In Western industrialized sodeties at least one in 800 of the population is affected by multiple sclerosis (MS). If the disease is recognized early and treated adequately the prospects are now better than ever for im- proving both the quality and length of life for people with MS. This condse, abundantly illustrated text provides a complete overview of MS for the internist, general neurologist and therapist. Including recent research findings in genetics, immunology and pathophysiol- ogy, the authors provide reliable and up-to-date guidance on the epi- demiology, diagnosis, prognosis and treatment of MS. Of particular interest to neuroscientists and neurologists will be the reviews of experimental models of MS, pathology of the demyelinated plaque, HLA assodations and the role of immune mechanisms. Envi- ronmental factors in the etiology of MS are examined, including the possible role of infectious agents. The clinical sections of the book in- clude discussion of neurological, sexual, psychological and cognitive disturbances, and rehabilitation measures are given spedal attention. Multiple sclerosis Multiple sclerosis Edited by ]iirg Kesselring Head of the Department of Neurorehabilitation Rehabilitation Center Valens, Switzerland Foreword by Professor W. I. McDonald National Hospital for Neurology and Neurosurgery, London CAMBRIDGE UNIVERSITY PRESS PUBLISHED BY THE PRESS SYNDICATE OF THE UNIVERSITY OF CAMBRIDGE The Pitt Building, Trumpington Street, Cambridge CB2 IRP, United Kingdom CAMBRIDGE UNIVERSITY PRESS The Edinburgh Building, Cambridge CB2 2RU, United Kingdom 40 West 20th Street, New York, NY 10011-4211, USA 10 Stamford Road, Oakleigh, Melbourne 3166, Australia © Cambridge University Press 1997 This book is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 1997 An updated and adapted translation of the German edition published by W. Kohlhammer GMBH, D-70549, Stuttgart, Germany, as Multiple Sklerose, second edition, by Jurg Kesselring. Printed in the United States of America Typeset in Palatino Library of Congress Cataloging-in-Publication Data Multiple Sklerose. English. Multiple sclerosis / edited by Jiirg Kesselring. p. cm. Includes bibliographical references and index. ISBN 0-521-48018-3 (hardback) 1. Multiple sclerosis. I. Kesselring, Jiirg. [DNLM: 1. Multiple Sclerosis. WL 360 M9618m 1996a] RC377.M83713 1996 616.8'34-dc20 DNLM/DLC for Library of Congress 96-6151 A catalog record for this book is available from the British Library ISBN 0 521 48018 3 hardback Contents Foreword by W. I. McDonald vii List of contributors ix List of abbreviations xi Part I General aspects Chapter 1 Historical perspective 3 Jiirg Kesselring Chapter 2 Pathology and experimental models 7 Hans Lassmann Chapter 3 Genetics and immunology 30 Walter Fierz Chapter 4 Epidemiology 49 Jiirg Kesselring Chapter 5 Pathogenesis 54 Jiirg Kesselring and Hans Lassmann Chapter 6 Pathophysiology of impaired neural transmission 63 Christian Hess Part II Clinical aspects Chapter 7 Symptomatology 71 Jtirg Kesselring Chapter 8 Diagnosis 87 Jiirg Kesselring and Christian Hess Chapter 9 Disease course 116 Jtirg Kesselring Chapter 10 Prognosis 121 Jtirg Kesselring vi Contents Chapter 11 Differential diagnosis 125 Jiirg Kesselring Chapter 12 Assessment of performance, ability, and disability 131 Jiirg Kesselring Part III Management and therapy Chapter 13 Symptomatic treatment and nutrition 135 Jtirgen Mertin Chapter 14 Therapy 148 Ludivig Kappos Appendix: Assessment Scales 169 References 179 Index 208 Foreword In the past two decades we have witnessed a Much has been learned about cellular mecha- remarkable growth in our understanding of nisms involved in pathogenesis and repair, and multiple sclerosis, and we are now on the the evolution of the lesion is now much better threshold of an era in which effective treatment understood through the exploitation of mag- seems possible. Though the aetiology of the netic resonance imaging (MRI) and spectro- disease is not yet fully understood, evidence for scopy. A secure early diagnosis can be made an interaction between an environmental factor earlier in the course of the disease through the (perhaps viral) with a genetic susceptibility fac- application of MRI, evoked potentials, and ce- tor has grown. Four new studies just published rebrospinal fluid analysis. (Ebers et al. 1996; Haines et al. 1996; Kuok- Developments in MRI have produced power- kanen et al. 1996; Sawcer et al. 1996) have con- ful new tools for monitoring the effectiveness of firmed that the latter implicates several chro- treatment. As a result, putative therapeutic mosomes; again, the HLA region of the 6th agents can be screened relatively quickly to see chromosome emerges as the most important.+ whether they have an influence on at least some aspects of the pathological process. One of •Ebers GC, Kukay K, Bulman DE, Sadovnick AD, the most encouraging developments has been Rice G, Anderson C, Armstrong H, Cousin K, the demonstration that a number of agents- Bell RB, Hader W, Paty DW, Hashimoto S, Oger most notably the beta-interferons-reduce the J, Duquette P, Warren S, Gray T, O'Connor P, Nath A, Auty A, Metz L, Francis G, Paulseth JE, frequency of acute pathological activity, and Murray TJ, Pryse-Phillips W, Nelson R, Freed- that this can be reflected in a modest decrease man M, Brunet D, Bouchard J-P, Hinds D, Risch in relapse rate. Convincing evidence for a use- N. A full genome search in multiple sclerosis. ful effect on disability (surely the most impor- Nature Genetics 13 (1996): 472-476. tant criterion for an effective treatment) is still Haines JL, Ter-Minassian M, Bazyk A, Gusella JF, Kim DJ, Terwedow H, Pericak-Vance MA, awaited. But the progress over the past five Rimmler JB, Haynes CS, Roses AD, Lee A, years gives grounds for optimism. Shaner B, Menold M, Seboun E, Fitoussi RP, In this timely book, the background to these Gartioux C, Reyes C, Ribierre F, Gyapay G, Weissenbach J, Ilauser SL, Goodkin DE, Lincoln advances is described; the areas of greater and R, Usuku K, Garcia-Merino A, Gatto N, Young lesser certainty are delineated and the pros- S, Oksenberg JR. (The Multiple Sclerosis Genet- pects for future progress are laid out; and the ics Group). A complete genomic screen for practical management of the patient as well as multiple sclerosis underscores a role for the ma- jor histocompatability complex. Nature Genetics of the disease are detailed. This is an exciting 13 (1996): 469-471. time for the study of multiple sclerosis, and Dr. Kuokkanen S, Sundvall M, Terwilliger JD, Tienari PJ, Kesselring and his colleagues show why. Wikstrom J, Holmdahl R, Pettersson U, Pelt- onen L. A putative vulnerability locus to W. I. McDonald multiple sclerosis maps to 5pl4-pl2 in a region syntenic to the murine locus Eae2. Nature Genet- National Hospital for Neurology and Neurosurgery ics 13 (1996): 477-480. London, England Sawcer S, Jones HB, Feakes R, Gray J, Smaldon N, Chataway J, Robertson N, Clayton D, Good- fellow PN, Compston A. A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22. Nature Genetics 13 (1996): 464-468.