Multiple Sclerosis Research in Europe: Report of a Conference on Multiple Sclerosis Research in Europe, January 29th–31st 1985, Nijmegen, The Netherlands. Sponsored by the Commission of the European Communities, as advised by the Committee on Medical Publ

408 Pages·1986·8.003 MB·English

by  S. Poser (auth.), Otto R. Hommes (eds.)

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