Oxford textbook of stroke and cerebrovascular disease 9780199641208, 019964120X

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Oxford Textbook of

Stroke and Cerebrovascular Disease

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Oxford Textbook of

Stroke and Cerebrovascular Disease Edited by

Bo Norrving Professor in Neurology Department of Clinical Sciences Section of Neurology Lund University Lund, Sweden

Series Editor

Christopher Kennard

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Great Clarendon Street, Oxford, OX2 6DP, United Kingdom Oxford University press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford is a registered trade mark of Oxford University press in the UK and in certain other countries © Oxford University Press 2014 The moral rights of the authors have been asserted First Edition published in 2014 Impression: 1 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University press, or as expressly permitted by law, by licence or under terms agreed with the appropriate reprographics rights organization. Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this work in any other form and you must impose this same condition on any acquirer Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America British Library Cataloguing in Publication Data Data available Library of Congress Control Number: 2013952006 ISBN 978–0–19–964120–8 Printed in China by C&C Offset Printing Co. Ltd Oxford University press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breast-feeding

Foreword

Stroke has always been a worldwide problem, but only now is it being recognized as a global, treatable, and preventable condition, largely through scientific advances and the work of stroke leaders such as the contributors to this volume. Knowledge accrues in pieces but is understood in patterns. The internet has made information available in unprecedented quantities, but of uneven value. Bits and bytes of information are but a few clicks away. However, these pieces have to be put in patterns, in context, and we need to recognize the fact that we still know much less than we need to know, hence the need for a comprehensive, credible, and accessible book. Bo Norrving and his international cast of authors offer such a volume. In addition to the usual chapters on anatomy, pathophysiology, diagnosis, treatment, and rehabilitation, there are chapters

on the increasingly recognized areas of silent infarcts and microbleeds, vascular cognitive impairment and dementia, and the long-term management of stroke. As a former President of the World Stroke Organization, the editor has led efforts to put stroke at the forefront of global health policy by working with the World Health Organization and the United Nations. This enlarged vision of stroke is reflected in a chapter on primary stroke prevention and one on healthcare services, topics that do not usually feature in books on stroke. May this book enjoy the broad readership that it deserves. Vladimir Hachinski, CM, MD, FRCPC, DSc, Dr. honoris causa X5 President, World Federation of Neurology

Preface

Stroke is huge by any measure: often cited data from the Global Burden of Disease project are that there are 6 million deaths due to stroke per year worldwide, 15 million cases of stroke per year, and 30 million persons who have survived a stroke. Other stroke measures are one new stroke every other second, every sixth second stroke kills someone, and one in six will have a stroke during their lifetime. Such numbers have different meanings to different stakeholders. For the patient who has developed a stroke, and for the carers, such data are of little interest (more than possibly telling that ‘you are in good company, welcome to the club’)— my own stroke is more than enough for me. For health personnel the figures are more alarming: how can we take good care of so many patients, do we have the beds at the stroke unit (and is there a stroke unit at all?), are there rehabilitation and follow-up resources available? Who can do the job, who have the right education and competence? For health administrators, healthcare planners, and politicians the numbers should be alarming: what are the precise numbers in my country or region? What is the trend? What can be done (and what can I do) to help and to prevent stroke? And, will the numbers affect the financial situation in my community? Fortunately the stroke scene is changing—the Cinderella tale being a good analogy of what has happened. Only a few decades ago (when I started in neurology as my first summer job) stroke had the lowest priority at the emergency department because there was no hurry and nothing could be done acutely. Stroke units were unheard of—at my local hospital there was even a hospital agreement by which patients who were impossible to rehabilitate (definition: age 65 years and above) were outsourced to various other departments (dermatology, renal disease, oncology . . . ) so that the burden of stroke to the hospital could be shared. Patients used to stay in bed for 1–2 weeks before any mobilization took place. Heparin treatment was widely used to prevent or treat progressing stroke whereas antiplatelets and statins were unknown at that time. Carotid surgery was performed by thoracic surgeons with rates of serious complication well above 10%. Any ultra-early therapy was regarded as doomed to fail since science told us that brain cells could not survive more than 5–10 minutes of ischaemia. Looking back, I have some difficulties understanding why stroke nevertheless caught my interest and attracted me.

Readers of this preface need not be told in detail what has happened  during the last few decades:  the introduction of acute neuroimaging and other diagnostic tools, the demonstration of acute thrombolytic therapy as one of medicine’s best buys, the glory of organized stroke care (including early mobilization), the development of secondary prevention strategies that have changed the prognosis after stroke drastically, and the demonstration that rehabilitation works—just to mention a few of the groundbreaking changes that have taken place. There has also been an avalanche of knowledge of mechanisms, causes, unusual features, stroke subtypes, and genetics. Advances in science have had a profound impact on clinical practice in stroke. Another major change is a focus on stroke prevention through joint actions with other non-communicable diseases (NCDs) that share similar risk factors. Stroke is not acting alone in this movement, but is part of the NCD cluster that has rightfully received high governmental attention during the last few years. Stroke shares many risk factors with heart disease, peripheral vascular disease, cancer, dementia, and pulmonary disease—just to mention a few members of the NCD family. The World Stroke Organization emphasizes three pillars in the Global Agenda for Stroke: prevention, acute care, and long-term management. The latter component has been particularly neglected and warrants much more attention in the future. Few areas in medicine have such broad outreach, involve so many sectors of healthcare, and have such a profound influence on public health as stroke. For this book I have had the privilege of working together with many of today’s most outstanding stroke scientists. I am grateful to all of you for sharing your deep knowledge, and for making yourselves available for the task. I take this opportunity to thank you all most warmly for your contributions to this volume. I also thank the very large number of people in the scientific stroke community, within the World Stroke Organization and regional stroke organizations, who have provided me with inspiration for the present work. I would also like to thank the staff at Oxford University Press for expert help and support in making this book available. My thanks go to Peter Stevenson who set me the task initially, to Eloise Moir-Ford for keeping track of all manuscript versions and chapter status, to Papitha Ramesh and Nic Williams for copy editing, and to the many other people at Oxford University Press who have been involved with this book. It has been a pleasure working with you.

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preface Finally, my thanks to my wife Lena and my three children (David, Marcus, and Maria) for having been (quite) tolerant of the intrusion of my out-of-usual-business-hours’ work into family pleasures and duties. It is my hope that the book will be read, will be disseminated broadly, and will finally lead to benefits for patients and carers.

Only at the latter stage has a textbook like this one served its ultimate purpose. Bo Norrving Lund, Sweden October 2013

Contents

List of Abbreviations  xi List of Contributors  xiii 1 Epidemiology of stroke  1 Valery Feigin and Rita Krishnamurthi 2 Risk factors  9 Arne Lindgren 3 Arteries and veins of the brain:

anatomical organization  19 Laurent Tatu, Fabrice Vuillier, and Thierry Moulin 4 Pathophysiology of transient ischaemic

attack and ischaemic stroke  35 Jong S. Kim 5 Pathophysiology of non-traumatic

intracerebral haemorrhage  51 Constanza Rossi and Charlotte Cordonnier 6 Spontaneous intracranial subarachnoid

haemorrhage: epidemiology, causes, diagnosis, and complications  61 Laurent Thines and Charlotte Cordonnier 7 Clinical features of transient

ischaemic attacks  79 David Calvet and Jean-Louis Mas 8 Clinical features of acute stroke  85 José M. Ferro and Ana Catarina Fonseca 9 Diagnosing transient ischaemic

attack and stroke  94 Bruce Campbell and Stephen Davis 10 Management of stroke: general principles  106 Mehmet Akif Topcuoğlu and Hakan Ay 11 Acute phase therapy in ischaemic stroke  124 Krassen Nedeltchev and Heinrich P. Mattle

12 Acute management and treatment of

intracerebral haemorrhage  130 Marek Sykora, Jennifer Diedler, and Thorsten Steiner 13 Acute treatment in subarachnoid

haemorrhage  139 Katja E. Wartenberg 14 Less common causes of stroke: diagnosis

and management  153 Turgut Tatlisumak, Jukka Putaala, and Stephanie Debette 15 Secondary prevention of stroke  163 Thalia S. Field and Oscar R. Benavente 16 Prognosis after stroke  185 Vincent Thijs 17 Silent cerebral infarcts and microbleeds  194 Bo Norrving 18 Complications after stroke  203 Hanne Christensen, Elsebeth Glipstrup, Nis Høst, Jens Nørbæk, and Susanne Zielke 19 Vascular cognitive impairment and dementia  215 Didier Leys, Kei Murao, and Florence Pasquier 20 Brain repair after stroke  225 Steven C. Cramer 21 Rehabilitation after stroke  234 Katharina Stibrant Sunnerhagen 22 The long-term management of stroke  243 Reza Bavarsad Shahripour and Geoffrey A. Donnan 23 Primary prevention of stroke  255 Anna M. Cervantes-Arslanian and Sudha Seshadri 24 Organized stroke care: Germany and Canada  270 Silke Wiedmann, Peter U. Heuschmann, and Michael D. Hill

Index

279

List of Abbreviations

ACA ACE AChA ACoA ADL ADL AF AHA AICA ARB ARER ASA AUC AVM BI CAA CADASIL CARASIL CAS CBV CEA CEAD CEAD CHS CMB CNS CSF CT CTV CVD CVT DALY DAVF DCI DNR DOAC DSA

anterior cerebral artery angiotensin-converting enzyme anterior choroidal artery anterior communicating artery activities of daily living Alzheimer disease atrial fibrillation American Heart Association anterior inferior cerebellar artery angiotensin receptor blocker absolute risk reduction American Stroke Association area under the curve  arteriovenous malformation Barthel Index cerebral amyloid angiopathy cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy cerebral autosomal recessive arteriopathy with subcortical infarcts and leucoencephalopathy carotid angioplasty and stenting cerebral blood volume carotid endarterectomy cervical artery dissection carotid endarterectomy Cardiovascular Health Study cerebral microbleed central nervous system cerebrospinal fluid computed tomography computed tomography venography cerebrovascular disease cerebral venous thrombosis disability-adjusted life year dural arteriovenous fistula delayed cerebral ischaemia do not resuscitate direct oral anticoagulant digital subtraction angiography

DVT DWI ECG eGFR ESO EVD FDA FFP FHS FLAIR GABA GOS GOS GRE HANAC HDL HERNS HR IA IAT ICH IDR IHD INR IST ITT LDL LP LUTS MAP MCA MET S MMSE MoCA MRI mRS MRV

deep vein thrombosis diffusion-weighted imaging electrocardiogram estimated glomerular filtration rate European Stroke Organisation extraventricular drain Food and Drug Administration fresh frozen plasma Framingham Heart Study fluid attenuated inversion recovery gamma-aminobutyric acid Glasgow Outcome Scale Glasgow Outcome Scale gradient echo hereditary angiopathy with nephropathy, aneurysm, and muscle cramps high-density lipoprotein hereditary endotheliopathy with retinopathy, nephropathy, and stroke hazard ratio intra-arterial intra-arterial thrombolysis intracerebral haemorrhage incidence density ratio ischaemic heart disease international normalized ratio International Stroke Trial intention-to-treat low-density lipoprotein lumbar puncture lower urinary tract symptoms mean arterial pressure middle cerebral artery metabolic syndrome Mini Mental State Examination Montreal Cognitive Assessment magnetic resonance imaging modified Rankin Scale magnetic resonance venography

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list of abbreviations MTT NCD NG NHS NICC NIHSS NINDS NMDA NOAC NVAF OCSP OHS PAR PbtO2 PCA PCC PChA PE PEG PET PFO PHS PICA PoCA PRN PSD RCVS RR RRR

mean transit time non-communicable disease nasogastric Nurses’ Health Study neurocritical care unit National Institutes of Health Stroke Scale National Institute of Neurological Disorders and Stroke N-methyl-D-aspartate novel oral anticoagulant non-valvular atrial fibrillation Oxfordshire Community Stroke Project Oxford Handicap Score population attributable risk partial pressure of cerebral tissue oxygen posterior cerebral artery prothrombin complex concentrate posterior choroidal arteries pulmonary embolus percutaneous endoscopic gastrostomy positron emission tomography patent foramen ovale Physicians’ Health Study posterior inferior cerebellar artery posterior communicating artery pro re nata (as needed) post-stroke dementia reversible cerebral vasoconstriction syndrome relative risk relative risk reduction

rtPA SAH SCA SCD SCI SCM SDB SD SES SIADH SITCH SLE SNP SWI TBI TCS Tmax TOAST TOF tPA TTP UK US VaD VCI WFNS WHO WHS WML

recombinant tissue plasminogen activator subarachnoid haemorrhage superior cerebellar artery sickle cell disease silent cerebral infarct silent cerebral microbleed sleep-disordered breathing standard deviation socioeconomic status syndrome of inappropriate secretion of antidiuretic hormone Surgical Trial in Intracerebral Haemorrhage systemic lupus erythematosus single-nucleotide polymorphism susceptibility-weighted imaging traumatic brain injury Takotsubo cardiomyopathy syndrome time to maximum Trial of Org 10172 in Acute Stroke Treatment time-of-flight tissue plasminogen activator time to peak United Kingdom United States vascular dementia vascular cognitive impairment World Federation of Neurological Surgeons Scale World Health Organization Women’s Health Study white matter lesion

List of Contributors

Hakan Ay Stroke Service, Department of Neurology, A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Oscar R. Benavente Stroke and Cerebrovascular Health, Vancouver Stroke Program, Brain Research Center, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, Canada

Valery Feigin National Institute for Stroke and Applied Neurosciences, Faculty of Health & Environmental Sciences AUT University, Auckland, New Zealand José M. Ferro Department of Neurosciences, Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal Thalia S. Field Vancouver Stroke Program, Brain Research Center, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, Canada

David Calvet Paris Descartes University, Centre de Psychiatrie et Neurosciences INSERM UMR 894, and Department of Neurology, Centre Hospitalier Sainte-Anne, Paris

Ana Catarina Fonseca Department of Neurology, Hospital de Santa Maria, Lisboa, Portugal

Bruce Campbell Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia

Elsebeth Glipstrup Mental Health Services, Bispebjerg Hospital, Copenhagen, Denmark

Anna M. Cervantes-Arslanian Boston University Department of Neurology, Boston, MA, USA

Nis Høst Department of Cardiology, Bispebjerg Hospital, Copenhagen, Denmark

Hanne Christensen Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark

Peter U. Heuschmann Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany

Charlotte Cordonnier Department of Neurology and Stroke Unit, Université Lille Nord de France, Lille, France

Michael D. Hill Calgary Stroke Program, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

Steven C. Cramer Departments of Neurology and Anatomy & Neurobiology, University of California, Irvine, Irvine, CA, USA Stephen Davis President, World Stroke Organization; Director, Neuroscience and Continuing Care Service; Director, Melbourne Brain Centre at RMH; Director of Neurology, The Royal Melbourne Hospital, Melbourne, Australia Stephanie Debette Université de Versailles Saint-Quentin-en-Yvelines, France; and Inserm U740, Université Paris, Paris, France; and Department of Neurology, Lariboisière University Hospital, DHU Neurovasc Sorbonne Paris-Cité, Paris, France; and Department of Neurology, Boston University School of Medicine, The Framingham Heart Study, Boston, MA, USA Jennifer Diedler Department of Neurology, University of Heidelberg, Heidelberg, Germany Geoffrey A. Donnan Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia

Jong S. Kim University of Ulsan, College of Medicine, Seoul, South Korea; and Stroke Center, Asan Medical Center, Seoul, South Korea Rita Krishnamurthi National Institute for Stroke and Applied Neurosciences, Faculty of Health & Environmental Sciences, AUT University, Auckland, New Zealand Didier Leys Université Lille Nord de France, Lille, France Arne Lindgren Department of Neurology Lund, Skåne University Hospital, Lund, Sweden Jean-Louis Mas Paris Descartes University, Centre de Psychiatrie et Neurosciences INSERM UMR 894 and Department of Neurology, Centre Hospitalier Sainte-Anne, Paris, France Heinrich P. Mattle Department of Neurology, Inselspital, Bern, Switzerland Thierry Moulin Service de Neurologie 2,Centre Hospitalier Universitaire, Université de Franche-Comté, Besançon, France

xiv

list of contributors

Jens Nørbæk Mental Health Services, Bispebjerg Hospital, Copenhagen, Denmark

Laurent Tatu Laboratoire d’Anatomie, UFR Sciences médicales et pharmaceutiques, Université de Franche-Comté, Besançon, France; and Service d’Explorations et pathologies neuro-musculaires, Centre Hospitalier Universitaire, Université de Franche-Comté, Besançon, France

Bo Norrving Department of Clinical Sciences, Section of Neurology, Lund University, Lund, Sweden

Turgut Tatlisumak Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

Florence Pasquier Université Lille Nord de France, Lille, France

Vincent Thijs Department of Neurology, University Hospitals Leuven, Leuven, Belgium

Kei Murao Université Lille Nord de France, Lille, France Krassen Nedeltchev Triemli Hospital, Zurich, Switzerland

Jukka Putaala Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland Constanza Rossi Department of Neurology and Stroke Unit, University of Lille Nord de France, Lille, France Sudha Seshadri Boston University Department of Neurology, Boston, MA, USA

Laurent Thines Division of Neurosurgery, Department of Neurosciences and Locomotive System, Lille University Hospital, Lille, France Mehmet Akif Topcuoğlu Hacettepe University Hospitals, Department of Neurology, Ankara, Turkey

Reza Bavarsad Shahripour Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia

Fabrice Vuillier Laboratoire d’Anatomie, UFR Sciences médicales et pharmaceutiques, Université de Franche-Comté, Besançon, France; and Service de Neurologie 2, Centre Hospitalier Universitaire, Université de Franche-Comté, Besançon, France

Thorsten Steiner Department of Neurology, University of Heidelberg, Heidelberg, Germany; and Department of Neurology, Klinikum Frankfurt Höchst, Frankfurt, Germany

Silke Wiedmann Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany

Katharina Stibrant Sunnerhagen Department of Clinical Neurosciences, University of Gothenburg, Institute of Neuroscience and Physiology, Sweden Marek Sykora Department of Neurology, University of Heidelberg, Heidelberg, Germany; and Department of Neurology, Comenius University, Bratislava, Slovakia

Katja E. Wartenberg Neurocritical Care Unit, Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany Susanne Zielke Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark

CHAPTER 1

Epidemiology of stroke Valery Feigin and Rita Krishnamurthi Introduction Stroke is the second most common cause of death worldwide and a frequent cause of adult disability in developed countries (1, 2). Stroke burden on families and society is projected to rise from approximately 38 million disability-adjusted life years (DALYs) lost globally in 1990 to 61 million DALYs in 2020 (3) due to population ageing. Stroke also has a large physical, psychological, and financial impact on patients/families, the healthcare system, and society (4, 5). Lifetime costs per stroke patient range from US$59,800 to US$230,000 (5). The majority (about 75%) of cases of stroke occur in people over the age of 65 years (6, 7), and about one-third of patients die of stroke within a year of onset (8, 9). Over half of survivors remain dependent on others for everyday activities, often with significant adverse effects on caregivers (10). Many factors increase the risk of stroke, and these are generally divided into two categories: modifiable and non-modifiable risk factors. Age, gender, and ethnicity are non-modifiable risk factors for stroke. Modifiable or potentially modifiable risk factors include a number of physiological and environmental factors and include hypertension, elevated total cholesterol, smoking, physical inactivity, alcohol consumption, and atrial fibrillation (11). Stroke mortality data are available from more than 24 countries (12, 13)  showing that, in general, rates have declined for several decades. In some countries, stroke mortality has declined since the early 1950s, but the rate of this decline has recently slowed (14–17). While large national or international stroke mortality data may be used for determining overall burden of fatal strokes and trends in stroke mortality, stroke mortality data are often not accurate (diagnosis classification bias) and have limited value for healthcare planning and organization. The role of changes in incidence and improved survival to downward trend in stroke mortality are not adequately quantified, chiefly due to difficulties in measuring stroke incidence accurately (18, 19); however the results from the World Health Organization (WHO) Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) project suggested that both declining and increasing stroke mortality were principally attributable to changes in case fatality rather than changes in incidence (20).

Importance of population-based studies Epidemiological studies form the basis of much of the medical research and current knowledge in stroke to inform health professionals about best strategies for stroke care organization,

prevention, and management. The gaps in knowledge in stroke prevention and management are continually filled by randomized control trials, case–control, and cohort studies (see Table 1.1). Some of the most informative studies on stroke burden and optimal healthcare organization have arisen from population-based stroke incidence and outcome studies. It is important that stroke is seen and studied in a population context, as a large proportion of the burden of care for stroke is borne outside the hospital sector (11–13). Further, changes in referral patterns can distort longitudinal trends derived from hospitalized cases. Assessing the need for prevention strategies and services is best achieved via population-based stroke registers to determine incidence and outcome (13). Data on population trends in stroke incidence reflect the success/ failure of prevention strategies, while trends in case fatality and outcome reflect changes in stroke management. Both are needed to plan stroke services given high healthcare costs and limited resources. Accurate and representative population-based data are also crucial to: (i) determine the true incidence, causes and outcome of stroke; (ii) implement evidence-based healthcare planning, across the care spectrum; (iii) evaluate the need for and impact of preventative/management strategies; (iv) address persistent uncertainty about what key factors (socioeconomic and health service) impact stroke recovery; (v) examine the natural course of recovery, in particular for cognitive and behavioural outcomes; (vi) provide information on access and satisfaction with stroke services; and (vii) identify service gaps/unmet needs to ensuring evidence-based policy, resource allocation, prevention planning, management services, and evaluation of service performance. Assessing the need for prevention strategies and services is most sensitively achieved with the use of population-based registers to determine the incidence and outcome of stroke. However, studying stroke in a population-based fashion is particularly challenging (19), so that such epidemiological studies are relatively rare compared with studies using mortality data, hospital-based stroke registers, or incidence studies in younger age groups only. In 1987, Malmgren et al. (23) published a list of 12 criteria related to definitions, methods, and mode of data presentation, by which the quality of population-based studies of stroke could be judged. These criteria have been updated by Sudlow et al. (19) in 1997 and most recently by Feigin et al. (Table 1.2) (24, 25). However, these criteria are so demanding in practice that even the stroke component of the WHO MONICA project is generally regarded as having failed to meet them (18). Even among many registers that are population based, many were limited to people under the age of 75 years, yet only half of all strokes occur in these age groups. Although ‘ideal’ stroke incidence studies based on both core

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oxford textbook of stroke and cerebrovascular disease Table 1.1 Common epidemiological terms Term

Definition

Comments

Incidence

The number of new cases of a disease that occur over a specified period of time

The incidence rate is a measure of morbidity (illness) and can be looked at in any population group such as males, persons exposed to a particular chemical toxin, etc.

Attack rate

A measure of how fast a disease is occurring in a population

Attack rates tell us how many new cases of a disease occur over a specific period of time

Prevalence

The proportion of the population affected by a disease at that time

Prevalence is calculated by dividing the number of people who have the disease by the number of people in the community. It provides a snapshot of who has the disease at that point in time and does not take into account the duration of the disease

Mortality

A measure of the proportion of deaths over a specific time period in a given population

Mortality is measured in the entire population at risk from dying from the disease, including both those who have and do not have the disease

Case-fatality

A measure of the proportion of deaths over a specific period of time in individuals with a specified disease

Case-fatality is a measure of the severity of that disease. In contrast to mortality, case-fatality is limited to those who already have the disease

Population attributable risk (PAR)

A measure of the proportion of disease incidence in a total population that can be attributed to a specific exposure

The PAR tells us the extent to which the elimination of a particular exposure would reduce the incidence rate of a particular disease in the whole population

Disability-adjusted life year (DALY)

Years of life lost to premature death and years lived with a disability of a specified severity and duration

DALYs are a means of expressing the overall burden of a disease. Each DALY is 1 lost year of healthy life

Randomized clinical trial (RCT)

A type of study design used to evaluate a particular intervention usually for the treatment or prevention of a disease. The subjects are randomly allocated to either the treatment (e.g. the test drug) or control (e.g. no treatment) group

An RCT can be used to study the effectives of a new drug to treat a condition compared to another drug or no treatment at all. In a ‘double-blind’ RCT both the subjects in the study and the researcher measuring the outcome are unaware of the allocation of the treatment groups, thus reducing bias

Cohort studies

A population with an exposure and a population without the exposure are followed to compare an outcome of interest between the groups

Typically, the study population must be followed up for a long period of time for the outcome of interest to develop. A well-known example is the Framingham study (21)

Case–control studies

A study design aimed to examine the possible relation of an exposure to a certain disease. A group with the disease (cases) is compared with a group without the disease (controls)

If there is an association of an exposure with a disease, there should be a higher prevalence of the exposure in the cases than in the controls

Adapted from Gordis (22).

and supplementary criteria (24, 25) are the most valuable source of information for developing evidence-based strategies for stroke prevention and health services, to address the problem of accurate and comparable stroke incidence studies in less affluent countries with limited resources where most strokes occur, a WHO stepwise stroke surveillance approach (26) can be recommended (Figure 1.1). An alternative approach for studying stroke incidence and prevalence in countries with very limited resources could include a combination of a stroke prevalence survey (e.g. door-to-door study) with a study of death certificates (verbal autopsy procedures) in the same community (Figure 1.2), as recently recommended by Feigin (27).

Stroke burden in high-income countries Historically, information on stroke incidence, prevalence, early case-fatality came predominantly from studies in high-income countries. In addition, long-term trends in stroke incidence in different populations are not well characterized, largely due to difficulties of population-based stroke surveillance (19, 28, 29). However recent studies in mid- to low-income countries

have allowed comparisons in stroke burden and current trends. A  recent systematic review of worldwide stroke incidence and early case-fatality (29) found that over the last four decades (1970–2008) there was a statistically significant 42% decrease in stroke incidence rates (1.1% annual reduction) in high-income countries (Figure 1.3A), with the more pronounced reduction in people younger than 75 years and in people with ischaemic stroke. This decrease may be attributable to the effective implementation of preventative measures and management of risk factors in these populations. However, in low- to middle-income countries stroke incidence rates for the same time period have increased by over 100% and currently exceed those in high-income countries. It was also shown that the risk of stroke is increasing with the age of the population in developed countries (Figure 1.4) (30). The reasons for this difference are unclear, but are a matter of great importance for two main reasons: (i) stroke is a leading cause of disability in adults and (ii) the elderly (the most stroke-prone age group) constitute the fastest-growing segment of the population. Currently (2000–2008), proportional frequency of ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage

CHAPTER 1

epidemiology of stroke

Table 1.2 Gold standards for an ‘ideal’ stroke incidence study Domains

Core criteria

Supplementary criteria

Standard definitions

• World Health Organization definition of stroke • At least 80% CT/MRI verification of the diagnosis of ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhagea • First-ever-in-a-lifetime stroke

• Classification of ischaemic stroke into subtypes (e.g. large artery disease, cardioembolic, small artery disease, other)a • Recurrent strokea

Standard methods

• Ascertainment of patients with TIA, recurrent • Complete, population-based case ascertainment, based on multiple overlapping strokes and those referred for brain, carotid or sources of information (hospitals, outpatient clinics, general practitioners, death cerebral vascular imaginga certificates)b • Prospective study design • ‘Hot pursuit’ of cases • Large, well-defined and stable population, allowing at least 100,000 person-years • Direct assessment of under-ascertainmenta by regular of observationb checking of general practitioners’ databases and hospital admissions for acute vascular problems and • Follow-up of patients’ vital status for at least 1 montha cerebrovascular imaging studies and/or interventions • Reliable method for estimating denominator (not more than 5 years old census data)b

Standard data presentation

• Complete calendar years of data; not more than 5 years of data averaged togetherb • Men and women presented separately • Mid-decade age bands (e.g. 55–64 years) used in publications, including oldest age group (≥85 years)b • 95% confidence interval around rates

• Unpublished 5-year age bands available for comparison with other studies

a New criteria. b Updated, modified from Sudlow and Warlow (19). Reprinted from Feigin and Carter (25) with permission.

Populationbased Step 3

Population coverage

Community events Module 6

Non-fatal events in community

Step 2

Hospitalbased

Cause of death (death certificate or verbal autopsy) Module 4

Step 1

Autopsy

Fatal events in community

Module 5

+ Subtype Hospital events & vital status Module 1

Events in hospital

+ Disability Module 3 Module 2 Comprehensive Expanded

Standard

in high-income countries were estimated as 82%, 11%, and 3%, respectively (29). Early (1-month) case fatality in high-income countries has decreased over the last four decades from 35.9% to 19.8%, potentially due to improved management of acute strokes, and possibly a shift towards less severe strokes. Overall, case-fatality within 1 month of stroke onset in high-income countries is currently about 23% and is higher for intracerebral haemorrhage

Fig. 1.1 STEP-wise approach to stroke surveillance. (Adapted from Truelsen et al. (24) with permission.)

(42%) and subarachnoid haemorrhage (32%) than for ischaemic stroke (16%) (30). A recent systematic review of population-based stroke incidence and prevalence studies showed the age-standardized prevalence of stroke in people aged 65 years and older ranges worldwide from 46–72 per 1000 population (Figure 1.5) (30). Stroke makes a significant contribution to disability burden in low- and middle-income

3

4

oxford textbook of stroke and cerebrovascular disease

Study population (about 25,000–30,000)

Stroke is not confirmed

Prevalence study (door-to-door survey)

Study of death certificates over the past 3 years

Questionnaire to identify subjects with possible stroke over the past 3 years

Stroke suspected (stroke mentioned in death certificate)

Clinical examination of screened positive subjects

Verbal autopsy procedure

Stroke confirmed

Stroke confirmed

First-ever stroke

First-ever stroke

Stroke not suspected

Stroke is not confirmed

Incident stroke cases

Fig. 1.2 An alternative approach for studying stroke epidemiology in resource-poor countries. (Reprinted from Feigin (25) with permission.)

countries (31), and the recent 2010 Global Burden of Disease Project ranked stroke as the fifth highest cause of DALYs worldwide in 2010 (an increase of 19% from 1990) (32). In terms of global variation, stroke burden was shown to be higher in China, Africa, and South America, and lower national income was associated with higher relative mortality and burden of stroke (33).

Stroke burden in low- to middle-income countries One of the major challenges in stroke epidemiology is the lack of good-quality epidemiological studies in developing countries (34). According to WHO estimates, death from stroke in developing (low- and middle-income) countries in 2001 accounted for 85.5% of stroke deaths worldwide (35), and the number of DALYs, which comprises years of life lost and years lived with disability (35), in these countries was almost seven times that in developed (high-income) countries (4, 27). Recent meta-analysis of population-based stroke incidence studies (29) showed that unlike high-income countries, the incidence of stroke in low- to middle-income countries has increased by 100% over the last four decades (1970–2008) (Figure 1.3B). Stroke incidence rates in low- to middle-income countries increased with increasing age in a similar manner to high-income countries (Figure 1.6). Although ischaemic stroke is the dominating stroke pathological type all over the world, the proportional frequency of intracerebral haemorrhage in low- to middle-income countries tends to be noticeably greater than that in high-income countries (Figure 1.7) (29). There is evidence from recent studies that the risk factors for stroke in middle- to low-income countries are similar to that in

high-income countries, including high blood pressure, smoking, and obesity, although the relative significance of stroke risk factors in high- and low- to middle-income countries may be different (see Chapter 2). The increase in stroke incidence in low- to middle-income counties may be attributed to the poor management of these risk factors. While early case fatality is similar to that of high-income countries, the decrease in early case fatality is not as high as that in high-income countries.

Gender and ethnic differences in stroke burden There are notable gender and ethnic differences in stroke incidence and outcomes both in high- and mid- to low-income countries. Both socioeconomic and ethnic differences in the risk of stroke have been seen in many countries (36–39). For example, higher risks have been observed among Maori and Pacific people in New Zealand (40, 41), and in the black populations in the United States (36) and United Kingdom (37), compared to the white population. Higher stroke attack rates in lower socioeconomic groups are probably related to several factors. As a general rule, lower socioeconomic groups are more frequently exposed to risk factors for cardiovascular disease, including hypertension, smoking, diabetes, and excessive consumption of alcohol (42). In addition, it has been suggested that lower socioeconomic groups have less access to, or make less effective use of, services that are important to the management of these risk factors, such as early detection and control of hypertension (43). Similarly, many of the ethnic differences in stroke risk have been attributed to differences in socioeconomic circumstances and exposure to risk factors (43). However, studies of cardiovascular disease have found that not all of the differences in attack rates among ethnic groups can be explained by differences

CHAPTER 1

(a)

epidemiology of stroke

Rochester, MN Tartu, Estonia Copenhagen, Denmark Dublin, Ireland North Karelia, Finland Saku, Japan Frederiksberg, Denmark Espoo-Kauniainen, Finland Soderham, Sweden Shibata, Japan Tilburg, Netherlands Oyabe, Japan2 Auckland, NZ Turku, Finland (1982) Dijon, France Ubmbia, Italy Malmo, Sweden Valley d'Aosta, Italy Perth, Australia Belluno, Italy Greater Cincinnati, USA Arcadia, Greece L'Aquila, Italy East Lancashire, UK Inherred, Norway Erlangen, Germany South London, UK Vibo Valentia, Italy Melbourne, Australia Scottish Borders region, UK Porto, Portugal Porto, Portugal2 Orebro, Sweden Barbados Lund-Orup, Sweden Oxfordshire, UK

400

350

300

250

200

150

100

50

0 1970-1979

1980-1989

1990-1999

2000-2008

(b) 250

Ibadan, Nigeria Ulan Bator, Mongolia Rohtak, India

200

Colombo, Sri Lanka Novosibirsk, Russia

150 Krasnoyarsk, Russia Martinique, French West Indies

100

Uzhgorod, West Ukraine Tbilisi, Georgia iquque, Chile

50

Matao, Brazil Mumbai, India

0 1970-1979

1980-1989

1990-1999

2000-2008

Fig. 1.3 (a) Age-adjusted annual incidence of stroke in high income countries per 100,000/year*. (b) Age-adjusted annual incidence of stroke in low to middle income countries 100,000/year*. (Reprinted from Feigin et al. (13) with permission.)

in conventional cardiovascular risk factors, suggesting genetic and other factors are important (44). Thus, there remains considerable uncertainty regarding the relative importance of stroke risk factor management and control and other factors in the aetiology of these inequalities.

There is also some evidence suggesting ethnic differences in stroke outcomes. In a recent prospective population-based study of 1127 patients with acute stroke in Auckland, New Zealand the risk of dependency, as measured by Frenchay Activities, at 6 months post-stroke was higher in non-Europeans (Asian and Pacific

5

oxford textbook of stroke and cerebrovascular disease 45.00

Cases per 1000 per year

40.00 35.00 30.00

Melbourne, Australia

Perth, Australia

Frederiksberg, Denmark Espo-Kauniainen, Finland Erlangen, Germany

South London, UK Oyabe, Japan Arcadia, Greece L’Aqulia, Italy Innherred, Norway

Belluno, Italy Auckland, NZ Novosibirsk, Russia French West Indies

25.00 20.00

Uzhgorod, Ukraine

15.00 10.00 5.00 0.00 c-SAH or C-SAH) Spinal arteriovenous malformation (C-SAH) Intracranial artery dissection (C-SAH) Cavernous malformation (ICH > c-SAH > C-SAH) Moyamoya disease (ICH > c-SAH > C-SAH) Cerebral vasculitis (c-SAH > ICH > C-SAH) Cerebral venous thrombosis (ICH > c-SAH > C-SAH) Cerebral amyloid angiopathy (ICH > c-SAH > C-SAH) Exceptional medical causes Pituitary apoplexy Embolic diseases (cardiac myxoma, choriocarcinoma or endocarditis) Sickle cell disease Sympathomimetic drugs abuse Anticoagulant therapy c-SAH: convexal SAH; C-SAH: cisternal SAH; ICH: intracerebral haemorrhage.

bifurcations) (45, 46) modulated by an individual genetic susceptibility and amplified by modifiable risk factors as smoking, arterial hypertension, and alcohol consumption. The overall annual risk of rupture on an unruptured intracranial aneurysm is about 1% per year but it is highly variable depending on different parameters: gender, age of the patient or previous history of SAH, location or size of the aneurysm, and associated risk factors. Patient characteristics associated with a higher risk of rupture are age older than 60, female gender, and smoking. Aneurysm characteristics associated with a higher risk of rupture are size greater than 5 mm, posterior circulation location, and symptoms due to the aneurysm other than SAH (2).

Benign idiopathic SAH Approximately 10–20% of SAH patients will not have a discernible cause of bleeding identified at the end of the workup (5, 10, 42, 47). Among those, one-third (5% of all SAH) will present a specific pattern often referred as benign perimesencephalic (or truncal) haemorrhage) (43). This subset of SAH is characterized by mild symptoms at onset, a typical pattern of haemorrhage on computed tomography (CT) (haemorrhage restricted to the cisterns surrounding the brainstem and suprasellar cistern with scant blood allowed in the ventricles or the proximal Sylvian fissure, Figure 6.3), a negative cerebral angiogram, an uneventful clinical course, and an excellent outcome (10, 19, 43, 47). Repeated angiography is not necessary when clinical and radiological presentations are typical and initial CT angiography (CTA)/angiography are negative (47). A venous origin of the bleeding has been suggested to explain its very limited extension (48).

Convexal SAH Convexal SAH (c-SAH) is characterized by the presence of blood collections in one or several adjacent sulci in the absence of blood at the basal cisterns of the brain or elsewhere (49). It is sometimes referred in the literature as ‘focal SAH’ or ‘focal superficial siderosis’. c-SAH has been described in various settings: vascular malformations (arterio-venous malformations, dural arterio-venous fistulae, cavernomas), arterial dissections, cortical venous thrombosis, vasculitis, reversible cerebral vasoconstriction syndrome (RCVS), posterior reversible encephalopathy syndrome, moyamoya disease and syndrome, infective endocarditis, coagulation disorders, and cerebral amyloid angiopathy (CAA) (50). While aneurysmal SAH typically present with acute headache, c-SAH are often unexpected findings or associated with transient neurological symptoms. c-SAH are increasingly recognized as a potential diagnostic in vivo biomarker of CAA (51). Retrospective data suggest that c-SAH in the context of CAA may be a warning sign of future SAH or ICH (52, 53).

Rare neurovascular causes of SAH These rare neurovascular causes of SAH account for 5% of all cases (5).

Cerebral arteriovenous malformations Arteriovenous malformation (AVM) ruptures are rarely disclosed by SAH (9–20% of cases) and usually it is in association with parenchymal (Figure 6.4) or ventricular haemorrhage (54–56). Similarly, SAH represents only 10% of AVM recurrent haemorrhages (57). When pure SAH is encountered in this context, the rupture of a

63

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oxford textbook of stroke and cerebrovascular disease A

B

Fig. 6.2 Angiographic ((A) 3D DSA, anterior view) and intraoperative ((B) left Sylvian fissure approach) aspect of a middle cerebral artery aneurysm.

prenidal feeding artery aneurysm should be searched for with CTA or conventional digitalized subtraction angiography (DSA). These aneurysms develop because of increased blood flow on the arterial pathways directed to the AVM (44). Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) will show the nidus and conventional DSA will depict its precise angioarchitecture.

Intracranial dural arteriovenous fistulae Dural arteriovenous fistulae (DAVFs) are constituted by direct arteriovenous shunts into the dural layer. Types II b, III and IV DAVF carry draining pathways involving cortical veins and are associated with a high annual risk of bleeding (8% per year). Haemorrhage is classically subdural but can either be parenchymal or subarachnoid (Figure 6.5) (58). Previous sinus thrombosis, head trauma or intracranial surgery can be the triggering factor for the development of this type of malformation (59). MRA could disclose dilated veins around the shunt area but final diagnosis will be provided with conventional DSA.

Spinal arteriovenous malformations A history of low cervical pain or stabbing pain between scapulae should evoke the diagnosis of spinal AVM or fistula

(Figure 6.6), particularly if intracranial investigations are negative and SAH concentrates at the posterior fossa or foramen magnum (60, 61). A spinal angiography will be needed to show the malformation.

Cervical or intracranial artery dissections Cervical artery dissection (CAD) is a classical differential clinical diagnosis of aneurismal SAH that should be considered when a thunderclap headache occurs (frequently after a history of neck trauma or unusual head movements). CADs are rarely associated with intracranial SAH unless the dissection extends to or arises from intracranial arteries (1.5% of cases) (42). In the context of CADs, SAH results from the direct disruption of the arterial wall or the rupture of a pseudoaneurysm (62). Imaging workup will entail, depending on local availability, CTA, DSA, cervical/transcranial Doppler, or MRI/MRA (Figure 6.7).

Others Cavernous malformation is usually a cause of intracerebral haemorrhage that rarely extents to other brain compartments. It is a very uncommon source of SAH and this could append in this context only with a very superficial pial lesion rupturing

Fig. 6.3 Typical pattern of a benign perimesencephalic haemorrhage on axial CT scan: haemorrhage restricted to the cisterns surrounding the brainstem (interpeduncular cistern) without blood in the ventricles or the proximal Sylvian fissures.

CHAPTER 6

spontaneous intracranial sah: epidemiology, causes, diagnosis, and complications A

B

Fig. 6.4 Subarachnoid haemorrhage with parenchymal haematoma ((A) axial brain CT scan) revealing an occipital arteriovenous malformation ((B) lateral view of left internal carotid angiography).

A

B

Fig. 6.5 Subdural, parenchymal and subarachnoid haemorrhages ((A) axial CT scan) in relation with the rupture of a right dural arteriovenous fistula with cortico-venous reflux and ectasia ((B) right common carotid artery angiography).

A

B

C

Fig. 6.6 Posterior fossa subarachnoid haemorrhage ((A, B) axial CT scan) revealing a cervical spine dural arteriovenous fistula ((C) 3D DSA of the left vertebral artery).

65

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oxford textbook of stroke and cerebrovascular disease A

B

Fig. 6.7 Posterior fossa subarachnoid haemorrhage ((A) axial CT scan) due to a left intracranial (V4 segment) vertebral artery aneurismal dissection ((B) MRA, anterior view).

in the subarachnoid space. Diagnosis is based on MRI disclosing the typical aspect of a nodular lesion with mixed intensity on T2-weighted sequence and surrounded by a haemosiderin halo (63). Moyamoya disease is a rare cerebrovascular disease consisting of a progressive steno-occlusion of main cerebral arteries in association with the development of neovessels at the base of the brain (lenticulostriate territory) and at the surface of the brain (leptomenigeal collaterals). In children, the disease is usually responsible for ischaemic symptoms but in adults, haemorrhage is the most frequent complication (50%). Although classical, isolated SAH in this context is quite uncommon (Figure 6.8) and could be the consequence of rupture of an associated aneurysm or fragile leptomeningeal neovessels (64). Cerebral vasculitis is a rare cause of SAH and should be suspected when SAH distribution is very peripheral (Figure 6.9). The diagnosis will be made with angiography showing irregularities of distal cortical arteries (42). Cerebral venous thrombosis may be diagnosed in a context of a thunderclap headache revealing a focal cortical SAH. Exploring sinuses and cortical veins is therefore mandatory in the setting of an isolated non-aneurismal SAH. A

B

Rare medical causes of SAH Pituitary apoplexy is a rare aetiology of SAH. It consists of a haemorrhagic necrosis of a pituitary macroadenoma leading to a rapid increase in tumour volume and sometimes its subarachnoid rupture. Neurological symptoms are a sudden retroocular or frontal headache in association with ophthalmological signs as decreased visual acuity, oculomotor nerves palsies, or bitemporal hemianopsia (5). Head CT scan will show a haemorrhage centred in the sella or suprasellar area. Embolic diseases as cardiac myxoma, choriocarcinoma, or endocarditis could be the source of cerebral arteries infiltration and dilatation until the formation of one or several pseudoaneurysms often referred as ‘mycotic aneurysms’. Diagnostic DSA will usually show typical and multiple small distal aneurysms, most of the times located in the middle cerebral artery territory. The main complication of these lesions is their rupture in the parenchyma or subarachnoid spaces (5). Sickle cell disease might be a direct cause of SAH in children and the pathophysiology in this context is similar to that of moyamoya disease (65). Sympathomimetic drug abuse, such as cocaine or phenylpropanolamine, might be a cause of SAH. In this case, the haemorrhage C

Fig. 6.8 Left Sylvian subarachnoid haemorrhage ((A, B) axial CT scan) associated with moyamoya disease ((C) left common internal carotid artery angiography showing distal ICA occlusion and leptomeningeal collaterals).

CHAPTER 6

spontaneous intracranial sah: epidemiology, causes, diagnosis, and complications

A

B

Fig. 6.9 Left convexal parietal subarachnoid haemorrhage. (A) Axial CT scan (white arrow-head) caused by cerebral vasculitis diagnosed on cerebral angiography. (B) Left internal carotid artery angiogram showing multiple irregularities (black arrowheads) of anterior and middle cerebral arteries branches.

usually occurs at a younger age but has the same prognosis as in the usual form. No evidence of associated toxic vasospasm or vasculitis was found on radiological examinations or during autopsy (1, 66, 67). The use of anticoagulant therapy is found in 5% of patients with non-aneurysmal SAH (43). Nevertheless, anticoagulants alone have been proven to be the cause of SAH in only 2.6% of intracranial haemorrhage (68).

Clinical diagnosis of subarachnoid haemorrhage Qualification of the headache The diagnosis of SAH is clinical in essence and will be later confirmed by a non-enhanced head CT scan or a lumbar puncture (LP). The pivotal symptom of SAH is a thunderclap headache. Unfortunately, headaches are not always specific and account for 4–5% of the referrals to the emergency departments among which, SAH represents only 1–2% of the causes (1, 69–71). Therefore it is very important to precisely know how to characterize an aneurismal SAH headache and to be able to differentiate it from the three main differential diagnosis:  migraine, tension headache, and RCVS (6, 72, 73). The goal is to appropriately triage patients in order to avoid overinvestigating the disease or, more seriously, misdiagnosing it, which would occur in about 5–12% of patients (43% in emergency departments and 32% at physicians’ offices) (1, 6, 72). In the first situation, inappropriate head CT scan then LP will be required. In the second eventuality, no head CT scan (73% of misdiagnosed patients) or LP (7% of misdiagnosed patients) will be performed (6). The average diagnostic delay in the context of SAH is around 3–4 days and during this period, the patient will be exposed to re-rupture (22%) with or without other complications as acute hydrocephalus, intraparenchymal haemorrhage, vasospasm (Figure 6.10), or decreased level of consciousness occurring in 39% of misdiagnosed patients (6, 72). In every instance, when the diagnosis is considered, all efforts have to be made to rule out or to confirm the diagnosis (wide indication of head CT scan), particularly in good clinical and good radiological grade patients (more than half of SAH patients)

which constitute the subgroup at the highest risk of misdiagnosis, and who will instead benefit the most from prompt treatment (8, 10, 69, 72).

Clinical presentation The following description focuses mainly on aneurismal SAH that combines the more typical features. If the diagnosis is (or should be) easy within the first hours, it is much more difficult to reconstitute the exact clinical sequence when the patient is admitted after a few days. None of the symptoms taken alone is pathognomonic of the disease. The irruption of blood in the intracranial subarachnoid spaces is accompanied by an acute and severe headache (called ‘thunderclap’), which is the pivotal symptom that should lead to consideration of diagnosis (5). The characteristics of the headache are quite specific. In one-third of patients, it is the only symptom (10). The onset is very sudden (like an ‘explosion’) with a peak intensity reached almost instantaneously (50%) or in a few seconds or minutes (15 seconds • Administration of heparin within 48 hours before the onset of stroke and an elevated activated partial thromboplastin time at presentation • Platelet count 12, ICH volume 3 cm and/or expansive behaviour or hydrocephalus

Evacuation and/or EVD

Pons, midbrain, medulla

–

Conservative

BG: basal ganglia, EVD: external ventricular drainage; ICH: intracerebral haemorrhage, IVH: intraventricular haemorrhage.

in four of 11 patients who underwent ultra-early surgery less than 4 hours after ictus. Results in the same study were better for patients operated in the 12-hour time-frame (82). Mortality rate in these patients was 18% compared to 29% in the conservative arm. However, this did not translate into improved functional outcome. In another small study, patients randomized to surgery had clot evacuation during the first 9 hours after symptom onset. No difference regarding outcome and mortality was found compared to medically treated patients (83). In the STICH trial, the average time from the onset of symptoms to surgery was 30 hours and only 16% of patients were treated within 12 hours. Interestingly, recombinant factor VII given pre- or perioperatively may decrease the rebleeding rate associated with ultra-early surgery and may represent an attractive adjunct option (84). In summary, no clear evidence indicates that ultra-early surgery improves functional outcome. In contrast, delayed evacuation by craniotomy seems to offer little benefit, even more so in comatose patients with deep seated haemorrhage.

Hemicraniectomy for supratentorial intracranial haemorrhage Only little evidence has been published about decompressive surgery following ICH. Murphy et  al. report 12 patients with supratentorial hypertensive ICH who underwent haematoma evacuation and decompressive hemicraniectomy (85). Of 11 surviving patients, six had a good functional outcome (mRS score ≤3) at a mean follow-up time of 17 months. In another small study on clot evacuation in patients with primary supratentorial haemorrhage, in 15 patients in whom progression of brain swelling was anticipated, decompressive craniectomy was performed after clot removal. The combination of decompressive craniectomy and haematoma evacuation showed promising results in a subgroup of severely compromised patients (86). An uncontrolled retrospective series of 23 patients who underwent hemicraniectomy without haematoma removal in putaminal haemorrhages was published in 2009. At 3 months, 13 patients had good outcome and ten had poor outcome including three deaths. However, included patients had also small haemorrhages and 16 patients had admission GCS score above 9 indicating relatively good admission status. Moreover, the indication for hemicraniectomy was not defined clearly.

Hemicraniectomy for cerebral sinus thrombosis In patients with large haemorrhagic venous infarcts, midline shift and impending transtentorial herniation may mean decompressive hemicraniectomy has beneficial effect. Until now, only case reports and small series indicate the advantage of this procedure. However, recent series including a literature review states that among all published cases taken together, 11 patients of 13 patients had an excellent outcome (mRS score ≤3) (88). Thus, this promising approach is being prospectively analysed as a part of the ongoing ISCVT-2 trial.

Surgery for cerebellar ICH Unlike with supratentorial haematomas, the indication for surgery in cerebellar haematomas is undisputed, despite the complete lack of prospective trials. A  class  I  recommendation of the current AHA-guidelines states that patients with cerebellar haemorrhage larger than 3 cm and neurological deterioration or brainstem

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oxford textbook of stroke and cerebrovascular disease compression and/or hydrocephalus from ventricular obstruction should have surgical removal of the haemorrhage as soon as possible (12). This recommendation is based on non-randomized series of patients reporting good outcomes for surgically treated patients with cerebellar haemorrhages larger than 3 cm, hydrocephalus, or brainstem compression. Conservative management of patients with smaller haemorrhages without signs of brainstem compression as decrease in vigilance seems to be justified (89, 90). No recommendation can be made for surgical evacuation of brainstem haematomas, because the tissue destruction caused by the initial bleeding precludes any benefit.

Intraventricular haemorrhage and hydrocephalus IVH occurs in up to 40% of all patients with ICH. Amount of intraventricular blood, time to clearance of the ventricles, and development of hydrocephalus were identified as independent predictors of poor outcome or death (91, 92). EVD is the treatment of choice. Intraventricular thrombolysis was proposed as an effective measure to hasten the resolution of the intraventricular blood clot, reduce the duration of EVD, decrease the severity and incidence of communicating hydrocephalus, and reduce IVH-associated mortality. At the moment, a prospective phase III study on intraventricular thrombolysis with rtPA is ongoing (CLEARIII).

Conclusion Medical treatments of ICH target mainly BP optimization and haematoma growth. Surgical treatment may represent an attractive and conclusive option to remove clotted blood, derive CSF, or combat intracranial pressure. Outcome effects of both medical and surgical approaches rely substantially on the follow-up neurocritical care. Despite great efforts in the last 10 years, effective evidence-based treatment for ICH remains still undefined. However, even with a scarcity of evidence, our understanding of ICH including definition of novel clinical targets is progressing rapidly.

References 1. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. A prospective study of acute cerebrovascular disease in the community: The Oxfordshire community stroke project—1981–86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 1990;53:16–22. 2. Hemphill JC, 3rd, Newman J, Zhao S, Johnston SC. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke. 2004;35:1130–1134. 3. Diringer MN, Edwards DF. Admission to a neurologic/neurosurgical intensive care unit is associated with reduced mortality rate after intracerebral hemorrhage. Crit Care Med. 2001;29:635–640. 4. Mirski MA, Chang CW, Cowan R. Impact of a neuroscience intensive care unit on neurosurgical patient outcomes and cost of care: evidence-based support for an intensivist-directed specialty ICU model of care. J Neurosurg Anesthesiol. 2001;13:83–92. 5. Muench E, Bauhuf C, Roth H, Horn P, Phillips M, Marquetant N, et al. Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation. Crit Care Med. 2005;33:2367–2372. 6. Georgiadis D, Schwarz S, Baumgartner RW, Veltkamp R, Schwab S. Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke. Stroke. 2001;32:2088–2092.

7. Georgiadis D, Schwarz S, Kollmar R, Baumgartner RW, Schwab S. Influence of inspiration:expiration ratio on intracranial and cerebral perfusion pressure in acute stroke patients. Intensive Care Med. 2002;28:1089–1093. 8. Kidwell CS, Saver JL, Mattiello J, Warach S, Liebeskind DS, Starkman S, et al. Diffusion-perfusion mr evaluation of perihematomal injury in hyperacute intracerebral hemorrhage. Neurology. 2001;57:1611–1617. 9. Herweh C, Juttler E, Schellinger PD, Klotz E, Jenetzky E, Orakcioglu B, et  al. Evidence against a perihemorrhagic penumbra provided by perfusion computed tomography. Stroke. 2007;38:2941–2947. 10. Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, et  al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (interact): A randomised pilot trial. Lancet Neurol. 2008;7:391–399. 11. Robinson TG, Dawson SL, Eames PJ, Panerai RB, Potter JF. Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke. Stroke. 2003;34:705–712. 12. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, et  al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults:  2007 update:  a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation. 2007;116:e391–413. 13. Steiner T, Kaste M, Forsting M, Mendelow D, Kwiecinski H, Szikora I, et al. Recommendations for the management of intracranial haemorrhage— part I:  spontaneous intracerebral haemorrhage. The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis. 2006;22:294–316. 14. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005;352:777–785. 15. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–2137. 16. Mayer SA, Davis SM, Skolnick BE, Brun NC, Begtrup K, Broderick JP, et  al. Can a subset of intracerebral hemorrhage patients benefit from hemostatic therapy with recombinant activated factor VII? Stroke. 2009;40:833–840. 17. Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63:1059–1064. 18. Firozvi K, Deveras RA, Kessler CM. Reversal of low-molecular-weight heparin-induced bleeding in patients with pre-existing hypercoagulable states with human recombinant activated factor VII concentrate. Am J Hematol. 2006;81:582–589. 19. Huttner HB, Schellinger PD, Hartmann M, Kohrmann M, Juettler E, Wikner J, et al. Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy:  Comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates. Stroke. 2006;37:1465–1470. 20. Steiner T, Freiberger A, Griebe M, Husing J, Ivandic B, Kollmar R, et  al. International normalised ratio normalisation in patients with coumarin-related intracranial haemorrhages—the INCH trial:  a randomised controlled multicentre trial to compare safety and preliminary efficacy of fresh frozen plasma and prothrombin complex— study design and protocol. Int J Stroke. 2011;6:271–277. 21. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et  al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–1151. 22. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et  al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med.365:883–891. 23. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med.365:981–992.

CHAPTER 12

acute management and treatment of intracerebral haemorrhage

24. Zhou W, Zorn M, Nawroth P, Butehorn U, Perzborn E, Heitmeier S, Veltkamp R. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke. 2013 Mar;44(3):771–778. 25. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke.42:3594–3599. 26. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32:2426–2432. 27. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367. 28. Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–461. 29. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–1297. 30. Oddo M, Schmidt JM, Carrera E, Badjatia N, Connolly ES, Presciutti M, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury:  a microdialysis study. Crit Care Med. 2008;36:3233–3238. 31. Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NE, et  al. Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK glucose insulin in stroke trial (GIST-UK). Lancet Neurol. 2007;6:397–406. 32. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25:457–507. 33. Schwarz S, Hafner K, Aschoff A, Schwab S. Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology. 2000;54:354–361. 34. Ginsberg MD, Busto R. Combating hyperthermia in acute stroke:  a significant clinical concern. Stroke. 1998;29:529–534. 35. Kollmar R, Staykov D, Dorfler A, Schellinger PD, Schwab S, Bardutzky J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2010;41:1684–1689. 36. Claassen J, Jette N, Chum F, Green R, Schmidt M, Choi H, et  al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology. 2007;69:1356–1365. 37. Passero S, Rocchi R, Rossi S, Ulivelli M, Vatti G. Seizures after spontaneous supratentorial intracerebral hemorrhage. Epilepsia. 2002;43:1175–1180. 38. Vespa PM, O’Phelan K, Shah M, Mirabelli J, Starkman S, Kidwell C, et al. Acute seizures after intracerebral hemorrhage:  a factor in progressive midline shift and outcome. Neurology. 2003;60:1441–1446. 39. Kamphuisen PW, Agnelli G, Sebastianelli M. Prevention of venous thromboembolism after acute ischemic stroke. J Thromb Haemost. 2005;3:1187–1194. 40. Kelly J, Rudd A, Lewis RR, Coshall C, Moody A, Hunt BJ. Venous thromboembolism after acute ischemic stroke: a prospective study using magnetic resonance direct thrombus imaging. Stroke. 2004;35:2320–2325. 41. Wijdicks EF, Scott JP. Pulmonary embolism associated with acute stroke. Mayo Clin Proc. 1997;72:297–300. 42. Mazzone C, Chiodo GF, Sandercock P, Miccio M, Salvi R. Physical methods for preventing deep vein thrombosis in stroke. Cochrane Database Syst Rev. 2004;4:CD001922. 43. Dennis M, Sandercock PA, Reid J, Graham C, Murray G, Venables G, et al. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1):  a multicentre, randomised controlled trial. Lancet. 2009;373: 1958–1965. 44. Lacut K, Bressollette L, Le Gal G, Etienne E, De Tinteniac A, Renault A, et al. Prevention of venous thrombosis in patients with acute intracerebral hemorrhage. Neurology. 2005;65:865–869. 45. Diener HC, Ringelstein EB, von Kummer R, Landgraf H, Koppenhagen K, Harenberg J, et  al. Prophylaxis of thrombotic and embolic events

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in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the protect trial. Stroke. 2006;37:139–144. Sherman DG, Albers GW, Bladin C, Fieschi C, Gabbai AA, Kase CS, et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL study): an open-label randomised comparison. Lancet. 2007;369:1347–1355. Adams HP, Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke. Circulation. 2007;115:e478–534. Boeer A, Voth E, Henze T, Prange HW. Early heparin therapy in patients with spontaneous intracerebral haemorrhage. J Neurol Neurosurg Psychiatry. 1991;54:466–467. Morgenstern LB, Hemphill JC, 3rd, Anderson C, Becker K, Broderick JP, Connolly ES, Jr, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010;41: 2108–2129. Fernandes HM, Siddique S, Banister K, Chambers I, Wooldridge T, Gregson B, et al. Continuous monitoring of ICP and CPP following ICH and its relationship to clinical, radiological and surgical parameters. Acta Neurochir Suppl. 2000;76:463–466. Ko SB, Choi HA, Parikh G, Helbok R, Schmidt JM, Lee K, et  al. Multimodality monitoring for cerebral perfusion pressure optimization in comatose patients with intracerebral hemorrhage. Stroke . 2011;42:3087–3092. Steiner LA, Czosnyka M, Piechnik SK, Smielewski P, Chatfield D, Menon DK, et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med. 2002;30:733–738. Diedler J, Sykora M, Rupp A, Poli S, Karpel-Massler G, Sakowitz O, Steiner T. Impaired cerebral vasomotor activity in spontaneous intracerebral hemorrhage. Stroke. 2009;40:815–819. Hemphill JC, 3rd, Morabito D, Farrant M, Manley GT. Brain tissue oxygen monitoring in intracerebral hemorrhage. Neurocrit Care. 2005;3: 260–270. Diedler J, Karpel-Massler G, Sykora M, Poli S, Sakowitz OW, Veltkamp R, et  al. Autoregulation and brain metabolism in the perihematomal region of spontaneous intracerebral hemorrhage: an observational pilot study. J Neurol Sci. 2010;295:16–22. Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992;77:584–589 Bereczki D, Liu M, do Prado GF, Fekete I. Mannitol for acute stroke. Stroke. 2008;39:512–513. Misra UK, Kalita J, Ranjan P, Mandal SK. Mannitol in intracerebral hemorrhage: a randomized controlled study. J Neurol Sci. 2005;234:41–45. Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med. 2000;28: 3301–3313. Schwarz S, Georgiadis D, Aschoff A, Schwab S. Effects of hypertonic (10%) saline in patients with raised intracranial pressure after stroke. Stroke. 2002;33:136–140. Wagner I, Hauer EM, Staykov D, Volbers B, Dorfler A, Schwab S, Bardutzky J. Effects of continuous hypertonic saline infusion on perihemorrhagic edema evolution. Stroke. 2011;42:1540–1545. Ogden AT, Mayer SA, Connolly ES, Jr Hyperosmolar agents in neurosurgical practice:  the evolving role of hypertonic saline. Neurosurgery. 2005;57:207–215. Dorman HR, Sondheimer JH, Cadnapaphornchai P. Mannitol-induced acute renal failure. Medicine (Baltimore). 1990;69:153–159. Wolf AL, Levi L, Marmarou A, Ward JD, Muizelaar PJ, Choi S, et  al. Effect of THAM upon outcome in severe head injury:  a randomized prospective clinical trial. J Neurosurg. 1993;78:54–59. Schwartz ML, Tator CH, Rowed DW, Reid SR, Meguro K, Andrews DF. The University of Toronto head injury treatment study: a prospective,

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79. Vespa P, McArthur D, Miller C, O’Phelan K, Frazee J, Kidwell C, et al. Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduction of hemorrhage volume and neurological improvement. Neurocrit Care. 2005;2:274–281. 80. Morgan T, Zuccarello M, Narayan R, Keyl P, Lane K, Hanley D. Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial. Acta Neurochir Suppl. 2008;105:147–151. 81. Kaneko M, Tanaka K, Shimada T, Sato K, Uemura K. Long-term evaluation of ultra-early operation for hypertensive intracerebral hemorrhage in 100 cases. J Neurosurg. 1983;58:838–842. 82. Morgenstern LB, Demchuk AM, Kim DH, Frankowski RF, Grotta JC. Rebleeding leads to poor outcome in ultra-early craniotomy for intracerebral hemorrhage. Neurology. 2001;56:1294–1299. 83. Zuccarello M, Brott T, Derex L, Kothari R, Sauerbeck L, Tew J, et  al. Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study. Stroke. 1999;30:1833–1839. 84. Sutherland CS, Hill MD, Kaufmann AM, Silvaggio JA, Demchuk AM, Sutherland GR. Recombinant factor VIIa plus surgery for intracerebral hemorrhage. Can J Neurol Sci. 2008;35:567–572. 85. Murthy JM, Chowdary GV, Murthy TV, Bhasha PS, Naryanan TJ. Decompressive craniectomy with clot evacuation in large hemispheric hypertensive intracerebral hemorrhage. Neurocrit Care. 2005;2:258–262. 86. Maira G, Anile C, Colosimo C, Rossi GF. Surgical treatment of primary supratentorial intracerebral hemorrhage in stuporous and comatose patients. Neurol Res. 2002;24:54–60. 87. Ramnarayan R, Anto D, Anilkumar TV, Nayar R. Decompressive hemicraniectomy in large putaminal hematomas: an Indian experience. J Stroke Cerebrovasc Dis. 2009;18:1–10. 88. Coutinho JM, Majoie CB, Coert BA, Stam J. Decompressive hemicraniectomy in cerebral sinus thrombosis: consecutive case series and review of the literature. Stroke. 2009;40:2233–2235. 89. van Loon J, Van Calenbergh F, Goffin J, Plets C. Controversies in the management of spontaneous cerebellar haemorrhage. A  consecutive series of 49 cases and review of the literature. Acta Neurochir (Wien). 1993;122:187–193 90. Da Pian R, Bazzan A, Pasqualin A. Surgical versus medical treatment of spontaneous posterior fossa haematomas: a cooperative study on 205 cases. Neurol Res. 1984;6:145–151. 91. Diringer MN, Edwards DF, Zazulia AR. Hydrocephalus:  a previously unrecognized predictor of poor outcome from supratentorial intracerebral hemorrhage. Stroke. 1998;29:1352–1357. 92. Tuhrim S, Horowitz DR, Sacher M, Godbold JH. Volume of ventricular blood is an important determinant of outcome in supratentorial intracerebral hemorrhage. Crit Care Med. 1999;27:617–621.

CHAPTER 13

Acute treatment in subarachnoid haemorrhage Katja E. Wartenberg Prognosis Current developments in neurocritical care including advanced continuous monitoring techniques, a shift of focus to immediate real-time normalization of pathophysiological states, and better recognition and management of complications following subarachnoid haemorrhage (SAH) have improved the level of care for SAH patients and their clinical outcome. The mortality rate has been reduced from 50% to 25–35% (1–3). Of all SAH patients 12% die before they reach medical attention (4, 5). Of the two-thirds of patients who survive, approximately 50% are permanently disabled, mainly due to neurocognitive deficits (20%), anxiety, and depression which occur in up to 80%. Many patients do not return to work or they retire early, and their relationships are affected (6, 7). Advanced age, poor clinical status, recurrent haemorrhage, larger aneurysm size, global cerebral oedema, delayed cerebral ischaemia, and medical complications impact functional outcome after SAH. Of all these factors, the clinical condition upon arrival in the hospital appears to be the single most important risk factor for poor outcome (8–11). The poor-grade patients (Hunt–Hess or World Federation of Neurological Surgeons Scale (WFNS) grade IV and V), 18–24% of the entire SAH population, present the greatest challenge. They have worse long-term functional outcomes and higher mortality rates (11–13). However, early and aggressive treatment of patients with severe SAH resulted in unexpected improvements of long-term outcome (14–16). In a Japanese study of 283 poor-grade SAH patients, 34% achieved afavourableoutcome (good recovery, moderate disability on Glasgow Outcome Scale (GOS 4 and 5)) at discharge. Improvement in WFNS grade was associated with favourable outcome (17). In another retrospective study of 47 WFNS grade 4 and 5 SAH patients who underwent coiling of the ruptured aneurysm and aggressive neurocritical care, good outcome (GOS 4 and 5) at 6 months was achieved in 53% (3). Of 70 vigorously treated patients with Hunt and Hess grade V SAH, 35 (50%) died. Of 26 patients with neurocognitive testing at 1 year, half of the patients, mainly young and highly educated individuals, all employed in full-time jobs prior to SAH, had mild cognitive deficits and were able to live a normal life (12). Furthermore, mortality rates are substantially higher and good long-term functional outcomes less often achieved at medical centres that treat less than 18 patients with SAH per year (18–20).

Clinical scores The clinical condition upon admission of a patient is most commonly rated with the Glasgow Coma Scale (GCS) (21),

Hunt–Hess scale (22), or the WFNS scale (23). The scales are listed in Tables  13.1–13.3. The reports about intra- and interobserver agreements are sparse and highly variable. However, obtaining a score on admission is recommended to have an estimate of long-term outcome (24). The Fisher scale is a radiological scale based on the amount and distribution of blood on computed tomography (CT) used to predict the future occurrence of delayed cerebral ischaemia (Figure 13.1) (25). A modification of the original Fisher scale with attention to thick cisternal and ventricular blood resulted in a more accurate association with symptomatic vasospasm (Figure  13.2) (26, 27).

General emergency and critical care management In acute SAH, the sudden rise of intracranial pressure (ICP) up to levels of the mean arterial pressure (MAP) results in an arrest of cerebral circulation which is clinically seen as loss of consciousness (28), and in development of global cerebral oedema as well as acute ischaemic injury on neuroimaging (Figure 13.3) (8, 29–31). While diagnosing the cause of SAH and preparing for aneurysm repair initial care should focus on: ◆

Stabilization of systemic oxygenation and haemodynamics to optimize cerebral perfusion and oxygen supply

◆

Control of ICP caused by hydrocephalus and/or global cerebral oedema

◆

Blood pressure control

◆

Seizure control

◆

Antifibrinolytic agents to prevent aneurysm rebleeding.

The resuscitation goals for SAH are presented in Table 13.4. The treatment of SAH starts with management of airway, respiration, and circulation, followed by evaluation of the level of consciousness. A complete blood count (CBC), metabolic panel, coagulation studies, troponin I, creatine kinase, urine analysis, urine toxicology screen, blood for type and crossmatch, an electrocardiogram, and a chest x-ray should be obtained. The next step is aimed at prevention of rebleeding which occurs in 9–17% of patients in the first 72 hours, 40–87% of those within the first 6 hours. Patients with high-grade SAH, loss of consciousness at index bleed, larger aneurysms, sentinel bleeds, angiography within 3–6 hours of symptom onset, delay to treatment, and incomplete

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oxford textbook of stroke and cerebrovascular disease Table 13.1 Glasgow Coma Scale (21)

Table 13.3 World Federation of Neurological Surgeons Scale

Eye opening Spontaneous eye opening with blinking at baseline response Eye opening to verbal command, speech, or shout

Verbal response

Motor response

4 points

Grade

3 points

I

15

Absent

Eye opening to painful stimuli

2 points

I

13–14

Absent

None

1 point

III

13–14

Present

Oriented

5 points

IV

8–12

Absent or present

Confused conversation, but able to answer questions

4 points

V

60  mmHg,

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A

B

C

D

acute treatment in subarachnoid haemorrhage

Fig. 13.1 Fisher scale (25) on non-contrast computed tomography. (A) Grade I: no subarachnoid blood, risk of symptomatic vasospasm 21%. (B) Grade II: diffuse, thin subarachnoid blood 1 mm, risk of symptomatic vasospasm 37%. (D) Grade IV: no or diffuse, thin subarachnoid blood with ventricular haemorrhage, risk of symptomatic vasospasm 31%.

and an arterial partial pressure of carbon dioxide of 35  mmHg, bolus administration of hypertonic saline may be the preferred treatment for ICP crisis. Hypertonic saline (23.5%) given for ICP control resulted in an increase in CBF in ischaemic regions and in augmentation of brain tissue oxygenation as well as in a decrease in ICP (44, 45). Multimodal monitoring including ICP, MAP, CPP, partial pressure of cerebral tissue oxygen (PbtO2), cerebral lactate, pyruvate, glucose, glycerol, and glutamate by microdialysis and reactivity indices may help to determine the optimal CPP threshold. The pressure reactivity index is calculated as the correlation coefficient between ICP and MAP to reflect cerebral autoregulation states. If autoregulation is disturbed, MAP changes are directly transmitted passively through a non-reactive vasculature to ICP (see Figure 13.4). The optimal CPP was defined as the CPP at the

lowest pressure reactivity index observed within a range of CPP (50–90 mmHg usually) (46).

Management of volume status Intravascular volume status should be monitored as reduced intravascular volume regulation resulting in hypovolaemia may increase the frequency of cerebral ischaemia and infarction (47– 50). Although placement of a central venous catheter is recommended for large-volume access and monitoring, central venous pressure (CVP) is an unreliable marker of intravascular volume (51, 52). Assessment of fluid status should not be based solely on CVP. Clinical examination of the patient, records of in- and output, hourly urine output, and stroke volume variation in intubated patients may be helpful variables. Routine placement of pulmonary artery catheters is not recommended (35). In general, intravenous

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oxford textbook of stroke and cerebrovascular disease A

B

C D

Fig. 13.2 Modified Fisher Scale (26, 27) on non-contrast computed tomography. (A) Grade I: no or minimal subarachnoid blood, no intraventricular haemorrhage risk of symptomatic vasospasm 24%. (B) Grade II: minimal subarachnoid blood with intraventricular haemorrhage, risk of symptomatic vasospasm 33%. (C) Grade III: diffuse or focal, thick subarachnoid blood, no intraventricular haemorrhage, risk of symptomatic vasospasm 33%. (D) Grade IV: diffuse or focal, thick subarachnoid blood with intraventricular haemorrhage, risk of symptomatic vasospasm 40%.

fluid management for patients with SAH should target euvolaemia (24, 35). Prophylactic hypervolaemia may be harmful (53–56). Isotonic fluids such as 0.9% saline at 1–1.5 mL/kg/hour can be used. Supplemental 250 ml boluses of crystalloid (0.9% saline) or colloid (5% albumin) solution can be given every 2 hours. However, crystalloids are preferred (35). Hypertonic saline solutions (2% or 3% sodium chloride/acetate, 1 mL/kg/hour) are an alternative to normal saline for patients suffering from refractory intracranial hypertension or symptomatic intracranial mass effect. The infusion is adjusted to maintain a sodium level of 150–155 mEq/L and serum osmolality of 310–320 mOsms/L. Hypotonic fluids should be avoided (24).

Prevention and treatment of seizures The frequency of seizures in SAH has been reported to be 1–7% at onset, although many of these events may represent tonic posturing. Approximately 5% experience seizures during hospitalization, and 7% will develop epilepsy during the first year after discharge (57, 58). The most important trigger for seizure is focal pathology

such as large subarachnoid clots, subdural haematoma, or cerebral infarction. A  seizure at the onset of SAH does not predict an increased risk for epilepsy (57). Routine use of phenytoin or fosphenytoin may worsen functional and cognitive outcome after SAH (59, 60) and is no longer recommended (24, 35). If seizure prophylaxis with other antiepileptic drugs such as levetiracetam is warranted to prevent rebleeding, they should be administered for 3–7 days only (35). Comatose patients may have non-convulsive seizures or status epilepticus (8–19%) (61–63). Therefore, continuous electroencephalographic monitoring (cEEG) is recommended in poor-grade SAH patients in stupor or coma. The effect of treatment of non-convulsive seizures in these patients is less clear (35).

Aneurysm repair Craniotomy and aneurysm clipping with microsurgical technique and preservation of the parent artery and its branches has long been considered the gold standard of aneurysm therapy. Clipping within 48–72 hours of presentation and safer microsurgical

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acute treatment in subarachnoid haemorrhage

interventional cerebrovascular experts and based on clinical and radiological characteristics such as: ◆

Clinical status of the patient

◆

Anticipated surgical difficulty based on anatomical location

◆

Anatomy of the access vessels (tortuosity, extent of arteriosclerotic change)

◆

Width of aneurysm neck in comparison to the dome and the parent artery (wide neck aneurysms are difficult to completely obliterate with coils, coils may migrate and be a source for emboli)

◆

Presence of an intracerebral haematoma with mass effect (24, 69).

Recent advances in technique including the balloon remodelling technique that holds the coils in the aneurysm cavity, liquid polymer coils and embolic agents, and endovascular stents through which coils can be employed into the aneurysm make treatment of broad neck aneurysm feasible. The skills of the treating interventionalist or neurosurgeon as well as the institution may have a great impact on outcome (24).

Fig. 13.3 Diffusion-weighted Imaging of a patient with Hunt–Hess IV subarachnoid haemorrhage, obtained on admission, showing acute ischaemic injury in the distribution of the bilateral anterior cerebral artery territory.

techniques result in permanent aneurysm obliteration in over 90% confirmed by intra- or postoperative angiograms as well as in low morbidity and mortality (5–15%) excluding giant aneurysms (64–67). The complication rate of clipping is highest when the aneurysm is large or located on the basilar artery (68–70). Aneurysms on the middle cerebral artery may be more amendable to surgery (71, 72). With the introduction of Guglielmi Detachable Coils (soft thrombogenic detachable platinum coils, GDC, Target Therapeutics, Fremont, CA) for endovascular therapy of aneurysms in 1991 (73, 74), coil embolization became an important alternative to craniotomy and aneurysm clipping. Obliteration of small-necked aneurysms is achieved in 80–90% of the cases with a complication rate up to 9% including perforation and cerebral ischaemia (75). For a short-term period endovascular coiling seems to be safer than clipping as demonstrated by the International Subarachnoid Hemorrhage Aneurysm Trial (ISAT). The ISAT study enrolled 2134 good-grade patients with mostly small aneurysms smaller than 10 mm in the anterior circulation in a randomized fashion to undergo aneurysm clipping or coiling. At 1  year, death and dependency was 23.5% after coiling and 30.9% after clipping (absolute risk reduction of death and dependence at 1 year 7.4% with coiling) which may be attributed to decreased brain retraction injury or intraprocedural rebleeding with coiling compared to clipping. This finding is further substantiated by previous and follow-up studies. There is a decreased risk of epilepsy with coiling after 1  year (14% vs 24%) as well. The main concern about endovascular therapy is an increased rate of rebleeding after several years due to coil compaction and aneurysm re-growth at the residual neck (recurrent haemorrhage 7% after coiling versus 2% with clipping after 1 year) (58, 76). The decision between surgical clipping and endovascular coiling should be made by a team of neurological, surgical, and

Delayed cerebral ischaemia Delayed cerebral ischaemia (DCI) is defined as development of new focal neurological signs, deterioration in level of consciousness, lasting for more than 1 hour, or the appearance of new infarction on CT or magnetic resonance imaging (MRI) when the underlying pathophysiology is thought to be vasospasm and other causes are excluded (77, 78). This definition has been found to be more meaningful than symptomatic vasospasm (new focal deficit and/or decrease in level of consciousness due to vasospasm), especially in poor-grade patients whose neurological deterioration may happen unrecognized. Arterial narrowing can be demonstrated angiographically in 50–70% and leads to delayed ischaemia in 19–46% after SAH (angiographic vasospasm, see Figure 13.5). Development of vasospasm begins on day 3 after SAH, is maximal at 5–14 days, and resolves by day 21. Presence of thick subarachnoid blood seen on admission CT and severe intraventricular haemorrhage are strongly associated with higher risk for vasospasm (Figures 13.1 and 13.2) (25–27, 79, 80). Prevention and management of DCI are listed in Table 13.4.

Monitoring for delayed cerebral ischaemia Observation in a neurointensive care unit with expertise (GCS exam hourly, National Institute of Health Stroke Scale (NIHSS) (81) 6-hourly), and daily transcranial Doppler ultrasonography (TCD) are simple and helpful monitoring tools (35). Decreased level of consciousness and focal signs such as aphasia or hemiparesis in a good grade SAH patient should prompt the clinician to take immediate action such as a confirmatory test (35). TCD is a non-invasive method used to diagnose vasospasm in the larger cerebral arteries with high specificity and variable sensitivity, dependent on the operator and other systemic conditions (82, 83). A mean flow velocity (Vm) of greater than 120 cm/second in the middle cerebral artery (MCA) is concerning for vasospasm, Vm above 200 cm/second is considered to be predictive, but dynamic changes of the mean flow velocities such as a twofold increase might be more sensitive for the diagnosis of vasospasm (82, 84). The Lindegaard index (Vm of the middle cerebral artery in relation to Vm in the extracranial internal carotid artery) above 6 also indicates the presence of arterial vasospasm (84–86). A high suspicion for DCI

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oxford textbook of stroke and cerebrovascular disease Table 13.4 Acute management and resuscitation goals of subarachnoid haemorrhage Blood pressure

Invasive monitoring Goal: systolic