THERAPEUTIC CLAIMS IN MULTIPLE SCLEROSIS Therapeutic Claims in Multiple Sclerosis SECOND EDITION William A. Sibley, M.D. Department of Neurology University of Arizona Tucson, AZ and the Therapeutic Claims Committee of the International Federation of Multiple Sclerosis Societies M MACMILLAN PRESS ©National Multiple Sclerosis Society 1988 All rights reserved. No reproduction, copy or transmission of this publication may be made without written permission. No paragraph of this publication may be reproduced, copied, or transmitted save with written permission or in accordance with the provisions of the Copy right Act 1956 (as amended), or under the terms of any license permitting lim ited copying issued by the Copyright Licensing Agency, 33-4 Alfred Place, London WC1E 7DP. Any person who does any unauthorised act in relation to this publication may be liable to criminal prosecution and civil claims for damages. First published: DEMOS PUBLICATIONS INC, New York, New York, USA. This edition published by: THE MACMILLAN PRESS LTD, Houndmills, Basingstoke, Hampshire RG21 2XS and London Companies and representatives throughout the world This book is written for informational purposes only. Nothing contained in it should be interpreted as a recommended treatment for any individual pa tient; such a decision can only be made by the patient's physician who can consider merits, risks, past history, associated illnesses, and many other fac tors. The opinions expressed about the general usefulness, or lack of useful ness, of various therapies are those of the Therapeutic Claims Committee of the International Federation of Multiple Sclerosis Societies (IFMSS) and are based on information available from a variety of sources, published and un published, and collective personal experience. ISBN 978-0-333-49242-0 ISBN 978-1-349-10872-5 (eBook) DOI 10.1007/978-1-349-10872-5 British Library Cataloguing-in-Publication Data is available. IFMSS Therapeutic Claims Committee William Austin Sibley, Chairman Professor of Neurology University of Arizona Chairman, Subcommittee on Therapeutic Claims Helmut J. Bauer Professor of Neurology, Emeritus University of Gottingen Vice-Chairman, Medical Advisory Board, IFMSS Kenneth P. Johnson Professor and Chairman of Neurology University of Maryland Reginald E. Kelly Physician and Dean Emeritus Institute of Neurology Queen Square, London Chairman, Medical Advisory Board, IFMSS W. Ian McDonald Professor, University Department of Clinical Neurology The National Hospital, Queen Square, London William J. Mcilroy Associate Professor of Neurology University of Toronto National Medical Advisor, MS Society of Canada Chairman-Elect, Medical Advisory Board, IFMSS Donald W. Paty Professor and Chairman of Neurology University of British Columbia Secretary, Medical Advisory Board, IFMSS Olivier Sabouraud Professor and Chairman of Neurology University of Rennes Medical Center Labe C. Scheinberg Professor of Neurology and Rehabilitation Medicine Albert Einstein College of Medicine Stanley van den Noort Professor of Neurology California College of Medicine Past-Chairman, Medical Advisory Board National MS Society, U.S.A. PREFACE Since publication of the first edition of Therapeutic Claims in Multiple Sclerosis, there have been numerous trials of treat ment conducted in many countries in an effort to find an effec tive therapy for MS. Several of these treatments have been re ported to have a positive effect in reducing the frequency of attacks or in slowing progression in well-designed studies. Ex amples include plasmapheresis, alpha- and beta-interferon, copolymer I, total lymphoid irradiation, and cyclophosphamide. Nevertheless, there are still conflicting reports about these and other therapies. There are several new members of the Therapeutic Claims Committee, and all members are actively treating patients with MS on a daily basis. All have participated, or are participating in, active trials of therapy with various agents. They have used most, if not all, of the treatment methods seriously advocated during the past two decades. As Chairman of the Committee, I have conducted a poll of the members about their current prac tices, and the results are summarized in this volume. All experienced neurologists agree that, in spite of certain encouraging signs, much more effective treatment is neces sary-both for the acute attack of MS and for progressively worsening MS. Although the exact cause of MS remains unknown, encour aging progress has been made in understanding triggering fac tors, and one may hope that this will result in more effective preventive measures. One of the most exciting developments in recent years has been a dramatic improvement in ability to measure the activity and progress of MS, and magnetic resonance imaging has been responsible for this. Since the essence of research is accurate measurement, it seems likely that progress will be more rapid in the next few years. vii This new edition summarizes these new developments. In ad dition, the general management and symptomatic treatment recommendations prepared with the advice of the Medical Management Committee of the IFMSS, chaired by Dr. Donald Paty, are reported in Chapter 5. Some of the descriptions of old treatments have been shortened or eliminated, in order to keep the book approximately the same size. The Committee remains indebted to Dr. Joe R. Brown, a for mer member chiefly responsible for writing the first edition. We wish also to express special gratitude to Dr. Byron Waks man, Vice President for Research and Medical Programs, Na tional Multiple Sclerosis Society, U.S.A., who has provided in valuable assistance as research consultant in reading and correcting the manuscript. He has also expertly handled the many important details necessary to bring the volume to pub lication. W. A. Sibley Chairman, Board of Editors viii PREFACE CONTENTS I. Introduction 1 The Central Nervous System What Is Multiple Sclerosis? The Diagnosis of Multiple Sclerosis: How Are the Plaques Detected? Who Gets Multiple Sclerosis? What Is the Cause of Multiple Sclerosis? What Is the Natural Course of Multiple Sclerosis, Without Treatment? How Is the Progress of Multiple Sclerosis Measured? II. History, Rationale, and Summary of Treatments in Multiple Sclerosis 17 Problems in Evaluation of Therapy Proper Treatment Trials Rationale and Summary of Treatments, Old and Recent Continuing Problems in Treatment Trials A Poll of the Committee III. Treatment for an Acute Exacerbation 31 Overview Inflammation Adrenocorticotropic Hormone and Adrenal Corticosteroids Agents Affecting Prostaglandin Pathways Protease Inhibitors Miscellaneous Antiinflammatory Agents Agents Affecting Catecholamine Pathways IV. Methods Used to Prevent Worsening of Multiple Sclerosis 47 ix Overview The Immune System and MS Immune System Immunosuppression Immune Modulation Desensitization or Specific Immune Tolerance Infection Interferon and Interferon Inducers Antiviral Chemotherapy V. Symptomatic and General Management of Multiple Sclerosis 93 Motor Disturbances Pain Fatigue Bladder, Bowel, and Sexual Disturbances Psychological and Cognitive Disturbances Vaccinations Diet Paroxysmal Symptoms Comprehensive Long-Term Management and Rehabilitation Symptomatic Treatments Affecting Spasticity Affecting Conduction Affecting Fatigue General Management: Diet VI. Miscellaneous and Empirical Treatments 123 Overview Miscellaneous Empirical Treatments Injected Materials Oral Administration Physical and Surgical Manipulations Diet Selected Bibliography 189 Index 191 X CONTENTS