Handbook of Epilepsy Treatment Handbook of Epilepsy Treatment, Third Edition Simon Shorvon © 2010 Simon Shorvon. ISBN: 978-1-405-19818-9 Handbook of Epilepsy Treatment Simon Shorvon, MA, MB BChir, MD, FRCP Professor of Neurology and Clinical Subdean, UCL Institute of Neurology, University College London Consultant Neurologist, National Hospital for Neurology and Neurosurgery, Queen Square London THIRD EDITION A John Wiley & Sons, Ltd., Publication This edition fi rst published 2010 © 2000, 2005, 2010 by Simon Shorvon Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientifi c, Technical and Medical business to form Wiley-Blackwell. 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No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Shorvon, S. D. (Simon D.) Handbook of epilepsy treatment / Simon Shorvon. – 3nd ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4051-9818-9 1. Epilepsy–Handbooks, manuals, etc. 2. Anticonvulsants–Handbooks, manuals, etc. I. Title. [DNLM: 1. Epilepsy–therapy. WL 385 S559h 2010] RC372.S528 2010 616.8′5306–dc22 2010015320 A catalogue record for this book is available from the British Library. Set in 9.25 on 11.5pt Minion by Toppan Best-set Premedia Limited Printed and bound in Singapore 01 2010 Contents Preface to the Third Edition, ix Acknowledgements, xii 1 Defi nitions and Epidemiology, 1 Defi nitions, 1 Frequency and population features of epilepsy, 3 2 Seizure Type and Anatomical Location of Seizures, 6 Seizure type, 6 Classifi cation of partial seizures by anatomical site of seizure onset, 12 3 Epilepsy Syndromes, 19 ILAE Classifi cation of the Epilepsies and Epilepsy Syndromes, 19 The epilepsy syndromes, 21 4 The Causes of Epilepsy, 33 Idiopathic epilepsy, 33 Symptomatic epilepsy of genetic or congenital origin, 36 Symptomatic epilepsy due to acquired causes, 54 Provoked seizures, 67 5 Principles of Treatment, 75 Why treat epilepsy? The aims of treatment, 75 The risks of epilepsy and its treatment, 76 Choice of antiepileptic drug therapy based on seizure type, 81 Treatment of specifi c epilepsy syndromes, 89 Principles of treatment of newly diagnosed patients, 96 Principles of treatment of patients with established active epilepsy, 101 Treatment of patients with epilepsy in remission, 104 Psychiatric disorders in epilepsy, 107 Life-threatening idiosyncratic reactions, 116 Complementary and alternative therapy in epilepsy, 118 Genetic counselling in epilepsy, 121 6 Treatment of Epilepsy in Specifi c Groups, 127 Treatment of epilepsy in children, 127 Treatment of epilepsy in patients with additional handicaps, 129 Epilepsy in elderly people, 132 Treatment of epilepsy in women, 136 7 Pharmacokinetic Principles of Antiepileptic Drug Treatment, 147 Drug absorption, 147 Drug distribution, 148 v vi Contents Drug elimination (metabolism and excretion), 150 Blood level measurements, 153 8 The Antiepileptic Drugs, 158 Carbamazepine, 158 Clobazam, 170 Clonazepam, 174 Eslicarbazepine acetate, 177 Ethosuximide, 181 Gabapentin, 185 Lacosamide, 189 Lamotrigine, 192 Levetiracetam, 199 Oxcarbazepine, 205 Phenobarbital, 210 Phenytoin, 218 Pregabalin, 229 Primidone, 232 Rufi namide, 235 Tiagabine, 238 Topiramate, 244 Valproate, 252 Vigabatrin, 261 Zonisamide, 267 Other drugs used in the treatment of epilepsy, 272 Acetazolamide, 273 Benzodiazepines, 275 Corticosteroids and ACTH, 278 Felbamate, 278 Piracetam, 281 Stiripentol, 285 9 The Emergency Treatment of Epilepsy, 287 How to deal with a seizure, 287 Status epilepticus, 288 Antiepileptic drugs used in status epilepticus, 307 10 The Surgical Therapy of Epilepsy, 314 Presurgical assessment – general points, 315 Surgery in epilepsy arising in the mesial temporal lobe, 321 Surgery in epilepsy arising in extratemporal regions and the temporal neocortex, 339 Cortical dysplasia (malformations of cortical development), 349 Surgery where no lesion is apparent on neuroimaging (‘MRI-negative cases’), 351 Hemispherectomy, hemispherotomy and other large resections, 352 Corpus callosectomy (corpus callosum section, corpus callosotomy), 356 Multiple subpial transection, 358 Vagal nerve stimulation, 359 Other functional surgical procedures, 362 Contents vii The organization of epilepsy surgery care: the epilepsy surgery centre, 364 Pharmacopoeia, 365 Antiepileptic drugs – indications in epilepsy, 367 Antiepileptic drugs – dose, average adult values, 369 Antiepileptic drugs – dose, interactions, 370 Antiepileptic drugs – dose, in children, 371 Antiepileptic drugs – summary of side effects, 372 Antiepileptic drugs – summary of metabolism, 374 Antiepileptic drugs – summary of pharmacokinetic values (typical adult values), 376 Antiepileptic drugs – modes of action, 377 Further Reading, 378 Index, 409 Preface to the Third Edition This monograph is part of the series of handbooks that epilepsy in the clinic. The internet, by its all inclusive are produced to accompany the large multi - authored nature, cannot take such a singular approach. reference books published by Wiley - Blackwell. The third This is the justifi cation for embarking on a third edition of the reference text Treatment of Epilepsy was edition. The fi rst two editions of the handbook were published in 2009 (edited by myself, Emilio Perucca and published 10 and 4 years ago, were both generously Jerome Engel), and this handbook is now also in its third received and, I hope, fulfi lled at least in part their purpose edition. of informing and improving epilepsy therapy. However, As we now enter the second decade of the age of the in epilepsy, as in all of medicine, treatment moves on, internet, the fi rst question to address when contemplat- knowledge has increased and fashions have changed and, ing a writing project is a fundamental one – are books of in the short span of these handbooks, much new this nature still required? In an age where information is information has arrived on the desks of physicians. The now readily available at a click of a Google button, does writing of a third edition is an opportunity to refl ect these a book have a function frozen as it is in form and in changes, and also, sad to say, to correct the all too obvious content, not unlike, some would argue, the fossilized defi ciencies of the previous editions. remains of past life forms? This is a question that is As I noted in the previous edition, this book contains already central to medical publishing. My own opinion pretty much everything I know about epilepsy therapy. on this matter is, however, clear – books that concentrate It is a worrying thought that all one ’ s professional knowl- and fi lter information are both necessary and desirable, edge can be compressed into a couple of megabytes (the in the fi eld of epilepsy treatment, as much as anywhere draft manuscript of the whole book amounted to less else, for at least three reasons: than fi ve megabytes, and could be saved onto a memory 1 Accuracy of information: comprehensive as the inter- stick smaller than my fi ngernail, but this is the rather net is, accurate it is not. There exists on the web much humbling reality). Another concern is that this is a single information that is phoney, wild and irresponsible, many author text, with the danger of bias and prejudice. My data that are inaccurate or uncorroborated, and much defence is that the disadvantages of single-authorship opinion that has more to do with kite - fl ying than medical need to be weighed against the advantages of coherence science. A book can avoid these snake - pits. and lack of omission, repetition or inconsistency. 2 Condensation of information into a short and concise Avoiding these in the writing of this book has been a form, in one easily accessible place: this I have tried to constant preoccupation. do here, avoiding repetition, redundancy or excessive The aim of this edition is exactly the same the aim of verbiage. Whether this is successfully achieved is a judge- the previous editions, and so is cited verbatim from the ment for the reader, but the condensation of data in the second edition: book is surely an overwhelming advantage over the diffuse nature of the information highway (now less of a The aim is to summarize the many and various treatments discrete path than a horizonless moor). of epilepsy in a clear yet comprehensive, and concise yet 3 Consistency of perspective and approach: this book is balanced and practical manner. Surgical as well as medical written from a single perspective – that of the practising therapy is included, as is the treatment of epilepsy in adults neurologist who specializes in epilepsy. This is not a sci- and children. Rare as well as common clinical problems are entifi c, theoretical or populist, but a medical, text. Its covered, and rarely – as well as commonly - used therapies. audience is the practising doctor who sees patients with It is intended to be a hands - on text which will guide clinical ix x Preface to the Third Edition practice and rational therapy, and to be a source of ready rize and extract data. Second, since the last edition there reference; a catalogue of epilepsy therapy. There is an have been licensed at least fi ve new antiepileptic drugs emphasis on factual information, which I have tried to give and a large range of novel drugs is also in the process of in a parsimonious and easily - digested form, but one that development. The widely predicted famine in the fi eld of still gives the reader a clear idea of the scientifi c basis of epilepsy therapy that so many foresaw in the past decade current practice. This scientifi c perspective is important has resolutely failed to materialize. Indeed, it is probably and, where possible, the text has endeavoured to be science - true to say that there have been more novel and exciting and evidence - based. In some areas of therapy an evidence therapies in current development since the publication of base, however, is lacking (perhaps especially in the area of the last edition than at any time in the history of epilepsy epilepsy surgery), and data informing longer - term therapy. It is not, I hope, too panglossian to think that outcome, risk and benefi t in particular are missing. In these these have incrementally improved treatment of many areas the book inevitably refl ects the author ’ s own preju- patients. Finally, the scientifi c information about drug dices and anecdotal experience. therapy has again improved, due to advances in clinical and molecular chemistry, and this is also incorporated The book is embedded in the experience gained from where possible in this book. Developments in the surgical my own clinical practice, now over 30 years of specializa- therapy of epilepsy have been less impressive, but there tion in epilepsy at the National Hospital for Neurology are some areas of incremental change that I hope also to and Neurosurgery, Queen Square, London, and is heavily have recorded. infl uenced by this. The book also refl ects the work of the As in the last edition, a number of editorial decisions International League Against Epilepsy, on whose execu- have been made that should be noted here. The summary tive committee I have served now for more than 17 years. of factual information in table form (for easy reference) These infl uences provide the context and a distinctive is a deliberate policy, but it should be recognized that, perspective, which I hope adds coherence and interest. especially in relation to pharmacological and pharmaco- I mentioned, in the previous edition, three develop- kinetic data, confl icting information commonly exists. ments in epilepsy therapy that had occurred in the years This can lead to contention, and the tables include leading up to 2005, and that I considered to deserve what I consider to be the most reliable data. It is special mention. The fi rst was molecular genetics – but important also to recognize that data do vary, and in now 5 years later one has to admit that in the therapeutic some places the data in the tables are not universally arena the impact has been less than hoped for. The goal applicable. Second, the contentious decision has been of therapy tailored to an individual ’ s genomic make - up, made, in the interests of readability and clarity, to omit which 5 years ago was trumpeted by colleagues and citations to the literature from the text. In the age of seemed within reach, now seems entirely unrealizable in PubMed and Medline, literature is now easily tracked, the foreseeable future. The second was the plethora of and citations can also be found in the relevant chapters guidelines – this torrent continues to fl ow, and now, in of the associated textbook. In place of this, a ‘ further my personal opinion, the downsides of this outweigh reading ’ section, listing key articles, books and review the advantages. This fashion for guidelines risks bland articles, with an emphasis on recent publications, has uniformity and guideline fatigue. Does the wearying been included; this seemed to me to be of more general audience really need the further imposition of more of utility. Finally, the reader should know that this these? The third thread of contemporary therapy identi- book, like its predecessor, is conceptually, and in many fi ed in the last edition was the importance of patient places actually, a condensation of the multi - authored involvement in medical decisions. This remains an textbook ( Treatment of Epilepsy , edited by Shorvon SD, important prerogative and in this edition too the impor- Perucca E, Engel J, Blackwell Publishing Ltd, Oxford, tance of two - way communication and of patient choice 2009). Much of the information in this handbook is emphasized. has its basis in the textbook (that indeed is a rationale of There are a series of signifi cant changes to this edition, this handbook) and the borrowing has often been which it is hoped will improve the book. First, the struc- heavy, sometimes word for word, and the infl uence ture has changed, which refl ects the greater attention to great. I would like to acknowledge here my debt of the causes of and the syndromes of epilepsy (now sepa- gratitude to my co - editors of this textbook, Professor rate chapters), as well as more detail on principles Emilio Perucca and Professor Pete Engel, and also to all of therapy, and a greater emphasis on tables to summa- the contributors to the multi - authored textbook (listed Preface to the Third Edition xi in the acknowledgement section), for without their work Finally, I repeat the health warning of the second this book would not exist. The textbook remains a land- edition: although every effort has been made in the prep- mark in the bibliography of epilepsy therapy. aration of this book to ensure that the details given are Finally, thanks too are due to the production crew at correct, it is possible that errors have been overlooked Wiley - Blackwell, Rebecca Huxley and Martin Sugden for (e.g. in pharmaceutical or pharmacokinetic data). The their expert guidance and assistance, and Lynne and reader is advised to refer to published information from Matthew, for whom the writing of this book has meant the pharmaceutical companies and other reference works lost time and the smoke of much midnight oil. to check accuracy. Simon Shorvon London 2010
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