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WYLLIESTREATMENT OFEPILEPSYPRINCIPLES AND PRACTICE

F I F T H E D I T I O N

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Editor-in-Chief

Elaine Wyllie, MDProfessor of Pediatric MedicineCleveland Clinic Lerner College of MedicineDirector of the Center for Pediatric NeurologyNeurological InstituteCleveland ClinicCleveland, Ohio

Associate Editors

Gregory D. Cascino,MD, FAANProfessor of NeurologyMayo Clinic College of MedicineChair, Division of EpilepsyMayo ClinicRochester, Minnesota

WYLLIESTREATMENT OFEPILEPSYPRINCIPLES AND PRACTICE

F I F T H E D I T I O N

Barry E. Gidal, PharmDProfessor, School of Pharmacy andDepartment of NeurologyChair, Pharmacy Practice DivisionUniversity of WisconsinMadison, Wisconsin

Howard P. Goodkin, MD, PhDThe Shure Associate Professorof Pediatric NeurologyDepartments of Neurology and PediatricsUniversity of Virginia

Charlottesville, Virginia

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Acquisitions Editor: Fran DestefanoProduct Manager: Tom GibbonsVendor Manager: Alicia JacksonSenior Manufacturing Manager: Ben RiveraMarketing Manager: Brian FreilandDesign Coordinator: Steve DrudingProduction Service: MPS Limited, a Macmillan Company

5th Edition 2011 by Lippincott Williams & Wilkins, a Wolters Kluwer businessTwo Commerce Square2001 Market StreetPhiladelphia, PA 19103 USALWW.com

All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any formby 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 andreviews. 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 China.

Library of Congress Cataloging-in-Publication DataWyllies treatment of epilepsy : principles and practice. 5th ed. / editor-in-chief, Elaine Wyllie ;associate editors, Gregory D. Cascino, Barry E. Gidal, Howard P. Goodkin.

p. ; cm.Other title: Treatment of epilepsyRev. ed. of: The treatment of epilepsy. 4th ed. / editor-in-chief, Elaine Wyllie. c2006.Includes bibliographical references and index.Summary: In one convenient source, this book provides a broad, detailed, and cohesive overview of

seizure disorders and contemporary treatment options. For this Fifth Edition, the editors have replacedor significantly revised approximately 30 to 50 percent of the chapters, and have updated all of them.Dr. Wyllie has invited three new editors: Gregory Cascino, MD, at Mayo Clinic, adult epileptologist withspecial expertise in neuroimaging; Barry Gidal, PharmD, RPh, at University of Wisconsin, a pharmacologistwith phenomenal expertise in antiepileptic medications; and Howard Goodkin, MD, PhD, a pediatricneurologist at the University of Virginia. A fully searchable companion website will include the full text

online and supplementary material such as seizure videos, additional EEG tracings, and more colorillustrationsProvided by publisher.ISBN-13: 978-1-58255-937-7 (hardback)ISBN-10: 1-58255-937-6 (hardback)1. Epilepsy. I. Wyllie, Elaine. II. Treatment of epilepsy. III. Title: Treatment of epilepsy.[DNLM: 1. Epilepsytherapy. 2. Epilepsydiagnosis. WL 385 W983 2011]RC372.T68 2011616.853dc22

2010024726

Care has been taken to confirm the accuracy of the information presented and to describe generally acceptedpractices. However, the authors, editors, and publisher are not responsible for errors or omissions or for anyconsequences from application of the information in this book and make no warranty, expressed or implied,with respect to the currency, completeness, or accuracy of the contents of the publication. Application of theinformation in a particular situation remains t he professional responsibility of the practitioner.

The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosageset forth in this text are in accordance with current recommendations and practice at the time of publica-tion. 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 insertfor each drug for any change in indications and dosage and for added warnings and precautions. This isparticularly important when the recommended agent is a new or infrequently employed drug.

Some drugs and medical devices presented in the publication have Food and Drug Administration(FDA) clearance for limited use in restricted research settings. It is the responsibility of the health careprovider 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 faxorders to (301) 223-2320. International customers should call (301) 223-2300.

Visit Lippincott Williams & Wilkins on the Internet: at LWW.com. Lippincott Williams & Wilkinscustomer service representatives are available from 8:30 am to 6 pm, EST.

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D E D I C AT I O N

To the Cleveland Clinic, which brought me on board as a young doctor and provided mecareer opportunities beyond my wildest imagination

To our Chief Executive Officer, Dr. Delos Cosgrove, whose visionary leadership hasbrought the Cleveland Clinic to where we are today, at the forefront of medical care

throughout the world

And to my husband, Dr. Robert Wyllie, Physician-in-Chief of the Cleveland ClinicChildrens Hospital, who provides the environment for all of us who care for children to

do our best work

Dr. Elaine Wyllie, on campus at the Cleveland Clinic

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vi

Harry S. Abram, M.D.Assistant Professor of Pediatrics and NeurologyMayo Clinic FloridaNemours Childrens ClinicDirector, Neurophysiology Laboratory, Departmentof PediatricsWolfson Childrens Hospital

Jacksonville, Florida

Andreas V. Alexopoulos, M.D., M.P.H.Cleveland Clinic Lerner Research InstituteCleveland Clinic Epilepsy CenterCleveland ClinicCleveland, Ohio

Ulrich Altrup, M.D. (Deceased)Department of NeurologyInstitute for Experimental Epilepsy ResearchMuenster, Germany

Frederick Andermann, O.C., M.D., F.R.C.P. (C.)Professor of Neurology and PediatricsMcGill UniversityDirector, Epilepsy ServiceMontreal Neurological Hospital and InstituteMontreal, Quebec, Canada

Anne Anderson, M.D.Associate Professor of Pediatrics, Neurology,and NeuroscienceBaylor College of MedicineMedical Director, Epilepsy Monitoring UnitInvestigator, Cain Foundation LaboratoriesTexas Childrens HospitalHouston, Texas

Gail D. Anderson, Ph.D.Professor of PharmacyUniversity of WashingtonSeattle, Washington

Alexis Arzimanoglou, M.D.Associate ProfessorUniversity Hospitals of Lyon and INSERM U821Head, Institute for Children and Adolescents with Epilepsy

IDEE and Pediatric NeurophysiologyHopital Femme Mere Enfant (HCL)Lyon, France

Thomas Bast, M.D.Head PhysicianEpilepsy Clinic for Children and AdolescentsEpilepsy Centre KorkKehl, Germany

Jocelyn F. Bautista, M.D.Assistant Professor of MedicineCleveland Clinic Lerner College of MedicineCleveland ClinicCleveland, Ohio

Selim R. Benbadis, M.D.

Professor of NeurologyUniversity of South FloridaDirector of Epilepsy and EEGTampa General HospitalTampa, Florida

T.A. Benke, M.D., Ph.D.Associate Professor of Pediatrics, Neurology, andPharmacologyUniversity of Colorado Denver, Schoolof MedicineChildrens HospitalAurora, Colorado

Anne T. Berg, Ph.D.Research Professor of BiologyNorthern Illinois UniversityDeKalb, IllinoisProfessor, Epilepsy CenterNorthwestern Childrens Memorial HospitalChicago, Illinois

William E. Bingaman, M.D.Head, Epilepsy SurgeryVice Chairman, Neurological InstituteThe Richard and Karen Shusterman Family Endowed Chairin Epilepsy SurgeryProfessor in SurgeryCleveland Clinic Lerner College of Medicine of Case WesternReserve UniversityCleveland ClinicCleveland, Ohio

Angela K. Birnbaum, Ph.D.Associate Professor of Experimental and ClinicalPharmacologyUniversity of MinnesotaMinneapolis, Minnesota

Jane G. Boggs, M.D.Associate Professor of NeurologyWake Forest UniversityWinston Salem, North Carolina

C O N T R I B U T I N G A U T H O R S

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Blaise F. D. Bourgeois, M.D.Professor of NeurologyHarvard Medical SchoolDirector, Division of Epilepsy and Clinical NeurophysiologyChildrens HospitalBoston, Massachusetts

Jeffrey W. Britton, M.D.Assistant Professor of NeurologyDivisions of Clinical NeurophysiologyEEG and EpilepsyMayo ClinicRochester, Minnesota

Paula M. Brna, M.D., F.R.C.P. (C.)Assistant Professor of PediatricsDalhousie UniversityPediatric NeurologistIWK Health CentreHalifax, Nova Scotia, Canada

Martin J. Brodie, M.D.Professor of Medicine and Clinical PharmacologyDivision of Cardiovascular and Medical SciencesUniversity of GlasgowClinical and Research Director, Epilepsy UnitWestern InfirmaryGlasgow, Scotland

Amy R. Brooks-Kayal, M.D.Professor of Pediatrics and NeurologyUniversity of Colorado School of MedicineChief and Ponzio Family Chair in Pediatric NeurologyChildrens HospitalAurora, Colorado

Richard C. Burgess, M.D., Ph.D.Adjunct Professor of Biomedical EngineeringCase Western Reserve UniversityDirector, MEG LaboratoryCleveland ClinicCleveland, Ohio

Richard W. Byrne, M.D.Professor and Chairman, Department of NeurosurgeryRush University Medical SchoolChicago, Illinois

Carol S. Camfield, M.D.Professor Emeritus of Child NeurologyDalhousie UniversityHalifax, Nova Scotia, Canada

Peter R. Camfield, M.D.Professor Emeritus of Child NeurologyDalhousie UniversityHalifax, Nova Scotia, Canada

Gregory D. Cascino, M.D., F.A.A.N.Professor of NeurologyMayo Clinic College of Medicine

Chair, Division of EpilepsyMayo ClinicRochester, Minnesota

Kevin E. Chapman, M.D.Department of Pediatric NeurologyBarrow Neurological InstituteSt. Josephs Hospital and Medical CenterPhoenix, Arizona

Jean E. Cibula, M.D.Assistant Professor of NeurologyUniversity of FloridaMedical Director, EEG LabUniversity of Florida Comprehensive Epilepsy ProgramShands Hospital at the University of Florida

Gainesville, FloridaRobert R. Clancy, M.D.Professor of Neurology and PediatricsUniversity of Pennsylvania School of MedicineChildrens Hospital of PhiladelphiaPhiladelphia, Pennsylvania

J. HelenCross, M.B., Ch.B., Ph.D., F.R.C.P.C.H., F.R.C.P.Prince of Waless Chair of Childhood EpilepsyUCL Institute of Child HealthHonorary Consultant in Paediatric NeurologyGreat Ormond Street HospitalLondon, England

Luigi DArgenzio, M.D.Epilepsy Fellow, Neuroscience UnitUCLInstitute of Child HealthLondon, United KingdomClinical Fellow in Paediatric NeurologyNational Centre for Young People with EpilepsyLingfield, Surrey, United Kingdom

Stefanie Darnley, B.A.Research Assistant in Neurology

Johns Hopkins University School of MedicineBaltimore, Maryland

Rohit R. Das, M.D., M.P.H.Assistant Professor of NeurologyUniversity of LouisvilleAttending Neurologist and EpileptologistKosair Childrens and University of Louisville HospitalsLouisville, Kentucky

Anita Datta, M.D., F.R.C.P.C.Clinical Assistant Professor of Pediatric NeurologyPediatric Neurologist/EpileptologistUniversity of SaskatchewanRoyal University HospitalSaskatoon, Saskatchewan, Canada

Norman Delanty, M.D., F.R.C.P.I.Honorary Senior Lecturer in Molecular andCellular TherapeuticsRoyal College of Surgeons in IrelandConsultant Neurologist, Epilepsy ProgrammeBeaumont HospitalDublin, Ireland

Robert J. DeLorenzo, M.D., Ph.D., M.P.H.George Bliley Professor of NeurologyProfessor of Pharmacology and ToxicologyProfessor of Molecular Biophysics and BiochemistryVirginia Commonwealth UniversityVirginia Commonwealth University Hospital

Richmond, VirginiaDarryl C. De Vivo, M.D.Sidney Carter Professor of Neurology and Professorof PediatricsColumbia University College of Physicians and SurgeonsNew York Presbyterian HospitalUniversity Hospital of Columbia and CornellNew York, New York

Contributing Authors vii

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Beate Diehl, M.D.Department of Clinical and Experimental EpilepsyInstitute of Neurology, University College LondonConsultant Clinical NeurophysiologistNational Hospital for Neurology and NeurosurgeryLondon, United Kingdom

Ding Ding, M.D., M.P.H.Associate Professor of Biostatistics and EpidemiologyFudan UniversityHua Shan HospitalShanghai, Peoples Republic of China

Joseph Drazkowski, M.D.Associate Professor of NeurologyMayo Clinic ArizonaPhoenix, Arizona

Franois Dubeau, M.D.Assistant Professor of Neurology and NeurosurgeryMcGill UniversityMontreal Neurological Hospital and InstituteMontreal, Quebec, Canada

Michael Duchowny, M.D.Professor of Neurology and PediatricsUniversity of Miami Miller School of MedicineDirector, Comprehensive Epilepsy Center,Brain InstituteMiami Childrens HospitalMiami, Florida

Stephan Eisenschenk, M.D.Associate Professor of NeurologyUniversity of FloridaDirector, UF/Shands Comprehensive Epilepsy ProgramShands HospitalGainesville, Florida

Dana Ekstein, M.D.Hebrew University School of MedicineHadassah University Medical Center

Jerusalem, IsraelChristian E. Elger, M.D., F.R.C.P.Professor of EpileptologyUniversity of BonnHead, Department of EpileptologyUniversity of Bonn Medical CentreBonn, Germany

Edward Faught, M.D.Professor of NeurologyEmory UniversityChief, Neurology ServiceEmory University Hospital MidtownAtlanta, Georgia

Jacqueline A. French, M.D.Professor of Neurology

New York University School of MedicineAcademic Director, ComprehensiveEpilepsy CenterNew York University-Langone Medical CenterNew York, New York

Neil Friedman, M.D., Ch.B.Center for Pediatric NeurologyNeurological Institute, Cleveland ClinicCleveland, Ohio

William Davis Gaillard, M.D.Professor of Neurology and PediatricsGeorge Washington University and Georgetown UniversityChief, Division of Epilepsy, Neurophysiology and CriticalCare NeurologyChildrens National Medical Center

Washington, D.C.Deana M. Gazzola, M.D.Instructor in NeurologyNew York University School of MedicineNew York University-Langone Medical CenterNew York, New York

Barry E. Gidal, Pharm.D.Professor, School of Pharmacy and Department of NeurologyChair, Pharmacy Practice DivisionUniversity of WisconsinMadison, Wisconsin

Frank G. Gilliam, M.D., M.P.H.Director of NeurologyGeisinger Health SystemWilkes-Barre and Danville, Pennsylvania

Robin L. Gilmore, M.D.Staff NeurologistMaury Regional Medical CenterColumbia, Tennessee

Tracy A. Glauser, M.D.Professor of PediatricsUniversity of Cincinnati College of MedicineDirector, Comprehensive Epilepsy CenterCincinnati Childrens Hospital Medical CenterCincinnati, Ohio

Cristina Y. Go, M.D.Neurologist and Clinical NeurophysiologistPaediatric Epilepsy Fellowship Training Co-directorThe Hospital for Sick ChildrenToronto, Ontario, Canada

Jorge A. Gonzlez-Martnez, M.D., Ph.D.Staff, Epilepsy SurgeryEpilepsy CenterCleveland Clinic Neurological InstituteCleveland, Ohio

Howard P. Goodkin, M.D., Ph.D.The Shure Associate Professor of Pediatric NeurologyDepartments of Neurology and PediatricsUniversity of VirginiaCharlottesville, Virginia

L. John Greenfield, Jr., M.D., Ph.D.Professor and ChairmanDepartment of NeurologyUniversity of Arkansas for Medical SciencesLittle Rock, Arkansas

Varda Gross-Tsur, M.D.

Associate ProfessorHebrew UniversityHadassah HospitalDirector, Child Development UnitShaare Zedek Medical Center

Jerusalem, Israel

Carlos A. M. Guerreiro, M.D., Ph.D.Professor of NeurologyUniversity of Campinas (Unicamp)Campinas, Sao Paolo, Brazil

viii Contributing Authors

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Marilisa M. Guerreiro, M.D., Ph.D.Professor of Pediatric NeurologyHead, Child Neurology SectionUniversity of Campinas (Unicamp)Campinas, Sao Paolo, Brazil

Renzo Guerrini, M.D.Professor of Child Neurology and PsychiatryUniversity of FlorenceDirector, Pediatric NeurologyChildrens Hospital A. MeyerFlorence, Italy

Ajay Gupta, M.D.Assistant Professor of Pediatric EpilepsyCleveland Clinic Lerner College of MedicineCleveland ClinicCleveland, Ohio

Andreas Hahn, M.D.Associate Professor of Neuropediatrics

Justus-Liebig-University GiessenAssistant Medical Director, NeuropediatricsUniversity Hospital Giessen

Giessen, GermanyStephen Hantus, M.D.Associate Staff Cleveland Clinic Epilepsy CenterCleveland, Ohio

Cynthia L. Harden, M.D.Professor of Neurology, Clinical Educator TrackDirector, Division of EpilepsyUniversity of Miami Miller School of MedicineAttending Neurologist

Jackson Memorial HospitalUniversity of Miami HospitalMiami, Florida

W. Allen Hauser, M.D.Professor of Neurology and Epidemiology

Columbia UniversityNew York, New York

Lara Jehi, M.D.Assistant Professor of NeurologyCleveland Clinic Lerner College of MedicineEpilepsy Center, Cleveland ClinicCleveland, Ohio

Stephen E. Jones, M.D., Ph.D.Imaging InstituteCleveland ClinicCleveland, Ohio

Stephen P. Kalhorn, M.D.Department of NeurosurgeryNew York University Langone Medical CenterNew York, New York

Andres M. Kanner, M.D.Professor of Neurological Sciences and PsychiatryRush Medical College at Rush UniversityDirector, Laboratories of Electroencephalographyand Video-EEG TelemetryAssociate Director, Section of Epilepsy and RushEpilepsy CenterRush University Medical CenterChicago, Illinois

Christoph Kellinghaus, M.D.Head of Section, Epilepsy/EEGKlinikum OsnabrckOsnabrck, Germany

John F. Kerrigan, M.D.

Assistant Professor of Clinical Pediatrics and NeurologyUniversity of Arizona College of MedicinePhoenixDirector, Pediatric Epilepsy ProgramCo-director, Hypothalamic Hamartoma ProgramBarrow Neurological InstituteSt. Josephs Hospital and Medical CenterPhoenix, Arizona

Prakash Kotagal, M.D.Head, Section of Pediatric EpilepsyEpilepsy CenterCleveland ClinicCleveland, Ohio

Gregory Krauss, M.D.Professor of Neurology

Johns Hopkins HospitalBaltimore, Maryland

Ruben Kuzniecky, M.D.Professor of NeurologyNew York UniversityCo-director, NYU Epilepsy CenterNew York University HospitalNew York, New York

Patrick Kwan, M.D.Division of NeurologyDepartment of Medicine and TherapeuticsThe Chinese University of Hong KongPrince of Wales HospitalHong Kong

Kay Kyllonen, Pharm.D., F.P.P.A.G.Clinical Specialist in PediatricsPharmacy Department

Cleveland ClinicCleveland, Ohio

Beth A. Leeman, M.D.Assistant Professor of NeurologyEmory UniversityPhysician, Neurology ServiceAtlanta VA Medical CenterAtlanta, GeorgiaAssistant in Neuroscience, Department of NeurologyMassachusetts General HospitalBoston, Massachusetts

Louis Lemieux, B.Sc., M.Sc., Ph.D.Professor of Physics Applied to Medical ImagingDepartment of Clinical and Experimental EpilepsyUCL Institute of NeurologyLondon, United Kingdom

Ilo E. Leppik, M.D.Professor of Pharmacy and Adjunct Professorof NeurologyDirector of Epilepsy Research and Education ProgramCollege of PharmacyUniversity of MinnesotaDirector of ResearchMINCEP Epilepsy CareMinneapolis, Minnesota

Contributing Authors ix

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Christine Linehan, Ph.D.Senior Researcher, Centre for Disability StudiesUniversity College DublinDublin, Ireland

Tobias Loddenkemper, M.D.

Assistant Professor of NeurologyHarvard Medical SchoolChildrens HospitalBoston, Massachusetts

Hans O. Lders, M.D., Ph.D.Professor of NeurologyCase Medical SchoolEpilepsy Center DirectorUniversity HospitalsCleveland, Ohio

Susan E. Marino, Ph.D.Assistant Professor and Director of Experimentaland Clinical PharmacologyCenter for Clinical and Cognitive NeuropharmacologyUniversity of MinnesotaMinneapolis, Minnesota

Robert C. Martinez, M.D.Instructor in Neurology, Epilepsy DivisionUniversity of Miami Miller School of Medicine

Jackson Memorial Hospital, University of Miami HospitalMiami, Florida

Gary W. Mathern, M.D.Professor of Neurosurgery and Psychiatry & BehavioralSciencesIntellectual and Developmental Disabilities Research CenterBrain Research InstituteDavid Geffen School of MedicineUniversity of California, Los AngelesNeurosurgical Director, Pediatric Epilepsy Surgery Programand Neurobiology of Epilepsy Research LaboratoryRonald Reagan Medical CenterLos Angeles, California

Michael J. McLean, M.D., Ph.D.Associate Professor of NeurologyVanderbilt University Medical CenterNashville, Tennessee

Kimford J. Meador, M.D.Professor of NeurologyEmory UniversityDirector of EpilepsyEmory University HospitalAtlanta, Georgia

Mohamad Mikati, M.D.Wilburt C. Davison Distinguished Professor of PediatricsProfessor of NeurobiologyDuke University

Chief, Division of Pediatric NeurologyDuke University Medical CenterDurham, North Carolina

Ghayda Mirzaa, M.D.Fellow, Clinical GeneticsDepartment of Human GeneticsUniversity of ChicagoChicago, Illinois

Eli M. Mizrahi, M.D.Chair of NeurologyProfessor of Neurology and PediatricsDirector, Clinical Neurophysiology Residency ProgramBaylor College of MedicineChief, Neurophysiology Service

St. Lukes Episcopal HospitalHouston, Texas

Ahsan N.V. Moosa, M.D.Epilepsy Center, Neurological InstituteCleveland ClinicCleveland, Ohio

Diego A. Morita, M.D.Assistant Professor of Pediatrics and NeurologyUniversity of Cincinnati College of MedicineDirector, New Onset Seizure ProgramCincinnati Childrens Hospital Medical CenterCincinnati, Ohio

Bernd A. Neubauer, M.D.Head, Department of NeuropediatricsUniversity of Giessen

Giessen, GermanyKatherine C. Nickels, M.D.Assistant Professor of NeurologySenior Associate ConsultantMayo ClinicRochester, Minnesota

Soheyl Noachtar, M.D.Professor of NeurologyHead, Epilepsy CenterUniversity of MunichMunich, Germany

Douglas R. Nordli, Jr., M.D.Professor of PediatricsNorthwestern University Feinberg School of MedicineLorna S. and James P. Langdon Chair of

Pediatric EpilepsyChildrens Memorial HospitalChicago, Illinois

Christine ODell, R.N., M.S.N.Clinical Nurse Specialist, NeurologyMontefiore Medical CenterNew York, New York

Karine Ostrowsky-Coste, M.D.University Hospitals of FranceInstitute for Children and Adolescents with EpilepsyIDEEand Pediatric NeurophysiologyHopital Femme Mere Infant (HCL)Lyon, France

Alison M. Pack, M.D.Associate Professor of Clinical Neurology

Columbia UniversityNew York Presbyterian HospitalNew York, New York

Sumit Parikh, M.D.Center for Pediatric NeurologyNeurological InstituteCleveland ClinicCleveland, Ohio

x Contributing Authors

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John M. Pellock, M.D.Professor and Chair of Child NeurologyVirginia Commonwealth UniversityRichmond, Virginia

Page B. Pennell, M.D.

Associate Professor of NeurologyHarvard Medical SchoolDirector of Research for Division of Epilepsy and SleepBrigham and Womens HospitalBoston, Massachusetts

Andrew Pickens IV, M.D., J.D., M.B.A.Medical Director, Duke Raleigh Emergency Department,Quality ImprovementRaleigh, North Carolina

Bernd Pohlmann-Eden, M.D., Ph.D.Professor of Neurology and PharmacologyDalhousie UniversityCo-director, Epilepsy ProgramQueen Elizabeth II Health Science CentreHalifax, Canada

Richard A. Prayson, M.D.Professor of PathologyCleveland Clinic Lerner College of MedicineSection Head, NeuropathologyCleveland ClinicCleveland, Ohio

Janet Reid, M.D., F.R.C.P.C.Section Head of Pediatric RadiologyChildrens Hospital Cleveland ClinicCleveland, Ohio

James J. Riviello, Jr., M.D.George Peterkin Endowed Chair in PediatricsProfessor of Pediatrics and NeurologyBaylor College of MedicineChief of NeurophysiologyTexas Childrens HospitalHouston, Texas

Howard C. Rosenberg, M.D., Ph.D.Professor of Physiology and PharmacologyUniversity of Toledo College of MedicineToledo, Ohio

William E. Rosenfeld, M.D.DirectorComprehensive Epilepsy Care Center for Children and AdultsChesterfield, Missouri

Jonathan Roth, M.D.Pediatric Neurosurgery FellowNew York University Langone Medical CenterNew York, New York

Paul M. Ruggieri, M.D.Head, Section of Neuroradiology and MRI

Cleveland ClinicCleveland, Ohio

Steven C. Schachter, M.D.Professor of NeurologyHarvard Medical SchoolChief Academic OfficerCenter for Integration of Medicine and Innovative TechnologyBoston, Massachusetts

Stephan Schuele, M.D., M.P.H.Assistant Professor of NeurologyNorthwestern UniversityFeinberg School of MedicineDirector, Northwestern University ComprehensiveEpilepsy Center

Chicago, IllinoisRaj D. Sheth, M.D.Professor of NeurologyMayo Clinic College of MedicineNemours Childrens Clinic


Shlomo Shinnar, M.D., Ph.D.Professor of Neurology, Pediatrics and Epidemiology andPopulation HealthHyman Climenko Professor of Neuroscience ResearchAlbert Einstein College of MedicineDirector, Comprehensive Epilepsy Management CenterMontefiore Medical CenterNew York, New York

Joseph I. Sirven, M.D.

Professor and Chairman, NeurologyMayo ClinicPhoenix, Arizona

Michael C. Smith, M.D.Professor of Neurological SciencesRush UniversityDirector and Senior Attending Neurologist,Rush Epilepsy CenterRush University Medical CenterChicago, Illinois

O. Carter Snead III, M.D.Professor of Medicine, Paediatrics and PharmacologyUniversity of TorontoHead, Division of Neurology (Pediatrics)Hospital for Sick ChildrenToronto, Ontario, Canada

Elson L. So, M.D.Professor of NeurologyMayo ClinicRochester, Minnesota

Norman K. So, M.B., B.Chir.Epilepsy CenterNeurological InstituteCleveland ClinicCleveland, Ohio

Erwin-Josef Speckmann, M.D.Professor EmeritusInstitute of Physiology (Neurophysiology)University of MnsterMnster, Germany

Martin Staudt, M.D.Professor of Developmental NeuroplasticityEberhard-Karls UniversityTbingen, GermanyVice Director, Clinic for Neuropediatrics andNeurorehabilitation, Epilepsy Center for Childrenand AdolescentsSchn-Klinik VogtareuthVogtareuth, Germany

Contributing Authors xi

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S. Matthew Stead, M.D., Ph.D.Assistant Professor of NeurologyMayo ClinicRochester, Minnesota

William O. Tatum IV, D.O.

Professor of NeurologyMayo Clinic College of MedicineDirector, Epilepsy Monitoring UnitMayo Hospital


Elizabeth A. Thiele, M.D., Ph.D.Associate Professor of NeurologyHarvard Medical SchoolDirector, Pediatric Epilepsy ProgramMassachusetts General HospitalBoston, Massachusetts

Elizabeth I. Tietz, M.D.Professor and Vice-Chair of Physiology and PharmacologyUniversity of Toledo College of MedicineToledo, Ohio

Ingrid Tuxhorn, M.D.Professor of MedicineCase Western Reserve UniversityCleveland Clinic Lerner Research CenterNeurologic Institute at the Cleveland Clinic Epilepsy CenterCleveland, Ohio

Basim M. Uthman, M.D., F.A.C.I.P., F.A.A.N.Professor of NeurologyDirector, Neurology ClerkshipWeill Cornell Medical College in QatarQatar Foundation Education CityDoha, Qatar

Fernando L. Vale, M.D.Professor and Vice-Chair, Department of NeurosurgeryUniversity of South FloridaTampa General HospitalTampa, Florida

Tonicarlo R. Velasco, M.D.NeurophysiologistDepartment of Neurology, Psychiatry andBehavioral SciencesUniversity of Sao PauloExecutive Director, Adult Epilepsy Surgery ProgramHospital das Clinicas de Ribeirao Preto-CIREPRibeirao Preto, Sao Paulo, Brazil

Elizabeth Waterhouse, M.D.Professor of NeurologyVirginia Commonwealth University School of MedicineRichmond, Virginia

Tim Wehner, M.D.Department of NeurologyPhillips-University

University Hospital MarburgMarburg, Germany

Howard L. Weiner, M.D.Professor of Neurosurgery and PediatricsNew York University School of MedicineNew York University Langone Medical CenterNew York, New York

Timothy E. Welty, Pharm.D., F.C.C.P.Professor and ChairDepartment of Pharmacy PracticeUniversity of KansasLawrence, KansasUniversity of Kansas Medical Center

Kansas City, Kansas James W. Wheless, M.D.Professor and Chief of Pediatric OncologyLe Bonheur Chair in Pediatric NeurologyUniversity of Tennessee Health Science CenterDirector, Neuroscience InstituteLe Bonheur Comprehensive Epilepsy ProgramLe Bonheur Childrens Medical CenterClinical Chief and Director of Pediatric NeurologySt. Jude Childrens Research HospitalMemphis, Tennessee

H. Steve White, Ph.D.Professor of Pharmacology and ToxicologyCollege of PharmacyUniversity of UtahSalt Lake City, Utah

L. James Willmore, M.D.Associate Dean and Professor of NeurologySt. Louis University School of MedicineSt. Louis University HospitalSt. Louis, Missouri

Sara McCrone Winchester, M.D.Pediatric Neurology FellowDepartment of Pediatrics, Division of Child NeurologyDuke University Medical CenterDurham, North Carolina

S. Parrish Winesett, M.D.Assistant Professor of NeurosurgeryUniversity of South FloridaTampa, FloridaMedical Director, Epilepsy Monitoring Unit

All Children HospitalSt. Petersburg, Florida

Elaine Wirrell, B.Sc. (Hon.), M.D., F.R.C.P.(C.)Professor of Child and Adolescent Neurology and EpilepsyDirector of Pediatric EpilepsyMayo ClinicRochester, Minnesota

Gregory A. Worrell, M.D., Ph.D.Assistant Professor of NeurologyMayo ClinicRochester, Minnesota

Elaine Wyllie, M.D.Professor of Pediatric MedicineCleveland Clinic Lerner College of MedicineDirector of the Center for Pediatric Neurology

Neurological InstituteCleveland ClinicCleveland, Ohio

Benjamin G. Zifkin, M.D.C.M., F.R.C.P.C.Epilepsy ClinicMontreal Neurological HospitalMontreal, Quebec, Canada

xii Contributing Authors

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When I started the first edition of this book as a newly mintedepileptologist at the Cleveland Clinic, most of our currentantiepileptic medications were still on the horizon and epilepsysurgery was in the early stages of development. Each successiveedition of the book chronicled sea changes in the field, from thedevelopment of powerful neuroimaging techniques, throughapproval of many new antiepileptic medications, to the emer-

gence of genetics as a force in epilepsy diagnosis. Today, with itsown neurodiagnostic procedures and plethora of effective treat-ment modalities, epileptology is one of the most rewarding andcomplex fields in medicine. And in society, epilepsy is starting toemerge from the shadows as patients and families bandtogether in support groups and gather information from theinternet. Persons with epilepsy are demanding, expecting, state-of-the-art health care at the same time that our field is growingmore complex every day.

Thats why we need this book now more than ever. Its rea-son for being is to provide health care professionals with themost up-to-date tools to care for persons with epilepsy, day inand day out. Thanks to the 144 world-renowned experts whoshared their knowledge with us, this fifth edition is a ready ref-erence for cutting-edge information about everything fromcomplex drugdrug interactions to age-related EEG manifesta-

tions of focal epileptogenic lesions. Its been an honor to craftthis work for all of us to use in our clinical practice.

Elaine Wyllie, MDProfessor of Pediatric Medicine

Cleveland Clinic Lerner College of MedicineDirector of the Center for Pediatric Neurology

Neurological InstituteCleveland Clinic

www.clevelandclinic.org/epilepsy

P R E FA C E

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It is a privilege and honor to be asked to write the foreword of the 5th Edition of Wyllies Treatment of Epilepsy. It is also aneasy task since I know the book well. The 4th edition is fre-quently pulled from my bookshelf when I have a question abouta patient with epilepsy, and I am looking forward to replacing itwith the 5th. While the first edition, published in 1993, was out-standing, each edition has achieved new heights. Recognizing

that it is very difficult to continuously improve a legendary text,the 5th edition will not disappoint.

Advances in the treatment of epilepsy continue to evolve at arapid rate as there is increasing awareness among both health-care workers and the public of the enormity of the condition.Epilepsy does not spare age, gender, race, or ethnic group and isone of the most common neurologic disorders encountered.Increased understanding of the etiology, pathophysiology, andgenetic underpinnings coupled with advancements in the med-ical, dietary, and surgical management of patients makes this anideal time to publish the 5th edition.

Elaine Wyllie, along with her associate editors GregoryCascino, Barry Gidal, and Howard Goodkin, has recruited anoutstanding group of authors who have provided a comprehen-sive, but not encyclopedic, review of the treatment of epilepsy.Each author is well known for their work in epilepsy.

The book is crafted in a logical and educationally soundmanner. Starting with the pathologic substrates and mechanismsof epilepsy, important chapters cover epidemiology, natural his-tory, genetics, and epileptogenesis (Part I). A key tool in the eval-uation of patients with epilepsy is the electroencephalogram andPart II of the book covers the basic principles of electroen-cephalography. A wonderful bonus in this section is a remark-ably complete atlas of epileptiform abnormalities.

Epileptic seizures and syndromes are detailed in Part III of thebook. The gamut of seizures and syndromes from the neonate to

the elderly are covered in considerable detail. Nonepileptic con-ditions that mimic epileptic seizures are reviewed and there is aheavy emphasis on seizures in special clinical settings, such asseizures in neurometabolic diseases, head trauma, and neurocu-taneous disorders.

Antiepileptic medications are reviewed in Part IV andepilepsy surgery in Part V. As the books title would indicate,

these topics are covered in considerable depth, either of whichwould qualify as a stand-alone monograph. Dr. Wyllie and hercolleagues understand that individuals with epilepsy frequentlyhave more issues than just seizures, and have devoted Part VI topsychosocial aspects of epilepsy.

The authors have crafted a highly integrated text, not an easytask when dealing with multiple authors. As such, the book iseasy to read and flows from one part to the other rather seam-lessly. While few readers will read the book cover to cover, theinterested student who wishes to review topics will find theprocess enjoyable as well as educationally rewarding.

While there are numerous textbooks dealing with epilepsyavailable, none do as much as Wyllie and colleagues in one vol-ume. Beautifully illustrated and attractively designed, the 5thvolume will undoubtedly retain its stature as the best book onepilepsy available. It is highly recommended for everyone inter-

ested in epilepsy, from the medical student to the seasonedepileptologist.Books like Wyllies Treatment of Epilepsy do not happen

without a great deal of work from the editors and authors.Kudos to all.

Gregory L. Holmes, MDProfessor of Neurology and Pediatrics

Chair, Department of NeurologyDartmouth Medical School Lebanon, New Hampshire

F O R E W O R D

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The fifth editions terrific associate editorsDr. GregoryCascino, Dr. Barry Gidal, and Dr. Howard Goodkineachbrought their own prodigious expertise, dedication, and goodhumor to the project. Ms. Jennifer Kowalak provided impec-cable editorial assistance, and Mr. Tom Gibbons at Lippincottshepherded the book smoothly through production. Mr. Dick

Blake, master teacher of dance and etiquette, remains aconstant inspiration and wellspring of creativity. And I oweeverything to Dr. Robert Wyllie, Physician-in-Chief of theCleveland Clinic Childrens Hospitalmy husband, dancingpartner, and father to our sons, Mr. Robert Wyllie andMr. James Wyllie, who make us proud.

A C K N O W L E D G M E N T S

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xvi

Section A Epidemiology and Natural History of Epilepsy

Chapter 1 Epidemiologic Aspects of Epilepsy 1Christine Linehan and Anne T. Berg

Chapter 2 The Natural History of Seizures 11D. Ding and W. A. Hauser

Section B Epileptogenesis, Genetics, and Epilepsy Substrates

Chapter 3 Experimental Models of Seizures and Mechanisms of Epileptogenesis 20T. A. Benke and A. R. Brooks-Kayal

Chapter 4 Genetics of the Epilepsies 34 Jocelyn Bautista and Anne Anderson

Chapter 5 Pictorial Atlas of Epilepsy Substrates 43Ajay Gupta, Richard A. Prayson, and Janet Reid

Chapter 6 Neurophysiologic Basis of the Electroencephalogram 60Erwin-Josef Speckmann, Christian E. Elger, and Ulrich Altrup

Chapter 7 Localization and Field Determination in Electroencephalography 73Richard C. Burgess

Chapter 8 Application of Electroencephalography in the Diagnosis of Epilepsy 93Katherine C. Nickels and Gregory D. Cascino

Chapter 9 Electroencephalographic Atlas of Epileptiform Abnormalities 103Soheyl Noachtar and Elaine Wyllie

Section A Epileptic Seizures

Chapter 10 Classification of Seizures 134Christoph Kellinghaus and Hans O. Lders

C O N T E N T S

PART I PATHOLOGIC SUBSTRATES AND MECHANISMS OF EPILEPTOGENESIS

Contributing Authors viPreface xiiiForeword xivAcknowledgments xv

PART II BASIC PRINCIPLES OF ELECTROENCEPHALOGRAPHY

PART III EPILEPTIC SEIZURES AND SYNDROMES

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Contents xvii

Appendix 10.A: Proposal for Revised Clinical and ElectrographicClassification of Epileptic Seizures 137Commission on Classification and Terminology of theInternational League Against Epilepsy (1981)

Chapter 11 Epileptic Auras 144Norman K. So

Chapter 12 Focal Seizures with Impaired Consciousness 153Lara Jehi and Prakash Kotagal

Chapter 13 Focal Motor Seizures, Epilepsia Partialis Continua,and Supplementary Sensorimotor Seizures 163Andreas V. Alexopoulos and Stephen E. Jones

Chapter 14 Generalized TonicClonic Seizures 184Tim Wehner

Chapter 15 Absence Seizures 192Alexis Arzimanoglou and Karine Ostrowsky-Coste

Chapter 16 Atypical Absence Seizures, Myoclonic, Tonic, and Atonic Seizures 202William O. Tatum IV

Chapter 17 Epileptic Spasms 216Ingrid Tuxhorn

Section B Epilepsy Conditions: Diagnosis and Treatment

Chapter 18 Classification of the Epilepsies 229Tobias Loddenkemper

Appendix 18.A: Proposal for Revised Classification of Epilepsiesand Epileptic Syndromes 235Commission on Classification and Terminology of theInternational League Against Epilepsy (1989)

Chapter 19 Idiopathic and Benign Partial Epilepsies of Childhood 243Elaine C. Wirrell, Carol S. Camfield, and Peter R. Camfield

Chapter 20 Idiopathic Generalized Epilepsy Syndromesof Childhood and Adolescence 258Stephen Hantus

Chapter 21 Progressive and Infantile Myoclonic Epilepsies 269Bernd A. Neubauer, Andreas Hahn, and Ingrid Tuxhorn

Chapter 22 Encephalopathic Generalized Epilepsy and LennoxGastautSyndrome 281S. Parrish Winesett and William O. Tatum IV

Chapter 23 Continuous Spike Wave of Slow Sleep and LandauKleffnerSyndrome 294Mohamad A. Mikati and Sara M. Winchester

Chapter 24 Epilepsy with Reflex Seizures 305Benjamin Zifkin and Frederick Andermann

Chapter 25 Rasmussen Encephalitis (Chronic Focal Encephalitis) 317Franois Dubeau

Chapter 26 Hippocampal Sclerosis and Dual Pathology 332Luigi DArgenzio and J. Helen Cross

Chapter 27 Malformations of Cortical Development and Epilepsy 339Ghayda Mirzaa, Ruben Kuzniecky, and Renzo Guerrini

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Chapter 28 Brain Tumors and Epilepsy 352Lara Jehi

Chapter 29 Post-Traumatic Epilepsy 361Stephan Schuele

Chapter 30 Epilepsy in the Setting of Cerebrovascular Disease 371Stephen Hantus, Neil Friedman, and Bernd Pohlmann-Eden

Chapter 31 Epilepsy in the Setting of Neurocutaneous Syndromes 375Ajay Gupta

Chapter 32 Epilepsy in the Setting of Inherited Metabolicand Mitochondrial Disorders 383Sumit Parikh, Douglas R. Nordli Jr., and Darryl C. De Vivo

Section C Diagnosis and Treatment of Seizures in Special Clinical Settings

Chapter 33 Neonatal Seizures 405Kevin E. Chapman, Eli M. Mizrahi, and Robert R. Clancy

Chapter 34 Febrile Seizures 428

Michael Duchowny

Chapter 35 Seizures Associated with Nonneurologic Medical Conditions 438Stephan Eisenschenk, Jean Cibula, and Robin L. Gilmore

Chapter 36 Epilepsy in Patients with Multiple Handicaps 451 John M. Pellock

Chapter 37 Epilepsy in the Elderly 458Ilo E. Leppik and Angela K. Birnbaum

Chapter 38 Status Epilepticus 469Howard P. Goodkin and James J. Riviello Jr.

Section D Differential Diagnosis of Epilepsy

Chapter 39 Psychogenic Nonepileptic Attacks 486

Selim R. Benbadis

Chapter 40 Other Nonepileptic Paroxysmal Disorders 495 John M. Pellock

Section A General Principles of Antiepileptic Drug Therapy

Chapter 41 Antiepileptic Drug Development andExperimental Models 506H. Steve White

Chapter 42 Pharmacokinetics and Drug Interactions 513Gail D. Anderson

Chapter 43 Initiation and Discontinuation of Antiepileptic Drugs 527Varda Gross Tsur, Christine Odell, and Shlomo Shinnar

Chapter 44 Hormones, Catamenial Epilepsy, Sexual Function,and Reproductive Health in Epilepsy 540Cynthia Harden and Robert Martinez

xviii Contents

PART IV ANTIEPILEPTIC MEDICATIONS

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Contents xix

Chapter 45 Treatment of Epilepsy During Pregnancy 557Page B. Pennell

Chapter 46 Bone Health and Fractures in Epilepsy 569Raj D. Sheth and Alison Pack

Chapter 47 Treatment of Epilepsy in the Setting of Renal and Liver Disease 576 Jane G. Boggs, Elizabeth Waterhouse, and Robert J. Delorenzo

Chapter 48 Monitoring for Adverse Effects of Antiepileptic Drugs 592L. James Willmore, John M. Pellock, and Andrew Pickens IV

Chapter 49 Pharmacogenetics of Antiepileptic Medications 601Tobias Loddenkemper, Tracy A. Glauser, and Diego A. Morita

Section B Specific Antiepileptic Medications and Other Therapies

Chapter 50 Carbamazepine and Oxcarbazepine 614Carlos A. M. Guerreiro and Marilisa M. Guerreiro

Chapter 51 Valproate 622Angela K. Birnbaum, Susan E. Marino, and Blaise F. D. Bourgeois

Chapter 52 Phenytoin and Fosphenytoin 630Diego A. Morita and Tracy A. Glauser

Chapter 53 Phenobarbital and Primidone 648Blaise F. D. Bourgeois

Chapter 54 Ethosuximide 657Andres M. Kanner, Tracy A. Glauser, and Diego A. Morita

Chapter 55 Benzodiazepines 668Lazor John Greenfield, Jr., Howard C. Rosenberg, and Elizabeth I. Tietz

Chapter 56 Gabapentin and Pregabalin 690Michael J. McLean and Barry E. Gidal

Chapter 57 Lamotrigine 704Frank Gilliam and Barry E. Gidal

Chapter 58 Topiramate 710William E. Rosenfeld

Chapter 59 Zonisamide 723Timothy E. Welty

Chapter 60 Levetiracetam 731 Joseph I. Sirven and Joseph F. Drazkowski

Chapter 61 Tiagabine 736Dana Ekstein and Steven C. Schachter

Chapter 62 Felbamate 741Edward Faught

Chapter 63 Vigabatrin 747Elizabeth A. Thiele

Chapter 64 Rufinamide 753Gregory Krauss and Stefanie Darnley

Chapter 65 Lacosamide 758Raj D. Sheth and Harry S. Abram

Chapter 66 Adrenocorticotropin and Steroids 763Cristina Y. Go and Orlando Carter Snead III

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Chapter 67 Newer Antiepileptic Drugs 771Deana M. Gazzola, Norman Delanty, and Jacqueline A. French

Chapter 68 Less Commonly Used Antiepileptic Drugs 779Basim M. Uthman

Chapter 69 The Ketogenic Diet 790Douglas R. Nordli Jr. and Darryl C. De Vivo

Chapter 70 Vagus Nerve Stimulation Therapy 797 James W. Wheless

Section A Identifying Surgical Candidates and Defining the Epileptogenic Zone

Chapter 71 Issues of Medical Intractability for Surgical Candidacy 810Patrick Kwan and Martin J. Brodie

Chapter 72 The Epileptogenic Zone 818

Anita Datta and Tobias LoddenkemperChapter 73 MRI in Evaluation for Epilepsy Surgery 828

Ahsan N.V. Moosa and Paul M. Ruggieri

Chapter 74 Video-EEG Monitoring in the Presurgical Evaluation 844 Jeffrey W. Britton

Chapter 75 Nuclear Imaging (PET, SPECT) 860William Davis Gaillard

Chapter 76 Magnetoencephalography 869Thomas Bast

Chapter 77 Diffusion Tensor Imaging (DTI) and EEG-Correlated fMRI 877Beate Diehl and Louis Lemieux

Section B Mapping Eloquent CortexChapter 78 Eloquent Cortex and the Role of Plasticity 887

Tobias Loddenkemper and Martin Staudt

Chapter 79 Functional MRI for Mapping Eloquent Cortex 899William Davis Gaillard

Chapter 80 The Intracarotid Amobarbital Procedure 906Rohit Das and Tobias Loddenkemper

Chapter 81 Intracranial Electroencephalography and Localization Studies 914Fernando L. Vale and Selim R. Benbadis

Section C Strategies for Epilepsy Surgery

Chapter 82 Surgical Treatment of Refractory Temporal Lobe Epilepsy 922Tonicarlo R. Velasco and Gary W. Mathern

Chapter 83 Focal and Multilobar Resection 937Paula M. Brna and Michael Duchowny

Chapter 84 Hemispherectomies, Hemispherotomies, and Other HemisphericDisconnections 948

Jorge A. Gonzlez-Martnez and William E. Bingaman

xx Contents

PART V EPILEPSY SURGERY

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Contents xxi

Chapter 85 Multifocal Resections or Focal Resectionsin Multifocal Epilepsy 957Howard L. Weiner, Jonathan Roth, and Stephen P. Kalhorn

Chapter 86 Nonlesional Cases 964Elson L. So

Chapter 87 Hypothalamic Hamartoma 973 John F. Kerrigan

Chapter 88 Corpus Callosotomy and Multiple Subpial Transection 984Michael C. Smith, Richard Byrne, and Andres M. Kanner

Chapter 89 Special Considerations in Children 993Ajay Gupta and Elaine Wyllie

Chapter 90 Outcome and Complications of Epilepsy Surgery 1007Lara Jehi, Jorge Martinez-Gonzalez, and William Bingaman

Chapter 91 Electrical Stimulation for the Treatment of Epilepsy 1021S. Matthew Stead and Gregory A. Worrell

Chapter 92 Cognitive Effects of Epilepsy and Antiepileptic Medications 1028Kimford J. Meador

Chapter 93 Psychiatric Comorbidity of Epilepsy 1037Beth Leeman and Steven C. Schachter

Chapter 94 Driving and Social Issues in Epilepsy 1051 Joseph F. Drazkowski and Joseph I. Sirven

Chapter 95 Achieving Health in Epilepsy: Strategies for Optimal Evaluationand Treatment 1057Frank G. Gilliam

Appendix Indications for Antiepileptic Drugs Sanctioned

by the United States Food and Drug Administration 1062Kay Kyllonen

Index 1064

PART VI PSYCHOSOCIAL ASPECTS OF EPILEPSY

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