Epilepsy a comprehensive textbook 3 vols (lippincott, 2006) 1

Table Of Contents VOLUME I Intr Table Of Contents VOLUME I Introduction: What Is Epilepsy? SECTION EPIDEMIOLOGY, PATHOLOGY, AND GENETICS OF EPILEPSY Overview: Epidemiology, Pathology, and Genetics Epilepsy: Historical Perspectives Neuropathology EPIDEMIOLOGY Incidence and Prevalence The Natural History and Prognosis of Epilepsy NEUROPATHOLOGY General Neuropathology of Epilepsy Hippocampal Sclerosis GENETICS Genetic Epidemiology EEG Traits SECTION II THE NEUROBIOLOGY OF EPILEPSY Overview: The Neurobiology of Epilepsy MECHANISMS OF NORMAL NEURONAL EXCITABILITY Control of Neuronal Excitability Excitatory Synaptic Transmission Neocortical Anatomy and Physiology Thalamocortical Anatomy and Physiology MECHANISMS OF EPILEPTOGENESIS AND EPILEPTOGENICITY Genetic Models of Epilepsy file:///C|/Documents%20and%20Settings/papa/Escritorio/engel/index.htm (1 of 5) [20/06/2008 23:36:10] Table Of Contents VOLUME I Intr Seizure Mechanisms and Vulnerability in the Developing Brain SECTION III PHENOMENOLOGY Overview: Phenomenology EPILEPTIC SEIZURES Simple Motor Seizures Limbic Seizures Epileptic Spasms STATUS EPILEPTICUS Generalized Convulsive Status Epilepticus Absence Status Epilepticus Myoclonic Status Epilepticus EPILEPTIC DISORDERS Classification of the Epilepsies SECTION IV DIAGNOSTIC EVALUATION Overview: Diagnostic Evaluation ROUTINE INVESTIGATIONS History and Physical Examination EEG Physiologic Basis of the Electroencephalogram and Local Field Potentials Ictal Electroencephalogram Polygraphic Recordings NEUROIMAGING Positron Emission Tomography file:///C|/Documents%20and%20Settings/papa/Escritorio/engel/index.htm (2 of 5) [20/06/2008 23:36:10] Table Of Contents VOLUME I Intr Magnetic Resonance Spectroscopy Computational Anatomy NEW DIRECTIONS Seizure Prediction Microdialysis Transcranial Magnetic Stimulation Cellular Imaging of Epilepsy NEUROPSYCHOLOGICAL EVALUATION LONG-TERM MONITORING VOLUME II SECTION V GENERAL TREATMENT CONSIDERATIONS Overview: General Approaches to Treatment GENERAL CONSIDERATIONS PRINCIPLES OF DRUG TREATMENT STRATEGIES FOR PHARMACOTHERAPY SPECIAL THERAPEUTIC CONSIDERATIONS ALTERNATIVE APPROACHES SECTION VI ANTIEPILEPTIC DRUGS ANTIEPILEPTIC DRUG DEVELOPMENT ANTIEPILEPTIC DRUGS SECTION VII SURGICAL THERAPY CANDIDATE SELECTION INVASIVE MONITORING TECHNIQUES FUNCTIONAL MAPPING TECHNIQUES file:///C|/Documents%20and%20Settings/papa/Escritorio/engel/index.htm (3 of 5) [20/06/2008 23:36:10] Table Of Contents VOLUME I Intr THERAPEUTIC SURGICAL PROCEDURES POSTOPERATIVE FOLLOW-UP SECTION VIII CLINICAL BIOLOGY OF EPILEPSY>/b> BIORHYTHMS AND THE AUTONOMIC NERVOUS SYSTEM COMORBIDITY NEUROENDOCRINOLOGY VOLUME III SECTION IX PSYCHIATRIC AND SOCIAL ISSUES PSYCHIATRIC ISSUES SOCIAL ISSUES SECTION X EPILEPSY SYNDROMES NEONATAL SYNDROMES SYNDROMES OF INFANCY AND EARLY CHILDHOOD SYNDROMES OF LATER CHILDHOOD AND ADOLESCENCE NON AGE-RELATED AND SPECIAL SYNDROMES DISEASES ASSOCIATED WITH EPILEPSY SECTION XI DISORDERS THAT CAN BE CONFUSED WITH EPILEPSY SYSTEMIC DISTURBANCES NEUROLOGICAL DISTURBANCES PSYCHIATRIC DISTURBANCES SECTION XII DELIVERY OF HEALTH CARE AND SOCIOECONOMIC ISSUES ORGANIZATION OF HEALTH CARE IN DIFFERENT COUNTRIES SPECIALIZED CENTERS FOR EPILEPSY file:///C|/Documents%20and%20Settings/papa/Escritorio/engel/index.htm (4 of 5) [20/06/2008 23:36:10] Table Of Contents VOLUME I Intr COST AND ALLOCATION OF RESOURCES file:///C|/Documents%20and%20Settings/papa/Escritorio/engel/index.htm (5 of 5) [20/06/2008 23:36:10] de http://ovidsp.tx.ovid.com/spb/ovidweb.cgi?targetFrame=1&S=FDNJ Back Save | Print Preview | Email | Email Jumpstart 2008 Lippincott Williams & Wilkins Philadelphia 530 Walnut Street, Philadelphia, PA 19106 USA, LWW.com 978-0-7817-5777-5 0-7817-5777-0 © 2008 by Lippincott Williams & Wilkins, A Wolters Kluwer Business 530 Walnut Street, Philadelphia, PA 19106 USA, LWW.com All rights reserved This book is protected by copyright No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright Printed in the USA Acquisitions Editor: Frances DeStefano Managing Editor: Leanne McMillan Developmental Editor: Dovetail Content Solutions, Keith Donnellan Production Editor: Bridgett Dougherty Manufacturing Manager: Benjamin Rivera Design Coordinator: Stephen Druding Compositor: Aptara, Inc Library of Congress Cataloging-in-Publication Data Epilepsy: a comprehensive textbook / editors, Jerome Engel Jr., Timothy A Pedley; associate editors, Jean Aicardi … [et al.] — 2nd ed p.; cm Includes bibliographical references and index ISBN-13: 978-0-7817-5777-5 (alk paper) ISBN-10: 0-7817-5777-0 (alk paper) Epilepsy I Engel, Jerome II Pedley, Timothy A [DNLM: Epilepsy WL 385 E6025 2008] RC372.E657 2008 616.8′53—dc22 2007032096 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, 28/05/2008 22:48 de http://ovidsp.tx.ovid.com/spb/ovidweb.cgi?targetFrame=1&S=FDNJ with respect to the currency, completeness, or accuracy of the contents of the publication Application of this information in a particular situation remains the professional responsibility of the practitioner The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of the health care provider to ascertain the FDA status of each drug or device planned for use in their clinical practice To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 International customers should call (301) 223-2300 Visit Lippincott Williams & Wilkins on the Internet: at LWW.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to pm, EST 10 28/05/2008 22:48 Ovid: Epilepsy: A Comprehensive Textbook de 41 http://ovidsp.tx.ovid.com/spb/ovidweb.cgi Editors: Engel, Jerome; Pedley, Timothy A Title: Epilepsy: A Comprehensive Textbook, 2nd Edition Copyright ©2008 Lippincott Williams & Wilkins > Front of Book > Editors Editors Jerome Engel Jr MD, PhD Jonathan Sinay Distinguished Professor of Neurology Neurobiology, and Psychiatry and Behavioral Sciences; Director of the UCLA Seizure Disorder Center, David Geffen School of Medicine at UCLA, Los Angeles, California Timothy A Pedley MD Henry and Lucy Moses Professor of Neurology and Chairman Department of Neurology, College of Physicians and Surgeons of Columbia University; Neurologist-in-Chief, The Neurological Institute of New York, The New York-Presbyterian Hospital at Columbia University Medical Center, New York, New York Associate Editors Jean Aicardi MD, FRCP Professor of Neurology University Hospital Robert Debre, Epilepsy Unit, Child Neurology and Metabolic Disease, Paris, France Marc A Dichter MD, PhD Professor of Neurology and Pharmacology University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Emilio Perucca MD, PhD, FRCP Professor Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia; Director, Laboratories for Diagnostics and Applied Biological Research, Institute of Neurology IRCCS C Mondino Foundation, Pavia, Italy Solomon L Moshé MD Vice Chair and Professor of Neurology Neuroscience and Pediatrics, Albert Einstein College of Medicine of Yeshiva University; Director of Child Neurology and Clinical Neurophysiology, Department of Neurology and Pediatric Neurology, Montefiore Medical Center, Bronx, New York Michael R Trimble MD Professor of Behavioral Neurology Institute of Neurology, London, United Kingdom Contributing Authors Eric Abadie Director 28/05/2008 22:53 Ovid: Epilepsy: A Comprehensive Textbook de 41 http://ovidsp.tx.ovid.com/spb/ovidweb.cgi Therapeutic Evaluation, Agence Francaise de Secunte Sanitaire des Products de Sante, Paris, France Carlos Acevedo MD, SCH Professor of Pediatric Neurology Universidad de los Andes, Department of Pediatric Neurology, Clinica Alemana de Santiago, Santiago, Chile Keryma A Acevedo MD Assistant Professor Department of Pediatrics, Northern Campus, University of Chile; Staff of Pediatric Neurology, Emergency Department, Clinica Alemana de Santiago, Santiago, Chile Bola Adamolekun MD, FWACP Director of Epilepsy Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee Jean Aicardi MD, FRCP Department, University Hospital Robert Debre, Epilepsy Unit, Children Neurology and Metabolic Disease, Paris, France Fiorenzo Albani MD Laboratory of Clinical Neuropharmacology, Department of Neurological Sciences, University of Bologna, Bologna, Italy Albert P Aldenkamp PhD Professor of Epileptology Department of Neurology, University of Maastricht, University Hospital Maastricht; Head Department of Behavioural Sciences, Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands Brian K Alldredge Pharm.D Professor of Clinical Pharmacy and Neurology University of California, San Francisco, California Abdul Aziz Al Semari MD Director Comprehensive Epilepsy Program; Chairman, Epilepsy Support and Information Center and Head, Section of Neurology, Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Kingdom of Saudi Arabia Michael J Aminoff MD, DSc, FRCP Professor and Executive Vice Chair of Neurology University of California School of Medicine; Attending Physician, Department of Neurology, University of Calfornia Medical Center, San Francisco, California Eva Andermann MD, PhD Professor of Neurology and Neurosurgery Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada 28/05/2008 22:53 Ovid: Epilepsy: A Comprehensive Textbook 16 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt P.22 40,41,42 reports of aphasia from lesions in the posterior-inferior left frontal By 1870, after considering Broca's convolution, Jackson observed that temporary dysphasia occasionally coexisted with Todd paralysis after focal motor seizures involving the right face, and the association of focal motor seizures sometimes with syphilitic nodules in the meninges over the contralateral middle cerebral artery Jackson142 concluded that focal motor seizures involving the face or hand probably originated in the lower part of the perirolandic cortex of the opposite cerebral hemisphere This radical departure from the conventional interpretation of the site of epileptogenesis received independent support within a comparatively short period from Fritsch and Hitzig's experimental studies of cortical stimulation and ablation in animals.98 This work provided convincing evidence of localized representation of motor function within the cerebral cortex During the next few years Jackson's concept of epilepsy became increasingly wide ranging: “Epilepsy is not one particular grouping of symptoms occurring occasionally; it is a name for any sort of nervous symptom or group of symptoms occurring occasionally from local dischargꀦ A paroxysm of ‘subjective’ sensation of smell is an epilepsy as much as is a paroxysm of convulsion; each is a result of sudden local discharge of grey matter.†Jackson's idea that all convulsions and epileptic manifestations were symptoms was at first criticized on the grounds that he had not studied “epilepsy proper,†but merely one variety of epileptiform seizure His reaction to this criticism consisted of convoluted and rather repetitive writing, in which he continued to draw a distinction between focal motor seizures and “epilepsy proper†to make his ideas more acceptable to his peers, in spite of his private belief that they were manifestations of epilepsy and even occasionally saying so In the 1870s experimental physiologists, such as Ferrier,90,91,92 began to map out aspects of localization of function in the animal cerebral cortex At the same time Jackson started to pay attention to the minor, often paroxysmal, expressions of human epilepsy He used the knowledge of the site of pathology in conjunction with the experimental animal findings to locate sites for the representation of various functions within the human cerebral cortex He accumulated data suggesting that the foot was represented in the upper part of the perirolandic cortex,145 and that the site responsible for auditory hallucinations and the so-called dreamy state or “intellectual aura†was in the anterior part of the temporal lobe.146,147 Jackson related visual hallucinations to the posterior half of the cerebral hemisphere without being able to more precisely localize the site of their origin He deduced that consciousness depended on intact function of an extensive part of the prefrontal cortex of at least one hemisphere.143 He attempted to explain the cortical origin of epileptic auras using these localizations and the belief that an epileptic discharge arose from a sudden release (at times he used the word “explosionâ€) of local brain energy If the localized discharge achieved sufficient intensity and extent of spread, the aura would progress to unconsciousness and even convulsing Extensive involvement of the prefrontal cortex by the discharge caused loss of consciousness, while involvement P.23 of the cortical motor areas produced contralateral convulsing Jackson had originally thought144 that unilateral motor cortex discharges might finally activate the uncrossed pyramidal pathway, and thus convert contralateral convulsing into bilateral convulsing Later, following Horsley's experiments,140 Jackson accepted the idea that the discharge must cross the corpus callosum and other brain commissures for bilateral convulsive movements to occur Thus, Jackson finally conceived, for the first time in the history of medicine, a single mechanism capable of explaining the full spectrum of epileptic phenomena: The aura, isolated or subsequent unconsciousness, contralateral and bilateral convulsive behavior His concept is the basis of the modern understanding of epileptogenesis Jackson's complete view was in place by 1890, after some 30 years of sustained intellectual endeavor His ideas did not include primary generalized epilepsy, but in his time, before electroencephalography (EEG) became available, there was no way of knowing that such an entity existed Jackson's writing is often difficult to follow He is often repetitive, using different wordings in different places for the same idea, leaving the reader uncertain if some subtle new insight was intended It is sometimes further complicated by consequences of Jackson's stated intention to abandon his comprehensive early vision of epilepsy and restrict the word to its then contemporary conventional meaning Thus, there is some justification for the view that Jackson's thought is more easily followed by reading his younger colleague 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 17 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt William Gowers William Gowers (1845–1915) Gowers was probably the most important of Jackson's colleagues In his monograph Epilepsy and Other Chronic Convulsive Disorders,121 he discussed epileptogenesis He used a reductionist approach weighing carefully clinicopathologic and experimental data to conclude the following: “The conclusion, then, is that all the phenomena of the fits of idiopathic epilepsy may be explained by a discharge of gray matter; that the hypothesis of vascular spasm is as unneeded as it is unproved; that there are no facts to warrant seeking the seat of the disease elsewhere than in the gray matter in which the discharge commences; that this is in most cases within the cerebral hemispheres, probably often in the cerebral cortex, although in some instances lower down even in the medulla oblongata; that epilepsy is thus a disease of the gray matter, and has not any uniform seat.†Unlike Jackson, who concentrated in one type, Gowers approached epilepsy as a whole His interest actually included other disorders including hysterical attacks, which he tried to distinguish from real epileptic fits In epilepsy the attacks tended to occur randomly and the limb movements did not resemble the pattern of voluntary movements, unlike the “quasi-purposive aspect and coordinated character†of the hysterical attacks He preferred the terms “hysteroid†and “co-ordinated convulsions†to avoid Charcot's confusing term “hystero-epilepsy.†In addressing the nature of Jackson's discharging lesion, Gowers used the term “sudden explosive discharge,†essentially the same words that caused Wills to be ridiculed two centuries before He postulated the storage of latent energy in each neuron and a resistance to prevent its appropriate release He also conceived that the frequent breaking of this resistance could produce repeated seizures as well as increase the nutritive capacity of nerve cells, leading to a facilitation of seizures Gower's espousal of Jackson's ideas, his critical consideration of alternative theories, and his concise statement in direct English made Jackson's ideas increasingly acceptable Gowers almost inevitably tended to soften and harmonize Jackson's more extreme views when writing of them To perceive, however, Gowers' book largely as a “translation†of Jackson's thought is to ignore the significance of Gowers' original insights into matters such as the effect of “resistance,†a notion similar to that of present-day inhibition, in explaining epileptic phenomena Therapeutics In addition to the more adequate interpretation of epileptic seizure mechanisms, in the first half of the 19th century an increasing disillusionment with the inadequacy of the available antiepileptic therapies had developed Those who believed seizures arose from cerebral congestion continued to employ venesection and other measures to divert blood from the brain Hall,122 quite independent of his studies on epilepsy, had already indicated the potential hazards of diminishing the blood volume too quickly The ancient method of applying a ligature proximal to the site of the appearance of an aura in a limb, itself a comparatively uncommon event, continued to have some demonstrable efficacy Hall,124 believing that laryngeal spasm contributed to the loss of consciousness during seizures, advocated and employed tracheostomy, but this approach never achieved any widespread use Recommendations for certain remedies continued (e.g., oil of turpentine205 and zinc oxide131) Esquirol87 and Sieveking225 made scathing comments about the vast array of ineffective antiepileptic drugs that had accumulated over the years: “In fact, there is not a substance in the materia medica, there is scarcely a substance in the world, capable of passing through the gullet of man, that has not at one time or other enjoyed a reputation of being an anti-epileptic.â€225 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 18 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt FIGURE Richard Caton (1842–1926), the discoverer of spontaneous electrical activity of the brain (EEG) and evoked potentials (From Brazier MAB A History of Neurophysiology in the 17th and 18th Centuries New York: Raven Press; 1984, with permission.) Into this scene of therapeutic destitute, one evening in 1857, came a totally unheralded event At a meeting of the London Medico-Chirurgical Society following Sieveking's presentation of 52 patients with epilepsy, Sir Charles Locock, the president of the Society, remarked that he had treated 15 women with hysterical (i.e., menstrual) epilepsy with potassium bromide, and had stopped the seizures in all but one Since potassium bromide could cause temporary impotence in males, he thought it might have useful effects in menstruating women His observation was never published, but it was recorded in the reports of the meeting published in the Lancet and the Medical Times and Gazette Radcliffe's208 experience with it, however, in “hysterical†epilepsy was even more encouraging, and he began to use it in all cases of epilepsy with generally good results Gradually the use of potassium bromide became widespread, particularly after Wilks246 rediscovered it He had sought an alternative to potassium iodide in treating syphilis and, in ignorance of Locock's report, tried potassium bromide He soon realized that its efficacy in controlling seizures due to cerebral syphilis was due to specific antiepileptic properties Thus, the first reasonably effective antiepileptic agent came into use By 1881 Gowers, after listing the numerous recommend antiepileptic therapies, wrote of potassium bromide: “And the present generation has witnessed an advance in the treatment of these diseases equaled in perhaps no other branch of therapeutics Thanks to the influence of one drug and its combinations, hundreds 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 19 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt of epileptics have been cured, and thousands are leading useful lives who would otherwise have been incapacitated by the disease.â€121 In 1886 Horsley, a pioneering English neurosurgeon, performed the first operations intended to relieve focal motor epilepsy by removing the probable focus of seizure in the human cerebral cortex after locating its expected site by electrical stimulation He continued this approach for some years,137,138,139 as it seemed to provide at least short-term benefit in seizure control P.24 Spontaneous Electricity from the Animal Brain In the mid-19th century, a renewed interest in the intrinsic electrical activity of muscle and nerve was sparked by Du Bois-Raymond's book Untersuchungen über Thierische Elektricitat (Investigations on Animal Electricity).77 In the second volume, an illustrated description of recording muscle potentials from the surface of the skin of a man established the basis for clinical electromyography Inspired by this book, Caton (Fig 7) at the Royal Infirmary School of Medicine in Liverpool used similar nonpolarizable electrodes and a mirror galvanometer to extend the work on animal nerve and muscle.51 Based on Fritsch and Hitzig's demonstration of motor responses following electrical stimulation of various cortical areas in the dog,98 Caton hypothesized that reversely peripheral stimulation might evoke local electrical responses in the brain In his historic paper,52 Caton was the first to demonstrate evoked cortical sensory responses in animals Of much greater importance was that Caton is the first person to observe the continuous spontaneous electrical activity of the brain He described “the existence of electrical currents…of the grey matter†and noted that “feeble currents of varying direction pass through the multiplier [amplifier] when the electrodes are placed on two points of the external surface, or one electrode on the grey matter, and one the surface of the skull.â€53 Caton's achievements are better appreciated considering the experimental conditions under which he worked, without electric lights, vacuum tubes, or electronic amplifiers, more than 25 years before the invention of the string galvanometer by Einthoven The Thomson mirror galvanometer that Caton used had a high-frequency response of only Hz A stationary “oxyhydrogen lamp†shone on the galvanometer mirror whose tiny movements reflected the light upon “a distant wall with a graduated scale some eight or nine feet in length.†The distance between the mirror and its image on the wall was his amplifier (multiplier) There was no photographic method to capture and hold the fleeting data once it had disappeared from the wall A candle flame was used for photic stimulation More than 50 years, however, would elapse before the first report of spontaneous electrical activity from the human brain was recorded The 20th Century By the end of the 19th century, there had been a marked quickening of the social conscience regarding care for the chronically ill and disabled Indeed, for almost four decades, institutional care for people with refractory epilepsy had been gradually recognized as the duty of society This in turn had generated organizations dedicated to establishing and running institutions thought appropriate for the care of disabled individuals There was also increased interest in these institutions and in the latter half of the 19th century the Hospital for the Epileptic and Paralysed, Queen Square, London, and the Colony-Farm, Bethel, near Bielefeld in Germany, were founded P.25 Yet, it was early recognized that the clinical study of epilepsy in some hospitals and institutions had built-in logistical problems: Even in the National Hospital, Queen Square, an early hospital bylaw explicitly forbade bed occupation by long-term chronic patients, thus litigating against the study of epilepsy.136 Indeed, Muskens,186 who had studied there, complained that the Hospital for the Epileptic and Paralysed had “… a tendency to pay too much attention to paralytic conditions.†The large number of colonies or colony farms for patients with refractory epilepsy provided ample opportunity for clinical studies With regard to the pathophysiologic understanding of the epilepsies, Jackson had elevated the cerebral cortex to play a prime role in the physiology of epilepsy, using the work of Fritsch and Hitzig98 and Ferrier's 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 20 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt ground-breaking findings summarized in The Functions of the Brain.92 While Jackson's hypothesis that “coarse pathology†such as tumors or infarcts was the cause of focal epilepsies, no such pathology could be seen in postmortem studies of many patients with epilepsy Lacking such evidence of focal pathology, other lines of investigation focused on systemic-metabolic factors thought to excite the brain were pursued Rapid advances in laboratory medicine were employed to analyze various relationships between chemical and metabolic parameters in the blood, cerebrospinal fluid, and urine By the turn of the century, an air of cautious optimism pervaded medical thinking on epilepsy as expressed by Robertson 215: “The subject of the pathology of epilepsy occupies at the moment a position of extreme interest… For long it has almost completely baffled every sort of scientific investigation to discover its essential nature But during the past five or six years investigations have been carried out which…have so far advanced our knowledge of the subject that today we stand within measurable distance of one of the greatest triumphs of medical science Already there is good reason to believe that this triumph will not be long delayed.†The modern reader would think that Robertson was referring to Hughlings Jackson's work In fact, his opinion was based on laboratory data that were collected in an attempt to discover putative systemic metabolic causes of seizures Indeed, enlightenment as to the true cortical pathology of seizure generation lay at least half a century and two world wars away, awaiting the development of undreamt of novel technologies The Organization of the Epilepsy Movement Various organizations, both lay and professional, played an important role in improving the management of epileptics Not only were the needs of the sufferers and their families recognized at last, but also professional attention was concentrated on their problems The social burden that had been borne in silence by families either at home or in mental asylums was going to be hopefully relieved by the introduction of “colonies†or “colony farms†that offered a more caring and peaceful alternative In Britain, the Charity Organisations Committee Report The Epileptic and Crippled Child and Adult in 1893, a historical landmark in social awareness, provided a clear picture of the needs of epileptics and the grave lack of available resources at that time to meet these needs Early surveys of similar facilities in other countries were published in the early issues of Epilepsia The establishment of the International League Against Epilepsy (ILAE) in 1909 marked a major initiative worldwide to organize professional interest in epilepsy but also address scientific and social aspects During the inaugural meeting in 1909, in Budapest, under the newly elected president, Prof A Tamburini, ILAE adopted Epilepsia as the League's official periodical and outlined the aims of the organization It continued as a quarterly periodical until 1915, when World War I forced its closure The first volumes are a rich historical source of the status of epileptology and the international activity of the professional epilepsy movement in the first decade of the 20th century The political chaos after World War I, combined with the Great Depression of 1929, delayed any resumption of the ILAE activity until the mid-1930s Coinciding with the second International Neurology Congress in London in 1935, a number of interested physicians met at Lingfield Colony, Surrey, to reactivate the League The ILAE once again undertook an international survey of the services and facilities available in various countries In volume of the second series of Epilepsia, considerable data had been assembled before World War II prevented members from corresponding with its editor Since 1941 the journal has been published in the United States to preserve continuity throughout the war years without interruption The ILAE was also preserved and resumed its active role after the war, constituting the central spindle of the professional world epilepsy movement ever since In 1961, the International Bureau for Epilepsy was established Two Damaging Diversions for Early 20th-century Epileptology Over the centuries, the clinical problems of epilepsy have always attracted wayward theories about its cause and treatment The early years of the 20th century saw the flowering of two such theories, both of which caused considerable difficulties for sufferers and retarded development of the management and the perception of epilepsy both in medical circles and the community The Autointoxication Theory of Epilepsy 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 21 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt The lack of neuropathologic evidence to underpin Jackson's concept of the role of the cortex in epilepsy had led even him to consider other causative factors such as a vascular mechanism.142 For years, the concept of seizure generation by blood-borne chemical agents had been entertained in various forms,79 and the knowledge of the epileptogenic proclivity of disorders like uremia and poisons such as lead helped bolster this concept.233,234 The last decades of the 19th century and the first three decades of the 20th century saw the expenditure of an enormous amount of time and money in the quest for this unknown trigger in patients without obvious “coarse pathology.†Bolten28 and Turner236 give a comprehensive summary of all the avenues hitherto explored Indeed, the amassing of these data inspired the already mentioned Robertson's215 sanguine statement at the century's turn Epilepsy was conceived by some as a metabolic disease, as presented by Munson at the National Association Meeting in 1906 Further, some senior neurologists in England held the concept of a “metabolic dyscrasia†underpinning seizure causation until late into the second decade of the 20th century.64 By the third decade of the 20th century, however, informed opinion was beginning to endow the brain and the brain alone with seizure generation and discharge.135 A byproduct of the autointoxication theory was the idea that the gastrointestinal tract was involved in seizures From the time of Galen, involvement of the stomach in “analeptic seizures†had held a prominent place in concepts of epilepsy Based on Bouchard's writings,30 autointoxication was also reckoned as the basis for epilepsy This concept focused attention on the gut, this time as a site of stasis and bacterial growth or fermentation resulting in toxin production The resultant absorption of bacteria or toxins, or both, was thought to give rise to the chemical triggers for seizure production, and accordingly strategies aimed at prevention of this cycle of events could possibly have a significant role in epilepsy management Bra's work32,33 in identifying bacteria in the blood of epileptic P.26 patients was supported by Reed's 209,210,211 series; despite evidence to the contrary, surgical maneuvers to eliminate putative causes of intestinal stasis and blockage were undertaken on individual patients 159 The Epileptic Constitution and Psychoanalytic Concepts of Epilepsy Refractory epilepsy had long been managed in mental asylums, and physicians working in them such as Esquirol87 had made substantial contributions to epileptology Berrios18 has canvassed the association of epilepsy with insanity and pointed out that this only ceased early in the 20th century Still the long-standing prejudicial opinion of “the epileptic personality,†common in asylum medicine, was prevalent in almost every mental health system of the time Clinical opinion, however, derived from an entirely different avenue served to strengthen the impression of a link between epilepsy and psychiatry Arising from the psychological trauma of World War I, the bizarre episodic events subsumed under the rubric “shell shock†were thought of as closely resembling epilepsy or being frankly epileptic Since the management of shell shock had been undertaken along psychoanalytic lines,215 it was thought appropriate to extend this to epilepsy Rows and Bond in their book Epilepsy, A Functional Illness: It's Treatment217 established significant acceptance of this concept Clark's earlier work at the Craig Colony (1914) had cemented the link of epilepsy with psychiatry His controversial paper “A Personality Study of Epileptic Constitution†referred to psychoanalytic statements by Pilcz and Ferenczi, who “…made the clever suggestion that a fit represented a regression to the infantile period of wish fulfillment.â€61 Clark's subsequent publication of a whole series of papers on this subject culminated in his article “A Psychological Interpretation of Essential Epilepsy.â€62 This alternative psychoanalytic explanation held the potential for grave damage.22 The addition of this psychoanalytic theory of the “epileptic constitution†to the already entrenched perception of the “epileptic personality†in fact constituted a disastrously negative perception of epilepsy by both the medical profession and the public Eventually, mainstream neurology overtook this misguided concept and Clark was subjected to public rejection at the October meeting of the New York Neurologic Society Speaker after speaker commented upon the complete absence of any scientific data to underpin his concept.62 Rejection was forthcoming from the other side of the Atlantic, too Kinnier Wilson, in his chapter “The Epilepsies†in Bumke and Foerster's 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 22 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt Handbuch,254 summed it up concisely: “Dismissing the evidence for visceral, metabolic, humoral and other physical causation, some allege that relief from intolerable pressure of unconscious conflicts is sought in, and accomplished by the epileptic “flight†into a fit; without stopping the enquire whether a ‘flight’ that lands the luckless sufferer in a fireplace or breaks his head open, is as convincing a proof of the validity of the theory as might have been wished.â€254 In addition, Wilson deprecated the term “essential epilepticâ€: “…the argument of the psychoanalytical school assigning him to an oral and erotic character, and egocentric and narcissistic personality can hardly apply, aside from the fact the conceptions are much too general to be of specific value in a matter of paroxysmal aetiology.†In retrospect, the modern reader is left with the question as to how all this could ever occur for, as Wilson implied, it simply defied common sense By the middle of the 20th century the psychoanalytic theory of epilepsy had all but gone from mainstream neurology Unfortunately, like the demonic possessions of the past, it took generations before it disappeared from community perception, and its echoes could be heard in psychiatry until quite late into the 1960s Important Figures in the Post-Jackson Era W Aldren Turner (1864–1945) contributed to the conceptual epileptology in the first three decades of the early 20th century81 and also played an important role in establishing the ILAE as a researcher and contributor to Epilepsia In keeping with the spirit of the times he espoused the cause of the social improvement of the sufferer His first paper235 actually discussed the advantages of epilepsy management in colonies, instancing the Chalfont Colony for Epileptics He correctly judged the severity of both medical and community problems occasioned by epilepsy, and the dire need for radical reform of management policies Subsequent papers examined prognosis, nature, treatment, and associated mental conditions All this culminated in his book Epilepsy – A Study of the Idiopathic Disease236 that was later summarized in his Morison Lectures.237 They both provide an informed current status report of epileptology of the period Turner's approach was descriptive and statistical, with large patient numbers derived from three admittedly disparate groups: Private practice, hospital consultancy, and the Chalfont Colony While fully aware of selection bias by including the patients from Chalfont, he demonstrated that mental decline depended on seizure severity, duration of epilepsy, and age of onset Although he mentioned “facies epileptica,†he did not link it to the use of bromides His book236 summarized his work and clearly depicted the innate problems of the concept of “idiopathic epilepsy.†Historically it provides a detailed summary of the pathologic processes currently thought significant in the genesis of epilepsy He noted Ammon horn sclerosis but did not recognize its significance The book contains the work on systemic body metabolism including examination of blood, sweat, urine, cerebrospinal fluid, and endocrine function during the ictus and interictally in an unsuccessful attempt to identify triggers for seizures In spite of this failure, the concept of the “systemic trigger†for seizures remained popular as expressed in Collier's “metabolic dyscrasia†64 and Brain's emphasis on metabolic factors in epilepsy.34 William Spratling (1862–1915) documented his vast experience as foundation director of the Craig Colony for Epileptics in New York in a textbook Epilepsy and Its Treatment.227 Particularly, Clark and Prout's chapters on the neuropathology of epilepsy and status epilepticus, common conditions in epileptic colonies, was groundbreaking work.23,59,60,223 Spratling's conclusions are also flawed by selection bias His basic concepts of the nature and causes of epilepsy offer an informative view of that period: They feature toxic-metabolic causes combined with an “inherited seizure proclivity†to explain the intermittent crises of refractory epilepsy He hardly mentions jacksonian concepts, although it is clear from the text that he had personally discussed epilepsy with Jackson Clark and Prout, on the other hand, emphasized the centrality of the cortex in seizure generation and in fact maintained that implication of its second layer (“a diseased state of the sensory elementsâ€) due to “active nuclear poisons†underlaid seizure generation Pathologic changes in Ammon horn were detailed, but their significance still remained uncertain This well-documented text displayed the reigning conceptual confusion in epileptology at the turn of the century 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 23 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt Hermann Oppenheimer (1858–1919), a prestigious German neurologist with numerous eponymous conditions named for him, offered a textbook that was the “gold standard†of neurology The section on epilepsy188 demonstrates again the universal confusion in the epileptology of that era Although he was fully accepting the jacksonian concepts on the role of the cortex, he also entertained possible implications of other brain sites and also felt that “toxicopathic†processes were involved P.27 in seizure generation as suggested by the monumental amount of laboratory data L J J Muskens (1872–1937), representing the younger generation of epileptologists at the turn of the century, came to be personally identified with the newly established journal Epilepsia, of which he became secretary to the editorial board, and then the newly founded ILAE, where he assumed the role of secretary general Even more importantly, he was central to the revival of the League in 1935 and republication of Epilepsia again in 1937 The 1928 English edition of his book Epilepsy—Comparative Pathogenesis, Symptoms, Treatment186 (preceded by Dutch and German editions) offers a documentation of his experimental work on epilepsy and clinical and sociologic aspects of the disease In his experiments on myoclonic seizures in animals, he used a toxicologic approach He thought that myoclonic activity was in fact reflex afterdischarge phenomena, and convulsive activity comprised an adaptive process designed to rid the body of toxic substances causing the seizures He sited the seizure activity in brainstem structures, but accepted an additional cortical influence on these “medullary convulsive centres.†His conceptualization of the type of experimental epilepsy he studied bears similarities to that of Prichard205 emphasizing the role of reflexes in seizure generation It is the final chapter of this book, where he discusses the global problem posed by epilepsy and describes his experience in the early days of the ILAE, that contains his main message to his colleagues working in this discipline This message of advocacy for international cooperation for advancing both clinical enterprise and research in epileptology by a cooperative global effort has accorded him, though only recently, with his proper place in the history of epilepsy.85 Samuel Alexander Kinnier Wilson (1878–1937) can be considered Hughlings Jackson's direct heir His early discovery, however, of hepatolenticular degeneration in 1912 delayed his entry into epileptology His first communication on epilepsy was on “Temporo-sphenoidal forms of Idiopathic Epilepsy.â€249 Jackson et al had well documented that “coarse pathology†(tumors, infarcts) occupying the temporal lobe could present with seizures, although seizures could also arise without any evident pathology The déjà vu phenomenon, which seemed peculiar to temporal lobe epilepsy, could also occur totally unassociated with seizures Wilson searched for an alternative etiology for these nonepileptic déjà vu episodes and pointed out that except for a few cases due to anoxic damage, most of them were simply inexplicable Wilson also confronted Jackson's use of the concept of “dis-inhibition†to explain the evocation of the psychic symptoms in temporal lobe seizures Eventually he reluctantly had to reject this altogether.25,253 His Harveian Lecture250 emphasized the concept of the epilepsies, the absolute failure of the psychoanalytic approach, and the unity of pathophysiology of the many “epilepsiesâ€: An explosive hyperactivity of the brain and the primacy of the brain in seizure generation and all clinical manifestations He took the jacksonian concept of “many epilepsies†to embrace the potential for seizures to emanate from many areas of the brain, not just the cortex By the same token, he felt that all epilepsy was manifestly not the same, and that the gloomy view of the condition that persisted in both lay and professional ranks should be abolished, for it handicapped the sufferer in many aspects of life, both medical and social.252 During the historical Royal Society's 1927 discussion on epilepsy, he studiously avoided any detailed consideration of metabolic factors in epilepsy, unlike most other speakers He simply reiterated his concept of the “epilepsies†and then underlined the primacy of the brain alone in seizure generation: “…a fit was the discharge, the setting free, of accumulated nervous energy in healthy neuro-mechanisms.â€251 In his Modern Problems in Neurology,253 Wilson devoted the first four chapters to problems in epileptology, in which he revised concepts of temporal lobe epilepsy mechanisms, discussed the role of inhibition in epilepsy, emphasized the concept of the “epilepsies,†and finally offered his usually optimistic prognosis The psychic symptoms of temporal lobe epilepsy, he decided, were simply a product of local epileptic irritation of that region of the brain, and he formally abandoned the jacksonian concept of disinhibition He then widened his conceptual views of the overall condition of “epilepsy†to embrace a broader range of clinical 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 24 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt phenomena The single most important tenet he emphasized above all was that epilepsy is always symptomatic and never a disease per se He called for great patience in the study of epilepsy: “Research will eventually disclose the cause of those conditions whose etiology currently eludes us.†In the last years of his life, Wilson was able to finish his two most important and almost identical chapters “The Epilepsies†in Bumke and Foerster's Handbuch der Neurologie254 and his own personal Textbook of Neurology, finally published posthumously in 1940,255 edited by his brother-in-law Ninian Bruce His immensely detailed grasp of the literature and documentation of the clinical aspects of epilepsy make it a very important resource in the history of the disease.25 His overall concepts constituted a departure point for the new epileptology that would be ushered in by Lennox to the 1935 London Congress on the use of EEG in the study of epilepsy, an innovation that would change the concept of the condition forever W A Adie (1886–1935) introduced pyknolepsy to an English audience in his address to the Royal Society of Medicine.1 Although this form of epilepsy had been reported by Friedmann97 and Heilbronner,130 Adie emphasized its uniqueness with its many, frequent short-duration attacks; occurrence in the early years of life; explosive onset; and excellent prognosis, and maintained that these features distinguished it from all other forms of epilepsy In the discussion that followed it was reported that “he was inclined to agree that the disease is only a variety of epilepsy, but its clinical characters are so distinct that it seems worthy of a separate name.†Adie introduced the concept of syndromology, with which epileptology continues now to be engaged in reformulating and revising His work could only be matched by Herpin132 and Janz and Mathes's early papers148 that delineated juvenile myoclonic epilepsy By the 1930s, a variety of medical, social, and legal issues relating to the care of persons with epilepsy had led to the foundation of the ILAE; the foundation of a dedicated journal, Epilepsia; the formation of a number of charities, institutions, and colonies for persons with epilepsy; and an increasing interest in medical research by philanthropic individuals and organizations Hughlings Jackson's concept of the discharging lesion certainly brought the cerebral cortex into focus as the structure most intimately involved with the production of “fits,†but the wide variation in the epilepsies, in their age of onset, semeiology, hereditary nature, and course, seemed to defy an explanation based largely on gross lesions of the cerebral hemispheres These developments certainly produced a medical culture that fostered the study of the epilepsies that influenced epileptology during the 1930s and 1940s, particularly due to the rise of electroencephalography 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 25 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt FIGURE Hans Berger (1873–1941) photographed in 1925, years before he published his discovery of the electroencephalogram (From Gloor P Hans Berger on the Electroencephalogram of Man New York, Amsterdam: Elsevier; 1969, with permission.) 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 26 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt FIGURE A 1931 recording by Berger showing spike-and-wave activity From O'Leary JL, Goldring S Science and Epilepsy New York: Raven Press; 1976: 129, with permission.) Electroencephalography and the Origins of Modern Epileptology Experimental Electroencephalographic Recordings during Animal Seizures Experimentally induced seizures were first recorded electroencephalographically by Kaufmann in 1912 in Russia.158 After reading about spontaneous and evoked electrical activity in P.28 the brain, he hypothesized that abnormal brain waves would be present during seizures By curarizing his dogs and performing meticulous craniotomies, he was able to ascertain that abnormal waves seen during tonic–clonic seizures originated in the cortex and were not injury potentials, movement artifacts, or evoked potentials Like his predecessors, Kaufmann had no facilities to photograph his data That same year, also in Russia, the first actual records of EEGs and evoked potentials in animals were preserved photographically and published by Pravdich-Neminski 202 Two years later, Cybulski and Jelenska-Macieszyna72 published the first photographs of paroxysms of abnormal cortical EEG activity during experimental seizures The paroxysms were of very much higher voltage than with spontaneous activity, but their galvanometers were too sluggish to record EEG spikes The Human Electroencephalogram The modern era of epilepsy might be dated to 1929, when Hans Berger (Fig 8) in Jena, Germany, published his discovery that the brain's electrical activity could be recorded from humans using electrodes placed on the scalp.16 Berger's eccentric research career, beginning with his studies of cerebral blood flow and culminating in his studies of the human EEG, has been detailed elsewhere.37,118,183 Berger viewed the dynamic, psychophysical interaction between mind and brain in terms of thermodynamics, and he systematically attempted to measure the energy delivered to the brain and transformed into heat and electricity within the cerebral cortex In this way, Berger hoped to arrive at a physical measurement of “psychic energy,†the component of cerebral energy that was transformed into emotions, sensation, feeling, and rational thought By 1931, he reported interictal EEG changes in epilepsy, and later that year he recorded human spike-and-wave activity With funding from the Carl Weiss Foundation to construct a high-impedance vacuum tube amplifier with a high-frequency response of 125 Hz, he was able to produce a more faithful EEG recording Berger's report in 1932118 contains a series of four photographic segments showing progressive EEG changes following a generalized tonic–clonic seizure as brain activity returned toward normal during an 11-minute period on a 53-year-old patient A report in 193317 shows a segment of recording from an 18-year-old girl during a brief period of simple automatic activity “with no other movement.†It appears to be very-high-voltage 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 27 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt spike-and-wave complexes at about Hz (Fig 9) Berger cited the classic animal experiments of Caton in 1875,51,52 as well P.29 12 13 as later reports by Beck in 1890 and Beck and Cybulski in 1892 on desynchronization of spontaneous cortical activity in dogs and rabbits produced by light and other sensory stimuli FIGURE 10 Left: William G Lennox, Erna Gibbs, and Frederick Gibbs (left to right, about 1936) examining an electroencephalogram (EEG) in the Boston City Hospital laboratory (Courtesy of Ellen Grass, personal collection.) Right: The first published recording of the EEG during epileptic attacks from nine of Lennox's petit mal patients by Gibbs, Davis, and Lennox in 1935 The continuous 3-Hz spike-and-wave complexes were associated with impaired consciousness (From Gibbs FA, Davis H, Lennox WG The electro-encephalogram in epilepsy and in conditions of impaired consciousness Arch Neurol Psychiatry 1935;34:1133–1148, with permission.) Although Berger's early papers described his experiments in detail and were supported by numerous photographs of the electroencephalograms, the immediate reception to Berger's work at home was one of open hostility, while the unanimous reaction outside of Germany was one of disbelief Indeed, most physiologists assumed that Berger had simply recorded some biologic or environmental artifact.29,182 Berger's approach to understanding brain function was at odds with the main thrust of 1930s German neurophysiology, which had become intensely focused on the problems of cortical localization Indeed, the leaders of German neurophysiology working at the Kaiser Wilhelm Institute for Brain Research in Berlin considered Berger a naïve amateur who rejected the prevailing logic of cortical localization and ignored recent developments in electronic amplification.156 As his opponents attempted to identify hundreds of different cortical areas in terms of their electrophysiologic profiles, they frequently defined their project in contradistinction to Berger's “holistic†interpretation of the EEG, and resisted use of the term “electroencephalogram†due to its holistic connotation.29,182 Validation for Berger's work on the human EEG came in 1934, when the distinguished Cambridge physiologist 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 28 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt E.A (later Lord) Adrian demonstrated a blocking in a recording made by Bryan Matthews and presented before the Physiological Society.2 By this time, a number of research groups in North America had also turned their attention to the human EEG The first recording of an EEG in North America was obtained in the winter of 1933–1934 in Hallowell Davis's physiology laboratory at Harvard University Subsequent demonstrations in Davis's laboratory kindled the interest of three young researchers, William Lennox, Erna Gibbs (nee Leonhard), and Frederic Gibbs, who had been primarily focused on measuring blood gases in experimental animals and patients in order to test the prevailing vasomotor theory of ictogenesis FIGURE 11 Tracy Putnam (1894–1975) (left) and H Houston Merritt (1902–1978) (right) Their studies marked the end of using pure empiricism in finding new anticonvulsant drugs Their imaginative approach and disciplined method identified phenytoin and instituted a method for evaluating potential anticonvulsants that remained in use for many years The Electroencephalographic Contributions to Epilepsy A growing number investigators quickly transformed EEG from a scientific curiosity into a promising clinical tool The first recording of the “egg and dart†or “spike and dome†pattern of petit mal seizures occurred in Davis's laboratory in December of 1934 This discovery ignited an explosion of EEG research in the Boston area Using a single-channel vacuum tube amplifier and ink writer, Gibbs et al.109 demonstrated that convulsive and absence seizures were accompanied by different EEG patterns and that “larval seizures†(i.e., interictal discharges) frequently demonstrated the same morphology as the corresponding ictal rhythm Over the following year, Gibbs et al (Fig 10) described EEG patterns that accompanied “psychomotor†seizures, the use of hyperventilation in provoking seizures, and the effects of phenobarbital and sodium bromide on the interictal EEG, and they performed the first invasive EEG recordings in a patient with intractable epilepsy.110,163,167 P.30 150 In 1936, Jasper independently demonstrated focal spikes in localization-related epilepsy At about the same time, Putnam and Merritt (Fig 11) embarked on their systematic survey of potential anticonvulsant compounds in the neurologic research laboratory at Boston City Hospital Putnam later recalled that it was Gibbs's belief that “every true seizure is attended by an electrical ‘storm’ in the brain†that led to the adoption of an electroconvulsive threshold model (in contrast, for example, to strychnine, camphor, or pentylenetetrazol models) for screening potential antiepileptic drugs By 1937, the Gibbses and their colleagues had redefined epilepsy in modern terms: “Epilepsy: A Paroxysmal Cerebral Dysrhythmia†clearly distinguished ictal EEG patterns for petit mal, grand mal, and “psychomotor†seizures; demonstrated the presence of subclinical seizures; and suggested a role for EEG 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 29 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt analysis in seizure prediction.111 That year, the first clinical department to formally perform and charge for EEG services in the United States was opened at Massachusetts General Hospital by Robert Schwab Other hospital laboratories quickly followed In an effort to establish valid EEG-clinical correlations, the Gibbs and Gibbs championed a “rough and ready†approach, relying on Grass's early portable amplifier-ink writer systems that used a two- or three-channel referential montages to screen large numbers of patients For most clinical EEG work, they advocated using a referential recording technique that seemed like epileptiform discharges, especially the 3-Hz spike-and-wave pattern of petit mal seizures They also emphasized the visual art of pattern recognition in electroencephalography.113 Tirelessly pursuing this streamlined approach to clinical EEG, Lennox and the Gibbses classified the epilepsies based on “pathognomonic†or archetypal EEG patterns, proposed that one could render a diagnosis of epilepsy based on a clinical history of spells and “larval seizures†captured in an interictal EEG, demonstrated the increased sensitivity of non–rapid eye movement (NREM) sleep for detection of epileptiform discharges, and enthusiastically—if prematurely—advocated for the surgical treatment of epilepsy Like Frederic Gibbs, Herbert Jasper also became aware of Berger's publications on the human EEG in the early 1930s Jasper's skepticism of Berger's work faded after he learned of Lord Adrian's EEG demonstration at the June 1934 meeting of the American Neurological Association (ANA) Jasper had recently become director of the psychology research laboratory at the Emma Pendleton Bradley Home near Brown University and, realizing the value of EEG work in understanding cerebral function, he asked Howard Andrews, an electronics engineer from the physics department, to design a suitable amplification and recording system Jasper had worked mostly in peripheral neurophysiology, and did not want to rely on an ink writer system, because the friction of this apparatus might dampen high-frequency EEG activity He also recognized the need to record the electrical activity of the brain and combined the high-frequency response of a fast Westinghouse mirror oscillograph with photographic equipment to record the mirror fluctuations Jasper and Carmichael recorded their first EEG on July 9, 1934 Unaware of the work already under way in Boston, they briefly reported the results of their study of six normal subjects and two pathologic cases to Science, the first report on the human EEG from a North American laboratory.149 Jasper emphasized the critical importance of instrumentation and recording technique in EEG above all else His early emphasis on bipolar recordings, his insistence on carefully constructed electrodes and oscilloscope-camera or ink-writing systems to avoid artifact and accurately localize EEG abnormalities, and his opposition to using EEG for the classification of seizures and epilepsies resulted in continuing controversy with the Gibbses Jasper's early work focused on the physiologic basis of the human EEG, but he soon turned to clinical applications Initially, he studied two overlapping populations: Patients with epilepsy referred by local physicians151 and “behavior problem children†admitted to the Bradley Home.71,152 While Jasper's study of children with attention disorders and behavioral problems established the value of routine EEG testing in this setting, it was his study of 55 epilepsy patients that led to the first set of criteria for identifying epileptogenic foci based on ictal and interictal discharges.151 In 1937, Wilder Penfield visited Jasper's EEG laboratory, which consisted of a maze of chicken wire, and later recalled that inside “was a young man, moving about like a bird in an aviary…a rara avis, Herbert Jasper, a young man driven by one creative idea after another He could, he said, localize the focus of an epileptic seizure by the disturbance of brain rhythms outside the skull I doubted that but hoped it might be true.â€199 Penfield finally was persuaded to operate on two of Jasper's subjects whose EEGs had demonstrated a focal P.31 abnormality With Jasper looking on from the observation room, the predicted lesion was found at surgery, and he invited Jasper to come to Montreal to continue his EEG studies on epilepsy patients After months of weekly trips from Providence to Montreal, Jasper and Penfield organized a 4-year research program on the EEG in the epilepsies Jasper's busy clinical neurophysiology laboratory opened in February 1939 While the Gibbses cast a wide net in their clinical EEG work, exploring EEG patterns in a variety of neurologic and medical conditions and functioning as consultant specialists in the emerging field of electroencephalography, Jasper had the demanding task of routinely predicting the location of a putative lesion during presurgical evaluation on the basis of the EEG findings Within years, Jasper had evaluated about 1,000 patients in the outpatient EEG department and performed dozens of intraoperative studies, recording the electrical activity of the cerebral cortex surface, subcortical structures, and epileptogenic lesions (in 1960) Penfield and Jasper provided the first descriptions of the focal and generalized seizures, 09/06/2008 21:56 Ovid: Epilepsy: A Comprehensive Textbook 30 de 53 file:///C:/Documents%20and%20Settings/papa/Escritorio/engel/chapt distinguished the EEG correlates of tonic and clonic seizure activity, described the interictal–ictal transition and the propagation of ictal rhythms across the cerebral cortex based on a series of electrocorticography studies, and concluded that persistent epileptiform discharges on electrocorticography after surgical resection had little prognostic value Perhaps most importantly, Jasper and Penfield reported that using Jasper's bipolar EEG technique, scalp EEG recordings from patients being evaluated for surgery accurately predicted a surgical lesion within to cm in 85% of cases These electrocorticography studies led Penfield and Jasper to distinguish the “seizure onset zone†from the “epileptogenic lesion,†which, at the time, was typically visualized on a pneumoencephalogram It is difficult to clearly establish the impact of EEG on the success of epilepsy surgery during these early years of EEG, but one account describes a dramatic increase in surgical cases168 and others suggest a precipitous decline in negative surgical explorations, from approximately 50% prior to introduction of routine presurgical EEG to