Table Of ContentUCLA FORUM IN MEDICAL SCIENCES
EDITORIAL BOARD
MARY A. B. BRAZIER, Editor-in-Chief
Carmine D. Clémente Carl M. Pearson
Louise M. Darling Sidney Roberts
George Eisenman Charles H. Sawyer
John L. Fahey Emil L. Smith
Victor E. Hall Reidar F. Sognnaes
William P. Longmire W. Eugene Stern
UCLA FORUM IN MEDICAL SCIENCES
NUMBER 17
EPILEPSY
ITS PHENOMENA IN MAN
Edited by
MART A. B. BRAZIER
BRAIN RESEARCH INSTITUTE
UNIVERSITY OF CALIFORNIA
LOS ANGELES, CALIFORNIA
A C A D E M IC P R E SS New York and London 1973
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1973, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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United Kingdom Edition published by
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Library of Congress Cataloging in Publication Data
Main entry under title:
Epilepsy: its phenomena in man
(UCLA forum in medical sciences, v. 17)
Six of the 16 papers were presented at the
Symposium on Electrophysiological Processes in the
Epilepsies, held during the alumni reunion of the
Brain Research Institute, University of California,
Los Angeles, in July 1972.
Includes bibliographies.
1. Epilepsy—Congresses. I. Brazier, Mary
Agnes Burniston, Date ed. II. Symposium on
Electrophysiological Processes in the Epilepsies,
University of California, Los Angeles, 1972.
III. California. University. University at
Los Angeles. Brain Research Institute. IV. Series.
RC373.E64 616.8'53 73-2060
ISBN 0-12-128650-9
PRINTED IN THE UNITED STATES OF AMERICA
CONTRIBUTORS TO THIS VOLUME
C. AjΜΟΝΈ MARSAN, National Institute of Neurological Diseases and
Stroke, Building 10/4N262, National Institutes of Health, Bethesda,
Maryland 20014
J. BANCAUD, Hôpital Sainte Anne, 1 Rue Cabanis, Paris 14, France
MARY A. B. BRAZIER, Brain Research Institute, University of California,
Los Angeles, California 90024
P. BUSER, Laboratoire de Neurophysiologie, Université Paris VI, 4 Place
Jussieu, 75230 CEDEX, 05, Paris, France
PAUL H. CRANDALL, Brain Research Institute, University of California, Los
Angeles, California 90024
Ο. D. CREUTZFELDT, Max-Planck-Institut für biophysikalische Chemie,
Karl-Friedrich-Bonhoeffer- Institut, D-3400 Göttingen-Nikolausberg,
Postfach 968, Germany
DAVID D. DALY, Department of Neurology, University of Texas, South-
western Medical School, 5323 Harry Hines Blvd., Dallas, Texas 75235
L. GOLDHAMMER, Department of Neurology, Georgetown University School
of Medicine, Washington, D.C., 20007
W. JANN BROWN, Department of Pathology, University of California School
of Medicine, Los Angeles, California 90024
ROBERT NAQUET,* Department de Neurophysiologie Appliquée, Institut de
Neurophysiologie et de Psychophysiologie, 13 Marseille 9, France
J. KIFFIN PENRY, National Institute of Neurological Diseases and Stroke,
Building 36/5D10, National Institutes of Health, Bethesda, Maryland
20014
H. PETSCHE, Institut für Hirnforschung, Osterreichische Akademie der
Wissenschaften Schwarzspanierstr. 17, A 1090 Wien, Austria
DANIEL A. POLLEN, Massachusetts General Hospital, Boston, Massachusetts
02114
P. RAPPELSBERGER, Institut für Hirnforschung, Osterreichische Akademie
der Wissenschaften, Schwarzspanierstr. 17, A 1090 Wien, Austria
GIAN FRANCO Rossi, Istituto di Neurochirurgia, Universitâ Cattolica del
Sacro Cuore, Via della Pineta Sacchetti, 00168 Rome, Italy
MADGE Ε. and ARNOLD Β. SCHEIBEL, Department of Anatomy, University of
California School of Medicine, Los Angeles, California 90024
* Present address: Laboratoire de Physiologie Nerveuse, Centre National de la Recherche
Scientifique, Groupe de Laboratoires de Gif, 91190 Gif-sur-Yvette, France.
χ C O N T R I B U T O RS TO THIS V O L U ME
JANICE R. STEVENS, University of Oregon School of Medicine, 3181 S. W.
Sam Jackson Blvd., Portland, Oregon 97201
J. TALAIRACH, Hôpital Sainte Anne, 1 Rue Cabanis, Paris 14, France
RICHARD D. WALTER, Department of Neurology, University of California
School of Medicine, Los Angeles, California 90024
PREFACE
In July 1972, the Brain Research Institute of the University of California,
Los Angeles, held a reunion of its alumni. The scientific program of this
reunion centered on eight symposia concerned with the various fields of
neuroscience relevant to the work of the Institute. Among these was a
symposium on Electrophysiological Processes in the Epilepsies. Of the six
distinguished speakers in that symposium, five came from overseas, thus
bringing an international overview to the problem of seizures, extending
from basic neurophysiological mechanisms to the modern approaches to
diagnosis and therapy.
In this volume, the papers given by the six alumni at the reunion have
been joined by ten further manuscripts, contributed on invitation by
workers in biomedical fields critical for the understanding of epileptogenesis.
It has thus been possible to extend the frontiers of the subject to the wider
field of the phenomena of epilepsy in man.
Mary A. B. Brazier
The first published photograph of the EEG changes in experimental epilepsy induced
by electrical stimulation of the cortex in a dog. Top record: Line III = Spontaneous
activity of the dog's cortex. Line IV = respiration. Line I = time marker. Middle
and bottom records: Induction of an experimental seizure, the upper one showing
stimulation and the lower one the resultant seizure activity. Line I = time marker
(A to Β = 1 second). Line II = stimulus signal. Line III = electrocorticogram. Line
IV = respiration. All records read from right to left.
The frequency response of these nineteenth century instruments made them incapable
of recording spikes; instead they recorded the disturbance caused by the seizure.
(From Cybulski, N., and Jelenska-Macieszyna, Prady cynnosciowe kory mozgowej.
Bull. Int. Acad. Sei. Cracovie, Ser. B, 1914:776-781.)
HISTORICAL INTRODUCTION: THE ROLE OF ELECTRICITY
IN THE EXPLORATION AND ELUCIDATION
OF THE EPILEPTIC SEIZURE
MARY A. B. BRAZIER
Brain Research Institute, University of California, Los Angeles, California
The role of electricity in the exploration of the epileptic nervous system
emerged from two major and, at first, independent lines of observation
and experiment. The fact that applied electricity could cause convulsions
was at first accepted as being the same as any other traumatic insult to
the brain—mechanical, thermal, or chemical. Such a view stemmed natu-
rally from the influential Haller's (31, 39) concept of irritability based on
experiments in which he pricked the brain and applied irritating fluids.
These experiments led him to the erroneous conclusion that gray matter
is insensitive to stimulation whereas white matter is the seat of sensation
and the source of movement.
The realization that the applied electricity interacted with that of the
cortical neurons had to wait for the discovery that the neurons were them-
selves the source of intrinsic currents.
In the earliest accounts, the electric stimulus is described as being ap-
plied within the brain rather than at its surface. In the mid-eighteenth
century the Abbé Fontana ( 25 ) and Caldani ( 13, 14 ) ( Galvani's predeces-
sor in the chair of anatomy at Bologna ) had convulsed their frogs by stimu-
lation with frictional electricity. All these studies were carried out before
evidence for the existence of "animal electricity" had made its contro-
versial entry into physiology through the experiments of Galvani (27) and
the attack on them by Volta (38). However, these rather indiscriminately
applied stimulations of the brain continued and were soon applied to higher
animals. Rolando (37), working in Sassari, extended the studies to pigs,
goats, sheep, dogs, and also birds, reporting his findings in a text printed
and illustrated by himself. But in the nineteenth century the goal was
refined from the production of the disorganized, generalized muscle move-
ments of the convulsion to an attempt to find brain areas that, on stimula-
tion, provoked specific localized muscle contractions. This search con-
tinued in spite of the discouraging dicta of two very influential men:
Magendie ( 36 ) who, because his own experiments had * failed, pro-
nounced the cortex inexcitable, and Flourens (24) who thought that sue-
2 MARY Α. Β. B R A Z I ER
cess in the search for localization was more likely to follow from ablation
experiments.
Yet why should these early workers have expected to find areas on the
cortical surface that on stimulation evoked specific muscle or even limb
movement? The neuron had not yet been identified as the unit of the ner-
vous system and the pyramidal fibers were not yet known to be processes
of cortical cells. Their hypotheses were extrapolations from the results of
those who used ablation techniques, from the fantasies of phrenology in
the first half of the nineteenth century, and from the startling claims of
Bouillaud (8), of Aubertin ( 1 ) and of Broca ( 10) that there was a localized
speech center in the human brain.
But meanwhile the search for localization of motor function persevered.
Cabanis (12), the celebrated Idéologue in the Age of Enlightenment, had
provoked convulsive movements in muscle groups that seemed to vary with
the region of the brain he stimulated. But the crucial experiments were
to come in 1870. As everyone knows, the pioneers were the two young
doctors in Berlin, Fritsch and Hitzig (26), who demonstrated that certain
regions of the cortex were excitable by electricity, as evidenced by elicited
movements. Although Ferrier (20, 21) followed up and expanded their
original findings in his classic book, "The Functions of the Brain" (22),
acceptance of these concepts even then was far from general. An attack
came from George Henry Lewes, whose name has almost faded from scien-
tific memory; he was then a respected authority, and his "Physiology of
Common Life" (31) was the best account of the nervous system available
at the time.
Lewes, better remembered for his notorious liaison with George Eliot,
wrote a pungent attack, both on Ferrier and on the original Fritsch-Hitzig
concepts of functional localization (35). He deplored "the increasingly
popular but thoroughly unphysiological conception of localisation." "We
should marvel," he wrote, "to witness so many eminent investigators cheer-
ing each other on in the wild-goose chase of a function localised in a cere-
bral convolution." Just because stimulation of a cortical area evoked a
movement that did not, in Lewes's opinion, prove it to be a motor center.
"We do not," he wrote, "consider the centre of laughter to be located
in the sole of the foot, because tickling the sole causes laughter." Lewes
employed italics to emphasize his statement "I do not think that Hitzig
and Ferrier have proved the grey substance to he excitable!'
He held that movements did not necessarily stem from involvement of
cortical gray matter for the electricity could well be conducted through
it without excitation until it reached the basal ganglia. This competing
theory, suggested long before by Couty ( 18 ), was brought into prominence
by Burdon Sanderson (11), the Jodrell Professor of Physiology at the Uni-
versity of London and a member of the Royal Society. He reached this
conclusion from experiments in which he undercut the cortex with a sharp
H I S T O R I C AL I N T R O D U C T I ON 3
knife and then produced, by stimulation below the cortical layer, the same
movements as he had evoked from the surface. This led him to direct stimu-
lation of the basal ganglia and his method of approach is an interesting
forerunner of modern stereotaxic methods. He wrote ( 11 ) :
In a brain hardened in alcohol, a needle plunged vertically, i.e. at right angles
to the surface, from the active spot for retraction of the opposite ear, reaches
the posterior part of the corpus striatum at a depth of from 10-12 millims.
If a horizontal incision is made in the living brain, at this depth, and is met
by two others, of which one is directed antero-posteriorly and the other trans-
versely, and the part comprised within the incisions removed, a surface of
brain is exposed in the deepest part of the wound which corresponds to the
outer and upper part of the corpus striatum. If now the electrodes are applied
to this surface, the movements . . . are produced in the same way as before,
but more distinctly, the active spots are quite strictly localised . . .
If the cortex were not the originator of movements, then the alternative
proposal was that they were secondary to sensation, and the direct effect
of the stimulation was sensory rather than motor. The sensation was viewed
as reaching the brain, where an "idea" then intervened and excited the
basal ganglia to activate their motor function. This interpolation of an idea
between sensation and motor output had in an earlier century differentiated
the views of Glisson (29) from those of Haller (39) who omitted "psychic"
perception between the irritation and the contraction. This hypothesis ap-
pealed to the Victorian mind because it provided a loophole for "free will"
and a "voluntary movement." Stimulation evoked a sensation the result
of which was that one willed to move a limb. This was much more ac-
ceptable than the thought of an automatic movement resulting from excita-
tion of certain spots in the brain.
But the cortex was to come into prominence again through a major dis-
covery—one which was eventually to be extremely important for the inves-
tigation of epilepsy (9). In the same year (1874) that Burdon Sanderson
published his claims for the basal ganglia, Richard Caton, a young lecturer
in physiology at the Royal Infirmary in Liverpool, applied to the British
Medical Association for a grant to search for electrical signs in the brain
of sensory impulses entering it from peripheral stimulation. He was given
the grant and within a year had found what he was looking for—namely,
a potential change when the animal received a stimulus such as a flash.
But more important, as later years were to reveal, was his observation that
his baseline was never still but always oscillated as long as the animal
was alive. Actually this was the discovery of the electroencephalogram
(EEG), published first in a brief note in the British Medical Journal in
1875 (15) and followed by a longer paper in 1877 (16).
Although demonstrated to the British Medical Association in London
and reported at the Ninth International Medical Congress in Washington
in 1887 (17) the discovery of the EEG went unnoticed by the clinical
