Table Of ContentGeneralized Epilepsy
M. Avoli P. Gloor G. Kostopoulos
R. Naquet
Editors
Genemlized Epilepsy
Neurobiological Approaches
With 196 Illustrations in 327 Parts
Birkhauser
Boston . Basel . Berlin
Massimo Avoli, M.D., Ph.D.
McGill University, Montreal Neurological Institute,
Department of Neurophysiology, Montreal, Quebec, Canada
Pierre Gloor, Ph.D.
McGill University, Montreal Neurological Institute,
Department of Neurophysiology, Montreal, Quebec, Canada
George Kostopoulos, M.D., Ph.D.
University of Patras Medical School, Department of
Physiology, Patras, Greece
Robert Naquet, M.D.
CNRS, Laboratoire de Physiologie Nerveuse,
Gif-sur-Yvette, France
Library of Congress Cataloging-in-Publication Data
Generalized epilepsy: neurobiological approaches/M. Avoli ... ret
al.], editors.
p. cm.
Includes bibliographical references.
ISBN-13: 978-1-4684-6769-7 e-ISBN-13: 978-1-4684-6767-3
DOl: 10.1007/978-1-4684-6767-3
l. Epilepsy-Congresses. I. Avoli, Massimo.
RC372.G44 1990 89-18352
616.8'53-dc20
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9 8 7 6 5 4 3 2 1
Preface
In recent years there has been intense interest in the basic mechanisms of
epilepsy. Many symposia and monographs have been devoted to this topic. These
reviews, however, have focused almost exclusively on studies performed in
models of partial (or focal) epilepsy. It was natural that scientists interested in the
fundamental mechanism of epileptogenesis at the cellular level were attracted to
work on models in which the epileptogenic dysfunction could be confined to
ever-smaller populations of neurons. Many of the most illuminating studies done
in this field in the recent past have been carried out in vitro on brain slices or on
dissociated neuronal cultures. Much valuable insight into the mechanisms of
epileptogenesis has been obtained in this manner.
One cannot, however, automatically assume that mechanisms elucidated in
such exquisitely "focal" models are applicable to forms of epilepsy in which
seizures from their very start involve the entire brain. One of the most difficult
questions that arises in this context is how epileptogenic dysfunction, which can
be understood in terms of mechanisms involving a few contiguous cells, can lead
to what appears to be a simultaneous onset of seizure discharge in virtually all
areas of the brain. Most of the workers who have made excellent contributions to
the understanding of the cellular mechanisms involved in epileptogenesis have
paid virtually no attention to this important problem.
We, the editors of this volume, therefore felt that the time had come to review
what is known about the basic mechanisms involved in generalized epilepsy,
including an assessment of the relevance of basic cellular mechanisms studied in
vitro or in focal models. We therefore decided to organize a symposium devoted
to this subject. It was held at the Montreal Neurological Institute from the 11th to
the 13th of June 1988 under the title "Generalized Epilepsy: Cellular, Molecular,
and Pharmacological Approaches." It appeared to us timely to organize such a
symposium, since to the best of our knowledge there has been no such symposium
devoted to the fundamental mechanisms involved in generalized epilepsy since
the one held in Marseilles in 1966. The Montreal Symposium of 1988 was a
stimulating experience for all those who attended it. The presentations not only
highlighted what is known concerning fundamental mechanisms of generalized
seizures but also made us acutely aware of how many gaps there are in our
knowledge. Many of the chapters in this volume are based on papers presented at
the 1988 Montreal symposium. It is hoped that they may stimulate many
researchers in the field of epileptology and goad them into approaching many of
the still unsolved problems of the mechanisms of generalized epilepsy.
v
vi Preface
The symposium from which this book originated was made possible thanks to
the generous support of Abbott Laboratories and Fidia Research Laboratories.
We wish also to acknowledge the financial contributions of Ciba-Geigy, Fonds
de la Recherche en Sante du Quebec, La Brasserie Labatt Limitee, McGill
University, the Medical Research Council of Canada, Merck Frosst, the Montreal
Neurological Institute, Park Davis, The Royal Trust, the Savoy Foundation (in
memoriam C. Bessette), and the Upjohn Company of Canada.
The Editors
Contents
Preface. . . . . . . . . . . . . . . . . . . .. ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl
Historical Introduction
H.H. Jasper ................................................ .
I Clinical Background
2 The Syndromes of Generalized Epilepsy
F.E. Dreifuss. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3 Unanswered Clinical Questions in Generalized Epilepsy
F. Andermann. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4 The Relationship Between Sleep Spindles and Spike-and-Wave
Bursts in Human Epilepsy
P. Kellaway, J.D. Frost, Jr., and J.W. Crawley................. 36
II Fundamental Cellular and Neurotransmitter Mechanisms
5 Membrane Properties of Cat Betz Cells Studied In Vitro
W.E. Crill, P.e. Schwindt, and W.J. Spain. . . . . . . . . . . . . . . . . . . . . 51
6 Changes in Extracellular Ions Associated with Epileptiform
Discharges
R. Pumain and U. Heinemann. . . . . . . ... . . . . . . . . . . . . . . .... . . . . . 61
7 Role of Neurotransmitters in the Genesis of Epileptiform
Discharges
K. Krnjevic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
8 Excitant Amino Acids in Epilepsy
e.L. Faingold and B.S. Meldrum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
9 Possible Epileptogenic Consequences of Misused GABAergic
Relationships
J. Champagnat, e. Silva-Barrat, S. Brailowsky, and Ch. Menini. . . 118
vii
viii Contents
10 Anticonvulsant Effects of Intracortical Chronic Infusion of GAB A
in Generalized Epilepsy
S. Brailowsky, C. Silva-Barrat, Ch. Menini, D. Riche, and
R. Naquet. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
11 In Vitro Electrophysiology of a Genetic Model of Generalized
Epilepsy
G. Kostopoulos and C. Psarropoulou. . . . . . . . ... . . . ..... .. . . . . . . 137
III Thalamic and Cortical Mechanisms in Absence Attacks
12 Spindling, Incremental Thalamocortical Responses, and Spike
Wave Epilepsy
M. Steriade .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
13 Physiology of Thalamic Relay Neurons: Properties of Calcium
Currents Involved in Burst-Firing
J.R. Huguenard, D.A. Coulter, and D.A. Prince. . . ..... . . . . . . . . . 181
14 Thalamo-Cortical Relationships in Generalized Epilepsy with
Bilaterally Synchronous Spike-and-Wave Discharge
P. Gloor, M. Avoli, and G. Kostopoulos...... . . .... . . . . . ... ... . 190
15 Focal and Generalized Epileptiform Activity in the Cortex: In
Search of Differences in Synaptic Mechanisms, Ionic Movements,
and Long-Lasting Changes in Neuronal Excitability
M. Avoli, P. Gloor, and G. Kostopoulos ...... ,. . . . .... . . . . . . . .. 213
16 Pharmacology of the Inhibitory Systems in Primary Generalized
Epilepsy of "Petit Mal" Type
R.G. Fariello. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
17 Spontaneous Spike-and-Wave Discharges in Wistar Rats: A Model
of Genetic Generalized Conconvulsive Epilepsy
M. Vergnes, Ch. Marescaux, A. Depaulis, G. Micheletti, and
J.-M. Warter . . . .. . . . . . ... . . . . ....... . . . . . . .... . . ... .. ... .. .. 238
18 Behavioral and Electrophysiological Studies of Absence Epilepsy
A.F. Mirsky and C.C. Duncan. . . . . . ....... . . . . ... . . . . . . . . . . .. 254
IV Photosensitivity
19 Focal Discharges in Photosensitive Generalized Epilepsy
R. Naquet and A. Valin ...................................... 273
20 Photosensitive Epilepsy of the Baboon: A Generalized Epilepsy
with a Motor Cortical Origin
C. Silva-Barrat and Ch. Menini ............................... , 286
21 Role of Dopamine in Generalized Photosensitive Epilepsy:
Electroencephalographic and Biochemical Aspects
L.F. Quesney and T.A. Reader...... ... . .. . . . .... . . . .. .. . . . . .. 298
Contents ix
22 Inferences Regarding the Visual Precipitation of Seizures, Eye
Strain, and Headaches
A.J. Wilkins, C.D. Binnie, C.E. Darby and
D. Kasteleijn-Nolst Trenite ................................... 314
V Generalized Convulsive Seizures
23 Animal Models of Generalized Convulsive Seizures: Some
Neuroanatomical Differentiation of Seizure Types
K. Gale..................................................... 329
24 Mechanisms Underlying Generalized Tonic-Clonic Seizures in the
Rat: Functional Significance of Calcium Ions
E.-J. Speckmann, J. Walden, D. Bingmann, A. Lehmenkiihler, and
U. Altrup . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
25 Substantia Nigra-Mediated Control of Generalized Seizures
S.L. Moshe and E.F. Sperber. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
26 Mesencephalic Structures and Tonic-Clonic Generalized Seizures
F. Velasco and M. Velasco ........................ . . . . . . . . . . . 368
VI Metabolic and Neurochemical Studies
27 Metabolic Studies of Generalized Epilepsy
J. Engel, Jr., R.F. Ochs, and P. Gloor. . . . . . . . . . . . . . . . . . . .. . . . . . 387
28 PET Studies of Generalized Epilepsy Induced by Convulsant
Drugs Acting at the GABA-Benzodiazepine Receptor Complex
M. Maziere, E. Brouillet, M. Kunimoto, M. Khalili-Varasteh,
Ph. Hantraye, R.H. Dodd, D. Fournier, B. Guibert, and
C. Chavoix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 397
29 Postictal Compensatory Changes in Cortical Alpha-l Receptors
and Adrenergic-Mediated Phosphoinositol Metabolism Following
Repeated Electroconvulsive Seizures in Rats
A.L. Sherwin, S. Dyve, F. Dubeau, W. Regenold, and
D. Guevremont. . . . . . . . . . . . . .. . ... . . . . . . . . . . . . . . . . . . . . . . . . . .. 407
VII Pharmacological Ag~nts and Generalized Seizures
30 Cellular Actions of Petit Mal Anticonvulsants: Implication of
Thalamic Low-Threshold Calcium Current in Generation of Spike
Wave Discharge
D.A. Coulter, J.R. Huguenard, and D.A. Prince. . . . . . . . . . . . . . . .. 425
31 Mechanisms of Anticonvulsant Action of Valproate: An Overview
and Perspective
R. Capek and B. Esplin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 436
x Contents
32 Sedative Drug Withdrawal Seizures: Cellular Electrophysiological
Mechanisms
P.L. Carlen, M.F. Davies, 1. Rougier-Naquet, J.N. Reynolds, and
1. Spigelman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 460
Index... .. .. . ... .... . .... .... ..... . ............................... 471
