Multiple Sclerosis Research in Europe COMMISSION OF THE EUROPEAN COMMUNITIES MULTIPLE SCLEROSIS RESEARCH IN EUROPE Report of a Conference on Multiple Sclerosis Research in Europe, January 29th-31 st 1985, Nijmegen, The Netherlands. Sponsored by the Commission of the European Communities, as advised by the Committee on Medical Public Health Research Editor Otto R. Hommes , MTP PRESS LIMITED ~ a member of the KLUWER ACADEMIC PUBLISHERS GROUP ~ LANCASTER / BOSTON / THE HAGUE / DORDRECHT for the Commission of the European Communities Published in the UK and Europe by MTP Press limited Falcon House lancaster, England British Library Cataloguing in Publication Data Multiple sclerosis research in Europe: report of a CEC Conference Nijmegen 29, 30, 31 January 1985. 1. Multiple sclerosis-Research-Europe I. Hommes, Otto R. II. Commission of the European Communities 616.8'34'007204 RC377 ISBN· 13: 978·94·010·8338·6 e·ISBN· \3: 978·94·009·4143·4 DOl: 10.1007/978·94·009·4143·4 Published in the USA by MTP Press A division of Kluwer Boston Inc 19 0 Old Derby Street Hingham, MA 02043, USA Library of Congress Cataloging In Publication Data Hommes, Otto R. (Otto RoelO Multiple sclerosis research in Europe. At head of title: MSRE. Report to the Commission of the European Communities of a Conference on Multiple Sclerosis Research in Europe. Includes bibliographies and index. 1. Multiple sclerosis-Research-Europe-Congresses. 2. Multiple sclerosis-Congresses. 3. Conference on Multiple Sclerosis Research in Europe (1985 : Nijmegen, Netherlands) I. Commission of the European Communities. II. Title. III. Title: MSRE. [DNLM: 1. Conference on Multiple Sclerosis Research in Europe (I 985 : Nijmegen, Netherlands) 2. Multiple Sclerosis-occurrence-Europe. WL 360 H768m 1985] RC377.H66 1985 616.8'34'007204 85-24053 ISBN·13:978·94·0I0·8338·6 © ECSC, EEC, EAEC, Brussels and Luxembourg, 1986 Softcover reprint of the hardcover 1st edition 1986 EUR 10312 EN Legal Notice Neither the Commission of the European Communities nor any person acting on behalf of the Commission is responsible for the use which might be made of the following information. Publication arranged by Commission of the European Communities Directorate·General Information Market and Innovation· Scientific and Technical Communication Brussels and Luxembourg. All right reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from the publishers. Contents Introduction xi Programme of the Conference xv List of Participants and Observers xxv SECTION I CLINICAL STUDIES Clinical Studies in Multiple Sclerosis S. Poser 3 2 Clinical Trials P. Rudge 13 3 Onset, Course and Prognosis of Multiple Sclerosis C. Confavreux 15 4 A Comparative Study Between Multiple Sclerosis Out-patients and In-patients Staying at a Specialized Multiple Sclerosis Clinic R. Medaer, M. Puystjens and H. Callaert 31 5 Incapacity and Disability in Multiple Sclerosis ]. M. Minderhoud, A. ]. A. Prange and H. Dassel 41 6 Immunosuppression with Cyclophosphamide in Multiple Sclerosis Patients R. E. Gonsette and L. Demonty 45 v vi CONTENTS 7 Anti-lymphocyte Serum in Severe Multiple Sclerosis R. Marteau, F. Lhermitte and H. de Saxce 49 8 Long-term Prescription of Azathioprine in Multiple Sclerosis. A Review of Published Series 0. Sabouraud and M. Merienne 55 9 Azathioprine Assessment in Progressive Multiple Sclerosis. Clinical Aspects I. E. Zeeberg 61 10 Dietary Therapy in Multiple Sclerosis D. Bates 71 11 An Eight Years Follow-up Study of Transfer Factor Treatment on the Course of Multiple Sclerosis A. M. Nordenbo and I. Zeeberg 81 12 Compact Manual for Multiple Sclerosis Registration in Clinical Research 0. Andersen, M. Andersson, T. Broman and I. Zeeberg 85 13 Comparison of Multiple Sclerosis Incidence Clinical and ABR Data Indicates a Higher Degree of Dissemination of Lesions in a Progressive than in a Remitting Course O. Andersen, U. Rosenhall and B. Runmarker 95 SECTION II IMMUNOLOGY 14 Multiple Sclerosis and Immunity: Facts, Fiction and Future Development J. Mertin 10 3 15 The Spectrum of Experimental Allergic Encephalomyelitis H. Lassmann and K. Vass 109 16 T Cell Subsets in Multiple Sclerosis M. A. Bach and E. To urnier-Lasserve 11 5 17 Functional Differences Between Cerebrospinal Fluid and Peripheral Blood T Cells in Multiple Sclerosis M. S. Wollheim and E. C. DeFreitas 123 CONTENTS vii 18 Characterization of T Cell Subsets and Macrophages in Active Demyelinating Multiple Sclerosis Lesions H. Nyland, S. Mork, R. Matre and A. Naess 131 19 Determination of Lymphocyte Subsets in Cerebrospinal Fluid (CSF) W. M. Nillesen and B. M. ]. Wtdehaag 141 20 la-presenting Cells in Early Multiple Sclerosis Lesions and Adjacent Normal Looking White Matter; A Morphological Study H. J. ter Laak and O. R. Hommes 143 21 Developmental Aspects of Oligodendrocyte Structure and Function M. Schachner 153 22 Monoclonal Antibodies against Oligodendrocytes; A Morphological Study H. J. ter Laak, M. Schachner and 0. R. Hommes 15 9 23 The Relationship of Immunological and Histological Abnormalities in Multiple Sclerosis I. V. Allen 163 24 Towards Cloning of Lymphoid Cells from Cerebrospinal Fluid F. Rotteveel, E. Braakman and C. J. Lucas 16 7 25 Activation of Natural Cytotoxic Activity In Vitro with Lymphocytes from Patients with Multiple Sclerosis E. Braakman, A. van Tu nen and C. ]. Lucas 17 5 26 Molecular and Cellular Basis of Autoimmune Encephalitogenesis H. Wekerle 185 27 Cytotoxic Antibodies in Multiple Sclerosis L. Rumbach, J. M. Warter, M. M. Tongio, C. Marescaux, S. Mayer and M. Collard 19 5 28 An Immunological Function for Astrocytes W. Fierz and A. Fontana 19 9 SECTION III BIOCHEMISTRY, NEUROBIOLOGY, MYELIN 29 The Biochemistry of Myelin J. M. Matthieu 209 viii CONTENTS 30 The Cerebrospinal Fluid Immunoglobulins in Multiple Sclerosis P. Delmotte 217 31 Multiple Sclerosis: A Two Stage Process? Studies on the Abnormalities of Cerebral Spinal Fluid by Means of Isotopic Cisternography D. Inzitari, G. Volpi, A. Castagnoli and L. Amaducci 225 32 CSF Immunoglobulins and Clinical Course H. Link 231 33 Immunoglobulin Abnormalities for IgG, IgA and IgM in Cerebrospinal Fluid of Multiple Sclerosis Patients K. J. B. Lamers, W. van Geel, ]. C. N. Kok, O. R. Hommes and B. Feenstra 241 34 Immunoglobulin IgG Abnormalities and the Oligoclonal Pattern of IgG in Multiple Sclerosis Brains K. ]. B. Lamers, W. van Geel, R. A. Wevers and O. R. Hommes 251 35 IgG Synthesis in Multiple Sclerosis D. Caputo, P. Ferrante, S. Procaccia, M. laffaroni and C. L. Cazzullo 257 36 Antigenicity of Galactosylceramide B. laIc, M. Monge, C. Lubetzki and N. A. Baumann 267 37 Immune Complexes and Complement in Multiple Sclerosis H. Jans 271 38 Myelin Basic Protein Like Reactivity in Normal Serum T. A. Out, P. C. Driediik and J. Baas 277 39 Blood-brain Barrier in Experimental Allergic Encephalomyelitis and Multiple Sclerosis. A Minireview J. J. Hauw and J. M. Lefauconnier 283 40 The Possible Role of Viral Infections in Multiple Sclerosis V. ter Meulen 289 CONTENTS ix SECTION IV HLA, EPIDEMIOLOGY, GENETICS 41 Multiple Sclerosis Cooperative Etiological Study in Italy C. Fieschi 295 42 A Multicenter Study of the Incidence of Multiple Sclerosis in Italy. Design of the Study G.Comi 305 43 HLA Markers and Course of Disease in Multiple Sclerosis M. Merienne, O. Sabouraud, R. Fauchet, M. Madigand, G. Semana, M. Gueguen, G. Dejour and G. Morel 31 5 44 HLA Antigens in Multiple Sclerosis Patients in the Benelux H. Carton, I. van de Putte, J. M. Minderhoud, J. M. Balen, O. R. Hommes, P. Reekers, R. Medaer, M. de Bruyere, D. Latinne and A. Bouckaert 323 45 HLA Antigens and Multiple Sclerosis in Barbagia, Sardinia: Preliminary Results P. L. Mattiuz, C. Conighi, M. T. Grappa, R. Tola and G. Rosati 329 46 Clinical and Immunogenetic Data of 33 Double Case Families with Multiple Sclerosis: A Starting Point for Further Analyses on the DNA Level H. Zander 333 47 Twin Studies in Multiple Sclerosis A. Heltberg 337 SECTION V IMAGING AND NEUROPHYSIOLOGY 48 The Role of Imaging in the Diagnosis of Multiple Sclerosis W. I. McDonald 345 49 Nuclear Resonance Imaging of Multiple Sclerosis Brain Lesions L. Rumbach, M. C. Caires, C. Scheiber, J. M. Warter, J. Chambron and M. Collard 349 50 Neurophysiological Studies in Demyelination and Remyelination T. A. Sears 353 51 Horizontal Eye-movement Abnormalities in Multiple Sclerosis and Optic Neuritis E. A. C. M. Sanders and]. P. H. Reulen 357 x CONTENTS 52 The Vestibulo-ocular Reflex in Multiple Sclerosis P. L. M. Huygen E. ]. ]. M. Theunissen and O. R. Hommes 363 53 New Possibilities in the Diagnosis of Multiple Sclerosis by Accurate Registration of Eye Movements with the DMI Method L. J. Bour and]. de Veth 373 54 A Parametric Study of Saccadic Eye Movements in Follow-up of Normals and Multiple Sclerosis Patients E. T. L. van Munster, P. L. M. Huygen, L. ]. Bour and 0. R. Hommes 383 55 Visual Evoked Responses in Definite and Suspected Multiple Sclerosis. Comparison of them to Cerebrospinal Fluid Oligoclonal Bands I. Milonas 393 Index 399 Introduction Multiple sclerosis is an unique disease with a tremendous impact on social life in countries with moderate climates. Its cause is unknown. In recent years however hopes have been raised that the disease might be fought, and possibly cured. With the disappearance of poliomyelitis as the main paralyzing disease multiple sclerosis has taken its place as the single disease that is responsible for paralyzing the young with an incurable affliction of long duration, for social disruption and for an economic impact that is estimated to be higher than heart disease1• A multi-national, mUlti-disciplinary approach to this extremely disabling disease is urgently needed in this phase of hopeful scientific developments. The Commission of the European Communities therefore sponsored a Con ference on Multiple Sclerosis Research in Europe on 29,30 and 31 January 1985 in Nijmegen, The Netherlands, with the aim of formulating practical proposals for such cooperation in the Communities. This volume contains the papers read at that conference. An extensive report of the discussions and recommendations of the conference was presented to the Commission of the European Communities in March 19852• It was felt that a general rating scale for use in clinical assessment of severity and course of the disease was urgently needed. Several of such scales already exist, but are not in general use1• In the last twenty years, prospects for treatment and even cure of multiple sclerosis have become more promising. However the design and execution oft reatment trials were hampered by many flaws, so that the results have remained open to criticism. Recent years have brought new tools to clinicians to perform reliable clinical trials. These trials will need large numbers of patients and these numbers can be only col lected in a short period of time by means of a coordinated effort on the part of a large number of clinical centers. European clinical centers could make a significant contribution. Brain tissues, CSF and blood cells of multiple sclerosis patients are needed for nearly all studies. These materials have to be well preserved. Multinational storage facilities for MS material should be made available as soon as possible. xi