Pediatric Epilepsy Diagnosis and Therapy - part 1 doc

Pediatric Epilepsy
Diagnosis and Therapy
Third Edition

Pediatric Epilepsy
EDITORS
JOHN M. PELLOCK, MD
Chairman, Division of Child Neurology
Vice Chair, Department of Neurology
Virginia Commonwealth University
Medical College of Virginia
Richmond, Virginia
BLAISE F.D. BOURGEOIS, MD
Professor of Neurology
Harvard Medical School
Director, Division of Epilepsy and Clinical Neurophysiology
Joseph J. Volpe Chair
Children’s Hospital Boston
Boston, Massachusetts
W. EDWIN DODSON, MD
Associate Vice Chancellor and Associate Dean
Professor of Pediatrics and Neurology
Washington University School of Medicine
St. Louis Children’s Hopsital
St. Louis, Missouri
A
SSOCIATE EDITORS
DOUGLAS R. NORDLI, JR., MD
Director, Children’s Memorial Epilepsy Center

Lorna S. and James P. Langdon Chair of Pediatric Epilepsy
Northwestern University’s Feinberg School of Medicine
Chicago, Illinois
RAMAN SANKAR, MD, PHD
Professor and Chief, Pediatric Neurology
Rubin Brown Distinguished Chair
David Geffen School of Medicine
Mattel Children’s Hospital
University of California, Los Angeles
Los Angeles, California
Diagnosis and Therapy
Third Edition
New York
Acquisitions Editor: R. Craig Percy
Cover Designer: Steven Pisano
Compositor and Indexing: Publication Services, Inc.
Printer: Sheridan Books, Inc.
Visit our website at www.demosmedpub.com
© 2008 Demos Medical Publishing, LLC. All rights reserved. This book is protected by copyright. No
part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means,
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permission of the publisher.
Library of Congress Cataloging-in-Publication Data
Pediatric epilepsy:diagnosis and therapy/edited by John M. Pellock, Blaise F.D. Bourgeois, W. Edwin
Dodson;associate editors, Douglas R. Nordli Jr., Raman Sankar.—3rd ed.
p.;cm.
Includes bibliographical references and index.
ISBN-13: 978-1-933864-16-7 (hardcover:alk. paper)
ISBN-10: 1-933864-16-8 (hardcover:alk. paper)
1. Epilepsy in children. I. Pellock, John M. II. Bourgeois, Blaise F.D. III. Dodson, W. Edwin

[DNLM: 1. Epilepsy. 2. Child. 3. Epilepsy—therapy. 4. Infant.WL 385 P3795 2008]
RJ496.E6P43 2008
618.92'853—dc22
2007032323
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Dedication

Contents
Preface xiii
Contributors xv
I BASIC MECHANISMS
Section Editor: Raman Sankar
1. Pathophysiology of Seizures and Epilepsy in the Immature Brain:
Cells, Synapses, and Circuits
Libor Velíšek and Solomon L. Moshé 1
2. Ion Channels, Membranes, and Molecules in Epilepsy
and Neuronal Excitability
Laxmikant S. Deshpande and Robert J. DeLorenzo 31
3. Channel Mutations in Epilepsy: A Neurodevelopmental Perspective
Edward C. Cooper 47
4. Metabolic and Pharmacologic Consequences of Seizures
Michael V. Johnston and John W. McDonald 65
5. Neuropathologic Substrates of Epilepsy
Caroline R. Houser and Harry V. Vinters 75
6. Epileptogenic Cerebral Cortical Malformations
Annapurna Poduri, Bernard S. Chang, and Christopher A. Walsh 101
7. Genetic Influences on the Risk for Epilepsy
Asuri N. Prasad and Chitra Prasad 117
vii
viii
II CLASSIFICATION, EPIDEMIOLOGY, ETIOLOGY, AND DIAGNOSIS
Section Editor: W. Edwin Dodson
8. Classification of Epilepsies in Childhood
Douglas R. Nordli, Jr. 137

9. Epidemiology of Epilepsy in Children
W. Allen Hauser and P. Nina Banerjee 147
10. An Approach to the Child with Paroxysmal Phenomena with
Emphasis on Nonepileptic Disorders
Arthur L. Prensky and Amir Pshytycky 165
11. Evaluating the Child with Seizure
Sejal Jain and Lawrence D. Morton 185
12. The Use of Electroencephalography in the
Diagnosis of Epilepsy in Childhood
Douglas R. Nordli, Jr. and Timothy A. Pedley 195
13. Basics of Neuroimaging in Pediatric Epilepsy
James M. Johnston, Matthew D. Smyth, and Robert C. McKinstry 213
III AGE-RELATED SYNDROMES
Section Editors: Blaise F. D. Bourgeois and Douglas R. Nordli, Jr.
NEWBORNS AND EARLY INFANCY
14. Neonatal Seizures
Eli M. Mizrahi 227
15. Severe Encephalopathic Epilepsy in Early Infancy
Shunsuke Ohtahara and Yasuko Yamatogi 241
INFANCY
16. Severe Encephalopathic Epilepsy in Infants:
Infantile Spasms (West Syndrome)
Richard A. Hrachovy and James D. Frost, Jr. 249
17. Myoclonic Epilepsies in Infancy and Early Childhood
Pierre Genton 269
18. Partial Epilepsies in Infancy
Kazuyoshi Watanabe 283
19. Febrile Seizures
Shlomo Shinnar and Tracy A. Glauser 293
CONTENTS

ix
20. Generalized Epilepsy with Febrile Seizures Plus (GEFS+)
Douglas R. Nordli, Jr. and John M. Pellock 303
CHILDHOOD
21. Lennox-Gastaut Syndrome
Diego A. Morita and Tracy A. Glauser 307
22. Childhood Absence Epilepsies
Phillip L. Pearl and Gregory L. Holmes 323
23. Benign Focal Epilepsies of Childhood
Colin D. Ferrie, Douglas R. Nordli, Jr., and Chrysostomos P. Panayiotopoulos 335
24. The Landau-Kleffner Syndrome and Epilepsy with
Continuous Spike-Waves during Sleep
James J. Riviello Jr. and Stavros Hadjiloizou 351
LATE CHILDHOOD AND ADOLESCENCE
25. Idiopathic Generalized Epilepsy of Adolescence
Reza Behrouz and Selim R. Benbadis 359
26. Progressive Myoclonus Epilepsies
Samuel F. Berkovic 367
VARIABLE AGE OF ONSET
27. Localization-Related Epilepsies: Simple Partial Seizures,
Complex Partial Seizures, and Rasmussen Syndrome
Prakash Kotagal 377
28. Selected Disorders Associated with Epilepsy
Lawrence D. Morton 387
IV GENERAL PRINCIPLES OF THERAPY
Section Editor: John M. Pellock
29. Treatment Decisions in Childhood Seizures
Shlomo Shinnar and Christine O’Dell 401
30. Comparative Anticonvulsant Profile and Proposed
Mechanisms of Action of Antiepileptic Drugs

H. Steve White and Karen S. Wilcox 413
31. Evidence-Based Medicine Issues Related to Drug Selection
Tracy A. Glauser and Diego A. Morita 429
32. Combination Drug Therapy: Monotherapy Versus Polytherapy
Blaise F. D. Bourgeois 441
CONTENTS
x
33. Adverse Effects of Antiepileptic Drugs
L. James Willmore, James W. Wheless, and John M. Pellock 449
34. Status Epilepticus and Acute Seizures
David J. Leszczyszyn and John M. Pellock 461
35. The Female Patient and Epilepsy
Mark S. Yerby 477
36. Teratogenic Effects of Antiepileptic Medications
Torbjörn Tomson and Dina Battino 489
37. Pharmacokinetic Principles of Antiepileptic Therapy in Children
W. Edwin Dodson 503
38. Dosage Form Considerations in the Treatment of Pediatric Epilepsy
William R. Garnett and James C. Cloyd 515
39. Principles of Drug Interactions: Implications for Treatment
with Antiepileptic Drugs
Barry E. Gidal 535
V ANTIEPILEPTIC DRUGS AND KETOGENIC DIET
Section Editors: Blaise F. D. Bourgeois and Raman Sankar
40. ACTH and Steroids
Rajesh RamachandranNair and O. Carter Snead, III 543
41. Benzodiazepines
Kevin Farrell and Aspasia Michoulas 557
42. Carbamazepine and Oxcarbazepine
W. Edwin Dodson 567

43. Ethosuximide, Methsuximide, and Trimethadione
Blaise F. D. Bourgeois 579
44. Felbamate
Blaise F. D. Bourgeois 585
45. Gabapentin and Pregabalin
Gregory L. Holmes and Philip L. Pearl 593
46. Lamotrigine
John M. Pellock 603
47. Levetiracetam
Raman Sankar and W. Donald Shields 611
48. Barbiturates and Primidone
Robert S. Rust 621
CONTENTS
xi
49. Phenytoin and Related Drugs
W. Edwin Dodson 639
50. Sulthiame
Dietz Rating, Nicole Wolf, and Thomas Bast 653
51. Tiagabine
Shlomo Shinnar, Richard Civil, and Kenneth W. Sommerville 661
52. Topiramate
Tracy A. Glauser 671
53. Valproate
Blaise F. D. Bourgeois 685
54. Vigabatrin
Günter Krämer and Gabriele Wohlrab 699
55. Vitamins, Herbs, and Other Alternative Therapies
Orrin Devinsky, Daniel Miles, and Josiane LaJoie 711
56. Zonisamide
John F. Kerrigan and John M. Pellock 727

57. The Ketogenic Diet
Douglas R. Nordli, Jr. and Darryl C. De Vivo 739
58. Inflammation, Epilepsy, and Anti-Inflammatory Therapies
Stéphane Auvin and Raman Sankar 751
59. Antiepileptic Drugs in Development
John R. Pollard and Jacqueline A. French 759
VI EPILEPSY SURGERY AND VAGUS NERVE STIMULATION
Section Editor: Douglas R. Nordli, Jr.
60. Surgical Evaluation
Michael Duchowny 769
61. Advanced Neuroimaging: PET-MRI Fusion
and Diffusion Tensor Imaging
Noriko Salamon 785
62. Surgical Treatment of Therapy-Resistant Epilepsy in Children
Gary W. Mathern and Olivier Delalande 791
63. Outcome of Epilepsy Surgery in Childhood
Shekhar Patil, J. Helen Cross, and William Harkness 801
64. Vagus Nerve Stimulation Therapy in Pediatric Patients: Use
and Effectiveness
James W. Wheless 811
CONTENTS
xii
VII PSYCHOSOCIAL ASPECTS
Section Editor: W. Edwin Dodson
65. Economics of Pediatric Epilepsy
Charles E. Begley 831
66. Quality of Life in Children with Epilepsy
Joan K. Austin and Nancy Santilli 837
67. Epilepsy, Cerebral Palsy, and IQ
W. Edwin Dodson 847

68. Academic Deficits and Interventions in Pediatric Epilepsy
Caroline E. Bailey and Rochelle Caplan 865
69. Cognitive Side Effects of Antiepileptic Drugs
David E. Mandelbaum and Christine L. Trask 873
Index 883
CONTENTS
As with the first and second editions, the goal of this
third edition of Pediatric Epilepsy: Diagnosis and Therapy
is to assist all professionals involved in the care of pediat-
ric patients with seizures and epilepsy. Our goal continues
to be the perfect result: no seizures, no side effects, and
no stigma to limit these children from achieving their
full potential.
The scope and depth of coverage of this book remains
unique in its field. We have again tried to balance discus-
sions of practical medical management with the scientific
basis of epilepsy and its treatment in a clear and concise
manner. The book focuses on the special issues of children
with epilepsy and is intended as both a practical guide and
a reference for clinicians and investigators. With many
more options for the treatment of epilepsy—including new
antiepileptic drugs (AEDs), vagus nerve stimulation, the
reintroduction of the ketogenic diet, increased emphasis
on quality of life, as well as improved presurgical evalua-
tion and surgical intervention—hope for a more normal
life for all children with epilepsy should continue to grow.
To accomplish all the new goals set for this third edition,
the previous editors asked Drs. Douglas R. Nordli and
Raman Sankar to join them as associate editors.
Since the publication of the second edition, there

has been a rapid expansion of basic knowledge, diagnos-
tic techniques, and treatments affecting the management
of epilepsy, including advances in basic neurosciences,
genetics, definition of syndromes, as well as medical and
surgical therapeutic approaches. Because of the increasing
familiarity and refinement of knowledge related to the
concept of epilepsy syndromes, a new separate section
Preface
has been added to this third edition. This section consists
of an expanded and comprehensive coverage of the syn-
dromes by age of onset, taking into account the difficul-
ties that can be encountered in making a fixed diagnosis
of a seizure type or epilepsy syndrome in young infants.
Although the precise diagnosis of epilepsy has become
more challenging and complex, the enhanced specificity
of the final diagnosis will continue to improve therapeutic
and prognostic accuracy. The diagnostic process has been
further improved by the growing knowledge of metabolic
disturbances, disease processes, and genetics of various
forms of epilepsy. This has led to an ever-expanding avail-
ability of new diagnostic tests, especially those related to
DNA analysis. Although the greater choice of diagnostic
testing does not always yield an etiology in every patient,
those patients without established etiology still have more
and better therapeutic options. There has been further
growth in the knowledge about clinical pharmacology of
AEDs. In particular, experience and comfort have grown
with the AEDs that had just been released at the time of
the second edition, with recognition of new indications
for some of these drugs. Throughout the discussion of

individual drugs, available knowledge is discussed regard-
ing their specific use and pharmacokinetics in newborns,
infants, older children, and adolescents. Adverse effects
are also covered, to include newer aspects as well as age-
related, gender-related, and pregnancy-related issues.
Epilepsy surgery has become one of the widely applied
standard therapeutic approaches to pediatric epilepsy,
and it has now truly been incorporated into the treat-
ment paradigms.
xiii
xiv
In this third edition, every chapter either has been
markedly updated or is a newly written chapter that
was not included in the second edition. In the initial sec-
tion on basic mechanisms of epilepsy, a new chapter by
Dr. Edward Cooper on the epileptic channelopathies has
been added because of the rapid and clinically relevant
expansion of knowledge in this area during the past few
years. Coverage of epileptogenic cerebral cortical mal-
formations has been enhanced by the contribution of
Drs. Christopher Walsh, Ann Poduri, and Bernard Chang.
A new section on age-related syndromes has been cre-
ated. This section is divided into groups of syndromes
by age of onset and provides a more comprehensive and
detailed coverage by several international authorities
in the field, such as Drs. Shunsuke Ohtahara, Richard
Hrachovy, Kazuyoshi Watanabe, Pierre Genton, Shlomo
Shinnar, Tracy Glauser, Gregory Holmes, Chrysostomos
Panayiotopoulos, Prakash Kotagal, and Samuel Berkovic.
All of the chapters in this section now follow a unified

structure. The section on general principles of therapy
now includes a discussion of the emerging evidence-
based approach to AED selection by Dr. Tracy Glauser.
The issues of fetal effects of epilepsy and fetal effects of
AEDs are covered separately by Drs. Mark Yerby and
Torbjörn Tomson.
Systematic coverage of individual drugs and other
medical treatment modalities was already quite extensive
in the second edition but has now been enhanced and
expanded to cover the newer drugs not covered previ-
ously, as well as updated to include new information on
the previously discussed drugs. A chapter on sulthiame by
Dr. Dietz Rating has been added, because of the unique role
of this drug in the treatment of the common syndrome of
benign rolandic epilepsy. Other new chapters cover vita-
mins, dietary considerations, and alternative therapies
(Dr. Orrin Devinsky); immunotherapy (Dr. Raman Sankar);
and AEDs in development (Dr. Jacqueline French). The
section on surgical treatment contains updated coverage of
neurophysiologic evaluation (including magnetoencepha-
lography), advanced imaging, surgical procedures, and out-
comes, in addition to an update on vagus nerve stimulation.
The section on psychosocial aspects has been expanded
and includes chapters on costs of pediatric epilepsy, quality
of life, intelligence, co-morbidities, and educational place-
ment, as well as cognitive side effects of AEDs.
We would be remiss in introducing this third
edition without acknowledging the contribution of
several of the previous authors who have now died.
Drs. Kiffin Penry and Fritz Dreifuss, two of the founding

fathers of pediatric epilepsy in the United States, have
left us to carry on their work. Dr. Eric Lothman died
quite prematurely, but his contribution to the under-
standing of the pathophysiology of seizures and epilepsy
remains current even in this edition and will do so for
years to come. In honoring these and others who have
encouraged and guided our careers, we hope that this
book meets the needs of those who care for children
with epilepsy as well as the children and families who
have to deal with seizures.
For some, epilepsy will be a transient and distant
memory, while for others epilepsy is an ever-present bur-
den. Evaluating and treating these children in the most
appropriate and efficient fashion while avoiding adverse
cognitive and psychosocial effects remains both challeng-
ing and rewarding, and it requires state-of-the-art knowl-
edge. We hope that you will find such knowledge in this
book, and we hope that this third edition of Pediatric
Epilepsy: Diagnosis and Therapy will help you and your
colleagues provide state-of-the-art care to your patients
and their families.
John M. Pellock, MD
Blaise F.D. Bourgeois, MD
W. Edwin Dodson, MD
Douglas R. Nordli, Jr., MD
Raman Sankar, MD, PhD
PREFACE
Contributors
Joan K. Austin, DNS, RN, FAAN
Distinguished Professor and Sally Reahard Chair

Indiana University School of Nursing
Indianapolis, Indiana
Chapter 66: Quality of Life in Children with
Epilepsy
Stéphane Auvin, MD, PhD
Department of Pediatric Neurology
Lille University Hospital
Pharmacology Laboratory
Lille Medical School
Lille, France
Chapter 58: Inflammation, Epilepsy, and Anti-
Inflammatory Therapies
Caroline E. Bailey, PhD
Assistant Professor
Department of Human Services
California State University
Fullerton, California
Chapter 68: Academic Deficits and Interventions in
Pediatric Epilepsy
P. Nina Banerjee, PhD
Gertrude H. Sergievsky Center
College of Physicians and Surgeons
Columbia University
New York, New York
Chapter 9: Epidemiology of Epilepsy in Children
Thomas Bast, MD
Department of Paediatric Neurology
Epilepsy Centre
Children’s Hospital
University of Heidelberg

Heidelberg, Germany
Chapter 50: Sulthiame
Dina Battino, MD
Fondazione I.R.C.C.S. Istituto Neurologico “Carlo Besta”
Milan, Italy
Chapter 36: Teratogenic Effects of Antiepileptic
Medications
Charles E. Begley
Co-Director, Center for Health Services Research
University of Texas Health Science Center at Houston
Houston, Texas
Chapter 65: Economics of Pediatric Epilepsy
Reza Behrouz, DO
Assistant Professor
Department of Neurology
University of South Florida College of Medicine
Tampa, Florida
Chapter 25: Idiopathic Generalized Epilepsy of
Adolescence
Selim R. Benbadis, MD
Professor and Director
Comprehensive Epilepsy Program
Departments of Neurology and Neurosurgery
University of South Florida and Tampa General Hospital
Tampa, Florida
Chapter 25: Idiopathic Generalized Epilepsy of
Adolescence
xv
CONTRIBUTORS
xvi

Samuel F. Berkovic, MD, FRS
Director, Epilepsy Research Centre
Department of Medicine
University of Melbourne
West Heidelberg, Victoria, Australia
Chapter 26: Progressive Myoclonus Epilepsies
Blaise F. D. Bourgeois, MD
Professor of Neurology
Harvard Medical School
Director, Division of Epilepsy and
Clinical Neurophysiology
Joseph J. Volpe Chair
Children’s Hospital Boston
Boston, Massachusetts
Part III: Age-Related Syndromes, Section Editor
Part V: Antiepileptic Drugs and Ketogenic Diet, Section
Editor
Chapter 32: Combination Drug Therapy:
Monotherapy Versus Polytherapy
Chapter 43: Ethosuximide, Methsuximide, and
Trimethadione
Chapter 44: Felbamate
Chapter 53: Valproate
Rochelle Caplan, MD
Professor
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, California
Chapter 68: Academic Deficits and Interventions in
Pediatric Epilepsy

Bernard S. Chang, MD, MMSc
Assistant Professor of Neurology
Harvard Medical School
Comprehensive Epilepsy Center
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Chapter 6: Epileptogenic Cerebral Cortical
Malformations
Richard Civil
Vice President, Global Product Safety
Cephalon, Inc.
West Chester, Pennsylvania
Chapter 51: Tiagabine
James C. Cloyd, MD
Professor and Lawrence C. Weaver Endowed
Chair–Orphan Drug Development
Director, Center for Orphan Drug Research
College of Pharmacy
University of Minnesota
Minneapolis, Minnesota
Chapter 38: Dosage Form Considerations in the
Treatment of Pediatric Epilepsy
Edward C. Cooper, MD, PhD
Assistant Professor
Department of Neurology
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 3: Channel Mutations in Epilepsy: A
Neurodevelopmental Perspective
J. Helen Cross, MB, ChB, PhD, FRCP, FRCPCH

Professor of Pediatric Neurology
Neurosciences Unit
UCL–Institute of Child Health
Great Ormond Street Hospital for Children
NHS Trust
London, United Kingdom
Chapter 63: Outcome of Epilepsy Surgery in
Childhood
Olivier Delalande
Service de Neurochirurgie Pédiatrique
Fondation Opthalmologique A. de Rothschild
Paris, France
Chapter 62: Surgical Treatment of Therapy-Resistant
Epilepsy in Children
Robert J. DeLorenzo, MD, PhD, MPH
George Bliley Professor of Neurology
Professor of Pharmacology and Toxicology
Professor of Molecular Biophysics and
Biochemistry
Virginia Commonwealth University
Richmond, Virginia
Chapter 2: Ion Channels, Membranes,
and Molecules in Epilepsy and
Neuronal Excitability
Laxmikant S. Deshpande, MPharm, PhD
Research Scientist
Department of Neurology
Virginia Commonwealth University
Richmond, Virginia
Chapter 2: Ion Channels, Membranes,

and Molecules in Epilepsy and
Neuronal Excitability
Orrin Devinsky, MD
Professor of Neurology, Neurosurgery and
Psychiatry
New York University School of Medicine
New York, New York
Chapter 55: Vitamins, Herbs, and Other Alternative
Therapies
Darryl C. De Vivo, MD
Sidney Carter Professor of Neurology
Professor of Pediatrics
College of Physicians and Surgeons
Columbia University
New York, New York
Chapter 57: The Ketogenic Diet
CONTRIBUTORS
xvii
W. Edwin Dodson, MD
Associate Vice Chancellor and Associate Dean
Professor of Pediatrics and Neurology
Washington University School of Medicine
St. Louis Children’s Hospital
St. Louis, Missouri
Part II: Classification, Epidemiology, Etiology, and
Diagnosis, Section Editor
Part VII: Psychosocial Aspects, Section Editor
Chapter 37: Pharmacokinetic Principles of
Antiepileptic Therapy in Children
Chapter 42: Carbamazepine and Oxcarbazepine

Chapter 49: Phenytoin and Related Drugs
Chapter 67: Epilepsy, Cerebral Palsy, and IQ
Michael Duchowny, MD
Professor of Clinical Neurology
University of Miami School of Medicine
Miami Children’s Hospital
Miami, Florida
Chapter 60: Surgical Evaluation
Kevin Farrell, MB, ChB, FRCPC
Professor
Division of Child Neurology
University of British Columbia
British Columbia’s Children’s Hospital
Vancouver, British Columbia, Canada
Chapter 41: Benzodiazepines
Colin D. Ferrie, MB, ChB, MD, MRCP, FRCPCH
Consultant Paediatric Neurologist
Leeds General Infirmary
Leeds, United Kingdom
Chapter 23: Benign Focal Epilepsies of Childhood
Jacqueline A. French, MD
Professor
Department of Neurology
New York University Medical School
New York, New York
Chapter 59: Antiepileptic Drugs in Development
James D. Frost, Jr., MD
Professor of Neurology and Neuroscience
Peter Kellaway Section of Neurophysiology
Department of Neurology

Baylor College of Medicine
Houston, Texas
Chapter 16: Severe Encephalopathic Epilepsy in
Infants: Infantile Spasms (West Syndrome)
William R. Garnett, PharmD
Professor of Pharmacy and Neurology
Department of Pharmacy
Virginia Commonwealth University
Richmond, Virginia
Chapter 38: Dosage Form Considerations in the
Treatment of Pediatric Epilepsy
Pierre Genton, MD
Hôpital Henri Gastaut–Centre Saint Paul
Marseille, France
Chapter 17: Myoclonic Epilepsies in Infancy and
Early Childhood
Barry E. Gidal, PharmD
Professor
University of Wisconsin
School of Pharmacy and Department of Neurology
Madison, Wisconsin
Chapter 39: Principles of Drug Interactions:
Implications for Treatment with Antiepileptic Drugs
Tracy A. Glauser, MD
Director, Comprehensive Epilepsy Program
Cincinnati Children’s Hospital Medical Center
Professor of Pediatrics and Neurology
University of Cincinnati College of Medicine
Cincinnati, Ohio
Chapter 19: Febrile Seizures

Chapter 21: Lennox-Gestaut Syndrome
Chapter 31: Evidence-Based Medicine Issues Related to
Drug Selection
Chapter 52: Topiramate
Stavros Hadjiloizou, MD
Division of Epilepsy and Clinical Neurophysiology
Department of Neurology
Children’s Hospital Boston
Instructor of Neurology
Harvard Medical School
Boston, Massachusetts
Chapter 24: The Landau-Kleffner Syndrome and
Epilepsy with Continuous Spike-Waves during Sleep
William Harkness, ChB, FRCS
Consultant Paediatric Neurosurgeon
Department of Neurosurgery
National Hospital for Neurosurgery and Neurology
London, United Kingdom
Chapter 63: Outcome of Epilepsy Surgery in
Childhood
W. Allen Hauser, MD
Professor of Neurology and Epidemiology
Gertrude H. Sergievsky Center
College of Physicians and Surgeons and Mailman
School of Public Health
Columbia University
New York, New York
Chapter 9: Epidemiology of Epilepsy in Children
Gregory L. Holmes, MD
Professor of Neurology and Pediatrics

Chairman, Department of Neurology
Neuroscience Center at Dartmouth
Dartmouth Medical School
Lebanon, New Hampshire
Chapter 22: Childhood Absence Epilepsies
Chapter 45: Gabapentin and Pregabalin
CONTRIBUTORS
xviii
Carolyn R. Houser, MD
Professor of Neurobiology
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, California
Chapter 5: Neuropathologic Substrates of Epilepsy
Richard A. Hrachovy, MD
Professor of Neurology
Peter Kellaway Section of Neurophysiology
Department of Neurology
Baylor College of Medicine
Michael E. DeBakey Veterans Affairs Medical Center
Houston, Texas
Chapter 16: Severe Encephalopathic Epilepsies in
Infants: Infantile Spasms (West Syndrome)
Sejal V. Jain, MD
Neurophysiology Fellow
Department of Clinical Neurophysiology
Virginia Commonwealth University
Richmond, Virginia
Chapter 11: Evaluating the Child with Seizure
James M. Johnston, MD

Department of Neurosurgery
Washington University–St. Louis
St. Louis, Missouri
Chapter 13: Basics of Neuroimaging in Pediatric Epilepsy
Michael V. Johnston, MD
Chief Medical Officer
Kennedy Krieger Institute
Professor of Neurology, Pediatrics and Physical
Medicine and Rehabilitation
The Johns Hopkins School of Medicine
Baltimore, Maryland
Chapter 4: Metabolic and Pharmacologic
Consequences of Seizures
John F. Kerrigan, MD
Assistant Professor of Clinical Neurology and Pediatrics
University of Arizona College of Medicine, Phoenix
Director of Pediatric Epilepsy
Barrow Neurological Institute
Phoenix, Arizona
Chapter 56: Zonisamide
Prakash Kotagal, MD
Head, Pediatric Epilepsy Section
Epilepsy Center
Cleveland Clinic Neurological Institute
Cleveland, Ohio
Chapter 27: Localization-Related Epilepsies:
Simple Partial Seizures, Complex Partial Seizures,
and Rasmussen Syndrome
Günter Krämer, MD
Medical Director

Swiss Epilepsy Center
Zurich, Switzerland
Chapter 54: Vigabatrin
Josiane LaJoie, MD
Assistant Professor of Neurology and Pediatrics
New York University School of Medicine
New York, New York
Chapter 55: Vitamins, Herbs, and Other Alternative
Therapies
David J. Leszczyszyn, MD, PhD
Medical Director, Center for Sleep Medicine
Assistant Professor, Division of Child Neurology
Virginia Commonwealth University
Richmond, Virginia
Chapter 34: Status Epilepticus and Acute Seizures
David E. Mandelbaum, MD, PhD
Professor of Clinical Neurosciences and Pediatrics
Warren Alpert Medical School of Brown University
Director of Child Neurology and the Children’s
Neurodevelopment Center
Hasbro Children’s Hospital
Providence, Rhode Island
Chapter 69: Cognitive Side Effects of
Antiepileptic Drugs
Gary W. Mathern, MD
Professor
Department of Neurosurgery, The Mental Retardation
Research Center, and The Brain Research Institute
David Geffen School of Medicine
University of California, Los Angeles

Los Angeles, California
Chapter 62: Surgical Treatment of Therapy-Resistant
Epilepsy in Children
John W. McDonald, MD, PhD
Director, The International Center for
Spinal Cord Injury
Kennedy-Krieger Institute
Department of Neurology
The Johns Hopkins School of Medicine
Baltimore, Maryland
Chapter 4: Metabolic and Pharmocologic
Consequences of Seizures
Robert C. McKinstry, MD, PhD
Associate Professor of Radiology and Pediatrics
Chief, Pediatric Radiology and Pediatric
Neuroradiology
St. Louis Children’s Hospital
Washington University
St. Louis, Missouri
Chapter 13: Basics of Neuroimaging in Pediatric
Epilepsy
CONTRIBUTORS
xix
Aspasia Michoulas, BSc Pharm, MD
Neurology Fellow
Division of Child Neurology
University of British Columbia
British Columbia’s Children’s Hospital
Vancouver, British Columbia, Canada
Chapter 41: Benzodiazepines

Daniel Miles, MD
Assistant Professor of Neurology and Pediatrics
New York University School of Medicine
New York, New York
Chapter 55: Vitamins, Herbs, and Other Alternative
Therapies
Eli M. Mizrahi, MD
Head, Peter Kellaway Section of Neurophysiology
Vice Chairman, Department of Neurology
Director, Baylor Comprehensive Epilepsy Center
Professor of Neurology and Pediatrics
Baylor College of Medicine
Houston, Texas
Chapter 14: Neonatal Seizures
Diego A. Morita, MD
Assistant Professor of Pediatrics and Neurology
Division of Neurology
Department of Pediatrics
Cincinnati Children’s Hospital Medical Center
University of Cincinnati College of Medicine
Cincinnati, Ohio
Chapter 21: Lennox-Gastaut Syndrome
Chapter 31: Evidence-Based Medicine Issues Related to
Drug Selection
Lawrence D. Morton, MD
Medical Director, Clinical Neurophysiology
Associate Professor, Neurology and Pediatrics
Virginia Commonwealth University
Richmond, Virginia
Chapter 11: Evaluating the Child with Seizures

Chapter 28: Selected Disorders Associated with
Epilepsy
Solomon L. Moshé, MD
Professor of Neurology, Neuroscience and Pediatrics
Vice Chair, Department of Neurology
Albert Einstein College of Medicine
Bronx, New York
Chapter 1: Pathophysiology of Seizures and Epilepsy in
the Immature Brain: Cells, Synapses, and Circuits
Douglas R. Nordli, Jr., MD
Director, Children’s Memorial Epilespy Center
Lorna S. and James P. Langdon Chair of Pediatric
Epilepsy
Northwestern University’s Feinberg School of Medicine
Chicago, Illinois
Part III: Age-Related Syndromes, Section Editor
Part VI: Epilepsy Surgery and Vagus Nerve Stimulation,
Section Editor
Chapter 8: Classification of Epilepsies of Childhood
Chapter 12: The Use of Encephalography in the
Diagnosis of Epilepsy in Childhood
Chapter 20: Generalized Epilepsy with Febrile Seizures
Plus (GEFSϩ)
Chapter 23: Benign Focal Epilepsies of Childhood
Chapter 57: The Ketogenic Diet
Christine O’Dell, RN, MSN
Critical Nurse Specialist
Department of Neurology
Montefiore Medical Center
Bronx, New York

Chapter 29: Treatment Decisions in
Childhood Seizures
Shunsuke Ohtahara, MD, PhD
Professor of Child Neurology, Emeritus
Department of Child Neurology
Okayama University
Graduate School of Medicine, Dentistry and
Pharmaceutical Sciences
Okayama, Japan
Chapter 15: Severe Encephalopathic Epilepsy in
Early Infancy
Chrysostomos P. Panayiotopoulos, MD, PhD, FRCP
Consultant Emeritus
Department of Clinical Neurophysiology and
Epilepsies
St. Thomas’ Hospital
London, United Kingdom
Chapter 23: Benign Focal Epilepsies of
Childhood
Shekhar Patil, MD, DM
Epilepsy Fellow
UCL–Institute of Child Health
Great Ormond Street Hospital for Children
NHS Trust
London, United Kingdom
Chapter 63: Outcome of Epilepsy Surgery in
Childhood
CONTRIBUTORS
xx
Phillip L. Pearl, MD

Department of Neurology
Children’s National Medical Center
George Washington University School of Medicine
Washington, DC
Chapter 22: Childhood Absence Epilepsies
Chapter 45: Gabapentin and Pregabalin
Timothy A. Pedley, MD
Henry and Lucy Moses Professor of Neurology
Chairman, Department of Neurology
Columbia University
New York, New York
Chapter 12: The Use of Encephalography in the
Diagnosis of Epilepsy in Childhood
John M. Pellock, MD
Chairman, Division of Child Neurology
Vice Chair, Department of Neurology
Virginia Commonwealth University
Richmond, Virginia
Part VI: General Principles of Therapy, Section Editor
Chapter 20: Generalized Epilepsy with Febrile Seizures
Plus (GEFSϩ)
Chapter 33: Adverse Effects of Antiepileptic Drugs
Chapter 34: Status Epilepticus and Acute Seizures
Chapter 46: Lamotrigine
Chapter 56: Zonisamide
Annapurna Poduri, MD
Assistant in Neurology
Division of Epilepsy and Clinical Neurophysiology
Children’s Hospital Boston
Boston, Massachusetts

Chapter 6: Epileptogenic Cerebral Cortical
Malformations
John R. Pollard, MD
Assistant Professor
Department of Neurology
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 59: Antiepileptic Drugs in Development
Asuri N. Prasad, MBBS, MD, FRCPC, FRCPE
Associate Professor
Departments of Pediatrics and Clinical Neurosciences
University of Western Ontario
London, Ontario, Canada
Chapter 7: Genetic Influences on the Risk for Epilepsy
Chitra Prasad, MD, FRCPC, FCCMG, FACMG
Associate Professor
Section of Genetics, Metabolism
Department of Pediatrics
University of Western Ontario
London, Ontario, Canada
Chapter 7: Genetic Influences on the Risk for Epilepsy
Arthur L. Prensky, MD
Professor of Neurology and Pediatrics, Emeritus
Division of Pediatric Neurology
Washington University School of Medicine
St. Louis, Missouri
Chapter 10: An Approach to the Child with
Paroxysmal Phenomena with Emphasis on
Nonepileptic Disorders
Amir Pshytycky, MD

Neurophysiology and Epilepsy Fellow
Department of Neurology
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
Chapter 10: An Approach to the Child with
Paroxysmal Phenomena with Emphasis on
Nonepileptic Disorders
Rajesh RamachandranNair, MD
Assistant Professor
McMaster University
Pediatric Epileptologist
McMaster Children’s Hospital
Hamilton, Ontario, Canada
Chapter 40: ACTH and Steroids
Dietz Rating, MD
Professor of Pediatrics
Director, Department of Paediatric Neurology
Epilepsy Centre
Children’s Hospital
University of Heidelberg
Heidelberg, Germany
Chapter 50: Sulthiame
James J. Riviello, Jr., MD
George Peterkin Endowed Chair in Pediatrics
Professor of Pediatrics
Department of Pediatrics
Section of Neurology and Developmental Neuroscience
Baylor College of Medicine
The Blue Bird Circle Clinic for Pediatric Neurology
Chief of Neurophysiology

Texas Children’s Hospital
Houston, Texas
Chapter 24: The Landau-Kleffner Syndrome and
Epilepsy with Continuous Spike-Waves during Sleep
Robert S. Rust, MA, MD
Thomas E. Worrell, Jr., Professor of Epileptology and
Neurology
Professor of Pediatrics
The University of Virginia School of Medicine
Co-Director, F. E. Dreifuss Comprehensive Epilepsy
and Child Neurology Clinics
Charlottesville, Virginia
Chapter 48: Barbiturates and Related Drugs
CONTRIBUTORS
xxi
Noriko Salamon, MD
Assistant Professor of Radiology
Department of Radiology
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, California
Chapter 61: Advanced Neuroimaging: PET-MRI
Fusion and Diffusion Tensor Imaging
Raman Sankar, MD, PhD
Professor and Chief, Pediatric Neurology
Rubin Brown Distinguished Chair
David Geffen School of Medicine
Mattel Children’s Hospital
University of California, Los Angeles
Los Angeles, California

Part I: Basic Mechanisms, Section Editor
Part V: Antiepileptic Drugs and Ketogenic Diet,
Section Editor
Chapter 47: Levetiracetam
Chapter 58: Inflammation, Epilepsy, and Anti-
Inflammatory Therapies
Nancy Santilli, MSN, PNP, FAAN
Vice President of Commercial Strategy and
Portfolio Planning
Endo Pharmaceuticals, Inc.
Chadds Ford, Pennsylvania
Chapter 66: Quality of Life in Children with Epilepsy
W. Donald Shields, MD
Professor of Neurology and Pediatrics
David Geffen School of Medicine
University of California, Los Angeles
Los Angeles, California
Chapter 47: Levetiracetam
Shlomo Shinnar, MD, PhD
Professor of Neurology, Pediatrics and Epidemiology
and Population Health
Hyman Climenko Professor of Neuroscience Research
Director, Comprehensive Epilepsy Management Center
Montefiore Medical Center,
Albert Einstein College of Medicine
Bronx, New York
Chapter 19: Febrile Seizures
Chapter 29: Treatment Decisions in Childhood Seizures
Chapter 51: Tiagabine
Matthew D. Smyth, MD, FACS, FAAP

Assistant Professor of Neurosurgery and Pediatrics
Director, Pediatric Epilepsy Surgery Program
St. Louis Children’s Hospital
Washington University
St. Louis, Missouri
Chapter 13: Basics of Neuroimaging in
Pediatric Epilepsy
O. Carter Snead III, MD
Head, Division Of Neurology
Department Pediatrics
Hospital For Sick Children
University of Toronto
Toronto, Ontario, Canada
Chapter 40: ACTH and Steroids
Kenneth W. Sommerville, MD
Vice President, Area of Neurology
Schwarz Biosciences, Inc.
UCB
Adjunct Assistant Professor of Medicine
Duke University
Raleigh, North Carolina
Chapter 51: Tiagabine
Torbjörn Tomson, MD, PhD
Professor of Neurology
Department of Clinical Neuroscience
Karolinska Institutet
Stockholm, Sweden
Chapter 36: Teratogenic Effects of Antiepileptic
Medications
Christine L. Trask, PhD

Clinical Assistant Professor
Department of Psychiatry and Human Behavior
Warren Alpert Medical School of Brown University
Pediatric Neuropsychologist
Rhode Island Hospital
Providence, Rhode Island
Chapter 69: Cognitive Side Effects of Antiepileptic
Drugs
Libor Velíšek, MD, PhD
Associate Professor of Neurology and Neuroscience
Albert Einstein College of Medicine
Bronx, New York
Chapter 1: Pathophysiology of Seizures and Epilepsy in
the Immature Brain: Cells, Synapses, and Circuits
Harry V. Vinters, MD, FRCP(C), FCAP
Professor of Pathology and Laboratory Medicine
and Neurology
Daljit S. and Elaine Sakaria Chair in Diagnostic
Medicine
David Geffen School of Medicine
University of California, Los Angeles
Chief, Section of Neuropathology
UCLA Medical Center
Los Angeles, California
Chapter 5: Neuropathologic Substrates of Epilepsy
CONTRIBUTORS
xxii
Christopher A. Walsh, MD, PhD
Chief, Division of Genetics
Children’s Hospital Boston

Howard Hughes Medical Institute
Beth Israel Deaconess Medical Center
Bullard Professor of Neurology
Harvard Medical School
Boston, Massachusetts
Chapter 6: Epileptogenic Cerebral Cortical
Malformations
Kazuyoshi Watanabe
Faculty of Medical Welfare
Aichi Shukutoku University
Chikusa-ku, Nagoya, Japan
Chapter 18: Partial Epilepsies in Infancy
James W. Wheless, MD
Professor and Chief of Pediatric Neurology
LeBonheur Chair in Pediatric Neurology
University of Tennessee Health Science Center
Director, LeBonheur Comprehensive Epilepsy Program
and Neuroscience Institute
LeBonheur Children’s Medical Center
Memphis, Tennessee
Chapter 33: Adverse Effects of Antiepileptic Drugs
Chapter 64: Vagus Nerve Stimulation Therapy in
Pediatric Patients: Use and Effectiveness
H. Steve White, PhD
Professor and Director
Anticonvulsant Drug Development Program
Department of Pharmacology and Toxicology
University of Utah
Salt Lake City, Utah
Chapter 30: Comparative Anticonvulsant Profile and

Proposed Mechanisms of Action of Antiepileptic
Drugs
L. James Willmore, MD
Associate Dean and Professor of Neurology and
Pharmacology and Physiology
Department of Neurology and Psychiatry
St. Louis University School of Medicine
St. Louis, Missouri
Chapter 33: Adverse Effects of Antiepileptic Drugs
Karen S. Wilcox, PhD
Research Associate Professor
Anticonvulsant Drug Development Program
Department of Pharmacology and Toxicology
University of Utah
Salt Lake City, Utah
Chapter 30: Comparative Anticonvulsant Profile and
Proposed Mechanisms of Action of Antiepileptic
Drugs
Gabriele Wohlrab, MD
Department of Paediatric Neurology
Epilepsy Centre
Children’s Hospital
University of Zurich
Zurich, Switzerland
Chapter 54: Vigabatrin
Nicole Wolf, MD
Department of Paediatric Neurology
Epilepsy Centre
Children’s Hospital
University of Heidelberg

Heidelberg, Germany
Chapter 50: Sulthiame
Yasuko Yamatogi, MD, PhD
Professor, Faculty of Health and Welfare Science
Okayama Prefectural University
Soja, Okayama, Japan
Chapter 15: Severe Encephalopathic Epilepsy in
Early Infancy
Mark S. Yerby, MD, MPH
Associate Clinical Professor of Neurology
Public Health and Preventive Medicine
Oregon Health and Science University
Portland, Oregon
Chapter 35: The Female Patient and Epilepsy
BASIC MECHANISMS
I