – Gabapentin has similar pharmacology to pregabalin. It is commonly used in the treatment of other neuropathic pain states and demonstrates efficacy in fibromyalgia,[25] though is not a commonly selected medication. – Sedative hypnotics including benzodiazepines and zolpidem are widely used for fibromyalgia and may be of benefit in improving sleep and reducing fatigue, though these medications are of limited benefit in other arenas and carry with them both side effects and the potential for abuse. – Opioids have been widely used for the treatment of fibromyalgia, despite a lack of evidence for their efficacy. Opioid use in the treatment of fibromyalgia is a particularly contentious topic and deserves further discussion. Appropriately, their use is becoming more and more limited due to concerns about addictive potential, opioid-induced hyperalgesia, and lack of efficacy. Many guidelines have been published delineating the clear lack of efficacy of opioids, though their widespread use continues.[26] Interestingly, patients have largely reported the most effective medications are those that had no evidence of efficacy, not to mention a high potential for abuse – hydrocodone, alprazolam, oxycodone, zolpidem, and clonazepam.[27] This clearly provides a dilemma for physicians. It is most likely that the perceived efficacy of these medications reflects interaction of these medications with the pleasure and reward systems rather than relief of the pain or other symptoms of fibromyalgia. Prescribing physicians should review the evidence and keep in mind the many deleterious effects and possible harm associated with chronic opioid therapy when deciding on treatment options. Non-pharmacologic treatments include CBT, exercise, physical therapy, sleep hygiene, and a wide variety of other CAM treatments. Among these, the best evidence exists for CBT and exercise.[28,29] Though high-quality evidence does not exist to support their use, many alternative therapies including

Chapter 29: Fibromyalgia and opioid-induced hyperalgesia

acupuncture, chiropractic care, and massage are commonly used by patients suffering from fibromyalgia, and anecdotal evidence suggests further, controlled studies may be indicated.

Case follow-up After a few office visits, you give the patient a diagnosis of fibromyalgia and recommend initial treatment with a combination of pregabalin, pain psychology, and light exercise. Your patient tells you that this treatment would take too much time and effort, and she seeks a second opinion. One year later she returns to you with similar complaints, but worsening of her pain. In the interim she has been taking opioids prescribed to her by another physician.

5. Does the worsening of her pain despite opioid therapy make you question your diagnosis? Are there any other diagnoses to consider at this point? Patients with fibromyalgia have altered opioid response. Harris et al observed that patients with fibromyalgia have decreased mu-opioid receptor availability.[30] Fibromyalgia patients were found to have more met-enkephalin-Arg6-Phe7 (MEAP) in their cerebrospinal fluid and concomitant lower pain threshold compared to chronic low back pain groups.[31] In a study of more than 8000 patients with chronic non-cancer pain, 7% of whom had fibromyalgia, potent opioids are more effective in pain control and functional improvement compared to non-

References 1.

2.

3.

opioids.[32] Clinically, many fibromyalgia patients do indeed find benefit with opioids. However, escalating doses of opioids has multiple side effects and complications. In this case, her complaint of worsening pain should prompt further investigation. One entity that should be specifically considered in this case is opioidinduced hyperalgesia (OIH). Opioid-induced hyperalgesia is defined as a state of nociceptive sensitization caused by exposure to opioids.[33] This causes a paradoxical response in which a patient receiving opioids actually experiences a worsening of pain or an increase in sensitivity to painful stimuli.[34] At least three types of evidence support the notion that patient exposure to opioids lowers their pain threshold.[35] First, several studies found that patients on methadone maintenance have lower pain threshold to cold pressors than patients not on methadone maintenance.[36] Second, some studies involving patients undergoing surgery suggest that acute high-dose infusions of opioids seem to increase postoperative opioid consumption.[37] Third, in healthy volunteers, remifentanyl infusion was found to aggravate pre-existing mechanical hyperalgesia. This hyperalgesia is attenuated by NMDA antagonist ketamine and clonidine infusion.[38] Clinically, opioidinduced hyperalgesia is suspected when patients are taking increasing doses of opioids but present with rapid tachyphylaxis or diffuse hyperalgesia to stimuli. It can often be difficult to distinguish OIH from other painful conditions, like fibromyalgia, but the diagnosis must be considered in someone using escalating doses of opioids with worsening diffuse pain. Treatment includes tapering off and discontinuing opioid therapy and can occasionally include supplementation with NMDA receptor antagonists.

Arnold LM, Hudson JI, Hess EV, et al. Family study of fibromyalgia. Arthritis Rheum. 2004;50(3):944–952.

Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62(5):600–610.

4.

The American College of Rheumatology. 1990 Criteria for the Classification of Fibromyalgia. Arthritis Rheum. 1990;33(2): 160–172.

Sperber AD, Atzmon Y, Neumann L, et al. Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol. 1999;94(12):3541–3546.

5.

Endresen GK. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes.

Rheumatol Int. 2003;23(5): 211–215. 6.

Walker EA, Keegan D, Gardner G, et al. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: II. Sexual, physical, and emotional abuse and neglect. Psychosom Med. 1997; 59(6):572–577.

7.

Baraniuk JN, Whalen G, Cunningham J, Clauw DJ. Cerebrospinal fluid levels of opioid peptides in fibromyalgia

219

Chapter 29: Fibromyalgia and opioid-induced hyperalgesia

and chronic low back pain. BMC Musculoskel Disord. 2004;5:48. 8.

9.

Best Pract Res Clin Rheumatol. 2007;21(3):427–445.

Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum. 1992;35(5):550–556.

18. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR). American Psychiatric Association. 2000.

Guedj E, Taieb D, Cammilleri S, et al. 99mTc-ECD brain perfusion SPECT in hyperalgesic fibromyalgia. Eur J Nucl Med Mol Imaging. 2007;34(1):130–134.

19. Barkhuizen A. Rational and targeted pharmacologic treatment of fibromyalgia. Rheum Dis Clin North Am. 2002;28:261–290.

10. Cook DB, Lange G, Ciccone DS, et al. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004;31(2):364–378.

20. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol Suppl. 2005;75:6–21.

11. Roizenblatt S, Neto NS, Tufik S. Sleep disorders and fibromyalgia. Curr Pain Headache Rep. 2011; 15(5):347–357.

21. Arnold LM, Keck PE, Welge JA. Antidepressant treatment of fibromyalgia: a meta-analysis and review. Psychosomatics. 2000; 41(2):104–113.

12. Arnold LM, Hudson JI, Keck PE, et al. Comorbidity of fibromyalgia and psychiatric disorders. J Clin Psychiatry. 2006;67(8):1219–1225. 13. Buskila D, Cohen H. Comorbidity of fibromyalgia and psychiatric disorders. Curr Pain Headache Rep. 2007;11(5):333–338. 14. Bartels EM, Dreyer L, Jacobsen S, et al. Fibromyalgia, diagnosis and prevalence. Are gender differences explainable? Ugeskr Laeger. 2009;171(49):3588–3592. 15. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38(1):19–28. 16. Changran A, Shaefer C, Ryan K, McNett M, Zlateva G. The comparative economic burden of mild, moderate, and severe fibromyalgia: results from a retrospective chart review and cross-sectional survey of workingage U.S. adults. J Manag Care Pharm. 2012;18(6):415–426. 17. Bennett R. Myofascial pain syndromes and their evaluation.

220

22. Capaci K, Hepguler S. Comparison of the effects of amitriptyline and paroxetine in the treatment of fibromyalgia syndrome. The Pain Clinic. 2002;14(3):223–228.

27. Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. An internet survery of 2,596 people with fibromyalgia. BMC Muscoloskelet Disord. 2007;8:27. 28. Goldengerg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292(19):2388–2395. 29. Falcao D, Sales L, Leite J, et al. Cognitive Behavioral Therapy for the treatment of fibromyalgia syndrome: a randomized controlled trial. J Muscoloskel Pain. 2008;16(3):133–140. 30. Harris RE, Clauw DJ, Scott DJ, et al. Decreased central μ-opioid receptor availability in fibromyalgia. J Neurosci. 2007; 27(37):10000–10006. 31. Baraniuk JN, Whalen G, Cunningham J, Clauw DJ. Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain. BMC Musculoskel Disord. 2004;5(1):48.

23. Fishbain D. Evidence-based data on pain relief with antidepressants. Ann Med. 2000;32(5):305–316.

32. Furlan A, Sandoval JA, MailisGagnon A, Tunks E. Opioids for chronic noncancer pain: a metaanalysis of effectiveness and side effects. Can Med Assoc J. 2006; 174(11):1589–1594.

24. Crofford LJ, Rowbotham MC, Mease PJ, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2005;52(4):1264–1273.

33. Sørensen J, Sjøgren P. Opioidinduced hyperalgesia. In Hanna M, Zylicz Z, eds. Cancer Pain. London: Springer. 2013: pp. 131–142.

25. Arnold LM, Goldenberg DL, Stanford SB, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial. Arthritis Rheum. 2007; 56(4):1336–1344. 26. Hauser W, Eich W, Herrmann M, et al. Fibromyalgia syndrome: classification, diagnosis, and treatment. Dtsch Arztebl Int. 2009;106(23):383–391.

34. Lee M, Silverman S, Hansen H, Paterl A, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14:145–161. 35. Angst A, Martin S, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology 2006;104(3): 570–587. 36. Compton MA. Cold-pressor pain tolerance in opiate and cocaine abusers: correlates of drug type

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and use status. J Pain Symptom Manage. 1994;9:462–473. 37. Guignard B, Bossard AE, Coste C, et al. Acute opioid tolerance: intraoperative remifentanil

increases postoperative pain and morphine requirement. Anesthesiology. 2000;93:409–417. 38. Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term

infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003;106: 49–57.

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Patient with myofascial pain syndrome: focus on functional restoration Tracy P. Jackson

Case study A 45-year-old male truck driver reported acute pain in his back after a collision with another motor vehicle 6 months ago, and filed a workers’ compensation claim at that time with his employer. He is an obese smoker, but otherwise healthy. He has been taking hydrocodone, cyclobenzaprine, and meloxicam and reports persistent 8/10 daily pain, sometimes up to 11–12/10. His MRI demonstrates degenerative disc disease with a broad-based central protrusion at L5/S1 without central canal or neuroforaminal stenosis. He has trialed a series of three epidural steroid injections, and a course of physical therapy which he could not complete because of pain. His physical exam reveals no focal neurologic findings, although he does report significant tenderness to palpation of his lumbar paraspinal musculature, and reports bending or twisting in any direction is painful. He has not been able to return to work and is applying for permanent disability benefits as a result of his inability to drive secondary to pain, limited range of motion, and difficulty with prolonged sitting. He is at your office with his case manager to request a functional capacity evaluation and is asking for pain medication to get to his next appointment with his primary treating physician; he ran out of pills from his last prescription a few days earlier secondary to “a really bad night” a few days ago. He says “nothing else works for my pain except the hydrocodone.” He has retained an attorney, as he is so frustrated with “getting the runaround from workers’ comp,” and is thinking of suing the driver who hit his truck.

1. What happens when an employee files a claim through workers’ compensation? The workers’ compensation (WC) system was developed by individual states in the USA in the early

twentieth century in order to strike a bargain between employer and employee rights. Employers agreed to be liable for payment for injuries incurred on the job regardless of fault in exchange for a limit to their liability; employees gave up the right to sue their employers in exchange for prompt and guaranteed payment. Although WC laws still vary by state, there are commonalities with regard to the process by which a claim is filed. The initial step is for the employee to notify the employer about the injury, whether acute (as in the case of the truck driver in a motor vehicle collision) or chronic (like wrist pain from repetitive keyboard usage). The employee may seek initial medical treatment from a physician of his choosing. The employer will immediately notify the insurer who then assigns a claims adjuster to the case. The claims adjuster will then review the insurance policy, request medical records for review, and take a report of the circumstances surrounding the injury from the employee, employer, and any witnesses. The adjuster will then make the decision to approve or deny the claim. Once a claim is approved, all further billing claims for healthcare related to the injury must go through the adjuster. Many times, the insurance carrier may hire a registered nurse case manager (NCM). The role of the NCM is to assist the injured worker (IW) in the planning and coordination of healthcare services and to be a liaison between the adjuster, the employer, the treating providers, and the patient. Although hired by the employer, the NCM is meant to be an advocate for the patient, helping the IW understand and navigate the complexities of the system and avail himself or herself of treatment options with informed consent.

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2. Why do some patients have an attorney? If the adjuster determines that injury is not workrelated, or that the injury is not caused by factors in the employer’s control, the claim is denied. The IW may file an appeal, and may even sue the employer if the IW can demonstrate intentional or egregious harm on the part of the employer. An involved third party (like the driver of the motor vehicle that struck the truck) may be subject to a personal injury lawsuit by the IW. If there is a dispute at any time between the IW and the employer/insurer, then an attorney is often retained by the IW to represent him. Many attorneys will accept these claims free of charge to the IW, or a state WC board may appoint an attorney to represent him upon request. Some IWs choose to have legal representation for the purposes of personal injury litigation; others choose to retain counsel in order to contest an adjuster’s denials of recommended medical care during the course of treatment. Attorneys for both sides may request a deposition with a physician to clarify that the patient’s symptoms (for example, pain) are related to the work injury, and/or to clarify the need for recommended services under dispute. The insurers or attorneys may also request a utilization review (UR) periodically, often involving an independent medical opinion from a non-treating physician to assist in determining medical necessity for proposed treatment plans. Of note, IWs seeking compensation via the legal system have higher mental health complaints at baseline compared to the non-compensation group, and these psychologic outcomes improve to a lesser degree by the time of settlement when compared to those not compensated with the aid of an attorney.[1] Claimants who retain an attorney secondary to dissatisfaction with the WC system also have longer times to settlement, higher cost, greater disability, and higher levels of post-settlement socioeconomic stress and catastrophizing at long-term follow-up.[2]

3. What are the different types of disability benefits and how is candidacy for these benefits determined? The level of disability is assessed in association with any WC claim in order to determine the amount of

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financial restitution for which the IW qualifies. A physician makes this determination through performance of a functional capacity evaluation (FCE). There are several published metrics for FCE, all of which are intended to provide an objective measure of the IW’s functional ability compared to the physical tasks required for employment, and to track outcomes of treatment and rehabilitation programs. Using FCEs, physicians recommend duty or time restrictions when IWs return to work. FCEs may also aid in designation of a degree of impairment, which is typically used to describe anatomic or functional loss in a particular organ or body part (eye, spine, lung, finger). Assignment of the degree of disability takes into account the effect of this impairment on the patient’s ability to function in work or society. There are four types of disability recognized by state WC programs, although the schedules for length and amount of reimbursement vary. These are: 1. Temporary total disability (TTD). Wage-earning capacity is lost, but just temporarily. 2. Temporary partial disability (TPD). Wage-earning capacity is only partially lost, on a temporary basis. 3. Permanent total disability (PTD). Wage-earning capacity is permanently and totally lost. 4. Permanent partial disability (PPD). A portion of wage-earning capacity is permanently lost. The determination of permanent benefits is predicated on the patient reaching maximum medical improvement (MMI) as deemed by a physician. This implies that no further healing or improvement is possible despite continuing medical care or rehabilitation. If there is any dispute as to the impairment rating, assignation of MMI, or disability recommendations by the primary treating physician, the insurer my request an independent medical evaluation (IME) by a qualified medical evaluator (QME). QMEs are trained and licensed specifically to evaluate IWs and must participate in continuing medical education surrounding the changing regulatory guidelines in the state in which they practice. WC disability benefits only cover impairments sustained on the job. However, IWs may be eligible for Social Security Disability benefits (SDI) if they have permanent impairments that preclude any gainful work in any capacity, regardless of the location of the disabling event. Receipt of SDI requires that the IW has paid social security taxes prior to the disabling event. Supplemental Security Income (SSI) is another

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federal subsidy program available to any disabled citizen with limited income or resources.[3–5]

4. What are pharmacologic options for our patient going forward? Medications This patient has received multimodal analgesic therapy with NSAIDs, muscle relaxants, and opioids and still reports 8/10 pain at baseline. The use of opioids is a controversial topic in management of chronic nonmalignant pain in both IWs and the population at large. Despite extensive investigation, there is still a lack of robust evidence that pain or functionality is improved in chronic non-malignant pain with opioid use longer than 12 weeks, and in fact, disability may be higher.[6] While opioids are clearly indicated for the management of acute pain secondary to injury, persistent opioid therapy in this patient, and all patients, should be carefully evaluated with individualized contextual assessment of the risks and benefits of ongoing opioid therapy. At a minimum, published clinical guidelines support opioids should provide both analgesia and increased activity as a result of this analgesia. Compared with IWs not prescribed opioids, odds of chronic work loss are estimated to be six times greater for IWs using schedule II opioids and 11–14 times greater for IWs with opioid prescriptions of any type for longer than 3 months, suggesting that opioid therapy may not arrest the cycle of pain and work loss.[7] Additionally, for those IWs who receive opioids long-term, opioid doses and cost increase substantially without clinically important improvement in pain and function, suggesting the benefit of chronic opioid therapy may not be effective in improving pain or reducing disability in the WC population.[8,9] Opioid therapy is also not without risk: The nationwide epidemic of opioid misuse and diversion is well documented.[10] For ongoing opioid therapy, adverse side effects and aberrant behavior should be absent, and screening and surveillance for opioid abuse is of paramount importance.[11,12] Risk factors for opioid misuse, abuse, or diversion include the following: 1. Past or current history of any substance abuse 2. Patterns: early refills, lost or stolen medication 3. Multiple ER visits, multiple doctors 4. Focus on opioids, won’t consider other options

5. Increasing dose with decreasing function 6. Patient’s belief of potential for addiction 7. “Excessive” opioid needs relative to other patients with same diagnosis[13] This patient has been on opioids > 12 weeks, abuses tobacco, and is requesting more opioids; he notes no demonstrable increase in function, no apparent sustained analgesia, and focuses on hydrocodone as the only medication that works. Given his risk factors, further surveillance and monitoring (controlled substance database query to check for multiple prescribers, urine drug screening, pill counts, close follow-up, etc.) is indicated if opioids are to be continued. Other options include opioid rotation, inpatient or outpatient detoxification from opioids, and trials of pharmacotherapy for chronic pain with antineuropathics or antidepressants. Medication management should be individualized and based on ongoing risk/benefit assessment in the broader context of multidisciplinary pain management strategies for patients refractory to initial treatment.[14–19]

5. Are there interventional options for our patient? As with medications, clinical guidelines for low back pain management recommend inclusion of interventional options within a multimodal plan. Options for interventional management of axial low back pain can target musculature (trigger point injections), facet joints (intra-articular steroid injections and radiofrequency ablation of medial branch nerves), epidural steroid injections (to which this patient has not responded), and sacroiliac injections, among others. However, IW status is relevant to consider when deciding upon interventional therapy, especially if initial or recurrent targeted interventional therapy is ineffective. This has been addressed in groups of IWs undergoing back surgery and spinal cord stimulation (SCS) for failed back surgery syndrome (FBSS). In one sample of IWs with FBSS, the high procedure cost of spinal cord stimulation (SCS) was not offset by lower costs of subsequent care.[20] In another trial of IWs randomized to either SCS, evaluation by a pain specialist without SCS, or neither intervention, < 10% of IWs in any group had reduced opioid use or improvement in any outcome measuring pain or function at 24 months.[21] Additionally, when combined with non-operative care, surgical treatment of

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lumbar disc herniation appears to result in no meaningful clinical change in pain or functional outcomes for IWs, as opposed to the improvements attributable to surgery in a non-compensated group.[22] These data encourage caution in applying traditional interventional approaches to IWs whose pain is not durably relieved in a timely fashion with such measures. In these IWs, pain may be exacerbated by a variety of confounding psychosocial factors specific to the WC system, and further treatment strategies should take these into account.

6. What type of physical therapy is best? Physical therapy has long been a mainstay of treatment for the management of low back pain. However, the type and degree of physical rehabilitation can vary widely. Limitations of the literature are a result of very little consistency in the described components of the therapy, the type or amount of therapist involvement, the duration of therapy, the intensity of therapy, or the outcome measures used to assess efficacy. The general consensus is that exercise therapy that consists of individually designed programs (including stretching or strengthening) delivered with supervision may improve pain and function in chronic non-specific low back pain.[23] Specifically with regard to IWs, physical therapy modalities are the main components of rehabilitation. Cohesive outpatient physical therapy programming (which may or may not involve some vocational counseling or psychologic support) are often referred to as “back school,” “work simulation programs,” and “work hardening.” The focus is generally on spinal mobility, trunk strength, endurance, coordination, lifting capacity, positional tolerance, cardiovascular fitness, and ergonomics, although this too can vary widely. “Intense” physical conditioning programs that involve some sort of workplace focus or simulation are likely to have a more significant effect on the amount of work loss than “light” physical conditioning.[24] In any case, it is clear that non-compliance with physical therapy in this patient predicts a poorer functional prognosis.

7. Is psychologic therapy necessary for this patient? The interface between IWs and the WC system results in high patient-reported frustration, financial strain,

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and mental distress independent of the injury or pain. This is attributed to limited healthcare access, conflicting medical opinions, poor understanding of the system, and confusion about decision-making authority.[25] Since psychosocial function is a key determinant of the capacity to rehabilitation in IWs, the ability to work and amount of work loss is mediated to a large extent by undiagnosed mental health comorbidities, and not purely somatic symptoms.[26] The fear avoidance model of pain (FAM) describes the cycle in which many patients with chronic pain, particularly in a WC setting, become progressively disabled. Pain catastrophizing is a psychologic feature describing those who have significant disabling anxiety regarding their ability to function in any context given the pain they experience. These patients often describe pain as > 10/10 on a numerical rating scale, as exhibited by this patient. As pain catastrophizing is the cognitive antecedent of pain-related fear, and pain-related fear is the emotional antecedent of depression and disability, catastrophizing and kinesiophobia are independent predictors of poor long-term pain-related outcomes. Furthermore, catastrophizing predicts long-term pain intensity and kinesiophobia predicts long-term work disability.[27] Workers who stay at work despite chronic musculoskeletal pain have lower levels of fear avoidance behavior, catastrophizing, and perceived workload. They also are more likely to accept their pain, and feel they have some control over both the pain and their life in general.[28] IWs who do not continue working tend to exhibit risk factors prior to injury. Occupational risk factors include:  Jobs that require effort beyond perceived physical capabilities  Low levels of job satisfaction  Poor working conditions  Poor rating by superiors  History of compensation for spinal condition  Litigation regarding compensation  Past receipt of work-related sickness payments[29]     

Psychologic risk factors include: Low level of schooling Low income Significant family dysfunction Depression, anxiety, anger, somatization High self-reported pain and disability levels

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 Low self-reported expectation of improvement  Catastrophizing[29–31] As many of these risk factors are psychosocial, and often preceded the injury, meaningful reduction in disability and/or return to work may require a comprehensive multimodal approach to pain management and rehabilitation. While over 70% of IWs are reported to recover and return to work within a few months of injury, only 50% of IWs out of work for 6 months will return to work, and virtually none return after 2 years.[32] Therefore, in the presence of occupational or psychological risk factors, particularly catastrophizing and kinesiophobia, early multidisciplinary rehabilitation is recommended. With little psychologic history, this patient already has been out of work for 6 months and exhibits catastrophizing, kinesiophobia, high self-reported pain and disability, and possible litigation regarding his compensation. It is critical that psychological support be initiated if there is a chance for meaningful functionality in the future. This may be best accomplished with a functional restoration program.

8. What is a functional restoration program? Functional restoration programs (FRPs) are also variously described as functional rehabilitation programs or biopsychosocial/comprehensive multidisciplinary rehabilitation programs. The fundamental key to efficacy is that any program designated an FRP must have components to simultaneously address physical, social, psychological, and occupational deficits in a team setting.[24] The crux of therapy uses daily graded activity with application of operant behavioral principles toward movement aversion. Greater than 100 hours of continuous outpatient therapy is needed for improved functionality and reduction in pain and work loss when compared to shorter outpatient or inpatient programming.[33] Many FRPs also include opioid detoxification in the curricula, and those IWs who undergo withdrawal of opioids during the program still experience significant and durable improvement in pain severity and functioning, with no difference compared in outcomes when compared to those who did not undergo detoxification.[34] Goals of FRPs are primarily functional and include:  Improvement in physical function

     

Improvement in general function (social) Increase in self-management Improvement in vocational disability Reduction in opioid/sedative medication Reduction in healthcare utilization Reduction in pain level[35]

The physical components must involve “progression by contract” and education regarding “hurt vs. harm” so that IWs may not stop participating secondary to pain. In order to be effective at reducing work loss compared to usual care, a therapist or team using cognitive-based behavioral coaching must directly supervise intensive physical training, which must be active (as opposed to passive hands-on work by therapist) and should address aerobic capacity, muscle strength, endurance, and coordination in a way that is relevant to working. The key psychologic interventions often include a tailored combination of the following:  Behavioral pain management  Muscle relaxation  Guided imagery for stress reduction  EMG/temperature-guided biofeedback  Cognitive behavioral skills  Assertiveness training  Crisis intervention and family counseling  Education into meaning of disability and unemployment Overall, when FRPs use these parameters, patients return to work faster, have fewer sick leaves, and report less subjective disability.[24,36] This also results in significant reduction in annual healthcare costs.[37] Furthermore, comparable outcomes have been reported in different states and countries, with different economic and social systems.[38] Readiness to self-manage pain is a critical factor predicting completion.[39] In the 20% who do not complete the programs, risk factors include older age, female gender, opioid dependence, antisocial or cluster B personality disorders, longer duration of pain, extreme disability or receipt of SDI/SSI at admission, and non-working status at discharge.[40,41] In this patient, a FRP coupled with opioid detoxification, initiated as soon as possible, likely offers the best chance for meaningful functional recovery.

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References 1.

Elbers NA, Hulst L, Cuijpers P, Akkermans AJ, Bruinvels DJ. Do compensation processes impair mental health? A meta-analysis. Injury. 2013;44:674–683.

2.

Chibnall J, Tait R. Legal Representation and dissatisfaction with workers’ compensation: implications for claimant adjustment. Psychological Injury and Law. 2010;3:230–240.

3.

http://www.tn.gov/labor-wfd/ wcomp.shtml.

4.

https://http://www.wcfgroup.com/ glossary-terms.

5.

http://www.ssa.gov/policy/docs/ ssb/v65n4/v65n4p3.html.

6.

Deshpande A, Furlan A, MailisGagnon A, Atlas S, Turk D. Opioids for chronic low back pain. Cochrane Database Syst Rev. 2007:CD004959.

7.

8.

9.

Volinn E, Fargo JD, Fine PG. Opioid therapy for nonspecific low back pain and the outcome of chronic work loss. Pain. 2009;142:194–201. Franklin GM, Rahman EA, Turner JA, Daniell WE, FultonKehoe D. Opioid use for chronic low back pain: a prospective, population-based study among injured workers in Washington state, 2002–2005. Clin J Pain. 2009;25:743–751. Bernacki EJ, Yuspeh L, Lavin R, Tao XG. Increases in the use and cost of opioids to treat acute and chronic pain in injured workers, 1999 to 2009. J Occup Environ Med. 2012;54:216–223.

10. Manchikanti L, Fellows B, Ailinani H, Pampati V. Therapeutic use, abuse, and nonmedical use of opioids: a tenyear perspective. Pain Physician. 2010;13:401–435. 11. Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic

228

non-cancer pain: Part 2 – guidance. Pain Physician. 2012;15: S67–116. 12. Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I – evidence assessment. Pain Physician. 2012;15:S1–65. 13. Manchikanti L, Atluri S, Trescot AM, Giordano J. Monitoring opioid adherence in chronic pain patients: tools, techniques, and utility. Pain Physician. 2008;11: S155–180. 14. Chou R, Huffman LH; American Pain Society; American College of Physicians. Nonpharmacologic therapies for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147:492–504. 15. Chou R, Huffman LH. Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147:505–514. 16. Chou R, Huffman LH. Nonpharmacologic therapies for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147:492–504. 17. Bouton C, Roche G, Roquelaure Y, et al. Management of low back pain in primary care prior to multidisciplinary functional restoration: a retrospective study of 72 patients. Ann Readapt Med Phys. 2008;51: 650–656, 56–62. 18. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations

from systematic reviews. Gen Hosp Psychiatry. 2009;31:206–219. 19. Morlion B. Chronic low back pain: pharmacological, interventional and surgical strategies. Nat Rev Neurol. 2013. 20. Hollingworth W, Turner JA, Welton NJ, Comstock BA, Deyo RA. Costs and cost-effectiveness of spinal cord stimulation (SCS) for failed back surgery syndrome: an observational study in a workers’ compensation population. Spine (Phila Pa 1976). 2011;36:2076–2083. 21. Turner JA, Hollingworth W, Comstock BA, Deyo RA. Spinal cord stimulation for failed back surgery syndrome: outcomes in a workers’ compensation setting. Pain. 2010;148:14–25. 22. Atlas SJ, Tosteson TD, Blood EA, et al. The impact of workers’ compensation on outcomes of surgical and nonoperative therapy for patients with a lumbar disc herniation: SPORT. Spine (Phila Pa 1976). 2010;35:89–97. 23. Hayden JA, van Tulder MW, Tomlinson G. Systematic review: strategies for using exercise therapy to improve outcomes in chronic low back pain. Ann Intern Med. 2005;142:776–785. 24. Schaafsma F, Schonstein E, Whelan KM, et al. Physical conditioning programs for improving work outcomes in workers with back pain. Cochrane Database Syst Rev. 2010: CD001822. 25. Kosny A, MacEachen E, Ferrier S, Chambers L. The role of health care providers in long term and complicated workers’ compensation claims. J Occup Rehabil. 2011;21:582–590. 26. Olaya-Contreras P, Styf J. Biopsychosocial function analyses changes the assessment of the ability to work in patients on long-term sick-leave due to chronic musculoskeletal pain: the role of undiagnosed mental health

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comorbidity. Scand J Pub Health. 2013;41:247–255. 27. Sullivan MJ, Adams H, Martel MO, Scott W, Wideman T. Catastrophizing and perceived injustice: risk factors for the transition to chronicity after whiplash injury. Spine (Phila Pa 1976). 2011;36:S244–249. 28. de Vries HJ, Reneman MF, Groothoff JW, Geertzen JH, Brouwer S. Workers who stay at work despite chronic nonspecific musculoskeletal pain: do they differ from workers with sick leave? J Occup Rehabil. 2012;22:489–502. 29. Valat JP, Goupille P, Vedere V. Low back pain: risk factors for chronicity. Rev Rhum Engl Ed. 1997;64:189–194. 30. Gatchel RJ, Polatin PB, Mayer TG. The dominant role of psychosocial risk factors in the development of chronic low back pain disability. Spine (Phila Pa 1976). 1995;20:2702–2709. 31. Feuerstein M, Callan-Harris S, Hickey P, et al. Multidisciplinary rehabilitation of chronic workrelated upper extremity disorders: long-term effects. J Occup Med. 1993;35:396–403.

32. Poiraudeau S, Rannou F, Revel M. Functional restoration programs for low back pain: a systematic review. Ann Readapt Med Phys. 2007;50:425–429, 19–24. 33. Snodgrass J. Effective occupational therapy interventions in the rehabilitation of individuals with work-related low back injuries and illnesses: a systematic review. Am J Occup Ther. 2011;65:37–43. 34. Townsend CO, Kerkvliet JL, Bruce BK. A longitudinal study of the efficacy of a comprehensive pain rehabilitation program with opioid withdrawal: comparison of treatment outcomes based on opioid use status at admission. Pain. 2008;140:177–189. doi: 10.1016/j.pain.2008.08.005. Epub 08 Sep 19. 35. Sanders SH, Harden RN, Vicente PJ. Evidence-based clinical practice guidelines for interdisciplinary rehabilitation of chronic nonmalignant pain syndrome patients. Pain Pract. 2005;5:303–315. 36. Guzman J. Multidisciplinary bio-psycho-social rehabilitation for chronic low back pain. Cochrane Database Syst Rev. 2008;23:CD002213.

37. Gatchel RJ, Okifuji A. Evidencebased scientific data documenting the treatment and costeffectiveness of comprehensive pain programs for chronic nonmalignant pain. J Pain. 2006;7:779–793. 38. Gatchel RJ, Mayer TG. Evidenceinformed management of chronic low back pain with functional restoration. Spine J. 2008;8:65–69. 39. Tkachuk GA, Marshall JK, Mercado AC, McMurtry B, Stockdale-Winder F. Readiness for change predicts outcomes of functional rehabilitation following motor vehicle accident. J Occup Rehabil. 2012;22:97–104. 40. Howard KJ, Mayer TG, Theodore BR, Gatchel RJ. Patients with chronic disabling occupational musculoskeletal disorder failing to complete functional restoration: analysis of treatment-resistant personality characteristics. Arch Phys Med Rehabil. 2009;90: 778–785. 41. Brede E, Mayer TG, Gatchel RJ. Prediction of failure to retain work 1 year after interdisciplinary functional restoration in occupational injuries. Arch Phys Med Rehabil. 2012;93:268–274.

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31

Musculoskeletal Pain

Spinal manipulation, osteopathic manipulative treatment, and spasticity Monika A. Krzyzek, John P. McCallin, Justin B. Boge, Dean Hommer, Prasad Lakshminarasimhiah, Rebekah L. Nilson, and Brandon J. Goff

Case study A 31-year-old male was referred to your office for spinal manipulation with a diagnosis of myofascial pain syndrome. He states that he has chronic low back pain and is asking for spinal manipulative treatment for symptomatic relief of his low back pain. On examination you notice that he has left-sided muscle spasm and somatic dysfunction of the lumbar spine at L5–S1 (rotated left side bent right). He also has mild spasticity, confined to the lower extremities, which upon further questioning you find out is from a benign but compressive meningioma that was neurosurgically removed from his thoracic spine when he was younger. His gait is altered due to lower extremity spasticity, and he has chronic low back pain that is worse when he ambulates or stands for a prolonged period of time. MRI shows chronic postsurgical changes, and mild facet hypertrophy, but is otherwise unremarkable.

1. Introduction to spinal manipulation Spinal manipulation is a technique that is employed by osteopathic physicians, chiropractors, physical therapists, and occupational therapists in the treatment of somatic dysfunction and pain that arises from misalignment of the vertebral segments. It is only one aspect of a broader field of manual therapy which includes a variety of interventions to address both joint and soft tissue dysfunctions. Specifically, manipulation of the spine involves passive, high, and low velocity thrust maneuvers that are performed before or at the physiologic end range of motion of synovial joints. Chiropractors refer to spine mobilization as an “adjustment,” while physical therapists call it a Grade V mobilization. Osteopathic physicians call spinal mobilization osteopathic manipulation therapy (OMT)

or osteopathic manipulative medicine (OMM). Spinal mobilization is a passive, high-velocity motion performed within the available physiologic range of motion at a dysfunctional segment. Somatic dysfunction may limit the motion of that vertebral segment, causing pain. Thus spinal manipulation, also known as HVLA (high velocity, low amplitude), attempts to restore proper motion and joint biomechanics to a spinal segment which has limited range of motion due to somatic dysfunction restriction. During spinal manipulation, the practitioner applies directed manual impulse, or thrust, to a joint, at or near the end of the physiologic tissue range of motion. This is usually accompanied by an audible “crack” or “pop” as the joint is moved through its restrictive/pathologic barrier. The reason for this audible “crack” is controversial; however it is widely thought to be a result of cavitation (implosion of gas bubbles) of the facet joint. Normal physiologic range of motion of the spinal segment is thus re-established by moving it through the restrictive barrier. The HVLA thrust is also thought to forcefully stretch contracted muscles. This sends afferent impulses from the muscle spindles to the central nervous system, causing an inhibitory response and relaxing the muscle. It is also thought that the stretch of the muscle causes stretching of the Golgi tendon apparatus which causes further relaxation of the tight muscle.[1–3] The basic principles of manipulation center around the premises that the body as a whole is a unit that is self regulating and self healing and that structure and function are reciprocally related. Somatic dysfunction is an alteration of function of the skeletal and myofascial structures, as well as associated vasculature, lympatics, and nerves. Somatic dysfunction is diagnosed on physical examination through tissue texture changes, asymmetry, restriction of motion,

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Table 31.1. Fryette’s Laws of Spinal Motion

Principle I

Seen when the spine is in NEUTRAL position. Sidebending and rotation which occur to the OPPOSITE side

Seen in TYPE I SOMATIC DYSFUNCTIONS (aka. Group curves, where more than one vertebral segment is out of alignment). The entire group curve will be rotated to the side of the convexity

Principle II

Seen when the spine is in a NON-NEUTRAL position (either flexed or extended). Sidebending and rotation which occur to the OPPOSITE side in the restricted segment

Seen in TYPE II SOMATIC DYSFUNCTIONS (when only one segment is out of alignment). Segment is restricted in motion and becomes worse with either flexion or extension

Principle III

When motion is introduced in one plane it will reduce motion in the other planes

A dysfunction of motion in one physiologic plane will negatively affect all the other planes of motion of the spine

and tenderness on palpation. Acute somatic dysfunction of a spinal segment will show restricted range of motion with tenderness around the segment. Skin temperature around the area tends to be warm and there can be increased skin moisture around the area, as apparent with increased skin drag. The muscle and soft tissue is boggy, edematous, erythematous, and there is segmental muscle hypertonicity. Chronic somatic dysfunction also shows restricted range of motion and tenderness, however the tenderness to palpation tends to be more dull than sharp (as in the acute phase) and the patient may experience paresthesias in the area. The skin is cool and dry and feels ropy, fibrotic, and decreased muscle tone can be appreciated with palpation.[2,3] Multiple reflexes or arcs can produce stimuli which can generate a dysfunction in an area other than the primary problem. These include the somato-somatic reflex, somato-visceral reflex, viscera-visceral reflex, and the viscera-somatic reflex. Facilitation, a lowered threshold of neuronal excitation, can further lead to dysfunctions in body regions that are innervated by the same pool of neurons as the original dysfunction.[1,2] At the atlanto-occipital joint sidebending and rotation occur in opposite directions. At the atlantoaxial joint, mainly rotation occurs, with very little flexion or extension. In most of the cervical spine (C2–C7), coupling is seen where sidebending and rotation occur in the same direction.[1–3] In the thoracic and lumbar spine, normal motion of the vertebral segments with regard to sidebending and rotation occurs in the opposite direction. When the motion of individual spinal segments becomes restricted, somatic dysfunction occurs. In other words, when a vertebral level is significantly flexed or extended, as compared to the others around it, sidebending and rotation occur in

the same direction, which goes against normal spinal segmental motion. Spinal motion is summarized in Fryette’s Laws in Table 31.1.[1,2]

2. Contraindications to spinal manipulation Absolute contraindications to spinal manipulation include: osteoporosis, osteomyelitis, vertebral fracture, dislocation, skeletal neoplasm in the area of treatment, rheumatoid arthritis (especially of the cervical spine due to risk of atlantoaxial subluxation due to ligamentous laxity), Down’s syndrome (due to high incidence of atlantoaxial instability), abdominal aortic aneurism, bleeding diatheses, spondylolysis, spondylolisthesis, myelopathy, caudal equina compression, cord compression, and nerve root compression with increasing neurologic deficit. Relative contraindications include: pneumonia, coagulopathy, use of anticoagulants, acute muscle injury, acute joint inflammation, acute whiplash, neurologic pathologies such as a radiculopathy, herniated intervertebral disc, vertebral artery stenosis, cerebrovascular accident, pregnancy, open wounds, recent surgery, and joint hypermobility.[1,3–5] Risks of spinal adjustments are rare, provided the patients are appropriately screened and treated by experienced manipulative practitioners. These risks include: vertebrobasillar accidents (CVA and TIA), vertebral artery dissection, disc herniations or worsening of an existent disc herniation, vertebral fractures, epidural hematoma, rib fractures, and spinal cord injury (e.g., quadriplegia and cauda equina syndrome). Serious risks, although rare, can cause significant morbidity and mortality and should be included in any spinal manipulation informed consent.[1,2,5,6]

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Chapter 31: Spinal manipulation, osteopathic manipulative treatment, and spasticity

3. Current literature considerations Strong randomized controlled trials for the use of spinal manipulation are lacking and more study into this area is needed. Some studies suggest that early spinal manipulation is effective for low back pain. Others show benefit for both short- and long-term outcome measures with spinal manipulation being better than placebo in treatment of acute low back pain.[7] Some studies point to spinal manipulation being more effective than general exercise but not specific home exercise programs or physical therapy but with spinal manipulation being more costeffective than formal therapy programs.[8] However, at this point, it is unclear whether spinal manipulation is more effective than physical therapy, massage, and other modalities.[7–9] There seems to be a difference between treating chronic versus acute pain and the part of the spine which is painful (cervical, thoracic, or lumbar). Overall there seems to be insufficient evidence to either support or refute the effectiveness of spinal manipulation on acute back pain, discogenic pain, or chronic back pain. Methodologic flaws in many of the studies make drawing conclusions and the development of clear guidelines difficult. Mechanism of injury, acuity, normal course of the disease process, or injury and cost-effectiveness, as well as side effects and risks and benefits all need to be weighted in the decision whether spinal manipulation is the correct course of treatment. We need to take into consideration that much of the acute spine (especially low back) pain improves on its own, therefore it is difficult to measure efficacy of therapies. Further studies are needed in the area of spinal manipulation as compared to other commonly used treatments such as structured physical therapy programs, specific home exercise programs, “back schools,” traction, bracing, acupuncture, biofeedback, and TENS (and other modalities) as well as medication management and interventional therapies.[10,11]

4. Introduction to spasticity Spasticity has been defined as an increase in muscle tone due to hyperexcitability of the stretch reflex and is characterized by a velocity-dependent increase in tonic stretch reflexes.[12] Spasticity is a component of upper motor neuron syndrome. Upper motor neuron syndrome can be seen in many conditions including stroke, spinal cord injury, traumatic

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Table 31.2. Modified Ashworth Scale

0

No increase in tone

1

Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension

1+

Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM

2

More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved

3

Considerable increase in muscle tone, passive movement difficult

4

Affected part(s) rigid in flexion or extension

brain injury, cerebral palsy, multiple sclerosis, and motor neuron disease, such as amyotrophic lateral sclerosis (ALS). Assessment of spasticity should include identifying which muscles or muscle groups are affected and how spasticity affects patient function, including mobility and ADLs. There are many ways to quantify spasticity. One of the most widely used scales is the Modified Ashworth Scale (Table 31.2).[13] An increase in spasticity over a patient’s baseline should raise suspicion for a noxious stimulus causing an aggravation of the patient’s spasticity. These factors can include urinary tract or other infections, urinary retention, constipation, a painful stimulus such as ingrown toenail, skin ulcer, or deep venous thrombosis (DVT). A cornerstone for spasticity management is prevention of these factors and early recognition and treatment.[14,15]

5. Spasticity management Spasticity can be managed non-pharmacologically, pharmacologically, and surgically. Non-pharmacologic treatments should be considered before moving to pharmacologic or other more invasive treatments. These interventions include daily ROM exercise programs, splinting and serial casting, cold and heat application, electrical stimulation, and vibration. When splinting and serial casting, special attention must be paid to skin integrity. Overlying skin must be frequently inspected for early evidence of skin breakdown.[14,15]

Chapter 31: Spinal manipulation, osteopathic manipulative treatment, and spasticity

There are many pharmacologic treatments that are mainstays in the treatment of spasticity. These treatments can include oral and IV medications as well as injectable neurolytics or neurotoxins.[14,15] GABA (gamma aminobutyric acid) is one of the main inhibitory neurotransmitters in the central nervous system. Some of the pharmacologic treatments have their effects on the GABA receptors. Baclofen is a GABA analog that binds to the GABA-B receptor decreasing calcium influx, ultimately reducing excitatory neurotransmitter release. Baclofen is often the drug of choice in treating spasticity related to spinal cord injury or multiple sclerosis. Sedation is one of the most common side effects. Patients and providers must be aware that abrupt discontinuation of baclofen can lower the seizure threshold. Another class of medications that acts on the GABA receptors is the benzodiazepines such as diazepam and clonazepam. These medications act on the GABA-A receptors and inhibit muscle contraction.[14,15] The alpha-2 agonists tizanidine and clonidine are centrally acting agents that decrease reflex activity. Common side effects of alpha-2 agonists are related to the alpha-2 adrenergic effects. These include hypotension, bradycardia, dizziness, and sedation. Although present with each, these side effects are generally less severe with tizanidine than clonidine.[14,15] While most of the oral pharmacologic treatments for spasticity are centrally acting, there is one agent that acts peripherally and therefore does not have the central side effects of the other medications. Dantrolene sodium, widely known for its use in malignant hyperthermia, acts peripherally on skeletal muscle decreasing calcium release from the sarcoplasmic reticulum, thereby inhibiting muscle contractions. This medication can be hepatotoxic and long-term use should be accompanied by routine monitoring of the liver function tests.[14,15] All of these oral and IV agents can affect spasticity in the entire body. For local treatment of spasticity, local injection of neurolytic agents or neurotoxins can be used.[14,15] The use of neurostimulation techniques, electromyography (EMG), or ultrasound for guidance can help localize the target site of injections for these local treatments and minimize the amount of medication required. The two most common neurolytic agents used are phenol and ethyl alcohol. Phenol causes protein denaturation and subsequent axonal necrosis. Ethyl alcohol is thought to cause dehydration of the nerve

tissues. The most common side effect is a dysesthetic pain when injected into a sensory or mixed nerve that can last for a significant amount of time. Because of this side effect these injections are usually only done on primarily motor nerves or in motor point blocks. For example, in a patient with a scissoring gait from adductor spasticity, a phenol injection of the obturator nerve can be performed with minimal side effects as the obturator nerve has only a small area of cutaneous sensory innervations.[14,15] Another common injectable treatment for spasticity is botulinum toxin. Botulinum toxin acts at the neuromuscular junction, presynaptically; it prevents release of acetylcholine by damaging the SNARE protein (Soluble N-ethyl-maleimide sensitive factor Attachment REceptor) and prevents contraction of the muscle. There are many different formulations of botulinum toxin and each has a different recommended dosing. In addition, it should be noted that there is no reliable conversion factor between the different types of botulinum toxin. Typically the peak effects of botulinum toxin are seen in 4–6 weeks after treatment and usually last 2–4 months.[14,15] A less common but effective pharmacologic treatment of spasticity involves intrathecal delivery of medication. Most commonly the medication delivered by this route is baclofen. The advantage this delivery system has is a significant increase in the potency of the medication with less systemic side effects. The primary disadvantage to this delivery method is the need for an invasive procedure for the implantation of the intrathecal pump. Additionally, intrathecal delivery of baclofen is generally more effective for lower extremity spasticity making it less ideal for the treatment of upper extremity spasticity. Complications of pump implantation include infection, pump failure, and tube dysfunction. In addition, the medication reservoir must be refilled periodically. Failure to refill the reservoir will result in the abrupt discontinuation of baclofen which, as described earlier, can decrease the seizure threshold. All of these factors must be taken into account when selecting patients for intrathecal baclofen. Prior to implantation, a trial must be performed. Typically this involves a lumbar puncture with delivery of 25 μg of baclofen into the intrathecal space. The level of spasticity is then monitored and compared to the preinjection level for the ensuing 4–6 hours. A decrease in one to two grades on the Modified Ashworth Scale in the desired muscle or muscle group would be

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considered a successful trial and pump implantation can then be considered. If an appropriate response is not obtained subsequent trials of increasing doses of 50, 75, and 100 μg may be considered.[14,15] If non-pharmacologic and pharmacologic treatments have failed to achieve satisfactory spasticity management and function, there are orthopedic and neurosurgical procedures that can be considered to assist with meeting these goals. These procedures include tendon lengthenings, tendon transfers, such as a split anterior tibial tendon transfer for equinovarus deformity, and neuroablative procedures, such as a dorsal rhizotomy or a myelotomy.[14,15] Finally it is well known that spasticity can result in multiple complications to include chronic pain, skin breakdown, altered gait, and difficulty with hygiene and other ADLs. An association has been identified

References 1.

2.

3.

4.

5.

6.

234

Modi RG, Shah N. Clinical Anatomy and Osteopathic Manipulative Medicine: COMLEX Review 2006, 1st ed. Malden, MA: Blackwell Publishing Inc. 2006. Savarese RG, Capobianco JD, Cox JJ. OMT Review: A Comprehensive Review in Osteopathic Medicine, 3rd ed. Jacksonville: OMT Review. 2003. Greenman PE. Principles of Manual Medicine, 3rd edn. Philadelphia, PA: Lippincott Williams & Wilkins. 2003. Cook C, Hegedus E, Showalter C, Sizer PS Jr. Coupling behavior of the cervical spine: a systematic review of the literature. J Manipulative Physiol Ther. 2006;29(7):570–575. Stevinson C, Ernst E. Risks associated with spinal manipulation. Am J Med. 2002;112(7):566–571. Di Fabio RP. Manipulation of the cervical spine: risks and benefits. Phys Ther. 1999;79(1):50–65.

between spasticity and heterotopic ossification, especially in patients with spinal cord injury and traumatic brain injury. However, before reducing spasticity, it is important to determine if the spasticity is benefitting the patient’s function. For example, a patient with lower extremity weakness may be using the spasticity to assist with standing or transfers, thereby achieving a higher level of function.[14,15]

Disclosure The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Army, Department of Defense or the US Government.

7.

Jonsson ALNE. Neck and Back Pain: The Scientific Evidence of Causes, Diagnosis, and Treatment. Philadelphia: Lippincott Williams & Wilkins. 2000.

8.

Bronfort G, Evans R, Anderson AV, et al. Spinal manipulation, medication, or home exercise with advice for acute and subacute neck pain: a randomized trial. Ann Intern Med. 2012;156(1 Pt 1): 1–10. doi: 10.1059/0003-4819156-1-201201030-00002.

9.

Chou R, Huffman LH. Nonpharmacologic therapies for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147(7):492–504.

10. Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for chronic low back pain: an update of a Cochrane review. Spine (Phila Pa 1976). 2011;36(13):E825–846. doi: 10.1097/BRS.0b013e3182197fe1.

11. Rubinstein SM, Terwee CB, Assendelft WJ, de Boer MR, van Tulder MW. Spinal manipulative therapy for acute low back pain: an update of the Cochrane review. Spine (Phila Pa 1976). 2013;38(3): E158–177. doi: 10.1097/ BRS.0b013e31827dd89d. 12. Lance JW. Symposium synopsis. In Feldman RG, Young RR, Koella WP, eds. Spasticity: Disordered Motor Control. Chicago: Year Book Medical. 1980: pp. 485–494. 13. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67(2): 206–207. 14. Braddom RL, Chan L, Harrast MA. Physical Medicine and Rehabilitation, 4th edn. Philadelphia, PA: Saunders/ Elsevier. 2011. 15. Cuccurullo SJ. Physical Medicine and Rehabilitation Board Review, 2nd ed. New York, NY: Demos Medical Publishing. 2009.

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Musculoskeletal Pain

Patient with ankle pain Jose E. Barreto and Thomas K. Bond

Case study A 42-year-old female presents with ankle pain and a history of previous “ankle sprains.” The patient has pain and swelling associated with running activities and lately even with walking activities.

1. What is the differential diagnosis? a. Chronic ankle sprain b. High ankle sprain (syndesmosis injury) c. Talar dome fracture or osteochondral defects (OCD) d. Peroneal tendon subluxation e. Midfoot injury or fracture The most common form of ankle pain experience acutely is the “sprained ankle.” Most people have either experienced this personally or know someone who has. An ankle sprain is the “spraining” or injuring via stretching, and, in severe cases, tearing of ankle ligaments. Thus, a “sprain” is the injuring of a ligament or ligaments; whereas, a “strain” is the injuring of a muscle or its corresponding tendon. There are different grades or degrees of severity of ligament strains. Grade 1 or mild sprains, where only a few fibers are affected and there is no laxity (“looseness”) of the injured ligament, nor corresponding resulting instability of the joint which the ligament is stabilizing; Grade 2 or moderate sprains involve an incomplete or partial tear of the ligament which leads to mild laxity of the ligament and resulting joint instability; Grade 3 or severe sprains are characterized by complete/full-thickness tears of the ligament with resulting gross ligamentous laxity and joint instability. A chronic ankle sprain is a chronic pain state which can develop when an ankle sprain is either inappropriately rehabilitated, or the ankle fails to

improve despite receiving appropriate physical therapy and rehabilitation. The chronic ankle sprain is characterized by ligament laxity with resulting joint instability, thus leading to chronic, daily pain, and possibly, swelling and decreased functional ability.

2. What risk factors predispose patients to have a chronic ankle sprain? a. b. c. d. e.

Athletes Traumatic injuries Grade 2 or 3 ankle sprains Inadequate physical therapy or no rehabilitation Hypermobility syndrome

3. Why is this condition overlooked? There are about 23 000 ankle sprains in the USA every day[1] – that is, approximately 9 million ankle sprains each year in the USA alone. Unfortunately, it is estimated that up to 40% of these ankle sprains may become chronic leading to chronic ankle pain for some 3.5 million patients each year.[2] Many patients receive only “passive” treatment of just waiting for symptoms to improve on their own. Many of these patients go back to their normal activities and even back to the playing field without adequate physical therapy, particularly proprioceptive exercises. Some physicians think that an ankle sprain will heal on its own, even in severe cases.

4. Describe the anatomy and pathophysiology of a chronic ankle sprain The foot and ankle have two principal functions: propulsion and support. The ankle joint is made up

Case Studies in Pain Management, ed. Alan David Kaye and Rinoo V. Shah. Published by Cambridge University Press. © Cambridge University Press 2015.

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of two joints: the talocrural and the subtalar joints. The talocrural joint – the true ankle joint which is made of the tibia, fibula, and talus – is a uniaxial, modified hinge, synovial joint responsible for dorsiflexion and plantarflexion. On dorsiflexion the talus is wedged between malleoli, so there is no inversion or eversion; this is the closed packed position of this joint.[3] The subtalar (talocalcaneal) joint is a synovial joint with three degrees of freedom, where supination and pronation occurs. It is supported by lateral and medial talocalcaneal ligaments but the main support comes from the interosseous talocalcaneal ligament which limits eversion. The distal tibiofibular joint is important to mention here since it can suffer in cases of high ankle sprain. This joint is a fibrous or syndesmosis type of joint. It is supported by four ligaments – anterior and posterior tibiofibular ligaments, inferior transverse ligament, and interosseous ligament. The pathophysiology/mechanism of injury of an ankle sprain typically is via extreme ankle inversion (foot rolling in), eversion (foot rolling out), or rotation (either rotating in or rotating out). The most common type of ankle sprain injury mechanism is the inversion/internal rotation: as the foot rotates out of the normal plane of space (foot on the floor), the sequence of injury usually is as follows: the first ligament injured is the antero-talofibular ligament (ATFL), which is located in the “front” of the ankle. With continued rotation or inversion of the foot, the next ligament to be injured is the CFL or calcaneofibular ligament – located on the “side” of the ankle. Lastly, with continued rotation/inversion, a severe injury will occur, i.e., the dreaded “Grade-3 ankle sprain,” which in addition to the ATFL and CFL, will also cause injury to the posterior talofibular ligament (PTFL) – located at the “back” of the ankle.

5. How do you diagnose a chronic ankle sprain? Patients will usually report a twisting or rolling of the ankle with or without an audible or perceived “pop,” which is typically the sound of the ligaments being injured. The symptoms of the sprain depend on the severity of the injury and the time course; thus, a mild/Grade 1 sprain may only demonstrate minimal pain and swelling at the time of ligament injury; whereas, more severe grades may show copious

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swelling, hematoma formation, severe pain, and inability to bear weight. It is also important to inquire if there was a history of previous sprain/injury, as well as the mechanism of injury. Onset of injury, ability to walk, run or bear weight, and whether there is pain elsewhere in the leg are also standard questions for the ankle history. The patient with chronic ankle sprain will typically give a history of multiple sprains, and an ankle which is “always swollen.” They may also state the ankle is “weak” and “rolls very easily” – demonstrative of ligamentous laxity and resulting joint instability. Physical examination starts with inspection for abnormal alignment, antalgic gait, color change, skin texture change, or visible edema. Next palpation for tissue texture changes, palpable edema, and tenderness is assessed. Range of motion testing, both active (AROM) and passive (PROM), are performed bilaterally to assess for asymmetry, restriction, or painful arc. Strength testing (AROM – against resistance) is used to assess integrity of the MTU (muscle–tendon unit) and its nerve supply. This is followed by “special tests” which are used to assess the integrity of the ligaments and thus the stability of the joint. Examples of the special tests for the ankle include: the anterior drawer test (ankle at 90 degrees, grasp heel and pull forward along with a posterior force with the other hand on distal tibia); the talar tilt test (ankle at 90 degrees, the heel is firmly adducted or inverted; the normal end feel is firm – increased laxity compared to the other side suggests damage to CFL); the external rotation test (foot external rotation with patient sitting and knee at 90 degrees and holding the tibia in fixed position; pain indicates syndesmosis injury – high ankle sprains); and the squeeze test (squeeze tibia and fibula together, pain distally indicates syndesmotic sprain). Diagnostic imaging typically begins with x-rays, which include the standard three views: ap (anteroposterior), lateral, and mortis views. With chronic ankle sprain, because of the ligament laxity and resulting joint instability, there may be osteoarthritis of the ankle joint. Additionally, there can be “holes” in the cartilage of the bones of the ankle joint resulting from abnormal gross joint movements, again from ligament laxity and joint instability. These lesions are called osteochondral defects (OCD). These osteochondral cartilage defect lesions are typically noted in the “talar dome”, or dome of the talus bone of the ankle mortise. OCD lesions can sometimes be seen on x-ray imaging, but are more

Chapter 32: Patient with ankle pain

easily demonstrated with CT scan or MRI. More recently, in the past several years, ultrasound (US) imaging has been utilized in sports/orthopedic medicine to evaluate the ligament damage in chronic ankle sprains. US allows the physician to evaluate the patient using no radiation, and also allows visualization of the ligaments, tendons, and joints dynamically in real-time – something which is impossible with other forms of imaging. The MRI is usually the study of choice due to its capacity to assess both intra-articular and extraarticular manifestations of lateral ankle sprains. However, it is less cost-effective and may have inferior resolution for partial tears compared to ultrasound. Laboratory studies are not helpful.

osteoarthritis (OA) of the knee. However, there are only case reports of anecdotal improvement in chronic ankle pain from OA. There is no scientific rationale or data to support the use of viscosupplementation/HA injections for chronic joint instability from damaged ligaments.

Acupuncture There have been a few case reports and low-quality studies in the literature showing short-term improvement in pain and QOL (quality of life) scores with acupuncture in acute ankle injuries. There was no evidence for the use of acupuncture with chronic ankle pain and joint instability.

Dry-needling

6. How should I treat this patient? Conservative approaches The typical initial treatment paradigm for the chronic ankle patient is physical therapy (PT). The PT interventions and modalities are targeted to address improving joint stability, ankle proprioception, and muscle activation and strengthening. Other techniques employed include taping (e.g., kinesiotaping), bracing, and modalities such as ice, heat, e-stim, and ultrasound.[4] Unfortunately, these techniques typically do not lead to resolution of pain and dysfunction in the chronic ankle pain patients with instability, as these techniques do not tighten ligaments which are damaged and in a laxity state. Typical analgesic therapy consists of non-steroidal anti-inflammatories or opioids.

Dry-needling is a technique which has recently come back into favor with physical therapists as a way to stimulate an immune system proliferative/healing response. Although there is an intuitive scientific rationale for its use in the treatment of the chronic ankle pain patient with joint hypermobility, there is no data showing its efficacy.

Radiofrequency ablation/radiofrequency coblation

There have been many interventions attempted for chronic ankle pain patients. Some of the more common ones are listed below:

These pain management procedures are performed by destroying or “ablating” one or more of the sensory nerves innervating the ankle. Recent studies have shown “good to excellent” results when measuring patient’s pain scores in the short-term of 3–6 months. These results returned to original baseline pain after 6 months – likely due to the fact these procedures do not address function (the ligament damage and resulting joint hypermobility), but only pain (by burning the nerve). Thus, the pain begins to return as the nerves begin to regenerate. Still, the evidence is robust as a pain management procedure for shortterm relief.[5]

Corticosteroid injections

Regenerative injection procedures

Although commonly used by physicians in the USA, steroid injections have not been shown to improve pain or dysfunction in chronic ankle pain; nor have they been shown to decrease need for pain medications, or slow time to surgical intervention.

Prolotherapy “Prolotherapy,” or proliferative injection therapy, is an injection technique performed with the intent of stimulating a “proliferative immune/healing response,” leading to a healing, and thus tightening, of damaged ligaments and tendons (Figures 32.1 to 32.3). Prolotherapy had been advocated for chronic joint pain and hypermobility secondary to supporting ligament damage for many decades. Quality evidence proving its

Procedural

Viscosupplementation/hyaluronic acid injections Viscosupplementation has shown some promise with chronic pain in other joints, particularly patients with

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Chapter 32: Patient with ankle pain

Figure 32.1. Ankle – lateral – prolotherapy injection: 1. posterior talofibular and posterior tibiofibular ligaments; 2. calcaneofibular ligament; 3. anterior talofibular ligament; 4. sinus tarsi; 5. bifurcate ligament (calcaneonavicular and calcaneocuboid ligaments) and dorsal cuboideonavicular ligament; 6. peroneus brevis tendon.

Figure 32.3. Ankle – plantar – prolotherapy injection: 1. plantar fascia – long plantar and short plantar ligaments; 2. plantar aponeurosis.

treatment as demonstrated by reports of reduced pain levels, increased range of motion, extended ability to exercise, reduced depression, reduced anxiety, and a reduction in medications needed.[6] The second case series report demonstrated post-prolo tissue healing via imaging evidence on high-resolution ultrasound and MRI of three patients with chronic ankle pain and arthritis from joint hypermobility.[7] Additional RCTs are needed. See Figures 32.1 to 32.3.

Platelet-based procedures Figure 32.2. Ankle – medial – prolotherapy injection: 1. anterior tibiotalar ligament; 2. tibiocalcaneal ligament; 3. posterior tibiotalar ligament; 4. tibionavicular ligament; 5. plantar arch ligaments (plantar calcaneonavicular, plantar cuboidonavicular); 6. tibialis posterior tendon; 7. tibialis anterior tendon; 8. plantar fasciaaponeurosis.

efficacy in this patient population is lacking. However, there have been two case series published supporting both clinical improvement and evidence of tissue healing on follow-up imaging studies. A case series report was done on patients treated for unresolved, chronic ankle pain at a volunteer charity clinic having limited resources and personnel between 2000 and 2005. Treatment consisted of injecting a dextrose solution at specific ankle sites to stimulate healing of ligaments, tendons, and joints. Patients, including those who were told by previous doctors that “nothing more could be done” or that “surgery was the only option,” responded favorably to

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These procedures, like Prolotherapy, are performed with the intention to stimulate healing through activation of the body’s immune response. Platelets are acquired via blood draw and concentrated by various methods. The standard, commercial grade centrifuge/ platelet processor can deliver a platelet-rich plasma (PRP) with concentrations of 3–7 times that of erythrocyte (RBC) poor serum. The Regenexx process can produce a platelet concentrate – the so-called Regenexx-SCP – of up to 20 times baseline. Platelet-rich plasma: Recent data has shown efficacy for PRP treatments in chronic ankle pain with OCD of the talus. These results demonstrated increased function and decreased pain scores up to 6 months post-procedure. Additional investigation including RCTs is needed.[8] Regenexx-SCP or “super-concentrated platelets”: Small case series for SCP treatments have demonstrated efficacy in improving function and decreasing pain.[9] Additional investigation including RCTs is needed.

Chapter 32: Patient with ankle pain

Surgical treatment options Open surgical repair for chronic ankle instability/hypermobility There are many different surgical techniques for addressing gross hypermobility of the ankle. One of the more well-known of these procedures is the “Broström-Gould repair,” which has been shown to be effective at correcting instability, and returning patients to pre-injury levels of function, even highlevel athletes. However, this and other surgical techniques been shown to be effective only for severe/ 3rd-degree ankle sprains with widening of the ankle mortise, and for those with certain associated fractures such as malleolar, distal fibular fractures, or detached talar dome fractures. Additionally, fractures at the 5th metaphyseal–diaphyseal junction (Jones’ fractures) may require surgical fixation as well in order to return the patient to high levels of function.

References 1.

2.

3.

Kannus P, Renström P. Treatment for acute tears of the lateral ligaments of the ankle: operation, cast, or early controlled mobilization. J Bone Joint Surg Am. 1991;73(2):305–312. Gerber JP, Williams GN, Scoville CR, Arciero RA, Taylor DC. Persistent disability associated with ankle sprains: a prospective examination of an athletic population. Foot Ankle Int. 1998;19(10): 653–660. Hubbard TJ, Hicks-Little CA. Ankle ligament healing after an acute ankle sprain: an evidencebased approach. J Athl Train. 2008;43(5):523–529.

4.

Open surgical repair for chronic ankle pain, OA/other causes Joint fusion: ankle arthrodesis. Ankle arthrodesis, or fusion, has been performed for many years with relative success controlling pain scores. More recently, studies have shown that Arthroscopy-assisted Ankle arthrodesis improves not only pain scores, but some aspects of function as well.[10] Total ankle arthroplasty (TAA). TAA has traditionally seen worse outcomes than other total joint replacements, such as knee and hip. However, with recent technologic advancements, some surgeries performed at TAA centers with highly specialized surgeons demonstrated improvement in function and pain scores in 46 patients (approx. 90% of study subjects) in one small study. Further research is needed including RCTs.

Kemler E, van de Port I, Backx F, van Dijk CN. A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types. Sports Med. 2011;41(3):185–197.

5.

Yeap EJ, Chong KW, Yeo W, Rikhraj IS. Radiofrequency coblation for chronic foot and ankle tendinosis. J Orthop Surg (Hong Kong). 2009;Dec;17(3): 325–330.

6.

Hauser R, Hauser MA, Cutla J. Dextrose prolotherapy injections for chronic ankle pain. Practical Pain Management. January 1, 2010.

7.

Fullerton BD. High-resolution ultrasound and magnetic resonance imaging to document tissue repair after prolotherapy:

a report of 3 cases. Arch Phys Med Rehabil. 2008;89(2):377–385. 8.

Smyth NA, Murawski CD, Haleem AM, et al. Establishing proof of concept: platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus. World J Orthop. 2012;3(7):101–108. doi: 10.5312/wjo.v3.i7.101.

9.

http://www.regenexx.com/ category/recent-results/anklecase-results/

10. Wang JL, Liu YJ, Li ZL, Wang ZG, Wei M. Outcome evaluation of arthroscopy-assisted ankle arthrodesis. Zhongguo Gu Shang. 2011;24(9):719–722.

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33

Musculoskeletal Pain

Patient with lateral epicondylosis or other focal tendinopathy Jose E. Barreto and Jeff Ericksen

Case study A 40-year-old male presents with a 2-month history of lateral elbow pain. He has taken over-the-counter medications with no relief.

1. What is the differential diagnosis? a. Lateral epicondylosis (LE) b. Posterior interosseous nerve (PIN) entrapment c. Partial or full-thickness tear of the extensor tendons d. Cervical radiculopathy at C6–C7 e. Rheumatoid arthritis Lateral epicondylosis is a painful condition of the lateral/extensor area of the elbow. This condition is also known as “tennis elbow” and lateral epicondylitis, but absence of inflammatory cells in the area have recently caused a change in the name to epicondylosis.[1,2] It is caused by repetitive or overuse injury of the common extensor mechanism; primarily the extensor carpi radialis brevis (ECRB). There is a higher incidence in patients older than 35 years. It has no gender predilection and affects 1–3% of the population.[3,4]

2. What risk factors predispose patients to developing sacral insufficiency fractures? a. Repeated wrist extension movements (occupational) b. Faulty biomechanics or technique (sports or occupational) c. Inadequate equipment d. Racquet sports

3. Describe the anatomy and pathophysiology of a lateral epicondylosis The elbow’s primary function is to help position the hand in an appropriate location for function. It has three cubital articulations: ulnohumeral (trochlear) joint, radiohumeral joint, and the superior or proximal radioulnar joint. It has a continuous capsule and a joint cavity with the three joints. It has 2 degrees of freedom. The ulnohumeral (trochlear) joint is a uniaxial hinge joint with an axis that is downward and medial which created the carrying angle. The radiohumeral joint is a uniaxial hinge joint between capitulum (humerus) and head of radius, it allows flexion and extension movements. The superior or proximal radioulnar joint is a uniaxial pivot joint. The annular ligament keeps its proper position. This joint allows the rotation movements of the head of the radius on supination and pronation. The lateral epicondyle and the lateral supracondylar ridge form the origin of the extensor tendons. These include the extensor carpi radialis longus, ECRB, extensor digitorum communis (EDC), and the extensor carpi ulnaris (ECU). Of these, the ECRB, EDC, and ECU are part of the common extensor tendon. Repetitive use and contraction of the forearm muscles, particularly eccentric contractions, can cause microtrauma and subsequent degeneration, immature repair, and tendinosis. Recent studies have confirmed the presence of fibroblasts, vascular hyperplasia, and disorganized collagen (angiofibroblastic hyperplasia) with a paucity of acute or chronic inflammatory cells. Limited blood supply of these tendons may be partly responsible for the tendinosis.[1,2]

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Also, following the tensegrity model, if you have a loose distal wrist joint then the proximal segment (the elbow) needs to compensate and overwork to stabilize the distal segment since the forearm extensor muscles cross two joints.

4. How do you diagnose a lateral epicondylosis? The pain is located at the elbow, sharp in quality, and is associated with occasional radiation distally and weakness of the wrist extensors. There can be swelling in the area and symptoms of numbness and paresthesias; in this case suspect an entrapment of the deep branch of the radial nerve (posterior interosseous nerve – PIN). On examination, there is tenderness to palpation over the lateral epicondyle and the area extending 1–2 cm distally. Also, examine your patients for tenderness on the insertion of the biceps tendon (focal palpation below radial head with the forearm in pronated position). This can be an indication of insertional tendinosis, which can occur in patients with sports or occupations that demand frequent supination movements. Special tests include the resisted wrist extension (RWE) test (pain reproduced with wrist extension against examiner’s resistance), the ECRB test (patient holds the elbow extended, the forearm pronated while making a fist and extending the wrist – the examiner applies resistance and pain indicates a positive test for LE involving the ECRB muscle), and the resisted middle finger test (pain on resisted extension of the middle finger – this tightens the fascial origin of the ECRB). Also, examine the neck and shoulders as these areas can cause referred pain to the elbow. A neurologic exam will help assess the status of the radial nerve and its branches which may get involved as well (entrapment of the deep branch of the radial nerve may occur as it passes through the arcade of Frohse/radial tunnel in the supinator muscles). Radiographic studies may help rule out an intraarticular pathology, bone involvement, calcification, or exostosis at the epicondyle or in the tendon close to the tendon attachment. This may be seen in 20% of cases, but has no prognostic indications. Ultrasound may show increased blood flow near the lateral epicondyle and tendinosis appears as hypoechoic swelling of the involved tendon with possible hyperechoic calcification and adjacent bone irregularity.

Magnetic resonance imaging can help assess intra-articular pathology and the soft tissues including ligaments and will identify tendinosis. If the patient is having pain and/or inflammation in other areas, consider lab work including an ESR and C-reactive protein (CRP).

5. Is there any other diagnostic testing that should be done? Grip strength, elbow, and wrist range of motion (ROM) examination will help assess functional status.

6. How should I treat this patient? Conservative approaches At the initial phase of treatment, the focus should be on pain relief. This can be accomplished by PRICEMM – protect, ice, compression, elevation, medication, modalities. Physical therapy should include stretching of wrist flexors and extensors (slightly), along with strengthening of the wrist (progress from isometric to concentric to eccentric), elbow, and shoulder muscles (rotator cuff). Eccentrics could be done with weight or with resistance given by the other hand. Other physical medicine treatment modalities include therapeutic ultrasound, heat, and soft tissue therapy. To control force loads you can use a counterforce brace (forearm strap), improve sports technique, develop two handed backhand stroke for tennis players, and control intensity, duration and frequency of activities. Prevention strategies include exercises to address flexibility and strength of the spine, shoulder, scapular stabilizers, and arm and forearm muscles. Tennis players should be instructed on proper technique such as striking the ball in front of the body with the wrist and elbow extended, allowing for upper arm and torso (not the wrist extensors) to provide stroke power. The racquet should be lightweight and of low vibration material (graphite, epoxies) and appropriate grip size (distance from tip of ring finger to the proximal palmar crease, along its radial border) and low string tension.

Procedural Interventions for LE include corticosteroids, although this is controversial and studies have shown it causes more harm.[5] Newer and more accepted treatments

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Chapter 33: Patient with lateral epicondylosis or other focal tendinopathy

Figure 33.1. Lateral elbow prolotherapy injection: 1. extensor carpi radialis longus tendon; 2. lateral (radial) collateral ligament; 3. common extensor tendon; 4. intra-articular injection; 5. lateral (radial) collateral ligament; 6. annular ligament; 7. lateral collateral ligament– anterior bundle.

include prolotherapy and platelet-rich plasma which have shown improvement.[6,7] Others include tenotomy and stem cell injections. Other treatments include surgery, ECSW, and acupuncture. For prolotherapy injections (Figures 33.1 and 33.2), it is important to treat the lateral collateral

References

Figure 33.2. Medial elbow prolotherapy injection: 1. pronator teres tendon; 2. common flexor tendon; 3. medial (ulnar) collateral ligament-posterior and anterior bands.

and annular ligaments since they play a big role in the stability of this area. Don’t forget to assess and treat the insertion of the biceps tendon below the radial head with the forearm in pronated position. This can be an indication of insertional tendinosis, which can occur in patients with sports or occupations that demand frequent supination movements.

nerve decompression: is outcome influenced by the occupational disease compensation aspect? Orthop Traumatol: Surg Res. 2011;97(2): 159–163.

1.

Bishai SK, Plancher KD. The basic science of lateral epicondylosis: update for the future. Tech Orthop. 2006;21(4):250–255.

2.

Walz DM, Newman JS, Konin GP, Ross G. Epicondylitis: pathogenesis, imaging, and treatment. RadioGraphics. 2010;30:167–183.

4.

Allander E. Prevalence, incidence and remission rates of some common rheumatic diseases and syndromes. Scand J Rheumatol. 1974;(3):145–153.

3.

Bigorre N, Raimbeau G, Fouque P-A, et al. Lateral epicondylitis treatment by extensor carpi radialis fasciotomy and radial

5.

Scarpone M, Rabago DP, Zgierska A, Arbogast G, Snell E. The efficacy of prolotherapy for lateral epicondylosis: a pilot

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study. Clin J Sport Med, 2008; 18(3):248–254. 6.

Coombes BK, Bisset L, Brooks P, Khan A, Vicenzino B. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013; 309(5):461–469.

7.

Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sport Med. 2006;34:1774–1778.

Section 3 Chapter

34

Musculoskeletal Pain

Knee osteoarthritis with emphasis on percutaneous regenerative medicine Jason Tucker, Christopher Centeno, and Jeff Ericksen

Case study A 52-year-old female (BMI 22) presents with a several year history of activity-induced right-sided knee pain accompanied by stiffness most bothersome upon first rising in the morning, prior to retiring at night, and after cooling down from heavy exercise.

1. What are the most common etiologies of chronic knee pain? The prevalence of the respective perpetuators of pain is dependent on age. In middle to elderly ages the following are commonly seen:  Knee osteoarthritis: Extrapolation from observational studies suggests that osteoarthritis of the knee has a lifetime incidence of close to 1 in 2 individuals with approximately 1 in 5 over the age of 45 suffering from the disease.[1] Since many of these epidemiologic studies require radiographic evidence of disease for diagnosis, prevalence rates may be erroneously low (see imaging section below)  Meniscal injury (degenerative > traumatic)  Crystal and autoimmune rheumatologic disease  Tendinopathies

2. What is knee osteoarthritis and what is the pathophysiologic basis for its development? The knee is a tricompartmental, synovial joint structure. The three cardinal compartments are the medial and lateral tibiofemoral compartments and the patellofemoral joint (PFJ), which are all lined by articular

cartilage (AC). The cell constituents of AC are chondrocytes and more recently it has been found to also possess progenitor cells.[2] In a non-diseased joint, unassisted cell components possess very limited ability to self-replicate, but they play an integral role in maintaining a state of equated turnover of the extracellular matrix (ECM). The ECM, which consists of proteoglycans (mainly aggrecan) and hyaluronic acid with reinforcement provided by collagen (mainly type II), encompasses the aforementioned cellular components.[3] Knee osteoarthritis (KOA) is a generally agerelated, inflammatory mediated, degenerative joint disease (DJD) that manifests as joint stiffness and pain leading to reduction in functionality and subsequent deterioration in quality of life.[4] DJD is a term synonymous with osteoarthritis and provides a partially accurate macroscopic portrayal, but at its microscopic core, OA is best defined as a low-grade, self-perpetuating inflammatory state.[4] A disruption of the normally homeostatic state of balanced anabolism and catabolism of the ECM with a shift toward favoritism of a catabolic environment eventually leads to macroscopic hyaline cartilage degeneration[3] and unbeneficial synovial overgrowth and inflammatory changes in addition to bony hypertrophy (osteophyte formation).[5] This exemplifies the fact that OA is a whole joint disease with triad involvement of the AC, subchondral bone, and synovial tissue (and possibly the fat pad).[4] Furthermore, since cartilage is thought to be aneural, a predominance of pain may arise from neurogenic inflammation whereby an overgrowth of sympathetic nerves within the synovium and subchondral bone combines with binding of pain producing biochemical peptides to these nerve endings.[6]

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The patient has a past medical history of an ipsilateral anterior cruciate ligament tear in her 20s. Other pertinent medical history includes morbid obesity (BMI 40) until gastric bypass surgery 3 years ago and a family history of OA in her mother and brother.

3. What are the common causes of KOA?[1] 1. Acute mechanical damage from a traumatic joint injury can create joint instability, catalyzing the evolution of OA from the ensuing chronic mechanical damage (see #2 below) over years or decades as a result of chronic cruciate and/or collateral ligamentous laxity and/or meniscal injury. Reasons for this may include: A. Sustained inflammatory milieu environment, including exposure of the joint to the harsh post-traumatic hemarthrosis atmosphere. B. Surgical imprecision in recreating the native biomechanical state and/or concurrent removal of injured meniscal tissue (ACL repair does not reduce the occurrence of posttraumatic OA). 2. Chronic mechanical damage is most commonly encountered when misalignment patterns lead to abnormal force distribution and consequent excess burden on focal areas. A. One prototypical example is obesity leading to an increased preponderance of varus knees, which can promote the development of or worsen medial compartment KOA. 3. Genetic predisposition from unfavorable hormonal influence and/or gene modulation, regulation, and expression. A. Aging females with a family history of osteoarthritis are at highest risk. 4. Metabolic syndrome (particularly obesity) is the most common modifiable risk factor (impact cannot be overemphasized taking into consideration this fulminant epidemic). 5. Iatrogenic chondrotoxic effects from intraarticular (IA) corticosteroids and anesthetics (lidocaine, ropivacaine, etc.).[7]

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4. What other type(s) of arthropathy need to be ruled out and how do they differ from OA?[8] 1. Rheumatoid arthritis (RA) and an effused osteoarthritic joint in a stage of active degradation could be confused if using an indiscriminate approach. RA is an autoimmune disease that typically presents in a distinctive enough fashion to make differentiation clear for the astute physician. RA classically presents with systemic symptoms, symmetrical polyarthritic involvement, erythema, profound calor, pain, and morning stiffness that last longer than 20–30 minutes. It usually occurs in small distal joints, but can affect the knee in roughly 1 in 4 cases. Further dissimilarities are provided in the examination, imaging, and lab sections below. 2. Calcium pyrophosphate dihydrate disease (CPPD), formerly called pseudogout, is a build up of calcium pyrophosphate crystals in the hyaline or fibrocartilage of the joint. It can be confused with gout because of the acute nature of the disease. The knee is involved more than 50% of the time. Both basic calcium phosphate crystals (BCP) and calcium pyrophosphate (CPP) crystals are commonly seen in patients with KOA. Whether the calcification occurs as a result of OA or predisposes one to develop OA is still under investigation.[9] 3. Gouty arthopathy (GA) occurs in as many as 10% of adults aged at least 50 years, but affects the knee much less commonly than CPPD. GA and CPPD may be difficult to clinically distinguish (see lab section below). GA and RA are clinically differentiated by lack of systemic symptoms and unilateral involvement in gout. Additionally, there are major distinctions in fluid and serum analysis. 4. Septic arthritis is an acute monoarticular arthritis that occurs with the introduction of a pathogenic organism into the joint. The infection can be directly introduced into the knee or “seed” from the blood (bacteremia) or a distant site. Rapid destruction is characteristically seen. Examples include inhabitation of the STD, Neisseria gonorrhea (NG), into the joint or the eruption of a Staphylococcus aureus infection inside a prosthetic knee. Joint infections iatrogenically induced by percutaneous injection are very rare.

Chapter 34: Knee osteoarthritis with emphasis on percutaneous regenerative medicine

5. Spondyloarthopathies are also a consideration but usually present with other distinguishing features such as the erythematous scaly rash seen with psoriatic arthritis. OA lacks systemic symptoms and profound erythema, but subtle warmth is possible. Morning symptoms should last no longer than 20–30 minutes and the development of the presence of significant pain is usually more insidious. There is an oligo-arthritic variant of OA where multiple joints are affected, but it usually presents asymmetrically. There are scenarios where bilateral OA occurs, which highlights the importance of combining knowledge with clinical experience. Unlike with OA, disease-modifying agents (DMARDs) exist for RA, including methotrexate and sulfasalazine and more recently allogenic biologics. Symptom mitigating agents such as NSAIDs and glucocorticoids can be utilized during flare-ups. Acute treatment for GA and CPPD is similar and can involve NSAIDs, corticosteroids, or colchicine depending on the circumstances. Chronic treatment for CPPD is similar to acute treatment; on the other hand, a uricosuric agent or urate production inhibitor is initiated within a few weeks for GA. OA treatment is addressed in detail below. The rest of the exam shows an antalgic gait, a subtle genus varus deformity, atrophy of the vastus medialis obliquus, quadriceps (Q) angle of 15 degrees, crepitus with ROM, and a+ bulge sign. There is lowgrade laxity on Lachman’s test and lateral opening upon varus (medial to lateral force application) stress compared to the contralateral side. The hip and foot exam are normal.

5. What does a pertinent exam of the knee consist of in a patient that is suspected of having knee osteoarthritis?[8,10] 1. Gait analysis – those with KOA tend to walk with an antalgic gait, spending less time in stance phase on affected side (assuming the pathology is unilateral). 2. Inspection – genu varus and valgus deformities are indicators of increased predisposition for development of OA or the current presence of frank OA. Unless abnormal hip–knee–ankle

angle contributed to KOA evolution, it may not be seen early in the disease course. The development of a varus knee has a more ominous course because the natural stance phase adduction moment ubiquitously causes greater load medially than laterally.[11] Atrophy of the vastus medialis (VMO) component of the quadriceps and/or a large Q angle can lead to break down of the patella femoral junction (PFJ). VMO weakness results in maltracking of the patella against the femoral trochlea and frictioninduced patella cartilage damage (chondromalacia). 3. Palpation – joint line tenderness (JLT) can be an indicator of disease presence but has a low specificity because it can also be indicative of meniscal or coronary ligament damage or meniscal extrusion with or without the concurrent presence of KOA. Gross deformities from synovial hyperplasia and osteophytes will be more evident in advanced disease. 4. ROM – crepitation on passive ROM testing is a sensitive but non-specific indication of either uni-, bi-, or tricompartmental KOA. It can also signify chondromalacia patella, redundant soft tissue (plica syndrome), or injury to the meniscus. As the disease worsens, ability to both actively and passively range the joint diminishes. 5. Provocative maneuvers – Bulge sign, Lachman’s, anterior/posterior drawer, medial/lateral stability, and McMurray’s test are well described and beneficial to evaluate for effusion, disruption of meniscal integrity, and instability, respectively. Evaluation of the integrity of the fibrocartilage is important because damage to the meniscus is intimately associated with the development of subsequent KOA. It is important to examine the joint above and below the knee and to examine the contralateral knee for individualistic comparison. A PA radiograph shows definite osteophytes and probable medial joint narrowing.

6. What imaging is currently used to diagnose KOA and is it adequate? PA, lateral, and sunrise semi-flexed (30 degree knee bend) standing radiographs have historically been

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the standard of care in the imaging work-up and diagnosis of KOA. In conjunction with the PA technique, the lateral view can provide additive information about the tibiofemoral joint and both the lateral and sunrise views are utilized to assess the PFJ. Experts are increasingly suggesting that there are likely pre-radiographic and even preimaging (see below) stages of KOA and that KOA should not be ruled out on the basis of a negative x-ray.[12] This is an essential point because there is ample support in the literature that disease in milder stages is more easily treated compared to end-stage disease. Technologic advancements in MR imaging and musculoskeletal ultrasound (MSKUS) are challenging the current standard of care, but have their own limitations.  MSKUS is limited by only being able to detect outer condyle damage due to inability to penetrate bone. It can also visualize synovitis, which can be an indicator of OA (as well as other arthropathies).  MRI is much more sensitive and can detect KOA in the pre-radiographic phase. It also has the ability to detect subchondral bone marrow lesions, which has been highly correlated with pain, rate of degradation, and progression to joint replacement. Unfortunately, more than 75% of asymptomatic individuals can have clinically irrelevant abnormalities on MR imaging.[13] Thus, analogous to other areas of the body, imaging is most advantageous when incorporated into the comprehensive clinical picture. Neither MSKUS nor MRI have yet to be routinely implemented into clinical practice, but there are protocols and classification systems evolving. OA, RA, gout, and CPPD all have distinctive appearances on radiographs. Briefly, in RA, bony erosions, washout osteopenia, and involvement of both the medial and lateral tibiofemoral compartments are all classic, whereas in gout, overhanging edges combined with tophi and bony erosions are virtually pathognomonic. In CPPD, chondrocalcinosis (CC), which is defined by horizontal white lines of CPPD crystals integrating into the articular and fibrocartilage, is characteristically seen. Four cardinal findings are classically described in OA and include osteophytes, subchondral sclerosis and cysts, and

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unicompartmental joint space narrowing. Further comparisons are beyond the scope of this chapter. The patient states that she has not had any blood work for at least a year and wonders whether this will be beneficial in determining her diagnosis.

7. Are there any labs that need to be ordered when working up a patient with knee pain? A synovial fluid aspirate should be sent for cell counts and crystal analysis if there is a reasonable suspicion for an infectious or crystalline arthropathy (notably gonorrhea is notorious for not exposing itself on routine gram stain and culture). Depending on the scenario, pertinent serum labs include but are not limited to a CBC, ESR, CRP, RF, ANA, and anti-CCP. Further discussion regarding these labs is outside the scope of this chapter. Many believe that biomarkers will eventually be of utility in diagnosing, monitoring, and treating OA by providing the physician with an earlier indicator of OA commencement (pre-imaging phase), prognostic information, and gauge of response to intervention. “Chondrodestructive” marker examples include metalloproteinases and interleukins. Chondroprotective or “regenerative” marker examples are bone morphogenic protein and transforming growth factor beta. “Omics” are being promoted as key in seeing the biomarkers reach clinical pertinency.[3] On return visit, as the patient’s pain specialist contemplates management options, she conveys to him that she had a steroid injection into her knee 6 months ago which resolved her pain for 2 weeks and then it gradually recurred to its previous level. The following options are contemplated:  Refer to an arthroscopic specialist for a “scope and clean out.”  Reinjection of intra-articular corticosteroids (CS) or injection of viscosupplementation (VS) with or without an anesthetic in the mixture.  Refer to an experienced therapist for formal physical therapy.  Refer to a musculoskeletal (MSK) regenerative specialist for consideration of imaging guided regenerative injection therapy.  Refer to a clinical psychologist as part of a multidisciplinary approach.

Chapter 34: Knee osteoarthritis with emphasis on percutaneous regenerative medicine

8. What are the traditional non-surgical treatment options for early KOA? Diet and exercise Implementation of a low calorie, well balanced diet with a concomitant formal exercise plan combines reduced caloric intake and adequate caloric expenditure to reduce joint wear and tear. Notably, exposing a healthy joint to exercise in moderation does not seem to induce the development of OA and can actually impede its progression. Other more invasive weight loss methods, such as gastric bypass surgery, should only be recommended in recalcitrant cases.

Physical therapy Referral to a reputable PT to strengthen supporting musculature and address any muscle imbalances is imperative in the appropriate circumstances. Supporting musculature weakness and/or imbalance can contribute to misalignment (see above).[1]

Pharmacologic intervention Medications can be temporarily beneficial if used judiciously and if no contraindications exist. OTCs like Tylenol and COX inhibitors are tried prior to progressively “climbing the ladder” to tramadol and in end-stage disease other more potent opioid products.[14] The brief use of opioids is also reasonable in mild stages of painful KOA to aid the patient in getting “over the hump.” Glucosamine, chondroitin, MSM, fish oil, vitamin D, and various herbs have also been implicated in maintenance of and improving joint health.

Orthotics Realigning braces with either varus or valgus torques can be beneficial. Alternatively, medial and lateral wedges with and without subtalar strapping can be utilized for lateral and medial KOA, respectively.[15]

Psychology therapy Clinical psychologists can be part of a multidisciplinary approach. KOA patients frequently have insomnia and CBT is beneficial in these cases.[16]

Traditional percutaneous injections Conventional injection treatment consists of a blind, “anatomically guided” injection of CS into the joint space usually in combination with an anesthetic such as 1% lidocaine. The literature is unequivocally clear that its effect vanishes after a period less than a month[17] (see above section for discussion regarding chrondrotoxic concern for CS and anesthetics). VS products are being increasingly utilized and have proven to be a more effective treatment option than CS.[18] Effects typically last at least 6 months and there may be a positive cumulative effect with repeated treatment.[19] VS can be cost prohibitive in uninsured populations.

9. What are the innovative non-surgical management options for early KOA? The “status quo” has chronically resulted in unacceptable outcomes, which frequently culminate with prosthetic joint replacement that inherently come with dangerous risks. As a result, new and revolutionary treatment options are developing and are frequently referred to as regenerative injection therapy (RIT). Examples include dextrose prolotherapy, PRP, and autologous mesenchymal stem cells (MSCs). The terminology for these clinically promising treatments is in a state of flux primarily due to the paucity of knowledge about their biologic mechanism of action(s) and effect(s) on imaging. The term RIT[20] is used because it describes the underlying hypothesized mechanism of placing injectate into and/or adjacent to areas of damaged tissue to induce regeneration of the structure. There is less objective support of DP’s and PRP’s[21] ability to regenerate tissue compared with MSC’s. Notably, if there is sustained reinstatement of functionality and acceptable attenuation of pain, there is debate about the importance of re-obtainment of the joint’s pristine macrostructure state. Studies with long-term outcome measures will be necessary to further clarify this. There is considerable variance in treatment intervals with RITs due to the lack of mechanism knowledge. DP consists of a hyperosmolar dextrose solution (15–25%) that is injected into extra-articular structures and/or the intra-articular joint space. As opposed to PRP/MSC, it has been used for many decades[22] and

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data supporting DP as an efficacious treatment for numerous types of MSK disorders, including KOA, is growing. Rabago et al recently reported in a three-arm double-blind RCT (N¼90) that DP outperformed normal saline (blinded) injections and PT (unblinded) over a period of 1 year.[23] Another recent KOA trial confirms that there may be a direct effect on pain.[24] Animal model data has suggested that DP strengthens, tightens, and regenerates EA structures via inflammatory mechanisms[22] and thus it may be best utilized primarily for tightening of thin, lax damaged extraarticular MSK structures, which likely indirectly has a positive effect in treating KOA (see above section on acute and chronic mechanical damage). Many feel that DP pioneered the ingenuity of the recent explosion of PRP and MSCs in clinical practice. In fact, EA DP, and IA MSC/PRP are being increasingly employed in combination. PRP is a centrifuged sub-portion of the blood that contains a concentration of platelets at least 2× higher than normal blood.[25] Although a select few are custom processing it in the lab, 99% of PRP is produced using commercial bedside centrifuges by either a single or double spin system. Within the past several years, generically produced PRP has been replaced by formulations that have varying concentrations of not only platelets, but also erythrocytes and leukocytes. Mounting evidence and expert opinion is that hematocrit poor and leukoctye controlled “highconcentration” PRP (> 5–10×) is more optimal than “bloody” PRP.[26] PRP has shown the ability to stimulate proliferation of MSCs and/or improve their chondrogenic differentiation potential.[27] Unpublished research supports the aforementioned formulation as being the most effective in proliferation of bone marrow MSCs (Centeno et al). Adding even more complexity is the decision of whether to “activate” the PRP prior to injection. Utilizing calcium, thrombin, collagen, or the freeze-thaw method prior to injection activates the platelet alpha granules to release precious growth factors that stimulate anabolic activity.[25,26] The prudency of activating IA PRP is not yet clearly defined. Although PRP KOA clinical studies are particularly divergent both in methodology and injectate composition (and many fail to provide essential details about preparation), evidence is virtually unanimously positive. About a dozen studies have culminated with Level I evidence demonstrating the short-term (6 months to 1 year) effectiveness of PRP for KOA.[25,28] Further

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research will focus on the production of PRP formulations with the most chondrogenic potential to be used with or without MSCs. MSCs are multipotent, adult stem cells that show clinical promise as therapeutic agents in regenerative medicine.[29] They are defined by their ability to selfreplicate and adhere to plastic. Some argue they are more accurately called progenitor cells because of the comparative limited ability for unlimited cell type differentiation in relation to embryonic stem cells. They have been used for years for orthopedic and arthritic treatment purposes[30] with increasingly sophisticated formulation and processing over time. MSCs can be isolated from many anatomic locations, including whole marrow aspirate, muscle biopsy, adipose liposuction aspirate, and synovium. For orthopedic uses, these sources have been compared by many authors for their ability to heal bone and cartilage with differences being noted. As a rule, the closer the source tissue is to the target tissue being treated, the more effective the MSCs appear to be at differentiation into the target tissue. Presently, there are two main sources for the MSC treatment of KOA: bone marrow (BM) and adipose tissue (AT).[29] Significant controversy exists over whether adipose or bone marrow is the better source for orthopedic tissue repair. While adipose MSCs are more prevalent and are capable of orthopedic tissue differentiation, production of orthopedic tissues from this type of cell requires the use of considerably more growth factors and can be deceptively more invasive. In addition, the intrinsic chondrogenic potential of adipose-derived MSCs doesn’t appear to be as robust as bone marrow-derived MSCs.[29] Bench side and animal studies[31] over the past decade are paving the way for blossoming translational clinical research.[30,32] Based on a US National Library of Medicine search there is report of over 1000 patients receiving BM MSCs for arthritic and bone diseases as opposed to less than 10 for AT MSCs. Essentially all published studies are case reports and case series,[32] but randomized controlled trials evaluating the percutaneous effectiveness of MSCs for KOA are beginning to surface (ClinicalTrials.gov Identifier: NCT01504464). See Figure 34.1. Undoubtedly, MSCs are most effective when cultured because of the exponential expansion that results. Based on a systematic literature review of over 800 patients, this has been proven to be safe when

Chapter 34: Knee osteoarthritis with emphasis on percutaneous regenerative medicine

Figure 34.1. 46-year-old white female with chondral lesion who failed arthroscopic debridement. Before FSPGR sagittals (top) with 1 year follow-up after cultured MSC injection (bottom). Same 3.0T MRI scanner and image settings used for both images. (Courtesy of the Centeno-Schultz Clinic.)

performed under a strict protocol that respects innate, built in safety mechanisms.[33,34] For example, a cessation of propagation signal is sent out upon confluence of cells with one another.[29] MSCs can be increased in number by exposure to growth factors like TGF-β and others, which is contained in PRP and platelet lysate.[35] Used in conjunction with augmenting growth factors and/or scaffolds for synergistic purposes and/or maximization of duration of action, autologous or possibly allogenic expanded MSCs discriminately injected in earlier stages of disease using imaging guidance provide the most realistic chance of making dangerous and invasive joint arthroplasty obsolete, except for the most recalcitrant cases. In the USA, the FDA has chosen to label MSCs that are more than minimally manipulated (i.e., cultured or digested fat at the bedside) as a drug with all of the regulations and stipulations associated with new drug development. Their usage is currently strictly prohibited in this country without an Investigational New Drug (IND) exemption and an extensive regulatory process. American MSK MSC specialists are circumventing this prohibition by treating patients with cultured MSCs in other countries with less stringent regulations.[29] Acupuncture and neural therapy are alternative treatments that are not discussed in this chapter.

10. What are the traditional surgical treatment options for early KOA? Most surgical techniques for symptomatic early stages of KOA utilize an arthroscopic approach. Arthroscopic “clean out” and debridement of fraying cartilage and hypertrophied synovial tissue is routinely

performed, but is ill-advised unless utilized in specific circumstances (such as with removing a known loose body or rectifying mechanical locking/catching).[36] Microfracture surgery is a technique that attempts to introduce bone marrow mesenchymal and hematopoietic stem cells into the joint by drilling holes into the central portion of the femoral condyle. It is ineffective in producing hyaline cartilage, but can create a fibrocartilage in areas of damage. There is diminution of success with increasing age and time from procedure.[37] Definitive treatment for end-stage disease is total knee arthroplasty (TKA). TKA is efficacious, especially in more elderly individuals who have become sedentary, but it can be extremely dangerous, with an overall 90-day mortality rate of close to 1%.[37] Frequency of morbidity and mortality increases with increasing age and comorbidities.[38]

11. What are innovative surgical treatment options for KOA? Most of these surgical techniques also use an arthroscopic approach. Microfracture repair (with the addition of PRP, MSC, VS, and other scaffolds), osteochondral autograft system (OATS), and autologous chondrocyte implantation (ACI) make up a preponderance of these options. OATS involves taking a chunk of healthy cartilage from a non-weight-bearing area and sewing it into a hyaline cartilage defect that is suspected to be causing pain. Unfortunately, persistent issues with unsustained integration have plagued this procedure thus far. ACI has proven to be superior to OATS but is most effective when used shortly after symptoms develop. Surgically implanted MSCs are also being explored.[39]

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Off loading and load redistributing techniques, including valgus osteotomies and tibiofemoral distraction, are not new ideas but have resurfaced as a solitary treatment or combination management with the above-mentioned methods. They appear to be effective and even disease modifying,[40,41] but their lack of practicality (requirement of weeks of nonweight-bearing), concern for complications, and presence of other less invasive alternatives (off loading braces) has resulted in these being performed infrequently. In unicompartmental disease, particularly for patients who are young and healthy, a partial knee replacement is an option. It attenuates recovery time but has poor longevity.[42]

References 1.

2.

3.

4.

5.

6.

250

Neogi T, Zhang Y. Epidemiology of osteoarthritis. Rheum Dis Clin North Am. 2013;39(1):1–19. Pretzel D, Linss S, Rochler S, et al. Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage. Arthritis Res Ther. 2011;13(2):R64. De Ceuninck F, Sabatini M, Pastoureau P. Recent progress toward biomarker identification in osteoarthritis. Drug Discov Today. 2011;16(9–10): 443–449. Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis. 2013;5(2): 77–94. Finnson KW, Chi Y, Bou-Gharios G, Leask A, Philip A. TGF-b signaling in cartilage homeostasis and osteoarthritis. Front Biosci (Schol Ed). 2012;1(4):251–268. Longo G, Osikowicz M, Ribeiroda-Silva A. Sympathetic fiber sprouting in inflamed joints and adjacent skin contributes to painrelated behavior in arthritis. J Neurosci. 2013;33(24): 10066–10074.

7.

8.

9.

12. Coalescence of surgery and injections Intense debate continues regarding whether surgical or percutaneous will be most advantageous moving forward. Level I evidence proving superiority of one over the other is logistically challenging and cumbersome. Analogous to interventional cardiology reducing the need for coronary artery bypassing grafting via sternotomy in the 1980s to 1990s, the advent of “Interventional Orthopedics,” coined by Centeno et al is primed to provide the best of both worlds. Research suggests that injection techniques, by fluoroscopy or arthroscopy,[43] allow precision placement of injectates; this avoids the risk of anesthesia and surgery.

Farkas B, Kvell K, Czömpöly T, Illés T, Bárdos T. Increased chondrocyte death after steroid and local anesthetic combination. Clin Orthop Relat Res. 2010; 468(11):3112–3120. Imboden J, Hellmann D. Current Diagnosis & Treatment in Rheumatology, 3rd edn (LANGE CURRENT Series). 2013. MacMullan P. Detection of basic calcium phosphate crystals in osteoarthritis. Joint Bone Spine. 2011;78(4):358–363.

observational study (Framingham Osteoarthritis Study). BMJ. 2012;345: e5339. 14. Van Laar M. Pain treatment in arthritis-related pain: beyond NSAIDs. Open Rheumatol J. 2012;6:320–330. 15. Segal NA. Bracing and orthoses: a review of efficacy and mechanical effects for tibiofemoral osteoarthritis. PM R. 2012;4(5 Suppl):S89–96.

10. Abhishek A, Doherty M. Diagnosis and clinical presentation of osteoarthritis. Rheum Dis Clin North Am. 2013;39(1):45–66.

16. Helminen. Effectiveness of a cognitive behavioral group intervention for knee osteoarthritis pain: protocol of a randomized controlled trial. Helminen EEBMC Musculoskelet Disord. 2013;29(14):46.

11. Vincent KR, Conrad BP, Fregly BJ, Vincent HK. The pathophysiology of osteoarthritis: a mechanical perspective on the knee joint. PM R. 2012;4(5 Suppl): S3–9.

17. Bellamy N, Campbell J, Robinson V, et al. Intra-articular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2005 18;(2):CD005328.

12. Guermazi A. Why radiography should no longer be considered a surrogate outcome measure for longitudinal assessment of cartilage in knee osteoarthritis. Arthritis Res Ther. 2011;13(6):247.

18. Bellamy N, Campbell J, Robinson V, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;19(2):CD005321.

13. Guermazi A. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based

19. Navarro-Sarabia F Coronel P, Collantes E, et al. A 40-month multicentre, randomised placebocontrolled study to assess the efficacy and carry-over effect of

Chapter 34: Knee osteoarthritis with emphasis on percutaneous regenerative medicine

repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project. Ann Rheum Dis. 2011;70(11):1957–1962. 20. Vora A. Regenerative injection therapy for osteoarthritis: fundamental concepts and evidence-based review. PM R. 2012;4(5 Suppl):S104–109. 21. Halpern B. Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med. 2013;23(3):238–239. 22. Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care. Primary Care: Clinics in Office Practice. 2010;37:69–80. 23. Rabago D. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11(3):229–237. 24. Rabago D, Kijowski R, Woods M, Patterson JJ. Association between disease-specific quality-of-life and magnetic resonance imaging outcomes in a clinical trial of prolotherapy for knee osteoarthritis. Arch Phys Med Rehabil. 2013;94(11):2075–2082. 25. Kon E, Filardo G, Di Matteo B, Marcacc M. PRP for the treatment of cartilage pathology. Open Orthop J. 2013;7:120–128. 26. Boswell SG, Cole BJ, Sundman EA, Karas V, Fortier LA. Platelet-rich plasma: a milieu of bioactive factors. Arthroscopy. 2012;28(3):429–439. 27. Mifune Y. The effect of plateletrich plasma on the regenerative therapy of muscle derived stem cells for articular cartilage repair. Osteoarthritis Cartilage. 2013; 21(1):175–185. 28. Patel S. Treatment with plateletrich plasma is more effective than placebo for knee osteoarthritis:

a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356–364. 29. Centeno CJ, Faulkner S. Regenerative orthopedics. In Wislet-Gendebien S, ed. Advances in Regenerative Medicine. InTech. 2011. DOI: 10.5772/25478. Available from:http://www. intechopen.com/books/advancesin-regenerative-medicine/ regenerative-orthopedics. 30. Centeno CJ. Partial regeneration of the human hip via autologous bone marrow nucleated cell transfer: a case study. Pain Physician. 2006;9(3):253–256. 31. Mokbel AN. Homing and reparative effect of intra-articular injection of autologous mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord. 2011; 15(12):259. 32. Orozco L. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation. 2013; 95(12):1535–1541. 33. Centeno C, Schultz J, Cheever M, et al. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther. 2010;5:81–93. 34. Peeters CM, Leijs MJ. Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthritis Cartilage. 2013;21(10):1465–1473. 35. Jonsdottir-Buch SM, Lieder R, Sigurjonsson OE. Platelet lysates produced from expired platelet concentrates support growth and osteogenic differentiation of mesenchymal stem cells. PLoS One. 2013;11:8(7).

36. Felson DT. Arthroscopy as a treatment for knee osteoarthritis. Best Pract Res Clin Rheumatol. 2010;24(1):47–50. 37. Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidencebased systematic analysis. Am J Sports Med. 2009;37(10): 2053–2063. 38. Singh JA, Kundukulam J, Riddle DL, Strand V, Tugwell P. Early postoperative mortality following joint arthroplasty: a systematic review. J Rheumatol. 2011; 38(7):1507–1513. 39. Roelofs AJ. Cell-based approaches to joint surface repair: a research perspective. Osteoarthritis Cartilage. 2013;21(7):892–900. 40. Intema F, Van Roermund PM, Marijnissen AC, et al. Tissue structure modification in knee osteoarthritis by use of joint distraction: an open 1-year pilot study. Ann Rheum Dis. 2011; 70(8):1441–1446. 41. Gomoll AH. High tibial osteotomy for the treatment of unicompartmental knee osteoarthritis: a review of the literature, indications, and technique. Phys Sportsmed. 2011;39(3):45–54. 42. Schroer WC, Barnes CL, Diesfeld P, et al. The Oxford unicompartmental knee fails at a high rate in a high-volume knee practice. Clin Orthop Relat Res. 2013;471(11):3533–3539. 43. Koga H, Shimaya M, Muneta T, et al. Local adherent technique for transplanting mesenchymal stem cell