Epilepsy: Mechanisms, Models, and Translational Perspectives

618 Pages·2010·19.22 MB·English

by  Jong Rho

EpilEpsy
Mechanisms, Models, and
Translational Perspectives
EpilEpsy
Mechanisms, Models, and
Translational Perspectives
Edited by
Jong M. Rho • Raman Sankar • Carl E. Stafstrom
Cover illustration courtesy of the Barrow Neurological Institute (Michael Hickman and Mark Schornak) (Copyright, Barrow
Neurological Institute 2009)
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Library of Congress Cataloging‑in‑Publication Data
Epilepsy : mechanisms, models, and translational perspectives / editors, Jong M. Rho, Raman Sankar, and
Carl E. Stafstrom.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4200-8559-4 (alk. paper)
1. Epilepsy. 2. Anticonvulsants--Therapeutic use. 3. Gene therapy. I. Rho, Jong M. II. Sankar, Raman. III.
Stafstrom, Carl Ernest. IV. Title.
[DNLM: 1. Epilepsy--physiopathology. 2. Epilepsy--therapy. 3. Anticonvulsants--therapeutic use. 4.
Epilepsy--genetics. 5. Gene Therapy. WL 385 E6432 2010]
RC372.E668 2010
616.8’53--dc22 2010000991
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
Dedicated to all who have devoted their lives
to furthering our understanding of epilepsy and
advancing the care of those afflicted by this disorder
Contents
Preface...............................................................................................................................................xi
Editors ............................................................................................................................................xiii
Contributors .....................................................................................................................................xv
Introduction .....................................................................................................................................xxi
SectIon I Scientific Foundations
Chapter 1 Pathophysiological Mechanisms of Seizures and Epilepsy: A Primer ........................3
Carl E. Stafstrom
Chapter 2 Blood–Brain Barrier, Blood Flow, Neoplasms,
and Epilepsy: The Role of Astrocytes ........................................................................21
Luca Cucullo, Nicola Marchi, Vincent Fazio,
Minh-Tri Nguyen, and Damir Janigro
Chapter 3 Metabolic Regulation of Seizures and Epileptogenesis .............................................35
Manisha Patel
Chapter 4 Brain Inflammation and Epilepsy ..............................................................................45
Teresa Ravizza, Silvia Balosso, Eleonora Aronica, and Annamaria Vezzani
Chapter 5 Drug Resistance in Epilepsy and Status Epilepticus ..................................................61
Jaideep Kapur and Edward H. Bertram
Chapter 6 Epilepsy with Complex Genetics: Looking Beyond the Channelopathies .................83
Asuri N. Prasad and Chitra Prasad
Chapter 7 Pathophysiology of Developmental Epilepsies .........................................................103
Judith L.Z. Weisenberg and Michael Wong
SectIon II Antiepileptic Drugs
Chapter 8 Mechanisms of Antiepileptic Drug Action ..............................................................123
Timothy A. Simeone
Chapter 9 Epilepsy and Disease Modification:
Animal Models for Novel Drug Discovery ..............................................................143
H. Steve White
vii
viii Contents
Chapter 10 Pharmacogenetics of AED Development .................................................................159
Russell J Buono, Thomas N. Ferraro, Dennis J. Dlugos, and Karen S. Wilcox
Chapter 11 Neuroprotective Strategies Using Antiepileptic Drugs ............................................173
Patrick G. Sullivan and Ryan D. Readnower
Chapter 12 Posttraumatic Seizures and Epileptogenesis: Good and Bad Plasticity ...................181
Christopher C. Giza
Chapter 13 Possible Roles of Nonsynaptic Mechanisms in Synchronization
of Epileptic Seizures: Potential Antiepileptic Targets? ............................................209
F. Edward Dudek, Li-Rong Shao, and John E. Rash
Chapter 14 A Mechanistic Approach to Antiepileptic Drug Interactions ..................................229
Gail D. Anderson
SectIon III epilepsy Surgery
Chapter 15 Advances in Structural and Functional Neuroimaging:
How Are These Guiding Epilepsy Surgery? ............................................................257
Hyunmi Kim, A. LeBron Paige, and Robert C. Knowlton
Chapter 16 Magnetoencephalography in Clinical Epilepsy:
A Translational Viewpoint .......................................................................................283
Jerry J. Shih and Michael P. Weisend
Chapter 17 What Have We Learned from Resective Surgery
in Pediatric Patients with Cortical Dysplasia? .........................................................301
Carlos Cepeda and Gary W. Mathern
Chapter 18 Nonsurgical Ablation for Epilepsy ...........................................................................319
Erich O. Richter, Marina V. Abramova, William A. Friedman, and Steven N. Roper
Chapter 19 Deep Brain Stimulation for Epilepsy .......................................................................345
Francisco Velasco, Ana Luisa Velasco, Luisa Rocha, Marcos Velasco,
Jose D. Carrillo-Ruiz, Manoela Cuellar, Guillermo Castro,
Fiacro Jimenez, and David Trejo
Chapter 20 Optical Imaging Techniques in Pediatric Neocortical Epilepsy ..............................361
Daryl W. Hochman and Michael M. Haglund
Chapter 21 High-Frequency Oscillations in Epileptic Brain ......................................................367
S. Matt Stead, Mark Bower, and Greg Worrell
Contents ix
SectIon IV Alternative therapies
Chapter 22 Special Treatments in Epilepsy ................................................................................381
Kevin Chapman and James W. Wheless
Chapter 23 Herbs and Botanicals ...............................................................................................407
Steven C. Schachter
Chapter 24 The Ketogenic Diet: Scientific Principles Underlying Its Use .................................417
Kristopher J. Bough and Carl E. Stafstrom
Chapter 25 Vagus Nerve Stimulation..........................................................................................441
Matthew M. Troester and Dean K. Naritoku
Chapter 26 Antiinflammatory Treatments for Seizure Syndromes and Epilepsy ......................459
Stéphane Auvin and Raman Sankar
SectIon V other Modulators of the epileptic State
Chapter 27 Impact of Neuroendocrine Factors on Seizure Genesis and Treatment ...................475
Pavel Klein and Jaromir Janousek
Chapter 28 Neurosteroid Replacement Therapy for Catamenial Epilepsy .................................501
Doodipala S. Reddy and Michael A. Rogawski
Chapter 29 Chronobiology and Sleep: Implications for Seizure Propensity ..............................515
Mark Quigg

Chapter 30 Pediatric Epilepsy: A Developmental Neuropsychiatric Disorder ...........................535
Rochelle Caplan
SectIon VI the Future of epilepsy therapy
Chapter 31 Novel Mechanisms of Drug Delivery.......................................................................551
Vijay Ivaturi and James Cloyd
Chapter 32 Early Seizure Detection: Considerations and Applications .....................................573
Christophe C. Jouny, Piotr J. Franaszczuk, and Gregory K. Bergey
x Contents
Chapter 33 Gene and Stem Cell Therapies for Treating Epilepsy ..............................................589
Janice R. Naegele and Xu Maisano
Chapter 34 Arresting Epileptogenesis: The Current Challenge .................................................609
Philip A. Schwartzkroin
Index ..............................................................................................................................................627
Preface
Epilepsy is an episodic neurological disorder that has afflicted humankind throughout recorded
history; yet, throughout the millennia, it has never been properly acknowledged as a disease with
a biological basis. In ancient times, epilepsy was referred to, somewhat ironically, as the “Sacred
Disease,” as it was imbued with negative references to the supernatural. Epilepsy was later believed
to represent a form of demonic possession and thus resulted in social stigmatization and persecu-
tion. It was only late in the 19th century that epilepsy began its long and arduous journey to being
justly recognized as a physical illness with complex pathophysiological substrates. Even today, the
public is not fully apprised of the true nature of the epilepsies (as they are now considered), and
efforts to expand awareness of this condition have been thwarted in large measure by deeply rooted
preconceptions promulgated through the ages.
Within the last half-century, significant progress has been made in our basic understanding of
the epileptic brain. Pivotal advances in drug development and surgical techniques, as well as the
emergence of innovative approaches such as electrical stimulation of the nervous system, have led
to a substantial reduction in the morbidity and mortality of patients with epilepsy (both children and
adults). At the same time, remarkable developments in the basic neurosciences have enhanced our
understanding of brain structure and function at ever finer levels of molecular, cellular, and genetic
detail.
The intrinsic complexities associated with attempts at understanding normal brain structure and
function lie at the heart of the challenges investigators face in deciphering the epileptic brain. The
development of universally effective therapeutic approaches for epilepsy patients has been the elu-
sive goal of clinicians and researchers since the early twentieth century. Yet, despite the availability
of many new pharmacological agents within the last generation, at least one third of the people with
epilepsy remain refractory to medical therapy, and an even smaller number of these individuals are
potential candidates for epilepsy surgery. It is this last frustrating reality that has been the focus of
many professionals in the epilepsy field.
Within the research arena, increasing focus has been placed on “translational” research (i.e., that
which bridges the gap between the laboratory and patient bedside); however, effective communica-
tion and interchange between clinicians and basic researchers have been difficult to achieve on a
widespread basis. It is clear that such interaction is paramount in the development of novel treat-
ments based on a detailed knowledge of fundamental mechanisms. This volume incorporates new
translational advances in bringing epilepsy therapies from the laboratory bench to the bedside and
back again.
We wish to collectively thank our mentors, colleagues, students, and, most of all, our patients and
their families for providing the inspiration and encouragement to help facilitate this “translational”
dialog. Additionally, we thank the publisher and our families for the support they have given us
throughout this project. Finally, we acknowledge the expert editorial and administrative assistance
provided by Pat Roberson and Heather Milligan.
Jong M. Rho, MD
Raman Sankar, MD, PhD
Carl E. Stafstrom, MD, PhD
xi
Editors
Jong M. Rho, MD, is a senior staff scientist at the Barrow Neurological Institute and St. Joseph’s
Hospital & Medical Center in Phoenix, Arizona. After obtaining an undergraduate degree in molec-
ular biophysics and biochemistry at Yale University, Dr. Rho received his medical degree from the
University of Cincinnati. Following a pediatric residency at the University of Southern California
Children’s Hospital of Los Angeles and a neurology residency at the University of California, Los
Angeles (UCLA), School of Medicine, he completed fellowships in pediatric neurology at the UCLA
School of Medicine and in neuropharmacology at the National Institutes of Health (NIH). Prior to
his current position, he held faculty appointments at the University of Washington and the Children’s
Hospital & Regional Medical Center in Seattle and the University of California at Irvine. Dr. Rho’s
main research interests are the mechanisms underlying the anticonvulsant and neuroprotective
effects of the ketogenic diet, neuropharmacology of anticonvulsant compounds, and the study of sur-
gically resected human epileptic tissue. His research activities have been sponsored by several NIH
research grants, as well as a variety of intramural and extramural public and private sector sources.
Dr. Rho has served on the editorial boards of Epilepsia and Epilepsy Currents and has been a regular
reviewer for research grants submitted to the NIH. In addition to an extensive list of publications in
basic science and pediatric neurology peer-reviewed journals, Dr. Rho has written numerous book
chapters and edited several books and is a popular national and international guest lecturer.
Raman Sankar, MD, PhD, is a professor of neurology and pediatrics and chief of pediatric neurol-
ogy at the David Geffen School of Medicine at UCLA. He holds the Rubin Brown Distinguished
Chair in Pediatric Neurology. Dr. Sankar obtained his doctorate from the University of Washington
in medicinal chemistry and was involved in teaching and research for several years prior to enter-
ing Tulane Medical School, where he obtained his medical degree. He trained in pediatrics at the
Children’s Hospital of Los Angeles and completed his training in neurology and pediatric neu-
rology at UCLA. His laboratory research pertains to mechanisms of seizure-induced injury and
epileptogenicity in the developing brain and is funded by the National Institute of Neurological
Disorders and Stroke (NINDS), National Institutes of Health (NIH). Current research includes
investigations on improving the throughput for screening compounds for antiepileptogenic action
on the developing brain and modeling the comorbidity of depression that accompanies epileptogen-
esis. He is one of the investigators in a NINDS-sponsored multicenter study on childhood absence
epilepsy. Dr. Sankar is a reviewer for research grants submitted to the NIH, Epilepsy Foundation,
CURE, American Epilepsy Society, and other organizations. He is a member of an active pediatric
epilepsy program at UCLA that is well known internationally for many advances in pediatric epi-
lepsy surgery. Dr. Sankar has authored more than 160 research articles, reviews, and book chapters
and has served on the editorial boards of Epilepsia and Epilepsy Currents. Dr. Sankar serves on
the professional advisory board of the Epilepsy Foundation. He is a member of the Commission on
Neurobiology of the International League Against Epilepsy
Carl E. Stafstrom, MD, PhD, is a professor of neurology and pediatrics and chief of the division
of pediatric neurology at the University of Wisconsin Medical School, Madison. He received his
AB from the University of Pennsylvania, followed by his MD and PhD degrees (the latter in physi-
ology and biophysics) from the University of Washington, Seattle. After completing a residency in
pediatrics at the University of Washington Children’s Hospital, Dr. Stafstrom trained in adult and
pediatric neurology at Tufts–New England Medical Center in Boston, followed by fellowships in
neurology research, epilepsy, and clinical neurophysiology at Children’s Hospital, Harvard Medical
xiii