Neurology and Rheumatology
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Table of contents :
Cover
Neurology
Introduction
o Central nervous system (CNS)
o Cortical homunculus
o Areas of the cerebral cortex
o Motor system
o Sensory system
o Peripheral nervous system (PNS)
Cranial nerves (CNs) and their diseases
o CN1: Olfactory Never
o CN2: Optic Never
o CN3: Oculomotor Nerve
o CN4: trochlear nerve & CN6: abducent nerve
o CN5: Trigeminal Nerve
o CN7: Facial Nerve
o CN8: Cochleo-vestibular nerve
o CN9: glossopharyngeal nerve
o CN10: Vagus nerve, CN11: Accessory nerve
o CN12: Hypoglossal nerve
o Speech
o Bulbar palsy
Cerebrovascular diseases
o Transient Ischemic Attacks
o Stroke
o Lacunar infarction (lacunar stroke)
o Cerebral venous sinus thrombosis
o Cavernous Sinus Thrombosis
o Subarachnoid hemorrhage
o Introduction
o Paraplegia
o Transverse myelitis
o Vascular diseases of spinal cord
o Syringomyelia
o Cauda equina
o Sciatica
o Disc lesion: spondylosis (degenerative) & disc prolapse (traumatic)
Extrapyramidal system
o Introduction
o Parkinsonism
o Chorea
o Athetosis & Dystonia
Cerebellum
o Introduction
o Cerebellar ataxia
o Sensory ataxia, Vestibular ataxia
o Nystagmus
Motor Neurone disease (MND)
Multiple Sclerosis (MS)
Peripheral neuropathy
o Introduction: types
o Peroneal muscular atrophy
o Refsum's disease
o Diphtheritic neuropathy, Leprotic neuropathy
o Lead neuropathy, Arsenic neuropathy, Alcoholic neuropathy
o Diabetic neuropathy
o Landry-Guillain-Barre Syndrome
o Beri - Beri
o Pellagra
o Subacute combined degeneration of spinal cord
Neuromuscular Junction Lesion
o Myasthenia Gravis
o Lambert-Eaton myasthenic syndrome
o Botulism
Diseases of voluntary muscle: Myopathies
o Muscular dystrophies
o Myotonias
o Familial Periodic Paralysis Syndrome
---
o Differential diagnosis of wasting of small muscle of the hand
o Epilepsy
o Brain tumors
o Hydrocephalus
o Idiopathic intracranial hypertension
o Headache
Infectious diseases of CNS
o Meningitis
o Encephalitis
o Brain abscess
o Tetanus
o Neurosyphilis
---
o Dementia
o Death
o Coma
Rheumatology
Content
o Introduction
o Collagen diseases
o Symptomology
o Investigations of rheumatological disease
Connective tissue diseases
o Rheumatoid arthritis
o Juvenile idiopathic arthritis (JIA)
o Seronegative spondyloarthropathy
o Ankylosing Spondylitis
o Reiter's syndrome & Post infectious reactive arthropathy
o Psoriatic arthropathy
o Enteropathic arthropathy
o Arthritis associated with infectious agents
o Systemic Lupus Erythematosus (SLE)
o Antiphospholipid Syndrome (APS)
o Scleroderma Or Systemic Sclerosis
o Inflammatory myopathies : Polymyositis, Dermatomyositis & Inclusion body myositis
o Polymyalgia rheumatica
o Fibromyalgia syndrome
o Sjogren's Syndrome: Sicca Complex
o Mixed Connective Tissue Disease (MCTD) (Overlap syndrome, Sharp's syndrome)
o Genetic disorders of collagen
o Charcot's Joint (Neuropathic Joint)
Vasculitic syndromes
o Introduction
o Polyarteritis nodosa
o Microscopic polyangiitis
o Giant cell arteritis (Temporal arteritis)
o Granulomatosis with polyangiitis (Wegener's granulomatosis)
o EOSINOPHILIC granulomatosis with polyangiitis (Churg Strauss Syndrome)
o Takayasu's arteritis (pulseless disease)
o Kawasaki disease (Mucocutaneous Lymph Node Syndrome)
o Behcet's disease
o Henoch-Schonlein purpura (Anaphylactoid Purpura)
o Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis= hypersensitivity angiitis)
o Cryoglobulinemia: cryoglobulinemic vasculitis
Crystal arthropathy
o Hyperuricemia & gout
o Pseudo gout & pseudo pseudo gout
Paget's disease
Degenerative joint disease : Osteoarthritis
Medical bone diseases: Osteomalacia & Osteoporosis
Amyloidosis
Citation preview
U RiO L Q£Y y:Zm
r
Mahi- oud Sewilam Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
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•
JaAlUll i)JlB »'% r.
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
© All rights reserved. This book is protected by c0p3night.N0 part ofit may be reproduced, stored in a retrieval system ,or transmitted in any Form by any means, electronic, mechanical, photocop3ing, recording or otherwise without written permission from the author
978/977/203/338/6
^jUI
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Neurology L E♦ Introduction
Topic
1 Page 1
0
Central nervous system (CNS)
1
0
Cortical homunculus
4
0
Areas of the cerebral cortex
5
Motor system Sensory system o Peripheral nervous system (PNS) ♦:♦ Cranial nerves(CNs)and their diseases o CNl: Olfactory Never o CN2: Optic Never
0
8
o
12 14
16 17
0
CN3: Oculomotor Nerve
22
o
CN4: trochlear nerve & CN6: abducent nerve
23
o
CNS: Trigeminal Nerve
24
o
CN7: Facial Nerve
27
o
CNS: Cochleo-vestibular nerve
33 35
o
CN9: glossopharyngeal nerve CNIO: Vagus nerve, CNll: Accessory nerve CNl2: Hypoglossal nerve Speech
38
o
Bulhar palsy
42
0 o 0
36 37
♦:» Cerebrovascular diseases 0
Transient Ischemic Attacks
44
o
Stroke
47
o
Lacunar infarction (lacunar stroke)
54
0
Cerebral venous sinus thrombosis
55
0
Cavernous Sinus Thrombosis
56
o
Subarachnoid hemorrhage
57
Introduction
77 78
o
Paraplegia Transverse myelitis Vascular diseases of spinal cord Syringomyelia Cauda equina
o
Sciatica
92
Disc lesion: spondylosis (degenerative)& disc prolapse (traumatic) Extrapyramidal system
93
♦:» o
Introduction
98
o
Parkinsonism
99
E 0 0 0 o
0
85 86 87 88
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
o Chorea o Athetosis & Dystonia Cerebellum
o Introduction o Cerebellar ataxia
o Sensory ataxia, Vestibular ataxia o Nystagmus Motor Neurone disease(MND)
Multiple Sclerosis(MS) Peripheral neuropathy Introduction; types o Peroneal muscular atrophy Refsum's disease
123 126
127
Diphtheritic neuropathy, Leprotic neuropathy Lead neuropathy, Arsenic neuropathy, Alcoholic neuropathy Diabetic neuropathy Landry-Guillain-Barre Syndrome
128
Beri- Beri
131
Pellagra Subacute combined degeneration of spinal cord
132
130
Neuromuscular Junction Lesion
Myasthenia Gravis
133
Lambert-Eaton myasthenic syndrome
136
Botulism
Diseases of voluntary muscle: Myopathies Muscular dystrophies Myotonias
138
Familial Periodic Paralysis Syndrome
142
141
o Differential diagnosis of wasting of small muscle of the hand o Epilepsy
145
o Brain tumors
151
o Hydrocephalus o Idiopathic intracranial hypertension
155 157
0 Headache
159
143
Infectious diseases of CNS
o Meningitis o Encephalitis
166
o Brain abscess
172
o Tetanus
173
o Neurosyphilis
174
170
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Nervous System
Classiflcations of nervous system :
A. Functional classirication (Neurophysiology):
0.^ 4 Pan
1. Autonomic function :
o o o 2. 3. B.
-r-MoU
It affects the unconscious neural control of the body physiology It innervates the cardiovascular, respiratory system, smooth muscle of the GIT & glands throughout the body The output of autonomic system is divided functionally into parasympathetic «& sympathetic nervous system Somatic function: motor system & sensory system Psychological function. Structural classification (Neuroanatomy): central & peripheral nervous system 1. Central nervous system (CNS): B. Spinal cord A. Brain : ® Cerebrum
® 31 segments:
® Cerebellum
o
8 cervical
® Brain stem :
o
12 thoracic
o
Midbrain
o
5 lumbar
o
Pons
o
5 sacral
o
Medulla
o
1 coxygeal
2. Peripheral nervous system (PNS): B. Cranial nerves A. Spinal nerves ® Number:
o 31 pairs o
Spinal cord
o
Brain & its stem
® Exit:
o Skull(cranium) ® Supply
o
Vertebral column
o
o
Cervical: UL
o
Thoracic:trunk
o
Lumbar: LL
o
Sacral: LL
o
Coxygeal: perineum
❖ Central nervous system (CNS)is formed of two main parts 1. Intracranial part:
o 12 pairs ® Origin:
Head & neck
Lateral
Central
sulcus
sulcus
White matter
A. Cerebrum:
Gray matter Paneto
occipital sulcus
1.
Formed of two cerebral hemispheres connected to each other by the corpus callosum & to the upper part of the
2.
The surface of each hemisphere is divided into four lobes: frontal, parietal, temporal & occipital.
brainstem by the two cerebral peduncles. 3.
Lobes are separated from each other by sulci (fissures):
o
Central sulcus separates the frontal lobe from the parietal lobe Parieto-occipital sulcus separates the parietal from the occipital lobe
o
Lateral sulcus (Sylvian fissure) separates the frontal & parietal lobes from the temporal lobe
o
4. Cerebral lobes are formed of: A. o o
Outer gray matter :
It's composed of aggregations of neuronal cell bodies forming the cerebral cortex It contains certain areas concerned with specific functions e.g. motor area (area 4)
B. Inner white matter: o
It's composed of nerve fibres
o
It conducts nerve impulses to & from cells of cortex
5.
At the base of each cerebral hemisphere there are several groups of nuclei situated at various levels within white matter, they form: basal ganglia, thalamus, subthalamus & hypothalamus
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
L
B. Brain stem :
A. Formed of: midbrain, pons & medulla. B. It is connected to the cerebral hemispheres by two cerebral peduncles and to the cerebellum on each side by the superior, middle & inferior cerebellar peduncles. cerebrum C. It contains:
1. All sensory & motor pathways entering & leaving the hemispheres. 2. Important collection of neurons which are involved in : Maintenance of arousal: the reticular activating system Maintenance of balance
Control of conjugate eye movement
Midbrain
Cardiorespiratory control
Pons
cerebellum
Medulla
0
Mid brain:
o
Pons:
0
Medulla:
o o o
Spinal cord
Nuclei of 3,4 Nuclei of 5,6,7,8 Nucleiof9,10,11,12
❖ N.B.: All cranial nerves have nuclei in the brain stem except cranial nerve 1 & 2 emerge from cerebrum so they are not considered cranial nerves but they are considered as tracts. ci
C. Cerebellum:
C2 C3 C4
o It lies behind the brainstem & occupies the posterior cranial fossa.
C5 C6 C7
2. Spinal part:
A. Spinal cord:
A. Site: It lies in spinal canal & ends at lower border of first lumbar vertebra in adults. B. Formed of:
o 31 segments: 8 cervical, 12 thoracic, 5 lumbar,5 sacral & 1 coxygeal. ni
❖ N.B.:
o Conus medullaris: the lowermost three segments of the spinal cord (S3,4,5) o Epiconus: the four segments of the spinal cord above the conus medullaris (L4,5,S1,2) C. Transverse section of spinal cord: formed of gray matter (cells) surrounded by white matter:
S3
Corns HMdllUMlS
Posterior (dorsal) tiorn 85
Grey matter
❖ N.B.:
o Lateral horn presents only in the thoracic & upper lumbar segments (T1^L3),has sympathetic function through sympathetic ganglion
' Lateral grey tiom
Anterior (ventral) horn
White matter
B. Posterior horn:
A. Anterior horn:
o It's nerve cell bodies called anterior horn cells(AHC)
o
o
o
It's nerve cell bodies at the end called substantia
gelaintosa of Rolandi(SGR) Has MOTOR function
Has SENSORY function
The fibers of grev matter extend outside the spinal cord forming the spinal nerves: o Receives dorsal (posterior) root of spinal nerve o Gives ventral (anterior) root of spinal nerve
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2. White matter contains nerve fibers which forms ascending & descending nerve fibers arranged in tracts:
-// From ttie brain
To the brain
Dorsal coiumns^t t
I
CorticospinaJ tracts
Senidoryhom Sensory root Lateral corticospinal tract
Sptnad nerve
Anterior corticospinal tract
Motor hom
Dorsal column
Motor rool
Lateral epinolhalafnlc
Spinothalamic tracts Sensory
tract
Motor
Lateral
Gradle fasciculus
corticospinal
Cuneate fasciculus
tract
Posterior
colunm
Posterior
tract
Dorsal nerve root
sptnocerebellar tract
Spinal nerve Lateral
spinotfialamic tract
Anterior nerve
Arlerior
root
spinocerebellar tract
Anterior
Anterior
corticospinal
spinothalamic
tract 1.
Ascending tracts (sensory):
II.
Descending tracts(motor):
A. Anterolateral system : for superficial sensation 0 Ventral & lateral spinothalamic tract
A. Pyramidal tracts: corticobulbar & corticospinal
B. Posterior column tracts (the dorsal column medial lemniscal system): for deep sensation:
B. 1) 2) 3)
0
Gracile & cuneate tract
C. Spinocerebellar tract for cerebellar information
tracts
Extra-pyramidal tracts: Rubrospinal tract Tectospinal tract Reticulospinal tract
4) Vestibulospinal tract 5) Olivospinal tract.
B. Cauda equina:
o Collection oflumho-sacral roots filling lower part of spinal canal below the lower border of LI vertebra .
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
M M
Cortical homunculus
Sonsory
Motor
Itlll ///
4\ ^ ^
//
Tongue Swallowing
Ptiarynx Somatic Motor cortex
eensory cortex
(precentral gyrus)
(postcentral gyrus)
M^^-5;Jntra"abdominal
❖ Definition:
o It is a physical representation ofthe human body in the cerebral cortex. ❖ Types: 1. Motor homunculus:
o The primary motor cortex is located in the precentral gyrus, and handles signals coming from the premotor area of the frontal lobes.
2. Sensory homunculus: o The primary sensory cortex is located in the postcentral gyrus, and handles signals coming from the thalamus. ❖ Body representation :
o The contralateral side of the body (not head) is represented as inverted (upside down)i.e. the feet at the top and the face at the bottom.
o The representation of the human body in the cortical homunculus is proportional to its importance not to the body region's physical size e.g. areas of the body with greater complex sensory (extensive sensory innervation) or motor (fine motor skills) connections e.g. oropharyngeal region, lips, face & hands are represented as larger area in the cortex while those with less complex connections are represented as smaller.
❖ N.B.: the dominant hemisphere: 1.
2. 3. o
o o
The centers in brain are bilaterally represented in cerebral cortex except speech centers which lie in the dominant hemisphere In right handed people, the dominant hemisphere is left cerebral cortex In left handed people: Mostly 70 % dominant hemisphere is left cerebral cortex
Few(15%)dominant hemisphere is right cerebral cortex Few (15%)bilaterally represented in cerebral cortex
Cerebral cortex
A. Frontal lobe
B. Parietal lobe
C. Temporal lobe D. Occipital lobe
❖ See the next table
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Ul
Prefrontal
Uncus
Paracentral 6
4 /3.1.2
Areas of the cerebral cortex
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
in the dominant hemisphere only
4. Supramarginal gyms(area 40)
dominant hemisphere only
2. Somatosensory association area (area 5, 7) 3. Angular gyms(area 39)in the
1. Cortical sensory area (area 1,2,3)(primary somatosensory cortex)
7. Paracentral lobule
o
6. Prefrontai area
Motor center for writing
words
o Recognition of objects placed in hands without
ofthe body o N.B.: the body is represented upside down (see before)
o Responsible for storage & recall of; a. Ideas of speech b. Ideas of complex voluntary motor activity
letters & numbers
o Responsible for reading, recognition & recalls of
visual information
a) Irritative : contralateral motor Jacksonian fits:
❖ Lesions
o
paralysis or sensory loss or incoordination
b. Apraxia: inability to perform complex motor activity IN ABSENCE OF
in repetition of words
o Alexia (Visual aphasia, word blindness): the patient can see but cannot read because he does not understand (recognize) letters & number a. Conduction aphasia : the patient can see & understand but find difficulty
information
b. Destructive: contralateral cortical sensory loss : inability to localize sensation perceived by thalamus i.e. loss of tactile localization, two points discrimination, stereognosis, graphesthesia, perceptual rivalry o Tactile agnosia: failure to recognize objeets placed in hands without visual
march)
a. Irritative: contralateral sensory Jacksonian fits (sensory fits i.e. numbness or tingling in one side of the body with focal onset & special
Incontinence of urine and stool
b) Reappearance of primitive reflexes e.g. grasping & groping reflexes
o Amnesia (impaired memory) o Dementia (impaired all mental power)
a) Mentality & personality disturbances e.g.
written words
o Writing aphasia (Agraphia): patient is unable to express his ideas in
words
o Irritative: attacks of conjugate eye deviation to opposite side ofthe lesion o Destructive: loss of conjugate eye deviation to opposite side ofthe lesion o Motor (verbal) aphasia: patient is unable to express his ideas in spoken
4. Offset by Todd's (transient) paralysis due to fatigue of Betz cells b) Destructive: contralateral motor paralysis o Contralateral hypertonia & hypereflexia
3. Spread with special march e.g. thumb ^ arm —> shoulder —> trunk ^ EL.
o Or big toe (if the lesion starts in the upper part of the motor area)
of the motor area)
o Either in the thumb or angle of mouth (if the lesion starts in the lower part
2. Onset: focal onset;
1. Site: Convulsions involving one side of the body
B. Parietal lobe:
o Perception of cortical sensation from opposite half
bowel evacuation
Higher center for mentality (short term memory & intelligence) & personality (behavior, planning, problem solving & decision making) o Inhibition of primitive reflexes which are present in newborn e.g. grasping & groping reflexes o Cortical inhibition (control) of bladder voiding &
o
o
dominant hemisphere only 5. Exner's area (area 45)in the dominant hemisphere only
Voluntary conjugate eye deviation to opposite side e.g. saccadic movement Motor center for speech i.e. production ofspoken
o
3. Area of conjugate eye deviation (area 8)= frontal eye field 4. Broca's area (area 44)in the
Initiation of voluntary motor activity of opposite half of body through pyramidal tract N.B.: Body is represented upside down (see before)
A. Frontal lobe:
o Partly supplies pyramidal & extra pyramidal tracts
o
o
❖ Functions
2. Premotor area (secondary motor area or area 6)
1. Motor area(primary motor area or area 4)
❖ Areas:
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Center for smell
deviation to opposite side e.g. pursuit movement
o Contralateral homonymous hemianopia, but never bilateral complete blindness as vision is bilaterally represented o Visual agnosia: patient can see but does not recognize objects, o Paralysis ofreflex conjugate eye deviation to opposite side
h. Destructive:
a. Irritative : visual hallucination
smell is bilaterally represented
o Destructive: slight impairment of smell hut never complete anosmia as
o Irritative: olfactory hallucinations
o Jargon aphasia(word salad): Patient can speak, but the words are meaningless & have no relation to each other(word salad).
D. Occipital lobe:
Occipital eye field: center for reflex conjugate eye
o Recognition & recall of images
o
2. Secondary visual area(18,19)=
Visual associative area
o Center (Perception)for vision
o Emotion & long term memory
o
1. Primary visual area(17)= Visual sensory area
4. Limbic system (Uncus)
FULL comprehension of written and spoken language
o Sensory center for speech & writing i.e. gives meaning for written and spoken language i.e.
dominant hemisphere
3. Wernicke's area in the
sounds
o Irritative: auditory hallucination o Destructive:slight impairment of hearing, hut never complete deafness as hearing is bilaterally represented o Auditory agnosia: patient can hear but does not understand (recognize)
C. Temporal lobe:
o Recognition & recalls of sounds & beard words
o Center (Perception)for hearing
2. Secondary auditory area(22)= auditory associative area in the dominant hemisphere only
1. Primary auditory area(41,42)= auditory sensory area
Motor system
❖ Motor system consist of four main components: Primary Motor
Coflex
si
.Upper Motor
Cortex
Pyramidai system (UMN): Controls opposite half of body
Neuron
Caudate Nucieue Thalamus
Putamen
^
/Substantia \Wyp£^irfaffiu« NIgra
Extra-pyramidai
Cerebellar
system: Controls
system: Controls
opposite half of body
same half of body Spinal Cord
Lower Motor Neuron
❖ System
1. Pyramidal(A)system
❖ Origin
= upper motor neuron (UMN) o Motor area (4)&
2. Extrapyramidal
premotor (6)
3. Cerebellar
o Originates from
4. Lower motor
neuron(LMN)
system
system o
Cerebellum
q At AHCs of the
centers situated at
different levels of
various level of
spinal cord
❖ Termination
CNS especially the basal ganglia. o At AHCs ofthe different levels of spinal cord
❖ Area of
o Controls opposite half of body
0 Controls same half of body
1. Initiation of voluntary motor activity
1) Coordination of voluntary motor activity 2) Maintenance of equilibrium
o Voluntary muscles.
control
❖ Function
1. Regulation of voluntary motor activity
2. Inhibition of muscle tone
3. Inhibition of deep reflexes
3. Regulation of
o
Transmission of
motor impulse from AHCs to
voluntary muscles.
emotional and associative movement
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Pathway of voluntary motor impulse: Upper & lower motor neuron systems: ❖ For a voluntary muscle to move, a nerve impulse originates from the opposite motor area to pass into two main neurons: UMN (A tract) & LMN.
1- Pyramidal system (UMN):
Cerebral motor cortex: area 4 «& 6
Genu and anterior 2/3 of posterior limb ofinternal capsule
Midbrain
Brain stem: corticobulbar tract, Pons
supply motor nuclei of cranial nerves
Medulla
Lateral corticospinal tract Ventral corticospinal tract 2- LMN: AHCs
1. Pathway of upper motor neuron(UMN)= pyramidal(A)tract: A. Origin : voluntary motor impulse originates from large pyramidal cells (Betz cells) in motor area 4 & to lesser extent in the cells of premotor area 6 B. Pathway:
1. 2. 3. o
Axon of these cells descend in the depth of cerebral hemisphere in the corona radiate. Pass in the internal capsule (genu and anterior 2/3 of posterior limb) Descend in mid brain, pons & medulla in the brain stem: Some of pyramidal tract fibers leave it to supply motor nuclei of cranial nerves of BOTH sides except lower halfof facial nucleus(7) all hypoglossal nucleus(12) which are supplied only from opposite A tract. These fibers are known as corticobulbar tract as they do not reach the spinal cord.
❖ N.B.: the pathway from the cerebral cortex down to cranial nuclei in the brainstem is known as corticobulbar tract.
4. In lower medulla:
o 85 % of fibers decussate to descend in white matter of opposite side ofthe lateral column ofthe spinal cord (lateral corticospinal tract) o 15 % of fibers descend directly in in white matter ofthe same side of the anterior column ofthe spinal cord (ventral corticospinal tract)
^ These fibers of pyramidal tract terminate at different level of AHCs of spinal cord (corticospinal tract)
❖ N.B.: the pathway from the cerebral cortex down to the AHCs in the spinal cord is known as corticospinal tract.
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2. Pathway of lower motor neuron(LMN): Formed of;
Spinal Cord
Lower Motor Neuron
1. Anterior horn ceils(AHCs):
o Special types of nerve cells present in the anterior horns of the H-shaped gray matter of spinal cord, o They receive the voluntary motor impulse from pyramidal tract from contralateral side only. o Their axons exit from the spinal cord as anterior roots. ❖ N.B.:
o The motor nuclei of the cranial nerves are similar in function to the A.H.C., as they form the cell bodies of the L.M.N. of the cranial nerves,
o Thus,lesion of a cranial nerve nucleus, like lesion of an A.H.C. is a L.M.N. lesion.
2. Peripheral motor nerve: carrying the motor impulse from the AHC to the voluntary muscle 3. Neuromuscular junction 4. Voluntary muscle.
10
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Muscle tone & Deep reflex
Higher control; mainly inhibition Constant slight stretch of muscle Dorsal root
^ Afferent sensory nerve
:i
AHCs
Efterent
Excited
motor nerve
A.H.C.S Ventral root
Subtetanic
contraction
TO brain
Mutcia
apindia
Quadrteapa
Hamatrlnga Patallar tandon
Efrarant naurona
❖ Muscle tone:
1. Deflnition: This is a spontaneous (involuntary) local axon stretch reflex. 2. Mechanism :
o Because of bone growth faster than soft tissue growth —>• length of the muscle shorter than the distance between its origin & insertion —> constant slight stretch of muscle —> stimulates some muscle spindles which send excitatory impulses through the afferent sensory nerve & the dorsal root to the A.H.C.^ the excited A.H.C.s send motor impulses through the ventral root & the efferent motor nerve to the muscle ^ this results in continuous reflex subtetatinic contraction of the muscle = Muscle Tone
3. Aim: to keep body posture
Deep Reflex(Tendon Jerk):
o
This is an induced local axon stretch reflex,
o It is induced by tapping the tendon of the muscle with a hammer.
o This tap stretches the muscle with synchronous stimulation of all muscle spindles & activation of the local axon reflex (as in muscle tone), resulting in a brief muscle contraction Stretch reflex arc control: muscle tone & deep reflex: 1. Control:
o Both are INHIBITED BY HIGHER CONTROL,through the pyramidal & extrapyramidal systems. 2. Lesion:
A. Upper motor neuron lesion(UMNL)= pyramidal(A)tract lesion :
a. Results in loss of inhibition of the intact reflex arc leading to increased muscle tone (hypertonia; spastieity or rigidity) & exaggeration of deep reflexes (hyperreflexia) below the level of the lesion with no wasting of the muscle.
11
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
b. Clonus:
Occurs in severe A lesion (stretch reflex arc is no longer inhibited)
Organic Clonus: induced by sudden sustained stretch of muscle tendon, resulting in a series of rhythmic contractions. It stops with relief oftendon stretch. Elicited in ankle, patella & wrist. Should be differentiated from hysterical clonus: where it continues after relief of tendon stretch Lower motor neuron lesion (LMNL):
B.
Results in interruption of the reflex arc leading to decreased muscle tone (hypotonia; flaccidity)& diminution of deep reflexes (hyporeflexia) at the level of the lesion, with wasting of the muscles. Difference between UMNL & LMNL
1.
UMNL
11.
LMNL
1. Lesion: 0
Lesion:
0 Lesion of AHC or motor roots or peripheral motor nerve or NMJ or voluntary muscle.
o Pyramidal tract lesion
2. Muscle lesion: o Muscle power 0 Paralysis (loss of muscle function) or
paresis(muscle weakness) below the level
I o Paralysis (loss of muscle function) or paresis (muscle weakness) at the level of the lesion
of the lesion 0
Muscle tone
o Hypertonia (spasticity) of clasp knife type
o Hypotonia (flaccidity) at the level of the lesion
below level of the lesion o
Muscle state
o
Fasciculations
o No wasting & if present it's late and slight wasting due to disuse atrophy
o Early and marked wasting due to loss of
o
0 Present in irritative lesions of AHCs
Absent
1
muscle tone
3. Reflexes: o Superficial reflexes
o Deep reflexes o Pathological deep reflexes o
Clonus
o
Plantar reflex
I
segmental supply of reflex o Hyperreflexia heiow the level of the lesion
o Lost if the lesion involve the segmental supply of reflex arc itself. o Hyporeflexia at the level of the lesion
o
o
Absent
0
Absent
o
Lost if the lesion above the level of
Present
0 May be present o Extensor response(BABINSKI SIGN): dorsiflexion of big toe ± fanning of other
0 Flexor response(Normal response): planter flexion oftoes or no response in severe cases.
toes
1
4. Others: o Trophic
o
I o Present e.g. ulcers & infections.
Absent
changes
Sensory system
*1* Sensation are classified into :
1. Somatic sensations: are mediated through somatic nerves: A. Superficial sensations:
a. Pain, temperature b. Touch:
B. C. 2. 3.
o Crude touch : light simple touch without accurate localization o Fine touch : touch that accurately localized & finely discriminating Deep (proprioceptive) sensations: vibration sense, muscle sense ,joint sense , nerve sense Cortical sensations: tactile localization, two points discrimination, stereognosis, graphesthesia, perceptual rivalry Visceral sensations: all sensation reaching CNS from internal viscera via autonomic nerves. Special sensations: vision, hearing, smell & taste reaching CNS via cranial nerves.
12
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Pathway of superficial and deep sensations:
Thalamus Thalamns
Lateral lemniscus
Lateral splnothalamic tract Temperature andpain
Anterior splnothalamic tract
Medial lemniscus Cuneate &
Crude touch
Gracile nuclei
Medulla oblongata Spinal cord
Cuneate & Gracile tracts
Dorsal root ganglion Lissauer s tract Substantia
gelatlnosa
I. o
Receptors in:
o Sensation e.g.
0 0
Pain «&
Temperature
Fine touch & Deep sensations
Superficial sensations o
II.
Deep sensations 0 Deep structures
Skin Crude
o
(simple)
Fine
o Vibration sense,joint sense,
touch
touch
muscle sense, nerve sense.
same
pathway as deep sensation
1. [Blorder neuron
o The cells of the dorsal (posterior root ganglion & it's axon. 0 This axon is divided into : a. The lateral branch forms the affere;nt sensory never.
b. The medial branch enters the spin:il cord to ascend a few segment forming ... —» Cuneate & Gracile tracts within the posterior —» Lissauer's tract column of the same side (along with fibers carrying fine touch) Cuneate Tract: carries fibers from upper Vi of body and lies laterally Gracile Tract: carries fibers from lower Vi of
body and lies medially.
o Site of relay of P' order neuron
2. blorder neuron
o
Substantia Gelatinosa of Rolandi
o
Gracile & Cuneate nuclei in medulla
o
Cells of Cuneate & Gracile nuclei in medulla &
(SGR)
o Cells ofSGR in the posterior horn of the spinal cord & it's
it's axon
axon
o
These axon crosses
to OPPOSITE side
o Spinal cord
o
Medulla
in : o
& ascend in... tract
0
Lateral
Ventral
Splnothalamic
Splnothalamic
Gracile & Cuneate
Then in ... lemniscus in brain
stem to relay in the
o Lateral(Spinal)
0
Medial
thalamus of the
^posite side. 3. ISl order neuron:
o Starts in the cells of the thalamus of the opposite side. 0 It's axon ascend to pass through the posterior limb ofthe internal capsule conducting the impulse to cortical sensory area (area 1, 2,3)in the parietal lobe.
13
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
III.
Cortical sensation:
'
o E.g. tactile localization, two points discrimination, stereognosis, graphesthesia, perceptual rivalry
o Mixture of superficial & deep sensation arriving to the thalamus via the P'& 2"'* order neurons & conducted from the thalamus, via the 3'^'' order neuron to the cortical sensory area (1,2,3) in the parietal lobe. Peripheral nervous system (PNS) A. Spinal nerves: Dorsal hom.
Dorsal
Somaltc aHerenl nbers
Intemeuron Dorsal
hom matter
Grey matter
root
Dorsal (track)/
/
\
Doreal
Sensory
-L.>r .Lateral (wm
Vtsceral eflerert lAers
ganglion Receptor Dorsal rrarve
Spinal ganglton Mixed
periptreral
Ventral horn
nerve
Muscle
Central
-Ventral nerve root
Ventral (front) Motor
I nerve trunk
neuron
1. Number: 31 pairs
2. Formation: each spinal nerve is formed by the combination of nerve fibers from the dorsal(posterior) and ventral (anterior) roots of the spinal cord. 3. Type: mixed nerve 4. Function : A. Somatic function:
o
1. Ventral(anterior) root: Composed of motor fibers "axons of AHCs"
o Its cell bodies lie in specific areas of the spinal
2. Dorsal(posterior) root: o Composed of sensory fibers
o Its cell bodies lie in a spinal ganglion (dorsal = posterior root ganglion) that is outside the spinal cord
cord itself. B. Autonomic function :
o Sympathetic fibers through thoracolumbar spinal nerves(T1-L3 levels) o Parasympathetic fibers in sacral plexus(82, S3 and S4 levels)
ntuitaiy staBt
B. Cranial nerves(CN): MIDBRAIN
1) Number: 12 pairs 1. Olfactory
2. Optic
3. Oculomotor
4. Trochlear
5. Trigeminal
6. Abducent
7. Facial
8. Vestibule-cochlear
9. Glossopharyngeal
10. Vagus
Mamniiaiy bodte
PONS
11. Accessory; has 2 part: 12. Hypoglossal 0 Cranial part
2—CNIO MEDULLA
0 Spinal part
❖ N.B.: Groups : 0 Ocular group o Bulbar group CN 3,4,6 CN 9,10,11,12
Cervical
spinal cord
2) Function: Nerve supply to head & neck A. Somatic Function :
1. Pure sensory nerves: special senses 0
CN 1 :smell
0
CN 2: vision
2. Pure motor nerves
0 Ocular group (3,4,6) 0 CN: 11,12
3. Mixed nerves o
The others
0 CN 8: hearing 14
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B. Autonomic function:
o Sympathetic supply through sympathetic chain o Parasympathetic supply through parasympathetic ganglions 3) Nuclei of cranial nerves are arranged in brain stem as follows: o
Mid brain:
o
Pons:
o
Medulla:
o o o
Nuclei of 3,4 Nuclei of 5,6,7,8 Nucleiof9,10,11,12
N,B.: All cranial nerves have nuclei in the brain stem except cranial nerve 1 & 2 emerge from cerebrum so they are not considered cranial nerves but they are considered as tracts.
4) Cortical control of cranial nerve :
Facial area of motor cortex
UMN corticobuiDar tract
Facial motor nucleus
of pons Superior division i
Inferior division
Muscles of facial expression: Frontalis Orbicularis oculi Buccinator
Orbicularis oris
Platysma
o Motor nuclei of cranial nerve in the brainstem receive fibers from cortico-bulbar tract of pyramidal tract of both sides EXCEPT lower part of CN 7 & CN 12 which have unilateral pyramidal fibers from the opposite side. 5) Lesion of CN are either :
o Upper Motor Neuron Lesion(UMNL): pyramidal tract lesion o Lower Motor Neuron Lesion(LMNL): nucleus, nerve, muscle
❖ N.B.: Unilateral paralysis in a CN with bilateral pyramidal tract supply is LMNL.
15
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cranial nerves(CNs)and their diseases
1- CNl: Olfactory Never: ❖
Function : sense of smell
❖ Pathway of smell: Olfactory bulb-..
Olfactory nerves
[/ \l
Olfactory bulb
Olfactory tract
....
)\
1 ]f~—T~
^
Cribriform plate Uncus
/ Olfactory epithelium
\ \ Mucus
o From receptors in olfactory mucosa,fibers of olfactory nerve pierce crihiform plate of ethmoid hone, run in olfactory groove to relay in olfactory bulb,
o
A new set offibers travels in olfactory tract to terminate in olfactory sensory area in uncus ofthe temporal lobe of both sides (bilateral represented)
Lesions:
A. Anosmia: loss of sense of smell: i.
1. 2. 3. a. b. ❖ 1) 2) 3)
P
Unilateral anosmia;
Traumatic: fracture base of skull (fracture cribriform plate) Inflammatory: basal meningitis Neoplastic: Olfactory groove meningioma Tumors ofthe inferior (orbital) surface offrontal lobe Foster Kennedy syndrome: these tumors cause: Ipsilateral anosmia : due to pressure on olfactory pathway Ipsilateral blindness: primary optic atrophy due to direct pressure on the optic nerve Contralateral papilledema : due to f intracranial tension
%
omc NIIIVI ATROPHV PAPiueoeMA
❖ N.B.: Unilateral lesion of uncus does not cause complete anosmia as the sense of smell is bilaterally represented.
ii.
Bilateral anosmia:
1. ENT causes e.g. common cold, atrophic rhinitis. 2. Kallmann's syndrome 3. Heredofamilial
4. Hysterical B. Parosmia :
o Definition: perverted smell e.g. strong scents as perfumes, smell abnormal usually unpleasant. o Etiology: post-traumatic C. Olfactory hallucinations
o Definition: perception of smell usually unpleasant in the absence of stimuli o Etiology e.g. temporal lobe epilepsy 16
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2- CN2: Optic Never: ❖ Function ; sense of vision
V Pathway of vision:
Left Visual Field
Left Visual ^
Visual Field
Temporal Retina
Nasal Retina
@RightVisual Field
Field
Temporal Retina
Left Eye
Right Eye
Optic nerve Optic chiasma Optic tract LGB
Posterior limb ofinternal capsule Optic radiation (upper & lower fibers)
Occipital lobe(area 17, 18, 19) Upper fibers of optic radiation in parietal i
genicuiate body
Superior field of vision Macula-
Inferior field of vision
Lower TempermI lob* lofanof rettna
radiation visua
cofiex
Lower fibers of optic radiation in temporal lobe
1. 2. 3. o o 4.
Receptors of vision are cones (for day vision)& rods (for night cession) of retina. From theses receptors, the nerve fibers converge and pass through the optic disc to form the optic nerve The optic nerve reaches the optic chiasma, where : The nasal fibers of the retina (which carry the temporal field of vision) cross (decussate) to the opposite optic tract The temporal fibers of the retina (which carry the nasal field of vision) proceed to the optic tract of the same side. The fibers of the optic tract then relay in lateral genicuiate body(LGB),from which new fibers arise and travel via posterior limb ofinternal capsule, then fan out forming optic radiation, where : o Upper fibers of optic radiation which carry information from superior retinal quadrants, which represents the inferior visual field quadrants pass through the parietal lobe. o Lower fibers of optic radiation which carry information from inferior retinal quadrants, which represents the superior visual field quadrants pass through the temporal lobe 5. Finally all optic radiation fibers end in area 17(vision is perceived), and area 18 & 19(recognition & recall of images) of occipital lobe. 17
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Lesions in optic pathway:
[
Left
Right
Left
Field
fieM
Lesion BEFORE optic chiasm
R^t
Temporal.
field
1. Monocular visual loss =
Lesion at optic nerve
Righteye
Lefteye
2. Bitemporal Hemianopia= Lesion at optic chiasm Monocular
Bitemporal Hemianopia
Loss
Lesion AFTER optic chiasm Chiasm
Homonymous
3. Homonymous Hemianopia =
Lesion at right optic tract
Hemianopia
4. Lower Homonymous
Quadrantanopia= Lesion at left parietal
Lower
4 Homonymous
Upper
Quadrantanopia
Homonymous
Radiation
Quadrantanopia
5. Upper Homonymous Quadrantanopia=
Lesion at left temporal Radiation - Meyer'sloop
CO
6. Homonymous Hemianopia
Homonymous Hemianopia With Central Sparirvg
With central sparring = Lesion at right occipital Pole
[| Lesion in optic nerve: o Ipsilaterai loss of vision
(primary optic atrophy) o
Loss of
ipsilaterai (direct) AND contralateral
(consensual) light reflex
3 Lesion in
3 Lesion in optic tract:
❖ Lesion in LGB or
optic chiasma:
o Bitemporal hemianopia o Bitemporal hemianopic paralysis of light pupillary reflex
3 Lesion in occipital
optic radiation: 0
Contralateral
homonymous hemianopia (bilateral halfblindness) o Hemianopic pupillary reaction: exposure of the nasal (seeing) side of the
3 Lesion in upper
lobe:
0
homonymous hemianopia (bilateral half blindness)
fibers of optic radiation : o
Contralateral
lower quandrantic homonymous hemianopia
o
fibers of optic
eye results in a pupillary reaction while exposure of the temporal(nonseeing) side results in no pupillary reaction
radiation: o
macular vision due to:
a. Macular fibers of each side are
bilaterally represented in occipital cortical
Contralateral
upper quadrantic homonymous hemianopia ❖ N.B.: Complete lesion of optic radiation:
Preservation of
(macular sparing)
3 Lesion in lower
retina of the affected
Contralateral
area
b. Double blood supply of occipital lobe (from the posterior &
Contralateral
middle cerebral
homonymous hemianopia
arteries) —> Thus in vascular lesions there is
macular sparing
o Preserved light reflex 18
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Reflexes:
iris sphincter muscle muscle
Pupillary constrictor
medial
muscle
■(
r,' oculomotor
rectus
muscle
/ nerve
CV_(parasympathetic part) nerve
ciliary ganglion
Ciliary ganglion
oculomotor nerve
Oculomotor
Optic tract
nerve —
Edinger
Westphal
Edinger-
nucleus
Westphal nucleus
lateral
Lateral
geniculate
geniculate
body pretectal region
nucleus
Pretectal nucleus -
radiation visual cortex
❖ Light pupillary reflex area
❖ Accommodation (near) reflex ❖ Reflex
A. Light pupillary reflex: B. Accommodation (near) reflex: o Normal pupil is Round, Regular, Reactive to light & accommodation o Light to one eye o Near object
❖ Stimulus
❖ Pathway
o Fibers from rods & cones of retina passes into optic nerve (afferent) —> optic chiasma —> optic tract o
Pretectal nucleus in the midbrain
(center){the fibers that reach the opposite side decussating around aqueduct ofsylvius}
0 Lateral geniculate body —> optic radiation primary visual area (17) in occipital lobe (center) area of conjugate eye deviation (8)in frontal lobe
—> Edinger Westphal nucleus(EWN)of both sides in midbrain —> both oculomotor nerve
^ ciliary ganglia —> short ciliary nerves ^ constrictor pnpillae muscles
CN)(efferent) —> -> 3 muscles:
o
Medial recti
o Constrictor pupillae & ciliary muscles through ciliary ganglia
❖ Response o Ipsilateral(direct)& contralateral (consensual) constriction of pupils
❖ Lesion
0 In optic nerve atrophy: absent direct & consensual light reflex o In oculomotor nerve palsy : ipsilateral absent direct & present consensual light reflex
0 Bilateral convergence (both medial recti contract) o Bilateral constriction of both pupil (bilateral miosis) by constrictor pupillae muscles, o Bilateral contraction (accommodation) of ciliary muscles^ convex lens —» focusing o In optic nerve atrophy: absent accommodation reflex
o In oculomotor nerve palsy: ipsilateral loss of accommodation reflex
19
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Ocular muscles
Sphincter pupillae m
Pretectai nucleus
Optic tract
rectu8
Cillaiy ggpgijon
al'aryn
oblique
1
Lateral
^
Edinger* Westphal
Oculomotor n : rectus
nucleus
Ophthalmic n Oculomotor nucleus
Long ciliary n
Dilator
iridis m
Carotid plexus
Inferior nfenor
oblique
rectus
Superior cervical ganglion
C8-T2 segments Parasympathetic Pathway Sympathetic Pathway B. Intra-ocular muscles
A. Extra-ocular muscles
A. 4 recti: superior, inferior, medial, lateral recti B. 2 oblique: inferior oblique, superior oblique
A. Pupil (iris): o Dilator pupillae muscle o Constrictor pupillae muscle
C. Lid muscles:
a. Levator palpeprae superioris(EPS): responsible for 70% of B. Lens: elevation of the upper eye lid o Ciliary muscle: responsible for light & accommodation reflex b. Muller's muscle(smooth muscle adjoining EPS): responsible for 30% of elevation of the upper eye lid ❖ Nerve supply: ❖ ALL striated (voluntary) extra-ocular muscles(4 recti, 2 oblique & EPS)are supplied by oculomotor nerve except: o Lateral rectus by abducent nerve(LR6) o Superior oblique by trochlear nerve(S04) ❖ Autonomic nerve supply: for smooth (involuntary) muscles: o Constrictor pupillae muscle & Ciliary muscle supplied by parasympathetic nerve supply through oculomotor nerve via short ciliary nerves o Muller's muscle & Dilator pupillae muscle supplied by sympathetic nerve supply (preganglionic sympathetic fibers originate from lateral hom cells of C8- T2 segments
relay in superior cervical sympathetic ganglion—> post ganglionic fibers ascend
around internal carotid artery as a plexus of nerves, the carotid plexus)through ophthalmic branch ofthe trigcmiual nerve via long ciliary nerves
❖ N.B.: The spino-ciliary reflex:
o To detect intact occular sympathetic pathway. o Pinching skin on one side of neck results in dilatation of ipsilateral pupil. *1* Causes of ptosis: 1. Congential 3. Oculomotor nerve(CN3)paralysis 2. Hysterical 4. Homer's syndrome
5. 6.
Myasthenia gravis Myopathy
7. Mechanical: edema & trachoma
20
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Causes of pupillary disorders:
❖ Causes of mydriasis
❖ Causes of miosis
1. 2. 3. 4.
Claude Bernard syndrome Holme's Adies myotonic pupil Optic nerve atrophy (blindness) Oculomotor nerve(CN3)palsy:
o 5. 6. 7.
Parasympathetic lesion: dilated fixed pupil. Marcus-Gunn pupil Drugs: atropine & cocaine 4. Drugs: morphine, pilocarpine Physiological: poor light & frightened person 5. Physiological: bright light & sleep
1. Horner syndrome 2. Argyll-Robertson pupil 3. Potine hemorrhage
❖ Marcus-Gunn pupil: relative afferent pupillary defect(RAPD):
m No light
Normal response to light
Positive RAPD of right eye
o In early (incomplete) optic nerve lesion where there is affection of afferent limb of light reflex e.g. optic neuritis o If a light source is swung from eye to eye, lasting 4 seconds on each, the affected pupil may paradoxically dilate. Lesion in ocular sympathetic pathway: A. Claude Bernard syndrome B. Horner syndrome 0 Irritative lesion in ocular sympathetic pathway o Destructive lesion in ocular sympathetic pathway 1. Exophthalmos 1) Enophthalmos 2. Lid retraction 2) Ptosis (partial) 3. Mydriasis 3) Miosis 4. Excess sweating + flush attacks 4) Anhydrosis + conjunctiva) congestion 5. Brisk cilio-spinal reflex 5) Loss of spino-ciliary reflex ❖ Difference between:
1. Causes
A. Holme's Adies myotonic pupil 0 It is a benign heredofamilial 0 Usually unilateral, of acute
B. Argyll-Robertson pupil a. Lesion in peri-aqueductal region ofthe midbrain (where light reflex & sympathetic pupillodilator fibers are close) e.g. Neurosyphilis, Syringobulbia b. Nerve lesion (of both short & long ciliary nerves) e.g.:
onset
0 Occurring usually in females
2. Pupil 3. Light reflex 4. Accommodation
0 0 0 0
Chronic alcoholism
o 0 o o
DM,multiple sclerosis(MS) Encephalitis Miotic, irregular, eccentric pupil Small irregular
0
Preserved accommodation
accommodation
reflex
0
5. Others
Dilated pupil Large regular Loss of light reflex Very slow reaction to
o
On relaxation from
accommodation, pupil dilates very slowly (tonic pupil) 0 It may be associated with lost
0 Sluggish response to cilio-spinal reflex & to mydriatics
ankle reflex
21
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
3- CN3: Oculomotor Nerve:
1. It lies in the midbrain anterior to the aqueduct of Sylvius & close to the midline. 2.
Motor nucleus
Its formed of several nuclei:
of Oculomotor"
a. The main motor nuclei to the extra-ocular muscles
Midbrain
EdingerWestphial
h. Accessory parasympathetic nuclei:
o Edinger Westphal nucleus to constrictor pupillae muscle o Perlia's nucleus to ciliary muscles 3. The oculomotor nerve passes forwards through the
Superior orbital fissure
Nucleus
Cavemous sinus
cavernous sinus to enter the superior orbital fissure «& supplying the following muscles of the eye:
Ciliary ganglion
B. Intra-ocular muscles
A. Extra-ocular muscles
1.
recti: superior, inferior, medial, lateral recti
2.
oblique: inferior oblique
A. o
B. Lens:
3. Lid muscles : o
Pupil: Constrictor pupillae muscle of the iris
Levator palpeprae superioris(LPS): responsible for 70% of
o
elevation of the upper eye lid
Ciliary muscle: responsible for light & accommodation reflex
Lesions:
Etiology : 1.
Infarction of 3'^'' CN e.g. atheroma or DM
2. Cavemous sinus thrombosis 3. 4.
Coning of temporal lobe Aneurysm of posterior communicating artery
5. Vascular lesions of the brainstem Lesion:
I.
Incomplete CN 3 lesion:
A. External ophthalmoplegia:
B. Internal ophthalmoplegia: ❖ Definition:
o Paralysis of extra ocular muscles (except SO & LR)with sparing parasympathetic autonomic innervation of the constrictor pupillae & ciliary muscles
o Selective loss of the parasympathetic autonomic innervation of the constrictor
pupillae & ciliary muscles with sparing of extra ocular muscle innervation
❖ Clinical picture:
1. Complete ptosis (paralysis of LPS) 2. No diplopia, Diplopia occurs only on passive elevation of eye lid 3. Divergent paralytic squint(external strabismus), the eye looks out & down due to unopposed action of SO & LR
11.
1. Ipsilateral Dilated fixed pupil (Mydriasis) 2. Loss of direct light & accommodation reflex while the consensual light reflex is preserved
Complete CN 3 lesion :3 D + loss of 2 reflexes + complete ptosis
»:» N.B.:
Bimxl vessels un pia mater supply surface of the nerve including pupillary fibres (tlainagrd by rompressive lesions I
A. In the oculomotor nerve:
❖ The autonomic fibers lie superficial to motor fibers : 1. Compression of the nerve by tumor results in affection of the superficial fibers with early mydriasis & lost light reflex 2. Infarction of the nerve by ischemia or DM results in sparing of the superficial fibers & so the pupillary reflexes remain intact B. Other causes of ophthalmoplegia: 1. Ocular cranial nerves: CN3,4 & 6 paralysis Vasa nervorum supply part of nerv e hut not pupillary 2. Ocular myasthenia fibres( damaged hy medical lesions ) 3. Ocular myopathy 4. Conjugate eye movement disorders JPugillarj^nbresUe^dorsal^ai^^ 5. Grave's disease
6. Homer's syndrome
22
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4- CN4: trochlear nerve & CN6: abducent nerve o
Cranial nerve :
o
Its nucleus lies in:
4- CN4: trochlear nerve:
6- CN6: abducent nerve:
o It supplies:
o Lower part ofthe midbrain o Superior oblique muscle; S04
o Etiology of the
1. Head injuries
o Lower part of the pons
o Lateral rectus muscle; LR6(abduction) 4V
2. Cavernous sinus thrombosis
lesion:
3. Aneurysm of internal carotid artery 4. Vascular lesions of the brainstem o
1. Dipiopia (double vision) only on looking down & out 2. Limitation of movement during examination for eye movement
Lesion:
1. Dipiopia only on looking outwards 2. Limitation during examination of eye movement in outward direction
3. Convergent paralytic squint(internal strabismus)
down & out
❖ N.B,: Horizontal conjugate gaze pathway for conjugate eye movement; FRONTAL CORTEX
Saccsdic Eye Movements ,
FronMI ay* BM
Oeutomown.
rtOtOB NERVe MEDIAL RECTUSM.
^ ^
OCULCNKIOTOR NUCLEUS
RECTUS M
«
\nld brain
MEDIAL LONGITUDINAL FASCICULUS
media
longUudinai rascicuius
ASDUCENS NUCLEUS
1. 2. 3. 4.
Contralateral cortical frontal eye field (area 8) Ipsilateral paramedial pontine reticular formation(PPRF) Ipsilateral abducent nucleus Contralateral Medial Longitudinal Fasciculus(MLF)
PARAMEDIAN PONTINE RETICULAR FORMATION
5. Contralateral oculomotor nucleus
❖ Etiology of conjugate eye palsy: Cortical
Pontine
lesion
lesion
Rl0ht Intemuelearophthalmople^ls(INO) Seizure
Failure of right adduction -r
leftatducting nystagmus
Cortex
%
Pons
Gaze
periphery of face —> center of face
2
Upper face ❖ Sensory affection:
❖ Site of the lesion:
I. Lesion starting from above e.g. lower
o Lower face anesthesia with normal upper face
pontine tumor
2. Lesion starting from below e.g. upper
o Upper face anesthesia with normal lower face
cervical lesions
3. Lesion starting from periphery e.g. Tabes dorsalis
0 Loss of sensations in center of face with preservation of peripheral sensation
4. Lesion starting from midline e.g. syringobulbia
o Loss of sensations in periphery offace with preservation of central sensation
B. Motor affection:
o
Weak muscles of mastication of same side of the lesion
o Deviation ofjaw to affected side due to the unopposed action of pterygoid muscles of healthy side.
C. Reflex affection:
a. Superficial reflexes: ❖ Ipsilateral loss of.... reflex o Comeal & Conjunctival
❖ Afferent 0
o
Palatal
❖ Efferent 0
CN7
0
CN 10
CN5
b. Deep reflexes : o Appearance ofjaw reflex (afferent 5 / efferent 5), in bilateral pyramidal tract lesion above the pons.
25
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Trigeminal Neuralgia: Tic Douioureux ❖ Definition:
o Severe attacks of pain along one or more ofthe sensory branches of trigeminal nerve usually maxillary & mandibular divisions Etiology: I. 11.
Primary: idiopathic : the commonest, seen in middle age females Secondary:
1. Alcohol intake
2. 3. o o o 4.
Post herpetic trigeminal neuralgia Compression of the trigeminal sensory root in cerebellopontine angle by : Tumors e.g. Acoustic neuroma Aneurysm or Arteriovenous malformation Vascular Anomaly e.g. tortuous and elongated superior cerebellar artery Multiple (Disseminated) sclerosis & DM
Clinical picture:
❖ FACIAL PAIN diagnosed on clinical ground alone: 1. Site:
o Along distribution of one or more of the sensory branches of trigeminal nerve, usually maxillary & mandibular divisions o
It is almost unilateral.
2. Onset: sudden onset 3. Character:
o Severe lancinating knife-like stabbing pain o Shooting, electric shock like pain 4. Duration: Short paroxysms lasting from seconds to minutes 5. Increased by: o JAW movements e.g. talking & mastication
6. Decreased by: spontaneous remission or by analgesics . 7. Associated symptoms: o The face is screwed up in agony with involuntary movement (tic) Differential diagnosis from other causes of FACIAL PAIN: ❖ D.D. of Facial pain: 1. Trigeminal Neuralgia
❖ Characters
o o o o o
Paroxysms of knife-like or electric-like pain Usually affects ophthalmic division Pain is followed by herpetic skin eruption Worsens in morning & tender over sinuses Pain behind eye with visual symptoms
5. Dental
o
Pain around mouth
6. Cluster headache
0 Pain above & behind the eye associated with autonomic
7. Costen's syndrome :
o Pain is in front of ear & aggravated by chewing
2. Post herpetic neuralgia 3. Sinusitis
4. Ocular (glaucoma)
symptoms e.g. lacrimation and or rhinorrhea Temporomandibular joint dysfunction 8. Tabes dorsaiis
o Early facial pain 0 Later loss of sensations in center offace with preservation
9. Atypical facial pain
0 Pain is diffuse & persistent
of peripheral sensation 0 Associated with depression
26
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Treatment:
A. Medical:
1. Carbamazeplne (antiepileptic): 600 -1200 mg / day orally suppress attacks in most patients 2. Analgesics B. Interveiitional:
o Trigeminal ganglion block or neurolysis
Trtg«mlnal N«rv»
C. Surgical 1. Trigeminal nerve root section
m Bunch,
S54 y.—-
2. Microvascuiar decompression
. ■■i.;' ' '--til-
h
Carbamazepine
7- CN7: Facial Nerve:
^onge
Cerebellum Trigeminal nerve
Radvlrtqutncy NM4e
❖ Nerve supply(= function): ❖
The facial nerve has three nuclei; Abducent nucleus
Facial colllculus Nucleus oftractus solicarius
Spinal nucleus and tract oftrigeminal nerve
Ceniculate ganglion
.O o/.
O
..
Superior salivatory and lacrimatory nuclei
A. The main motor nucleus(motor part):
B. The sensory nucleus (sensory part): solitary nucleus
C. The parasympathetic nucleus (autonomic part):
1. Muscles of expression offace
0
o The superior salivatory nucleus supplies submaxillary, sublingual salivary glands, the nasal & palatine glands o The lacrimal nucleus supplies the lacrimal
o Platysma o Posterior belly of digastric o Stapedius & Stylohyoid
Taste sensation from anterior 2/3 of
2. Four other muscles:
tongue o
The floor of the mouth
& the palate
gland
27
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
ASOUCENS
❖ Pathway:
NUCLEUS
FACIAL
MOTOR
NERVE PROPER
NUCLEUS
SUPERIOR
SALIVATORY NUCLEUS
INTERNAL
FACIAL CANAL
AUDITORY MEATUS
SOLITARY TRACT NUCLEUS
OENICULATE
WTEHMEDIATE
QANOUON
NERVE
QREATER SUPERFICIAL
PETROSAL NERVE SPHENOPALATINE QANOLION LACRIMAL OLAND
SUBMANDIBULAR OANOUON
A. Motor pathway:
SUBMANDIBULAR OLAND
1. Motor nucleus is located in pons.
BUBLINQUAL OLAND
2. Control:
Pyramidal fibers:
B. The lower part of the facial nucleus:
A, The upper part of the facial nucleus:
o Bilateral pyramidal supply from both sides o Unilateral pyramidal supply from the contralateral side only ii. 3.
Extra-pyramidal fibers: for emotional and associated movement
Motor fibers form a loop around 6"' nerve nucleus, then pass laterally to emerge at lower pons, then runs laterally between 6"^ & S"" cranial nerve in cerebellopontine angle to enter through the internal auditory meatus into facial canal.
4. 5.
In facial canal, motor part offacial nerve becomes adherent to its sensory & autonomic parts. It then leaves canal through stylomastoid foramen, passes through the parotid gland to divide into its terminal branches.
B. Sensory & autonomic pathway: In facial canal lies the geniculate ganglion (contains unipolar cells), their processes divides into two parts : Peripheral part: runs laterally & divides into: A. Greater superficial petrosal nerve: o It relays in sphenopalatine ganglion It gives autonomic supply to lacrimal gland.
1
Chorda tympani:
It leaves canal before stylo-mastoid foramen. It supplies submaxillary & sublingual salivary glands & gives taste sensation to anterior 2/3 oftongue Central part:
It joins the motor part of the nerve, enters cranial cavity through internal auditory meatus as nervus intermedius. Nervus intermedius enters brain stem at the pontomedullary junction to terminate in the solitary nucleus in medulla. A new set of fibers from the nucleus cross to opposite side, runs up to lower part ofcortical sensory area, where taste sensation from anterior 2/3 of tongue is perceived.
28
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Unilateral lesion of facial nerve:
Right
Left
(LtnsiDt LEStM
I
Corticobulbar fibers J
Right
lesion
Left Facial nucleus lesion
Lower 1/2 of facial nucleus
^Facial nerve
lesion
Lower 1/2 of
Same side of the face
opposite side of the face
UPPeg MOTOR NEUTION LESiON
LOWER MQTOP NEURON LESION
Droopy eyelid, dry eye, or excessive tear*
Facial paralysis
twitching, or weakness
Drooping corner of
mouth, dry mouth impaired taste
❖ Unilateral UMNL of facial nerve:
❖ Unilateral LMNL of facial nerve:
❖ Etiology: o Same causes of hemiplegia e.g. vascular, traumatic, o Nuclear: pontine lesion
inflammatory, ncoplastic, dcmyclinating(MS),
0 Infra-nuclear lesion: cerebellopontine angle,
degenerative(MND)
facial canal & extra-cranial lesion
❖ Lesion:
1
o Supra-nuclear lesion i.e. affecting A tract above facial motor nucleus in the pons.
I
o Nuclear lesion i.e. affecting the facial motor nucleus
0 Infra-nuclear lesion i.e. affecting the facial nerve itself.
❖ Clinical picture:
1
A. Paralysis ofthe muscles oflower half of the face on the
opposite side of the lesion (supplied from the opposite A
A. Paralysis of the all muscles of the upper & lower halves of the face on the same side of the lesion.
❖ In addition; there are: I to 5 + 6. Inability to raise eyebrows with absence of
tract only): the affected side shows: 1. Obliteration of the naso-labial fold
2. Dropping of the angle of the mouth with drippling of saliva
wrinkles offorehead
3. Accumulation of food behind cheek
7. Bell's phenomenon :
4. 5. B. C.
0 Inability to close the eye & rolling up on trial
Inability to blow the cheek Inability to show teeth properly Paralysis involves the voluntary movements It spares the emotional & associative movements which are supplied by extra A fibers
D. Paralysis is associated with hypertonia & hyperreflexia. E. There is associated hemiplegia on the same side ofthe facial paralysis.
B. Paralysis affects voluntary movements C. Paralysis affects emotional & associative movements.
D. Paralysis is associated with hypotonia & hyporeflexia. E. If there is hemiplegia, it is on the opposite side of the facial paralysis (crossed hemiplegia).
29
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
|
❖ Bilateral UMNL OR bilateral LMNL of facial nerve: paralysis of ALL muscles of THE WHOLE FACE: Etiology of bilateral facial nerve paralysis : 1. Bilateral Acoustic neuroma
2. 3. 4. 5. 6.
Bilateral Bell's palsy & Botulism Guillain-Barre syndrome Syphilis, Sarcoidosis, Spirochetes(Lyme disease) Malignancy e.g. Leukemia Multiple sclerosis(MS)
N.B.: Myasthenia gravis, Myotonica dystrophia —> weakness of facial muscles ^ facial paralysis Clinical differentiation :
A. Bilateral UMNL of facial nerve
B. Bilateral LMNL of facial nerve
1. Glabellar reflex
o Exaggerated
o
Lost
2. Jaw reflex
o
o
Absent
Present
❖ Localization of lesion in unilateral LMN facial paralysis = causes of unilateral LMNL facial paralysis:
ABDUCENS
»M>CL£US
SUPERIOR SALIVATORV TRACT NUCLEUS
MOTOR NUCLEUS
OF VII FACIAL NERVE PROPER GENtCULATE
GANGLION
INTERNE CMTE NERVE
CHORDA TYMPAM
SPHENOPALATINE QLiON
SUBMANCNBULAR OANGUON
'SUBUNGUAL GLAND
30
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Localization of lesion in unilateral LMN facial paralysis = causes of unilateral LMNL facial paralysis:
cortex
upper face
SUPRANUCLEAR
kNwfoce CENTRAL
NEUROLOGICALJ EXAM
NUCLEAR INFRANUCLEAR CEREBELUOPONTINE ANGLE
f
INTERNAL AUDITORY CANAL
ENG
bolonce
^ . AUDIOLOGIC czSheonnq jXRAY
(J
GENICULATE GANGLION
.i TEAR TEST
locriiTtal glond i
STAPEDIAL REFLEX
chordo tymponi
Wtonguei taste TYMPANOMASTOlO
sublinguol
1 SALIVATION
submondibular
i FACIAL
EXTRACRANIAL
! MOVEMENT ❖ Site of lesion
1.
0
11.
Nuclear lesion
Facial motor nucleus in
the pons.
A. Cerebellopontine angle
Infra-nuclear lesion
B. Facial canal lesion:
11 C. Extra cranial facial
lesion : after it's exit
lesion:
from the stylomastoid foramen
❖ Etiology
1 1. Vascular: vertebrobasilar
1. Inflammation: basal
1. Infective: Herpes
insufficiency & MiilardGubler syndrome Infective: poliomyelitis, Encephalitis Neoplastic: astrocytoma, glioma Demyelinating e.g. multiple sclerosis(MS) Degenerative e.g. motor
meningitis 2. Neoplastic: acoustic
zoster & otitis media 2. Trauma: fracture base
2. 3. 4. 5.
neuroma & meningioma
& during mastoidectomy
3. Neoplastic: facial neuroma
4. BELL'S PALSY
1. Neuropathy: DM, leprosy 2. Myopathy: facio scapulo humeral 3. Myasthenia gravis & Myotonia 4. Parotid causes: tumor
invasion, surgery.
neuron disease(MND) ❖ Clinical picture:
1. Paralvsis of facial muscles on affected side of unilateral LMNL features(mention them from 1 to 7) 2) J, lacrimation IF greater 2) i lacrimation 2. NO impainnent in superficial petrosal lacrimation, salivation, & 3) i salivation nerve is involved 4) i taste on anterior 2/3 of taste. 3) i salivation & taste on tongue anterior 2/3 of tongue
IF chorda tympani is involved 3. ± LMNL of cranial nerve
palsy on same side or hemiplegia on opposite side
4) Hyperacusis(f 5) 5th,6th,8th cranial hearing)IF nerve to nerve palsy on same side stapedius is involved 6) Ipsilateral cerebellar ataxia
31
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Bell's palsy (idiopathic facial nerve paralysis)
Definition:
o Acute non suppurative inflammation offacial nerve with swelling near to stylomastoid foramen o Usually unilateral, may be recurrent & sometimes run in families. Etiology: 1. Autoimmune: evidenced by high immunoglobulin levels in serum 2. Viral infection e.g. Herpes simplex virus or herpes zoster virus 3. Vascular ischemia :
o Trigger factor following air draft(wind, air condition, driving with car window down) sheath in stylomastoid foramen, with edema & ischemia —> compression of facial nerve
inflammation of nerve
Clinical picture:
A. Onset: acute onset(over 48 hours) with posterior auricular pain following exposure to air draft or without pain. B. One or two days later : 1. Features of unilateral LMNL of facial nerve in FACIAL CANAL:
o Paralysis of facial muscles on affected side ofLMNL features i.e. affect all Vz offace (mention them from 1 to 7) o Features offacial nerve paralysis in facial canal 2. It may occasionally present with bilateral LMNL offacial nerve. C. Long standing cases: 1. Corneal ulcers
2. Hemifacial spasm : irregular painless clonic spasm of the facial muscles 3. Atrophy and facial asymmetry due to incomplete recovery 4. Aberrant re-innervation:
o o a. b.
Regenerating facial fibers anastomose with trigeminal fibers When patient moves his jaw while eating or speaking, there may be : Winking (jaw-winking) Lacrimation (crocodile tears)
Differential diagnosis: o
From causes of unilateral facial weakness due to nuclear & infra-nuclear lesion ❖ Treatment:
1. Physiotherapy: o Massage of facial muscles
soiimm
o
Infra-red irradiation of face
fnamsoione
o
Galvanic stimulation offacial muscles
2. Drugs:
o Corticosteroids: oral prednisolone(Img /kg/ day), to decrease inflammation & edema o Corneal ulcer protection e.g. Sun glasses during daytime & eye ointment during sleep 3. Surgical:
o For facial nerve palsy: decompression of facial nerve or facial nerve grafting o For facial asymmetry : plastic operation o For aberrant re-innervation : section of regenerating fibers ❖ Prognosis : o Most patients: SO % recover in 4-6 weeks o The remaining: 20% need surgical interference 32
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
8- CN8: Cochleo-vestibular nerve:
This nerve is composed of two divisions: cochlear & vestibular. Vestibular
V Pathway:
»— Vestibular nerve internal acoustic meatus
Auditory area
Cochlear nerve
vestibute
Medial
Pons ^
genicuiate body Lateral lemniscus
Cochlear Cochlea
division
(containing spiral ganglion) vestibulocochtear nerve (Vlli)
A. Cochlear division for hearing pathway: Function: hearing Pathway:
Fibers originating from the ganglion cells of the cochlea pass centrally from the inner ear through internal auditory canal where they are joined by vestibular division Then they pass through cerehello-pontine angle to enter the brainstem, where they relay in the cochlear nucleus in the lower pons In the nucleus new fibers arise; some ascend in the lateral lemniscus ofthe same side while the remainder decussate
& ascend in the lateral lemniscus of the opposite side, to reach the medial genicuiate body(MGB) After relaying in the MDB,the fibers pass the auditory sensory area in temporal lobe where hearing is bilaterally represented. ❖ Lesion of cochlear division results in
❖ Etiology: cerehello-pontine angle tumor e.g. acoustic neuroma, meningitis ❖ Lesions: o o
Irritative lesion : Tinnitus Destructive lesion: Deafness
B. Vestibular division for equilibrium pathway: ❖ Function: equilibrium ❖ Pathway: o Fibers originating from the vestibule (utricle / saccule)& semicircular canals of the inner ear —> internal auditory canal to join cochlear division —> cerehello-pontine angle to enter the brain stem where they relay in the vestibular nuclei of the brain stem.
o
From these nuclei, three fibers takes pathwavs to :
1. ArChicerehellum : concerned with equilibrium 2. Medial longitudinal bundle : concerned with synchronous movement of eyes, head & neck 3. Cerebral cortex : concerned with orientation of individual consciously in space i.e. the perception of sense of vertigo ❖ Lesion of vestibular division results in :
1. Vertigo 2. Spontaneous nystagmus 3. Ipsilateral incoordination.
33
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Vertigo
Definition:
A. Sense of rotation of the body in steady environment OR the environment rotates in relation to the body (i.e. subjective or objective) B. Characters :
1. It Persists in all position : Supine, Sitting & Standing 2. It is Aggravated by movements of head
3. It is Associated with autonomic manifestations e.g. nausea, vomiting, pallor & bradycardia. C. It should be differentiated from dizziness where the unsteadiness (postural instability) NOT associated with sense of rotation
Etiology:
I. Peripheral vertigo: labyrinthine or S"" cranial nerve: A. Physiological: Motion sickness e.g. car, air & seasickness B. Pathological: 1) Benign paroxysmal positional vertigo: The most common cause o Etiology: idiopathic o Mechanism : canalithiasis i.e. dislodgment of otoliths of inner ear from the utricle to semicircular canals
o Description of vertigo: a. Postural : during changing the position e.g. rolling over in bed, or rising from chair
^
b. Associated with nystagmus c. Mild & transient, lasting < 30 seconds
2) Vestibular neuritis & labyrinthitis
K-F
3) Meniere's disease 4) Otitis media & Otosclerosis
5) Ototoxic drugs e.g. aminoglycosides e.g. streptomycin II.
^eptornVfj
^Injection U-S^'
Central vertigo: cerebrum, brainstem or cerebellum:
1. Vascular:
a. b. c. d. 2. 3. 4. 5.
Vertebrobasilar insufficiency Posterior inferior cerebellar artery occlusion Migraine tICT Inflammatory: Encephalitis Neoplastic: cerebellopontine angle tumor e.g. Acoustic neuroma Demyelinating: Multiple sclerosis(MS) Degenerative: MND,cervical spondylosis
^:f
Differential diagnosis: Psychogenic vertigo:
o Acute anxiety (panic state) presented by dizziness where the unsteadiness (postural instability) NOT associated with sense of rotation
o It responds to tranquilizers ❖ Treatment: A. Treatment of the cause
Dramamme
Betaserc Betahistine dihydrochloride 24 mg 50 tablets
B. Drugs:
1. Anti-histaminics: dramamine ± tranquilizer e.g. trifluoperazine
Cinnarizine Stugeron
2. Betahistine. 3. Cinnarizine.
34
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
9- CN9: glossopharyngeal nerve:
o The glossopharyngeal nerve leaves the skull through jugular foramen ❖ Nerve supply:
A. The main motor nucleus
(motor part):
0 Stylopharyngeus muscle 0 Superior constrictor muscle of the pharynx
B. The sensory nucleus (sensory part):
C. The parasympathetic nucleus
o
0 Parasympathetic fibers to parotid gland
Tonsils
o Pharynx 0 Posterior 1/3 of tongue : general
(autonomic part):
& taste sensation
Lesion: Jugular loramen
1. Ipsilateral loss of pharyngeal reflex (afferent 9/efferentlO) 2. Ipsilateral loss of taste & general sensation over post 1/3 oftongue
Oioaaopharyngeal nerv« {IX)
Vagus rwrw (X)
N.B.: accessory nerw (XI)
o Isolated lesion of glossopharyngeal nerve is rare
o Glossopharyngeal nerve lesion usually damaged in association with the vagus & accessory nerves as they pass through the jugular foramen at the skull base (jugular foramen syndrome = Vernet's syndrome) Glossopharyngeal neuralgia ybnlnttMi \
Etiology: ■Mi/
I.
J
Primary: idiopathic : the commonest, seen in middle age females
■KT^giowoplMfyngMl
II. ^ Secondary : 1.
Alcohol intake
2.
Post infection
3. Compression of the glossopharyngeal nerve by : o
Tumors
o o o 4.
Aneurysm or Arteriovenous malformation Vascular Anomaly Bone : Elongated styloid process Muitiple (Disseminated) sclerosis & DM
Sty loid process Glossopharyngeal n
Clinical picture: ❖ THROAT PAIN diagnosed on clinical ground alone: 1. Site:
o Along distribution of glossopharyngeal nerve e.g. back ofthe throat(pharynx, tonsils), tongue, tonsil or ear o
It is almost unilateral.
2. Onset: sudden onset 3. Character:
o Severe lancinating knife-like stabbing pain o Shooting, electric shock like pain 4. Duration: short paroxysms lasting from seconds to minutes 5. Increased by:
o THROAT movement e.g. talking & swallowing 6. Decreased by: spontaneous remission or by analgesics. 7. Associated symptoms: o Weight loss because the patient is afraid to eat from pain
35
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Treatment:
A. Medical:
1. Carbamazepine (antiepileptic): 600 -1200 mg / day orally suppress attacks in most patients 2. Analgesics B. Interventional:
o Glossopharyngeal ganglion block or neurolysis C. Surgical
1. Glossopharyngeal nerve root section 2. Microvascular decompression SplMn Stomach
10- CNIO: Vagus nerve:
Kldnay
The vagus nerve has three nuclei: A. The main motor nucleus
B, The sensory nucleus
(motor part): o Soft palate o Pharynx o Larynx
C. The parasympathetic nucleus(autonomic part):
(sensory part): o
o Inhibitory parasympathetic to heart, respiratory
Skin over external
auditory meatus o
tract & GIT (secretory & motor)
Thoracic and abdominal viscera
Lesion: Bulhar symptoms: Palato-pharyngeo-laryngeal paralysis: true hulhar pasly ❖ Palato-pharyngeo-laryngeal paralysis:
1. Bulhar symptoms: dysphagia, dysarthria, dysphonia (hoarseness of voice)& nasal regurge 2. Ipsilateral loss of palatal & pharyngeal reflexes 3. Drop of palatal arch on paralyzed side & shift of uvula to opposite side of paralysis 4. Others:tachycardia & constipation vagus nerve
11- CNll: Accessory nerve:
Cranial root of accessory nerve
Spinal root of
❖ Pure motor nerve
accessory nerve magnum
Accessory nerve
Muscles of
palate Muscles of
pharynx Muscles of
larynx
Spinal accessory nerve
Formed of two parts:
Trapeaus
Stemocleidomastoid
B. Spinal part:
A. Cranial part: o
It arises in the medulla
o It runs with the vagus nerve o
It shares in the motor innervation of
soft palate & pharynx
o It arises from the AHC ofthe upper five cervical segments, ascend
along the spinal cord and enters the cranial cavity through foramen magnum.
o It joints the cranial portion to exit through the jugular foramen to supply the stemomastoid & trapezius muscle.
❖ Lesion:
o Ipsilateral paralysis of: a. Stemomastoid muscle: weakness in turning the head to the opposite side of paralysis
b. Trapezius muscle : shoulder drop in the same side ofthe paralysis 36
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ 12- CN12: Hypoglossal nerve: Pure motor nerve
❖ Nerve supply: It carries motor fibers to intrinsic muscles ofthe tongue
❖ Lesion:
Lt UMNL
Rt UMNL
Weak muscles
7*^-}—Nucleus ,
ambiguus
Uvula I
Hypoglossal
"Hypoglossal Tongue
nucleus
nucleus
Deviation of the tongue to same side of LMNL
Deviation ofthe tongue to opposite side of UMNL
The tongue always deviates toward the weak paralyzed muscles whether the lesion is supranuclear or nuclear^J Bilateral UMNL
Bilateral LMNL
Spastic tongue
Flaccid tongue
❖ Remember that:
1. Motor nuclei of CN 12 in the hrainstem receive unilateral fibers (in 50 % of people)from cortico-hulhar tract from the opposite side
2. Muscles ofthe tongue are pushing muscles while uvula muscles are pulling muscles.
A. UMNL
B. LMNL:
o Unilateral: deviation of the tongue to opposite side of
o Unilateral: deviation ofthe tongue to same side of
UMNL
LMNL
0 Bilateral: inability to protrude tongue (spastic tongue) 0 Bilateral: inability to protrude tongue (flaccid o In both cases there is neither wasting nor fasciculation
tongue) 0 In both cases there is wasting & fasciculation, tongue is sickle, corrugated & wasted
37
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ N.B.: Nerve supply to the tongue:
Motor: Hypoglossal {XII), except Palatoglossus: Pharyngeal branch of Vagus(X)
A. Motor :
Postartor 1/3
o Hypoglossal nerve except palatoglossus by pharyngeal branch of 10"' CN Sensory and Taste:
B. Sensory:
Glossopharyngeal (IX)
1. Anterior 2/3:
o
General sensation : 5'" CN Sensory: Lingual branch of V3
o Taste sensation by T'" CN
from Trigeminal (V)
2. Posterior 1/3 :
o General & taste sensation by 9'" CN
Taste: Chorda tympani branch of Facial (VII), carried by lingual branch
Speech
Antarior 2/3
❖ Process of speech involves two stages:
1. Speech formulation : A. Sensory system for language input: 1. Visual areas for written speech:
2. Auditory areas for spoken speech:
o 17: primary visual area ^ reception of visual impulses 0 18,19: secondary visual area —> recognition ofimages o 39: Angular gyrus —> recognition of letters & numbers
0 41,42 : primary auditory area ^ hearing o 22 : secondary auditory area —> recognition of sounds
o Wernicke's area is required for both cases ^ sensory center for writing & speech ^ giyes meaning for written and spoken words i.e. FULL comprehension of written and spoken language B. Motor system for language output: o Broca's area (44): motor center for speech o Exner's area (45): motor center for writing C. Associative system:
o Supramarginal gyms (area 40): storage of ideas of speech & complex voluntary movement —» Deject in all previous mentioned areas cause aphasia
All previous mentioned areas are situated in DOMINANT hemisphere except area 17,41,42 which are situated in both hemispheres.
2. Speech articulation : ❖ It is the function of the following systems : 1. UMN: pyramidal tract for voluntary control 2. LMN:
o Cranial nuclei: concemed with articulation (5,7,10,12), their nerves, NMJ & the muscles they supply. 3. Extrapyramidal tract: for speech to be expressive 4. Cerebellum : for coordination ofthe muscles of speech
Defect in all previous mentioned areas cause dysarthria.
38
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Mechanism of speech:
//
Spoken speech
Written speech
\
0
Primary auditory area (41,42)
Primary visual area (17)
0 Secondary auditory area (22)
Secondary visual area (18,19) arcuate
fasciculus
0 Angular gyrus(39) Brocas
Wernicke's area
0
V ❖ Wernicke's area (sensory center for writing & speeeh):
1. FULL comprehension of visual & auditory information i.e. gives meaning for written and spoken language 2. Determination of thoughts & choice of words to be expressed .
0 Arcuate fasciculus
READING
HEARING
(Band of white matter running deep to the supramarginal gyrus and insula) V-
o Broca's area (44): motor center for speech o Exner's area (45): motor center for writing lit motor cortex
Wemicke'i
Broeat
Motor cortex: area 4 & area 6
Cranial nerves
Stimulate speech muscles resulting in production of spoken words -> SPEAKING
39
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
o
39
because he
no relation to each other.
words
44
words
o Expressive aphasia: The patient understand visual & auditory stimuli, but he can't express his ideas in spoken
o
1) Verbal aphasia
o
written words
express his idea in
numbers but he can't
Agraphia: The patient understand visual & auditory stimuli, letters &
45
2) Writing aphasia
C. Motor (expressive-non fluent) aphasia
%
40
2. If a child is bom blind (area 39 will not develop)& hence he will not be able to write.
1. If a child is bom deaf(area 22 will not develop) hence he cannot imitate sounds, the lack of speech is called deaf aphasia (mutism).
❖ N.B.:
numbers
letters &
recognize
does not
cannot read
not
meaningless & have
but does
recognize objects
the words are
hear but does not
recognize sounds
The patient
can see but
can see
& auditory stimuli but find difficulty in repetition of
The patient understand visual
Word salad: The
patient can speak, but
Fndoy Soturdoy Sunday
Word deafness:
tz
Hursdou
Tuesday Wednesday
Arcuate fasciculus
o ❖ Definition
40
o
❖ Lesion in area: Wemicke's area
The patient can
o
blindness:
22
❖ Subtypes: 4. Jargon's aphasia o Conduction aphasia
Word
o
o
3. Auditory agnosia
aphasia
B. Associatise
patient
ABG 123
o
aphasia (alexia)
2. Visual
A. Sensory (receptive-fluent) ap lasia
The
18,19
agnosia
1. Visual
❖ Types:
❖ Definition : inability of formulation of speech, in absence of lesion ofsense (vision or hearing) organs, or mental defect
1. Aphasia:
❖ Speech disturbance:
|
2. Dysarthria :
❖ DeHnition : difficulty in articulation of speech with normal formulation i.e. normal speech center UPPER MOTOR NEURONS 1
fj
iT
\
BRAINSTEM
^
r1
(BULBAR)
A
/
I 3
1V
/>
\
f
f
LOWER MOTOR
NEURONS
tongue
Types: Slurred speech ;
o Disturbance in the production of consonants especially labials (e.g. B, M)and dentals (e.g. C,D,T) is affected due to:
A. Bilateral pyramidal lesion (lesion of the cortico-hulhar fibers) e.g. pseudobulhar palsy B. LMN of cranial nerves concerned with speech : ■ Nuclear: true bulbar palsy ■
Nerve: lesion in 5, 7, 10, 12
■ ■
Neuromuscular junction: myasthenia Muscles: facio scapulo humeral myopathy
Staccato speech:
Explosive speech with separation of syllables : monosyllabic speech It occurs in cerehellar lesions as in hereditary ataxia & MS Scanning speech (Slurred-staccato): In combined pyramidal & cerehellar lesions Monotonous speech: Expressionless & monotonous speech Due to extra pyramidal lesion e.g. parkinsonism
'
I
41
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Bulbar palsy
❖ Paralysis of the muscles supplied by lower four cranial nerve (9"", 10''',11'''&12'''): Palato-pharyngeo-laryngeal paralysis leading to bulbar symptoms :
o Dysphagia o o o
^
Dysarthria Dysphonia : hoarseness of voice Nasal regurgitation
❖ Bilateral lesions of 9"^, 10"', 11* & n*" cranial nerves present as pseudobulbar palsy or true bulbar palsy ❖ N.B.:
o Unilateral bulbar palsy can occur but is ALWAYS OF LMNL since A supply cranial nuclei of BOTH side.
P *1* Pseudobulbar palsy (bilateral t
❖ Definition
1. Inflammation
❖ True bulbar palsy (bilateral LMNL)
UMNL)
$
o Bilateral pyramidal tract lesion o Bilateral affection oflower four cranial nuclei or (corticobulbar tract) above pons their nerves ❖ Etiology: o Encephalitis o Bulbar poliomyelitis 0 General paralysis of insane of 0 Diphtheria syphilis
2. Immunological
0 Multiple sclerosis
o Myasthenia gravis o Landry-Guillain-Barre Syndrome
3. Neoplastic
o
4. Vascular
o Bilateral (double) hemisphere
5. Degenerative
0
o
Midline brain tumor
Midline brain stem tumor
0 Medullary infarction (Vertebrobasilar stroke)
stroke Motor neurone disease of Betz cells
0 Motor neurone disease in medullary nuclei o Syringobulbia
❖ Clinical picture: 1. Quadriplegia
o
Present
o
2. 5"" CN: jaw reflex
o
Present
o
Absent
3. ri-CN
4. 9*''&10">CN
o 0 0 o o
Exaggerated glabellar reflex Spastic face especially lower half Exaggerated emotional lability Hypoacusis (spastic stapedius) Exaggerated palatal & pharyngeal
o o 0 o o
Lost glabellar reflex Flaccid face, both upper & lower half Lost emotional response Hyperacusis (flaccid stapedius) Lost palatal & pharyngeal reflex
5. 12'" CN
o Spastic tongue
o Flaccid, atrophic (small & wasted)tongue
o
0
Absent
reflex
No fasciculations
Fasciculation's
42
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cerebrovascular diseases
❖ Definition :
o Diseases of blood vessels and blood supply to the brain.
❖ Types of cerebrovascular diseases:
t i
Ischemic Stroke
i
V>
Hemorrhagic Stroke
Blood vessels ruptm
Blood dots stop the flow of blood into brain tnsue
Thrombotic Stroke
Blood lesKs mto brain tissue
Embolic Stroke
area ol bleeding
.area deprtvnd
.area deprived
of blood
vot blood
Cerebral
Hemorrhage
Tatty phxtue or blood dot
Break in blood vessel
(embolism) breaks
Blood dot(thrombus)
away arid hows to
tilocksflowtrflilood In brain.
brain where k
I.
(aneurysm)in brain.
blocks an aitery.
Global injury :irreversible ischemic/hypoxic encephalopathy
o Generalized reduction of cerebral perfusion e.g. cardiac arrest, prolonged hypoxia or hypoglycemia , II.
Focal injury:
A. Cerebral ischemia: 1. Cerebral insufficiencv
a. Transient Ischemic Attacks(TIAs)= Mini stroke
b. Posterior reversible encephalopathy syndrome(PRES)due to hypertensive encephalopathy, SLE, TIP,eclampsia 2. Cerebral infarction (Ischemic stroke): o
The most common cause: 85 % of cases
o Etiology: 1) Thrombosis 2) Embolism B. Cerebral hemorrhage (hemorrhagic stroke): hemorrhagic syndromes o
Less common cause : 15 % of cases
o Etiology: 1) Intra-cerebral hemorrhage 2) Subarachnoid hemorrhage(SAH) 3) Subdural or extra-dural hemorrhage C. Hemorrhagic infarction:
o Infarction on top of hemorrhage as in SAH with cerebral vasospasm o Hemorrhage on top of infarction as in ischemic stroke with anticoagulant therapy
43
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Transient Ischemic Attacks(TIAs)= Mini stroke
❖ Definition :
o Temporary neurologic deficit ofsudden onset & short duration of cerebral ischemia without cerebral infarction due to disturbance in carotid or vertebral arteries.
❖ Duration & subtypes : ❖ Type 1. Transient Ischemic Attacks(TIAs) 2. Reversible Ischemic Neurologic Deficit(RIND) 3. Prolonged Reversible Ischemic Neurological Deficit(PRIND)
❖ Duration 0
❖ Outcome
Few minutes to maximum 24 hours
0 Complete
0 >24 hours to < 3 days 0 >24 hours to < 7 days
recovery
❖ Pathophysiology :
❖ TIAs are characterized by a temporary reduction or cessation of cerebral blood flow in a specific neurovascular distribution as a result of partial or total occlusion typically, due to: A. Stenosis of a small penetrating vessel.
External -....^11
B. Acute thromboembolic event.
fm 'H
carotid
artery
V
K1 ■
Etiology:
II
■ ""W "
■
■
■ carotid
■
artery
J
1
1. Cerebral microemboli from :
o o 2. 3.
Ulcerated atherosclerotic plaque in aortic arch, carotid & vertebrobasilar. Mural thrombi in a diseased heart e.g. atrial fibrillation Vasculitis e.g. PAN & SLE Hyperviscosity e.g. polycythemia
I* f
❖ Risk factors: I.
1. 2. 3. 4.
Emboli
Non modifiable:
Age > 45 years old Sex: male > female (4:1) Positive family history Personality: Type A
II.
Modifiable:
A. High risk:
1. Heart diseases e.g.: o Atrialfibrillation o Valvular heart disease e.g. rheumatic mitral valve disease o Acute myocardial infarction ± left ventricular mural thrombus
2. 3. 4. 5.
Hypertension Hyperglycemia(DM) Hyperlipidemia Cigarette smoking
180
B. Low risk:
1. 2. 3. A: 5. o o
Obesity,]saturated fat in diet Physical inactivity Psychological Stress, Heavy alcohol intake Hypercoagulable state (thrombophilia): Hyperuricemia, Homocystinemia Polycythemia 44
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Ulcer
Clinical picture :
A. Symptoms according to site (see later): o Carotid insufficiency : carotid TIAs
o Vertebrobasiiar insufficiency: Vertebrobasiiar TIAs B. Signs:
o In acute attack: there is a focal neurologic deficit o In between attack: patient is free. C. Examination for arterial tree:
1. Palpation: o Decrease common carotid artery pulsation in neck o Decrease internal carotid artery pulsation in tonsillar fossa 2. Auscultation:
o Bruit over common carotid artery or external carotid artery. Prognosis :
o TIAs is warning sign to develop ischemic stroke o 1/3 of cases with TIAs are MORE LIABLE to have permanent brain damage if attack last longer time
Risk of developing ischemic stroke is classified according to ABCD^ score: 1. Age > 60 years : 1 point 2. BP > 140/90: 1 point 3. Clinical picture: o Unilateral weakness : 2 point o Speech disturbance without weakness: 1 point 4. Duration of the attack:
o 10-59 minute : 1 point o >60 minute : 2 point 5. Diabetes mellitus : 1 point
Interpretation : Score / risk ratio: 1-3 : low o 4-5: moderate o > 6 : high Differential diagnosis:
1. 2. o o
Stroke (ischemic or hemorrhagic) From other causes of vertigo e.g.: Multiple sclerosis Migraine with aura
o
Meniere's disease
if
/
o Cervical spondylosis 3. From other causes ofsyncope e.g. e.g. Hypoglycemia ,orthostatic Hypotension & arryhtmias 4. Convulsions 5. Cancer or mass lesion
Investigations: as ischemic stroke. ❖ Treatment:
1- Medical:
80 A- Treatment of risk factors: 140
1. HTN with antihypertensive drugs: target blood pressure detached thrombus —> paradoxical embolism through ASD, VSD or foramen ovale
Detached b Odd clot
C. Rare sources:
o
Fat emboli : bone fracture
o Air emboli: pneumothorax o Parasitic emboli: Hydatid or malaria o Malignant cell emboli
11.
Hemorrhagic stroke:
A. Incidence: the less common cause: 15% of cases
B. Pathogenesis: abrupt arterial rupture leads to : 1. Accumulation of blood within the brain parenchyma
2. Increase in local tissue pressure followed by abrupt onset of shearing forces & physical destruction. 3. The mass effect of the hematoma induces:
o Neuronal & glial cell death due to inflammation & apoptosis o
Breakdown of blood brain barrier
Vasogenic edema Epldural hemorrhage
Subarachnoid
Types of intracranial hemorrhage:
P
hemorrhage
Subdural
Intracerebral
hemorrhage
hemorrhage
A. Intra-cerehral hemorrhage:
o o o B. C. D.
Bleeding in the brain substance and my leak into the ventricles, It is fatal as blood may compress vital centers in brain stem The commonest artery causing intra cerebral hemorrhage:lenticulo-striate branch ofmiddle cerebral artery Subarachnoid hemorrhage: bleeding into the subarachnoid space Subdural hematoma : bleeding between the dura mater and the arachnoid mater Epidural (extradural) hematoma : bleeding between the dura mater and the skull Etiology of intracranial hemorrhage: Aneutystr
1. Non-traumatic(or spontaneous) hemorrhage: A. Rupture intracranial aneurysm & AV malformation (angioma) o The commonest cause of subarachnoid hemorrhage
malformation
B. Hemorrhage: 1. Hemorrhage in brain tumor
2. Hemorrhagic blood diseases e.g. Hemophilia & purpura 3. Cerebral amyloid angiopathy
Beta-Amyloid
4. OVERDOSE OF ANTICOAGULANTS
C. Hypertension: o The commonest cause of intra-cerehral hemorrhage
Marevarf Warfarin
II.
Traumatic hemorrhage :
The commonest cause of subdural hematoma & subarachnoid hemorrhage
48
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Types: I ,I
II
90%) Mild hyperventilation (target PCO2:30-35 mmHg) Avoid Cough by antitussive & avoid Constipation by laxatives
5.
Drugs:
o o
UOal
m MANNITOL I.V.
A. Diuretics :
a) Mannitol 20 % or Hypertonic Saline 3 % IV (osmotic diuretics) wsmb) Furosemide (Lasix) after mannitol infusion. c) Acetazolamide(Carbonic anhydrase inhibitor) B. Others: Dexmedetomidine, Magnesium, Lidocaine & Aminophylline . 6. Electrolytes: correct electrolytes especially sodium after mannitol intake. Norm ovolemia 7. Epilepsy prophylaxis: anticonvulsants for seizures : Normoglycemia V^ORMA/ Normothermia Phenytoin 15 mg/kg then 5 mg/kg/day o 8. Fluids, glucose, temperature: Maintain normovolemia, normoglycemia, normothermia o Avoid hyper or hypo —> both are injurious (mild hypothermia may be indicated only in resistant refractory(ICT) o Avoid hypotonic fluids e.g. glucose containing solutions. o 9. Intervention: 1. 2. 3.
Drainage of CSF via lumbar puncture Decompressive craniectomy with dural expansion if refractory to medical treatment. External ventricular drainage if there is obstructive hydrocephalus & Evacuation of hematoma if present 50
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
3- Specific treatment for ischemic stroke:
1. Limitation of infarction size :
A. Medical revascularization by fibrinolytic (Thrombolytic) therapy
WN0M2S689
Thrombus
SSrtn''*'
ase'rt.pA
d^aradollon produoU
u, WIU)
1. 2. 3.
Agents:IV Alteplase : IV recombinant tissue plasminogen activator(rt-PA) Best time: during first 3 to 4.5 hours after the onset of symptoms Dose: 0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% of dose given as bolus over 1 minute.
4. Contraindications :
I.
Absolute contraindications:
11.
a. Clinically
0
b. Past history
o History of ischemic stroke or head trauma within 3 month ago. o History of intracranial/spinal surgery within 3 month ago o History of intracranial hemorrhage, aneurysm or AV
Onset > 4.5 hours
fistula.
Relative contraindications
o Rapidly improving symptoms suggestive of TlAs o Recent lumbar puncture within 1 week
o Recent surgery within 2 weeks o Recent GIT malignancy or bleeding within 3 weeks
o History of oral anticoagulants or heparin intake in past 48 hours c. Present
history
o BP > 185 /110, resistant to IV drugs
o Glucose < 50 or > 400 mg/dl
o Platelets < 100,000 / mm3,INR >1.7, aPTT >40 s, or PT
o
Seizure at onset of stroke
>15 s
o Subarachnoid hemorrhage Or Intracranial hemorrhage on CT
B. Mechanical revascularization (thrombectomy)= endovascular therapy(EVT):
o Mechanical clot disruption is an alternative for patients in whom fibrinolysis is ineffective or contraindicated. o Methods e.g. Penumbra System, Stent-retriever system, Merci Retriever, 2. Blood pressure control: 1. N.B.:
o Cerebral Perfusion Pressure(CPP)= Mean Arterial Pressure(MAP)- Intracranial Pressure(ICP) o Thus t MAP ^ t CPP while t ICP ->iCPP —> Because ischemic strokes can be associated with increase in ICP so permissive moderate hypertension (fMAP)is considered an adaptive response to maintain cerebral perfusion pressure(CPP)to the brain & so aggressive treatment of hypertension may reduce perfusion to penumbra & worsening cerebral ischemia. 2. N.B.:
o If hypertension associated with target-organ damage e.g. aortic dissection, it's managed according to the protocol mentioned in hypertensive emergency in cardiology book. o Vasopressor drugs can be used if the blood pressure is very low e.g. cardiogenic shock (myocardial infraction) to improve cerebral blood flow.
51
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
A- During the acute phase of ischemic stroke: from the onset to 72 hours: B. Hypertension control in rt-PA candidates:
A. Hypertension control in non-rt-PA candidates : 220
1) BP < —mmHg:
1. BP < — mmHg without target-organ damage:
'
0 Blood pressure should be monitored without treatment. 220
110
^
o Blood pressure should be monitored without treatment.
2. BP > —mmHg:
2) BP
0
0 Before IV thrombolysis BP should be less than —
120
mmHg:
®
Gradual reduction of 10- ISVo in the BP over 24 hours.
185
mmHg.(J, risk of ICH; hemorrhagic transformation) o During & after IV thrombolysis: gradual reduction of 15 - 25 % in the BP over 24 hours
IV Drugs used for 2: 3. Nicardipine 4. Na Nitroprusside
1. Labetalol: the initial drug of'ehoice 2. Cievidipine A. Initial dose
0 0.5 pg/kg/min o 1-2 mg/h rV 0 5 mg/h lY 10-20 mg IV over 1-2 min B. Titrate the dose every 10 minutes to maximum dose: o 10 pg/kg/min o 21 mg/h o 15 mg/h o 300 mg o
B- After the acute phase of ischemic stroke: after 72 hours
o BP may decrease spontaneously during the acute phase ofisehemic stroke(|sympathetie hyperactivity), however for neurological stable patients who remain hypertensive (>140/90 mmHg)> 3 days after an acute ischemic stroke, initiation of antihypertensive should be considered. 3. Antiplatelet: BAyaii
A. Aim : as TIAs
B. Indications : as TIAs
C. Timing: o
In non-rt-PA candidates within 24-48 hours of ischemic stroke onset
o In rt-PA candidates: after 24 hours from administration of alteplase D. Drugs : as TIAs but: o Aspirin: initial dose 325 mg/day then 75mg/day for life
Marevani
E. Duration : as TIAs
Warfarin Sodium I mg
4. Anticoagulant:
100 tablets
A. Aim: as TIAs B. Indications : as TIAs
C. Timing: delayed according to the size of infraction : 1. Size of ischemie stroke:
A. MUd
B. Moderate
C. Massive
2. Started ... days after ischemic stroke onset
0
o
0
3
6
12
♦t* N.B.: exclusion ofICH; hemorrhagic transformation by CT or MRI is important before using anticoagulant. D. Drugs :as TIAs E.
Duration : as TIA 5.
Treatment of the cause:
A. Cerebral thrombosis (thrombotic stroke): o Control for risk factors of cerebral atherosclerosis e.g. DM B. Cerebral embolism (emboiic stroke):
o Treatment of souree of emboli e.g. MS with AF
V N.B.: Neuroprotective Agents e.g. Magnesium infusion ; o Not recommended as they show no efficacy in improving outcomes after ischemic stroke.
52
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4- Specific treatment for hemorrhagic stroke e.g. intra-cerebral hemorrhage: 1. Blood pressure control: 1. SBP 220 mmHg:
V
o Aggressive BP reduction with continuous intravenous infusion and frequent BP monitoring . PLASMINOGEN
2. Anti-flhrinolytic:
Tranexamic acid
o E.g. tranexamic acid & epsilon aminocaproic acid o Aim : prevention of clot lysis —* I re-bleeding
PLASMIN ASH
1
o Risk : f cerebral ischemia FIBRIN
X
FIBRIN DEGRADATION PRODUCTS
3. Surgery: o Surgical evacuation of hematoma o
Intra-ventricular evacuation show no benefits
❖ Treatment of the cause e.g. warfarin toxicity (overdose): A. Stop oral anticoagulant for : o 2-4 days for prophylactic indications e.g. prevention of DVT o 2-4 weeks for therapeutic indications e.g. AF
B. 1. 2. 3.
N.B,: consider left atrial appendage occlusion ifthere is contraindicationfor anticoagulant. Reversal of anticoagulation hy : h Vitamin K 10 mg IV infusion Fresh frozen plasma Prothrombin complex concentrate
4. Recombinant factor Vila
C. Correction of thromhocytopenia hy platelet transfusion
53
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Lacunar infarction (lacunar stroke)
Deflnition & incidence:
o Small(0.5 - 1.5 cm)infarction due to occlusion of single deep small penetrating arterioles that arise from larger blood vessels that provide blood to the brain's deep structures, o Incidence: the most common type of ischemic stroke(25 % of all ischemic strokes) ❖ Etiology & risk factors: ❖ Etiology: 1. Micro-atheroma : the most common mechanism of arterial stenosis or occlusion. 2. Micro-embolism :
o
Non cardiac embolism from carotid atheroma
o
Cardiac embolism from atrial fibrillation
3. Lipohyalinosis : segmental vessel wall thickening in sustained hypertension ♦I*
Risk factors:
1. Age: old age 2. BP: chronic uncontrolled hypertension 3. Cigarette smoking 4.
DM
❖ Clinical picture: five classical lacunar syndromes:
I. Pure motor stroke
o
❖ The classic syndromes 3. Dysarthria/ciumsy 2. Ataxic hemiparesis: o
The second most
4. Pure
hand:
frequent
The most common
5. Mixed
sensory
sensorimotor
stroke
stroke:
type: 33-50% ❖ Anatomical location of the infraction: o
Posterior limb of
o
Posterior limb of the
capsule or basilar
internal capsule. basilar part of pons,
part of pons
and corona radiate.
the internal
o The pons
o
The
o
Thalamus and
adjacent posterior
thalamus
internal
capsule ❖ The main presenting symptom:
1. 2. o o o
Hemiparesis ± may be present: Dysarthria Dysphagia Transient sensory symptoms
o
Combination of
o
0 Dysarthria with
o
Paresthesia
o
Combined
or hemi-
hemiparesis
symptoms:
hypoesthesi
with hemi-
Hemiparesis (more In LL) with ipsilateral
a
hypoesthesia
cerebellar and motor
UL clumsiness
hemiataxia
*i* Differential diagnosis from cortical infarctions and intracranial hemorrhages: o True cortical signs (aphasia, visuospatial neglect, gaze deviation, and visual field defects) are always absent in lacunar strokes
❖ Investigation:
o CT scan show small punched out hypodense areas at site of lacunae ❖ Treatment:
1. IV recombinant tissue plasminogen activator during first 4.5 hours of stroke onset without contraindications 2. AntiplateletS (aspirin) within 48 hours (N.B. Anticoagulants (heparin and warfarin) show no benefit over aspirin with regards to five year survival)
3. Control of risk factor e.g. HTN 54
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cerebral venous sinus thrombosis Definition;
o
Formation of a blood clot in the dural venous sinuses (which drain deoxygenated blood from the brain back to the heart); most common transverse sinus ,superior sagittal sinus(SSS)& cavernous sinus. Superior saeHtai
❖ Etiology:
liaui
Inferior sagittal
1. Idiopathic
Superior pelrusal
sinus
©
2. Cerebral:
Cascrnous sinus
o
Trauma
o o 3. o 4.
Infection (meningitis, sinusitis) Surgical intervention Hypercoagulable states (thrombophilia) e.g. Antiphospholipid syndrome & sickle cell disease Drugs e.g. Oral contraceptives ,corticosteroids
Straight sinus ■ Transverse sinuS'
.Sigmoiil sinus Internal.lugular
❖ Pathogenesis :
inferior petrosal sinus
vein
o Thrombosis of dural venous sinuses
venous infarction —> cerebral edema —>• petechial hemorrhages
❖ Clinical picture: A. Symptoms of t ICT :
o Persistent headache (thunderclap headache), Blurring of vision (Papilledema)& Projectile vomiting. o N.B.: Feverfollowing headache by days in case ofinfection B. Symptoms of cranial nerve affection especially: o 2(visual defect), 3 (diplopia), 7(facial weakness)& 8(Tirmitus & deafness). C. Symptoms of cerebral affection : o Focal neurological deficits(END)if venous infraction occurs e.g. Hemiparesis o Confusion, Convulsions, Coma
Investigations: I.
Laboratory:
1. CBC
2. APTT,PT&INR.
3. D-Dimer level: positive D dimer level support the diagnosis but negative values doesn't exclude the diagnosis. 4. Hypercoagulability : protein C, protein S , antithrombin III 5. Risk factors: blood glucose, lipid profile, uric acid & homocysteine level.
n.
Imaging:
1. Non contrast CT & MRI: o o
For the cause e.g. sinusitis For the complication e.g. infarction or hemorrhage
2. Contrast CT:
Cord sign (thrombosed cortical vein) Dense triangle sign (fresh coagulated blood in the SSS) Empty delta sign (nonenhanced thrombus in SSS surrounded by enhanced collateral) o 3. CT venography & MR venography (the gold standard). o
o
Treatment: Anticoaguiation
o Parental anticoagulant(heparin) during the acute stage then oral anticoagulant for several months until MRI or MRV shows sinus patency. 55
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cavernous Sinus Thrombosis
❖ Introduction : anatomy of cavernous sinus: o Cavities located at base of the skull on either side of sella turcica which encloses cavernous portion of internal
carotid artery, 3'''',4*^ ,6* cranial nerves en route to apex of orbit and ophthalmic and maxillary branch of
trigeminal nerve.
Internal carotid artery I Cmrmaus stnus Oadomotar nen* TroeUear nerve
Definition of cavernous sinus thrombosis:
o
OpkOuimic nerve
Formation of a blood clot in the cavemous sinus
Abdureni nerve
❖ Etiology as cerebral venous sinus thrombosis plus:
Maxillary nerve
❖ Extension of bacterial or fungal infections from dangerous area e.g.
o Orbital, nasal, sphenoid & ethmoid sinuses, dental, pharynx or tonsils o Organisms : Staphylococcus aureus (common), streptococcus, pneumococcal & anaerobes Periorbttiiffdeiiui
Clinical picture: A. B. I.
1.
Symptoms of flCT & cerebral affection as cerebral venous sinus thrombosis Symptoms of cranial nerve affection: OCULAR manifestations;
Proptosis, Periorbital edema & ecchymosis
2.
Lateral gaze Palsy(6* ON)
3.
Ptosis, ophthalmoplegia, J, visual acuity up to Blindness Start unilateral then spreads to other eye by intercavemous sinuses
4. II.
Oiemosis
TRIGEMINAL nerve affection :
Localized headache to the regions innervated by ophthalmic and maxillary branches Localized sensory loss to the regions innervated by the ophthalmic and maxillary branches Loss of corneal reflex
❖ Investigation: A. Eundus examination : papilledema B. CSF: abnormal profile resembling purulent meningitis C. Imaging: 1. Non contrast CT & MRI :
o For the cause e.g. sinusitis o For the complication e.g. infarction or hemorrhage o For the diagnosis : increased density in thrombosed cavemous sinus 2. Contrast CT & MRI:
o Filling defects in thrombosed cavemous sinus o Dilated superior ophthalmic vein 3. CT venography & MR venography (the gold standard): o
It will show the absence of venous flow in the affected cavemous sinus
Treatment:
1. Treat of the cause e.g. infection by : A. Antimicrobial therapy : antistaphylococcal IV antibiotics for at least 3 weeks
o Nafcillin or oxacillin plus a third- or fourth-generation cephalosporin ± metronidazole for anaerobes B. Surgical drainage of infected paranasal sinuses 2. Anticoagulant: to reduce morality from brain ischemia
3. Corticosteroids: to reduce inflammation and edema but after antibiotic coverage 56
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Subarachnoid hemorrhage(SAH)
❖ Deflnition: bleeding in subarachnoid space between arachnoid membrane and the pia mater. Etiology: Bkiod vessel
1.
Non-traumatic(or spontaneous)subarachnoid hemorrhage:
A. Rupture : 1. Intracranial aneurysm :
a. b. o o o
Congenital aneurysm Acquired aneurysm: Atherosclerotic aneurysm Mycotic aneurysm e.g. subacute baeterial endocarditis Syphilitic aneurysm, Polyarteritis nodosa Arteriovenous
.
malformation
The saccular(berry) aneurysm is the most common shape of intracranial aneurysm| 2. AV malformation B.
Hemorrhage (with extension ofblood to the subarachnoid space):
1.
Hemorrhage in brain tumor
2.
Hemorrhagic blood diseases e.g. Hemophilia & purpura
3. 4.
Cerebral amyloid angiopathy overdose of anticoagulants
C.
Hypertension
The most common(80% of cases) etiology of nontraumatic SAH from ruptured intracranial aneurysm.
H.
i
Traumatic subarachnoid hemorrhage
❖ The commonest causes ofSAH are head trauma & rupture ofintracranial aneurysm. Clinical picture: Type of patient: age: o 10-20 years old in AV malformation o 40-60 years old in intracranial aneurysm
Clinical picture of intracranial aneurysm before rupture: 1. Asymptomatic : may remain silent 2. Compression (space occupying lesi A. Anterior
0
communicating
artery aneurysm
artery aneurysm
Cranial nerve 2 or
0 CN 3 before entering
optic chiasma o
C. Internal carotid artery aneurysm in cavernous
B. Posterior
communicating
Visual field defect
aneurysm
sinus
❖ Compress o Cranial nerve 3,4, 6,
ophthalmic branch of CN 5
cavernous sinus
o CN 3 palsy
D. Basilar artery
❖ Clinical picture: 0 Ophthalmoplegia o Facial pain 0 ± Exophthalmos.
0 Compression of midbrain or pons
o CN palsies & o Long tract manifestation e.g., Hemiparesis
RUPTURE: 90 % of cases the first presentation when they rupture giving clinical picture ofSAH o Precipitating factor for rupture: Strain, Stress, Severe cough or Sexual intercourse.
57
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
II.
Clinical picture of subarachnoid hemorrhage:after rupture of iutracrauial aueurysm:
1- Symptoms & signs of increased ICT: Persistent headache; thunderclap headache : Onset: Sudden
Character: Severe explosive headache (the worst headache everfelt) Increased hy flexion of the neck Site: Starts at the back of the head & upper neck, later on become generalized Radiation : due to irritation of spinal sensory roots by bloody CSF o Shoulder & upper limbs o
Lower back & lower limbs
B. Blurring of vision (Papilledema) C. Projectile vomiting
2- Symptoms & signs of meningeal irritation : Meningismus ❖ Symptoms: 1. Pain:
o Back ofthe head & upper neck o Shoulder & upper limbs o
Lower back & lower limbs
2. Neck STIFFNESS
3. Body: opisthotonos (high arched hack) 4. Fever : pyrogenic reaction due to absorption of blood Signs:
D1
Q
D2
. it
'--.rr
1
A. Neck rigidity with painful neck flexion B. Positive Lasegue's sign:
o While the patient is lying in the supine position, with his hip & knee joints fully extended o Raising the leg by flexing the hip is limited & painful. C. Positive Kernig's sign: While the patient is lying in the supine position, with his hip & knee joints flexed at 90° Extension of the knee is limited & painful. Positive Brudzinski's sign: Neck sign : passive flexion of neck leads to flexion of both hips & knees. Leg sign ; passive flexion of one hip leads to flexion of the other hip and knee 3- Symptoms & signs of cranial nerve affection & ocular manifestations: b
-
tt
.
-
-
1. Cranial nerve signs due to pressure by blood: o The most commonly affected nerves are : Optic nerve(CN2^ blindness)& Ocular cranial nerves (3,4,6)
2. Ocular(eye)symptoms & signs ;
\' ^
o Photophobia o Papilledema due to f ICT
o Flame like retinal hemorrhage due to blood in the subarachnoid sheath of optic nerve
^
4- Symptoms & signs of cerebral affection due to pressure by blood or CEREBRAL VASOSPASM: o Disturbed conscious level(DCL): Confusion, Convulsions & Coma o Focal neurological Deficits(motor or sensory) e.g. hemiplegia ❖ N.B.: clinical picture depends on vascular origin ofaneurysm —> middle cerebral artery, anterior cerebral artery vertebrobasilar, posterior cerebral artery aneurysm —>■ either main artery or branch occlusion (see later in vascular occlusive syndromes) 58
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Complications Arteryspatm
•V 1. o o
2.
3. 4. 5.
Re-bleeding:
Incidence : within the first 3 days after SAH (bad prognosis) Presents with early neurological deficits with deteriorating conscious level Vasospasm with delayed cerebral ischemia/infarction (ischemic stroke): Incidence : 4-14 days after SAH (reactive vascular narrowing due to irritative effect of blood on vascular smooth muscle) Presents with delayed neurological deficits with deteriorating conscious level Intracranial Hypertension (tICT)-> cerebral edema Hydrocephalus : due to obstruction of CSF flow by blood Hyponatremia due to SIADH or cerebral salt wasting syndrome
1)
6. Convulsions : due to cortical irritation by blood & damage 7. Neurogenic & cardiogenic pulmonary edema 8. Neurogenic myocardial ischemia/infarction :
o SAH —> injury of posterior hypothalamus —> f catecholamine release from adrenal medulla —>• hyperdynamic circulation —>■!" myocardial oxygen demand myocardial ischemia and failure with transient ECG changes and elevated troponin I & CK-MB Differential diagnosis: 1. 2. 3. o
From other causes of thunderclap headache e.g. cavernous sinus thrombosis From other causes of intracranial hemorrhage From other causes of coma with meningeal irritation signs e.g.: Meningitis & Encephalitis Investigations :
I. For diagnosis of SAH: A. CT scan : the first investigation to be done o If blood is detected in subarachnoid space, the diagnosis is settled and lumbar puncture is not needed. B. o
1. o
o o
Lumbar puncture for CSF examination :
It is indicated if CT is normal with clinical suspicious of SAH Aspect:
Blood stained which is constant in all sampling tubes Xanthochromia in supernatant fluid (Hb degeneration) N.B.: sampling in post-traumatic lumbar puncture, blood diminishes in successive sampling tubes with clear supernatantfluid
4.
Pressure: High Proteins: Markedly increased WBCs: Normal or slightly increased
5.
RBCs: increased
6.
Chloride: Normal
7.
Glucose: Normal
2. 3.
|— vortobra spinal cord Corwrospinai
Microbiology: Sterile II. For detection of the cause e.g. to diagnose & detect the site of intracranial aneurysm: 1. Digital subtraction angiography the gold standard 2. CT angiography & MR angiography HI. For detection of the complication e.g. Transcranial Doppler ultrasonography for cerebral vasospasm
8.
❖ Treatment:
1- General: care of comatose (see before)
2- Treatment for intracranial hypertension by cerebral dehydrating measure (see before) o Don't forget seizure prophylaxis 59
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
3- Specific treatment for SAH: reduad
bhodfhw
1- Blood pressure control:
permon
hypertatshB . mcnosed
biAiaton
perfushn
A. Untreated aneurvsms :
B. Treated aneurysms (coiled or clipped):
o Systolic blood pressure < 160 mmHg i.e. 120- ' 1 SOmmHg
0 Systolic blood pressure > 160 mmHg i.e. 160-200mmHg until resolution of the neurological deficit or occurrence
o Aim : to prevent re-bleeding
0 Aim : to prevent vasospasm with delayed cerebral
of complication infarction
Drugs used : labetalol and nicardipine Avoid: nitroglycerin and nitroprusside • • cerebral vasodilation —>1ICT
Tranexamic acid
2- Anti-fibrinoiytic: X
FIBRM DEGRADATION PRODUCTS
o E.g. tranexamic acid & epsilon aminocaproic acid o Aim : prevention of clot lysis —> J, re-bleeding o Risk : f cerebral ischemia 3- Treatment of aneurysm: I
Anemysm
Occlusion therapy: 1 Minimally invasive procedure: endovascular Coiling: A. Technique:
coiled
o Tiny platinum coils are threaded via catheter in aneurysm blocking blood flow into aneurysm B. Indications :
o Prophylactic to prevent rupture or Therapeutic to reduce bleeding Surgical procedure: direct Clipping of its neck at craniotomy II.
Adjuvant therapy :
A. Indications:
1. Non-surgical cases e.g. hemorrhagic blood disease 2. Difficult surgical cases e.g. Multiple aneurysms, Huge or Inaccessible aneurysm B. Steps:
Aneurysm clipped
1. Avoid precipitating factors for rupture 2. Analgesics for headache 3- Treatment of complications:
Nimotop
A. Vasospasm protection:
30 mg 1. Nimodipine(CCB): a. Onset & offset: should be started when a diagnosis of SAH is made and continued for 3 weeks h. Dose : as Ions as blood pressure can be maintained:
o 60mg/4 hours if no hypotension occurs o 30 mg / 2 hours if hypotension occurs Route: orally or by nasogastric tube. Cerebral angioplasty & intra-arterial vasodilator. Triple H therapy : Permissive Hypertension:
Stop any antihypertensive medications to prevent hypotension. Use vasopressors to achieve BP target as discussed before. Hydration: maintain normal volume status and avoid hypovolemia Hemoglobin : avoid anemia, hemoglobin target > lOgm/dl N.B. current recommendation is against hypervolaemia
haemodilution
B. Hydrocephalus: External ventricular drainage (Ventriculostomy) or shunting.
60
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
■
Neurogenic bladder
4- Removal of
Corticospinal tract: o
pyramidal inhibition
Bilateral control
p
Lies most medial in the sninal cord
o
Pontine micturition center
on micturition
3- Sensory pathway o Pyramidal inhibition on micturition iilii-r i
Bcilcx of micturi
""
1
6
Wi
5- Efferent: S2,3,4
2- Afferent: S2,3,4 sensory parasympathetic fibers
motor
parasympathetic fibers
J 1- Stimulus: sense of fullness —►
6- Contraction of biadder wai!& relaxation
stimulate stretch & chemical receptors
of its sphincter and it's evacuation
❖ Physiological introduction
Urinary bladder control & innervation :
Hypogastric nerve
^ Pelvic splanchnic nerve[ 1. Cortical micturition center:
o Paracentral lobule of frontal lobe; conscious control (inhibition) of micturition 2. Pontine micturition center
3. A. o B.
The autonomic nerve supply of the bladder smooth muscle: Sympathetic supply: Til,12 «& LI,2 segments via hypogastric plexuses and nerves: Stimulation of sympathetic causes relaxation of the detrusor muscle and contraction ofthe neck Parasympathetic supply: S2,3,4 segments via pelvic nerves: o Stimulation of parasympathetic causes contraction of the detrusor muscle and relaxation ofthe neck o N.B.: somatic supply to external voluntary sphincter from S2,3,4 segments via pudendal nerves ❖ Act of micturition
Fullness of bladder by acidic urine stimulate stretch & chemical receptors in the wall of urinary bladder Afferent impulses are carried by S2, 3,4 sensory parasympathetic fibers to sacral part of spinal cord, then ascend in posterior column to cortical center where the sensation of fullness of bladder received (N.B. cortical center developed with myelination of A tracts after the age of 1 year). Efferent impulses descend from the cortical center through pyramidal tract bilaterally to sacral part of spinal cord bilaterally, then through S2, 3,4 motor parasympathetic fibers, leading to contraction of bladder wall & relaxation of its sphincter and it's evacuation (because of pyramidal tract inhibition on micturition is released). ❖ N.B.:
o Unilateral lesion would not produce bladder disturbance since bladder is bilaterally supplied by A tract, o So for any disturbance in urinary bladder function, the lesion should be BILATERAL.
61
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Etiology of neurogenic bladder
UMNL
Autonomic bladder
Sensory atonic bladder
Motor atonic bladder
A. UMNL: pyramidal tract lesion above the level of the reflex arc:
1. Acute spinal cord lesion : retention of urine with overflow 2. Gradual spinal cord lesion: A. Partial lesion: B. Complete lesion: o Pathogenesls 0 Uninhibited bladder due to uncontrolled over o Destruction of descending fibers in the spinal activity of Parasympathetlc supply cord leading to loss of voluntary control 0 Precipitancy of micturition: frequency, o Clinically: 0 Automatic bladder: complete regular urgency, urge incontinence evacuation of bladder by spinal reflex arc
LMNL:lesion at the level of the reflex arc (pelvic & pudendal nerves) I.e. disease of the conus medullarls or sacral nerve root.
A. Lesion In the afferent fibers :
B. Lesion In the efferent
C. Lesion In both afferent & efferent fibers
sensory atonic bladder:
fibers : motor atonic
or sacral(S2, 3,4) segments spinal cord:
retention of urine with
bladder
autonomic or autonomous bladder
overflow
0
Absent sense of fullness
0
0 Retention of urine + huge size of bladder
Preserved sense of
o Loss of both reflex or voluntary control of
fullness (painful) 0
o Dribbling of urine (over flow)
o
moderate size of bladder
o Incomplete, Irregular, Involuntary bladder evacuation as it depends on myogenic
o Inability to evacuate the
bladder voluntary 0
micturition
Retention of urine +
Absent sense of fullness
contraction of bladder
Catheterlzatlon is needed
62
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Hemiplegia
Deflnition:
o Paralysis of one side of body due to UNILATERAL pyramidal(A)tract lesion (unilateral UMNL)ABOVE the
level of 5"' cervical segment ofthe spinal cord, that may occur at any point from the contralateral cerebral cortex (motor area) to ipsilateral 5th cervical segment ofthe spinal cord.
❖ N.B.: the beginning of origin of brachial plexus starts at C5 which supply the muscles ofthe upper limbs, so lesion below the 5"" cervical segment may spare upper limb & affects lower limb only.
Etiology: 1.
Vascular causes; stroke :THE MOST COMMON CAUSE
o 2. 3. 4.
Ischemic (thrombosis or embolism) & hemorrhagic Inflammatory/infective: meningitis, encephalitis, brain abscess Neoplastic: meningioma, glioma Demyelinating: multiple sclerosis(MS), disseminated encephalomyelitis(DEM)
5. Traumatic: cerebral laceration, subdural hematoma
6. Congenital: cerebral palsy 7. Hysterical: no organic lesion ❖ Onset & course: VbiWwai m.i III I I
i—iwn II ■ »I ii»«iiiiimi
o Acute onset & regressive course: vascular, inflammatory, traumatic lesions o Gradual onset & progressive course: neoplastic lesions o Remittent & relapsed course : DS & TlAs
❖ Clinical picture: 1. According to the onset: 1. Acute lesions e.g. vascular lesions:
❖ The clinical picture passes through two stages: 1. Stage of flaccidity (shock stage): due to neuronal shock 2. Stage of spasticity (stage of established hemiplegia): due to recovery from neuronal shock 2. Chronic (gradual) lesions e.g. neoplastic lesions: o The hemiplegia passes direetly to the stage of spasticity 2. According to the site of the lesion (level): cerebral, brainstem or spinal cord 3. According to the etiology e.g. Ischemic(thrombosis /embolism) or hemorrhagic stroke. A. Stage of flaccid paralysis(shock stage): 1.
On the paralyzed side there is A. Early: due to neuronal shock 0
Duration : 2-6 weeks
B. Later: Recovery stage: 0 after recovery from the shock stage, stage of spasticity starts
1. Muscle tone
2. Deep reflexes
0 Complete lost(flaccid paralysis) o
Absent
0 Babinski sign
3. Plantar reflex
II.
0 Reappearance then gradual increase
If the onset of flaccid paralysis associated with coma e.g. hemorrhage, diagnosis of paralyzed side determined by signs of lateralization.
63
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B. Stage of spastic paralysis (stage of established hemiplegia): 1. Paralysis: 1. Paralysis of one side of body :
o Damage above the pyramidal tract decussation (i.e. above the crossover corticospinal tract in the lower medulla) leading to contralateral (opposite side) paralysis,
o Damage below the pyramidal tract decussation (i.e. below the crossover corticospinal tract in the lower medulla) leading to ipsilateral(same side) paralysis. 2. Paralysis of pyramidal distribution:
o It affects progravity (weak muscles) more than antigravity(strong muscles) ❖ Thus :
o Upper limbs: extensors (progravity) are weaker then flexors o Lower limbs: flexors (progravity) are weaker than extensors o It affects distal more than proximal muscles ❖ Thus : o
The hands is weaker than shoulder
o The foot is weaker than hip o Skilled movement of fingers & toes are mostly affected
2. Disturbance of muscle tone :
❖ Hypertonia (spastlcity) of clasp knife type: o It affects antigravity (stronger muscle tone) more than progravity(weaker muscle tone) ❖ Thus :
o Upper limbs: flexors (antigravity) are more spastic than extensors o Lower limbs : extensors (antigravity) are more spastic than flexors o In both upper limbs & lower limbs adductors are more spastic than abductors 3. Disturbance of deep reflexes: 1. Hyperreflexia: exaggerated deep reflexes in both upper & lower limbs on the paralyzed side 2. Pathological deep reflexes appear (normally inhibited by pyramidal) e.g. Adductor & Patellar reflexes 3. Clonus may be present e.g. in ankle, patella & wrist. 4. Superficial reflexes: o Planter reflex : extensor response (Babinski sign) on the paralyzed side; dorsiflexion of big toe ± fanning of other toes
o Loss of superficial reflexes as abdominal & cremasteric reflexes on the paralyzed side 5. Gait:
o If the patient can walk, his gait is circumduction due to spasticity of extensors & adductors oflower limbs. ❖ N.B.:
o o 1. 2. 3.
Sphincters usually are intact in hemiplegia as it's unilateral pyramidal tract lesions If you get bladder disturbance in hemiplegia, think ofthe following possibilities : Mild pyramidal affection of other side as well (in cerebral atherosclerosis) Double stroke (recent attack & old stroke of the other side) Affection of bladder center(ACA lesion, supplying paracentral lobule of frontal lobe)
64
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
♦♦♦ Clinical picture of hemiplegia may vary according to : A. Site of the lesion (level) B. Cause of the lesion
Cortical Subcortical
Internal capsule
Motor
Capsular
Brainstem: crossed hemiplegia
Contralateral
^3,4 Midbrain
paralysis
[5,6,7,8 Pons ~|9,10,11,12 MeduBa
^
Lower
Upper motor neuron
medulla Ipsilateral paralysis
y
Spinal hemiplegia
Lower motor neuron
(Rnaf.common pathway)
Cerebral: cortical
Cerebral: capsular
Brain stem
Spinal
^Iwa
M III
65
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
A. Site of the lesion (level): 3 level of hemiplegia : cerebral, brainstem or spinal cord:
I.
Cerebral:
1.
Hemiplegia associated with U.M.N.L of facial & hypoglossal cranial nerves on opposite side of lesion, but
o
In face:
A.
Lower facial muscle are affected (upper is bilaterally supplied)
B.
Tongue is occasionally affected (unilateral pyramidal supply in 50 %)leading to :
without any cranial nerve paralysis on the same side of the lesion.
o o
2.
Paralysis oftongue muscles opposite the side of UMN lesion. Deviation of tongue to the hemiplegic side by normal tongue muscle
"ft
The cerebral lesion may be in one of three sites: B. Subcortical:
C. Capsular:
f
A. Cortical:
clinically as cortical lesion 1. Coma if the lesion is extensive
f
1
j. "1
2. Convulsion if the lesion is irritative
3. Contralateral paralysis usually monoplegia (one limb) specially in vascular lesions
If
1) NO Coma 2) NO Convulsion
3) Complete hemiplegia associated with U.M.N.L of facial & hypoglossal nerves on
opposite side; i.e. both of hemiplegia & cranial nerves lesion are on the same side of the body i.e. on opposite side of UMN lesion
5. Contralateral Homonymous Hemianopia if the lesion is in occipital lobe
4) Contralateral Hemihypoesthesia on the opposite side of lesion of all modalities 5) Contralateral Homonymous hemianopia may occur if the fibers of the optic radiation in the
6. Aphasia & agraphia if lesion in the dominant hemisphere
capsule are involved 6) NO Aphasia, NO Agraphia
4. Contralateral cortical sensory loss if the lesion is in parietal lobe
❖ Cortical lesions usually leads to monoplegia (one limb) specially in vascular lesions due to 1. Wide distribution of Betz cells in area 4
2. The medial part of motor area supplied by blood supply different from the lateral part:
^i»e»
a. Medial part: lower limb area, supplied by anterior cerebral artery b. Lateral part: face & upper limb area, supplied by middle cerebral artery 11.
❖ 1. 2. ❖
Brainstem :crossed hemiplegia:
Results in crossed hemiplegia characterized by: Contralateral (opposite side of the lesion) hemiplegia (pyramidal tract in brainstem) Ipsilateral (same side of the lesion) cranial nerve palsy of LMNL nature (cranial nerve nuclei) Main cause of brain stem hemiplegia is occlusion of pontine branches of vertebrobasilar system 1.
Midbrain lesion
1. Weber's
syndrome
2. Benedikt's
syndrome
11.
III.
Pontine lesion
1. Millard
2. Foville
syndrome
syndrome
Gubler
Medullary lesion
1. Avellis
2. Jackson's
syndrome
syndrome A. Hemiplegia on opposite side of lesion
B. 3'''' cranial nerve paralysis on same
B.6"'& 7'"
B. Loss of
B. 9"" & 10'"
B. 10'" & 12'"
side of the lesion
cranial nerve
conjugate
cranial nerve
cranial nerve
C. Hemiataxia
paralysis on same
deviation of
paralysis on
paralysis on same
(intention tremors)
side of the lesion
eye to same side
same side of the
side of the lesion
on opposite side of
of the lesion
lesion
lesion due to
due to lesion in
affection of red
medial
nucleus
longitudinal bundle
66
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
III.
Spinal cord :Brown Sequard Syndrome = Hemisection of spinal cord: spinal hemiplegia
❖ Definition:
o Unilateral lesion above C5 i.e. lesion is on one side of the cord between C1 - C5 segments ♦♦♦ Etiology 1. Trauma: stab wound
2. Tumor 3. Disc prolapse
■ Contralateral superficial I sensory loss for pain &
4. Disseminated sclerosis
I temperature
Ipsilateral localized LMNL & loss of all sensation
Ipsilateral hemiplegia & deep sensory loss
Touch diminishes on both side
❖ Remember ; in spinal cord : o Pyramidal tract supplies the same side of the body
o
Posterior column tracts(deep sensation & fine touch)supplies the same side of the body
o
❖ Clinical picture:
Spinothalamic tract supplies the opposite side of the body (Pain & Temperature, Crude touch)
A. At level of lesion :
PcHterlor root
Ant«mr root
1. Ipsilateral localized LMNL of muscles supplied by anterior roots in affected segment 2. Ipsilateral loss of all sensation of area supplied by posterior roots in affected segment. B. Below level of lesion :
1. Ipsilateral hemiplegia(UMNL) 2. Ipsilateral deep sensory loss 3. Contralateral superficial sensory loss for pain & temperature 4. Touch diminishes on both side
❖ N.B.: in spinal hemiplegia: o No speech affection o
No coma
o
No convulsion
67
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B. Causes of the lesion (hemiplegia):
o
2. Onset
o Rapid: taking Hours
3. Prodroma
0
4. Fever
Old
C. Hemorrhage
B. Embolism
A. Thrombosis
1. Age
o Any age especially young o Old 0 Dramatic or apoplectic 0 Sudden taking seconds o
OfTlAs
Absent
0 High o
Absent
6. Headache & Convulsion
o
Rare
7. Consciousness
o
Preserved
8. Pupiis
0 Normal, equal
o
Dilated & irreactive
10. CVS
0 May be high 0 ± cardiac insufficiency
11. CSF
0
12. CT & MRI
o Hypodense area
o 0 0 o
Usually high ± LV hypertrophy Blood & t intracranial tension Hypersense area
5. Vomiting
9. BP
0
Common
o Deep coma & neck rigidity o
Normal
0 ± valvular lesion(MS)
Clear
❖ N.B.: Causes of transient hemiplegia: 1. 2. 3. 4. 5.
Transient Ischemic Attacks(TIA) Post epileptic : Todd's Paralysis Cerebral aneurysm
Carotid hemiplegia : in transient occlusion of big artery as carotids Congestive attacks of GPI(general paresis ofthe insane in syphilis)
6. MS&DEM 7.
9.
Hypertensive Encephalopathy Hemiplegic migraine Hysterical hemiplegia:
Type of the patient: usually young neurotic female Etiology: psychological & in front of people . Association: anxiety, palpitation & hyperventilation Examination : Babinski reflex is absent
Investigation: CT & MRI: normal
Investigations: as stroke
❖ Treatment;
1. Care of comatose : see stroke 2. Treatment of the cause : see stroke
68
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Vascular occlusive syndromes ❖ Introduction
The internal capsule Definition :
o It's a broad band of white fibers lying in the depth of the cerebral hemispheres where myelinated fibers converge from all parts of the cerebral cortex and descend into the brainstem .
o It's formed of anterior limb, genu (knee)& posterior limb. o Site : lies medial to lentiform nucleus & lateral to head of caudate and thalamus
Projection fibers passing through internal capsule:
Associative fibers
Pyramidal fibers
M
o:
Dorsal half
Lentirorm
Ventral half
1. Anterior limb:
2. Genu
3. Posterior limb:
A. Anterior part:
B. Posterior part:
A. Anterior part:
B. Posterior part:
0
o
0 Corticospinal fibers
0 Sensory radiation(
Associative fibers : fibers to and from
prefrontal area of cerebral cortex
Corticobulbar fibers
—> So pyramidal tract descend in posterior ('A) part of anterior limb, genu & anterior QA)part of posterior limb This fibers supplying the arm are followed by those supplying the head, trunk & lastly the lower limb
from thalamus
areal, 2, 3)
0 Auditory radiation (from M.G.B. —> area 41,42)
o Visual (optic) radiation (from L.G.B. —>• area 17)
❖ Blood supply: 1. Anterior limb
2. Genu
3. Posterior limb
A. Dorsal (Superior) half: 0 Lenticulostriate artery: capsular branch of middle cerebral artery B. Ventral (Inferior) half: 0 Heubner's artery: capsular branch of o Thalamogeniculate artery: capsular branch anterior cerebral artery of posterior cerebral artery
Blood supply of the brain
Blood supply ofthe brain formed of two main systems : I. Carotid system (two intemal carotid arteries) II. Vertebrobasilar system (two vertebral arteries) 69
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I.
Carotid system:
CavemoinSlmA
❖ Internal carotid artery(ICA)anatomy: ntemal Carotid
mca
CMavn
aca
Cavernous sinus
Mhx-5
'Internal carotid artery, entering carotid canal
if- .nr
Opthalmic
Anterior Cerebral
Artery
Artery Middle Cerebral
Artery Posterior Communicating Artery
Cavernous
^
Internal
Sinus
Carotid Artery
1. The internal carotid artery begins at bifurcation of the common carotid artery, where it usually possesses a localized dilatation called carotid sinus. 2.
Each internal carotid artery(ICA)enters cranial cavity through carotid foramen & canal to enter cavernous sinus
where it lies lateral to optic chiasma. 3. ICA gives in the sinus three small branches:
A. Ophthalmic artery (which gives central retinal artery) B. Anterior choroidal artery (supply choroidal plexus) C. Posterior communicating artery 4. Then ICA ends by dividing into two terminal branches: A. MIDDLE CEREBRAL ARTERY B. ANTERIOR CEREBRAL ARTERY
❖ Internal carotid artery(ICA)occlusion :
❖ Type of patient: most commonly affecting male patient between 4 - 6 decades mainly due to atherosclerosis. B. Stroke : complete carotid occlusion
A. Carotid T.l.As: partial carotid occlusion (ICA insufficiency):
❖ Symptoms may be preceded by TIAs.
❖ TRANSIENT recurrent attacks of one or more of the
❖ Clinical picture: 1) Contralateral homonymous hemianopia
following:
1. Headache
spontaneous urination, defecation & sweating
b) Squeezing glans penis ^ reflex erection &
ejaculation
2) Piere Marie Foix test:
^
0 Aim: To detect paraplegia passing from extension to flexion o Technique: firm passive plantar flexion oftoes & foot 0 Result: spontaneous withdrawal reflex i.e. spontaneous flexion of hip, knee & dorsiflexion of ankle 3)Examination to determine paraplegia with a level or not.
80
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Clinical picture of FOCAL paraplegia: paraplegia WITH LEVEL:
I- At the level of the lesion:
A- Vertebral manifestations only present vertebral causes: 1. Localized pain or tenderness 2. Localized deformity or swelling
B- Radicular manifestation only present in extramedullary causes: nerve root affection: 1. Posterior root affection :
o Early: girdle pain in the back referred to distribution of affected root & f on straining, sneezing & coughing o Late: radicular sensory loss (hyposthesia or anesthesia) in dermatome supplied by affected root 2. Anterior root affection :
o Localized LMN weakness in muscles supplied by affected root^.—
C- Spinal cord manifestation: Localized LMNL with fasciculations due to affection of AHCs
II- Spinal cord manifestations below level of the lesion :
A- Motor affection :
o Paralysis with BILATERAL UMNL signs due to interruption of the descending pyramidal tracts at the level of the focal lesion, so the pyramidal tracts will not reach below that level.
.J Paraplegia may passes by two stages :stage of flaccidity & stage of spasticity Clinical picture depends on site of compression
o In cervical region
Below cervical region
Pyramidalfibers twist longitudinal during crossing the midline, so the sacral fibers are
Extra medullary compression
Intra medullary compression
the most medial fibers then lumbar, then thoracic and finally the cervical fibers which
5
are the most lateral.
A. Extra medullary compression: 1.
B. Intramedullary compression:
In cervical region: quadriplegia
0 The march of paralysis is UL then LL of same side followed by LL then UL of other side.
11.
0 The march of paralysis is both LL are affected
first, then both UL. Below cervical region: paraplegia :
0 Asymmetrical paralysis of both LL: a) Usually starts in one limb before the other
o Symmetrically & simultaneously paralysis of both LL
b) Severer in one side more than the other
81
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B- Sensory affection :
Intra medullary compression
Extra medullary compression
The fibers of spinothalamic tract arranged that the cervical fibers are the most medial fibers then thoracic, then lumbar and finally the sacral fibers which are the most lateral.
A. Extra medullary compression:
❖ Sensory level below which ALL l YPES of sensation are decreased
❖ Explanation : a) Superficial sensory loss due to compression of spinothalamic tract b) Deep sensory loss due to compression of posterior column tracts —> So, these tracts will not carry sensation from parts of the body below the level of the lesion
B. Intramedullary compression: 1. Sensory affection : ❖ Jacket sensory loss of a dissociative nature
❖ Explanation : a) Jacket: cervical and upper thoracic fibers are the most medial
b) Sensory loss : hyposthetic area with normal sensations above & below it
c) Dissociative nature: selective loss of pain & temperature with sparing offine touch & deep sensations This is due to interruption of decussating fibers of spinothalamic tract by mid line lesion, while touch & deep sensation ascend in posterior column without decussation in spinal cord. 11.
Sacral sensation:
❖ Sacral spare ❖ Explanation :
❖ Sacral affection
❖ Explanation : 0 Preserved sensation or late sensory loss over the saddle area o Early sensory loss over the saddle area (S3,4,5) as the sacral fibers lies in outermost (S3,4,5) is as the sacral fibers lie far from mid line lesion part of spinothalamic tract in cord.
AA
C- Sphincteric affection :
0
Intra medullary compression
Extra medullary compression
52 53 54
Pyramidal fibers controlling bladder lie medially in cord
1. In acute lesion : retention of urine in shock stage followed by precipitancy of urine 2. In gradual lesion: o
Lesion
A. Extra medullary compression
B. Intramedullary compression
Complete transection of spinal cord
o Etiology o Timing
o
Start early Automatic bladder
o Sphincteric affection
82
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Investigations :
Extra medullary compression: markedly J, CSF pressure Complete dynamic block
Intra-medullary compression: Moderate J, CSF pressure Partial dynamic block
i
Froin's syndro
1. CT Scan &
A. Extra medullary compression I. Imaging: Lesion outside spinal cord
B. Intramedullary compression
Lesion inside spinal cord
MRI:
diagnostic 2. Plane X-ray of
the spine 3. Myelography
o Vertebral destruction e.g. Trauma, Tumor or TB spine
o
Normal
o Narrow intervertebral disc ± osteophytes in disc prolapse
o Radio opaque dye (myodil) is injected into subarachnoid space & seen by X rays: o Normally : myodil moves freely throughout the subarachnoid space
o Abnormally: a. Complete block with short tail: saddle shape 11. 1. CSF Pressure in the manometer:
2. Queckenstedt's test(Unreliable test)
b. t width of cord with long tail : fusiform shape
CSF examination:
0 Normally CSF pressure: 10-15cmH2O 0 Abnormally: a. It is markedly diminished i.
s m ri
b. It is moderately diminished
Normally:
o Bilateral jugular vein compression below angle of mandible normally leads to rapid rise in CSF pressure
0 On release of compression: rapid drop of pressure to normal. ii. Abnormally: a. Complete dynamic block: b. Partial dynamic block: ■ No CSF pressure changes due to complete obstruction of ■ Less rise & less drop of CSF subarachnoid space pressure due to incomplete obstruction of subarachnoid space
3. CSF contents
o Froin's syndrome (triad): due to marked t in proteins: a. Spontaneous coagulation (marked t in proteins)
o No significant changes
b. Cytoalbuminous dissociation (t protein - normal cells) c. Xanthochromia : Yellowish discoloration of CSF Investigations for the cause:
1. Fundus examination : for diagnosis ofDS
2. Blood picture : for subacute combined degeneration, leukemic deposits
3. Chest X ray : exclude pulmonary TB & bronchial carcinoma
83
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Comparison between extra-medullary compression & intramedullary compression: A. Extra medullary compression I. History
B. Intra medullary compression
1. Duration
0 Long
0
Short
2. Onset
0 Painful (posterior root irritation) II. Clinical picture
o
Painless
1. Motor paralysis
o Asymmetrical paralysis of both LL
o Symmetrically & simultaneously paralysis of both LL
0 UL then LL of same side followed by LL
o
below cervical
region
2. March of paralysis in cervical region 3. Sensory
o Sensory level below which ALL TYPES of
o Jacket sensory loss of a dissociative
sensation are decreased
nature
o Sacral affection: early sensory loss from saddle area
4. Sphincteric
0
Both LL are affected first, then both UL.
then UL of other side.
Late disturbance
o Sacral spare: preserved sensation or late sensory loss over the saddle area 0 Early disturbance
affection
5. Vertebral signs
0 Present(tenderness, deformity)
!
III. 1. CT&MRI
o
Absent
Investigations 0 Lesion inside spinal cord
o Lesion outside spinal cord
(diagnostic) o
Normal
2. Xray
0
3. Myelography
o saddle shape block (short tail)
0 fusiform shape block (long tail)
4. CSF
0 Marked drop in CSF pressure o Complete dynamic block
o Moderate drop in CSF pressure o Partial dynamic block
o Froin's syndrome
0 No Froin's syndrome
Vertebral lesion
❖ Treatment :
1. General: care of comatose (see stroke)
2. Specific treatment: treatment of the cause e.g. o Medical e.g. Vitamin B12 replacement in SCD
o Surgical removal of the tumor or decompression laminectomy for intra-medullary lesion.
84
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Inflammatory diseases of spinal cord: acute transverse myelitis (acute myelopathy)
Definition : Spinal cord
o Acute inflammation affecting gray & white matter of several segments of spinal cord & functionally transects the spinal cord. . Etiology: o
1. Idiopathic 2. Infection:
A. Viral: influenza, Herbs zoster, EBV,CMV,rabies B. Bacterial: TB, syphilis, diphtheria 3. Immunoiogical: o
Post vaccination
o Associated with vasculitis e.g. SEE 4. latrogenic : post lumbar anesthesia 5. Toxic: IV heroin
6. Demyelinating: MS,DEM Clinical picture: Posterior root
tr
Antentir root
1. Acute onset with fever & regressive course 2. At the level of the lesion :
o Posterior root affection : radicular pain or sensory loss (hyposthesia or anesthesia) in dermatome supplied by affected root
o Anterior root affection : Localized LMNL with weakness in muscles supplied by affected root ❖ Stage:
A. Shock stage: 2-6 weeks:
1. Motor
0 Flaccid paraplegia or quadriplegia (ascending myelopathy)
2. Sensory
0 Sensory level below which ALL TYPES of sensation are decreased (due to
3. Reflexes
0
Areflexia
4. Sphincteric affection
0
Retention of urine with overflow
B, Recovery stage:
0 Spastic paraplegia or quadriplegia (ascending myelopathy)
affection of spinothalamic & posterior column tracts) 0 Hypereflexia with Babinski sign o Precipitancy of micturition
❖ Differential diagnosis: 1. Acute cord compression 2. Anterior spinal artery occlusion 3. Guillain-Barre syndrome Investigations: 1. CSF examination :
o Increased both cells & proteins o in DS : high immunoglobulin level 2. MRI: to exclude cord compression ❖ Treatment:
o Supportive treatment o Corticosteroids : prednisone, ACTH
85
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Vascular diseases of spinal cord
Acute anterior spinal artery occlusion
❖ Etiology: 1. CVS: thrombosis, embolism, dissecting aortic aneurysm, hypotension
2. Vasculitis: polyarteritis nodosa and systemic lupus erythematosus 3. Metabolic : DM
4. Mechanical: tumors, abscess, disc fragments
❖ Clinical picture:
J ❖ As transverse myelitis except in sensory affection :
o Sensory level below which there is dissociative sensory loss: selective loss of pain & temperature with sparing of touch & deep sensations ❖ Explanation : o Anterior spinal artery supplies pyramidal tract & spinothalamic tracts o While posterior spinal arteries supply the posterior column tracts Acute posterior spinal artery occlusion ❖ Damage to posterior column tracts ± posterior horns 1. Segmenta! anesthesia & areflexia 2. Sensory affection:
o Sensory level below which there is dissociative sensory loss: selective loss of touch & deep sensations with sparing pain & temperature sensations
filled with fluid
Fluid-filled cyst (syrinx)
Spmfficord Subdural space
86
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Syrinx Definition :
o Syrinx is a rare, fluid-filled neurological cavity within : 1. Brain stem: SYRINGOBULBIA: lesion affecting the medulla. II.
Spinal cord: SYRINGOMYELIA :
1. Lower cervical & upper thoracic segments (Cervico-thoracic): THE COMMONEST SITE 2. Lumbar segments:clinical picture ofepiconus lesion 3. Lower end ofspinal cord: clinical picture ofconus lesion Syringomyelia Definition:
o INTRAMEDULLARY focal spinal cord lesion characterized by cavitation around central canal in gray matter of spinal cord surrounded by gliosis (thick tissue of glial cells) Etiology:
1. Primary: idiopathic, may be due to developmental abnormalities (congenital). 2. Secondary :intramedullary spinal cord tumor with central necrosis & hemorrhage Pathology: "V o o
Proliferation of congenital undifferentiated mesenchymal cells remnants of glial tissue.
Blockage of the exit foramina of the fourth ventricle —> CSF can't escape into the subarachnoid space —> f pressure in the ventricle which communicating to the central canal of spinal cord which expands & gets bigger & longer over time —> compressing & destroying the center of the spinal cord. ❖ Sites: see before.
M
❖ Clinical picture of CERVICAL syringomyelia: Type of patient: o Age: 15-35 years old.
o Chronic disease with gradual onset & slowly progressive course B. Clinical picture:
_L
Motor manifestations:
a.
Early, in UL:
o
Localized LMNL weakness with fasciculation
o
Due to AHCs compression
b. Later,in LL : Spastic paraplegia o Due to LL pyramidal tract
compression
c. Latest, in UL: Quadriplegia
o Due to UL pyramidal tract
compression
2. Sensory manifestations: A. Jacket sensory loss of a dissociative nature
(selective loss of pain & temperature with sparing oftouch & deep sensations) ❖ Explanation : o Due to affection of decussating fibers of spinothalamic tract near the central canal while sparing the posterior columns as it's fibers away from the central canal. Sacral spare as the sacral fibers lie far from the central canal. Sphincteric manifestations:
Early bladder affection(A fibers controlling bladder lie medially in cord) Autonomic manifestations:
Due to affection of reticulospinal tract leading to:
Trophic changes of skin e.g. ulcer, infection, Charcot's joint Mors'an's syndrome : vasomotor changes e.g. coldness, cyanosis Associated skeletal deformities e.g. pes cavus & spina bifida
87
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Investigations:
o
MRI
o Myelography ❖ Treatment;
1. X-ray irradiation of the affected region of the cord 2. Symptomatic: massage, physiotherapy 3. Surgical: decompression laminectomy
Syringobulbia
Cl
Syringobnibia
C2 C3 C4
Pathology:
C5 C6 C7 C8
o
Lesion affecting the medulla.
T1,,
o Lesion may start in medulla or may be upward extension of a cervical syringomyelia
T2
o
T3
Lesion involves :
T4i
1. Spinal nucleus of the trlgemlnal(CN 5) nerve
T5
2. Vestlbular(CN 8)nucleus 3. Bulbar(CN 9,10,11,12) nuclei.
T6
Tti T8 T9
TIO Til
Clinical picture
T12 LI
L2
1. Pain in face followed by loss of sensation of dissociative nature
L3
2. Vertigo : affection of 8"^ nucleus
L4
3. Bulbar symptoms with lost palatal & pharyngeal reflexes 4. Wasting of tongue & fasclculatlon 5. Argyll Robertson pupil
L6
Conus medullaris &
•SI
Epiconus form part of the spinal cord
S3
bpicoDus
SI
|S4
Conus medullaris
Cauda equine: nerve roots
Cauda equlna
❖ Anatomical Introduction:
o During intrauterine life, the rate of growth ofthe vertebral column is faster than the rate of growth of the spinal cord, so that at birth, the vertebral column Is longer than spinal cord,
o The spinal cord normally ends at the junction of LI and L2 vertebra. o Below this level, the spinal canal is filled by the collection of lumbosacral roots, are termed : cauda equine Definitions:
o Cauda equine: collection of lumbosacral roots in the spinal canal below the lower border of LI o
Conus medullaris: the lowermost three sesments ofthe spinal cord(S3,4,5)
o Epiconus: the four sesments ofthe spinal cord above the conus medullaris (L4,5,S1,2) -
88
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cauda equina lesion ❖ Definition:
It is a radiculopathy (root disease) affecting the lumbosacral roots, mostly due to compression ♦♦♦ This lesion affects the lower limbs (unilateral or bilateral) with sphincteric disturbances ♦♦♦ Etiology of cauda equina lesion (as extra medullary lesions of paraplegia): 1. Congenital: spinal bifida 2.
Traumatic:
o Fracture dislocation oflumbar vertebrae o Post traumatic lumbar disc prolapse 3. Inflammatory:
o Pott's disease of lumbar vertebrae(TB of the spine) o Radiculitis : syphilitic, Herpes Zoster 4. Neoplastic:
o Vertebra; primary (osteoma, hemangioma)& secondary (metastases) o o 5. a)
Meningeal: meningioma Radicular(Roots): neurofibroma Degenerative (pars interarticularis defects): Lumbar spondylosis:
o Degenerative changes(as osteoarthritis) ofthe spinal column (vertebral joints & intervertebral discs) b) Lumbar spondylolisthesis: o Forward displacement of one vertebra over a lower vertebrae below
❖ N.B. Sciatica is oneform ofcauda equina lesion.
❖ Clinical picture of cauda equina lesion:
Posterior root
Femoral nerve Anteri
Sciatic nerve
"Pudenda! plexus'
A. Motor manifestations: anterior
B. Sensory manifestations: posterior root affection
root affection
o Paralysis or paresis of one or both LL of LMNL nature
1. Early : radicular pain & paresthesia at the onset: a) Due to posterior root irritation
b) Pain increased by movement of LL, coughing, sneezing, straining 0 The distribution ofmuscle weakness depends on the affected root
c) Referred to the LL:
0 Femoral nerve distribution if upper lumbar roots affected 0
Sciatic nerve distribution if lower lumbar & sacral roots affected
2. Later: radicular sensory loss: the distribution ofradicular sensory loss depends on the affected root
0 Motor & sensory manifestations are usually unilateral, but if bilateral they are asymmetrical.
89
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Distribution ofmotor & sensory affection depend on the affected root;
Hip Flexion L2
Knee extension I
HIP
L3 KNEE
Anal\
S3,4,5^Knee Flexion S2 Ankel dorsiflexion L4
PlantarfleMonof j
®dorsiflexion
ankle & toes 1
^5
SI
❖ Root:
1. Action
2. Muscle
o
L2
o Flexion of the hip
o Iliopsoas
0
L3
o
Extension of the knee
o Quadriceps
o
L4
o
Dorsiflexion of ankle
o
L5
o
Dorsiflexion of toes
o
o
SI
o
Plantar flexion of the ankle
Anterior tibial group
o
Calf muscles
& toes
o
S2
B. Distribution of sensory affection:
A. Distribution of muscle affection :
0
0 S3,4,5 o
Flexion of the knee Anal Contraction
0 Hamstrings 0 Anal & perianal muscles
0 o o o o o o o o
LI: Upper 1/3 of front of thigh Middle 1/3 of front of thigh Lower 1/3 of front ofthigh Antero-lateral aspect ofthigh, front of knee Antero-medial aspect of leg Medial aspect of dorsum of foot Big toe Lateral aspect ofthigh Lateral aspect of leg
o
Middle 1/3 of dorsum offoot
o
Middle 3 toes
o Postero-lateral aspect of thigh & leg o
Lateral 1/3 of dorsum of foot
o
Little toe
0 Posterior aspect of thigh, leg & sole of foot 0 Saddle area : Anal, perianal and gluteal region
C. Reflexes lost: according to affected root:
o Deep reflexes e.g. Knee reflex = L2,3,4 o Superficial Reflexes e.g. Cremasteric reflex = LI D. Autonomic manifestations :
1. Sphincteric affection: o Occur in bilateral lesion of S2,3,4 leading to bladder affection o Clinical picture: a) Sensory atonic bladder(sensory root lesion) b) .Motor atonic bladder(motor root lesion) c) Autonomic bladder (both roots affection) 2. Vasomotor changes:trophic ulcers, coldness & cyanosis
90
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Clinical picture of epiconus & conns medullaris lesion:
L4-S2^s^
&tSCi /
SiiJiifflllx J
1. Lesion
2. Etiology 3. Segments affected 4. Motor weakness
❖ Epiconus lesion: o Causes of intramedullary compression o
❖ Conus medullaris lesion:
o 83,4,5
L4,5, Sl,2
o Paralysis or paresis of one or both
o
Absent
LL of LMNL nature in muscles
supplied by L4,5 «& Sl,2 o Sensory loss in the dermatomes supplied by L4,5 & SI,2 usually
5. Sensory loss
of dissociative nature
nature
o
0 Lost ankle reflex (S1,2 mainly S1) with preserved knee reflex
6. Reflexes lost
o Lost in saddle area: usually of dissociative N.B.: NO motor or sensory deficits in LL
o Lost anal reflexes (S3,4,5)
(L2,3,4)
0 Precipitancy of urine
7. Autonomic
o Early urinary incontinence(autonomic bladder) o Early stool incontinence
manifestations
o Early impotence
Differential diagnosis of cauda equina lesion & polyneuropathy: *1* Cauda equina lesion: Symmetry o Asymmetrical (if bilateral) Sensory loss o Radicular Upper limb 0 Not affected Sphincteric affection 0 Commonly affected (late)
1. Lesion
2. 3. 4. 5.
6. Bed sores
o
7. X-ray & CSF
o Changes of block are present
❖ o o o
Polyneuropathy: Symmetrical Glove & stocking May be affected (late)
o
Absent
Common
❖ N.B.: LMN weakness of ankle muscles(L 4,5 - S 1,2) may be due to:
A. Radicular cauda equina or segmental epiconus lesion: B. Peripheral nerve lesion : ^ Differentiated by: glutens maximus power(L5,S 1,2), tested by hip extension : o
Weak
o
Intact
❖ Investigations & treatment: see paraplegia.
91
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Sciatica
❖ Definition :
o Radicular pain along distribution of sciatic nerve (L4,5, SI,2,3) i.e. along back ofthigh, leg & foot Etiology (types) of sciatica:
o
Radicular sciatica: compression of lumbo-sacral roots: Compression in the spinal canal: Acute lumbar disc prolapse, fracture or dislocation Lumbar spondylosis
o
Lumbar canal stenosis
2,
Compression in intravertebral foramina:
A. 1. o
o
B. 1. 2. 3.
Neurofibroma, radiculitis
Plexus sciatica: compression of sciatic plexus over sacroiliac joint in the pelvis: Pelvic abscess, fracture pelvis Pregnant retroverted uterus Malignant tumors ofthe bladder, rectum & ovaries
C. Nerve sciatica : affection of sciatic nerve itself: Neuritis :
diabetic neuritis (the commonest cause of neuritis)
Pressure on nerve by dislocated head offemur or piriformis muscle Wrong injection in the nerve Referred sciatica : due to hip joint or sacroiliac joint disease
The most common causes of sciatica:Acute disc prolapse & Lumbar spondylosis Posterior root
Clinical picture:
Krj
I. Sensory manifestations : posterior root compression A. Early : radicular sciatic pain & paresthesia at the onset: 1. Due to posterior root irritation
Anten
2. Pain along the:
o Compressed root o Entire course of sciatic nerve: low back, gluteal region, posterior aspect ofthigh, leg, outer 3 toes 3. Pain increased by:
o Walking (stretches the nerve) specially downhill: neurogenic pseudo-claudication (intact LL pulsation) o 4. o 5. B.
Coughing, straining & sneezing Pain relieved by: Bed rest on a hard mattress in cases of disc prolapse Examination:tenderness on direct pressure on the sciatic nerve Later: radicular sensory loss:
o Hypoesthesia (decreased sensation) or anesthesia(sensory loss) o The distribution ofsensory loss depends on the compressed root or along course ofsciatic nerve (see cauda equina) IT.
Motor: anterior root compression
o LMNL in muscle supplied by sciatic nerve : dorsiflexors ofankle & toes & flexors of knee (see cauda equina) III.
Reflexes:
o Ankle reflex (S1,2 mainly S1)is usually lost o Knee reflex(L2,3,4) may be present or absent IV. Special signs:: 1. Back signs :
o Rigidity of paravertebral muscles and limited mobility of spine o
Loss of normal lumbar lordosis
2. Signs of meningeal irritation : o
Due to traction on roots of sciatic nerve
o Positive Lasegue's, Kemig's & Brudzinski's signs 92
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Investigations:
1. CT- MRI,Plain X ray, Myelography for disc lesion 2. Blood glucose for DM 3. Plain x-ray for hip joint
4. Rectal & vaginal examination for suspected tumors.
❖ Treatment: treatment of the cause e.g. disc prolapse
Disc lesion: spondylosis (degenerative)& disc prolapse (traumatic)
Intervertebral Olee
CartilaKinoui plate
❖ Anatomical introduction of disc structure:
Annului flbroiui
Nucleui puipoiuf
Spinal cord PoiterJor
Normal disk
Intervertebral disc is formed of:
longitudinal ligament
Spinal nerve
1. Nucleus pulposus : central gelatinous part 2. Annulus librosus:fibrous tissue ring surrounding the nucleus
Anterior
longitudinal
jl|ament
3. Cartilaginous plate above & below.
Intervertebral discs are kept in position by anterior & posterior longitudinal ligaments Pathology of spondylosis:
Gradual progressive DEGENERATION of intervertebral disc affects mainly freely mobile discs (cervical & lumbar regions) as they more subjected to the process of wear & tear with age, leading to : pinched nerve
Pressure
collapsed disc.
Bone spurs tosteophylet)
Disc aepeneraiioo • flanemng of me csk Bone spurs (osleophyles)
1) Degeneration of annulus fibrosus with protrusion (herniation) of nucleus pulposus with subsequent compression of adjacent structure. 2) Sclerosis of the adjacent surfaces of the vertebra
3) Lipping or osteophytes formation due to calcification of prolapsed parts & ligaments ❖ Predisposing factors: 1. Old age 2. Occupational: excessive mobility of the spine as in labourers 3. DM
❖ Pathology of acute disc prolapse: am*
Mechanisms of disc prolapse: TRAUMA :
Lifting heavy weight in the forward bending position causes acute(sudden) RUPTURE in
annulus fibrosus with herniation of nucleus pulposus leading to compression of spinal roots. Incidence:
o
The commonest sites between L4 - L5 & between L5-S1
o
The commonest cause of sciatica
93
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Differentiation between acute & chronic disc lesion
A. Acute disc prolapse 1. Lesion 2. Age 0 Any age 3. Etiology o Traumatic Acute
B. Spondylosis 0
Middle & old age
o Degenerative o Chronic(Gradual)
4. Onset
0
5. X-ray
0 Narrow intervertebral space o 0 No degenerative changes
Sclerosis ,lipping & estophytes
❖ Clinical picture depends on: I.
According to the level
1. Cervical level (cervical spondylosis): quadriplegia 2. Thoracic level (thoracic spondylosis); paraplegia 3. Lumbar level (lumbar spondylosis): present with sciatica or cauda equina lesion (since no AHC are present) II. o
Site of prolapse:
Since the weakest part of annulus are the lateral and posterior part, the herniation will be either :
a) Lateral: radiculopathy —> nerve root compression b) Posterior: myelopathy —> spinal cord compression c) Posterolateral : myeloradiculopathy : tonic atrophy
❖ Clinical picture of CERVICAL spondylosis: present with one of the following:
1- Lateral prolapse: causing radiculopathy = nerve root compression:
Posterior root
A. Motor manifestations: anterior
root compression 0 Paralysis or paresis of one or both ULs of LMNL nature
o The distribution ofmuscle weakness depends on the compressed root
B. Sensory manifestations: posterior root compression
1. a) b) c) 2.
Early:radicular pain & paresthesia at the onset: Due to posterior root irritation Pain increased by movement of neck, coughing, sneezing \ Referred to the shoulder & upper limbs(brachial neuralgia) Later: radicular sensory loss in the UL dermatome: the distribution of sensory loss depends on the compressed root
94
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
*t* Distribution ofmotor & sensory affection depend on the compressed root: Elevation
Abduction
of shoulder
of shoulder
Extension of
Flexion of elbow
elbow
Extension of wrist
Flexion of wrist & movement of small muscles of hands
❖ Distribution of muscle affection : ❖ Root
o
€1,2
❖ Action
o
❖ Muscle
❖ Distribution of sensory affection: ❖ Sensory affection • Lateral aspect of neck
❖ Root
Lateral movement of neck
o
• €3,4
•
•
€5
•
€6
manubrium anteriorly • Lateral aspect of arm • Lateral aspect of forearm,
Stemomastoid &
o
€3,4
o
Elevation of shoulder
trapezius o Supra and inffaspinatus
o
€5
o
Abduction of shoulder
o
o
€5,6
o
Flexion of elbow
o Biceps &
Deltoid
•
€2
brachioradialis
o
€6,7
o
Extension of elbow
o Triceps
thenar eminence and thumb •
€7
•
o
€7,8
o
Extension of wrist
o
Extensors of wrist
o
€8,T1
o
Flexion of wrist &
o
Flexors of wrist
Shoulder down to
n 00
• Middle aspect offorearm, middle of palm & middle 3 fingers • Medial aspect of forearm, hypothenar eminence and little finger
•
T1
• Medial aspect of arm
movement of small muscles of hands C. Reflexes:
1. o o o 2.
Inverted Reflex
Reflexes lost according to compressed root e.g. Biceps : C5,6 Brachioradialis (Supinator reflex): C5,6 Triceps: C6,7 Inverted supinator reflex:
o Pathological reflex occurring when lesion involve 5"* cervical segment o Characterized by: a. Weak or lost biceps reflex(LMNL,C5,6) b. Exaggerated triceps reflex(UMNL,€6,7)
Inverted
c. On eliciting brachioradialis reflex:
■ ■
Flexion of fingers will occur instead of flexion of elbow Due to irradiation of nerve impulse in spinal cord with stimulation of AHC of C8-T1.
2- Posterior prolapse: causing myelopathy = spinal cord compression = extra-medullary compression: 1. At the level of compression; in upper limbs:
o Localized LMNL with fasciculations due to AHCs compression 2. Below the level of compression; in lower limbs: a. Pyramidal(A)tract compression :
o Paralysis (paraplegia or quadriplegia) with UMNL signs below level of compression o Bladder disturbance: rare, late & occur with severe lesions b. Spinothalamic tract compression:
o Superficial sensory loss below level of compression c. Posterior column compression:
o Rarely affected, spared being away from disc o If affected, deep sensory loss(sensory ataxia) below level of compression
95
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
3- Postero-lateral prolapse: causing myeloradiculopathy: nerve root & spinal cord compression
A. At the level of compression; in upper limbs : TONIC ATROPHY of muscles :
o COMBINED signs ofLMNL(weakness, wasting & fasciculations)& UMNL(hypertonia and hypereflexia) B. Below the level of compression; in lower limbs: o Weakness with signs of UMNL 4- Important signs: 1. Hoffman sign:
o Reflex contraction of the thumb & index after nipping the middle finger 2. Lhermite sign:
o Electric like sensation in the back & limbs on bending the neck,
o It's due to posterior column affection in the cervical region.
Differential diagnosis of brachialgia (brachial neuralgia):
❖ It's severe radicular pain along distribution of the brachial plexus(C5 to TI)
in the shoulder & UL
❖ Etiology:
1. Cervical spondylosis & disc prolapse:
o Pain is related to neck movement: passive neck extension ^ electric radiation in UL ± LL o Painful limitation of neck movement with rigidity & localized tenderness . 2. Cervical radiculitis (Brachial neuritis):
o o o 3. o 4. a. b. c.
,45
Diffuse constant pain unrelated to neck movement Tendemess along course of nerve (mononeuritis multiplex) Later(within 1 month): UL weakness & wasting Thoracic inlet(outlet)syndrome e.g. Pancoast tumor «& cervical rib Clinical picture: Homer's syndrome, constant pain in medial side of arm & forearm. Referred pain (visceral disease): Angina & myocardial infarction Frozen shoulder syndrome Complex regional pain syndrome
■ ■■
0«9*n«rative Chang«K Cervicat Spine
d. Gall bladder disease
Investigations:
J
Narrow
disc spaco
1.
MRl & CT scan:
o
MRI is the investigation of choice
o
It can detect & localize small lesions
. -%)■
2. X- ray:
o Narrow intervertebral spaces o Sclerosis of the adjacent surfaces of the vertebra
o Lipping or osteophytes formation due to calcifieation of prolapsed parts & ligaments o Obliteration of normal cervical lordosis (straight spine) 3. Myelography: o Anterior filling defect due to disc protrusions and compression of the cord.
96
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
'
❖ Treatment: 1. Medical:
a. Analgesics e.g. NSAIDs b. Muscle relaxants 2. a.
Physiotherapy: Plastic collar for cervical lesion : not more than 3 months to avoid muscle fibrosis
b. Lumbar corset for lumbar lesions c.
Short wave therapy
4.
Bed rest for 2 - 3 weeks on a hard matrix for lumbar lesions causing sciatica Surgical: nucleolysis or decompression laminectomy is indicated in :
a.
Failure of medical treatment
3.
Laminectomy Bone spur
b.
Intolerable recurrent pain
c.
Progressive neurological lesion e.g. motor or sensory deficits
Spinal Cord
Flaccid paraplegia Lower Motor
❖ Definition:
Neuron
o Paresis or paralysis of both LL of LMNL picture Etiology:
1. 2. 3. 4.
AHCs lesion at lumbo-sacral region: epiconus lesion, motor neuron disease Root lesion at lumbo-sacral region: cauda equina lesion Peripheral nerve lesion : polyneuropathy Neuromuscular junction lesion : myasthenia gravis
MS
5. Muscle lesion: myopathy
6. Shock stage of spastic paraplegia (remain from 2-6 weeks)following acute injury of pyramidal tract e.g. transverse myelitis
Clinical picture: 1.
Clinical diagnosis : paraplegia with LMNL picture: hypotonia, hyporeflexia, wasting & fasciculations
2.
Anatomical diagnosis according to site : AHCs, root, nerve, NMJ, muscle . Etiological diagnosis : see cause
3.
Quadriplegia
1.
2. 3. 4. 5. 6.
Cervical spondylosis : four limbs show pyramidal signs Marie's ataxia : pyramidal + cerebellum lesion signs Friedreich's ataxia: pyramidal + posterior column + peripheral nerve + cerebellum lesion signs Subacute combined degeneration of the cord: pyramidal + posterior column + peripheral nerve lesion signs Pellagra : pyramidal + peripheral nerve lesion signs Motor neuron disease : purely motor disease + fasciculation N.B.:from 2 -^6:
All these diseases are bilateral symmetrical, the pyramidal lesion startsfrom below upwards in the spinal cord & 7.
the sphincters are usually spared Myopathy : purely motor disease
8.
Neuropathy : weakness (distal more than proximal) with stock & glove hyposthesia 97
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Extrapyramidal system caudiitt' St
putamm
❖ Definition:
exOv pailidus
o The descending motor pathway that influence motor activity without passing in pyramidal system (corticobulbar and corticospinal tracts).
maljmu»
ubthdiamic nudeus
Pathway & tracts: sub&tantia nigra
A. The extra-pyramidal motor fibers originates at several areas of brain (mainly suppressor area in frontal lobe), then descend in the corona radiate, pass via the internal capsule intermingled with the pyramidal fibers and terminate at the basal ganglia.
❖ BASAL GANGLIA (the major contribution in the extrapyramidal motor system), formed of: 1. Caudate nucleus
2. o o B. 1.
Lentiform nucleus which is formed of globus pallidus (external & internal segments) & putamen N.B.: neurotransmitters in EG e.g. -(dopamine, GABA)& -I- (acetylcholine, glutamic acid) N.B. caudate nucleus -t- putamen = corpus striatum Signals from the globus pallidus are discharged to: Thalamus, hypothalamus & subthalamus
2. In the brain stem c. Medulla
b. Pons
a. Midbrain:
o Pontine reticular nuclei o Substantia nigra (reticulospinal tract) 0 Red nucleus (rubrospinal tract) o Tectum of midbrain (tectospinal tract)
0 Vestibular (vestibulospinal tract) o Inferior olivary nucleus (olivospinal tract)
N.B.:
The MAJORITY ofthese tracts form INHIBITORY circuit through lentiform nucleus on motor area 4
leading to inhibition of excessive movements and muscle tone while the minority are facilitatory through caudate nucleus.
—> So normal balance in the basal ganglia is needed for normal function. ❖ Functions & lesions:
❖ Lesions of extrapyramidal system
❖ Functions of extrapyramidal system
1. Regulation and integration of voluntary movement
1) Involuntary static movement(tremors during rest): hvoerkinesia of two types:
b. Dysrhythmic and irregular in a. Rhythmic and Regular chorea, athetosis & dystonia in parkinsonism o NB: tremors increase with emotion, stress, anxiety, fatigue & disappear during active movement and sleep. 2. Regulation and maintenance of emotional & associative movement
2) Disturbance of emotional & associative movement:
a. Reduced (bradykinesia) e.g. mask face in
b. Exaggerated (excess grimacing) in chorea
parkinsonism
3. Regulation and maintenance (mainly inhibition) of muscle tone
3) Disturbance of normal muscle tone:
a. Rigidity (Hypertonia) in
b. Hypotonia in chorea
parkinsonism
c. Alternation of hyper & hypotonia in athetoses_and dystonia Movement disorders Caudate Nucleus
Cortex
1. Parkinsonism (Shaking palsy)
Uidemue
Putamen
2. Chorea 3. Athetosis
4. Dystonia 5. Other abnormal movements :
^ubstantia \Hvvolhala/T)us
o Tics, Drug induced movement disorder o Fasciculations, Myoclonus
Nigra
98
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Parkinsonism (Shaking palsy)
Definition:
o It is a condition which there are static tremors associated with bradykinesia & rigidity (hypertonia) ofthe muscles ofthe body.
❖ Pathophysiology:
o The manifestation of parkinsonism are due to neurotransmitter imbalance in the basal ganglia & substantia nigra due to decreased level of dopamine & relative increase in acetylcholine levels Dindnished
•ubstantia nlgra
Etiology: O
A. Idiopathic: paralysis agitans : the commonest cause
o Due to degeneration ofsubstantia nigra (the neuromelanin, pigmented cells becomes pale) o This degeneration leads to deficiency of dopamine in the brain, o The age of onset > 50 years. o Sex incidence: both sexes are equally affected . B. Heredofamillal: bepatolenticular degeneration; Wilson's disease: for more details see GIT BOOK C. Secondary:
.iw
Stooped posture Masked fadal
expression
1. Inflammatory: post encephalitis 2. Vascular: cerebral atherosclerosis
Ri^ty Forward tilt
3. Toxic:
o o 4. 5.
of trunk
Carbon monoxide & manganese poisoning, Flexed elbows & wrists Drugs(dopamine antagonists): metoclopramide, reserpine, phenothiazinci Tumors: neoplasm of basal ganglia Trauma: minute hemorrhage in basal ganglia of boxers
❖ Clinical picture:
Reduced arm swinging
Slightly ffexed hips & knees
Tremblir^ of extremities
A. Static tremors(Hyperkinesia):
Shuffling, short stepped gait
1. Involuntary static movements characterized by: o Regular, Rhythmic, at a Rate of 4-8 / seconds
o Giving pill rolling appearance with the thumb moving Rhythmically back & forward on the palm. 2. 3. 4. 5.
Affect DISTAL muscles more than proximal They begin unilaterally in the upper limbs then spread to all four limbs Static tremors increased by emotional stress, anxiety & fatigue. Static tremors decreased by voluntary activity, sleep
Pill rolling tremors
B. Bradykinesia: loss of emotional & associative movement:
1. Mask face:immobile, with infrequent blinking 2. Monotonous speech 3. Loss of arm swinging during walking
99
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
C. Hypertonia of RIGIDITY type: ❖ Rigidity (Hypertonia) affecting : o
More in PROXIMAL muscles than distal muscles
o More in the flexors ofthe neck, trunk & limbs resulting in the generalized flexion attitude (gorilla like attitude) ❖ It leads to :
1. Speech :
o Monotonous (rigid muscles of articulation + loss ofemotional movements)^^ o Drooling of saliva (difficult swallowing) 2. Neck : flexed + nodding (static tremors) 3. Trunk: flexed UL and LL (Gorilla like attitude) 4. Tone: rigidity; types:
o o 5. 6.
Uniform resistance present throughout movement it is termed : lead pipe rigidity Resistance intermittent & interrupted by tremors it is termed : cog wheel rigidity Deep reflexes: inhibited (due to rigid muscles) Gait difficulty in starting the act of walking leading to:
a. Festinated (short steps)
b. Shuffling (noisy walking) c. Kinesia paradoxa:
o Inability to stop movement with propulsion and retropulsion when the patient is pushed forward or backward »:♦ N.B.:NO:
1. NO weakness (Normal muscle power), there is badykinesia only. 2. NO sensory i.e. purely motor disease 3. NO sphincteric disturbances 4.
NO fasciculations
N.B.: Difference between rigidity & spasticity : ❖ Spasticity
❖ Rigidity 1. Site of lesion 2. Distribution
o
Extra A tract
0
A tract
o Distal > proximal
o
Proximal > distal
o
Flexors of UL
o
Flexors of UL
o
Flexors oftrunks
0
Extensor of trunk
o
Flexors of LL
0
Extensor of LL
o Lead pipe or cogwheel 0 Clasp knife (initial resistance with terminal release) o Hyperreflexia 4. Deep Reflexes o Hyporeflexia
3. Character
D. Clinical picture of tbe cause: the comments causes: paralysis agitans, post-encephalitic, atherosclerosis:
1. Age
❖ Paralysis agitans o 40-60 years
❖ Post-eneephalitic o Any age
o Over 60 years
❖ Atherosclerosis
2. Onset
o
Gradual
o
Acute
0
Gradual
3. Course
o Progressive
o
Regressive or stationary
o
Remission & exacerbation
4. Rigidity
o
o Rigidity & tremors equally marked
o Rigidity more than tremors
5. Associations
o
o Pyramidal signs o Body weight: Obesity
o
Tremors more than
rigidity None
Amnesia
o BP: Hypertension o Occulogyrie Crisis: sudden spasm of o Pyramidal sign o Coronary heart disease conjugate movement of eye o DM especially upwards o Diabetes Insipidus o Impotence or amenorrhea o Greasy face. Sialorrhea o Glabellar reflex(Myerson's sign)
100
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Differential diagnosis ; A. From other causes of static tremors
B. From other causes of gait disturbances e.g. normal pressure hydrocephalus C. From causes of Parkinson plus syndromes e.g. : 1. Multiple system atrophy(Shy-Drager syndrome)
2. Progressive supra-nuclear palsy (Steele-Richardson-Olszewski syndrome) 3. Pick's disease
4. Corticobasal degeneration & olivo-ponto-cerebellar atrophy 5. Dementia with Lewy bodies ❖ Treatment:
1. Medical treatment;
♦♦♦ Aim to decrease acetyl choline or to increase dopamine level A. Anticholinergic drugs: N.B.: Anticholinergic drugs are best prescribed for tremors.
1. Natural belladonna :
o E.g. atropine & hyoscine o Rarely used nowadays
o Side effects : blurring of vision, dry mouth, tachycardia, urine retention, constipation 2. Synthetic belladonna :
a. E.g.:
o Trihexyphenidyl e.g. Artane & Parkinol: 2-5 mg tablets o Benztropine (Cogentin): 2 mg tablets
b. Dose : 1-2 tablets /Shours according to the severity c. Side effects as atropine but less prominent Levodopa CarbidofM
Levodopa
I DOC Dc^mine
Dopamine
B. Dopaminergic drugs: A. Exogenous dopa:
Perftheral
Centra
1) Levo - dopa : dopamine precursor
a. Principle: dopamine can't cross BBB, while levo-dopa(dopamine precursor) can cross BBB
b. Dose : 1/2 gram oral/day to be increase gradually Vi gram every 3 days, maximum dose up to to 4-6 4-b gram/day gram/day c. Side effects:
o CNS : hypotonia, hallucinations, chorea, confusion, depression & epilepsy o CVS; arrhythmia & palpitations o GIT: nausea, vomiting 2) Levo dopa -i- carbidopa : Sinemet: a. Principle:
o L- dopa is markedly decarboxylated in liver to dopamine before passing BBB resulting in marked side effects (peripheral action of dopamine).
o Addition of carbidopa to L- dopa, inhibits extracerebral decarboxylation of L- dopa & thus reduces side effects, o Carbidopa itself doesn't pass BBB. b. Dose: o o
One tablet of sinemet = 250 mg L- dopa + 25 mg carbidopa Dose 1 tablet/ day | & by 1/2 tablet every 3 days till the case improves N.B.: Sinemet are best prescribed for bradykinesia & rigidity 101
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
N.B.: On and off phenomenon:
After long term treatment with L-dopa the patient may show signs of parkinsonism (under treatment) alternating rapidly with signs of chorea (over treatment), as if being turned on & off.
Dose of L-dopa should be reduced & other drugs as bromocriptine are given Circulation
ODC inhibitors 'Carbldopa COMT Inhibitors
t Dopamlne avaiiabtllty
(central) 'Tolcapono
3-OMD
Dopamine
DDC
L-DOPA ■"
L-OOPA
Dopamine
I Dopamine I receptors
COMT
MAO-B
COMT Inhibitors
MAO-B inhibitors -Stlegllin*
(peripheral) •Tolcapona •Entacapont
Presynaptic neuron
Postaynaptic neuron.
Blood-brain barrier
B. Degradation inhibitors: o Monoamine oxidase (MAO) B inhibitors e.g. Selegiline
o
Catechol-O-methyl transferase (COMT) inhibitors e.g. Toleapone
C. Reuptake inhibition :
o It prevents uptake of dopamine by neurons e.g. NMDA (N-Methyl-D-aspartate) receptor antagonists e.i Amantadine hydrochloride o Dose: 100 mg/day D. Dopamine agonist: They mimic the action of dopamine at receptor sites. Ergot class: Bromocriptine: 2.5 mg/ day in conjunction with sinemet Non ergot class: Pramipexole 0.125 mg/8hours Ropinirole : 0.25 mg/8hours
C. Adjuvant drugs: 1. Physiotherapy 2. Antioxidants e.g. vitamins C & E 3. Muscle relaxants for rigidity
2. Surgical treatment:
A. B. C. o o
Deep brain stimulation of globus pallidus or subthalamic nucleus Destruction of globus pallidus : pallideetomy, thalamotomy Recently: transplantation Autologous transplantation of suprarenal tissue in basal ganglia Fetal brain cell transplantation in basal ganglia 102
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Chorea
Definition :
The manifestation of chorea are due to neurotransmitter imbalance in the basal ganglia especially caudate nucleus due to decreased level of Gamma-Amino-Butyric Acid(GABA)
Characterized by involuntary static movements:Irregular, non-rhythmic(dysrhythmic) tremors: 1. 2. 3. 4.
Rapid Sudden jerky PSEUDO-PURPOSIVE movements Increased by emotion & stress Decreased by sleep. Involve any part of the body, including the face, trunk and/or limbs
Dementia
Etiology: A. Idiopathic: senile chorea
B. Heredofamilial: Huntington's chorea C. Secondary: 1. Immunological: rheumatic chorea
2. Infective: post encephalitic 3. Vascular: hemiballismus
4. Toxic: chorea gravidarum. 5. Tumors:tumors ofthe basal ganglia Clinical picture: Hemiballismus
Huntington's chorea
'
❖ Hemiballismus
Huntington's chorea
❖ Etiology
1 o
Vascular insult of comus luisii in suhthalamus
(infarction or hemorrhage) o
1
cerebral cortex
choreic movements
characterized by excessive grimacing & gross movements which interfere with feeding & walking 3. Cerebral cortex (frontal lobe) degeneration —» o Mentality & personality changes : amnesia, dementia & antisocial behavior
o Appearance of primitive reflexes Treatment:
1. Phenothiazines
2. Haloperidol to control movements 3. Genetic counseling to detect carriers Clinical varieties of chorea:
1. Classic type:see later in rheumatic chorea 2. Chorea gravis: Severe form which interfere with Speech, Swallowing & Sleep. 3. Chorea gravidarum:
o Occurs usually in primigravida(5* month)and may recur in subsequent pregnancy, o Due to stress of pregnancy associated with eclampsia & history of rheumatic chorea. 4. Hemichorea : affect one side 5. Maniacal chorea:excitement and insomnia
6. Chorea mollis(paralytic chorea): o Severe hypotonia where it may assume a hemiplegia or quadriplegia with absence of UMNL or LMNL o Choreic movement are still present.
103
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I
Rheumatic chorea: Sydenham's chorea ❖ Type of patient; o
One ofthe MAJOR criteria ofrheumatic fever
o May be associated with other rheumatic manifestations in 10% but never with rheumatoid arthritis, o ESR is normal(exudative lesion) o Age:5 -15 years o
Sex:females more than males
❖ Clinical picture:
1. Hyperkinesia: choreic movements
❖ 1. 2. 3. 4.
Involuntary static movements characterized by: Irregular, non-rhythmic (dysrhythmic) tremors Rapid Sudden jerky pseudo-purposive movements Increased by emotion & stress Decreased by sleep.
5. Affect tongue,face, trunk & extremities muscles, being more PROXIMAL than distal e.g.:
a. Excess grimacing of facial muscle b. Excess jerking movement of shoulder, shaking of hands and feet. c. Inability to keep the tongue protruded (unsupported by her teeth)
2. Hypotonia: 1. Muscle flaccidity 2. Inhibited deep r.eflex & kneejerk is pendular(large number of oscillations) 3. When the patient stretches his arms,there is Choreic hand (scaphoid or boat shaped hand) o
Flexion at wrist
o o 4. o 5.
Overextension at metacarpophalangeal and interphalangeal Joints Fanning offingers When the patient elevates and supinates his arms: They deviate downwards and laterally & become pronated. Speech is low
3. Emotional instability: sudden laughing or sudden crying. ❖ Treatment:
1. Treatment of rheumatic fever: bed rest, acetyl salicylic acid & prednisone 2. Treatment of rheumatic chorea: reserpine, haloperidol & tranquilizers.
104
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Athetosis
❖ Definition :
❖ Lesion in lentiform nucleus specially globus pallidus ❖ Involuntary static movements characterized by: 1. Irregular, non-rhythmic (dysrhythmic) tremors 2. Slow, Snake-like movements
3. Involve DISTAL muscles more than proximal muscles i.e. extremities (especially hands & fingers) and the face on each side
4. Associated with hypertonia
❖ Etiology:
1. Congenital: kernicterus (hyperbilirubinemia in infants) & hypoxic neonatal brain damage. 2. Acquired : post-encephalitic
❖ Treatment: Anticholinergic drugs
Dystonia ❖ Definition :
❖ Lesion in striatum
♦♦♦ Involuntary static movements characterized by: 1. Irregular, non-rhythmic (dysrhythmic) tremors 2. Very slow sustained muscle contraction leading to Torsion or Twisting like movements 3. Involve neck, trunk & PROXIMAL muscles of extremities
4. Associated with hypertonia during movement & normal tone in between
lia: j
Types of dystonia:
/■ '
\ 1.
deformans
o
11. Partial (focal): 2. Oromandibular dystonia
Generalized
Dystonia musculorum
Familial disorder which starts in childhood.
I. Cervical dystonia: Spasmodic torticollis (wry neck) o
3. Focal dystonia of the hand:
Writer's cramp
Dystonia of
o
sternomastoid leads to
turning of head to opposite side, specially when patient is walking
Constant biepharospasm (involuntary prolonged tight eye closure) associated with dystonia of mouth & jaw muscles
o
Spasm & pain in muscles of hand & forearm on
attempting to write
❖ Treatment:
0 Anticholinergics & dopaminergic drugs o Botulinum toxin injection o Myotomy or section of spinal accessory nerve 105
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Differential diagnosis of extrapyramidal irregular movements B. Athetosis
A. Chorea 1. Definition
C. Dystonia
❖ Involuntary static movements characterized by Irregular, non-rhythmic (dysrhythmic)tremors o Very slow sustained muscle 0 Slow Snake like 0 Rapid Sudden, contraction leading to Torsion or movements jerky Twisting like movements pseudopurposive
2. Lesion
0
Caudate nucleus
3. Site
0
Trunk and
0 Globus pallidus 0 Mainly in extremities
0
Striatum
0 Mainly in trunk and if in extremities proximal > distal (hands & finger) i.e. distal >
extremities
proximal o Hypertonia
0 Hypertonia during movement and
4. Tone
0 Hypotonia
5. Common
0
Rheumatic fever
0 Post encephalitic 0 Congenital
0
See before
o As parkinsonism
normal tone in between
causes
6. Treatment
0 Familial in the generalized type
Other abnormal movements: Tics:
Involuntary, Irregular, repeated simple movements due to stress or anxiety e.g. blinking & turning the head Drug Induced movement disorder e.g. Antipsychotics (neuroleptics) e.g. phenothiazine & haloperidol A. Acute dystonic reaction B. Neuroleptic malignant syndrome C. Tardive dyskinesia —> For more details see PSYCHIATRY book for the author
3. Fasciculations (involuntary muscle twitches):
Definition : Fasciculation means spontaneous contraction of GROUP of muscle, it's visible & even palpable N.B.: Fibrillation means spontaneous contraction of SINGLE muscle fiber, it's hardly visible except in tongue Technique: all limbs percussed by finger flickering or by light percussion by hammer Types:
v-'T
NeuromuKuw
junction
Spinal cord Musde fibers (cells)
A. Physiological fasciculation 1. Etiology
2. Type 3. Muscle Wasting
B. Pathological fasciculation
o Anxiety, fatigue, coffee, smoking o Irritation of AHCs e.g. a) MND,syringomyelia b) Peroneal muscle atrophy, cervical compression o
Coarse
o
Fine
o
Absent
o
Present
o Giant potentials
4. EMG
4. Myoclonus: ❖ Definition:
o Involuntary, irregular, sudden, briefjerky, shock-like contraction of a muscle or a group of muscles. ❖ Etiology: A. Epileptic disorders associated with myoclonus, e.g. aura of grand mal & myoclonic petit mal epilepsy B. Progressive myoclonus :
o Familial e.g. Lipid storage diseases o Degenerative: e.g. Alzheimer's disease C. Metabolic disorders associated with myoclonus: o Hyponatnemia & hypocalcemia o Renal, hepatic, or hypoxic encephalopathy. ❖ Treatment: clonazepam + treatment of cause
106
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Static tremors
o Rhythmic oscillatory movements due to alternating contraction of opposing muscles group appear at rest & disappear by movement
❖ Etiology: A. Fine; jamplitude, t frequency (rapid):
B. Coarse; f amplitude,jfrequency (slow):
O I' Sign : when the patient look to one side : a. Nystagmus in abducting eye (lateral rectus) b. Weakness in adducting eye (medial rectus)
114
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Motor Neurone disease(MND)
❖ Definition
(AHCs)
o It is a systemic degenerative disease of gradual onset and progressive course affecting the MOTOR SYSTEM ONLY WITHOUT sensory involvement, sphincteric disturbances, cerebellar sings or ocular nerve affection, o There is degeneration affects upper motor neuron(UMN)or lower motor neuron(LMN)or both in the brain & spinal cord. Etiology:
❖ The exact etiology is unknown: o May occurs as sporadic or familial (autosomal dominant).
UMN
Pathogenesis:
1. GLUTAMATE excitotoxicity: o Excessive stimulation of glutamate receptors on motor neurone cells may cause destruetion of motor neurone 2. Oxidative stress: super oxide dismutase mutation 3. Growth factors & immunoglobulin abnormalities
Clinical picture:
Glutamate excitotoxicity LMN
❖ Type of patient: 1. Age of onset: middle and old age
r
2. Sex : commoner in males
AHCs
3. Gradual onset and progressive course ❖ Clinical picture:
o Since it's a systemic disease; symptoms & signs are usually BILATERAL, o Depends on whether UMN or LMN or both are affeeted in the brain & spinal cord. ❖ Clinical types: 1) Brain stem lesion : 1.
U.M.N. affection:
11.
L.M.N. affection:
V 1. Syndrome of: 2. Degeneration of: 3. Clinically tetrad of:
4. Quadriplegia
Syndrome of pseudobulbar palsy:
❖ Syndrome of true bulbar palsy:
o Corticobulbar tract(UMNL)
0 Medullary cranial nerve nuclei(LMNL) 0 Dysphagia, Dysarthria, Dysphonia(loarseness of voice)& nasal regurgitation o Present with signs of UMNL in o Absent UL and LL
5. Jaw reflex
6. Emotional & mood
0 Present if lesion is above pons o Exaggerated emotional lability
0
0 Exaggerated
o
0 Spastie tongue
0 Flaccid, atrophic (small & wasted)tongue
o
o
Absent
o Lost emotional response
changes
7. Palatal & pharyngeal
Lost
reflex
8. Tongue & fasciculations
No fasciculations
Fasciculation's
115
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2)Spinal cord lesion:
U.M.N. affection
L.M.N.(AHCs)affection 1.
11.
U.M.N. affection:
L.M.N. affection:
❖ Syndrome of primary lateral sclerosis:
❖ Syndrome of progressive muscular atrophy
0 Degeneration of corticospinal tract with bilateral symptoms & signs of UMNL (paralysis, hypertonia, hyperreflexia , no or late mild wasting , no trophic changes & no &
o Degeneration of A.H.C with symptoms & signs of LMNL (paralysis, hypotonia, hyporeflexia, wasting ,trophic changes & fasciculation) o Weakness according to the affected site:
fasciculation)
■
0 Weakness according to the affected site:
Commonest site in lower cervical & lumbar
1. Spastic quadriplegia: if lesion at cervical region(C1 to C5)
region hence it stats early in UL distally(hands
2. Spastic paraplegia: if lesion is below cervical region
—» forearm ^ shoulder) and late in LL
3)Mixed lesion: there are combined symptoms & signs of upper & lower motor neuron lesion: A)Mixed spinal lesion: the commonest type (85%): ❖ Syndrome of AMYOTROPHIC LATERAL SCLEROSIS(ALS): A. In upper limbs: TONIC ATROPHY of muscles:
o COMBINED signs of LMNL (weakness, wasting & fasciculations)& UMNL (hypertonia and hypereflexia) B. In lower limbs:
o Weakness with signs of UMNL
❖ The definite diagnosis of ALS requires the presence of upper & lower motor lesion signs in at least 3 spinal
regions (cervical, thoracic, lumbosacral) without bulbar region OR 2 spinal regions PLUS involving bulbar region (muscles of the face, mouth, and throat).
B)Mixed bulbar lesion: Mixed bulbar palsy & similar picture of combined affection.
❖ Differential Diagnoses:
1. From other causes of pseudobulbar palsy e.g. Multiple Sclerosis 2. From other causes of true bulbar palsy e.g. Guillain-Barre syndrome
3. From other causes of limb UMNL signs e.g. syringomyelia & cervical spondylosis with myelopathy 4. From other causes of limb LMNL signs e.g. Spinal Muscular Atrophy Investigations
A. Biochemical: it may show f Creatinine phosphokinase & f CSF protein . B. Radiological:
o MRI of brain 8c cervical spine to exclude other causes that mimic MND e.g. cervical spondylosis C. Instrumental: Nerve conduction studies and electromyography(EMG):
o For confirming the diagnosis of MND and for excluding other causes that mimic MND. Edaravone
Treatment:
A. Supportive treatment:
Na
tatanmi Ei
Riluzole
1. Genetic therapy under trial
2. Vitamins especially vitamin E helps retention of creatine in body Glutamate
3. Physiotherapy
ROS production
B. Drugs that may slow the functional decline in patients with MND: 1. RILUZOLE: ANTI-GLUTAMATE DRUG Cell death
2. EDARAVONE: ANTIOXIDANT DRUG
116
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Demyelinating diseases Mitochondrion
V)' Nucleus
❖ Introduction :
Axon
m
terminal
Myeiin
'^^/sheath
Dendrite
%
Node of
Synapse
%^ranvier schwann cell Axon
The basic unit of communication in the nervous system is the nerve cell (neuron); which is formed of: Dendrites
Cell body Axons which could be:
A. Myelinated nerve fiber
B. Unmyelinated nerve fiber
o Surrounded by myeiin sheath so has faster nerve impulse transmission, o Not surrounded by myeiin sheath so o Myeiin sheath formed by :
has slower nerve impulse
a) Oligodendroeytes in the CNS (brain & spinal cord) b) Schwann cells in the PNS (cranial & spinal nerves)
transmission
4. Axon terminal
❖ In neuropathies, the nerves may be damaged in CNS or PNS at: 1. Cell body —> neuronopathy 2. The axon —> axonopathy 3. The myeiin sheath —> myelinopathy
Demyetination in MS
cell body
damaged myeiin (demyelination) myeiin!
nerve fibre (axon
Demyelinating diseases ❖ Definition :
o Diseases charaeterized by loss of myeiin sheath of neurons that may be permanent or recurrent. ❖ It includes:
I.
Demyelinating disorders of the central nervous system:
A. Myelinoclastic disorders, in which acquired factors attack PREFORMED normal myeiin: Immune-mediated inflammatory ;
MULTIPLE SCLEROSIS(MS)= Disseminated Sclerosis(DS) Acute Disseminated encephalomyelitis(ADEM) Neuromyelitis optica (Devic's disease) Infection e.g. progressive multifoeal leukoencephalopathy
Toxins e.g. central pontine myelinolysis and extrapontine myelinolysis: a) Etiology:
ICU patients with rapid correction of hyponatremia Alcoholic liver & liver transplantation b) Clinical picture : of the cause with :
Pontine myelinolysis(pons & lower midbrain): bulbar symptoms with quadriplegia Extrapontine myelinolysis (cerebellar & extrapyramidal manifestation) e.g. Ataxia, Parkinsonism, Choreoathetosis & Dystonia.
Leukodystrophic disorders (dysmyelinating), in which genetic factors attack normal myeiin SYNTHESIS or turnover e.g. metachromatic leukodystrophy 11.
Demyelinating disorders of the peripheral nervous system:
1. Guillain-Barre syndrome
2. Chronic inflammatory demyelinating polyneuropathy 117
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Multiple Sclerosis(MS)= Disseminated Sclerosis(DS)
❖ Definition:
❖ It is immune-mediated inflammatory demyelinating disease that attacks myelinated axons in the central nervous system (brain & spinal cord) characterized by : 1. Affection of white matter of CNS
2. Resulting in multiple plaques of demyelination of CNS with reactive gliosis resulting in impairment of its function. 3. Distribution is patchy in CNS,and lesion can be easily detected by MRl.
,
eel bo^ ^
axon damaged myelln
myolin
❖ Etiology: ❖ Unknown most probably due to autoimmune mechanism: •' distorted messages 1. CSF examination shows increase in immunoglobulin content specially immunoglobulin G 2. Genetic association with HLA-DRBl.
3. Associated with other autoimmune Diseases e.g. autoimmune thyroiditis, DM type 1 4. Patient improves with immunosuppressive Drugs ❖ Pathogenesis:
o Antibodies occurs against myelin sheath ofthe axons ^ inflammation & injury to the nerves -> scaring (sclerosis) ^ impaired nerve signal transmission NORMAL
INFLAMED
DETACHED
SCARRED
❖ Precipitating factors: 1. 2. 3. 4.
Pregnancy & labour Physical fatigue Infection e.g. Epstein-Barr virus(EBV) Stress, Surgery, Trauma
5. Low vitamin D levels
❖ Clinical picture:
A. Type of patient & onset & course of the disease:
1. Age : 3'''^ & 4"^ decades 2. Sex : commoner in females
3. Onset & course : acute or gradual onset with remission & exacerbation
4. Symptoms & signs: any myelinated area of CNS can be affected B. Clinically:
1- General constitutional symptoms:
1. FATIGUE,PAIN (neuropathic or muscuioskeletai) and exertional exhaustion 2. Lack of sleep and dizziness 2- Mentality dysfunction:
1. Cognitive impairment: lack of attention, concentration, memory, and judgment. 2. Dementia, DEPRESSION,Euphoria, Emotional lability or Epilepsy .
3- Speech dysfunction: Dysarthria e.g. Slurred, Staccato or Scanning speech j 118
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4- Cranial nerve dysfunction:
1. Optic nerve(CN2)affection : OPTIC NEURITIS; o Painful eye movement o BLURRED VISION(COMMON) o
Visual field & color vision defects
o VISUAL LOSS(COMMON)
Temporal pallor of optic disc (characteristic)
o
Oculomotor nerve(CN3)affection: DIPLOPIA(COMMON) Ophthalmoplegia
2.
Internuclear ophthalmoplegia (characteristic) Trigeminal nerve(CN5)affection : Trigeminal neuralgia;
o
3.
FACIAL NUMBNESS(COMMON) Facial nerve (CN7):
o
4.
FACIAL WEAKNESS: unilateral or bilateral facial palsy of UMNL(COMMON)or LMNL(rare) Hemifacial spasm or facial myokymia (characteristic): irregular painless twitching of the facial muscles
o
o
Cochleo-vestibular nerve affection (CN8): VERTIGO(COMMON) Clossopharyngeal(CN9)& vagus(CNIO) affection : pseudo bulbar palsy (rare)
5. 6.
5- Spinal cord dysfunction:
1. Motor system dysfunction (UMNL): muscle cramping secondary to spasticity o Monoparesis, hemiparesis
o PARAPARESIS,quadriparesis (N.B. symptoms may be associated with acute transverse myelitis) o 2. A. o o
Pseudobulbar palsy Sensory system dysfunction: Spinothalamic tract lesion : Early patient complains of PARESTHESIA Late : superficial sensory loss
TOILET
B. Posterior column lesion :
o Deep sensory loss with sensory ataxia
o Positive Lhermitte's Sign: Electric like sensation in the back & limbs on bending the neck due to posterior column affection in the cervical region. 3. Autonomic dysfunction:
o Bladder dysfunction: URGENCY(COMMON),incomplete bladder emptying , incontinence o Bowel dysfunction: CONSTIPATION(COMMON),incomplete bowel evacuation, incontinence o Sexual dysfunction : impotence 6- Cerebellar system dysfunction:
Features of cerebellar ATAXIA e.g. gait disturbance, dysarthria , nystagmus, and kinetic tremor. 7- Uhthoffs phenomenon: HEAT INTOLERANCE:
o Worsening of symptoms in multiple sclerosis when the body gets overheated e.g. from hot weather, exercise & fever.
o Mechanism, increase in body temperature slows or block the conduction of nerve impulses in demyelinated nerves ❖ N.B.: THE CLASSIC EARLY SYMPTOMS OF MS IN BLUE COLOR. 119
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
C. Clinical types: courses :
RRMS
SPMS
PPMS
PRMS
1. Relapsing remitting MS: 85 % a. Benign MS: attacks of temporary neurological deficitsfollowed by period ofremission b. Malignant MS: attacks of permanent neurological deficitsfollowed by period ofremission 2. Progressive MS: 10% a. Primary progressive MS:
o b. o 3. o
Since onset of the MS, continuous deterioration occurs without periods ofremission Secondary progressive MS: After years of relapsing remitting MS,continuous deterioration occurs without periods ofremission Progressive relapsing MS:5% Since onset of the MS,continuous deterioration occurs with superimposed A D. N.B:
A. Clinically isolated syndrome: possible MS
o First attack of the disease e.g. optic neuritis, suggestive of MS lasting for at least 24 hours, but not fulfilling diagnostic criteria of MS B. Radiologically isolated syndrome: radiological evidence suggestive of MS in absence of clinical evidence. ❖ Differential diagnosis: A. From other immune-mediated inflammatory demyelinating diseases e.g.: 3. Neuromyelitis optica 2. Progressive multifocal 1. Acute disseminated encephalomyelitis leukoencephalopathy(PML): (Devic's disease) (ADEM) ❖ Differentiating points of MS: monophasic illness characterized by :
❖ Triggered by viral infection or postvaccination with :
1. Acute onset with fever
2. Encephalitis (symptoms & signs of parenchyma! involvement e.g. behavioral and personality changes)
with encephalopathy : 0 Confusion, Convulsion, Coma 3. Spinal cord : acute transverse myelitis
❖ Restricted to: ❖ Triggered by viral(John 1. Optic nerve: optic Cunningham virus) infection neuritis with multifocal signs e.g.: 2. Spinal cord : acute 1. Frontal lobe: hemiparesis & transverse myelitis behavioral and personality changes 2. Parietal lobe: aphasia 3. Occipital lobe: hemianopia 4. Cerebellum : ataxia
4. Signs of meningismus (meningeal irritation) ♦♦♦ Investigations: serology (autoantihodies & CSE)& MRI can differentiate between them. B. Spinal cord lesionSi:
1. Spinal cord inflammation e.g. acute transverse myelitis 2. Spinal cord infarction e.g. acute anterior spinal artery occlusion 3. Spinal cord compression e.g. astrocytomas
4. Spinal cord degeneration: subacute combined degeneration ofthe spinal cord (vitamin B12 deficiency) C. Others :
1. NeuroSyphilis 2. Sarcoidosis
3. Vasculitis : Neuro-Beh9et's disease, SLE & PAN 4. Paraneoplastic Encephalomyelitis
120
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Investigations:
1. Fundus examination:
IgG uniform band
Revised McDonald's criteria for diagnosis of multiple sclerosis:
Dissemination in space
A. Attack:
o
Dissemination in time
B. Clinical lesion :
C. Requirements for diagnosis for MS: one of the following :
0
>2
0
1
❖ Dissemination in space, demonstrated by : A or B A. > 1 MRI lesion in > 2 areas in brain or spinal cord
>2 0
Non
B. Further clinical attack at different CNS site
❖ Dissemination in time, demonstrated by : a or b or c a. Old or new MRI lesion o o
>2
1
o 0 0(insidious neurological deficit suggestive of MS; primary progressive MS)
1 (clinically isolated syndrome)
b. Further attack at different time
c. Positive CSF oligoclonal bands ❖ Dissemination in space AND time demonstrated by ; o
One of A or B or C PLUS one of a or b or e
o 1 year of disease progression AND at least 2 of the following : 0
—
a. > 1 brain MRI lesion
b. >2 spinal cord MRI lesion c. Positive CSF oligoclonal bands
Treatment:
1- General:
1. Avoid precipitating factor 2. Physiotherapy & vitamins 3. Symptomatic treatment for corresponding lesion e.g. paraplegia 2- Remission induction: treatment of MS with acute relapse (exacerbation): 1.
Corticosteroids:
A. Start by:
o ACTH :80 lU by IM/day for 1 weeks, then 40 lU/day for another week OR o Methyl prednisolone: 1 gm IV infusion /day for I weeks 6. Continue with:
o Prednisone 1 mg/kg/day orally for 1 week, then gradual tapering 2. IVIG & Plasmapheresis if not responding to corticosteroids
Methylprednisolone
IsOLU-MEDRe i 1000m lOOOmg
3- Remission maintenance: prophylaxis against relapses: Aim:
1. To decrease frequency and severity of relapses 2. To prevent worsening of the condition
A.Immune modulators drugs: disease modifying agents for MS: o Interferon beta-la, interferon beta-lb
o Alemtuzumab, natalizumab, ocrelizumab, daclizumab o
Cladribine
o Glatiramer acetate, mitoxantrone, teriflunomide o Fingolimod, dimethyl Fumarate
B.Immunosuppressive drugs: Methotrexate, Azathioprine, Cyclophosphamide.
I lmuran
Azathioprine Tablets
122
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Peripheral neuropathy
❖ Definition
o Inflammation (neuritis) or degeneration of the peripherai nerves ± cranial nerves resulting in impairment of the conductivity ofthese nerves leading to motor, sensory & autonomic manifestations (autonomic neuropathy). ❖ Types:
1. Mononeuropathy: focal type Definition: affection of single nerve in one limb Classifications: A. B. ❖ o o o
Acute: trauma, ischemia or inflammation e.g. sustained pressure by tourniquet or wrong injection Chronic compression: the most common cause; ENTRAPMENT(COMPRESSIVE)NEUROPATHY; Etiology :
Obesity, Myxedema Amyloidosis, Acromegaly, rheumatoid Arthritis Pregnancy, CKD patient on hemodialysis,DM
o o o 0 o o
Meralgia paresthetica Tarsal tunnel syndrome Peroneal tunnel syndrome Radial tunnel syndrome Cubital tunnel syndrome Carpal tunnel syndrome
A. Compressed nerve: B. Site of compression: 0 Lateral cutaneous nerve of thigh o Under inguinal ligament o
Posterior tibial nerve
o
At tarsal tunnel
o Common peroneal nerve
o
At head of fibula
o
Radial nerve
o
At arm
o
Ulnar nerve
o
At elbow
0
Median nerve
0
Under flexor retinaculum
Clinical picture of carpal tunnel syndrome:
Wasting & weakness of mainly in thenar muscles (adductor pollicis brevis) Pain & sensory loss in lateral palm, thumb index and middle finger and lateral half of ring finger Exacerbation of pain by : o Flexion of wrist; Phalen sign o Tapping retinaculum : Tinei sign Treatment:
o Local steroid injection o Surgical decompression
2. Mononeuropathy multiplex (multiple mononeuropathy); multifocal type Definition : affection of> 2 nerve in one limb. Etiology: 1.
Infective: Lyme disease, Leprosy, parvovirus B19, HIV
2.
Immunological:
o
Sarcoidosis
o
Collagen diseases e.g. Rheumatoid arthritis, PAN,SEE, Scleroderma
o
Vasculitis e.g. Cryoglobulinemia, Churg Strauss Syndrome , Wegener's Granulomatosis
3.
latrogenic:irradiation
4.
Metabolic/endocrinal: amyloidosis & DM 123
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
3. Polyneuropathy; generalized type: ❖ Definition:
o
Clinical syndrome characterized by BILATERAL SYMMETRICAL affection of peripheral and / or cranial nerves leading to motor, sensory & autonomic manifestations. Etiology:
A. HEREDOFAMILIAL:
o Peroneal muscle atrophy o Hypertrophic interstitial polyneuropathy o
Friedreich's ataxia
o
Refsum disease
B. SECONDARY(ACQUIRED):
□ 1.
Infective :
o o o o 2.
Viral e.g. Rabies, mumps, measles Bacterial e.g. Diphtheria Mycobacterial e.g. Leprosy Critical illness polyneuropathy : due to sepsis Immunological:
o
Sarcoidosis
o o o 3. a) b) o o 4. 5. 6. o o
Collagen diseases e.g. Rheumatoid arthritis, PAN, SLE, Scleroderma Guillain-Barre syndrome Chronic inflammatory demyelinating polyneuropathy latrogenic; drugs & toxins: Drugs: INH, sulfonamides, steroids Toxins : Inorganic : metal neuropathy due to lead, arsenic, mercury neurotoxicity Organic : alcohol Metabolic: Amyloidosis, Porphyria, Chronic Renal Failure & DM Endocrinal: acromegaly, myxedema, thyrotoxicosis Neoplastic: Bronchogenic carcinoma. Leukemia, Lymphoma Paraproteinemic polyneuropathy e.g. multiple myeloma & Waldenstrom macroglobulinemia
7.
Nutritional:
❖ Vitamin deficiency ❖ Clinical picture: o B1 (thiamine)
o
o B3(niacin) o B6(pyridoxine) o B12(cobalamin)
o Pellagra o Sideroblastic anemia, sensory neuropathy, dermatitis o Subacute combined degeneration(SCD)of spinal cord
Beri beri
124
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ General clinical picture of POLYneuropathy:
1
Motor:
❖ Bilateral & symmetrical weakness or paralysis of LMNL; resulting in 1. Weakness & wasting in LL > UL, distal muscles > proximal muscles, extensor > flexors; leading to Bilateral foot & wrist drop (weakness of distal extensors) 2. Muscle tone: Hypotonia
3. Hyporeflexia or absent deep reflexes with early loss of ankle & preserved knee reflex . 4. High steppage gait due to foot drop 5. Cranial nerve palsy specially 3,6,7,10. ■%
2. Sensory:
❖ Affecting SAME distri rution: distal nerve affection ❖ Sensation affected
A. Early: B. Later:
1. Superficial sensation:
2. Deep sensation: 0 Tender calf muscles e.g. DM & Guillan - Barre syndrome 0 Superficial sensory loss: glove o Deep sensory loss e.g. loss of muscle & vibration & stocking hyposthesia sense. o Hyporeflexia or absent deep reflexes with early loss of ankle & preserved knee reflex . o Sensory ataxla
0 Pain & paresthesia
❖ N.B: deep reflexes: decreased (hyporeflexia) or lost (areflexia) in peripheral neuropathy due to LMN lesion of the reflex arc due to affection of sensory (afferent) nerve fibers or motor (efferent) nerve fibers.
3. Autonomic: autonomic neuropathy (see later in diabetic neuropathy).
4. Specific features : according to etiology (see below)
125
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Specific types of polyneuropathy
Peroneal muscuiar atrophy Charcot-Marie-Tooth disease
Hereditary motor and sensory neuropathy type I
Incidence:
o Heredofamilial autosomal dominant polyneuropathy of gradual onset & very slow progressive course occur in & Z""* decades.
❖ Ciinicai picture: Swiiw
I
iiiil^
1- Motor:
❖ Bilateral, symmetrical polyneuropathy of gradual onset & very slow progressive course occur distaiiy eariy in LL then progress later to U.L.: 1. Muscle state: Wasting occur distaiiy early in LL,later on UL may be affected:
o Wasting starts in peronii muscle then the anterior tibial group, then ascend to involve muscles of lower 1/3 ofthe thigh resulting in inverted Champagne Bottle appearance o Wasting offorearm occurs later. 2. Muscle power: Marked discrepancy between wasting & weakness; this is very peculiar to this disease : o MARKED degree of muscle WASTING with mild degree of muscle weakness o It is due to its very slow course and elastic tissue replacement of muscles 3. Muscle tone: hypotonia; frog position
2- Sensory: 1. Impaired superficial sensation e.g. glove & stocking hyposthesia 2. Impaired deep sensation e.g. o
Loss of vibration sense
o Loss of deep reflexes 3. Hypertrophic neuropathy: visible & palpable nerves e.g.
Common
o
Peroneal nerve felt at neck offibula
nerve
o
Ulnar nerve felt at the elbow
peroneal
Fibula
3- Skeletal deformities:
\\\\ o FES CAVUS,hammer toes, talipes equinus, kyphoscoliosis 4- ± Associations:
1. Degeneration of AHCs -* Fasciculations. 2. Degeneration of pyramidal tract —» Babinski sign 3. Degeneration of cerebellum —» Friedreich's ataxia. 126
Fnedreich*s ataxia
%
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
phytanic acid in tissues
accumulation of
Due to lack of phytanic acid hydroxylase enzyme(essential for phytanic acid metabolism) —>•
& l""* decades
storage disease during P'
Heredofamilial lipid
Nerve deafness
cranial never:
o
Plasmapharesis
diet
units IM
serum 100.000
Antidiphteritic
o
o
Restrict phytanic acid in
type: affecting peripheral nerve mainly motor
2. Generalized
3,7,10
Lymphadenopathy & fever
o o
o
o
7
Cranial never:5&
thickening
exposure in occupation
to chronic
poisoning due
Chronic lead
UL > LL
❖ Treatment:
patches o Glove & stocking hyposthesia with trophic changes (ulcers, gangrene)
Maculoanesthetic
o
127
poisoning due to chronic exposure in occupation
Chronic arsenic
Mainly sensory LL > UL
Mainly sensory
o
Stop exposure to offending agent.
o
o
vitamin Bl.
particular
Vitamins
Stop alcohol
(see GIT)
of alcoholism
confabulation
psychosis.
Amnesia,
syndrome:
4. Other features
o
b. Korsakoff
encephalopath y: ataxia. ophthalmoplegi a, confusion.
a. Wernicke
syndrome:
Korsakoff
of Wernicke —
3. Clinical picture
o
alcoholism.
in gums,colic. constipation
diarrhea
c) GIT:jaundice.
of skin
3) Other clinical picture of chronic arsenic poisoning a) Hyperkeratosis of palm & sole b) Depigmentation
o
o
Alcohol intake
1. History of
o
Alcoholic
neuropathy
d. GIT : blue line
hypertension
c. CVS:
encephalopathy
b. CNS:
anemia
Skin :
sideroblastic
hemolytic anemia.
a. Anemia :
poisoning:
chronic lead
3) Other clinical picture of
o
2) Distribution : o Mainly motor
nerves
3.
o
Arsenic neuropathy
1) History of occupation
o
Lead neuropathy
auricular, ulnar, & lateral popliteal
o Peripheral neuropathy(mainly sensory) e.g. great
o
2. Nerves: irregular
immunity
1. Good cell mediated
type:
B. Maculo-anesthetic
Clinical picture:
Dapsone : 100 mg day/orally for 2 years Rifampicin: 600 mg/day orally for 6 months
Nose destroyed septum & epistaxis
—> leonine face
Nodules over face
3. Skin & mm :
o
2. Systemic :
immunity
No cell mediated
1.
1. Localized type :affecting
❖
J.VR —>J.BP—> reflex f HR GIT: Gastric-emptying tests for delayed gastric emptying Genitourinary : urodynamic tests for urinary bladder function Sudomotor (sweat glands function): axon reflex test or thermoregulatory test 1,1,III
.Ml
129
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Landry-Guillain-Barre Syndrome Acute Infective Polyneuropathy
Acute Inflammatory Demyelinating Poly- Radiculo - Neuropathy(AIDP) Exposed axon^
Etiology:
❖ Auto-immune disease secondary to URT of GIT infection : 1. Bacteria : Campylobacter jejuni: the most common
2. Viruses: Cytomegalovirus (l"** most common),EBV
Damaged myelin
❖ Pathogenesis:
o Infection ^ antibodies against the myelin sheath of the peripheral nervous system (cranial & spinal nerves) • immune demyelination Clinical picture: A. Febrile stage :
o Influenza like picture e.g. FHAM without nervous symptoms B. Latent stage:
o The patient is asymptomatic for 1- 4 weeks C. Paralytic stage: 1. Motor: acute onset of severe weakness of ASCENDING in nature:
o Flaccid paralysis of LL—>• trunk —> respiratory muscle (respiratory failure) o Characteristically PROXIMAL weakness more than distal (contrary to other types ofPN) o No wasting despite of severe muscle paralysis 2. Sensory : a) Superficial sensation: o Early : pain & paresthesia
o Later; superficial sensory loss: glove & stocking hyposthesia b) Deep sensation : Early : tender calf(t muscle sense)
1.
ii.
o o o 3.
Later : deep sensory loss : Loss of deep sensation e.g. lost muscle sense Loss of deep reflexes Sensory ataxia Cranial nerves especially 3,1,9 8c 10 e.g. bilateralfacial palsy with bulbar symptoms Differential diagnosis:
B. Chronic inflammatory demyelinating
A. Landry-Guillain-Barre
polyneuropathy
Syndrome 1. Onset & Course
0 Acute onset with rapidly
2. Muscle weakness
0
Proximal more than distal
3. Cranial nerves
o
Affected
4. Nerve conduction
o Patchy slowing of motor
progressive course over weeks
0 Diffuse slowing of motor conduction
conduction
studies
5. Respond to
o Gradual onset with slowly progressive course over months (at least 2 months) o Affection of proximal & distal muscles o Not usually involved
0
o
Ineffective
Effective.
Corticosteroids
Investigations:
1. CSF : CYTOALBUMINOUS DISSOCIATION :
o t CSF protein (due to inflammation of nerve roots), with normal WBCs count 2. Biochemical: fESR,fPNLs (leukocytosis) 3. Serology: Antibodies to glycolipids of myelin sheath : positive in 70 % of patients 4. Electrophysiological studies : nerve conduction studies o Early normal o After weeks show marked patchy (multifocal) slowing of motor conduction
130
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Treatment:
if!
A. General treatment: Bed rest, Physiotherapy, vitamins B. Symptomatic treatment e.g. respiratory failure
lid
C. Specific treatment:
tll.-G!obu!inS"
o Plasmapheresis & IVIG (intravenous immunoglobulins): treatment of the choice o Corticosteroids was used before & proved to be INEFFECTIVE. ❖ Prognosis: o
Good in 85 % of cases
o Recovery occur within 3-4 weeks
Deficiency diseases 1- Beri- Beri:
„
Pyruvate
Thiamine .
■
AGetaldeliycljei
pyruvatp ^MorlViuo ^
decafboxMl§fie
^OllCT fflOM
❖ Etiology : o J, vitamin B1 (J,Thiamine)^ —>], pyruvate decarboxylase which is essential for CHO metabolism production with f pyruvic acid. ❖ Types: 1. Wet type : in children : high CO failure & edema 2. Dry type : in adults: polyneuropathy mainly sensory 3. Cerebral type :
I energy
o Wernicke's encephalopathy (confusion, amnesia, ataxia, nystagmus & ophthalmoplegia) ❖ Investigations: o I Thiamin in blood & urine while pyruvic acid f o Therapeutic test with vitamin B1 ❖ Treatment:
o Thiamine lOOmg daily and vitamin B complex o Treatment of complications e.g. HP 3- Subacute combined degeneration (SCD)of spinal cord
2- Pellagra:
^wnuwi mi
I inrii 1 1 i i i i i i i
.1.iiiiiuLi»wew«wwaT^
Blood
CNS: cerebral cortex degeneration (dementia). Peripheral nerve degeneration (1), Pyramidal tract degeneration(2)
3- Posterior column degeneration
131
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Deficiency diseases Subacute combined degeneration (SCO)of spinal cord
Pellagra
❖ Definition:
o Combined bilateral degeneration of subacute onset of posterior columns, pyramidal tracts & peripheral
Multiple deficiency disease due to lack of vitamin B3 (niacin) or its precursor tryptophan.
nerves as a result of vitamin B12 deficiency ❖ Etiology: 1. i intake
o
o Dysphagia
Deficient intake of vitamin B
o Deficient intake of protein of high biological value e.g. maize eater 2. i absorption:
Starvation
o Malabsorption
o Lack of animal product e.g. Vegetarians A. Gastrectomy, gastritis, gastric carcinoma B. Pernicious anemia (Addison anemia)
o
C. Heal disease:
o
Gastroenteritis Parasitic infestation
o Regional ileitis, T.B, Diphylopotharium latum o Blind loop syndrome & Malabsorption syndrome D. Drugs e.g. colchicine & neomycin.
o Drugs e.g. isoniazid
I storage: T requirements:
o
Liver cirrhosis
Liver cirrhosis
o
Carcinoid tumor (excess
o Pregnancy
conversion of tryptophan to serotonin)
o Malignancy
5. t 'oss:
6. i Utilization:
o Hartnup's disease (renal loss of Tryptophan)
o Inbom enzyme deficiency o
Lack of transcobalamin 11.
❖ Clinical picture Cutaneous: dermatitis
A- Blood: Megaloblastic Anemia :
Bilateral & symmetrical dermatitis followed by byperkeratosis (rough, scaly, desquamated skin)&
1. 2. 3. —>
pigmentation. Site :
Anemia ((, RBCs), Liability for infection (], WBCs) Bleeding tendency (J, platelets) For more details see hematology bookfor the author.
a®
Sun exposed areas: face, neck, dorsum of hand Friction areas: trochanters, elbow,, knees, heels GIT: diarrhea:
Mouth: Stomatitis & atrophic glossitis (red painful glazed tongue) Stomach: Dyspepsia, anorexia, nausea & vomiting Intestine: Diarrhea
Organs : Hepatosplenomegaly CNS:
Manifestation due to cerebral cortex degeneration: Dementia & Depression
Manifestation due to peripheral nerve degeneration: peripheral neuropathy(mainly sensory): a) Muscle tone: hypotonia b) Sensation:
1) o o 2) o
Superficial sensation: Early : pain & paresthesia Later: superficial sensory loss: glove & stocking hyposthesia Deep sensation : Deep sensory loss
o Lost ankle reflex 3. Manifestation due to pyramidal tract degeneration: o Bilateral A lesions in the spinal cord from below upwards,
so early paraplegia(LL weakness)& later quadriplegia (four limbs weakness) o Reflex: Exaggerated knee reflex with Babinski sign 4. Manifestation due to bilateral posterior column degeneration: o Deep sensory loss with SENSORY ATAXIA
The distribution of vibration sense by tuning fork can discriminate deep sensory loss due to peripheral nerve degeneration (j on medial malleolus) or due to posterior column degeneration ([on anterior superior iliac spine) ❖ Treatment: Ofthe cause + :
Vitamin B12, Img IM repeated 5 times with 2 days
1. Diet rich in protein and vitamin B complex. 2. Nicotinamide: 500 mg IV/day
interval then 1 mg every 3 months for life.
132
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Neuromuscular Junction Lesion
1. Immunological: myasthenia (primary, neonatal, congenital), Lambert—Eaton myasthenic syndrome 2. Infection: botulism
Primary Myasthenia: Myasthenia Gravis ❖ Definition:
o Disorder of transmission at neuromuscular junction, manifesting clinically by easy fatigability of skeletal muscles, especially on repetition of movement, relieved by rest. Etiology:
Acetylcholine'.ti
AUTO-IMMUNE disease:
Antibody
Thymufl
Normal
1. Anti acetyl choline receptor antibodies(85% of cases):
o There is produetion of antibodies against post-synaptic nicotinic acetylcholine receptors at the neuromuscular junction leading to their destruction. 2. Thymic dysfunction(75% of cases) lead to :
o Antibodies released from B lymphocytes defectively controlled by T lymphocytes due to thymic gland dysfunction (thymic hyperplasia or thymoma) with increased rate of receptor destruction. Triggering factors:
1. latrogenic (drugs) e.g. Aminoglycosides, Penicillamine, Ciprofloxacin 2. Immunization, Infection
3. Stress, Surgery
4. Menstruation, Pregnancy and Postpartum period r
Ll
Clinical picture:
A. Type of patient, onset & course:
o Age & sex : usually 20-40 years & more in females
o B. a) b) c)
Gradual onset with relapsing & remitting course The disease affects skeletal muscles ONLY & characterized by : Easy fatigability of muscles on repetition of movement(exercise)& relieved by rest. Diurnal variation: the motor power is good in the early morning & is worst at the end ofthe day Associations e.g. Thymic hyperplasia, Thymoma, Thyrotoxicosis
d) DESCENDING march course, affecting the following muscles :
1. Ocular:
The earliest site —> external ophthalmoplegia: ptosis, diplopia & squint(N.B. pupils are never affected). In some cases they may be the only museles affected WITHOUT systemic involvement throughout illness: it's called OCULAR MYASTHENIA GRAVIS 2.
Jaw muscles: hanging jaw
o
Leading to hanging open mouth, with impaired speech occur
3. Facial muscles : o
Leading to an expressionless appearance with bilateral weakness of eye closure On smiling there is a charaeteristic smile : myasthenic snarl; everted lips without retraction due to buccinators weakness
Bulbar(true bulbar palsy): Dysphagia, Dysarthria, Dysphonia (hoarseness of voiee)& nasal regurgitation 133
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I
5. Skeletal muscles of the body(GENERALIZED MYASTHENIA GRAVIS):
/6l^o\
s/
UL > LL, proximal muscles > distal muscles —> leading to affection of shoulder girdle. Neck muscles affection leads to head drop
Respiratory muscles affection leads to dyspnea & respiratory failure Cardiac muscles affection leads to HF & DEATH N.B.:
Atrophy is late
Reflexes and sensory exams are normal i.e. purely motor disease Crisis:
B. Cholinergic crisis
A. Myasthenic crisis
o Inadequate anticholinesterase treatment
1. Etiology 2. Pathogenesis
3. Clinical picture
4. Diagnostic test:
o
Excessive anticholinesterase treatment
o o 1. 2.
Drug induced, infection, surgery o tacetyl choline at the motor end plate i acetyl choline at the motor end plate Sudden generalized weakness especially respiratory muscles; respiratory distress 2) With muscarinic symptoms e.g. miosis, Without muscarinic symptoms salivation, bradycardia,... o Worsening 0 Improvement
Edrophonium test 5. Treatment
o
Anticholinesterase
0
Mechanical ventilation
o Stop Anticholinesterase o Give Atropine 0 Pralidoxime 500 mg IV
o Plasmapheresis Investigations: A. Clinical test:
1. Induction of fatigue by repetition of movement: o Ask patient to look upwards then after 2 seconds ptosis occur & movement of eye slowly downwards to neutral position 2. Walker's test:
o Apply the sphygmomanometer cuff to the arm and raise the pressure above the systolic & ask the patient to do rapid repetitive movements with his hand till exhaustion occurs, o Then release the cuff; if the case is myasthenia, ptosis will occur within 10 seconds (acidosis release Igfrom motor end plate) B. Pharmacological test: 1. Neostigmine test:
o 2.5 mg IM neostigmine —> improvement of muscle fatigue & ptosis in 20 minute 2. Edrophonium test:
o 8 mg IV edrophonium —> improvement of muscle fatigue & ptosis in 2 minute C. Laboratory tests: 1. Serology:
1) First investigation:
0 85 % of patients are seropositive myasthenia gravis: positive anti acetyl choline receptors antibodies
2) Further investigations :
o
Anti-striated muscle antibodies &
anti titin antibodies suggest presence of thymoma
o 15 % of patients are seronegative myasthenia gravis i.e. negative anti acetyl choline receptors antibodies 0 Positive anti muscle specific kinase antibodies(MuSK).
2. Radiological: X-ray chest, CT, MRI: for thymoma 3. EMG; characteristic decremental(|amplitude) response with repetitive stimulation 4. Muscle biopsy: lymphorrhages i.e.ft lymphocytes around MEP
134
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Treatment;
A. Treatment of the cause e.g. thymoma o Thjmiectomy or thymus irradiation
B. Treatment of complications e.g. myasthenic crisis or cholinergic crisis; see before. C. Specitic treatment:
1. Anticholinesterase drugs:
o They interfere with cholinesterase, the enzyme responsible for the breakdown of acetylcholine, allowing receptor stimulation.
o Neostigmine: 15 mg/8hours o Pyridostigmine: 60mg/8 hours
❖ N.B.: Add atropine (muscarinic inhibitor) to block unwanted muscarinic action ofreleased acetyl choline. 2. Corticosteroids:
o In patient not responding to anticholinesterase drugs 3. Immunosuppressive:
o Azathioprine & cyclophosphamide in patient not responding to corticosteroids 4. IV Immunoglobulins(IVIG)& plasmapheresis to decrease level of anti-acetyl choline receptors antibodies N.B,: Thymoma in internal medicine:
1. Aplastic anemia(pure red cell aplasia) 2. Mediastinal syndrome 3. Myasthenia gravis
Secondary Myasthenia Myasthenic - Myopathic Syndrome Lambert-Eaton myasthenic syndrome(LEMS)
Lambert-Eaton
syndrome (antibody) Ca2^ channel
Ca2+—
Synaptic ,
0^0*0 o o Active
^ O °a° Synaptic
■ .A.V
°.one
ACh
O oS-
^
v.v.
cleft
Botulism
(toxin)
Myasthenia gravis (antibody)
ACh
receptors
Postsynaptic muscle membrane
135
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Lambert-Eaton myasthenic syndrome
❖ Myasthenia Gravis ❖ Definition :
0
It is an autoimmune disease due to
0 It is an autoimmune disease due to antibodies
antibodies against post-synaptic
against pre-svnantic calcium channels at the
nicotinic acetvlcholine receptors at the
neuromuscular junction
neuromuscular junction leading to their
choline
release of acetyl „
destruction.
❖ Clinical picture:
4»
J)
1. More in
o
Females
0
Males
2. Effect of
o
Increase weakness
o Improve weakness transiently but worsen Shortly atterwara
repeated efforts
(exercise) 3. Diurnal
J.Nrcflcxia
o
Present
o
Absent
o
Uncommon
0
Common
\Asceiiding^O^^
variation
4. Mnscle pain 5. Muscle weakness
0 Descending march course: weakness starts at eyes(ocular muscles) and
0 Ascending march course : weakness starts at limbs(LL > UL)and moves up with sparing
moves down including bulbar muscles
ocular & bulbar muscles
6. Reflexes
o
Normal
0 Decreased (hyporeflexia) or absent
7. Autonomic
0
No
0 Yes; dry mouth, impotence, orthostatic
8. Co-existing diseases
0
hypotension \ 0 Paraneoplastic syndrome ; small cell carcinoma of the lung o Polymyositis & SLE
symptoms
o Thymic hyperplasia 0 Thymoma 0 Thyrotoxicosis
§
❖ Investigations: I. Antibodies
0 Antibodies to acetyl choline receptors
2. EMG:
0 Decremental (J, amplitude) response with repetitive stimulation
0 Antibodies to voltage gated calcium channel o Incremental response (famplitude) with repetitive stimulation(Lambert-Eaton phenomenon); this because repeated stimulation squeezes the vesicles at the NMJ & releases the acetylcholine stored within them.
❖ Treatment
1- Anticholinesterase with good response
I) Guanidine hydrochloride helps release of
acetyl choline. 0 N.B. Poor response to anticholinesterase 2- Corticosteroids, Immunosuppressive & P asmapheresis 3) K channel blocker : 3- Thymectomy o 3,4-diaminopyridine 0 Fampridine Botulism
lillMbll l',|(
Etiology:
Ingestion of clostridium botulinum in contaminated vegetables (green beans and mushrooms), smoked and salted fish, and canned salmon
Botulinum toxins bind to the neurone and prevents the release of actylcholine across the synaptic deft FLACCID paralysis Clinical picture:
SUDDEN(WITHIN 2-3 DAYS)ONSET of descending paralysis starts by ocular muscles and moves down including bulbar & respiratory muscles —> generalized weakness in UL & LL NO fever is apparent & nausea and vomiting are NOT usually prominent. Investigations: clinically diagnosis; EMG:INCREMENTAL response (famplitude) with repetitive stimulation Sample of serum, stools & food analyzed for the toxin & organism Treatment: as Lambert-Eaton myasthenic syndrome + : Trivalent botulism antitoxin within 12 hours after ingestion (after test of allergy) 136
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Diseases of voluntary muscle: Myopathles ❖ Ciasslflcatlons:
1. Primary myopathy: genetically determined myopathles
1. Muscular dystrophies 2. Myotonla
3. Familial periodic paralysis: hypokalemlc, hyperkalemlc, normokalemlc. 2. Secondary myopathles: acquired myopathles
1. o o o
Inflammatory myopathles: Polymyositis Dermatomyositis Inclusion body myositis
—> For more details see rheumatology book. 2. Immunologlcal: o
Rheumatoid arthritis
o
Sarcoidosis
3. latrogenlc: drug induced myopathy o Proximal myopathy Induced hy e.g. Alcohol, Statins & Steroids.
o Malignant hyperthermla Induced by psychotropic drugs & anesthetic agents e.g. Halothane & succinylcholine •o Myasthenlc syndrome Induced by Aminoglycosides ,Penicillamine, Propranolol , Ciprofloxacin & Lithium 4. Infection :
o Sepsis causing critical illness myopathy 5. Endocrlnal:
o o o 6. o o 7. o
Acromegaly Gushing syndrome Myxedema Electrolytes : Hypocalcemia or hypercalcemia Hypokalemia or hyperkalemia Neoplastlc : Bronchogenic carcinoma
o
Ovarian carcinoma
137
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Muscular dystrophies
Definition : Whi
o Inherited disorders with gradual progressive degeneration of skeletal muscles (progressive muscular dystrophies) without central or peripheral nervous system involvement. ❖ Etiology:
❖ Genetically determined muscular dystrophies are classified into : 1. X-Linked recessive pseudohypertrophic types :
o Mutation on short arm of X chromosome 2. 3. o o
J. dystrophin protein —> sarcolemmal tear & muscle fiber necrosis
Duchenne and Becker muscular dystrophy Autosomal dominant: facioscapulohumeral muscular dystrophy Autosomal recessive : limb girdle type: Erb's muscular dystrophy
Protein
Muscle fibre membrane
Dystrophin
Leyden-Mobius muscular dystrophy
Muse e fi ament
❖ Pathophysiology:
1. Genetic (heredofamilial) block in conversion of creatine to creatinine to get energy; leading to: TCPK
I Creatine| > Creatinine
2. Dellciency of energy leads to Degeneration of muscle fibers with replacement by fibro-fatty tissues: o Little fibrofatty tissue may lead to atrophy of muscle
o Excess fibrofatty tissue may lead to pseudohypertrophy of muscle.
-^1^^
❖ Clinical picture of progressive muscular dystrophy:
A. Type of patient:
1. Age: young age(E'- 2"'' decade) 2. Onset & course: gradual onset, progressive course '
B. Symptoms & signs:
1. LMNL:
A. Skeletal muscle lesion is LMN nature: weakness & wasting with hypotonia & hyporeflexia B. Skeletal muscle lesion is bilateral, symmetrical & PROXIMAL more than distal : o
The shoulder & arm are more affected than forearm & hand
o The hip & thigh are more affected than the leg & foot
138
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
C. The weakness and wasting of muscles that develop early during intra-uterine life e.g. shoulder, trunk, & pelvic girdle muscles results in :
Pot belly abdomen
Hyperlordosis
Gower sign
Waddling gait Winging of scapula
V Clinically:
Due to weakness of:
1. Gower sign (climbing test): patient climbs on himself on getting up
o Gluteus maximus & spine extensors
2. Waddling (clumsy) gait:
0
Gluteus medius & minimus
(abductors of hip)
3. Exaggerated lumbar lordosis to prevent himself from falling forward
0
Extensors of the trunk
by the effect of gravity 4. Pot belly abdomen 5. Winging of scapula
o
Abdominal muscles
o
Serratus anterior & trapezius
D. Facial muscles may be bilaterally weak (facio-scapulo-humeral type) E. Selectivity of the involved muscles:
m i^i '
1. Affected (atrophied) muscles: o Serratus anterior, Latismus dorsi. Rhomboids
0
o Sternal head of pectoralis major o Lower fibers of trapezius muscle
0 Clavicular head of pectoralis major o Upper fibers oftrapezius muscle
2. Spared muscles : Sternomastoid
0 Abdominal muscles(Beevor's sign)
2. Pseudo-hypertrophy: o Muscles are usually wasted & atrophic.
o In certain types as Duchenne type, muscles are hypertrophied but still weak (pseudo-hypertrophy) 3. Skeletal deformities:
o Fibrosis & contracture of involved muscles leading to skeletal deformities e.g.: ■
FES CAVUS ,Talipes equinus,Kyphoscoliosis
4. CVS system:
o Myocardial lesions: ECG changes, cardiomyopathy, arrhythmia, HP especially in Duchenne type
tl
5. Sensory changes,fasciculation, sphincteric troubles: ABSENT i.e. pure motor disease "1. 6. Causes of death in myopathy: 1. Infections: especially orthostatic pneumonia 2. Respiratory failure due to respiratory muscle paralysis 3. Cardiomyopathy(HE)especially in Duchenne type
139
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Clinical types of progressive muscular dystrophy:
1- Shoulder girdle type: UL > LL:
muscular dystrophy
B. Facio-scapulo-humeral muscular dystrophy: Landouzy Dejerine muscular dystrophy
Autosomal recessive
o
A. Scapulo-humeral muscular dystrophy: Erb's 0
Autosomal dominant
2- Pelvic girdle type: LL > UL
A. Atrophic type(Autosomal recessive): Leyden-Mobius muscular dystrophy
^
B. Pseudo hypertrophic type(X-Linked recessive): Duchenne and Becker muscular dystrophy | ^ 1. Age of onset
❖ Duchenne muscuiar dystrophy
❖ Becker muscular dystrophy
o
o
1 St decade
2nd & 3rd decade
2. Course
0 Progressive (severe form)
0 Slowly progressive (mild form)
3. Skeletal deformities
o
0
Absent
4. EGG
o Cardiomyopathy 0 Complete absence
o
Abnormal form
5. Dystrophin protein
Present
3- Other rare types:
1. Distal type of Gower(muscles of hand & foot) 2. Ocular type (ptosis)
I 11 ;
\
3. Oculo-pharyngeal type
Investigations: 1. Estimation of serum enzymes :
o Muscle degeneration leads to f creatine phosphokinase(CPK), SOOT,LDH 2. Estimation of creatine & creatinine in urine :
B. In myopathy:
A. Normally 1) Creatine
0 Absent in urine except in pregnancy
& infants < 2 years 2) Creatinine 0 Present in urine (normal level is 22 mg / kg / 24 hour urine).
0
Present in urine
o
Decrease in urine because the diseased muscles can't use their creatine & metabolize it to creatinine
3. Creatine tolerance test:
o 2 gm creatine administration by mouth lead to excretion of excess amount of creatine in urine (due to lack of the ability to retain creatine & lack of the ability of conversion of creatine to creatinine in case of myopathy) 4. EMG: I amplitude & duration of motor units 5. Muscle biopsy : confirm the clinical diagnosis o
Deficient Dystrophin
o Degeneration of muscle fibers & it's replacement by fibro fatty tissue
00piirsQ^ Treatment:
A. 1. 2. 3.
Supportive treatment: Genetic counseling in pregnancy as a prophylactic Vitamins especially vitamin E helps retention of creatine in body Physiotherapy
B. Drugs that may slow the functional decline in patients with Duchenne Muscular Dystrophy with a confirmed mutation of the DMD gene: o
ETEPLIRSEN: EXON 51 SKIPPING DRUG
140
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Myotonias ❖ Deflnition :
❖ Myotonic phenomenon is DELAYED RELAXATION of skeletal muscles AFTER CESSATION OF :
Voluntary stimulation (voluntary myotonia):
After clinch fist, patient is unable to open hand except very late Mechanical stimulation (percussion myotonia):
Tap of thenar eminence, leads to adduction of thumb with delayed abduction Tap of the tongue leads to dimple formation Electrical stimulation:
2-3 milliamperes are enough to produce muscle contraction (hyperexcitable). Normally 6 milliamperes is needed
The myotonic phenomenon due to due to CHLORIDE channelopathy i.e. defective chloride ion membrane conductance in the skeletal muscle cell
Frontal bald ing
The myotonic phenomenon : "Hatctiet" fades
A. Improves by: 0 Repetition (exercise)& warmth
o
Rest & cold
0 Ca-
o
K+
o Quinine, Procainamide
'lut;
B. Worsens by:
due to atrophy of temporalis muscle
Myotonia atrophica
Ptosis and Cataracts
drooping mouth due to weakness of facial muscles
0 Cholinergics : Neostigmine
Wasting of
Types:
sternocleidomastoid muscle
1. Myotonia congenita(Myotonia hypertrophica = Thomson's disease) 2. Myotonia atrophica(Myotonic dystrophy)
IViyotonia atrophica
3. Myotonia acquisita: associated with acquired conditions e.g. myxedema & hyperkalemia 4. Myotonia paradoxical(paramyotonia congenita): worsening occurs with exercise ❖ Myotonia congenita I. Heredity
o
❖ Myotonia atrophica
Autosomal dominant
2. Age
o
L'& 2"'* decades
o 3'''' & 4"^ decades
3. Sex
o
Common in females
o
4. State of the
0 Myotonia -l-
muscle
Common in males
❖ Atrophy of muscles specially:
o TRUE hypertrophy of ALL
( 1
0 Facial muscles: myopathic face o Bilateral ptosis
muscles ot body
0 Wasting of sternomastoid and neck muscles 0 Wasting of distal muscles sparing hand &feet 5. Dystrophic change
0 Negative
6. ECG
o
L
?JK
o
Frontal boldness
0 Cataract & testicular atrophy o Ischemic changes
Normal
>M|y (|||^^\^
7. The diagnosis is confirmed by DNA testing Treatment; 1.
2. 3. 4. 5.
Quinine sulfate: 300 mg t.d.s membrane stabilizer Procainamide: 500mg/8hours Potassium exchange resin & Prednisone —^ Reduce K Phenytoin : 100 mg t.d.s Calcium gluconate: 10- 20 ml IV daily
141
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Familial Periodic Paralysis Syndrome
Definition :
Genetically determined disorders characterized by of recurrent attacks of muscle weakness (flaccid) related to serum potassium:
1. High serum potassium: hyperkalemic periodic paralysis 2. Low serum potassium: hypokalemic periodic paralysis 3. Normal serum potassium : normokalemic periodic paralysis ❖ Types:
1. Etiology
A. Hyperkalemic periodic paralysis o Familial (primary) 0 Secondary to excess of K+ e.g. Renal failure & K retaining diuretics (spire nolactone) o
B. Hypokalemic periodic paralysis
0 Familial (primary) 0 Secondary to loss of K+ e.g. Hyperaldosteronism & K lo=ing diuretics
Onset in P' decade
o 2. Pathogenesis:
3. Precipitating factors
Onset in 2"'' decade
0
Cold
0 Calcium channelopathy 0 Excess CHO (glucose) meal
0
Exercise
0
0
Onset: Immediate
0 Onset usually on awakening in morning
o Sodium channelopathy
Rest after exercise
1. Weakness start in LL,then generalized
4. Clinical picture
2. Duration of attack: minutes to hours
2- Duration of attacks: hours to days
3- Free in between attacks 5. Serum K
o
0 Low 5m Eq/L
6. Treatment:
a. Therapeutic :
b. Prophylactic
0 IV KCI drip with ECG monitor
o IV calcium gluconate 0
Lasix
0
Glucose + insulin
0
Thiazide diuretics
0 Low CHO diet + high K o
Acetazolamide 250 mg / day
sarcolemma
N.B.: Channelopathies: Sodium channelopathy: Hyperkalemic periodic paralysis Chloride channelopathy: Myotonia Calcium channelopathy:
Hypokalemic periodic paralysis Lambert-Eaton myasthenic syndrome
142
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Differential diagnosis of wasting of small muscle of the hand:
Spinal Cord
❖ Small muscle of the hands supplied by C8-T1. Lower Motor Neuron
❖ Etiology :
1. Anterior horn cell lesions:
1. Poliomyelitis:
o Acute onset of fever with flaccid paralysis & asymmetrical wasting(LL > UL)
associated with bulbar poliomyelitis in young age (bmonth -2 years) with regressive or stationary course, o
No sensory changes
2. Syphilitic amyotrophy.
/I
3. Transverse myelitis at C8 & T1 segments 4. Anterior spinal artery occlusion.
5. Intramedullary lesions e.g. syringomyelia & hematomyelia 6. Motor neurone disease
2. Anterior roots & spinal nerve lesions: cervical affection : 1. Cervical spondylosis 2. Cervical Pott's disease 3. Cervical neurofibromatosis 4. Fracture & dislocation of cervical vertebra. Anterior
5. Primary & secondary tumors of cervical vertebra
serene mitsde First rib
Comprussion of
Brachial plexus
artery, nerves — Clavide.
3. Lower brachial plexus injury: 1. 2. ♦J* a.
Klumpke's paralysis: secondary to birth injury Thoracic inlet (outlet) syndrome: Etiology: Aneurysm of the subclavian artery
b.
Pancoast tumor
c.
Cervical rib
First nb
Subdavian artery Subclavian vein
d. Developmental abnormalities in the scalenus muscles e. Enlarged cervical LN ❖ Features of cervical rib:
1. 2. 3. 4.
Asymptomatic in 10 % of cases. Motor : wasting of small muscle of the hand Sensory: paresthesia over ulnar side of arm & forearm (C8- Tl) Vascular changes e.g. Adson's sign:
o Loss of radial pulse on abduction & external rotation of shoulder with rotating head to the ipsilateral side with extended neck following deep inspiration. 5. Investigations e.g. X-ray: complete or incomplete rib
4. Peripheral nerve lesion: causes of mononeuropathy, mononeuropathy multiplex & polyneuropathy.
5. Neuromuscular lesion e.g. Myasthenia gravis
6. Muscle lesion e.g. distal type of Gower myopathy & myotonia atrophica
143
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
7. Other causes:Disuse atrophy as in : 1. Rheumatoid arthritis 2. Scleroderma
3. Dermatomyositis
4. Long standing UMNL in upper limbs ❖ CAUSES OF;
❖ Causes of motor neuropathy:
❖ Causes of sensory neuropathy:
❖ Causes of autonomic
1. Lead neuropathy
1. 2. 3. 4. 5. 6. 7. ❖
1. 2. 3. 4.
neuropathy:
2. Landry-Guillain-barre syndrome 3. Diphtheria 4. Porphyria
❖ Causes of metabolic neuropathy
Diabetic neuropathy Alcoholic neuropathy Vitamin deficiency neuropathy Arsenic neuropathy Leprotic neuropathy Amyloidosis Uremic neuropathy Causes of hereditary
Amyloidosis Uremic neuropathy Diabetic neuropathy Landry-Guillain-barre syndrome
❖ Causes of hypertrophic
(palpable thickened nerve)
neuropathy
neuropathy
1. Acromegaly 2. Porphyria 3. Chronic liver & renal failure 4. DM
1. 2. 3. 4.
Amyloid polyneuropathy Peroneal muscle atrophy Porphyric neuropathy Mitochondrial neuropathy
5. Hypothyroidism
1. Hypertrophic interstitial neuropathy 2. Refsum's disease
3. 4. 5. 6.
Peroneal muscle atrophy Myxedema Acromegaly Leprosy
7. Neurofibromatosis
8. Amyloidosis ❖ Causes of pseudohypertrophy
❖ Causes of purely motor disease:
❖ Causes of tender calf muscles:
1. Motor neuron disease
1. Early diabetic neuropathy
2. Myasthenia gravis
2. DVT
3. Marie's ataxia
3. Landry-Guillain-barre syndrome 4. Myositis
1. 2. 3. 4.
❖ Causes of lost ankle &
❖ Causes of Lost ankle &
of muscles:
4. Myopathy 5. Poliomyelitis
Duchene muscle dystrophy Becker muscle dystrophy Myxedema Late cases of acromegaly
6. Parkinsonism & chorea
❖ Cranial nerve involvement in
specific disease: 0 Diphtheria: 3,7,10 0 Leprotic neuropathy: 5 & 7
0 Landry-Guillain-barre syndrome: o
3,7,9,10 Diabetes mellitus : 2, 3,4,6,7
o
Sarcoidosis: 8
exaggerated knee reflex
preserved knee reflex 0
Friedreich's ataxia
0
0 0 0 o 0
SCD & pellagra Peripheral neuropathy Epiconus lesion Cauda equina lesion of S1 Holmes- Adies myotonic pupil
o SCD & pellagra
Friedreich's ataxia
o Syphilis : 7 & 8 ❖ Causes of pes cavus: o
Friedreich's ataxia
0 Peroneal muscle atrophy 0 Duchenne myopathy o Syringomyelia
144
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Epilepsy Atonic seizures(drop attacks): sudden loss of postural tone.
Special sensory fits (hallucinations)
Simple partial seizures(NO loss of consciousness): part of or whole LIMB OR one side ofthe BODY.
1) Aura:
2) Absence:
Olfactory hallucinations
Distant look with staring eyes & unresponsive
3)Automatism e.g. cbaining of teeth
4)Amnesia
❖ Complex partial seizures: disturbed consciousness
146
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
o
3.
o
I.
Generalized seizures
seizures)
consciousness (absence
Attacks of loss of
o
There is sudden loss of
consciousness of short
attacks/day) the patient looks dazed and staring without falling to the
1) Pyknolepsy: o High frequency(30 -100
associated with:
B. Atypical: the loss of consciousness may be
on the face
duration (few seconds), with cessation of motor activity or speech. o There is a blank expression
o
4. Fits, may be: A. Typical:
Hyperventilation
Photic stimulation.
o
improves at puberty. 2. NOT preceded by aura and NOT followed by sequelae. 3. Precipitating factors:
1. It starts in childhood and
o
Carbamazepine & Phenytoin
Autonomic : vomiting
o
—
1
It starts between 12-16
...
o Lifelong treatment with
clonic seizures.
with generalized tonic-
o The jerks disappear later in the morning o Few years later the jerks may be accompanied
combing and toothbrushing difficult.
activities as hair
AWAKENING making
years old. o Frequent myoclonic jerks upon
o
4.
b.
3. a.
2.
or a group of muscles It may occur in the muscles of the face, palate or extremities. It may be of 2 types: Single : simple myoclonus As a part of the aura in grand mal epilepsy or with myoclonic petit mal epilepsy. Juvenile myoclonic epilepsy:
contraction of a muscle
1. There is a sudden, brief jerky, shock-like involuntary
clonic movements
Attacks ofinvoluntary
C. Myoclonic Epilepsy:
Ethosuximide
o
147
Clonazepam
II.
Partial seizures
consciousness.
There is NO loss of
a) Simple partial seizures
o
Carbamazepine
luuc;
jamais-vu phenomenon
hallucinations (irritation of the uncus). d) Depersonalization, Derealization, Deja-vu or
c) Olfactory and gustatory
sensory area).
(irritation of the auditory
c) Sensory Jacksonian fits: paresthesia of one side of the body. 3. Special sensory fits: a) Visual hallucinations (irritation of the visual sensory area). b) Auditory hallucinations
whole limb
body. 2. General sensory fits: which may be: a) Focal fits: paresthesia of part of a limb or of the
movement of one side of the
b) Motor Jacksonian fits:
whole limb
a) Focal fits: movement of part of a limb or of the
1. Motor fits: which may be:
brain (motor or sensory areas), the fits may be:
t.
o
/viiiiiesia lor ine aiiacK
prevented.
become violent if
leave the room, he may
The patient may walk and
movements of limbs.
There may be chaining of teeth, smacking, licking of lips or semi purposeful
Automatism:
questions
The patient appears distant with staring eyes and may not respond to
Absence:
Emotion of fear or Elation
Deja-vu or jamais-vu phenomenon
Derealization
Depersonalization or
hallucinations
Olfactory and gustatory
Aura:
Absence, Automatism and Amnesia(syndrome of 4A):
which is followed by
The fit starts with an Aura
seconds to few minutes
Seizures last from few
temporal lobe (temporal lobe epilepsy)
The lesion is in the
consciousness
There is disturbed
b) Complex partial seizures
Start focally in one region of the brain i.e. focal seizures
V According to the site of the excitatory focus in the
o
o
1 efficacy of OCPs. Choice of anti-epileptic drugs: I.
Generalized seizures
A. Grand Mai epilepsy:
II.
C. Myoclonic
B. Petit Mai
Epilepsy:
Partial seizures
a) Simple partial
Epilepsy:
seizures
b) Complex partial seizures
0 Broad spectrum anticonvulsants e.g. valproic acid (sodium valproate) & lamotrigine 0 Carbamazepine 0 Phenytoin & Phenobarbital
0 Carbamazepine 0 Gabapentin 0 Phenytoin & Phenobarbital
0
0
0
Ethosuximide
o Clonazepam Levetiracetam
Levetiracetam
•t' N.B.: unclassified epilepsies —>■ valproic aeid is the drug of choice.
❖ Doses: Vo«WIIBMBW«B.lirinl«IIB» two antiepileptic drugs to control seizures
b. Resectable seizure foci with low probability of causing functional impairment
149
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Status Epilepticus
❖ Definition, etiology, complications:
'—
3Di^w
1. Convulsive status epilepticus :
2. Non convulsive status epilepticus:
o Persistent attack of seizure lasting > 30 minutes OR
o Prolonged confusional state with behavioral changes of abrupt onset lasting > 30 minutes
o >2 sequential seizures repeating within 30 minutes
without convulsions but with evidence of seizures
without recovery of consciousness between seizures
❖ The commonest cause is inappropriate withdrawal of antiepileptic drugs
❖ Complications: If convulsions are not stopped rapidly, coma deepens & death may occur due 1. Respiratory failure 2. Heart failure
3. Hyperpyrexia
❖ Management: IT IS A MEDICAL EMERGENCY
A. General:
1. Maintain : ABC
o Put patient on ground to avoid falling with eare of comatose o Adequate airway & oxygenation,± endotracheal intubation if needed o Record vital signs regularly with treatment of hyperthermia (cooling foments) 2. Sampling:
o Venous blood for level of antiepileplic drugs, glucose, electrolytes & C.B.C o Arterial blood for state of pH, p02, pC02 & bicarbonate level.
3. Cerebral dehydration measures e.g. dexamethasone, furosemide & mannitol. B. Specific
Xe3323.013-0I ,
Waminehci y£cnoN.usf, . -'Wiyuso
?»TECT fBOM
A. Thiamine 100 mg IV (to avoid precipitating Wemicke's encephalopathy)followed by dextrose if there is hypoglycemia. B. If seizure activity does not terminate within 5 minntes, start anticonvulsant medications: 1. Benzodiazepines: lorazepam or diazepam IV slowly: A. Lorazepam:
B. DIAZEPAM:
o 10 mg IV slowly o 4 mg IV slowly 0 It can be repeated once only after 5 minutes if seizure persist
3.
If seizure continue after 10 min of stepl: PHENYTOIN or fosphenytoin (prodrug of phenytoin with less risk thrombophlebitis so can be given faster) Dose: 15 mg/kg IV infusion If seizure persist after 20 min of step 2,give:
o
PHENOBARBITONE
2. o o
o
4. o
Dose: 15 mg / kg IV infusion If seizure persist after 30 min of step 3: GENERAL ANESTHESIA by thiopental or propofol with assisted ventilation 150
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Brain tumors
❖ Brain tumors are space occupying neoplasm within cranial cavity. ❖ ClassiHcations:
A. Primary intra-cranial tumors(10%): Glit^iastoma
❖ Tumor arising from: 1. Arachnoid layer of meninges
❖ E.G.:
0 Meningioma
4. Blood vessels
0 a. b. o
5. Cranial nerves
0 Acoustic neuroma of 8"' cranial nerve
6. Lymphoid tissue
0 Primary cerebral lymphoma
2. Brain tissue
3. Pituitary tumors
Gliomas e.g. glioblastoma, astrocytoma, medulloblastoma Suprasellar: craniopharyngioma Intrasellar : acidophil, basophil, chromophobe adenoma Hemangioma & hemangioblastoma
B. Secondary extra-cranial tumors:
1. Metastatic tumors from lung, breast & GIT carcinoma: the commonest cause. 2. Tumors of nasopharynx invading brain stem ❖ Clinical picture:
1.
General symptoms & signs of increased ICT:
❖ Increased ICT is due to:
1.
Tumor itself act as a space occupying lesion, compress brain tissue & blood vessels
2.
Obstruction of venous return & ventricular pathway of the brain leading to impediment of CSF drainage
3.
(obstructive hydrocephalus) ->' ■ f New vessels formation with abnormal permeability leading to brain edema '
4.
Hemorrhage into or degeneration ofthe tumor
roc usi
Symptoms & signs of increased ICT: 2. Vomiting ❖ Etiology:
I. Headache
0 Stretch of meninges or blood
0 Stimulation of vomiting
vessels.
3. Papiliedema o Pressure on optic nerve
center in medulla
❖ Characters: o Dull aching. 0 Peak in the morning, alleviated at the end of day o t by coughing, straining, stooping & sneezing (f ICT)
0 Projectile, not related to
I 0 Blurring of vision followed by
meal, not preceded by nausea, gradual diminution of vision: o It is more in the morning & concentric contraction of field of usually accompanies vision headache & temporarily o Complete Blindness: due to post papilledemic optic atrophy
relieve it
❖ Value: o No significant value in localization of tumor 0
o
More common in infratentorial tumors
| 0 Ophthalmoscope: a. Blurring of optic disc, congested tortuous retinal vein, thin arteries,
N.B.:
a. Supratentorial tumors present with
retinal hemorrhage & exudates. b. Later on post papilledemic optic atrophy with complete blindness
frontal headache of late onset
b. Infratentorial tumors present with occipital headache of early onset
151
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4. False localizing signs:
❖ This signs are due to f ICT regardless the site of the tumor: 3rd ventricle
7Hvoothalannus Optic Chlasm
/
Optlc^erve
C: falx cerebri 6th CN
WWwV
Anteno
&
U: uncus
Posterior
Itultary
M: midbrain
SellaTurcIca
Pituitary
T: cerebellar tonsils
A. Cranial nerve palsy especially abducent nerve (6th CN): thin and runs a long course in cranial cavity 1. Lateral ventricle dilatation:
2. 3rd ventricle dilatation:
3. 4th ventricle dilatation:
0
0 Hypothalamic syndrome( hypothalamus compression) o Panhypopituitarism (pituitary gland
o Vomiting(++ vomiting center) 0 CUSHING TRIAD: hypertension, bradycardia, bradypnoea(++
Pressure on frontal lobe
leading to mental confusion
vasomotor center)
compression)
0 Bitemporal Hemianopia (optic chiasma compression) C. Herniation syndrome :
11.
I. Supratentorial herniation a) Subfalcine herniation: the b) Transtentorial(Uncal)
Infratentorial herniation e.g. Tonsillar herniation
herniation:
most common type
1. Herniated part
0 Uncus oftemporal lobe through
o The innermost part ofthe frontal lobe (cingulate gyrus)
tentorial hiatus.
o Cerebellar tonsils through foramen magnum(CONING)
beneath the falx cerebri 2. Pressure on the:
0
Blood vessels in the frontal
0
o
Midbrain
Medulla
0 Upper cervical spinal cord
lobes
3. Leading to :
0 Anterior cerebral artery
formation
stroke
0 Compression of cardiorespiratory centers in medulla ^ BP instability, irregular respiration & DCL o Tonsillar impaction in foramen magnum —> intractable headache, neck stiffness &
o Compression of reticular confusion &
disturbed conscious level
0 Compression of 3'''' cranial nerve & its nucleus^
ipsilateral dilated fixed pupil
forced head tilt.
A. Plateau waves:
o Episodes of increased ICT by coughing, straining, stooping & sneezing lasting for minutes associated with neurological manifestations o It's due to failure of vascular auto regulatory mechanism of ICT
II.
Specific symptoms & signs depends on site & type of tumor: TRUE localizing signs:
1. Cerebral tumors:
❖ Lesion:
❖ Tumor A. Frontal lobe tumor B. Parietal lobe tumor
C. Temporal lobe tumor D. Occipital lobe tumor
152
o
Irritative lesion
o
Destructive lesion
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
trigeminal
r\.
2. Cerebellopontine angle tumor:
bniinstwir
❖ Incidence: the most common neoplasms in the posterior fossa
ttiildbraih pons
.cochlear ^facial
❖ Etiology:
nerve
nerve
•'.iTt^ulla
1. The commonest: acoustic neuroma
2. Rarely meningioma, medulloblastoma, pontine glioma, primary cholesteatomas
■.cerebelluiti
❖ Clinically: 1. Ipsilateral cerebellar ataxia : hemiataxia on the same side ofthe lesion
2. Ipsilateral affection of5'^ 7'^ 8"', cranial nerve: progressive facial pain & hyperesthesia, facial palsy & deafness 3. Contralateral hemiplegia (pyramidal compression in pons) 3. Pituitary tumor:
I.
Suprasellar tumor: craniopharyngioma (arises from remnant of Rathke's pouch)
A. Hypothalamic syndrome :
o Polyphagia (obesity), hypersomnia, diabetes insipidus, disturbed body temperature. B. Panhypopituitarism
C. Bitemporal Hemianopia II.
• subarachnoid space(SAS). ❖ o o ❖
Absorption: By subarachnoid vilii(one way valve) in subarachnoid space to cerebral venous sinuses —> IJV. Lateral Ventricles Some CSF is absorbed around spinal nerves into spinal veins. Foramen of Monro Properties :
o
Clear colorless fluid
o
Volume : 125-150 ml
3.
50 years old.
B. Character : sudden onset, increased frequency & severity C. Associated with :
1. Signs of flCT : Persistent headache. Blurring of vision (Papilledema), Projectile vomiting 2. Signs of meningismus: neek stiffness & fever 3. Head trauma
4. Disturbed conscious level or focal neurological Deficits 5. Rash
6. Risk factors for cancer or HIV
Migraine Wii
❖ Definition:
❖ Complex disorder characterized by intense throbbing headache associated with autonomic manifestations e.: nausea & vomiting. ❖ Incidence:
o Commoner in females than males (3:1) o Commoner in urban areas (psychological stress) o Commoner in perfectionistic people Etiology & precipitating factors:
Etiology :
Idiopathic Genetic: heredofamilial in 80%
1.
Recently mutation on chromosome 19 was discovered Precipitating factors : Migraine Triggers; 4 M Mental & physical exertion
2. Menses 3.
Meals : Chocolate (rich in phenylethylamine), Cheese (rieh in tyramine). Cigarette smoking & aleohol
4.
Medications : YD as nitrates, CCD 160
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Pathogenesis:
Periphorai neuren Brain blood vosul
Throbbing poin
Control
IV Inflommolion Piptid* ralooM
vc
VD
Aura
Headache
Neiirovascular theory:
Migraine triggers^ sterile neurogenic inflammation of trigeminal nerve ^ abnormal over excitation with
release of vasoactive neuropeptides e.g. calcitonin gene-relatedpeptide & substance P —>• trigeminal & nearby dural blood vessels dilation & inflammation.
Serotonin (5-HT)theory:
2.
Initial increase in blood serotonin level leads to its action on serotonin receptors(5-HTl)in smooth muscles of
A.
cerebral blood vessels resulting in their vasoconstriction & reduction of cerebral blood flow —> aura
Later, degradation of serotonin & decrease of its blood level, resulting in cerebral vasodilation ^ headache
B.
C. N.B.:
Serotonin receptors in other parts of body(5-HT2 & 5-HT3)are similarly affected, resulting in extra-cerebral vascular changes & activation ofsome autonomic reflexes e.g. nausea & vomiting Calcium uptake theory (hypoxic theory):
3.
Onset of migraine is due to a focal cerebral hypoxia associated with the rapid entry of calcium into brain cells & into smooth muscle cells of cerebral arteries
This causes vasoconstriction of these arteries(aura) with rebound (reactive) vasodilation (headache)
o
4.
Dopai^ine theory:
o
Abnormal dopaminergic stimulation leading to headache of migraine with nausea & vomiting Clinical picture of CLASSIC migraine: Prodrome —> Aura —»Headache^ Resolution
A. Phase 1: prodromal symptoms several days before the attack: 1. Mood changes 2. Drowsiness & fatigue 3. Food craving
B. 1. 2. 3. 4. 5.
Phase 2: migraine aura Etiology: vasoconstriction of cerebral blood vessels May precede or accompany the headache phase Develop gradually, over 5- 20 minutes & last less than 1 hour Site : on opposite site of coming headache Symptoms:
A. VISUAL:
o Flashes of light, Scotomas o
Bright zig zag lines (fortifications)
B. Sensory: paresthesia & numbness C. Motor: weakness
C. Phase 3: headache of migraine 1. Etiology: Rebound (reactive) vasodilation of cerebral blood vessels 2. Onset: gradual, pain builds up over a period of 1- 2 hours 3. Course :recurrent episodes of headache
4. Duration : lasting from 3 hours to 3 days 5. At least 2 from the following pain characteristics: o Character: Throbbing (pulsatile) headache
o Site: usually unilateral fronto-temporal pain or at periorbital region, o Radiation: spread unilaterally to involve the whole side of the head o Severitv: moderate to severe pain
o Aggravated by routine physical activity, bright light, sounds & stress o Relieved by quiet dark room & sleep 6. Associated with > 1 of the following : o
Nausea and or vomiting
o
Photophobia and or phonophobia (f sensitivity to light and sounds)
D.
V I /
U Tur «•!
Phase 4: the resolution phase:
During which the intensity of migraine symptoms gradually abates. 4 V
161
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Types:
A. Classic migraine(20% of cases): always preceded by aura B. Common migraine(80% of cases): o THE MOST FREQUENT TYPE OF MIGRAINE o Not preceded by aura (mild VC stage) C. Migraine variants:
Ophthalmoplegic migraine : associated with transient extra-ocular palsy Retinal migraine : associated with transient diminution of vision Eacial migraine : associated with transient facial palsy Hemiplegic migraine : associated with transient hemiplegia Basilar artery migraine: Prodroma is similar to vertebra-basilar TIAs followed by severe occipital headache Status migrainous: migraine attacks, longer than 3 days despite of treatment. Migraine equivalents:
Aura followed by neuro-somatic(CNS,CVS,GIT)symptoms instead of headache.
3
❖ Treatment :
1- During attack:
I- Adjuvant therapy:
1. Rest: in dark quiet room 2. Analgesics : NSAIDs e.g. aspirin or ibuprofen 3. Dopamine antagonist e.g. metoclopramide & prochlorperazine (orally or IV). o Used to treat migraine o
Antiemetic effect
♦J* N.B.: dopamine antagonist are commonly combined with diphenhydramine to minimize the risk of akathisia. Triptans
II- Abortive therapy: SEROTONIN AGONIST
Mechanism of action:
o They stimulate serotonin receptor in cerebral BY (which are abnormally dilated during headache) leading to VC & relieving of headache ❖ Drugs:
A. Selective serotonin agonist(5-HTI): TRIPTAN THERAPY
B. Non selective serotonin agonist: ERGOT alkaloids
o Serotonin receptors in cerebral BV o Serotonin receptors ail over the body a. Sumatriptan b. Zolmitriptan c. Rizatriptan a) Ergotamine b) Dihydroergotamine Orally SC nasal Orally Orally SC/IV/IM
1. Act on
2. Drugs 3. Route
spray
4. Starting dose
50-
6
5
2.5
1
100
... mg
5. Dose can he repeated after 2 hours if no improvement with maximum daily dose: 200 12 40 2 mg for IV 10 30 6 3 mg for SC & IM
o N.B. Caffeine(lOOmg) may be added 6.
Contraindications
to potentiate VC action of ergotamine 1. Pregnancy 2. Cerebrovascular diseases (transient ischemic attacks, stroke)
3. Cardiovascular diseases (angina, MI & uncontrolled hypertension) 4. Peripheral vascular diseases (Raynaud's disease & limb ischemia).
162
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2- Between attacks (prophylactic or preventive therapy): 1.
Avoid precipitating factors : avoid migraine triggers.
II.
1) Serotonin antagonists: o Pizotifen o Methysergide 0 0.5 mg o 1 mg/Shours
A. Class
B. Drug C. Dose:
o Weight gain
effect
o Retroperitoneal fibrosis
s
III.
o
80-240
o
10-30
mg/day 0 See cardiology book 0 N.B.:|3B drugs of choice in migraine due to stress mg/day
/Shours D. Side
2) Beta blocker: o Propranolol 0 Timolol
3) Calcium channel blocker Flunarizine o Verapamil o 10 mg/day 0 80 -240 before sleep mg/8hours
0
0 Weight gain 0 Depression 0 Extrapyramidal disorders
Other drugs & measures
TENS 1.
Antidepressants e.g. Tricyclic antidepressants e.g. Amitriptyline
2.
Antihistaminies e.g. Promethazine Antipsyehotics e.g. Chlorpromazine Antiepileptie e.g. valproic acid in family history of epilepsy or positive EEG of epilepsy Botulinum toxin A injection to the scalp and temple Calcitonin gene-related peptide inhibitors e.g. erenumah,fremanezumah & galcanezumah. Devices e.g. transcutaneous electrical nerve stimulation(TENS) Estrogen supplementation in menstrual migraine.
3.
4. 5. 6.
7. 8.
Temporal Arteritis(Giant Cell Arteritis): see RHEUMATOLOGY hook
163
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cluster headache
Histamine Cephalgia, Horton Syndrome
Definition & clinical picture:
0000
9000
000 0
000 0
000
0000
000 0
0000
A. Definition: o
Complex headache disorder characterized by circadian regularity & occurrence in clusters(1-2 cluster/year); each cluster lasting from weeks to months, separated by remission from months to years.
B. Incidence: o
90% in middle aged
o
Male: female ratio: 5: 1
c.
Precipitating factors : Alcohols & cigarette smoking Physical activity & mental stress
1. 2. 3. 4. D. o
1
Climate: seasonal changes especially season of allergy & hot weather. Drugs: nitroglycerin, histamine injection Pathogenesis :
Central disinhibition of trigeminal nociceptive pathways (trigeminal autonomic cephalalgia)
pain
Cluster headache characterized by: '^0 0 0 0^
^0 0 0 0>
1.
Frequency : 1-8 times /day or every other day for weeks to months
2.
Onset: sudden, peaking in 15 minutes, usually by night often waking the patient from sleep
3.
Course : Episodic or chronic cluster headache
4.
Duration : lasting from 15 minntes to 3 honrs per episode
5. Pain characters:
o
Character: excruciating, stabbing, sharp, and lancinating Site: strictly unilateral peri or retro-orbital pain, or at temporal region Radiation: may spread gradually to the involve check,jaw & ear (migrainous neuralgia).
o
Severity: very severe pain resulting in agitation and restlessness (suicidal headache)'^^^
o
o
o
Aggravated by precipitating factors (see before)
o
Relieved by cold weather
6. o o
o o
7.
Associated with > 1 of the following autonomic symptoms (all ipsilateral): Forehead and facial sweating Conjunetival injection or lacrimation Miosis, ptosis, or eyelid edema Nasal congestion or rhinorrhea NOT preceded by aura & NOT associated with nausea, vomiting, photophobia or phonophobia
fsoptin sdlupmi
Treatment as migraine plus:
Verapamil I predniiolone In abortive therapy add OXYGEN therapy. In preventive/prophylactic add e.g.: Calcium channel bloekers, the most effective agent CORTICOSTEROIDS: prednisolone : 60mg/day for 5 days decreasing gradually by 10 mg every 3 days
164
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Differential diagnosis ;
❖ Headache of migraine
❖ Tension headache ❖ Incidence
o
THE MOST COMMON
Commoner in female
Cluster headache
90% in middle aged
Commoner in females than
males (3:1)
o
Male: female ratio: 5: 1
0
Commoner in urban areas
0
Circadian regularity & occurrence in clusters (1-2 cluster/year)
CAUSE of headache
o
❖
o
0
(psychological stress) 0 Commoner in perfectionistic people
o
Cluster headache; 1-8 times
/day or every other day lasting from weeks to months, separated by remission from months to years.
❖ Precipitating factors
o
Stress ,Sleep deprivation
o
Stressful uncomfortable
o
position Eye Strain
❖ Migraine Triggers; 4 M o Mental & physical exertion 0
Menses
o
Meals: Chocolate (rich in phenylethylamine), Cheese (rich in tyramine), Cigarette smoking & alcohol
0
0 Alcohols & cigarette smoking o Physical activity & mental stress
0 Climate: seasonal changes especially season of allergy & hot weather,
o
Medications : VD as nitrates,
Drugs: nitroglycerin, histamine injection
CCB
Pathogenesis
o It the sum of nociceptive input into brain stem
0
Rebound (reactive)
0
blood vessels
neurons from vascular
Central disinhibition of
trigeminal nociceptive pathways (trigeminal autonomic cephalalgia)
vasodilation of cerebral
structure, myofascial &
pain
muscular sources
❖ Characterized by: A. Onset
o
Gradual
o
Gradual, pain builds up over a period of 1- 2 hours
o
Sudden, peaking in 15 minutes, usually by night often
B. Course
o
Episodic
0
Recurrent episodes
o Episodic
o
Chronic
0
Chronic
o
Lasting from 30 minutes to
0
Lasting from 3 hours to 3
0
Lasting from 15 minutes to 3
waking the patient from sleep
C. Duration
days 7 days D. At least 2 from the following pain characteristics: 1.
Character
0 Pressure or tight bandage
2.
Site
o
0 Throbbing (pulsatile)
D) pain characteristics: 0 Excruciating, stabbing, sharp, and lancinating
headache
sensation
Bilateral fronto-occipital
hours per episode
o
Usually unilateral fronto-
o
temporal or at periorbital
area
region
region. 3.
o
Radiation
Spread unilaterally to
o
involve the whole side ofthe
0 Mild to moderate pain
0 Moderate to severe pain
5. Aggravated by routine physical
o
NO
0
May spread gradually to involve the check,jaw & ear (migrainous neuralgia)
head
4. Severity
Strictly unilateral peri or retro-orbital, or at temporal
o
Very severe pain resulting in agitation and restlessness (suicidal headache)
Yes
activity 6.
Relieved bv
0
Analgesics & sedatives
0
Quiet dark room & sleep
o
Cold weather
7.
Associated with:
o
NO
o
>1
o
No
o
Nausea and or
o
vomiting Photophobia and or phonophobia
E. > 1 of the following autonomic symptoms (all ipsilateral): 0 Forehead and facial sweating 0 Conjunctival injection or lacrimation
0 Miosis, ptosis, or eyelid edema o
Nasal congestion or rhinorrhea
165
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Infectious diseases of CNS
Meningitis
❖ Definition:
❖ Inflammation of membranes covering the brain & spinal cord (meninges) including the dura, arachnoid & pia matters :
o Pachymeningitis : Inflammation of dura mater (rare)
INFECTED MENINGES
o Leptomeningitis : Inflammation of arachnoid mater & pia matter(common) ❖ Etiology:
I.
Septic meningitis : acute purulent meningitis Inflammation and infection
A. The CSF contains mainly polymorphs B. Caused by pyogenic (pus forming) bacteria:
1. MENINGOCOCCAL INFECTION is the most common cause of septic meningitis 2. Streptococcus pneumoniae & haemophilus influenza
II.
Aseptic meningitis:
i 1- Infective causes: subacute lymphocytic meningitis: ❖ The CSF contains mainly lymphocytes: ❖ Caused by non-pyogenic organisms e.g.: 1) Bacterial:
o Tuberculosis & Treponema pallidum (Neurosyphilis) o Brucellosis & Borrelia burgdorferi(Lyme disease) o Mycoplasma pneumonia & Rickettsia
2) o o o
VIRAL INFECTION: the most common cause of aseptic meningitis Rabies virus, Poliovirus (Poliomyelitis), Enterovirus, Echovirus, Coxsackievirus Herpes Simplex, Herpes Zoster virus, Epstein-Barr virus Cytomegalovirus Human immunodeficiency virus infection(HIV)
o Measles, Mumps 3) Fungal infection:
Rhinocerebral mucormycosis
O Cryptococcosis (Cryptococcus neoformans; fungal infection in immunocompromised patients leading to meningoencephalitis) O Mucormycosis (rhinocerebral mucormycosis; fungal infection in immunocompromised patients especially DKA causing nasal sinusitis with orbital cellulitis leading to proptosis, ophthalmoplegia & meningoencephalitis). 2- Non-infective causes:
A. latrogenic; Drugs e.g.: o NSAIDs, Allopurinol, Azathioprine o INTRATHECAL route for medications e.g. intrathecal methotrexate B. Immune-mediated inflammatory disease e.g.: o SEE, RA & Beh9et disease o
Sarcoidosis
C. Irritation e.g. Subarachnoid hemorrhage D. Malignant Infiltration e.g. leukemia
166
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Meningococcal meningitis: Acute cerebrospinal fever
Etiology:
1. Causative organism : neisseria meningitides (meningococci) 2. Source of infection: nasopharyngeal carrier :
)
i
^ 4L
Organism is implanted on nasopharynx and invade blood stream by passing through respiratory epithelium leading A. B. C. 3. 4. 5.
meningococcemia which settles in different parts of the body: Meninges leading to meningitis (meningococcal meningitis) Adrenal glands with multisystem organ failure (fulminating type) Other metastatic infection: Skin, eye, CVS, genitourinary,joints. Mode of infection: droplet infection Incubation period: 3-4 days (range 1-10 days) Common in overcrowding : schools , soldiers barracks
❖ N.B.: THE CLASSIC TRIAD OF BACTERIAL MENINGITIS CONSISTS OF:
Clinical picture:
1. Acute onset with fever 2. Neck stiffness.
1- General symptoms & signs:
3. DCL or headache
1. 2. 3. 4.
Temperature : acute high fever up to 40°c BP : usually normal except in severe cases there is hypotension Pulse :tachycardia except in high ICT there is bradycardia Respiration : tachypnea or irregular
5. RASH:
o Hemorrhagic skin rash, on trunk and extremities occur in 4' day in 40% of people in purpura fulminans i 2- Symptoms & signs of increased ICT: I -
'
1. Acute severe HEADACHE
2. Blurring of vision 3. Nausea & vomiting
3- Symptoms & signs of meningeal irritation: meningismus e.g. pain, neck stiffness 4- Symptoms & signs of cranial nerve affection & ocular manifestations: 1. o
2. o
o
Transient cranial nerve paralysis due to exudation around nerves: The most commonly affected nerves are ocular cranial nerves (3,4,6), 7 & 8. Ocular (eye)symptoms and signs : Photophobia Papilledema due to f ICT
I 5- Symptoms & signs of cerebral affection due to ischemia from vascular inflammation or CEREBRAL I VENOUS SINUS THROMBOSIS: -
A. Ataxia
B. Cortical Blindness
C. Disturbed eonscious level(DCL): Confusion, Convulsions & Coma
D. Focal neurological Deficits(motor or sensory) e.g. hemiplegia 167
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Clinical types of meningitis: 1. 2. o o
Acute meningococcal meningitis Chronic meningococcal meningitis: Lymphadenopathy & papilledema Meningismus & cranial nerve paralysis
3. Fulminating type : Waterhouse-Friderichsen syndrome: i.
Definition:
o ii. a. o o
Severe systemic infection leading to death from meningococcal septicemia before meningeal symptoms appear. Clinical picture: Acute fulminating meningococcal septicemia associated with: Addisonian crisis: due to bilateral adrenal gland hemorrhage —> adrenal failure with shock up to coma Purpura fulminans: due to increased capillary fragility —> diffuse petechial hemorrhage up to gangrene
b. Death occur within 24 hours due to :
o Septic shock, multisystem organ failure & DIC
❖ Complications: w
1. CNS:
o
Cerebral venous sinus thrombosis
o Decreased hearing or deafness
o o o o
Intracranial Hypertension (tlCT) —> cerebral edema Hydrocephalus : due to obstruction of CSF flow by organized exudates Convulsions : due to cortical irritation by organized exudates Focal neurological deficits e.g. Hemiplegia
2. Electrolytes: o Hyponatremia due to SIADH 3. Eye: o
Blindness
o Conjunctivitis, keratitis, iridocyclitis 4. CVS:
o o 5. 6.
Septic shock Pericarditis, myocarditis, endocarditis Genitourinary: nephritis, pyelitis, epididymitis, orchitis Joint: septic arthritis
Differential diagnosis of meningitis: 1.
Subarachnoid hemorrhage:
o
Sudden onset
o
CSF: see later
CT: blood in subarachnoid space Encephalitis & brain abscess: o Symptoms & signs of parenchymal involvement: cerebrum, brain stem & cerebellum o Glucose and chloride contents ofCSF are normal 3. Extra-cranial infection associated with neurological manifestations e.g.: Clinical picture of the cause : A. With signs of meningeal irritation e.g. pneumonia B. Without signs of meningeal irritation e.g. typhoid 4. Other causes of meningitis: A. Other causes of pyogenic meningitis e.g. : o Streptococcus pneumoniae & haemophilus influenza differentiated by CSF culture B. Other forms of lymphocytic meningitis : 1) Viral meningitis: o More benign course (mild & self limiting within 10 days) o
2.
o
CSF : see later
2) TB meningitis: o
Insidious onset with clinical picture of TB toxemia & primary TB focus (chest) Mild signs of meningeal irritation
o
CSF : see later
o
168
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Investigations: 1. CT/MRI:
o To exclude subarachnoid hemorrhage and intracranial mass o To detect any complications e.g. focal neurological deficits 2. Lumbar puncture with CSF examination is the gold standard for diagnosis : ❖ Acute bacterial
❖ Normal
1. Aspect 2. Pressure
o
Clear
o
10-15
0 Cloudy
o 3. Proteins
4. Cells: WBCs
o
Bloody
o
Increased
Normal or
mg/100ml 0 0-5/HPF, mainly
0
0-5/HPF
o
720-750
0
50-80
6. Chloride
o
Increased
o
mainly polymorphs
Increased
Increased
mainly lymphocytes
(50-500 mm^) o
o
o
mainly lymphocytes
(1000-5000 mm^)
mg/100ml
7. Glucose
o
Normal
increased o
o
Normal or
slightly
(10-2000 mm^)
Decreased
Increased
Normal
mg/lOOml 0
8. Microbiology
Clear
Increased
20-40
lymphocytes 5. Cells: RBCs
o
Increased
❖ SAH
meningitis o
cmH20 0
Viral
❖ TB meningitis
meningitis
1
0
o Organism on gram stain or
Sterile
Ziehl Neelsen stain or culture
CSF culture
o
Sterile / virus
(Lowenstein-Jensen
isolation by
medium or Bactec
virus culture
o
Sterile
system) 3. Blood:
o CBC: leukocytosis o Blood culture of meningococci is positive in septicemia 4. Detection of source of infection e.g. Chest X-ray for pneumonia
Vancomycin
Treatment:
EqwvttHXN I 9 McrMmmnMi
^aij-r-n'
.uu loMi•
I. Prophylaxis: 1. Hygienic measures: isolate patient, avoid overcrowding 2. Chemoprophylaxis: Rifampicin orally 600 mg/12hours for 2 days for contacts
3. Immunoprophylaxis: meningococcal life attenuated vaccine for children, travelers & epidemics. II. Therapeutic: i. Specific: 1) IV antibacterial drugs for 7-10 days :
o IV empirical antibiotics should be started before results of blood culture or CSF analysis o Follow the result of microbial sensitivity if not corresponding with the empirical antibiotics o
Treatment include A-l- B:
A. 3'''' generation cephalosporin; either Cefotaxime : 2 g IV /4 hours or Ceftriaxone : 2g IV / 12hours 1. High prevalence(>2%)
2. Low prevalence( Myelopathy B. Symptoms & signs of meningeal irritation in meningoencephalitis 2- Specific clinical picture e.g. viral infection: A. Proaromai symptoms:
o Fever, fatigue, headache, anorexia, malaise, myalgias(FHAM) 170
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B. Specific e.g.: 1. Herpes simplex virus o
Reactivation of latent HSV-
1, leading to transmission of virus along a nerve axon, to
2. Herpes zoster virus o
Reactivation of latent varicella
3. Rabies(Hydrophobia) o
Transmission of rabies virus to man
via infected (rabid) animal bite (usually from a dog) or through skin
zoster virus to transmission of virus
along a nerve axon, to the brain
abrasions (IP: 1-3 months)
the brain
Clinical picture:
❖ Depends on ganglion involved :
1. Period of lethargy
A. Dorsal root ganglion involvement:
1) Frontal lobe irritation: behavioral and personality changes 2) Temporal lobes irritation: o Olfactory & gustatory hallucinations
o Complex partial seizures
o Confusion, FHAM Unilateral vesicular rash, with
o
burning painful sensation along course of affeeted nerve, may lead to post-herpetic neuralgia
I. Period of excitability:
Pain & numbness around the bite
After 1-3 weeks the vesicles crust
over and leave irregular pigmentation & scarring of skin Gasserian involvement(CN 5):
V
3
Agitation, restlessness, hallucinations Spasmodic contraction of pharyngeal & laryngeal muscles precipitated by any attempt to water leading to hydrophobia & a profuse flow of
V''
c. Herpes zoster ophthalmicus :
Affects ophthalmic branch of trigeminal nerve with eye & corneal
saliva
Convulsions
Period of generalized paralysis:
uleeration, ocular muscle weakness
& panophthalmitis. 2. Trigeminal neuralgia :
o Affects maxillary or mandibular branch of trigeminal nerve with vesicles & pain along their
o Coma & death occur from respiratory paralysis
distribution.
C. Geniculate ganglion involvement
(CN 7);
Ramsav-Hunt svndrome:
Vesicles & pain in external
auditory meatus assoeiated with L.M.N. facial palsy on same side N.B.: von Economo Encephalitis lethargica: 1. It's characterized by acute onset of influenza like symptoms followed by few days by somnolence, (drowsiness up to deep sleep) with inverted sleep rhythm. 2. Eye: ocular paralysis, oculogyric crisis & Argyll Robertson pupil 3. Extra A e.g. parkinsonism, athetosis, chorea, dystonia 4. A Signs e.g. monoplegia or hemiplegia 5. Treatment: symptomatic & supportive treatment
Investigations: 1. CT, MRI, EEC
2. Lumbar puncture with CSF analysis 3. Brain biopsy is the gold standard in diagnosis Treatment:
A. B. o o
General symptomatic treatment. Specific treatment for viral infection : IV Acyclovir in herpes simplex & herpes zoster, Human rabies immune globulin, rabies vaccine in rabies 171
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Brain abscess
❖ Etiology: Mastoiditis
❖ Intracranial inflammation with subsequent abseess formation ❖ Source of the infection:
1. Contiguous suppurative focus: o Direct extension from ear, nose & throat inflammation
2. 3. o o o
e.g. otitis media, mastoiditis, paranasal sinusitis, dental sepsis Trauma e.g. fracture skull or intracranial surgery Hematogenous spread from a distant focus e.g. Cyanotic heart disease & endocarditis Chronic lung infections e.g. Abscess, empyema, bronchiectasis, Abdominal and pelvic infections
o
HIV infection.
Mastoid
Edema
air cells
Mastoiditis
❖ Pathology: infection is POLY-MICROBIAL,common organisms : o Anaerobic organism, streptococcus, staphylococcus, pseudomonas, proteus, actinomyces, Candida, o In AIDS, the commonest organism is toxoplasmosis. ❖ Clinical picture: 1. General symptoms: A. Fever, malaise: occur in 50 % of cases B. Headache:
o Early headache is diffuse & not localized o
A suddenly worsenins headache, followed by sisns ofmenimismus, associated with abscess rupture.
2. Symptoms & signs ofincreased ICT 3. Symptoms & signs of meningeal irritation (meningismus)
4. Symptoms & signs ofspace occupying lesion; focal neurologic deflcit according to site of abscess e.g o Frontal lobe abscess : mental confusion, motor aphasia & hemiparesis >. o Cerebellar abscess : ataxia, kinetic tremors & nystagmus Investigations: 1. CBC: Leukocytosis 2. CT scan & MRI: of choice, diagnostic ♦♦♦ N.B.: lumbar puncture rarely needed, and contraindicated in t ICT as it may precipitate trans-tentorial herniation Treatment: A. Medical:
❖ Indications :
o Early small sized abscesses o Multiple abscesses o
Inaccessible abscesses. Duration : 1-2 month
❖ Drugs : 1. Antibiotics:
a) Dental infection
b) Otitis media, mastoiditis, and sinusitis c) Penetrating traumatic & postsurgical
o
Penicillin PLUS:
o 3'''' generation cephalosporin PLUS:
0
Metronidazole
o Vancomycin
2. Anticonvulsant e.g. phenytoin for seizure prophylaxis 3. Corticosteroids: to reduce brain edema B.
Surgical resection or CT guided stereotactic brain aspiration:
1.
No response to medical treatment. Large size abscess, or significant mass effect Fear of rupture in ventricle (too close) with fatal outcome
❖ Indications: 2. 3.
172
1'^ ll
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Tetanus
❖ Etiology: o Wound contamination by clostridium tetani spores in soil o Tetanospasmin toxin blocks the release of the inhibitory neurotransmitters (glycine and gamma-aminobutyric acid) at spinal synapses, —>■ SPASTIC paralysis
IT Clinical picture:
|
1. Incubation period: 3 days to 3 weeks
3
2. Clinical picture: HYPEREXCITABILITY to external stimulus e.g. light and sound with muscle SPASM leading to :
Continuous
siC.Tetani
stimulation by
Excitatory-
excitatory
transmitters
transmitter:
♦
W
spastic paralysis
BM
Tetanospasmin ^
'9
Inhibitorv transmitter
Inhibitory transmitters
o o o o
release
blocked
Risus sardonicus (Facial muscles), Trismus (lock jaw; Jaw muscles), Opisthotonus (high arched hack; Extensors of the back) Dysphagia (Pharyngeal muscles) Dyspnea, cyanosis, respiratory failure & Death (Respiratory muscles)
❖ Investigations: ❖ Diagnosis: clinical diagnosis;
• Laboratory diagnosis for specimens from the depth of the wound is examined.
❖ Treatment: | -o..„
,
1. Tetanus antitoxin ; Human tetanus immunoglohulin (HTIG) 2. Local debridement of the wound
3. Metronidazole or penicillin
Botulism: see before
173
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Neurosyphilis
Etiology:
o Treponema pallidum infection either sexually transmitted, transplacentally or fresh blood transfusion o Neurosyphilis occurs after many years from the primary infection (Tertiary stage). ❖ Clinical picture:
1- Vascular lesion :
o Stroke (endarteritis obliterans of large cerebral & spinal vessels) usually associated with syphilitic aortitis. 2- Meningeal lesion :
1. Cerebral lesion: clinical picture of aseptic meningitis
2. Spinal lesion (hypertrophic pachymeningitis): extra-medullary compression ^focal paraplegia/quadriplegia. 3- Parenchymatous lesion :
A.
General paresis of insane (GPl): Dementia paralytica Pre paralytic, Mental stage :
o
Dementia with mentality & personality disturbances (frontal & temporal lobes atrophy)
B.
Paralytic, Motor stage :
1.
❖ The dementia is associated with :
a) b) c) d)
Pyramidal manifestation e.g. paralysis with signs of UMNL
C.
Extrapyramidal manifestation e.g. choreoathetosis Myoclonic epilepsy Argyll Robertson pupil Tabes dorsalis (posterior root & posterior column degeneration): syphilitic myelopathy; Muscle tone: hypotonia Superficial sensation early radicular pain, later: superficial sensory loss Loss of deep sensation :
o
Lost muscle sense (Abadie's sign)
2. A. B.
o o
D. E.
Loss of deep reflexes Sensory ataxia Sphincteric troubles e.g. sensory atonic bladder Argyll Robertson pupil
V
3. Rare forms : o o o
Syphilitic amyotrophy : anterior horn cell lesion e.g. UL wasting & fasciculations Erb's syphilitic paraplegia Syphilitic optic atrophy
❖ Investigations: 1 1. Lumbar puncture with CSF examination 2. Direct detection of the organism; dark-field microscopy or immunofluorescence 3. Serologic tests of syphilis: A. Non-specific tests:
B. Specific tests:
o Treponemal antibodies, o Regain antibodies o Venereal Disease Research Laboratory(VDRL) o Fluorescent Treponemal Antibody(FTA)test o Treponema Pallidum Haemagglutination Assay(TPHA) o Rapid Plasma Reagin(RPR)test 0 Enzyme Immune-Assay(ElA)and Western blot. ❖ Treatment: Penicillin or erythromycin for penicillin sensitive patient. 174
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
■N
Dementia
Definition:
o Progressive deterioration of cognitive function (thinking and judgment), memory, behavior & personality due to disease of cerebral hemispheres. » Etiology:
A. Dementia associated with neurological disease : 1. VASCULAR: multi-infarction, cerebral arteritis e.g. SLE 2. Tumors : frontal / temporal lobes 3.
Infection :
o Encephalitis (Herpes simplex & syphilis) o Tuberculous meningitis 4. Degenerative : o
ALZHEIMER'S DISEASE
o Parkinsonism, Normal Pressure hydrocephalus o Pick's disease: Frontotemporal dementia o o
Huntington's Chorea, Creutzfeldt-Jakob disease Dementia with Lewy bodies
5. Traumatic : chronic traumatic encephalopathy e.g. boxers B. Dementia associated with systemic disease :
1. Endocrinal: Hypoparathyroidism , hypothyroidism , Gushing's syndrome 2.
Neurofibriilsn ■■ tangles
Metabolic: Liver & renal failure
3. Nutritional: vitamin B1, B12, B3 deficiency diseases 4. Drug abuse e.g. alcoholic dementia Amyloid -
plaques N.B.: the commonest causes are Alzheimer's disease & vascular causes.
Pathogenesis of Alzheimer's disease:
o Deposition of neuritic plaques (P amyloid peptide & degenerative neurons) in different part of brain o Decreased level of cholinergic markers & increased deposition of glutamate in neocortex Clinical picture of Alzheimer's disease:
o Gradual onset with slowly progressive course over 10 years o More common in the elderly (>50 years ) but early onset is familial (autosomal dominant) o Mortality rate is about 10 % 1. Early:
1) Amnesia of recent events or information, causing the patient to repeat himself 2) Disability : At first he is aware of his disability then loses this awareness 3) Difficulty in performing usual work and cognitive functions e.g. planning & decision making 2.
Later:
J
1) Progressive memory loss, disorientation to time, place & person 2) 3) 4) 5) 6)
Behavioral & personality changes Apraxia: inability to perform complex motor activities Agnosia: inability to recognize objects, persons & places Patient cannot be left unattended & ends with mutism & incontinence Primitive reflexes reappear e.g. grasping & groping reflexes
175
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Differential diagnosis : depressive pseudodementia
1. Onset
o
Gradual
❖ Depressive pseudodementia o Rapid
2. Course of cognitive decline
o
Constant
o
Fluctuating
3. Duration
o
Long term
o
Short term
4. Amnesia 5. Mood
o Patient is concealing amnesia o Patient is highlighting amnesia o Consistently depressive o Variable
6. Respond to questions
o Patient try
❖ Dementia
o
Patient answers with short sentences
❖ Investigations:
o Alzheimer's disease diagnosed mainly by history & clinical investigations
o Investigations are done to exclude a treatable cause in early onset dementia e.g. hypocalcemia ❖ Treatment:
1) Prophylaxis : o
Antioxidants
o Intellectually demanding activities 2) Active treatment to slow progression of the disease Donepezll
No binding
Memantine
Glutamate
NMDA receptor
Acetylcholinei
Acetylcholinesterase
(AChE)
o Cholinesterase inhibitors: Donepezil & Rivastigmine o Glutamate receptor antagonist: Memantine
5 As TO ALZHEIMER PIAGNOSIS r A mnasia WhoamiA f^emoty Loss...
Anomia^
Where am i?\ Who are
inability To
^ ,
you?i
Remember Names/ What do
of Things...
Jud^metTt
lyou call this^ ^
again?
Concentration Attention
fl praxia Misuse Of Objects Because Of Failure
To identify Them...
Why doesn't
this pen wor(:?l I can t say
Agnosia inability To
the words
What is
that on my whatyacail-
want.
phasia
^ inability To Express
Recognize FamiiiaN.,Jt? Objects, Tastes, Sounds,
Oneself Through
Speech...
And Other Sensations.,
176
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Brain death
❖ Definition of brain death:
Sa
o Irreversible & diffuse brain injury resulting in absence of clinical hmm function o Cardiovascular activity may persistfor up to 2 weeks ❖ Criteria of brain death:
1- Coma:
o NO response to both verbal & painful stimuli (N.B.: spinal reflexes may be retained)
• ■)
2- ABSENCE of any potentially reversible causes of marked CNS depression 1. NO CNS depressant drugs especially barbiturate over dose 2. NO neuromuscular blocking agents 3. NO drug intoxication 4. NO electrolyte / acid-base / endocrine disturbance 5. NO hypothermia (temperature < 32° C)
3- ABSENT respiratory drive: Apneic oxygenation test is positive:
Ill); HIT
o Pre oxygenate with 100 % oxygen for 10 minutes through mechanical ventilator o Disconnect the patient from mechanical ventilator with oxygen supply direct through endotracheal tube,
NO spontaneous
PCO2 > 60 mmHg ^
breathing etTorts
o Test is positive when PCO2 > 60 mmHg with NO spontaneous breathing efforts. 4- ABSENT brainstem reflexes: ALL MUST BE ABSENT:
1. Pupillary light reflexes 2.
Comeal reflex
3. Oculocephalic reflex
4. Vestibule-oculogyric : no deviation of eyes to irrigation of each ear with 50 cc of ice water 5. Pharyngeal (gag) & tracheal reflex 6. Sucking / rooting reflex
5- Confirmatory test: 1.
|
Electro-cerebral silence : isoelectric or flat BEG
2. Absent cerebral perfusion :
o
Absent cerebral blood flow assessed by cerebral angiography (N.B. supratentorial lesion may have preserved cerebral blood flow)
6- Two evaluation separated by 6-8 hours:
o Usually performed by two specialists e.g. neurologist, neurosurgeon, anesthetist, o Absent cerebral perfusion : assessed by cerebral angiogram
177
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Coma
❖ Definition:
o Clinical state of profound unconsciousness from which the patient can't be aroused even by painful & vigorous stimuli. ❖ Introduction:
❖ State of consciousness or alertness depends on:
Cortex
1. Intact cerebral cortex
2. Intact reticular activation system (RAS): o Site: collection of nuclei in brain stem, hypothalamus & thalamus
o Connections:receives impulses from all sensory tracts & transmits impulse diffusely through ascending fibers to cerebral cortex
Thalamus Reticular
o Aim : awakening & activation of cerebral cortex
Brainstem
Activating System
❖ So,for coma to occur, lesion may be:
1. Extensive diffuse (bilateral) cerebral cortex damage 2. Brain stem lesion : a small lesion of RAS
3. Combined damage to cerebral cortex & brainstem
❖ Grading of conscious level by Glasgow coma scale(GCS): using three criteria:
Open vour eyei
(O 0- I
Eye opening
"■)
are you?
Verbal response
\^Tiere
WhM'e Wh« are you?
WTiore are yiifal
^ \(1iere are you? ^ Moieum
©S
( • 0--' BLA...BLA i ' J- -^
aaaa
nc):
(?'©=
I Liti up your arra Motor response
1. A. B. C.
Eye opening; 4 grades 0 4 Spontaneous 0 3 To speech 0 2 To pain o
D. None
1
2. Verbal response; 5 grades
A. Oriented to time, place & person
0
5
B. Confused
o
4
C. Inappropriate words D. Inappropriate sounds
o
3
0
2
E. None
0
I
1. Normal i.e. complete
2.
3. Motor response; 6 grades 0 6 A. Obeys
B. C. D. E.
Localize to pain Withdraw to pain Flex to pain Extend to pain
0
5
0
4
F.
None
Disturbed conscious
A. Eye opening B. Verbal response C. Motor response
0 0 0
Spontaneous (4) Oriented to time, place & person (5) Obeys (6)
o o
Variable
0 0 0
D. Score
0
15
o
4-14
0
Variable
o
Variable
3
0
2
0
1
3. Coma (complete loss
level (DCL)
consciousness
0
of consciousness) None (I) None(l) None(l) 3
❖ Etiology: A. Organic causes :
I. Intra-cranial causes = coma with lateralizing signs 11. Extra-cranial causes = coma without lateralizing signs B. Hysterical causes.
178
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I.
Intra-cranial causes(coma with lateralizing signs): local causes in the brain:
1. Traumatic head injury e.g. cerebral concussion, contusion, laceration 2. Inflammatory: encephalitis, meningitis & brain abscess 3. Neoplastic: primary (brain tumor)& secondaries 4. Vascular:
a. Hemorrhage : Cerebral hemorrhage, Subarachnoid hemorrhage & Subdural hematoma b. Cerebral embolism & Cerebral thrombosis c. Hypertensive enceDhalopathv
N.B.: Ail causes (unilateral lesion) leading to coma with lateralizing signs EXCEPT HYPERTENSIVE ENCEPHALOPATHY.
Signs of lateraiization: Head: tilting the head to one side Eyes: Unequal pupil Conjugate eye deviation to one side Face: facial asymmetry Jacksonian fits
Deep reflexes & Muscle tone: Unilateral asymmetrical response(hypo or hyper) Response to painful stimuli:
Normal limb: moves with painful stimuli Paralyzed limb: more flaccid & drops passively Superficial reflexes:
Unilateral Babinski sign on paralyzed limb (N.B. bilateral Babinski sign can occur in deep coma)
XL
Extra-cranial causes(coma without lateralizing signs): general causes with 2ry effects on the brain:
1. Toxic:
1. Aspirin (salicylate) poisoning:
o FEVER, hyperventilation, bleeding tendency, vomiting, dilated pupil 2. Atropine (Belladonna) poisoning :
o FEVER, hot flushed dry skin, hallucination, dilated pupils, tachycardia 3. o o 4. o 5. o 6.
Alcohol poisoning: Hypothermia, flushed face & conjunctiva Characteristic mouth odor, f alcohol level in blood Barbiturates poisoning: Hypothermia, Cardio-respiratory failure, | barbiturates level in blood Morphine & opioid poisoning : Hypothermia,Pinpoint pupil, respiratory depression, bradycardia Carbon monoxide poisoning: o Cherry red skin, no respiratory distress despite of lack of oxygen 7. Others: Lead & cyanide poisoning
2. Metabolic encephalopathy: diffuse cerebral dysfunction due to systemic metabolic disturbance: A. Organ failure: 1. Respiratory failure: hypercapnic encephalopathy 2. Hepatic failure: hepatic encephalopathy 3. Renal failure: uremic encephalopathy
179
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B. Endocrinal:
1. 2. 3. 4. 5. 6.
Anterior pituitary ; panhypopituitarism Posterior pituitary: diabetes insipidus Thyroid gland: myxedema coma and thyroid storm Parathyroid gland: hypo & hyperparathyroidism Adrenal glands: Addisonian crisis Pancreas: DM with all types of coma C. Electrolytes & acid - base disturbances 1. Potassium: fK, J, K 2. Sodium : t Na, J,Na
3. Calcium :f Ca(hypercalcemic crisis), J,Ca (tetany) 4. Acid base imbalance(pH): t (alkalosis),),( acidosis) D. Others:
1. Mitochondrial encephalopathy: encephalopathy associated with mitochondrial DNA abnormalities e.g. MELAS syndrome and MERRF syndrome.
2. Nutritional encephalopathy e.g. Wemicke-Korsakoffsyndrome due to thiamine deficiency or alcoholism 3.
Physical causes:
1. Heat stroke 2.
Hypothermia
4. Cardiac causes: i
1.
Cardiac arrhythmias
2. Cardiac arrest 5. Infections:
1. Meningitis, encephalitis 2. Malaria especially cerebral type 3. Status typhosus
4. Septicemia & fulminating infections e.g. peritonitis, pneumonia
^ASPIRIN Etiology of febrile coma:
1. 2. 3. 4. 5.
Toxic: Aspirin & atropine (belladonna) poisoning Metabolic: hepatic failure & OKA Endocrinal: thyrotoxic crisis, Addisonian crisis & DKA Vascular: subarachnoid hemorrhage & pontine hemorrhage Physical: heat stroke
6. Fevers: all causes of fevers causing coma
7. Associated: any type of coma associated with secondary infection e.g. pneumonia ❖ Differential diagnosis of coma: 1. Psychogenic
2. Psychiatric: Catatonic Schizophrenia, Conversion Disorder 3. Locked in syndrome: fully conscious patient who is quadriplegic and unable to speak 4. Persistent vegetative state: state of wakefulness without awareness. 5. Brain death : irreversible loss of all brainstem functions
180
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Clinical approach to comatose patient:
rI A. History(from relatives): V.
1. Onset: o o
Sudden onset: cerebral hemorrhage Subacute onset e.g. cerebral thrombosis
o
Gradual onset: brain tumor
2.
History of convulsion, heat injury, drug intake e.g. morphine, barbiturates, insulin
3.
History of long standing disease e.g. DM,liver failure & chronic renal failure
4.
History ofsun exposure: heat stroke B. Examination:
1.
General examination:
A. Vital signs: I. Temperature
0 Hyperthermia : see causes offebrile coma
2. Pulse
0 Tachycardia: thyrotoxic crisis
3. Blood pressure 4. Respiration
0 Hypertension: hypertensive crisis
0 Rapid & deep (Kussmaul breathing): in DKA or renal failure
0 Hypothermia : hypopituitarism, hypothyroidism , morphine, alcohol, barbiturate poisoning, peripheral circulatory failure (cardiac causes) 0 Bradycardia : hypothyroidism , morphine poisoning & f ICT o Hypotension: Addisonian erisis 0 Slow & deep : in morphine & barbiturate poisoning
B. Mouth odour:
1. Acetone odour : OKA
2. Alcohol odour : alcohol poisoning 3. Fetor hepaticus: hepatic failure 4. Uriniferous odour : renal failure C. Skin examination:
1. Dry skin: DKA & atropine (belladonna) poisoning 2. Dry skin with urea frost: chronic renal failure
3. Moist sweaty skin: hypoglycemic coma 4. Cherry red skin: carbon monoxide poisoning 5. Skin rash in Waterhouse-Friderichsen syndrome 6. Palmer erythema in alcoholism & liver cell failure 7. Needle marks : drug addiction
8. Scratch marks : LCF, CRF,DM,.... Etc (see hepatology book for medical causes of itching) D. Eye examination : i. Pupillary examination: 1. Dilated fixed (irreactive to light):
o Unilateral: 3"''' nerve compression in uncal hemiation o Bilateral: Belladonna poisoning 2. Constricted :
o Unilateral: Homer's syndrome (in hypothalamic lesions)
o Bilateral: pontine hemorrhage & morphine poisoning (pin point pupil) ii. II.
Fundus examination:for papilledema in cases of f ICT CNS examination:
A. Coma with signs of meningeal irritation : in meningitis & subarachnoid hemorrhage B. Coma with signs of lateralization for intra-cranial unilateral lesion
III.
Other systems examination e.g. CYS,chest & GIT examination
181
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
C. Investigations:
1. Imaging: 1. Plain X-ray skull for : o
Fracture in cases of trauma
o Features of t ICT in cases of brain tumors 2. CT «& MR]the most important investigations:
Hypertensive encephaiopathy Intra-cerebral hemorrhage —>• coma with lateralizing signs
o Very accurate in diagnosis site & size of intracranial lesion
(diffuse brain edema) —► coma without lateralizing
2. Laboratory investigations: ; A. Blood examination :
1.
Blood picture : leukocytosis in bacterial infection
2.
Blood film : for malaria
3.
Blood levels : for glucose, urea & creatinine, bilirubin, electrolytes
4.
Blood gases : for respiratory failure Blood toxicological study : may be needed
5. B.
C.
Urine examination : glucose, acetone, albumin Lumbar puncture with CSF examination :
Lumbar puncture done in coma with signs of meningeal irritation AFTER EXCLUDING increased ICT by CT to avoid brain herniation.
o o
Purulent in meningitis Bloody in subarachnoid hemorrhage
Coma (unrousable and unresponsive state)
D. Management: o
Treatment of the cause
o
Care of the comatose : see stroke
_
Hyperglycaemla
Stroke
CENTRAL Causes
/Tlwombsiis / Emboli}
Septicaemia
Trauma!
Hypothyroidism S&mire
Hypoxia & Hypercapnia Cardiac Arrest
OTHER ORGANS
Hepatic Ettcephalopathy
Ti AddisonianCfcis
• • • Electrolyte abnormality
*
*
•
Uraemic
^ Encephaiopathy Carbon Monoxide \
Poisoning
\
Hypogtycaemia Aspinn Sedatives
use s
TOXINS
fopathy
Tricyclics Opiates
Substance abuse/ Overdose
182
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Rheumatology Topic
Page
o Introduction
1
o Collagen diseases o Symptomology o Investigations of rheumatological disease
2 5
6
❖ Connective tissue diseases o Rheumatoid arthritis
o Juvenile idiopathic arthritis(JIA) o Seronegative spondyloarthropathy o Ankylosing Spondylitis o Reiter's syndrome & Post infectious reactive
9 20 22
23 25
arthropathy o Psoriatic arthropathy o Enteropathic arthropathy o Arthritis associated with infectious agents o Systemic Lupus Erythematosus(SEE)
31
o Antiphospholipid Syndrome(APS)
38
0 Scleroderma Or Systemic Sclerosis
40
o Inflammatory myopathies:Polymyositis, Dermatomyositis & Inclusion body myositis o Polymyalgia rheumatica o Fibromyalgia syndrome o Sjogren's Syndrome: Sicca Complex o Mixed Connective Tissue Disease(MCTD) (Overlap syndrome, Sharp's syndrome) o Genetic disorders of collagen o Charcot's Joint(Neuropathic Joint)
45
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
27 28
29
48
49 50 51
Vasculitic syndromes o Introduction
52
o Polyarteritis nodosa
55
o Microscopic polyangiitis
56
o Giant cell arteritis(Temporal arteritis) o Granulomatosis with polyangiitis(Wegener's
57 58
granulomatosis)
o EOSINOPHILIC granulomatosis with polyangiitis(Churg Strauss Syndrome) oTakayasu's arteritis (pulseless disease) 0 Kawasaki disease(Mucocutaneous Lymph Node
59
60 61
Syndrome) o Behcet's disease
62
0 Henoch-Schonlein purpura (Anaphylactoid
63
Purpura)
o Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis= hypersensitivity angiitis) o Cryoglobulinemia: cryoglobulinemic vasculitis ♦♦♦ Crystal arthropathy
64
0 Hyperuricemia & gout o Pseudo gout & pseudo pseudo gout
66
❖ Paget's disease ❖ Degenerative joint disease : Osteoarthritis ❖ Medical bone diseases: Osteomalacia &
65
71 72 w
• 73
ft1
Osteoporosis V Amyloidosis
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
77
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Introduction Cortical
(hard)trane,
Tratjecuiar
(spongg)tjooft
❖ Bone anatomy: Periosteum
I
_ Arttcidar, cartilage
1- Structural types of bones in adult: f
1. Cortical bone :
o The hard outer layer of bones o Formed from Haversian system 2. Cancellous(trabecular) bone: o
^u
Blood
vessels
arrow
MeduUary cavi^
Epiphyseal plate
The internal tissue of the skeletal bone
o Formed of interconnecting network oftrabeculae, separated by spaced filled with bone marrow 2- Bone marrow.
3- Bone matrix:
A. Component of bone matrix: t.
1
1
1. Type 1 collagen (a fibrillar protein): the main organic component 2. Small amounts of other collagens & non-collagenous proteins B. Function of bone matrix:
o Organic component of bone forms a framework, upon which mineralization occurs. o Mineralization confers upon bone the property of mechanical rigidity, which complements the tensile strength and elasticity derived from bone collagen, o Bone mineral is composed mainly of calcium & phosphate laid down in the form of hydroxyapatite. 4- Bone cells for skeleton shaping and remodeling throughout life:
3. Osteocytes
2. Osteoblasts
1. Osteoclasts
o Responsible for bone resorption o Responsible for new bone formation 0 Responsible for sensing mechanical strain on skeleton tendon
❖ Joints:
cartHaK*
Joint capsule
Hbnws
CartilapniHis
Symnal
•ynovUri mtmbrane
syiravlal fli4d
❖ Two types of joints that link the bones: 1. Fibrous & flbro cartilaginous joints found in skeleton with little range of movement e.g. vertebral discs 2. Synovial joints : found in in skeleton with wide range of movement e.g. knee ❖ The joint capsule & synovial membrane:
o The bones of synovial joints are connected together with joint capsule o The inner surface ofjoint capsule is lined by synovial membrane o
Bursae:
■ ■
Definition: hollow sacs lined with synovium & filled with small amount of synovial fluid. Importance: they help tendons & muscles move smoothly in relation to the bones & other articular structure. 1
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Collagen diseases
❖ Collagen diseases are a heterogenous group of systemic disorders sharing certain features 1. Etiological: most probably immunologic origin with autoantibodies production 2. Pathological; inflammation of serosai membranes, connective tissues & blood vessels. 3. Clinically include both: o Specific involvement of various organ
o Non-specific feature of fever, malaise and weight loss. *** Classification of collagen diseases: 1. Classic collagen diseases:
1. Rheumatoid
arthritis(RA) 2. Juvenile
idiopathic arthritis (JIA)
4. Systemic lupus erythematosus (SLE) 5. Antiphospholipid Syndrome(APS)
3. Arthritis associated with
infectious agents
6. Seronegative spondyloarthropathies;
0 Ankylosing spondylitis 0 Reiter's syndrome & Post infectious reactive
7. Scleroderma
8. Polymyositis & Dermatomyositis 11. Polymyalgia
arthropathy o Psoriatic arthropathy o Enteropathic arthropathy
12. Fibromyalgiasyndrome
0
13. Genetic disorders
Undifferentiated
9. Sjogren's syndrome 10. Overlap syndrome
rheumatica
spondyloarthropathy
of collagen.
2. Vasculitic syndromes: mem
1. Large vessel vasculitis:
2. Medium vessel
3. Medium to small vessel
vasculitis:
0
Giant cell arteritis
0 Polyarteritis
0 Takayasu's arteritis 0
nodosa
Aortitis associated with
0
ankylosing spondylitis
0 Hepatitis B virus
Kawasaki disease
4. Small vessel vasculitis:
vasculitis:
o Wegener's granulomatosis
0 Cutaneous leukocytoclastic
o Churg-strauss syndrome o Microscopic polyangiitis
0 Henoch-Schonlein purpura
0
o Cryoglyobulinemic
related
Vasculitis of connective tissue disease
o
Behcet's disease
vasculitis
vasculitis
o Paraneoplastic syndrome
o Buerger's disease (thromboangiitis obliterans) Classification of arthritis
1- Inflammatory or non-inflammatory arthritis:
o Inflammatory arthritis in majority of rheumatoid diseases e.g. rheumatoid arthritis & SLE
o Non inflammatory arthritis e.g. trauma, osteoarthritis, hemarthrosis (hemophilia)& Charcot joint. 2- Pain ± sings of inflammation: a. Arthralgia: Joint pain without sings of inflammation b. Arthritis: Joint pain with sings of inflammation: o Swollen,± effusion o Redness, hotness & tenderness o
Limitation of movement
3- According to duration: o
Acute: < 6 weeks
o
Chronic :> 6 weeks
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4- Character:
a. Migratory (fleeting from joint to joint) e.g. rheumatic fever & gonococcal arthritis b. Additive e.g. systemic rheumatic diseases e.g. rheumatoid arthritis c. Intermittent e.g. gout & pseudo gout. 5 - Distribution:
o Centripetal distribution i.e. polyarthritis starts at small joints then spreads proximally to involve large joints e.g. rheumatoid arthritis
o Centrifugal distribution i.e. polyarthritis starts at large joints then spreads distally to involve peripheral small joints e.g. Ankylosing spondylitis
6- Deformity:
o Deformity if the lesion is erosive e.g. rheumatoid arthritis & Chronic gout 7- Stiffness:
1. Morning stiffness :
a. Definition : sense of stiffness (tightness when attempting to move joints) in diseased joint on arising in the morning or after a prolonged period of inactivity b. o o 2.
Timing: > 1 hour in inflammatory arthritis e.g. rheumatoid arthritis
Ab to Histones
Liver: Primary biliary cirrhosis, autoimmune hepatitis Normal people : elderly & relatives of SEE patients
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Different patterns of immunofluorescence microscopy for ANAs:
o
irmv
2. Homogenous (Diffuse) pattern 3. Nucleolar pattem 4. Centromeric pattern
C. Clinical associations
B. Autoantibodies
A. Pattern
1. Peripheral (rim) pattern :
o Anti double stranded DNA(dsDNA) antibody o Anti histone antibody o Anti-chromatin (anti-nucleosome) antibody o Antinucleolar antibody
0
o
o
Anti centromere antibodies
Positive in active SEE
0 Dmg induced SEE 0 EE phenomenon o Early scleroderma Limited scleroderma
(CREST syndrome)
5. Speckled pattem produced by anti- 0 Anti smith (sm) antibody: extractable nuclear antigen 0 Anti Ro antibody (anti SSA: anti-Sjogren antibodies & can be distinguished by ELISA:
syndrome antigen A)
o
SEE
0 SEE & Sjogren's syndrome
0 Anti La antibody (anti SSB: Sjogren
o Sjogren's syndrome
syndrome antigen B) o Anti-Ul ribonucleoprotein(RNP)
0 SEE & overlap syndrome
antibodies
o
Anti Jo-1 antibodies (anti histidine-tRNA
ligase antibodies) 0
Anti-Mi-2 antibodies
0 Anti-Scl-70 antibodies (Anti-topoisomerase antibodies) 4.
0 Polymyositis & dermatomyositis 0
Scleroderma
Anti-neutrophil cytoplasmic antibodies(ANCAs): Autoantibodies, mainly ofthe IgG type, against antigens in the cytoplasm of neutrophil. Different patterns of immunofluorescence are distinguished:
Atypical(aANCA)against elastase, lactoferrin & bactericidal permeability-increasing protein: Autoimmune hepatitis
Primary biliary cirrhosis Primary sclerosing cholangitis B. Perinuclear(pANCA)against myeloperoxidase
C. Cytoplasmic(cANCA)against Proteinase 3 (PR3-ANCA):
(MPO-ANCA):
0 Microscopic polyangiitis in 90 % of cases
0 Wegener's granulomatosis in 90% of cases
0
Wegener's granulomatosis in 10 % of cases
o
Polvarteritis nodosa in 10 % of cases
O 0
Microscopic polyangiitis in 10 % of cases Polyarteritis nodosa in 5 % of cases
0 Churg-strauss disease o Goodpasture syndrome
0 Idiopathic crescentic glomerulonephritis o Inflammatory bowel diseases 0 Same causes of aANCA
2. Radiological:
1. X-rays, ultrasound, MRI & CT 2. Bone scintigraphy using Tc 99m
3. Bone densitometry & dual energy x-ray absorptiometry(DEXA) 3. Interventional:
1. Joint aspiration :examination of synovial fluid: o Normal color and viscosity : clear to pale yellow, transparent, high viscosity o Normal WBCs count < 200 mm^ with less than 25 % polymorphonuclear leukocytes(PMNL) o
Gram stain & culture
o Polarized light microscopy
2. Arthroscopy : direct visualization of the joint & biopsies.
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Rheumatoid arthritis
Definition:
o Chronic systemic inflammatory disease characterized by articular (rheumatoid arthritis)& extra-articular manifestation (rheumatoid disease), most probably due to autoimmune mechanism,
o It the most common form of inflammatory arthritis (1 - 3% of population) Etiology: 1
W-
1. Autoimmune ;
o Infiltration of synovial membrane with lymphocytes & plasma cells. 2. Genetic predisposition : o Positive family history
o Human leukocyte antigen(HLA)association e.g. HLA DR4, HLA DR3 3. Infection : especially mycoplasma or Epstein Barr virus B Ceil
❖ Theory:
Plasma Cell Autoantibodies
Macrophage activation
TNFa —Inflammation
TCell
I { Osteoclast
erosion
W Preosteoclast
(monocyte)
Infection of the synovial membrane will attract T-lymphocytes with release of lymphokines —> transformation of Blymphocytes into plasma cells —> abnormal IgG release(IgC of altered molecular configuration) —> formation of IgM (rheumatoid factor)^ react with Fc altered portion of Ig G.
These two antibodies bind each other in the presence of complement forming an immune complex in synovial membranes which become engulfed by polymorphonuclear leukocjdes, with release of lysozjmies and cytokines causing synovitis & cartilage damage
80 % of patient are sero positive (rheumatoid factor detected in the serum)& 20% are sero negative (better prognosis) Pathology: three main lesions: Lossd
cattiiage
Arthritis:
Synovitis: inflammation of the synovial membrane with effusion.
Ankytosis
Pannus formation : hyper proliferation of synovial membrane form characteristic pannus eroding articular cartilage Fibrosis and bony ankylosing occur leading to joint deformity & sublaxation
synovmni
Erasiofl
Subcutaneous rheumatoid nodules: In 25 % of cases
Exclusive in seropositive patient.
Granulomatous lesions formed of central fibrinoid degeneration, surrounded by fibrous tissue. Vasculitis (Arteritis): involving: Small arteries
Rarely big arteries as aorta causing aortic regurgitation.
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Clinical picture:
A - Type of the patient:
o 1 - 3% of population o Females are affected more than males (3:1)
o Age : peak onset is 30-50 years B - General manifestations :
o Fever, malaise, anorexia, weight loss
o These manifestation may precede articular manifestations C- Articular manifestations: Arthritis
❖ Arthritis: Distribution, Description, Deformities, Complications 1- Distribution: Iiimm I.IB I N>iiwMrw-w.» popliteal effusion with hemiatioii Posterior rupture ofthis cyst may occur in the calf, causing severe pain similar to DVT Disuse atrophy^ wasting ofsmall muscles of hands(Rheumatoid myopathy) Drop : finger drop or foot drop due to spontaneous tendon rupture
6.
Osteoporosis
o
o
4.
Baker's
Common sites lor rhcumutoiil nodules
D- Extra-articular (systemic) manifestations: 1- Skin:
1. Subcutaneous rheumatoid nodules:
A. Type of patient: in 25 % of cases, exclusive in seropositive patient B. Appear in :
o Pressure areas e.g. Elbows, extensor surface offorearms, ischial tuberosities o Tendon sheaths e.g. Achilles tendon
C. Complications : Stenosing tenosynovitis —>■ triggering of fingers 11
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2. Raynaud's phenomenon
3. Peripheral (fingers & toes) ulceration & digital gangrene due to cutaneous vasculitis 4. Palmar erythema & Pyoderma gangrenosum. 2- Neuropsyehiatrie:
A. Psychiatric: depression & psychosis B. Cerebral:
1. Neuropathy: due to
o Vasculitic neuropathy (vasculitis of vasa nervosa): sensory or motor neuropathy specially mononeuritis multiplex
o Entrapment neuropathy: carpal or tarsal tunnel syndrome due to compression of peripheral nerves by hypertrophied synovium
2. Myopathy ; wasting of small muscles of the hand. 3. Convulsion 4. Chorea
5. Cerebral vasculitis
stroke (hemiparesis)
4m>
3- Occular lesions:
1. Conjunctivitis 2. Episeleritis (painless)
3. Scleritis (painful) that ends by scleromalacia (thinning of the solera —> affected area appearing blue reflecting the color of the underlying choroid.) 4. Iritis & anterior uveitis are not common
5. Sjogren's syndrome 4- Cardiovascular system
1. Pericardial: pericarditis ± pericardial effusion ± eonstrictive pericarditis 2. Myoeardial: myocarditis, cardiomyopathy 3. Endoeardial: o
MS
o AR due to vasculitis 4. Blood vessels:
o Coronary vasculitis with coronary artery occlusion —> ischemic heart disease ^ angina pectoris or myocardial infarction
5- Chest:
1. Pleura :
a. Pleurisy b. Pleural effusion:
o o 2. o o
In 25 % of cases in seropositive patient, The effusion fluid is an exudative with high LDH and low glucose level. Lung: Pneumonitis due to bronchiolitis obliterans or drug induced e.g. methotrexate Interstitial pulmonary fibrosis
o Caplan's syndrome : combination of subcutaneous rheumatoid nodules with pneumoconiosis (intrapulmonary rheumatoid nodules). 3. Pulmonary vessels:
o Pulmonary vasculitis with pulmonary hypertension & cor pulmonale
12
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
6- Hematological & reticuloendothelial system (RES): A. Blood:
1. Normocytic normochromic anemia due to : o
Anemia of chronic disease
o Autoimmune hemolytic anemia o Felty's syndrome
2. Microcytic hypochromic anemia due to : iron deficiency anemia due to chronic blood loss: a. Iron sequestration in synovium
b. NSAID induced GIT bleeding 3. Megaloblastic anemia :
o Folic acid deficiency e.g. Methotrexate & sulfasalazine 4.
Pancytopenia :
B
o Felty's syndrome (due to hypersplenism) o Drug induced BM depression e.g. methotrexate RES: Hepatosplenomegaly & LN enlargement in : o
Still's disease
o Felty's syndrome o Amyloidosis
❖ N.B.: Felty's syndrome:
Triad of seropositive RA (5 % of cases) with splenomegaly & neutropenia. ± Complications:
Huge splenomegaly —> Hypersplenism —> Pancytopenia.
Liver enlargement(due to lymphocytic infiltration of the liver). Lymphadenopathy
Others: Serious infection, Skin ulceration, Skin pigmentation & polySerositis. 7- Renal:
Renal affection is RARE,causes of glomerulonephritis in rheumatoid arthritis: Drug induced glomerulonephritis e.g. NSAIDs, Gold & Pencillamine Amyloidosis of kidney Renal vasculitis
Clinical picture:
Simple proteinuria, nephrotic syndrome & renal failure
❖ 1. 2. 3.
N.B.: Causes of lower limb edema in rheumatoid patient: CVS: pericardial effusion or biventricular heart failure due to myocarditis Chest: corpulmonale due to interstitial pulmonary fibrosis or pulmonary hypertension Renal: nephrotic syndrome due to amyloidosis or drug induced glomerulonephritis
❖ 1. 2. 3. 4.
N.B.: Differential diagnosis of patient complaint arthropathy with proteinuria Rheumatoid arthritis ^ nephrotic syndrome(drug induced OR amyloidosis). SLE -+ glomerulonephritis(nephrotic OR nephritic ). Any arthropathy —> NSAID —> minimal lesion glomerulonephritis FMF: Arthritis, Polyserositis & Amyloidosis kidney
8- GIT:
1. Anorexia, nausea, vomiting 2. Peptic ulcer 3. Abdominal pain : a. Pancreatitis
b. Peritonitis c. Mesenteric vasculitis • ► mesenteric vascular occlusion
13
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Criteria for diagnosis:
1- 1987 American College of Rheumatology criteria for diagnosis: ❖ Patients can be said to have rheumatoid arthritis if they have > 4 of the following criteria: 1. Morning stiffness > 1 hour 2. Arthritis of> 3 joints
3. Arthritis of hands joints (PIP, MCP or wrist) 4. Symmetrical arthritis
o 1^4 criteria must be present for at least 6 weeks 5. Subcutaneous rheumatoid nodules 6. Serum rheumatoid factor
7. Characteristic x-ray finding : erosions and or peri articular osteopenia
2- The 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for rheumatoid arthritis!
j j
^
—
Patients with score < 6 need frequent assessment ❖ Score
❖ Item
1. Joint involvement
o 1 large joint o 2—>■ 10 large joints
o o
1
o 1^3 small joints (if it is associated with large joints arthritis, large joints not counted) o 4^10 small joints (if it is associated with large joints arthritis, large joints not counted)
o
2
o
3
o
0
5
0 Negative rheumatoid factor and negative anti-cyclic citrullinated peptide antibody (ACCA)
o
0
o
Low positive RF or low positive ACCA
0
2
o
High Dositive RF or high positive ACCA
o
3
o
Normal CRP and normal FSR
o
0
o
Abnormal CRP or abnormal FSR
o
1
>10 joints with at least one small joint
0
2. Serology (at least one test result is needed for classification)
3. Acute phase reactants (at least one test result is needed for classification)
4. Duration of symptoms 0
6 weeks
o
1
❖ Factors associated with poor prognosis in rheumatoid arthritis :
1. Male patient, HLA-DR4 2. Clinical picture: o Polyarticular onset o Extra-articular symptoms o Functional disability 1 year after onset of disease 3. Investigations: o High rheumatoid factor value (in absence of HCV) o X-ray erosions within 3 years of onset of disease
14
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Differential diagnosis:
A.
Differential diagnosis from other causes polyarthritis e.g. Osteoarthritis & rheumatic fever
1. 2. 3. 4.
Immune-mediated inflammatory disease Affecting Small joints of the hands Distal interphalangeal joints are Spared Morning Stiffness > I hour
♦> Rheumatoid arthritis
❖ Osteoarthritis
1) 2) 3) 4) 5)
Degenerative bone disease Affecting weight bearing joints Distal interphalangeal joints are affected Morning stiffness < 30 minutes Gelling stiffness (few minutes)
5. Positive extra-articular manifestations
6) Negative extra-articular manifestations
6. Positive laboratory test
7) Negative laboratory test
❖ Rheumatoid arthritis ❖ Rheumatic fever (Rheumatic arthritis) o Inflammatory/immunological disease 0 Post streptococcal pharyngitis 0
>6 weeks
o
■ joint space narrowing
o
Bone erosion
o 0
Bony ankylosis Joint deformity ± sublaxation
C. Interventional:
1. Aspiration & analysis of synovial fluid : o Color and viscosity : yellow to white, translucent to opaque, low viscosity
o WBCs count 2000-50,000 mm^, with more than 70 % polymorphonuclear leukocytes (PMNL) o o 2. 3.
I Glucose (synovial fluid glucose is lower by 25 mg than serum glucose) J. Complement. Arthrography Arthroscopy & biopsy. ❖ N.B.: Markers to monitor disease activity (active diseases) and drug efficacy: 1. Clinically:
o o 2. A. B.
Pain & tenderness over joint Morning stiffness. Laboratory : Anemia(|hemoglobin) Acute phase reactants : I ESR & t C reactive protein, )■ Platelets: Thrombocytosis
*t* Management of rheumatoid arthritis:
1- General measures:
1.
Rest:
A. B. C. 2. 3.
Physical rest: complete bed rest during acute phase then gradual activity is allowed Emotional rest: sedatives & psychological support Articular rest by removable splints to reduce deformity & pain ^ Physiotherapy & relaxation therapy (when acute phase subsides). Acupuncture.
16
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2- Specific therapy: A. Analgesics:
Acetaminophen:
Class:
❖ Action
❖ Drug & doses
Non steroidal anti inflammatory drugs(NSAIDs) o Cyclooxygenase 1 & 2 inhibitors
o Inhibit prostaglandins
Mechanism of action
synthesis o Analgesic, antipyretics. o Acetaminophen
o Dose: 500- 1000 mg 16hours
Analgesic, antipyretics & anti-inflammatory Cyclooxygenase 1 inhibitors:
Aspirin: 500mg/4 hours Indomethacin: 50 mg/8hours Diclofenac sodium : 50 mg/8hours Ketoprofen lOOmg/8hours Cyclooxygenase 2 inhibitors:
Celecoxib: 100-200/day ❖ Side effects
Meloxicam: 7.5-15 mg /day Allergy
o Liyer toxicity
9^
Aplastic anemia & Platelet dysfunction Bronchial asthma, BP: Hypertension Peptic ulcer, gastritis, especially with cyclooxygenase 1 inhibitors Imnaired liver & renal function :
!* Liver : transammitis ,Reye s syndrome Renal Interstitial Nephritis, Na & H2O retention
B. Anti-inflammatory drugs: 1. Cyclooxygenase 1 or 2 inhibitors 2. Corticosteroids : a. Mechanism of action:
o Anti-inflammatory & immunosuppressive — leucocyte trafficking & i inflammatory mediators b. Dose:
o Low dose of prednisone: 7.5 mg /day o High dose in extra-articular manifestations C. Disease Modifying Anti-Rheumatic Drugs(DMARD): see table D. Biological Response Modifiers(BRMS): see table
3- Interventional:
1. Intra-articular injection :
A. Intra-articular steroid injections: ❖ Indications:
o Inflammation of the tendon e.g. Achilles tendonitis o Painful joint not responding to medical treatment o Carpal tunnel syndrome ❖ Complications: o Infection: septic arthritis o Failure with rebound of pain B. Intra-articular Yttrium 90 or erbium injection (medical synovectomy) 2. Surgical: o Synovectomy
o Arthroplasty : artificial prosthesis e.g. for hip & knee joint o Arthrodesis :joint fixation e.g. for ankle & stemoclavicular joint
17
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
..
.
❖ Mechanism of action:
o
Little anti-inflammatory & analgesic effect
7.5 - 15 mg once / week (oral, SC,IM)
synthesis
o
D
o 2-4 mg/kg /day orally
o
lymphocytes
inhibitor
Calcineurin
o
o
t risk of lymphoma
-0 o Nephrotoxicity
2. D-penicillamine
❖ N.B.: old treatment not used nowadays: 1. Gold salts e.g. Oral(auranofm) or IM (sodium aurothiomalate)
pneumonia Alopecia, oral ulcer
fibrosis & interstitial
o Megaloblastie anemia o Interstitial pulmonary
❖
T
C. Cyclosporine
o BM depression , Hypersensitivity rash, Hepatotoxicity, GIT irritation
o
o Inhibits purine synthesis
o Inhibit dihydrofolate
reductase —> inhibit DNA
B. Azathioprine
A. Methotrexate
❖ Drug: Leflunomide
❖ Doses:
X
18
o Teratogenicity
❖ Side effects:
o Reversible alopeci^^^^^^
o
Loading : 100 mg /day for 3 days orally o Maintenance : 10-20 mg/day orally Pregnancy category
o
o Immunomodulatory which inhibits dihydroorotate dehydrogenase enzyme —» jPyrimidine synthesis—* J, proliferative activity of lymphocyte
Mechanism of action:
o
♦> Drug class: 2. Pyrimidine synthesis inhibitor
B
Megaloblastie anemia (Inhibit dihydrofolate reductase) o Reversible depression of sperm count
o
o
o
4.
inflammatory effect
effect & anti-
Inhibit neutrophil trafficking with immunomodulatory
ne
Chloroquine & Hydroxychloroqui
Antimalarial
o
o
every 6 months)
fundus examination
Comeal opacity & retinopathy (do
psH
C
200-400mg/day Igm/day orally| then o gradually to 2-3gm orally /day over few weeks
sulfapyridine & 5 aminosalicylate (mesalazine) — prostaglandins
intestinal bacteria into
It is metabolized by
Sulfasalazine
O
o
o
o
o
3. Anti-inflammatory
Disease Modifying Anti-Rheumatic Drugs(DMARDs): induction of remission
o Alter immunological reaction by acting on T-cell lymphocyte or macrophages, with inhibition of interleukins
'l* Mechanism of action :
1 1. Immunosuppressive drugs:
1
♦
♦
❖ Drugs that slow disease activity & progression (J, ESR & J, rheumatoid factor) ❖ DMARX)are slow acting dmgs & their effect takes 2- 4 months to appear
.
|
1
1
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Mechanism of action & drugs:
Recombinant
soluble TNG alpha receptor fusion protein
o Reactivation of dormant viral infection e.g. hepatitis B
URT infection
Reactivation of latent TB
o
o
t risk of infection e.g.:
19
month thereafter
month thereafter
dosing at 2"'* & 4"*
750 mg IV infusion followed by additional
❖ Doses:
antigen presenting cells & T lymphocytes
Interact between
Mechanism of action:
week,then every
week
o 40 mg SC every other
o
❖ Drug: Abatacept
week, then every 2
dosing at 2"'' & 6"'
3 mg /kg rV infusion, followed by additional
Monoclonal antibodies
Adalimumab
blockade
❖ Drug class 2. T cell co-stimulatory
Contraindications: active TB, multiple sclerosis & congestive heart faiiure.
4.
o
Infliximab
Reaction to injection Transient BM depression
3. Fleadache
2.
1.
Side effects
week
o 50 mg SC once/
o
Etanercept
interaction with cell surface TNF receptors —> J. TNF activity
macrophages & lymphocytes o TNF inhibitors bind to TNF in circulation & joint —> preventing
o TNF alpha which is pro inflammatory cytokines produced by
1. Tumor necrosis factor(TNF)inhibitors:
o
surface
months
repeated after 6
week, then
once daily
o 400mgIV infusion monthly
receptor
antibodies interleukin 6
antagonist
Monoclonal
CD20 on B cell
o
Tocilizumab
receptor
Interleukin 1
o
receptor:
interleukin 6
antibodies
5. Monoclonal
antibodies against
Monoclonal
Anakinra
antagonist
receptor
Interleukin 1
o 1 gm IV at 0 & 2"'' o lOOmgSC
o
Rituximab
3. B- cell depletion
❖ Biological Response Modifiers(BRMs); biologic DMARDs o Drugs that slow disease activity & progression & minimizing side effects seen with DMARDs o BRMs are rapid acting drugs & their effect takes 2-4 weeks to appear
Juvenile idiopathic arthritis(JIA)=juvenile rheumatoid arthritis(JRA)= juvenile chronic arthritis(JCA) ❖ 3 criteria must be met to diagnose JIA :
1. Arthritis persistent for > 6 weeks 2. Age of onset 6: 1 o Affects < 4joints o Asymmetrical pauciarthritis affecting large joints more than
o
Sacroiliitis: in late childhood
o
onset oligoarticular JIA & affects boys with HLA-B27.
o Altered epiphyseal development
Growth retardation
C
o A. Characteristicfever spikes occur at same time every day with spontaneous return to normal. B. Evanescent(fleeting) salmonpink macular rash, lasts < 1 day, over trunk at height offever C. Hepatosplenomegaly & lymphadenopathy D. Polyserositis 2. Pauciarthritis or polyarthritii appears weeks later 3. Amyloidosis is common
❖ Serology:
o Rheumatoid factor is usually negative o Antinuclear antibody: positive in 80% of cases
o Good prognosis
0 Rheumatoid factor may be positive in 30% of cases. 0 Antinuclear antibody: positive in 40% of cases
❖ Prognosis: 0 Moderate prognosis
o Rheumatoid factor is usually negative o Antinuclear antibody: positive in 20 % of cases
o Poor prognosis
20
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4. Enthesitis-relatccl JIA:
5. Psoriatic JIA:
Diagnosed if there is A. Children with arthritis & enthesitis
A)Children with arthritis and psoriasis
B. Or children with arthritis with at least 2 of the following
1) Acute symptomatic anterior uveitis : pain, redness &
1) Dactylitis
photophobia
2) Nail pitting 3) Onycholysis 4) Positive family history of psoriasis in the first degree
2) Inflammatory lumbosacral pain 3) Sacroiliac joint tenderness 4) Presence of HLA B27 antigen
relatives
5) Positive family history of anterior uveitis, ankyiosing
spondylitis, or inflammatory bowel disease 6. Undifferentiated arthritis.
❖ Differential diagnosis: A. Causes of fleeting, intermittent skin rash : B. Causes of arthritis in children : 1. Juvenile onset of Still's disease 2. Rheumatic fever
3. Cutaneous features of lupus erythematosus are usually induced by sunlight 4. Leukaemia cutis
3) Arthritis associated with infectious agents: septic & viral arthritis 4) Hemophilia. 5) Henoch-schonlein purpura 6) Familial Mediterranean fever
❖ Investigations: Swwaamariiiiiriir i
i iii*>-i.jirMMwiMwiMawwgiiii/
1. As rheumatoid arthritis in addition:
o Rheumatoid factor & Antinuclear antibody: the importance was mentioned earlier 2. Synovial fluid aspiration: to exclude sepsis. ❖ Treatment:
o
As rheumatoid arthritis in addition to steroid treatment for uveitis.
21
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Seronegative spondyloarthropathy (Seronegative spondyloarthritis)
It includes:
1. 2. 3. 4.
Ankylosing spondylitis Reiter's syndrome & Post infectious reactive arthropathy Psoriatic arthropathy Enteropathic arthropathy: arthritis associated with inflammatory bowel disease; ulcerative colitis and Crohn's disease.
5. Undifferentiated spondyloarthropathy
■** General features:
1. Negative rheumatoid factor 2. Central joints affection more than peripheral joints A. Central joints: o Inflammation affecting joints of the spine: spondylitis o Inflammation affecting sacroiliac joints: sacroiliitis B. Peripheral joints: asymmetrical affection 3. Positive family history 4. HLA-B27 found in most of patients except in Behcet's disease HLA B5 is found. 5. Aortic root fibrosis —> aortic incompetence. 6. Eye: red eye 7. Erythema nodosum 8. Spondyloarthropathy:
Enthesitis
ActfUra
tendon
Synovitis
A. Synovitis : inflammation of synovial membrane arthritis B. Enthesitis: inflammation at the enthesis i.e. inflammation at the site of insertion of tendons, ligament & capsule to bone e.g. : o Achilles tendonitis & Plantar fasciitis —»■ heal pain o Metatarsalgia —»• forefoot pain C. Dactylitis (sausage digits) is inflammation of an entire digit (a finger or toe) due to synovitis & enthesitis.
22
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Ankylosing Spondylitis = Marie Strumpell Disease
❖ Definition:
o
Disease characterized by arthropathy starting at the axial joints (sacroiliac & spinal joints) with marked fibrosis & fusion of the vertebrae
Syndesmophyte
❖ Etiology:
Inflammatfon
formation
1. Idiopathic 2. HLA-B27 found in 95% of patients
Erosion
❖ Pathology :
Syndesmophytes
1. Square shaped vertebrae bodies due to erosion of their comers. 2. Bamboo spine:
o Periostea! reaction with new bone formation around vertebrae (i.e. Bony bridging between vertebral bodies = Syndesmophytes) spread up and down from vertebral body with fusion —> bamboo spine 3. Calcification of anterior longitudinal ligament.
4. Extra-articular lesions: ^e below. ❖ Clinical picture:
1- Type of patient: o
Male : female ratio is 3:1
o Age of onset 20 - 40 years old. 2 - General manifestations:
Costovertebral
o Fever, malaise, anorexia, weight loss.
Joints
3- Articular manifestations:
1. Axial arthropathy: A. Sacroiliac joints involvement: Bilateral sacroiliitis :
B. Spine involvement: spondylitis
o Low BACK PAIN & morning stiffness improved by movement & exercise 0 Ending in stooped posture «& shuffling gait o Ending in fixed dorsal kyphosis 0 Positive tests for sacroiliac joints involvement is by inducing 0 Positive tests for lumbar spine involvement: pain through : limited movement(anterior flexion) of a) Anterior push for sacrum lumbar spine through:
b) Pelvic springing: eversion of anterior superior iliae spines c) Lateral side compression of the pelvis
■
Schober & Modified Schober test: distance < 15 cm
C. Other joints:
o Costovertebral joints involvement causes: limited chest expansion with chest pain aggravated by breathing o Atlantoaxial sublaxation: causing cervical cord compression (paraplegia or quadriplegia) or sudden death. 2. Peripheral arthropathy (peripheral arthritis)::
o Asymmetrical POLYarthritis with centrifugal distribution i.e. polyarthritis starts at large joints (hip & shoulder Knee & elbow —> ankle & wrist) then spreads distally to involve peripheral small joints(MCP & PIP) 3. Enthesopathy:
A. Enthesitis: Achilles tendonitis & Plantar fasciitis —> heal pain B. Dactylitis (sausage digits) 23
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4- Extra-articular (systemic) manifestations: 1.
Anterior uveitis & iridocyclitis
2.
Aortitis, Aortic regurge, myocarditis, pericarditis, conduction defects Apical lung fibrosis, restrictive lung disease Amyloidosis of the kidney, IgA nephropathy.
3. 4.
5. Others : o
Abdomen: ulcerative colitis & crohn's disease
o
Prostate: sterile prostatitis Modified New York criteria for diagnosis:
X ray evidence of sacroiliitis + one of the following: 1. History of back pain 2. Limited lumbar movement
3. Limited chest expansion
Differential diagnosis:
1. From diffuse idiopathic skeletal hyperostosis (DISH): o Marked calcification and ossification of paraspinous ligaments, o Sacroiliac joints are not involved in DISH 2. From other causes of back pain e.g. disc prolapse or osteoarthritis
1. E.G.
0 Ankylosing spondylitis
B. Non inflammatory arthritis o Mechanical : Disc prolapse
2. Sex
0
Male > female
o
Male = female
3. 4. 5. 6. 7.
0
Insidious
o
Acute
A. Inflammatory arthritis
o Degenerative: Osteoarthritis Type of onset Age at onset Duration of back pain Effect of exercise (activity) on pain Effect of rest on pain 8. Periodicity of pain :
0 Usually < 40 years old o Usually > 3 month 0 Improve
o Any age o Usually < I month
0
0 Improve
Worse
0 Severe morning stiffness(> 30
o
Worse
o Mild morning stiffness( symmetrical marginal syndesmophytes gives the characteristic bamboo spine, o Calcification of anterior longitudinal ligament.
♦I* N.B.: The vertebral disc is preserved, unlike in spondylosis. j ❖ Treatment: as rheumatoid arthritis
Reiter's syndrome & Post infectious reactive arthropathy
Reiter's syndrome
o Clinical triad of conjunctivitis, arthritis & urethritis following infectious dysentery o Reiter's syndrome is now considered to be a form of reactive arthritis
Reactive arthropathy
❖ Etiology:
o It is sterile arthritis (i.e. viable microorganisms can't be cultured) which occurs following infection, o
Incidence increases in HL B27 +ve
o The infection occurs before the onset of arthritis by 1 -4 weeks o Causative organisms:
1. Chlamydia trachomatis for urogenital infection (urethritis) 2. Salmonella, shigella, yersinia & campylobacter jejuni for GIT infection ❖ Clinical picture:
1- Type of patient:
o Young adults, aged 20-40 years in o
Male to female ratio: 15: 1. 25
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2 - General manifestations:
o Fever, malaise, anorexia, weight loss. 3- Articular manifestations:
1. Peripheral arthropathy (peripheral arthritis): o Asymmetric, OLIGO arthritis, usually involve bigjoints oflower limbs: knees, ankles and/or feet, o Wrists and digits are less common, o
Erosions occur in chronic cases
2. o o 3. A. B.
Axial arthropathy: in HLA - B27 +ve patients Unilateral asymmetrical sacroiliitis Spondylitis Enthesopathy: Enthesitis: Achilles tendonitis & Plantar fasciitis —> heal pain Dactylitis (sausage digits)
4- Extra-articular (systemic) manifestations:
1. CNS: meningoencephalitis and neuropathy 2. Ocular:sterile conjunctivitis, anterior uveitis 3. Cardiac: Aortitis, Aortic regurge, myocarditis, pericarditis, conduction defects 4. GIT : ileitis, colitis
5. Genitourinary: non-gonococcal urethritis, prostatitis, cystitis, salpingitis 6. Mucocutaneous:
a. PAINLESS oral ulcers : mouth, tongue and palate b. Keratoderma blennorrhagicum: o Macules on palms & soles, became vesicular, pustular then keratotic . c. Circinate balanitis :
o Circinate ulcers on penis ❖ Investigations: A. Biochemical:
1. Blood:
o o o 2.
Leukocytosis, normocytic normochromic anemia tESR Negative rheumatoid factor. Urine analysis: sterile pyuria.
B. Radiological: X-ray:
o Juxta articular osteoporosis o
Sacroiliitis
o Ankylosing spondylitis-like spine Treatment:
A. General measures :
o Bed rest with physiotherapy
o Symptomatic treatment e.g. sulphacetamide eye drops for conjunctivitis B. Specific therapy:
1. Treatment for the cause e.g. antibiotics to eliminate triggering infection e.g. tetracycline for urethritis 2. Articular disease:
a. In mild cases: NSAIDs manage most patients b. In severe cases: DMARDs as Methotrexate, Azathioprine & Sulphasalazine. c. In resistant cases: intra-articular steroids
26
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
P$oriatic arthropathy ❖ Definition:
o Sero-negative inflammatory arthritis with coincidental psoriasis o
Incidence increases in HL B27 +ve
V Types:
Type
1. Asymmetric oligoarthropathy
2. Symmetric polyarthropathy
❖ Clinical picture o Asymmetric involvement of both small and large joints o Dactyiitis(sausage digit) o
As rheumatoid arthritis with NEGATIVE rheumatoid factor & ABSENT
❖ Incidence:
o 40% -70 % of psoriatic patients
o 30% of psoriatic patients
subcutaneous nodules.
3. Psoriatic spondyioarthritis
o Spondylitis with sacroiliitis o ± conjunctivitis & iritis
4. DISTAL interphaiangeai arthropathy with psoriatic nail
o
disease.
DIP involvement
0 Nail changes : Pitting , Subungual hyperkeratosis , Onycholysis & transverse
0 20% of psoriatic patients o 10 % of psoriatic patients
Ridges 5. Arthritis mutilans: severe
destructive arthropathy
0 Telescopic deformity (see before in rheumatoid arthritis)
0 immune (Antigen -antibodies) complexes ^ complement activation —> initiate inflammation 2. Genetic : higher incidence of SEE among: o Females (X- chromosomes disease) o o o
HLA association HLA B-8, DR2 Monozygotic twins Relatives of SEE patients
3.
Environmental factors:
o
Ultraviolet B light
o 4. o o o
Infection: specially with Epstein Barr virus, HBsAg (Australia antigen) Endocrinal: SEE flares up during : Pregnancy & post-partum period
5.
Drug induced SEE:
Contraceptive pills
Hormonal (estrogen) replacement therapy. A. Drugs that induce (cause) SEE: o Procainamide and quinidine
B. Drugs that flare (exacerbate) SEE :
1. Antiarrhythmics 2.
Anti-inflammatories
o
Penicillamine and sulfasalazine
0
Para-aminobenzoic acid
3.
Antimicrobial
0
Tetracycline, Minocycline,
0
Penicillin, sulfonamide
0 0
Mephenytoin Hydrochlorothiazide
isoniazid 4.
Anticonvulsants
5. Antihypertensives 6. Hormonal therapy 7. Biologies
o o o 0
Phenytoin Hydralazine, methyldopa Contraceptive pills Interferon alpha
o Tumor necrosis factor inhibitors e.g. Golimumab
Pathology of SEE:
1. Vasculitis: cutaneous, cerebral, coronary, pulmonary, renal &_mesenteric vasculitis. Antinuclear antibody
2. Synovitis: non erosive (non deforming) 3. Polyserositis
4. Kidney: Silver wire loop lesion
5. Spleen : onion-skin lesions in splenic arteries due to disposition of collagen around them. 6.
Connective tissue lesions: EE cell phenomenon
A. Lupus Erythematosus cells:
o The neutrophil that has engulfed the degraded nuclear material of another cell. B. Lupus Erythematosus bodies or hematoxylin bodies:
Nucleus pushed
o The degraded nuclear material from an injured cell is easily stainable with hematoxylin, that appear as large purple amorphous inclusion body that nearly fi lls the cytoplasm displacing the nucleus peripherally C. Non specific, found in : o Systemic Lupus Erythematosus: 80 % of cases
o Others (20 % of cases) e.g. rheumatoid arthritis, scleroderma, dermatomyositis, polyarteritis nodosa, chronic hepatitis (lupoid), acquired hemolytic anemia, and Hodgkin disease.
31
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Clinical picture:
A- Type of patient:
Female to male ratio 10:1 ,Age: peak 13 - 40 years old, Course : remission & exacerbation B- General manifestations:
o
Fever: due to infection or active disease
o Malaise, anorexia, weight loss
C - Articular manifestations: Musculoskeletal: P* common
1. In majority of cases: mainly arthralgia «& myalgia 2. In minority of cases(30 % of cases): o Mild transient non erosive (non deforming) arthritis 3. In chronic cases :
A. Jaccoud's arthropathy:
o Inflammation of the joint capsule and subsequent fibrotic retraction leading to ulnar deviation deformity due to metacarpophalangeal joint subluxation B. Avascular necrosis of the hip may occur with steroid therapy D - Extra-articular (systemic) manifestations:
1- Skin (Mucocutaneous manifestation: 2"" common): DISCOID lupus erythematosus(DLE): 1. Acute cutaneous lupus:
A. Lupus malar rash :erythema over the butterfly area of face (nose & cheeks)sparing the nasolabial folds B. Photosensitive lupus rash: exposure to sunlight exacerbates skin rash even systemic manifestation C.
Others: maculopapular lupus rash & bullous lupus.
2.
Subacute cutaneous lupus:
A.
Annular polycyclic lesions
B.
Psoriasiform lesions A. Classic discoid rash
,/j,yi,/2y2y7,/2/j B. Discoid
C. Lupus
lupus/lichen planus overlap
panniculitis (profundis):
D. Chilblains
lupus
1 (
lupus
o Papulonodular with
with
B OOOO g
o Telangiectasia o
0 Papules with
F. Tumid
❖ Non scaly erythematous: o Plaques
❖ Adherent scalv ervthematous :
0 Plaques with
E. Hypertrophic (verrucous)lupus
o
■1
\OQQO>^
Flat topped
Follicular
violaceous
plugging
lesions
0
Painful subcutaneous nodules
o o
o
Hyperkeratotic
like
lesions
0 That may end by scarring & dys-pigmentation (hyper or hypopigmentation)
Urticarial lesions
0
Without
scarring & without dyspigmentation ❖ Most frequent site: o
Localized: above the neck
o
0 On sun-exposed
0
Face
areas: face,
o
Proximal
i.e. Acral
limbs
lesions
Generalized:
extensor
above and
surfaces of
o
Distal limbs
0 On sun-exposed areas
0
Face
o
Trunk
forearms, upper trunk) G. Mucosal lupus: oral and conjunctiva! ulceration below the neck
32
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4. Alopecia:
o Nonscarring alopecia: diffuse thinning and fragility ofthe hair with visible broken hair o Scarring alopecia : due to DLE on scalp 5. Others lesions due to vasculitis:
A. Raynaud's phenomenon
B. Peripheral (fingers & toes) ulceration & digital gangrene due to cutaneous vasculitis C. Purpuric rash with elevated edge 2- Neuropsychiatric:
1. Psychiatric : depression & psychosis
❖ N.B.: Psychosis due to lupus must be differentiated from steroid induced psychosis which occurs in the first weeks of steroid therapy at doses of> 40 mg of prednisone or equivaient, it resolves over several days after steroids are decrease or stopped. 2. Cerebral:
❖ N.B.: Cerebral manifestations due to :
o Lupus cerebritis, vasculitis, thrombosis, infection, metabolic derangement or drug induced a
o Neuropathy: mononeuritis multiplex, peripheral or cranial neuropathy o Myopathy o
Convulsions
o
Chorea & ataxia
o Cerebral vasculitis —> TIAs, stroke (hemiplegia), acute confusional state. Coma o Transverse myelitis 3- Ocular lesions:
1. Conjunctivitis 2. Episcleritis 3. Scleritis
4. Iritis & anterior uveitis
5. Sjogren's syndrome
6. Fundus: Retinal vasculitis can cause infarcts, cytoid bodies which appear as hard exudates 4- Cardiovascular system:
1. Pericardial: pericarditis ± pericardial effusion ± constrictive pericarditis 2. Myocardial: myocarditis, cardiomyopathy 3. Endocardia!: Libman-Sacks endocarditis :
o Sterile non infective verrucous endocarditis affecting mitral valve (or less commonly aortic valve) ending in MR or rarely MS 4. Blood vessels:
A. Coronary vasculitis with coronary artery occlusion
ischemic heart disease
angina pectoris or myocardial
infarction
B. Hypertension C. Thrombosis(venous, arterial)
❖ N.B.: Child bom to mother with SEE —> congenital conduction defects
33
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Detached blood clot
5- Chest: ^nr-m—i
A. Pleura : pleurisy ± pleura! effusion B. Lung: 1. Alveolar hemorrhage & ARDS 2. Pneumonitis due to SLE or drug induced e.g. methotrexate
Blood
3. Interstitial pulmonary fibrosis 4. Shrinking lung syndrome :
o Restrictive lung disease (dyspnea with episodic pleuritic chest pain & decreased lung volume) without imaging findings of interstitial fibrosis or pleura! diseases but only elevated diaphragm o Etiology : unknown, most probably due to myositis or myopathy affecting both sides of diaphragm. C. Pulmonary vessels:
1. Pulmonary vasculitis with pulmonary hypertension & cor pulmonale 2. Pulmonary embolism secondary to DVT —> recurrent pulmonary infarction ❖ N.B.: Causes of dyspnea in SLE:
1. CVS: pericardial effusion or hiventricular heart failure due to myocarditis 2. Chest: o
Pleural effusion
o Corpulmonale due to interstitial pulmonary fibrosis or pulmonary hypertension o Pulmonary embolism secondary to DVT
6- Hematological & reticuloendothelial system '(RES)n 1. Blood:
i.
Pancytopenia:
A. Anemia:
B. Leukopenia:
C. Thrombocytopenia:
0
o
o
Anemia of chronic disease
Differential count:
o Lupus nephritis ending by chronic kidney disease.
Lymphopenia: in
o Autoimmune hemolytic anemia o Drug induced BM depression
active disease
Autoimmune
thrombocytopenia o
In active disease
2. RES: hepatosplenomegaly & generalized lymphadenopathy 3. Antiphospholipid syndrome: o Clinical picture: Unexplained recurrent spontaneous abortions with recurrent thrombosis
o Investigations: Antiphospholipid antibodies : lupus anticoagulant, anticardiolipin antibodies & anti-P2 glycoprotein I antibodies
4. Immune deficiency & infection : due to leukopenia and hypocomplementemia 7- Renal: lupus nephritis: A. Clinically:
1. Asymptomatic with abnormal sediments : proteinuria, hematuria, casts 2. Nephrotic syndrome, nephritic syndrome 3. Acute or chronic renal failure
❖ N.B.: Nearly all patients with SLE have histological evidence of renal involvement despite the absence of clinical signs.
B. Serologically: 1. tAnti-DNA 2. I Complement(hypocomplementemia)
34
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
C. Histopathology : Renal biopsy :
❖ N.B.: Renal biopsy may be needed to classify the type of disease activity, assess chronicity & guide immunosuppressive therapy. SSiiSSr
❖ International Society of Nephrology(ISN)and the Renal Pathology Society(RPS) classification:
1. 2. 3. 4. 5.
Class I: minimal mesangial lupus nephritis Class II: Mesangial proliferative lupus nephritis Class III: Focal lupus nephritis (active and chronic; proliferative and sclerosing)
Class rV: Diffuse lupus nephritis (active and chronic; proliferative and sclerosing; segmental and global)
Class V: Membranous lupus nephritis 6. Class VI: Advanced sclerosis lupus nephritis ❖ Treatment: o
Class I & II: corticosteroids
o Class III-V : add immunosuppressives e.g. azathioprine, cyclophosphamide o Class: VI: renal dialysis
i
8- GIT:
1. PAINLESS oral ulcers
2. Anorexia, nausea, vomiting ± hematemesis (esophagitis, esophageal ulcers, gastritis, peptic ulcer) 3. Abdominal pain: o
Pancreatitis
o
Peritonitis
o
Mesenteric vasculitis —> mesenteric vascular occlusion
N.B.: differential diagnosis of patient complaint arthropatby with oral ulcers: o Reactive arthritis (Reiter syndrome) o Inflammatory bowel disease o
SLE
o Vasculitis e.g. Behcet's disease
❖ Criteria of diagnosis of SLE :
I- According to 1997 revised criteria of American College of Rheumatology: at least 4 of the following II disorders must be present: 1. Malar rash 2. Discoid rash
3. Photosensitivity 4. Painless oral ulcers
5. Polyserositis : pleurisy or pericarditis 6. Peripheral joint arthritis: 2 or more peripheral joints 7. Proteinuria, cellular cast
8. Psychosis or seizures 9. Pancytopenia 10. Positive antinuclear antibodies 11. Positive anti dsDNA or anti-Sm antibodies
35
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2- 2012 SLICC: systemic lupus erythematosus international collaborating clinics classification criteria for SLE:
The patient has biopsy proven lupus nephritis with positive ANA or positive anti dsDNA OR
Patient satisfies four of the criteria, including at least one clinical & one immunologic criterion : A. Clinical criteria:
1. Acute or subacute cutaneous lupus 2. Chronic cutaneous lupus 3. Oral or nasal ulcers in the absence of other causes e.g. Behcet's disease
4. Nonscarring alopecia in the absence of other causes e.g. alopecia areata 5. Synovitis involving two or more joints 6. Serositis in the absence of other causes e.g. Renal failure:
o Typical pleurisy for more than 1 day OR pleural effusions OR pleural rub o Typical pericarditis (pericardial pain) for more than 1 day OR pericardial
B. Immunological criteria: 1) ANA
2) Anti-dsDNA antibody 3) Anti-Sm antibody 4) Antiphospholipid antibody positivity: o Lupus anticoagulant o High-titer anticardiolipin antibody level
5) Low complement(J.C3, J.C4, or I
effusion OR pericardial rub
7. Renal : proteinuria > 500 mg /24 hours OR red blood cell casts 8. Neurologic: psychiatric or cerebral manifestations 9. Hemolytic anemia
CH50)
6) Direct Coombs' test in the absence of hemolytic anemia
10. Leukopenia(< 4000/mm3 at least once) or lymphopenia( 1 episodes) vascular thrombosis 2. Recurrent unexplained gestational morbidity
3. Anti-|32 glycoprotein I antibodies(IgG and/or IgM) 38
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Investigations: A. Biochemical:
1. Blood picture:
o Thrombocytopenia, hemolytic anemia, TTP, o Prolonged partial thromboplastin time (fails to be corrected by plasma) 2. Serology :
o Lupus anticoagulant on at least 2 occasions at least 12 weeks apart, o Medium to high titre of anticardiolipin antibodies (IgG and/or IgM) o Anti-p2 glycoprotein I antibodies (IgG and/or IgM) o ANA: usually negative B. Radiological: to confirm thrombotic event o
CT, MRI brain, chest, abdomen
o o
Doppler ultrasound: for DVT Echocardiography
❖ Treatment:
A. For thrombosis: IV or SC heparin followed by warfarin therapy for life B. For complications: 1. During pregnancy:
o Patients with history of thrombosis in previous pregnancies should receive therapeutic dose of heparin during pregnancy and for 6 weeks postpartum
2. Hemolytic anemia or thrombocytopenia in secondary APS : IV corticosteroids 3. Catastrophic antiphospholipid Syndrome: : o Plasma exchanges, intravenous immunoglobulin, cyclophosphamide
Migraine Stroke Transient ischaemic attack
Pulmonaiy emboiism Cardiac vaive pathology Coronary artery disease Renai vein thrombosis Renai infarction
Thrombotic microangiopathy Antiphospholipid syndrome nephropathy Recurrent early miscarriage Intrauterine fetal death
Early or severe pre-eciampsia (or both) Intrauterine grow/th restriction Raynaud's phenomenon Livedo reticularis
Deep vein thrombosis
APS
39
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Scleroderma Or Systemic Sclerosis
❖ Definition:
o It's a connective tissue disorder characterized by thickening, hardening, & fibrosis of skin with involvement of muscles, blood vessels & internal organs most probably due to autoimmune mechanism. ❖ Etiology: idiopathic, most probably due to autoimmune mechanism.
❖ Pathology 1. Skin:
4. Deposition of collagen in skin, blood vessels & internal organs 5. Late hardening & adherence to underlying tissue ± calcification 2. Muscles: myositis ± atrophy in cardiac, skeletal & smooth muscles. 3. Blood vessels:
o Vasculitis : causing Raynaud's phenomenon o Endarteritis obliterans: causing ulcers, pulmonary hypertension Clinical picture: Nto«r^iogw>esis and bushy capHiaries
A- Type of patient: o
Females : male ratio 3 to 1
o Mean age 20-50 years old. B- Cutaneous manifestations: AvafCUMT
A. Early :
1. Raynaud's phenomenon :
o It is the FIRST & COMMONEST presentation occurs in most patients with systemic sclerosis(70% of cases) o It may occur years before other clinical pictures.
o It is due to vasospasm of peripheral arteries causing color changes (Pallor-+ Cyanosis ^ Redness) o Associated with nail fold capillaries abnormality (erythema, dilated capillaries, tortuous, dropped out capillary loops) can be detected before other clinical pictures. 2. Non pitting edema 3. Skin induration with sausage swelling B. Later :
1. a.
Skin tightening: Begins on :
Distal part of limbs i.e. The fingers of hands
flexion contracture with limitation of both flexion & extension
of fingers o
The face: taut, expressionless, with beaked nose «& slit like mouth opening (fish mouth appearance)
5.
Then the proximal parts of the extremities & trunk Lastly to the thorax and abdomen. Skin hardening & adherence to underlying tissues Skin shinnying with atrophy (loss of skin adnexa)& ulceration Skin dyspigmentation : Hypo or hyperpigmentation Skin calcinosis (calcifications) & telangiectasia
6.
Peripheral (fingers & toes) ulceration & digital gangrene due to cutaneous vasculitis
b. c.
2. 3. 4.
40
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
C- Non cutaneous (systemic) manifestations:
1- Articular manifestations
1. In majority of cases : mainly arthralgia & myalgia 2. In minority of cases :
o Mild transient non erosive (non deforming) arthritis 3. In chronic cases :
o Leathery crepitus in affected tendon sheath (tenosynovitis) or joints o Muscles wasting & osteoporosis from immobilization
o Myopathy due to associated myositis (sclera-dermato-myositis) 2- Neurological:
Headache & stroke from hypertensive renal crisis 3- Cardiovascular system: uncommon & late
1. Pericardial: pericarditis ± pericardial effusion ± constrictive pericarditis 2. Myocardial: myocarditis, restrictive cardiomyopathy 3. Endocardial: thickening, resulting in MR & TR 4. Blood vessels:
o Coronary vasculitis with coronary artery occlusion —> ischemic heart disease —> angina pectoris or myocardial infarction o Hypertension
5. Conduction pathways: heart block (fibrosis of conduction pathways)
4- Chest: leading cause of death
1. Pleura : Pleurisy 2. Lung: A. Restrictive hypoventilation due to:
o Tight skin & diaphragm
o Costovertebral joints involvement causes; limited chest expansion with chest pain aggravated by breathing o Interstitial pulmonary fibrosis
B. Aspiration pneumonia due to over flow from esophageal reflux C. t incidence of bronchial carcinoma 3. Pulmonary vessels:
,
o Pulmonary vasculitis with pulmonary hypertension & cor pulmonale
5- Renal:
1. Persistent urinary abnormalities
2. Vasculitis of renal blood vessels : hypertension & chronic renal failure 3. Scleroderma renal crisis: o
The most serious
o
Due to endarteritis obliterans of interlobular renal arteries
o Clinical picture : abrupt onset of: a. Acute renal failure
b. Malignant hypertension c. Microangiopathic hemolytic anemia
Schislocytfl
41
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
6- GIT:
1. Mouth: inability to open mouth (fish mouth appearance) 2. Esophagus specially lower 1/3: o Esophageal hypomotility —>• loss of peristalsis with dysphagia
o Loss of lower esophageal tone ^ GERD with regurgitation leading to aspiration pneumonia 3. Stomach:
o Gastric hypomotility —>• anorexia, nausea, distension, pain o Hematemesis : due to rupture offragile gastric blood vessels (gastric antral vascular ectasia = Watermelon Stomach) 4. Small intestine : stagnant loop syndrome:
o a. b. c.
Intestinal hypomotility leading to stagnation of intestinal contents which favors overgrowth of bacteria leading to: Consumption of folic acid & vitamin B12^ megaloblastic anemia Deconjugates bile salts (release bile acids —> damage mucosa) Diarrhea & malabsorption
5. Large intestine :
o Constipation due to pseudo-diverticulae (wide mouthed)& atony
42
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2. Linear scleroderma
o
2. Graft Versus Host Disease 3. Lichen sclerosus
o
o
o
o
o
c)
Raynaud's phenomenon Esophageal hypomotility Sclerodactyly Telangiectasia
Calcinosis
43
1. Phenylketonuria 2. Porphyria cutanea tarda 3. Myxedema D. Deposition : 1. Scleromyxedema 2. Systemic amyloidosis 3. Nephrogenic systemic fibrosis
o
SEE.
e.g. polymyositis or
autoimmune disease
Scleroderma associated with other
4) Overlap syndrome
4. Eosinophilia-myalgia syndrome by L-tryptophan
3. D-Penicillamine
1. Bleomycin 2. Carbidopa
E. Occupational e.g. Silica F. Toxic or iatrogenic:
Acute renal failure
o Pulmonary fibrosis
of:
organ involvement with a greater risk
Severe internal
syndrome:
It is known as CREST
extremities (fingers, & feet)& face
involvement is not severe
b)
extremities, trunk, in addition to distal
WITHOUT skin
manifestation
Proximal
face.
b) Internal organ
involvements
hardening to
o Internal organs
sine scleroderma
3) Systemic sclerosis
distal extremities (fingers, & feet = sclerodactyly)&
a) Diffuse skin
systemic sclerosis:
B. Systemic scleroderma (Systemic Sclerosis): 2) Diffuse cutaneous
1) Limited cutaneous systemic sclerosis: a) Limited skin hardening to
C. Metabolic:
limbs, head and face.
Bands or streaks of hardened skin on the
A. Genetic e.g. progeria B. Immune-mediated/inflammatory : 1. Bosinophilic fasciitis
2. From scleroderma mimickers:
the trunk & limbs.
by: 1. Begins as discolored skin area (lighter or darker skin) then develop whitish center & purple border 2. May be itchy, hairless, waxy and shiny. 3. Localized (few patches) or generalized(many patches) on
of hardened skin characterized
o Circumscribed oval patches
involvements
o Skin manifestation WITHOUT internal organs
1. Morphea
A. Localized scleroderma:
1. From other variants of scleroderm a:
Differential diagnosis of scleroderma:
Investigations: A. Biochemical:
1. Blood picture: o t ESR & CRP
o
Normocytic normochromic anemia & microangiopathic hemolytic anemia may occur
o Microcytic hypochromic anemia o Megalobiastic anemia 2. Serological: a. Positive rheumatoid factor in 30 % of cases
b. Positive ANA in 80 % of cases with nucleoiar or speckled pattern c. Antibodies to extractable nuclear antigens :
o Anti scl-70 antibodies(15 % of cases) associated with diffuse cutaneous systemic sclerosis o Anticentromere antibodies(25 % of cases) associated with limited cutaneous systemic sclerosis (CREST syndrome) B. Imaging: 1. Nail fold capillaroscopy : A. Primary Raynaud's disease :
B. Secondary Raynaud's disease in scleroderma :
o Nail fold capillaries are normal
o Nail fold capillaries abnormality (dilated capillaries, tortuous, dropped out capillary loops) can be detected before other clinical pictures.
2. Plain chest X-ray : interstitial lung fibrosis
3. X-ray with barium swallow : dilated esophagus with gastroesophageal reflux 4. X-ray hands : o Calcification (calcinosis) around fingers o Resorption of the tuft of the distal phalanges C. Interventional:
1. Esophageal manometer : show lack of distal peristalsis &J, esophageal sphincter pressure 2. Pulmonary function test: restrictive pattern 3. Skin biopsy ^ collagen in denuis ❖ Treatment:
❖ General measures & symptomatic treatment: 1.
Raynaud's phenomenon :
2.
Alpha blocker e.g. Prazocine Phosphodiesterase 5 inhibitor e.g. sildenafil Calcium channel blocker e.g. nifedipine Dipyridamole & low dose aspirin to prevent platelet aggregation Endothelin receptor antagonist e.g. Bosentan Endoscopic thoracic sympathectomy Others : topical nitroglycerin & IV prostaglandins Interstitial pulmonary fibrosis: Corticosteroids & Cyclophosphamide
3.
Pulmonary hypertension : Bosentan
4.
Renal crisis & hypertension : ACEI e.g. captopril ± dialysis
o o o o o o o
5. GIT: o o
Broad spectrum antibiotics for bacterial overgrowth Proton pump inhibitors & Pro kinetic drugs for esophageal involvement ❖ Specific therapy:
1. D-penicillamine : J, collagen production ^ I progression of skin disease. 2. Corticosteroids:
o Indicated for treatment of inflammatory myositis, pericarditis or pulmonary fibrosis 3. Immunosuppressives:
o Methotrexate, Azathioprine, Cyclosporine & Cyclophosphamide o Indicated in rapidly progressive cases 44
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Inflammatory myopathies:Polymyositis, Dermatomyositis & Inclusion body myositis Polymyositis & Dermatomyositis • i--- t
iimiwiijii'l^
❖ Etiology:
❖ Auto immune inflammation ofskeletal muscles (polymyositis) with or without skin lesion (dermatomyositis) ❖ It may be precipitated by viral infection : 1. Human immunodeficiency virus(HIV) 2. Human T-cell lymphotrophic virus type I 3. Coxsackievirus B.
❖ Pathology:
Lymphocytic cellular infiltration of muscles with patchy necrosis specially around blood vessels ❖ Classifications:
1. 2. 3. 4.
Adult polymyositis Adult dermatomyositis Childhood dermatomyositis
PM / DM associated with malignancy
5. PM / DM associated with other eonnective tissue disease e.g. mixed connective tissue disease ❖ Clinical picture:
A- Type of patient: o Type of onset: insidious o Age of onset: 30-50 years old o
Female to male ratio 3 : 1
f^ch 7qo\
B - General manifestations:
it J
o Fever, malaise, anorexia, weight loss
C- Muscular manifestation :
A. The most common presentation is: muscle weakness (myopathy):
1. Bilateral proximal symmetrical muscle weakness affecting shoulder & pelvic girdle
difficulty in climbing stairs
or rising from low chair
2. Esophageal muscle weakness —> dysphagia, regurgitation & aspiration pneumonia 3. Pbaryngeal, laryngeal, respiratory muscle weakness dysphagia, dysphonia, dyspnea with respiratory failure. B. 1. 2. o
Myalgia & myositis causing : Early: pain & tenderness Late: ending by: Wasting & atrophy
o Calcinosis & fibrosis in damaged muscle causing flexion contracture C. Occular & facial muscles are spared. 45
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
D- Cutaneous manifesations:
♦t' Several types that may be transient or predominant
1. Heliotropic rash: violaceous rash on upper eyelids with eyelid edema. 2. Erythroderma :
o Extensive erythema over the forehead, malar area with affection of nasolabial folds & chin 3. Gottron's sign: symmetrical erythema over the ; o Extensor surface of metacarpophalangeal joint & proximal interphalangeal joint o
Extensor surface of the elbows & knees
4. Shawl sign: diffuse flat erythema over the upper back & shoulder 5. V sign: diffuse flat erythema over the anterior neck & chest (V shaped area) 6.
Mechanic's hand:
o Rough cracking skin at the finger tips with irregular dirty lines 7.
Others:
A. Raynaud's Phenomenon with nail fold capillaries abnormality B. Periungual erythema C. Calcification :
o Localized to fingers : calcinosis circumscripta o Or generalized ; calcinosis universalis D. Healing by Depigmented scars.
Calcification
E- Other features:
1. Joints: arthralgia or mild transient non erosive (non deforming) arthritis 2. CVS: myocarditis causing heart failure, arrhythmias. 3. Chest: interstitial pulmonary disease. 4.
Cancer:
o About 20% of patients with PM or DM, malignancy may precede or follow onset (by up to 3 years) o This occurs particularly in males after the age of 40 years o o 5. o o 6.
So, you must to search for malignancy Common sites: Lung , Stomach, Colon , Prostate, breast & ovary Abdomen : in Childhood dennatomyositis At age 4-10years old Recurrent abdominal pain due to vasculitis Antisynthetase syndrome:
o About 20 % of patients with PM or DM have antibodies to aminoacyl t RNA synthetase enzymes o These patients are more liable to; a. Raynaud's phenomenon b.
Mechanic's hand
c. Non erosive (non deforming) arthritis d. Interstitial pulmonary fibrosis 46
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Differential diagnosis: 1. From causes of primary & secondary myopathies (see neurology) 2. From causes of muscle weakness: Motor neuron disease, myasthenia gravis ❖ Investigations: A. Biochemical: 1. Blood:
o tESR o t Muscle enzymes: CPK, LDH,aldolase, AST
"t* N.B.: normal CPK does not exclude the diagnosis 2. Serological: o ANA,rheumatoid factor are positive o Myositis-speciflc antibodies(MSAs): anti-Jo-1 antibodies, anti-Mi-2 antibodies 3. Tumor markers for malignancy B. Radiological: o MRl can detect active myositis & guides the site of biopsy o Imaging screen for malignancy. C. Interventional:
1. Muscle biopsy :
o The definitive test to establish the diagnosis, there is atrophy, fibrosis, necrosis & degeneration 2. EMG:
o To differentiate between myopathic(myopathy + irritability of muscles)& neuropathic causes of muscle weakness ❖ Treatment:
1. Prednisone
2. Immunosuppressive : Prednisone, Methotrexate, Azathioprine, Cyclophosphamide 3. IVIG
4. Rituximab: anti CD20 monoclonal antibodies
5. Removal of tumor if present: dramatic improvement 6. Physiotherapy
Inclusion body myositis
Indu^ bodies vacuoles
o o 1. 2. o 1. 2.
The most common inflammatory muscle disease in older patient usually > 50 years old The disease is characterized by slowly progressive weakness and wasting affecting : Both distal and proximal muscles, most apparent in the finger flexors and knee extensors Or isolated erector spinae weakness(droopy neck) Diagnosis: Anti cytoplasmic 5'-nucleotidase antibodies
Muscle biopsy : cytoplasmic vacuoles and filamentous inclusions in the muscle fibers
47
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Polymyalgia rheumatica
❖ Definition :
o It is a clinical syndrome characterized by PROXIMAL symmetrical muscle pain (myalgia) with stiffness in the : ■
Neck & back
■ ■
Proximal muscles of the upper limbs: shoulders, upper arms Proximal muscles of the lower limb: hips (thighs & buttocks)
❖ Etiology : 1. Autoimmune
2. HLA DR4 association
W
'
^
3. Triggered by viral infection e.g. the human parvovirus B19 ❖ Clinical picture: | J
1. Type of patient: elderly patient, age of onset is 70 years old 2. General manifestations : Fever, fatigue, malaise, anorexia, weight loss 3. Muscle pain with stiffness affecting mainly
©
o
Neck & back
o o 4. 5.
Proximal muscles of the upper limbs: shoulders, upper arms Proximal muscles of the lower limb: hips (thighs & buttocks) Early morning stiffness with night pain. 50% of patients associated with temporal arteritis
6. On examination :
o Tender muscles, later on become atrophic. o Active movements: painful restriction o Passive movements: preserved Differential diagnosis: 1. Rheumatoid arthritis.
2. Inflammatory myopathy. 3. Fibromyalgia. 4. Cervical spondylosis. 5. Cancer
❖ Investigations: o tHighESR&CRP o N.B. very occasionally the ESR is low in early course ofthe disease ❖ Treatment:
1. Corticosteroids:
o Dramatic response within 3 days o 10 20 mg prednisolone/day and then tapering after 4-8 weeks o 5-10 mg/day as a low dose maintenance may be required for a time 2. Immunosuppressive: methotrexate or azathioprine.
48
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Fibromyalgia syndrome
❖ Deflnition
o Chronic WIDESPREAD DIFFUSE muscle pain and tenderness ❖ Etiology:
o Idiopathic, may be due to sleep abnormality and reduced threshold to pain at certain sites. Clinical picture: Type of patient: Young or middle-aged Females > males
B. Fibromyalgia is a syndrome that consists of the following signs and symptoms:
Persistent(>3 month) widespread diffuse pain :
Focal tender points on both sides of the body, above and below the waist, including the axial spine Muscle stiffness
Fatigue; disrupted and unrefreshing sleep Cognitive difficulties Others :
Functional impairment of activities of daily living Anxiety and/or depression & Multiple unexplained symptoms Diagnosis, differential diagnosis & investigations:
❖ It is diagnosed by exclusion of other causes that can mimic fibromyalgia : o Autoimmune disease : Rheumatoid arthritis, Systemic lupus erythematosus, Polymyalgia rheumatic o Hypothyroidism, Hyperparathyroidism, Addison Disease
*1* All investigations are normal and the value is for exclusion of other causes of muscle pain . Criteria for diagnosis: ❖ 2010 American College of Rheumatology(ACR), fibromyalgia diagnostic criteria (FDC): i.
Two tests used for assessment:
1. Widespread pain index(WPI)quantifies the extent of bodily pain on a 0-19 scale by asking patients if they have had pain or tenderness in 19 different body regions 2. Symptom severity scale (SSS) quantifies symptom severity on a 0-12 scale by scoring problems with fatigue, cognitive dysfunction and unrefreshed sleep over the past week Interpretation of results: A. Physician administrated 2010 ACR FDC
11.
B. Patient self report 2010 ACR FDC questionnaires 1) WPI -HSSS> 13 2) The symptoms have been present at a similar level for at least 3 months 3) The patient does not have another disorder that would otherwise explain his or her pain 1. WPI > 7-t SSS >5 or WPI 3-6 +SSS >9
Treatment:
1. Psychotherapy 2. Aerobic exercise
3. 4. 5. 6.
Analgesics e.g. NSAIDs Benzodiazepine e.g. alprazolam Muscle relaxants e.g. cyclobenzaprine Antidepressant e.g. amitriptyline & fluoxetine (SSRI) 49
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Sjogren's Syndrome: Sicca Complex Definition:
o Chronic inflammatory autoimmune disorder, characterized by progressive lymphocytic infiltration & destruction of o
exocrine glands Associated with HLA-B8 , HLA-DR3
❖ Types: 1. Primary Sjogren's syndrome:
o Sicca complex with no other connective tissue disease o Associated with high incidence of lymphoproliferative disorders e.g. lymphoma 2. Secondary Sjogren's syndrome:
3. Sicca complex with another connective tissue disease e.g. rheumatoid arthritis (the commonest), SLE, Scleroderma, polymyositis & mixed connective tissue disease can occur. ❖ Clinical picture: A- Glandular manifestations: Sicca complex:
❖ 1. 2. 3.
Due to destruction lacrimal, salivary & skin glands by inflammatory cells leading to: Dry eye (keratoconjunctivitis sicca ,xerophthalmia) loss of tears comeal ulcers Dry mouth (Xerostomia) —> oral ulcers, halitosis (bad mouth odour)& enlarged functionless parotids Dry nose, dry skin & dry vagina
B- Extra- glandular (systemic) manifestations: 1. Associated Autoimmune diseases: autoimmune thyroiditis, myasthenia gravis, chronic active hepatitis & primary biliary cirrhosis. 2. Arthritis(non erosive polyarthritis), Peripheral neuropathy, Pulmonary fibrosis & Cryoglobulinemia. 3. Dysphagia (J,esophageal motility) & Enlarged LN: lymphadenopathy with increased incidence of lymphomas 4. Renal tubular acidosis & glomerulonephritis. 5. Raynaud's phenomenon. Investigations: A. Biochemical:
1. Serological: o Positive rheumatoid factor & antinuclear antibody o Anti-Ro(SS-A) antibodies: can cross placenta & cause congenital heart block o
Anti La (SS-B) antibodies.
2. Virology to exclude other causes of dryness e.g. HCV 3. Regular follow up to detect early lymphoproliferative changes in primary Sjogren's syndrome. B. Eyes: 1. Schrimer's test:
o o 2. o
Demonstrate decreased lacrimal gland secretion by capillarity using standard fdter paper Wetting of < 5 mm in 5 minutes indicates defective tear production (normally a young person moistens 15 mm) Rose-Bengal test: Demonstrate keratitis by corneal uptake of stain
C. Interventional :
o Labial salivary gland biopsy : lymphocytic infiltration & destruction Treatment: 1. General measurers: o o
o
2.
Xerophthalmia: artificial tear drops with comeal protection Xerostomia: oral hydration, mouth wash, sialagogues (Pilocarpine) Vaginal dryness is treated with lubricants e.g K-Y jelly. Specific therapy: steroids «& immunosuppressives e.g. hydroxychoroquine, methotrexate 50
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Mixed Connective Tissue Disease(MCTD)(Overlap syndrome, Sharp's syndrome) ❖ Definition:
Features of at least 2 connective tissue disease coexisting in the same individual e.g. SLE,Scleroderma, rheumatoid arthritis & polymyositis Clinical picture:
Type of patient: common in females at 4"' decade ❖
Clinically: 1. Insidious onset: Raynaud's phenomenon is very common
2. Any feature of SLE, scleroderma, polymyositis may be found 3. High incidence of pulmonary manifestation 4. Low incidence of renal disease & CNS disease
❖ Investigations: 1. Same as SLE,PSS, polymyositis 2. ANA has a speckled pattern
3. Anti-Ul ribonucleoprotein(RNP)antibodies : auto-antibodies to ribonucleoprotein(RNP)is characteristic 4. Anti-DNA antibodies are negative. ❖ Treatment:
o As SLE / PSS / polymyositis & rheumatoid arthritis specially steroids & immunosuppressive (Methotrexate) Genetic disorders of collagen ❖ Marfan Syndrome
♦> Osteogenesis Imperfecta
❖ Ehlers Danlos Syndrome
❖ It is inherited disorder of collagen (autosomal dominant), characterized by 0 High arched palate 0 Dislocated or sublaxated eye lens
o
Genetic weakness of connective tissue:
o
Blue sclera
1. Skin hyperelasticity 2. Skin bruising (Purpura): due to lack of
support of capillaries by connective tissue
o Hypermobility ofjoints due to wealc ligaments causes early degenerative changes ofjoints o
Scoliosis
o Tall patients (span> height) with arachnodactyly: with positive
o Short stature with stunted growth 0 Fragile bones with repeated
wrist & thumb test, o
fractures & bone deformities
Pectus excavatum or carinatum
o Otosclerosis, causes
0 Mitral valve prolapse 0 Aortic regurgitation & dissecting Aortic aneurysm
conductive deafness
Charcot's Joint(Neuropathic Joint) Pathophysiology: Loss of nervous supply to the joint^ loss of protective pain sensation —> repeated trauma —> joint damage Etiology :
1. Peripheral neuropathy : specially DM,leprosy 2. Syringomyelia 3. Tabes dorsalis of Syphilis Clinical picture: 1. Swollen
2. Painless ,deformed hypermobile joint 3. They are liable to crystal deposition. Treatment: 1. Treatment of the cause
2. Joint support 3. Surgical fusion
51
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Vasculitic syndromes
Definition
❖ Clinical syndrome characterized by idiopathic infianimation of blood vessels (arteritis or venulitis or both). Artery with Inflammation
Decreased blood fhm
Pathology ❖ The inflammation of blood vessels can be :
1. Size; Large, medium, medium to small or small sized vessels
2. Segmental(portion of blood vessel wall) or global (the whole blood vessel wall) 3. Site: Localized (single location) or generalized (scattered lesion) 4. Severity:
o Mild : affecting only skin and surface areas
o Severe : affecting also deep tissues with systemic manifestations Classification of vasculitis: according to size of predominantly involved vessel: Small-Vessel Vasculitis
Medium-Vessel Vasculitis
L Arteriole
Capillary
Venule
Large artery
Small artery Medium artery
Aorta
Medium to Small-Vessel Vasculitis
Lame-Vessel Vasculitis
1. Large vessel vasculitis
2. Medium vessel
o
0 Polyarteritis nodosa
3. Medium to small vessel vasculitis
vasculitis
Giant cell arteritis
o Takayasu's arteritis
o
o
0 Hepatitis B virus
Aortitis associated with
ankylosing spondylitis
Kawasaki disease related
4. Small vessel vasculitis
o Wegener's granulomatosis o Churg-strauss syndrome o Microscopic polyangiitis o
Vasculitis of connective tissue disease
o
Behcet's disease
o Buerger's disease (thromboangiitis
o
Cutaneous
leukocytoclastic o
vasculitis Henoch-Schonlein purpura
o Cryoglyobulinemic vasculitis
o Paraneoplastic syndrome
obliterans)
Pathophysiology:
o Immune complexes (antigen-antibody) deposition o Autoantibodies e.g. ANCA o Lymphocytic cell infiltration o
Endothelial cell activation
o Pro inflammatory cytokines e.g. interleukin 6 & soluble interleukin 2 receptor —> All leading to vasculitis leading to vascular occlusion and ischemia
organ damage.
52
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Clinical picture which raise suspicion of vascuiitis:
f
A. Constitutional symptoms : Fever, fatigue, malaise, anorexia, weight loss
B. Ischemia in YOUNG AGE OR IN ABSENCE OF risk factors for atherosclerosis e.g. o Angina & MI M
o
TlAs & stroke
o
Jaw claudication or limb claudication
C. Multisystem involvement: I
urpura ivedo
ticularisi
Peripheral ulceration
1. Musculoskeletal: myalgia, arthralgia or arthritis (usually oligoarticular) 2. Mucocutaneous : o Oral ulcers
o Raynaud's phenomenon
o Purpuric rash with elevated edge (palpable purpura): leukocytoclastic purpura o Peripheral (fingers & toes) ulceration & digital gangrene due to cutaneous vascuiitis o
Bluish reticular rash i.e. Livedo reticularis Dermal or subcutaneous nodules
CNS: mononeuritis multiplex Fundoscopic changes:consistent with vascuiitis
Renal: ischemic renal failure or glomerulonephritis ♦♦♦ Approach to a case of vascuiitis:
1- Exclude vascuiitis mimickers:
1. Atherosclerosis
2. Vascular spasm e.g. iatrogenic : ergots, cocaine 3. Fibromuscular dysplasia 4. Embolic conditions:
o Endocarditis, atrial myxoma, cholesterol emboli
5. Thrombophilia (conditions| with thrombotic tendency) o DIG, thrombocytopenic thrombotic purpura, o Antiphospholipid syndrome, widespread malignancy
2- Exclude conditions which can cause secondary vascuiitis: 1. Connective tissue diseases
2. Cryoglobulinemia. 3. Cancer
4. Infections: hepatitis B, C 3- Decide:
o Decide extent of organ involvement, size of vessels, try to fit findings into specific entity. 53
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
4- Distribution of vasculitis:
1. Age:
o Kawasaki disease in pediatrics o Takayasu's arteritis young or middle age o Giant cell vasculitis in geriatrics(>50 year old) 2. Sex, race & geography : o Behcet's disease: male dominance in middle East
o Takayasu's arteritis: female dominance in Asian Investigations: 1- Biochemical:
1. General: CBC,ESR,CRP,liver function test, renal function test & viral serology 2. Specific: A. Rheumatoid factor, ANA
B. Anti-neutrophil cytoplasmic antibodies(ANCA) C. Antiphospholipid antibodies D. Serum complement, cryoglobulins 2- Radiological: A. Vascular imaging :
1. Duplex : arterial and/or venous, it describes flow velocities, narrowing & aneurysms 2. Angiography: has the highest diagnostic
3. CT & MR angiography: less invasive, describe vessel wall and surrounding tissue accurately B. Other tests:
1. X-ray and CT scan for: Chest and paranasal sinuses (in Wegener's granulomatosis) 2. Echocardiography 3. Abdominal US or CT with contrast
4. Neurophysiological studies : EMG & nerve conduction studies
3- Interventional: Biopsies
o Biopsies needed for confirmation o Sites: skin, muscle, sural nerve, renal artery, temporal artery Treatment:
1. Corticosteroids: the main line of treatment
o Prednisolone: Low dose, moderate dose, or high dose:
o Methylprednisolone: pulse therapy: in life threatening acute progressive cases 2. Immunosuppressives:
o Indications : steroid sparing treatment or adjuvants in steroid resistant cases
o Drugs: Methotrexate, Mycophenolate mofetil, Azathioprine, Cyclophosphamide, cyclosporine 3. Rituximah: and CD20 monoclonal antibodies for Wegener's granulomatosis
4. IV immunoglohulin & high-dose acetylsalicylic acid : for Kawasaki disease 5. Plasmapheresis: in life-threatening situations 6. Interventional (stenting) & surgery: if indicated.
54
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Polyarteritis nodosa(PAN)= Classic Polyarteritis nodosa = Kussmaul disease ♦♦♦ Deflnition:
o Systemic necrotizing vascuiitis that affect medium sized vessels
o Fibrinoid necrosis ofthe wail of blood vessels —>■ healing with fibrosis —> weak points ^ micro aneurysm formation ^ thrombosis & hemorrhage (aneurysmal rupture) ^ organ ischemic & infarction o
More common in male than in females.
Etiology:
Circulating immune complex disease related to : 1. Drugs : sulfonamides, penicillin, tetracycline
2. Infection with Hepatitis B virus (HBsAg positive) & HCV ❖ Clinical picture:
1.
Type of patient: Onset at 40-50 years Male-female ratio 3:1
General manifestations: fever, fatigue, malaise, anorexia, weight loss Musculoskeletal(Articular) manifestations: Arthralgia, myalgia, myositis
Asymmetrical non erosive arthritis of large joints of lower limbs Mucocutaneous (skin) manifestations: o Raynaud's phenomenon
o Purpuric rash with elevated edge (Palpable purpura): leukocytoclastic purpura o Peripheral (fingers & toes) ulceration & digital gangrene due to cutaneous vascuiitis o
Bluish reticular rash i.e. Livedo reticularis
o
Subcutaneous nodules
5. CNS:
o
Headache, Convulsion
o Hemiplegia (stroke) either ischemic or hemorrhagic e.g. subarachnoid hemorrhage o Mononeuritis multiplex
6. Occular: retinal hemorrhage, blindness 7. Cardiac:
A. Pericardial: pericarditis B. Myocardial: myocarditis C. Blood vessels:
o Coronary vascuiitis with coronary artery occlusion —>■ ischemic heart disease —> angina peetoris or myocardial infarction
o
Hypertension
8. Chest: LUNG INVOLVEMENT IS RARE
9. GIT: abdominal pain due to: o
Intestinal ischemia (intestinal ansina) —> postprandial abdominal pain
o
Mesenteric vascuiitis ^ mesenteric vascular occlusion
o
Pancreatitis
o
Peritonitis
10. Renal:
o Gloinerulonephritis (nephritic or nephrotic syndrome) ending in CRF (renal infarction)
o Spontaneous rupture of aneurysms can result in retroperitoneal hemorrhage or perinephric hematoma 55
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Investigations: A. Biochemical:
1. Blood:
o Anemia, thrombocytosis, leukocytosis o t ESR & CRP 2.
Serology:
A.
Serum complement level: J.C3,|C4, ], CH50(HBV-related PAN)
B. Autoantibodies: o o
o
C. 3.
Antineutrophil cytoplasmic antibodies(ANCA): NEGATIVE,(ANCA is rarely positive < 10 % of cases) Antinuclear antibody : NEGATIVE,ifit is positive —> it is mostly lupus vasculitis. Rheumatoid Factor : NEGATIVE, ifit is positive —> it is mostly rheumatoid arthritis complicated with vasculitis. Virology : HBsAg is positive in 25 % Urine analysis: glomeralonephritis ^ hematuria, proteinuria, casts
B.
Radiological:
o
Angiography: shows microaneurysms (diagnostic)
C. Interventional: o
EMG
o
Biopsy from muscles, nerves, kidney & vessels (vessel picture is diagnostic) Treatment:
1. Prednisone : 1 -2 mg / kg / day
2. Immunosuppressive : Cyclophosphamide 2 mg / kg/day
Microscopic polyangiitis Definition : o
Systemic necrotizing vasculitis that affect SMALL sized vessels including arterioles, capillaries & venules. The main clinical picture is : as polyarteritis nodosa but with lung involvement:
PULMONARY (alveolar hemorrhage)- renal (glomerulonephritis) syndrome Investigations :
POSITIVE PERINUCLEAR antineutrophil cytoplasmic antibodies.
56
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Giant cell arteritis(Temporal arteritis) ❖ Definition:
o Granulomatous vasculitis affecting cranial vessels especially temporal & ophthalmic arteries o Other sites include intracranial, eoronary, mesenteric vessels. Pathology:
o Inflammatory infiltrate of lymphocytes, plasma cells and giant macrophages around the media of blood vessels leading to reduction of lumen of artery and distal ischemia o Perivascular inflammation leads to pain & tenderness in overlying skin. Clinical picture: 1. Type of patient:: o Age: above 50 years old. o
Female: male ratio 4 : 1
2. General manifestations: fever, fatigue, malaise, anorexia, weight loss 3. A. B. C.
Musculoskeletal (Articular) manifestations: Arthralgia Polymyalgia rheumatica (in 50% of patients ). Jaw or tongue claudication :
o Claudication increased by chewing or talking due to ischemia of masseter & temporalis muscles 4. Mucocutaneous (skin) manifestations: i. o
Temporal or occipital arteritis :
On examination :
a. Tender, Thick, Tortuous b. Prominent & Beaded
c. Decreased arterial pulsation ii.
Scalp tenderness on brushing hair
5. CNS :
A. Headache; characterized by : o
USUALLY THE FIRST SYMPTOM
o Newly onset headache
o Site: localized; unilateral(temporal or occipital) o Character: throbbing o Associated with: facial pain B. Blindness:
o Ophthalmic arteritis —> posterior ciliary artery occlusion —> acute anterior ischemic optic neuropathy -
■ blindness
C. Transient ischemic attacks & ischemic stroke (intracranial arteritis) ❖ Investigations: A. Biochemical: blood: Leukocjdosis, fESR & CRP o N.B.:So new onset ofheadache in old persons| with ESR should raise the suspicion ofgiant cell arteritis. B. Radiological: angiography for temporal artery & other vessels C. Interventional : Biopsy from temporal artery o Mention the pathology. o N.B.: negative biopsy does not exclude the diagnosis. ❖ Treatment:
o Steroids of ehoice, tapered with deeline of ESR. 57
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Granulomatosis with polyangiitis(Wegener's granulomatosis)
❖ Definition :
Necrotizing granulomatous vasculitis that affect medium to small vessel vessels
It IS characterized by:
B. 1. General manifestations: fever, fatigue, malaise, anorexia, weight loss 2. Musculoskeletal manifestations: arthralgia 3. Mucocutaneous manifestations:
o Purpuric rash with elevated edge (Palpable purpura): leukocytoclastic purpura o Peripheral (finger & leg) ulceration & digital gangrene due to cutaneous vasculitis o
o
Subcutaneous nodules
4. Neurological: Mononeuritis multiplex, peripheral or cranial neuropathy & Meningitis 5. Ocular lesion:
o Conjunctivitis, scleritis & uveitis o Optic nerve vasculitis & retinal artery occlusion
o Proptosis (due to inflammation of the retro-orbital tissue) & Diplopia(due to entrapment of the extraocular muscles) 6. Ear : otitis media & hearing loss 7. Chest: granulomatous vasculitis ofupper & lower respiratory tracts: A. Upper respiratory tracts: epistaxis, septal perforation & saddle nose B. Lower respiratory tracts: cough, hemoptysis & dyspnea
8. Renal: necrotizing glomerulonephritis, hematuria, RBCs casts, proteinuria ❖ Investigations:
o Cytoplasmic Anti-neutrophil cytoplasmic antibody positive in 90 % of cases ❖ Treatment: MMf#
o Corticosteroids & immunosuppressive e.g. Cyclophosphamide.
58
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
EOSINOPHILIC granuiomatosis with polyangiitis(Churg Strauss Syndrome) Definition:
o Autoimmune eosinophilic granulomatous inflammation of medium & small sized blood vessels in persons with a history of airway allergie hypersensitivity (atopy). ❖ Clinical picture:
A.
Allergic stage :
1. Bronchial asthma :
o
Persistent bronchial asthma is a central feature of Churg Strauss Syndrome Asthma may precede vaseulitis by up to 10 years.
2.
Allergic rhinitis:
o
o
Rhinorrhea
o
Paranasal sinusitis
o Nasal polyps & nasal obstruction B. Eosinophilic stage: o o
o o
Hypereosinophilia : eosinophil blood count > 500/mm^ General: fever, fatigue, malaise, anorexia, weight loss Pulmonary: eosinophilic pneumonia: cough, dyspnea, wheezy chest GIT: eosinophilic gastroenteritis: abdominal pain, diarrhea
C. Vasculitic stage : 1. Mucocutaneous (skin) manifestations:
o Purpuric rash with elevated edge (Palpable purpura): leukoeytoclastic purpura o Peripheral (finger & leg) uleeration & digital gangrene due to cutaneous vaseulitis o
Subcutaneous nodules
2. CNS: mononeuritis multiplex or polyneuropathy 3. CVS:
o Pericarditis, constrictive pericarditis, myocarditis, myocardial infarction
f
o Hypertension (renovascular stenosis) 4. Pulmonary: cough, hemoptysis 5. GIT:
a. Due to : mesenteric vaseulitis —> mesenteric vascular occlusion —> intestinal ischemia
b. Clinical picture: o Abdominal pain with bloody diarrhea o Intestinal gangrene, perforation & peritonitis
❖ Investigations :
1. Biochemical:
o Blood picture : hypereosinophilia; eosinophil blood count > 500/mm^ o Serology : positive PERINUCLEAR antineutrophil eytoplasmic antibodies 2. Radiological : chest X ray: o Transient pulmonary infiltrates 3. Interventional: Blood vessel biopsy:
o Showing histologieal evidence of extravascular eosinophils ❖ Treatment:
Corticosteroids & immunosuppressive e.g. Cyclophosphamide. 59
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I
Takavasu s
Takayasu's arteritis (pulseless disease)
arteritis
Definition
o
It is chronic granulomatous pan-arteritis affecting the aorta and its primary branches (subclavian or carotid artery narrowing)& large arteries in the upper or lower limbs. Clinical picture: T1AS& Stroke
Middle eerebral artery
Vertebral artery Common carotid artery HTN,HF ANGINA, MI.
Aniaurosis fugax
Arch of aorta
Claudication:
jaw, arm & leg.
1. Type of patient:
o Age: < 40 years old at disease onset, o
Sex: females more affected
Bruit over carotid or
o Race: Asian countries such as Japan, Korea, China, India 2. General manifestations : fever, fatigue, malaise, anorexia, weight loss
subclavian arteries or the abdominal aorta
3. Musculoskeletal manifestations: arthralgia
4. Mucocutaneous manifestations: Peripheral (fingers & toes) ulceration & digital gangrene ft • 5. Ocular : amaurosis fugax or blindness
*
6. Neurological;
w
o
Jaw claudication
o TIAs, Stroke (ischemic or hemorrhagic) o
Carotid bruit
7. CVS:
o Hypertension (renovascular stenosis), Heart failure o Angina or MI o Arm or leg claudication or both
o Absent or decreased pulsation of one or both brachial arteries (pulseless disease)^ unequal radial pulsations
o Asymmetrical blood pressure measurement: difference of> 10 mm Hg in systolic blood pressure between both arms
o
Bruit over one or both subclavian arteries or the abdominal aorta
8. Chest: pulmonary hypertension
Investigations:
1. CT&MRI
2. Angiography: o Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities ❖ Treatment:
o Medical : Corticosteroids & immunosuppressive e.g. Cyclophosphamide. o Surgical : Bypass graft surgery 60
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Kawasaki disease(Mucocutaneous Lymph Node Syndrome) Definition:
o Idiopathic acute vasculitis of medium sized vessels occurs exclusively in young children o Most common cause of acquired heart disease in children with peak age < 5 years old. ❖ Clinical picture:
❖ Diagnostic Criteria:
❖ Fever persisting Five days with > Four of the following:
1.
Conjunctivitis : bilateral non purulent conjunctivitival erythema
2.
Cervical lymphadenopathy > 1.5 cm in diameter
3. Mncosal Membrane involvement:
Red fissured of lips, strawberry tongue, buccal erythema of oropharynx
o
5.
Polymorphic rash involving the trunk and extremities. Peripheral extremity changes:
A.
Acute phase : erythematous rash: erythema of palm and soles with edema of hands and feet
4.
B. Subacute phase: periungual desquamation: peeling from tips of fingers and toes Associated Features:
Acute phase : IRRITABILITY
Aseptic meningitis & Anterior uveitis Pericarditis, myocarditis
Pneumonitis & Hepatic, renal, and GI dysfunction o
2. 3.
Pancreatitis, genitourinary (Orchitis, meatitis, urethritis & vulvitis) Subacute phase : arthritis Convalescent phase : Beau lines : Deep transverse grooves across the nails Coronary arteritis CORONARY ARTERY ANEURYSM or thrombosis ^ MYOCARDIAL INFARCTION OR SUDDEN DEATH.
Investigations: 1. Biochemical:
o t TLC, I ESR, I CRP,thrombocytosis. o
Positive anti-endothelial cell antibodies ..
2. Imaging :
o Echocardiography to detect coronary aneurysms. ❖ Treatment:
1. o o 2.
Aspirin: High (anti-inflammatory) dose : in acute febrile phase Low (anti-platelet) dose: in subacute phase IV Immunoglobulin reduces coronary aneurysm formation 61
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Behcet's disease
❖ Definition: 1*
o Idiopathic systemic vasculitis of BOTH arteries AND veins of ALL sized, o
It is associated with HLA B5
❖ Clinical picture:
❖ Diagnostic Criteria:
❖ Recurrent PAINFUL oral ulcers (aphthous or herpetiform), at least 3 times /year plus 2 of the following in absence of other systemic diseases;
1. Recurrent painful genital ulcers.
2. Ocular Behcet's disease : anterior or posterior uveitis, hypopyon, iridocyelitis, retinal vascuhds or optic neuritis 3. Skin lesions e.g. erythema nodosum, acneiform nodules, pseudofolliculitis or papulopustular lesions 4. Positive pathergy test:
o Erythematous papule > 2 mm diameter developing 24-48 hours following a needle prick on forearm Associated Features:
Bram stem
1. Musculoskeletai manifestations:
o Non erosive asymmetrical oligoarticular involving big joints of lower limbs 2. Mucocutaneous manifestations: cutaneous vasculitis
o Peripheral (finger & leg) ulceration & digital gangrene o Erythema nodosum, acneiform nodules, pseudofolliculitis or papulopustular lesions. 3. Neuro-Beh^et's disease: Parenchymal neuro-Beli^et's disease
A. Parenchymal neuro-Beh^et's disease (Meningoencephalitis): diffuse or foeal NEUROPSYCHOLOGICAL dysfunction: 1. Cerebrum :
o Confusion (cognitive dysfunction & psychosis): memory loss with behavioral and persona ity ehanges o
Convulsion, coma
o Aphasia, hemiparesis, hemihypoesthesia. 2. Brain stem: o o
3. ❖ B. o o
Cranial nerve paralysis Long tracts (pyramidal or sensory tracts) manifestations. Thrombosis\ Cerebellum : ataxia & dysarthria Myelopathy N.B.: encephalomyelitis : Inflammation of brain parenchyma & spinal cord Non parenchymal neuro-BehQct's disease : Cerebral venous thrombosis and aseptic meningitis, Headache & intracranial hypertension
Aortic arch aneurysm
4. Vascular -Behfet's disease: 1.
Venous:
A. Superficial thrombophlebitis
B. Hypercoagulability(thrombosis): o DVT limbs/rVC/SVC with pulmonary embolism
o Budd-Chiari syndrome with hepatic injury o
Cerebral venous thrombosis with ischemic stroke
II.
Arterial:
a) Aneurysms : aortic arch & pulmonary aneurysms (hemoptysis) b) Vasculitis complicated by ischemic/infarction end organ damage e.g. 0 Limbs (ulceration & gangrene), cerebral (stroke), coronary (angina, MI), pulmonary(pulmonary hypertension, infarction), mesenteric(GIT ulceration, MVO —> abdominal pain & GI bleeding).
62
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Investigations:
♦> Behcet's syndrome is of clinical diagnosis, laboratory findings are non specific & reflect the inflammatory state| e.g. ESR & slight leukocytosis Treatment: 1. Corticosteroids
2. Colchicine : 0.5 - 1 mg/day 3. Immunosuppressives e.g. Cyclophosphamide.
4. Tumor necrosis factor(TNF)inhibitors e.g. Infliximab & Etanercept 5. Anticoagulation : patients with thrombosis
Henoch-Schonlein purpura (Anaphylactoid Purpura) ❖ Etiology:
o Allergic form of purpura (type III hypersensitivity), affecting children, usually following streptococcal sore throat by 1-3 week.
o The reaction involves formation ofimmune complex (IgA + antigen + complement)-> small vessel vasculitis o It the most common cause of non thromboeytopenic purpura in children Clinical picture: 1. Purpura:
o Palpable purpurie rash mainly over buttocks & extensor surface of legs. 2. Arthritis:
o Non erosive polyarthritis of large joints e.g. ankles, knees, and elbows o Periarticular hemorrhage —> tender, swollen joints. 3. Glomerulonephritis: IgA nephropathy Asymptomatic proteinuria, hematuria
Nephritic syndrome (only 5-10%
CRF).
Abdominal pain :
Anorexia, nausea, vomiting, upper or lower GIT bleeding Bloody stool due to affection ofsubmucosal intestinal blood vessels(DD intussusception). Investigations: A. Biochemical:
a. Hematological:
1. Normal platelet count Prolonged bleeding time,+ve Hess capillary fragility test. Normal CT, APTT,PT, TT.
h. o o c. B. o
Anemia from bleeding, Serological: Elevated serum levels of IgA Complement levels : usually normal For complications: renal function tests: impaired + RBCs casts. Interventional: Skin biopsy: IgA deposits can be demonstrated in the vessel wall. ❖ Treatment:
1. Corticosteroids.
2. Symptomatic treatment 63
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Leukocytoclastic Vasculitis (Hypersensitivity Vasculitis= hypersensitivity angiitis) ❖ Definition:
o It is small vessel hypersensitivity vasculitis characterized histopathological by perivascular neutrophil infiltration associated with nuclear fragmentation causing fibrinoid necrosis ofSMALL blood vessels, o Types: 1. Cutaneous small vessel vasculitis only.
2. Cutaneous small vessel vasculitis associated with larger vessel vasculitis or systemic disease. Etiology: 1. Idiopathic: 50% of cases 2. Infection :
o Beta-hemolytic streptococcal infection upper respiratory tract infections o Hepatitis C virus secondary to the presence of cryoglobulins. o
HIV infection
3. Inflammatory bowel disease, ulcerative colitis, or Crohn's disease 4. latrogenic drugs e.g.: o
Antibiotics: beta-lactams
o
NSAIDs
o
Diuretics
o
Foods or food additives
5. Immunological: Collagen-vascular diseases o
Rheumatoid arthritis
o Systemic lupus erythematosus o Sjogren syndrome o Henoch-Schonlein purpura 6. Malignancy: lymphoproliferative diseases
❖ Clinical picture:
1. Mucocutaneous manifestations:
o Purpuric rash with elevated edge (Palpable purpura)commonly on legs o
Urticarial rash
o
Bluish reticular rash i.e. Livedo reticularis
o
Subcutaneous nodules
2. Multisystem involvement if associated with larger vessel vasculitis or systemic disease
64
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Cryoglobulinemia: cryoglobulinemic vasculitis
Definition & types:
❖ Cryoglobulins are circulating immunoglobuiins which precipitate out in cold. ❖ It takes three forms:
A. Type
1. Cryogiobuiinemia type I:
2. Cryoglobulinemia type II
Monoclonal cryoglobulinemia B. Antibodies
o
o Monoclonal Ig mainly IgM having rheumatoid factor activity
C. Disease
o o o o
3. Cryoglobulinemia type III: polyclonal type
Mixed cryoglobulinemia
o Monoclonal IgM having rheumatoid factor activity plus polyclonal IgG or IgA
o Polyclonal IgM having rheumatoid factor activity plus polyclonal IgG or IgA
Lymphoproiiferative diseases e.g.: o Infections e.g. HCV & HIV Multiple Myeloma o Autoimmune diseases e.g. SLE & Sjogren's syndrome Waldenstrom's Macroglobulinemia Non Hodgkin's Lymphoma Chronic lymphocytic leukemia
Vr_Vi_V
Clinical picture:
A. Hyperviscosity disease(CNS,ocular, CVS, Chest) (for more details about clinical picture, see hematology book) B. Vasculitis:
1. General manifestations: Fever, fatigue, malaise, anorexia, weight loss
rpnra
2. Muscuioskeletal manifestations: aithralgia 3. Mucocutaneous manifestations:
o Raynaud's phenomenon
o Purpuric rash with elevated edge (Palpable purpura) or urticarial rash o Peripheral (finger & toes) ulceration & digital gangrene 4. Multisystem involvement:
o o o o
Peripheral neuropathy Glomerulonephritis Liver dysfunction due to underlying hepatitis C Lymphadenopathy Investigations:
1. Biochemical:
o Positive cryoglobulins & rheumatoid factor o Complement level : J,C3, J,C4, J, CH50 2. Interventionai:
o Biopsy (skin, nerves, renal) show IgM/G depositions Treatment:
1. Treatment ofthe cause e.g. Antiviral therapy 2. Steroids and plasmapheresis . ❖ Crystal arthropathy : 1. Monosodium urate(MSU)crystals ^ gout 2. Calcium pyrophosphate dihydrate crystals(CPPD) pseudo gout 3. Hydroxyapatite(HA)crystals —> pseudo pseudo gout V.
65
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Hyperuricemia & gout
❖ Definition:
❖ Group of disorders characterized by a derangement in purine metabolism manifested by : 1. Hyperuricemia
2. Deposition of mono-sodium urate crystals in : A. Joints : acute & chronic gouty arthritis B. Tissues : gouty tophi
C. Kidneys: uric acid stones & gouty nephropathy. ❖ N.B.: Biochemistry : hypoxanthine-guanine phosphoribosyl transferase
xanthine oxidase
hypoxanthine
o Purines —> inosine monophosphate xanthine oxidase
xanthine
> urie acid
❖ Etiology:
1- Renal gout: J, uric acid excretion
1. Primary: idiopathic may be genetic, isolated tubular defect 2. Secondary: A. Diseases:
o Renal failure (acute, chronic) o Acidosis (Lactic acidosis, ketoacidosis) o
Lead intoxication
207.2
B. Drugs : o
Alcohol
o Aspirin small dose(< 2 g/d) o Pyrazinamide o Cyclosporine o
Diuretics: Furosemide, Thiazides
o
Ethambutol
2- Metabolic Gout: fsynthesis of uric acid : 1. Primary: Genetic A. Lesch-Nyhan syndrome: X-linked recessive disease : o Characterized by juvenile gout, choreoathetosis, mental retardation and seif mutilation
o fUric acid due to deficiency of hypoxanthine-guanine phosphoribosyl transferase enzyme responsible for retransformation of xanthine & hypoxanthine into their mother substance resulting in excess uric acid production. B. Glucose-6-phosphate dehydrogenase deficiency with type I glycogen disease 2. Secondary: excessive cell turnover A. Blood:
o Malignancy : Leukemia, Lymphomas specially with chemotherapy o Chronic hemolysis B. Psoriasis & Sarcoidosis
C. Exogenous : excess dietary purine as meat, kidney, sea food, legumes, mushrooms ❖ N.B.: Association of gout with DM due to 1. Genetic predisposition for both 2. Chronic acidosis 3. Renal failure in DM
66
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Clinical picture: 1- Type of patient;
o More common in males (10:1) than females (in females usually occurs after menopause) o Age: > 40 years old
2- Asymptomatic hyperuricemia:
o Just elevation of serum uric acid without clinical symptoms in 90 % of patients. ❖ N.B.:
o Urate crystals themselves are not irritating & can be found in asymptomatic joints(90% of patients). 3- Symptomatic:
N.B.:
When urate crystals become phagocytosed by leucocytes —> stimulate their lysosomal enzymes, cytokines and chemotactins which can elicit an inflammatoiy reaction —> Acute arthritis(10 % of patients) Minority of patients showing acute gouty arthritis with normal serum uric acid. A- Acute gouty arthritis: A. Precipitating factors:
1. Disease: infection, dehydration & acidosis 2. Drugs: o Furosemide, thiazides & alcohol
o Rapid lowering ofuric acid thatfollow initiation oftreatment can partially dissolve the urate crystals and trigger acute attack, this can be minimized by using a lower starting dose ofallopurinol(1OOmg/d)or by concurrent use of oral colchicine (0.6 mg/J2hours)for thefirstfew weeks. 3. Diet: excess proteins e.g. Meat
4. Trauma & prolonged walking (leading to shedding of crystals from local deposits). B. Attacks of acute gouty arthritis: o
Acute onset of severe pain
o It often develops overnight & reaches a peak within hours, often waking the patient in the early morning o Attacks can be repeated & gradually condition passes into chronic stage C. Joints affected : a. Distribution :
1. General manifestation: fever, malaise
2. Podagra: Monoarthritis usually the first metatarsophalangeal joint of big toe in 50% of cases 3. Other joints include: ankle, heels, knees, wrists, elbows & fingers including distal interphalangeal joints. 4. Hips & shoulders are usually spared b. Description : o
Swollen
o REDNESS, hotness & tenderness o
Limitation of movement
c. Deformity: no deformity (Not erosive) D. Course :
Typical attacks : severe attacks lasting 1- 2 weeks Petit attacks: milder attacks lasting few days Inter-critical gout: asymptomatic periods between acute attacks. Differential diagnosis Redness(erythema) over joints e.g. septic, crystal arthritis & rheumatic fever
Differential diagnosis from mono arthritis e.g. septic arthritis 67
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
B- Chronic gout:
1- Chronic gouty arthritis:
o Asymmetrical POLYarthritis with remission & exacerbation o Joint destruction with secondary osteoarthritis Deformity : deformed (Erosive) o
2- Tophaceous gout: Gouty Tophi
1. Site : monosodium urate crystal deposition in soft tissue around joints, cartilage (ear pinna)& bursae
2. Shape : yellowish white subcutaneous nodules that may ulcerate & discharge a chalky pasty material 3- Gouty uephropathy: 1. o 2. o
Acute urate uephropathy : Precipitation of uric acid in renal tubules ■ acute renal failure Chronic urate uephropathy chronic interstitial nephritis Precipitation of uric acid in renal iuterstitium
chronic renal failure
3. Uric acid urolithiasis:
o Precipitation of uric acid in urinary tract(in acidic urine)^ uric acid stone obstructive uephropathy o Uric acid crystals act as nidus for calcium stone formation —> calcium oxalate stone —>• obstructive uephropathy Investigations: A. Biochemical:
1. Blood picture: Leukocytosis, fESR & CRP 2. Serum uric acid : o
Normal
0
o
Female
0
2.6-6
o
Male
o
3.5-7
o >6 mg/dl o >7 mg/dl
Raised
❖ N.B.:
o Minority of patients showing acute gouty arthritis with normal serum uric acid, so normal serum uric acid does not exclude the diagnosis ofgout t-'i'. i'- .. . 3. Renal: a.
b.
Kidney function lest: may be impaired Uric acid level in urine(normally 300-600 mg / day):
o
I in renal gout t in metabolic gout
4.
For the cause e.g. DM & myeloproliferative disorders
B.
Radiological:
o
1. Renal US 2. o o o
For joints: X-rays: Narrowing & destruction ofjoint spaces Gouty erosions(bony tophi) occurring as para articular punched out defects with well defined borders Tophi: eccentric soft tissue swellings.
C. Interventional: 1. o
o
2. o o
3.
Aspiration from joint fluid : synovial fluid contains Color and viscosity : yellow to white, translucent to opaque, low viscosity
WBCs count 2000-50,000 mm^, with more than 70% PMNL Polarized light microscopy shows monosodium urate(MSU)crystal: Needle-shaped Negative birefringent within WBCs Biopsy from tophi. 68
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Treatment:
1- Asymptomatic hyperuricemia:
o Treatment by allopurinol is recommended only in 1. Strong family history of gout or uric acid stones 2. Serum uric acid level >11 mg/dl 3. Excretion of> 1100 mg /day of uric acid in urine 2- Treatment of acute gouty arthritis:
1- General: Bed rest with plenty of fluids
2- Anti-inflammatory drugs:
1. Non-steroidal anti-inflammatory drugs(NSAID): A. Large dose:
Brufen®800 rag
o Indomethacin : 50 mg / 6-8 hours orally o Ibuprofen : 800 mg t.d.s. B. Low dose after improvement(24-48) hours for one week
IbiiproJonum
o Don t use aspirin because it can alter uric acid level & potentially prolong & intensify an acute attack
2. Colchicine:
A. Action : J, leukocyte migration, J, their phagocytic activity, | release of lysozymes & interleukins B. Contraindicated in hepatic or renal insufficieney C. Dose:
a. 1) 2) 3) b.
Colchicine
Tradition regimen: 0.6mg /h until: Symptoms of arthritis subsides GIT toxicity develops: Nausea, vomiting or diarrhea Maximum of6 mg have been administered Low dose regimen:
CAPSLH^S
o Initially 1.2 mg, then 0.6 mg one hour later for a total dose of 1.8 mg 3. Corticosteroids:
A. Indications : patients in whom full dose of colchicine or NASID are either contraindicated or ineffective B. Prednisolone :40 - 80 mg/day for 3 - 4 days C. Intra-articular steroids (5-10 mg triamcinolone) in acute mono-articular cases ❖ N.B.:
o Allopurinol and uricosuric drugs are of NO value in treatment of acute gouty arthritis o Colchicine small dose is effective in preventing further attack of gout.
3- Treatment of chronic gouty arthritis, gouty nephropathy & gouty Tophi: 1- General:
1. Treatment of the eause
2. Bed rest with plenty of fluids: 2-3L/day 3. Diet: limit meat, liver, brain
4. Avoid: diuretics, aspirin, alcohol 5. Weight reduction is also advised 69
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
2- Hypouricemic drugs: drugs that decrease serum uric acid:
30 % of the body uric acid is derived trom dietary sources
30 % uric acid produced / day excreted through GIT. Pegloticase
XO inhibitor Xanthine oxidase
Purine metabolism
Uricase (not found in human
> Uric acid
> Allantion
70 % of the body unc acid is derived from endoppnoiis niirlne metabolism
Uricosuric drugs
70 % uric acid produced / day excreted through kideny.
1. Uricosuric drugs:
2. Xanthine oxidase inhibitor ❖ Mechanism of action
0 Decrease uric acid proximal renal tubular reabsorption
0 Inhibits xanthine oxidase enzyme essential for conversion of
o Probenecid :500mg/12 hour o Lesinurad: 200 mg /day 0 Benzbromarone & sulfmpyrazone
0 Allopurinol: 100-300 mg/day orally
1. Increase dose gradually with plenty offluids
1) Not used in acute gouty arthritis as it may precipitate acute gouty arthritis so started 4 weeks after acute attack
hypoxanthine & xanthine to uric acid ❖ Drug «& dose 0 Febuxostat: 40 mg / day
❖ Precaution : & alkalinization of urine
1
I
2. Colchicine(1 mg / day)is given as prophylaxis to avoid precipitation of: o
Uric acid urolithiasis
o
Acute gouty arthritis
❖ Side effects
o Allergy o
Renal stones
o GIT upset
0 Allopurinol hypersensitivity syndrome (skin rash, eosinophilia, hepatic necrosis and renal failure) Allergy, 0 BM depression, Dermatitis, diarrhea, and elevation of serum liver enzymes,fever
o Pegloticase is a recombinant porcine uricase. o
Uricase (urate oxidase) ^ allantoin( more Mechanism of action: uric acid ■
soluble & so less precipitation)
o Dose : 8 mg TV infusion every 2 weeks 4. Other lines of treatment:
A. NSAIDS : for chronic arthritis
B. Treatment of urate nephropathy : o Allopurinol o Plenty of fluids
o Alkalinization of urine by sodium bicarbonate or carbonic anhydrase inhibitor(Acetazolamide) C. Surgical removal: oftophi & renal stones may be needed
»:♦ N.B.:
o Hypouricemic drugs should be given as a prophylaxis during treatment of lymphoproliferative disorders
o Causes of hypouricemia: Hereditary, Hypouricemic drugs, Pregnancy, Fanconi syndrome
70
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I
Pyrophosphate arthropathy: pseudogout - chondrocaldnosis
Definition:
o Deposition of calcium pyrophosphate dihydrate crystals(CPPD) in & around joints resulting in calcification of articular cartilage (chondrocaldnosis) Etiology: A. Primary : Idiopathic B. Secondary: 1. Familial Hypocalciuric Hypercalcaemia 2. Hyperparathyroidism (Hypercalcemia), Hypothyroidism 3. Hypomagnesaemia, Hypophosphatasia
4. Hemochromatosis, Hepatolenticular Degeneration (Wilson's disease) 5. Hemodialysis in CKD Elbow Osteoarthritis
Clinical picture:
f. Asymptomatic CPPD 2. Pseudogout: acute CPPD crystal arthritis 3. Pseudo-rheumatoid arthritis: chronic CPPD
o Only radiographic finding of chondrocalcinosis 0 Acute mono-arthritis similar to acute gouty arthritis 0 Symmetrical polyarthritis for months
crystal inflammatory arthritis 4. Pseudo-osteoarthritis
o Chronic osteoarthritis affecting atypical joints as
5. Pseudo-neuropathic arthritis
0 Severe destruction (Charcot joint like) with no underlying
metacarpophalangeal joints, wrist, elbows, shoulders. neurological disorder
❖ Investigations: A. Radiological: X-ray:
1. Chondrocalcinosis & calcification of fibrocartilage as meniscus, symphysis pubis, triangular cartilage of wrist 2. Osteoarthritis
B. Interventional: Aspiration from joint fluid: synovial fluid contains: a. Increased proteins & polymphonuclear leukocytes (25,000 - 100,000 / mm3) b. Polarized light microscopy shows calcium pyrophosphate dihydrate crystals: o Rhomboid shaped o Weakly Positive birefringent crystals Treatment; 1. Treatment of cause 2.
NSAID specially indomethacin
3. Colchicine 4. Intraarticular corticosteroid 5.
Joint aspiration to remove crystals Hydroxyapatite arthropathy : pseudo pseudo gout
Hydroxyapatite crystals —> pseudo pseudo gout Affecting female more than males Shoulder joint is the commonest site but it may occur at knee, hip or elbow.
71
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Paget's disease
❖ Definition :
o Localized disorder of bone remodeling that typically begins with excessive bone resorption followed by increase in bone formation due to autoimmune mechanism triggered by viral infection Osteoclasts
❖ Pathophysiology:
Osteoblasts
New bone
A Resting
Bone resorption
Itr Bone formation
Resting
1. Abnormal osteoclast —> t bone resorption
2. t osteoblasts(f in number with normal morphology) —> rapid f in bone formation 3. Then bone formation dominates:
o New bone has a disorganized pattern, hypervascular state & weaker compared to normal adult bone 4. The most common sites: femur, pelvis, tibia skull & lumbosacral spine . Clinical picture:
1. Type of patient: o
Sex: male to female 3:2
o Age : 5* decade 2. Skeletal manifestations:
o BONE PAIN: THE MOST COMMON
o Pathologic fractures o Bone deformities: bowed legs and skull changes 3. Neurological manifestations: o
Headache,
o Hearing loss, Vertigo, tinnitus
o Dysesthesias and weakness from nerve root compression
Postenor root
4. Cardiovascular manifestations:
o Symptoms and signs of congestive heart failure. ❖ Investigations: A. Biochemical:
1. Calcium, phosphorus, and PTH : levels are normal
2. t markers of bone resorption : deoxypyridinoline and type I N-terminal telopeptide
3. t markers of bone formation: t alkaline phosphatase and serum osteocalcin, type I pro collagen peptide B. Radiological: X-ray pelvis, skull or spine : 1. Osteolytic / osteosclerotic lesions 2. Thick bone trabeculae
Treatment:
A. Medical:
1. 2. 3. B.
Bisphosphonates Calcitonin analogues Plicamycin (Mithramycin) Surgical treatment: decompression 72
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
❖ Osteoarthritis Muscle
Bursa
Normtl kiifia ; Otieoarthrltic knee
Eroded cartilage
Synovlal
SubcMindfal
membrane
1
1
:
1
ftOIW V \
Liganwnts ^
XN.
/
/
Synovlal
-^
i
Cartllagt
\
Bone
: Femur \
| refflodeiling
^J
Cartilage breaking
Joint capsule
Synovium
Tendon
f
'/
Hm>J /
Cartilage B^e ends
rub together
Normal joint
1
Joint fluid —
^and sclerosis
\
^^down
—jfK)>Z
1
Osteoarthritis
Menlscal
..^damage
Ca^te—' Heberden s
—rr
node
^
Q Mentecus
Bouchard's
t i™
\ Hl
—-Synovial hypertrophy
\iy : ^Osteophytes
node
\|H| \
I^ T
/
i \ Fitmta /\
1
/
/
CMCjoint
Heberden t Node
Boudicurd'i Node
Osteomalacia
Normal
Osteoporosis
•9^
«■
i
I bone mass
i bone minerals (soft bones) ■** Osteoporosis
V Osteomalacia
PMD (■Jtrsi')
U L4
*T.Scc#*
L1-14
Bmmis*
THIGH BONE Dm Oueonenu
73
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
1.
11.
Degenerative joint disease
Medical bone diseases:
ii.
Osteomalacia
Osteoarthritis = Osteoarthrosis =
Osteoporosis
Osteoarthropathy Definition
Degeneration of articular cartilage ofjoints,
o Softening ofthe bones due
proliferation of bone & cartilage at the joint
to defective bone mineralization due to
margin forming osteophytes. Osteoarthritis is the most common form of joint disease
inadequate amount of phosphorus, calcium & vitamin D —> j bone building
Risk factors:
process
with exposure of bone, ending in
Wear and tear.
Aging.
o
Osteomalacia in children
Genetic factors.
(growing bones) is known as
Obesity: loading stress on weight bearing
rickets.
joint e.g. knee Smoking
o
The most common
metabolic bone disease
characterized by reduced bone mineral density
(jbone mass) weakening of previously constructed bone
o WHO define osteoporosis as bone density > 2.5 standard deviations below the young adult value of same age & sex
o WHO elassifications : a. Normal: T score > -1
b. Osteopenia: T score between -1 &-2.5
c. Osteoporosis: T score < -2.5 ❖ Etiology
A. Primary osteoporosis:
A. Primary osteoarthritis:
A. Disorders of vitamin D:
o Etiology: idiopathic(may be hereditary)
1. Vitamin D deficiency:
1. Juvenile
o Inadequate sunlight exposure o Malnutrition, malabsorption
2. Idiopathic (young adult)
affecting elderly obese($ > c?) with no previous joint damage. o Commonly affect joints: hands (distal and proximal interphalangeal joints)& weight bearing joints; hip, knee & spine. B. Secondary osteoarthritis:
2. Abnormal vitamin D metabolism :
o
rickets type I: autosomal
o Etiology: secondary to intra or extra articular
recessive disorder due to lack
bone disease:
1. Congenital: congenital hip dislocation, hypemiobility, Ehlers-Danlos Syndrome
Liver & renal failure
o Vitamin D dependent
of 1 a hydroxylase enzyme
3. Involutional:
o Type I: post-menopausal osteoporosis: J, estrogen —vfrisk of vertebral fracture o Type II: age-related (senile osteoporosis): jrenal production of calcitriol {1.25 (0H)2 03} -> t risk of hip
unresponsiveness: vitamin D dependent Rickets type
fracture) B. Secondary osteoporosis (type III):
o Sero negative arthropathy
II: autosomal recessive
1. Endocrinal:
3. Metabolic & endocrinal:
disorder due to absence of
Hypogonadism Hyperparathyroidism Hyperthyroidism Gushing syndrome
o
Diabetes mellitus
3. End organ
2. Inflammatory/immunological: o
Rheumatoid arthritis
o Previous joint damage : Charcot's joint (neuropathic joint). Hemophilia
1. I Calcium:
o o o o
o DM,gout
o Hypoparathyroidism o Malnutrition, malabsorption
2. Malnutrition,
vitamin D receptors
o Acromegaly
o Hemochromatosis, Hepatolenticular Degeneration (Wilson's disease)
B. Lack of mineralization:
o Obesity
2. Drugs: o Aluminium (antacids, renal failure)
o Occupation : maluse or over use ofjoints 5. Deformity: flat foot, genu varum & genu valgum 6. Traumatic: intra articular fracture, repeated
o Phenytoin & Fluoride C. Hypophosphatemia (normal vitamin D): o Familial hypophosphatemic
4. Mechanical:
rickets
dislocation
❖ Pathology:
o Fanconi syndrome
o Loss of cartilage with diminution ofjoint
o
space
o Secondary calcification o Osteophytes(spur)formation ❖ N.B.: Spondylosis result from similar changes in spines (See neurology)
Renal tubular acidosis
D. Hypophosphatasia (normal Ca,P and vitamin D): o Primary disturbance of bone matrix due to J, alkaline phosphatase
Malabsorption 3. Malignancy:
o Multiple myeloma o
Disseminated carcinoma
4. Connective tissue disease:
o Marfan syndrome o Osteogenesis imperfecta o
Rheumatoid arthritis
5. Miscellaneous
o o o o o
Prolonged immobilization Chronic alcoholism, smoking Chronic heparin therapy Chronic liver failure: primary biliary cirrhosis Chronic renal failure
(osteodystrophy)
74
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Clinical picture Asymptomatic Bone pains, tenderness Pathological fracture:
Symptoms:
Progressive joint pain, which:
t By exercise (activity)& J. by rest. Stiffness :
The most common sites of pathological fractures are :
Brief morning stiffness (short duration < 30 minutes) Gelling stiffness: sense of renewed stiffness
Forearm: Colics' fracture
Spine: vertebral fracture
Femur: hip fracture
in diseased joint after prolonged inactivity
Deformities: kyphosis, vertebral collapse with loss of height
( 50 years old
Family history of amyloidosis Age > 50 years old Hemodialysis in CKD > 5 years Chronic infection or inflammation e.g. rheumatoid arthritis, Familial Mediterranean Fever Cancer: multiple myeloma or Flodgkin's lymphoma
77
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
I
❖ Clinical picture:
1) Asymptomatic until organ failure. 2) General: Fever, fatigue, malaise, anorexia, weight loss 3) Mucocutaneous manifestations:
1. 2. 4) 1.
Cutis dyschromica: Hyperpigmented and hypopigmented macules over larger areas of the body. Purpura, particularly periorbital. Neurological manifestations : Postural hypotension (autonomic dysfunction)
2. Peripheral neuropathy (irritation of nerves) 3. 4. 5) 1. 2.
® f 1 n ]\
Carpal/tarsal tunnel syndrome: Numbness in hands or feet Dizziness & fainting episodes Cardiovascular manifestations : the most common cause ofdeath Arrhythmias Restrictive cardiomyopathy with heart failure
6) GIT
1. Macroglossia with difficult swallowing 2. Hepatosplenomegaly 3. Malabsorption syndrome
4. 7) 1. 2.
Alternating bouts of constipation & diarrhea (autonomic dysfunction) Renal manifestations: the mostfrequent site ofamyloidosis Enlargement of kidneys and proteinuria leading to lower limb edema Nephrotic syndrome
3. Renal failure
❖ Investigations: A.
For amyloidosis: biopsy
1.
Tbe main method for diagnosis is tissue biopsy Tissue sample is obtained from : o Skin, SC fat of abdomen, or tissues of rectum (rectal snip) o Gums, nerves, liver or kidneys Tissue sample is stained by Congo red Tissue sample is viewed under polarized light microscopy shows an apple green birefringence. For multiple organ dysfunction:
2.
3. 4. B.
Biochemical:
1. Liver & kidney function tests 2. Urine analysis: proteinuria in renal amyloidosis 3. Blood:
11.
o Prolonged PT / PTT : acquired factor X deficiency o Howell-Jolly bodies : may be seen despite presence of spleen due to functional hyposplenism Radiological: Abdominal US : hepatosplenomegaly or enlarged kidneys Treatment:
A. General measures: diet o o
B. 1. o
Nutritionally sound diet provides body with a good energy supply Special diets : low salt diet Specific measures: Primary amyloidosis: no cure, helpful drugs are: Melphalan (Alkeran): anticancer treatment
o
Prednisone : reduces inflammation
o
Pain killers
2.
Secondary amyloidosis :
3.
TTT Htlphalan
Hydrochlorldt
of the cause
•WrnMMlM**.
Treatment ofthe causes to delay / prevent occurrence of amyloidosis in chronic inflammatory conditions e.g. Colchicine in FMF. Transplantation for affected organ: In renal amyloidosis : kidney transplantation, dialysis In cardiac amyloidosis : heart transplantation Stem cell transplantation. 78
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
E
MaIhan®®dl Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
m
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
HEPATOLOGY GASTROENTEROLOGY AND
ENDOCRINOLOGY
Mahmoud Sewilaii Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
8iiraDi!.aii!ii»8 DCJ'O'iBcafliL EaaBDeoia
EBW0©D®C3 MCQs
Wrlttiii S Ofil Quistlons Mahmoud Sewillam Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Mahmoud Sewilam Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Paraclinical Made Easy
i
i"
Supported By Video lessons on CD
X-Rays
Clinical Pathology EGG
Mahmoud Sewilam Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
DERMATOLOGY made EASY Supported
^"^ideo Lessons in CD
V'
Mahmoud Sew Ham Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
A,
Including a CD of
Previous
Exam Questions
Mahmoud Sewilam Kasr Al-Ainy School of Medicine Cairo University
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Other available books by the author .Cardiology & Nephrology
.Pulmonology, Hematology & Infection
.Hepatology, Gastroenterology & Endocrinology .Sewilam's Internal Medicine Revision :
MCQs,Cases, Written & Oral Questions .Sewilam's Clinical Medicine
.Paraclinical Made Easy :
X-Rays, Clinical pathology & ECG •Dermatology
.Psychiatry
University Book Centre Sayed Mahmoud 103 matahaf el Maniai St., Cairo Tei.: 25329005
Mob.: 01223698600 r 01091111168
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم
Other available books by the author .Cardiology & Nephrology
.Pulmonology,Hematology & Infection .Hepatology, Gastroenterology & Endocrinology .Sewilam's Internal Medicine Revision :
MCQs,Cases, Written & Oral Questions •Sewilam's Clinical Medicine
.Paraclinical Made Easy :
X-Rays, Clinical pathology & ECG .Dermatology .Psychiatry
University Book Centre Sayed Mahmoud •i?'' "" ■ ■
. c'-
■
103 matahaf el Manial St., Cairo
Tel.: 25329005 Mob.: 01223698600 ^ 01091111168
اﺷﺗري ﻧﺳﺧﺗك إذا ﻧﻔﻌك اﻟﻛﺗﺎب وادﻋم ﺗﺣدﯾﺛﮫ ﺑﻧﯾﺔ ﻧﺷر اﻟﻌﻠم