Epilepsy Therapy Project

November 2009

The Epilepsy Therapy Project (ETP) exists to bring effective, safe and tolerable therapies to people living with epilepsy and seizures. It is not acceptable that still today, 1/3 of those with epilepsy, some one million kids and adults in the United States alone, live with seizures uncontrolled by any available therapy and that the existing treatments too often bring with them debilitating side effects. And it is not acceptable that the problem of epilepsy is not discussed and that epilepsy research has not attracted a level of philanthropic support commensurate with the unmet medical need. We need to work to continue to bring the spotlight on epilepsy and to rally support for the new therapies needed to stop seizures and unacceptable side effects.

In the early months of 2009 we have won some important victories in the area of epilepsy awareness with a cover story on the unsolved nature of epilepsy appearing in Newsweek magazine featuring ETP Co-founder Dr. Orrin Devinsky, and with a Talk of the Nation interview with Orrin and myself on National Public Radio.

In the area of direct action to advance new therapies, we have seen important progress in the activities of the ETP in 2008 and into the early months of 2009. These include our March 2008 and April 2009 Epilepsy Pipeline conference where we brought together several hundred scientists, entrepreneurs, investors and industry participants involved in new therapy development. Also, in 2008 we funded a number of important grants serving to advance promising therapy projects selected for their potential to impact patients in a timeframe that matters by our scientific and business advisory boards. We also made good progress enhancing the content of our epilepsy.com and epilepsy.com/professionals websites and in particular launched a new innovation center (epilepsy.com/innovation) to support scientists, entrepreneurs and investors.

As an organization, I am happy to say that with support and leadership from our President Joyce Cramer, and our Executive Director Kim Macher, we made strides in board involvement and had a record year relative to financial contributions from our board and from individual contributors. We need to make ongoing progress in our fund raising efforts, but I am gratified with the commitment shown by our board and community against the backdrop of evident economic and financial challenges of the last 18 months.

Support from industry through unrestricted educational grants declined in 2008 and despite the increase in individual support; we had to tighten our budget. I want to thank Joyce, Kim and our web director, Karen Dredske for finding ways to cut our costs and overhead, allowing us to maintain our support for grants and investments in new therapies and our other programmatic activities.

As we look into 2009, we are more than ever determined to make a difference in accelerating the path of new therapy development. And with the ongoing financial challenges facing academic and industry labs and enterprises, our grants, investments and programs are more important than ever.

Thanks to all of you whose efforts and contributions sustain the Epilepsy Therapy Project and work to eliminate seizures and side effects for the millions of people living with epilepsy in our country and around the world.

Sincerely,

Warren Lammert
Chairman and Co-Founder

The mission of epilepsy.com/professionals is to inform and empower doctors, nurses and other health care providers. We believe that the knowledge and experience of the epilepsy experts who contribute to epilepsy.com/professionals, as well as their informed opinions will assist clinicians when caring for patients facing newly diagnosed epilepsy as well as patients struggling with epilepsy that has resisted treatment.

	Carl W. Bazil, MD, PhD, is an Associate Professor of Clinical Neurology, College of Physicians and Surgeons at Columbia University. He is the Interim Director of the Columbia Comprehensive Epilepsy Center, and the Director of the Neurology Division of the Columbia Comprehensive Sleep Center. Dr. Bazil received his undergraduate degree from the Massachusetts Institute of Technology, and his PhD (pharmacology) and medical degree from Emory University. He was a Neurology Resident at New York University, and served as Chief Resident and Instructor there. He was a Clinical Fellow in Epilepsy/EEG at the Neurological Institute of Columbia Presbyterian Medical Center, Columbia University. He is board certified in Neurology, Clinical Neurophysiology, and Sleep Medicine. Dr. Bazil’s research interests are primarily in the interaction between sleep, sleep disorders, and epilepsy, as well as in finding new treatments for epilepsy. He is currently the Principal Investigator of a study of a new drug for epilepsy, and of a device trial for refractory epilepsy that uses deep brain stimulation. He has also received grants for sleep studies for epileptic patients from Columbia University and the Epilepsy Foundation of America; and has been an Investigator for studies involving the safety, tolerability and efficacy of a variety of epilepsy drugs. Dr. Bazil is a member of the American Academy of Neurology, the American Neurological Association, the American Clinical Neurophysiology Society, and the American Academy of Sleep Medicine. He is a Member of the Editorial Board of Epilepsy.com, the epilepsy section editor for Current Neurology and Neuroscience Reports, and an Ad Hoc Reviewer for Epilepsia, European Journal of Neurology, Physiology and Behavior, Annals of Neurology, Archives of Neurology, Sleep,Journal of Clinical Sleep Medicine, Neurology, Pediatrics, Brain, Clinical Therapeutics, and Neuroscience Letters. Dr. Bazil has published over 60 articles in professional journals, has written a book for patients on epilepsy, has edited a book on sleep and epilepsy, and has contributed 14 chapters to various texts in his field. Dr. Bazil has been an invited lecturer at numerous national and international meetings mainly on the topic of sleep and epilepsy.
	Carol S. Camfield is Professor of Pediatrics at the Dalhousie University Medical School in Halifax, Nova Scotia where she is in the Division of Child Neurology. She received her BS, MD and pediatric training from the University of Michigan and was a Robert Wood Johnson Scholar at McGill University in epidemiology before moving with her family to Halifax. There she and her husband, Peter, created and followed a large population-based cohort of children with epilepsy over the past 20 years. Many publications have followed from the inception of this group which describe the natural history of childhood epilepsy, management and treatment and long-term social outcomes of these children. Carol is also interested in quality of life issues and the impact and management of pain in children with severe cognitive impairments. Both the The Clinical Investigator Award of American Epilepsy Society/Milken Family Foundation and the Wilder Penfield Award of the Canadian League Against Epilepsy have been awarded to the Camfields. Carol has authored more than 200 peer reviewed publications, 35 book chapters and given numerous presentations. She serves on the Editorial Boards of Pediatric Neurology, Journal of Child Neurology and Epilepsy & Behavior and is a reviewer for many journals. She was one of the founding members of the Epilepsy Association of Nova Scotia and has been on its BOD for the past 25 years with a special interest in education. She is active on several Committees of the ILAE and American Epilepsy Association and is a past board of director of Epilepsy Canada.
	James Cloyd, PharmD, is Professor of Pharmacy, Lawrence C. Weaver Endowed Chair for Orphan Drug Development and Director of the Center for Orphan Drug Research. He also serves as Co-Director of the Epilepsy Research and Education Program at the University of Minnesota College of Pharmacy. He received his BS from Purdue University in 1971 and his PharmD from the University of Kentucky in 1976 where he concurrently completed a 3 year hospital pharmacy residency. From 1985-1986, he studied clinical pharmacokinetics during a fellowship at the University of Washington. Dr. Cloyd has been funded by the National Institutes of Health, foundations, and the pharmaceutical industry to support his research, which focuses on orphan drug development and antiepileptic drug clinical pharmacology. He has published over 100 articles, book chapters, and monographs and advised 18 graduate students and post-doctoral fellows. Dr. Cloyd is a recipient of the Research Achievement Award from the American Pharmacists Association and the Weaver Medal for Distinguished Contributions to Pharmacy Education and Research given by the University of Minnesota College of Pharmacy. He is a Fellow of the American Pharmacists Association and the American College of Clinical Pharmacy. He lectures to pharmacy students, neurology residents, and health professionals on neurotherapeutics and the application of clinical pharmacology principles to AED therapy. His teaching has been recognized by the University of Minnesota, which has designated him a Morse Alumni Distinguished Teaching Professor and a member of the Academy of Distinguished Teachers.
	Joyce A. Cramer is President of the Epilepsy Therapy Project (ETP), a non-profit organization advancing new therapies for people living with epilepsy , and Associate Research Scientist at Yale University School of Medicine, New Haven, CT. Her academic career includes several decades of work in epilepsy and clinical trials to evaluate treatment outcomes. She developed methods for the evaluation of antiepileptic drug efficacy and adverse effects, study design and management, and enhancement of medication compliance, as well as instruments to assess quality of life, treatment satisfaction, and other patient-reported outcomes. Her publications include 5 books, more than 180 peer-reviewed manuscripts, 35 book chapters, and numerous abstracts, covering topics in medicine, neurology, psychiatry, research design, medication compliance & persistence, quality of life, and other patient-reported outcomes. The books are titled: Quantitative Assessment in Epilepsy Care, Quality of Life and Pharmacoeconomics: An Introduction, Alcohol and Seizures, Patient Compliance in Medical Practice and Clinical Trials, Patient Recruitment in Clinical Trials. Joyce has been a member of the ETP Governing Board since its inception. Her professional activities have included positions as Treasurer of the American Epilepsy Society (AES), AES Board of Directors, Chair of the Board of Trustees of the AES-William G. Lennox Fund. She also has served on the Board of Directors of the Society for Clinical Trials and the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). She currently serves on the Editorial Boards of Epilepsy & Behavior, Acta Neurologica Scandinavica, and Management Advisory Board for Value in Health. She has served on the Editorial Board for Epilepsia, chaired the ILAE Commission on Outcome Measurement, and the ISPOR section on Medication Compliance. She was Associate Editor of epilepsy.com and professionals.epilepsy.com, website resources for patients, families, and healthcare providers. She has received the Ambassador Award from the International League Against Epilepsy (ILAE) and the AES Service Award, as well as the International Research Promotion Council/World Scientist Forum Award: Eminent Scientist of the Year, and was twice awarded the ISPOR Distinguished Service Award.
	Orrin Devinsky is Professor of Neurology, Neurosurgery, and Psychiatry at NYU School of Medicine. He directs the NYU Epilepsy Center and the Saint Barnabas Institute of Neurology and Neurosurgery (INN). He received his B.S. and M.S. from Yale University, M.D. from Harvard Medical School and interned at Boston’s Beth Israel Hospital. He completed neurology training at the New York Hospital-Cornell Medical Center and his epilepsy fellowship at the NIH. His epilepsy research interests include: quality-of-life, cognitive and behavioral issues in epilepsy, surgical therapy, and new medications. He has published widely in epilepsy and behavioral neurology, with more than 200 articles and chapters and more than 15 books. He has chaired several committees of the American Epilepsy Society and has served as a Board member. He is active on the national boards of both the American Academy of Neurology and the Epilepsy Foundation. He is the Co-Editor of epilepsy.com, Epilepsy and Behavior, and Reviews in Neurological Diseases. Furthermore he is on the Editorial Board of several journals, and serves as a reviewer for many journals.
	Robert Fisher is Maslah Saul MD Professor of Neurology and Director of the Stanford Comprehensive Epilepsy Center. He received his Ph.D. in the Neurosciences in 1976 and a M.D. in 1977, from Stanford University. He then took specialty training in internal medicine at Stanford and in neurology at Johns Hopkins, where he was Co-Director of the Epilepsy Program for eleven years. He formerly was Chairman of the Department of Neurology, Chief of the Epilepsy Center at Barrow Neurological Institute in Phoenix, and Newsome Professor of Clinical Neurology at the University of Arizona. Dr. Fisher’s professional goal is to derive new treatments for previously untreatable seizure disorders by merging information from research laboratories with clinical practice. He is author or co-author of over 120 peer-reviewed publications in medical journals, three books on epilepsy and two monographs. He frequently chairs symposia and meetings, speaks at national or international conferences on subjects related to seizure disorders, has been on review boards for national grant applications, and currently serves on the editorial board of several epilepsy and EEG-related journals. He has won research awards from the Klingenstein Foundation, the Epilepsy Foundation of America and the National Institutes of Health. His peers named him to be listed 1996-2007 in Best Doctors in America. He was given the Ambassador Award from the International League Against Epilepsy. Dr. Fisher has served as President of the Epilepsy Society of Arizona; founding chair of the AES Public Education Committee and of the Research Committee; chair of the EFA Research Initiative Campaign, EFA Research Grants and Fellowships Committee, and the EFA Advocacy Committee; EFA Executive committee and as a member of the AES Research Awards Committee and AES Secretary for three years. He is Past-President of the American Epilepsy Society, and has served on the Board of the International League Against Epilepsy and as Editor-in-Chief of the Journal, Epilepsia.
	Dr. William R. Garnett received his Bachelor of Science in Pharmacy from the Medical College of Virginia/Virginia Commonwealth University in 1969 and his Doctor of Pharmacy degree from the Philadelphia College of Pharmacy and Science in 1973. Dr. Garnett joined the faculty at the University of North Carolina in 1973 and taught there from 1973 to 1976. While at UNC, Dr. Garnett learned to appreciate good basketball and still bleeds "Carolina Blue" during basketball season. In 1976 Dr. Garnett moved to the Virginia Commonwealth University/Medical College of Virginia where he is currently Professor of Pharmacy and Neurology. Dr. Garnett has been actively involved in clinical epilepsy research for over 25 years. He has been involved in the evaluation of new antiepileptic drugs, the assessment of new formulations of antiepileptic drugs, the evaluation of drug-drug interactions with antiepileptic drugs, the assessment of side effects with antiepileptic drugs, the pharmacoeconomics of epilepsy care, and determination of quality of life in patients with epilepsy. Dr. Garnett has published and presented widely in the area of epilepsy and antiepileptic drug therapy. He has published over 155 peer reviewed articles and 55 book chapters. His publications in the area of epilepsy include chapters in Managing Epilepsy and Co-Existing Disorders, Antiepileptic Drugs 5th edition, Pharmacotherapy: A Pathophysiologic Approach,Pediatric Epilepsy: Diagnosis and Therapy, Applied Pharmacokinetics, and Clinical Pharmacokinetics. His articles have appeared in Epilepsia, Neurology, Epilepsy Research, Clinical Therapeutics, Current Medical Research and Opinion, etc . He has made more than 1200 presentations at local, state, and national meetings. He is a Senior Editor for Long-Term Care Interface. Dr. Garnett has been actively involved in a number of professional organizations as an officer, committee chairperson, and committee member. He is a fellow of the American College of Clinical Pharmacy. He is the 1996 recipient of the ACCP Education Award. In the fall of 1997 he was an invited by the Ministry of Health in the Republic of Singapore to be a visiting lecturer and clinical specialist.
	Patricia Gibson is an Assistant Professor in the Division of Neurology at Wake Forest University School of Medicine. She received a BS in Psychology and Sociology from Radford University, followed by a Masters in Social Work from the University of Tennessee. Ms. Gibson is Associate Director of the Comprehensive Epilepsy Center at Wake Forest, where she provides individual, group and family counseling and is actively involved in medical student, nursing and patient education. She also serves as Director of the Epilepsy Information Service, a nationwide telephone information line for patients and their family members. Ms. Gibson has organized and conducted numerous regional as well as national and international conferences on epilepsy, including an annual conference at the American Epilepsy Society meeting titled Advances in the Management of Epilepsy and the Epilepsy Clinic and an annual Pediatric Epilepsy Symposium in the Southeast. She set up the Epilepsy Medication Fund for the state of North Carolina in 1987 and heads three major fundraisers for this fund. She is past President of the Epilepsy Foundation of North Carolina and serves on the Professional Advisory Board of this organization. She also serves on the Professional Advisory Board of the Tuberous Sclerosis Alliance and previously on the professional advisory board of C.U.R.E. (Citizens United for Research in Epilepsy).
	Cynthia L. Harden, MD is an associate professor of neurology and neuroscience at the Weill Medical College of Cornell University in New York City. Affiliated with the Comprehensive Epilepsy Center at this institution for 12 years, Dr Harden is also an associate attending in neurology. Dr Harden has lectured and conducted continuing medical education courses on a diverse list of epilepsy-related issues—including women’s and children’s concerns, the uses of new antiepileptic drugs, the effect of newer antiseizure treatments on sexual function, and new avenues for treating brain disease—to such groups as the American Academy of Neurology, the American Psychiatric Association, and the New York Academy of Medicine. A member of several professional societies, including the American Epilepsy Society and the American Academy of Neurology, Dr Harden serves as an officer in the epilepsy section of the Academy and is a member of its Therapeutics and Technology Assessment Subcommittee. Dr Harden’s research interests include assessing the effects of hormonal changes on epilepsy. For instance, in a study where Andrew Herzog, MD, MSc, is principal investigator, which is supported by the National Institute of Neurological Disorders and Stroke, she is exploring the effect of progesterone treatment versus placebo in women with epilepsy. Under a similar grant, Dr Harden was principal investigator in another study where she assessed hormone replacement therapy in menopausal women. Her privately funded research includes investigating the effects of add-on anastrozole in men with epilepsy. Dr Harden has also examined mood and anxiety disorders in people with epilepsy in response to various treatments and psychogenic pseudoseizures. Dr Harden is an ad hoc reviewer for Neurology and Epilepsy Research, among other journals. She has also authored or collaborated on nearly a score of book chapters and more than 35 articles for peer-reviewed journals, such as Epilepsia, Pediatric Neurology, the Journal of Epilepsy, and the Journal of Neuroscience. After earning her medical degree at the University of Wisconsin Medical School in Madison, Dr Harden served her internship and a year’s residency in internal medicine at St. Luke’s Hospital in New York City. She stayed in New York City to complete her residency training in neurology at Mount Sinai Hospital and a fellowship in clinical neurophysiology at Albert Einstein College of Medicine.
	Bruce Hermann is Professor and Director of the Matthews Neuropsychology Section in the Department of Neurology at the University of Wisconsin School of Medicine and Public Health in Madison WI. He currently serves as Chair of the Professional Advisory Board of the Epilepsy Foundation. He is an Associate Editor for Epilepsia and serves on the editorial board for Epilepsy and Behavior. His research interests include the neuropsychological and behavioral complications of the epilepsies in children and adults, cognitive and quality of life outcomes following epilepsy surgery, and the effects of epilepsy on cognitive and behavioral development in children with epilepsy and the effects of chronic epilepsy on cognitive aging.
	Dr. Andres M. Kanner is a senior attending physician in the department of Neurological Sciences at Rush University Medical Center in Chicago, where he has also been director of the Laboratory of Electroencephalography and Video-EEG-Telemetry since 1991, when he joined the staff at the Rush Epilepsy Center. He also holds the positions of Associate Director of the Section of Epilepsy and of the Rush Epilepsy Center. He is also Professor of Neurological Sciences and Psychiatry at Rush Medical College. Dr. Kanner was born and raised in Mexico City and received his MD (cum laude) from the Faculty of Medicine of the National Autonomous University of Mexico in Mexico City. He came to the United States in 1977 and completed a residency in Psychiatry at the Long-Island Jewish Hillside Medical Center in New Hyde Park, New York. In addition, Dr. Kanner completed a research fellowship in Child Psychiatry, sponsored by the National Institute of Mental Health, at the College of Physicians and Surgeons of Columbia University in New York City. It was during his training in psychiatry that Dr. Kanner became interested in epilepsy and went on to complete a residency in neurology at the Department of Neurology of Mount Sinai Medical Center in New York City. He completed his training with a fellowship in epilepsy and clinical neurophysiology at the Cleveland Clinic Foundation in Cleveland, Ohio. Dr. Kanner is triple boarded in neurology, psychiatry and clinical neurophysiology. Dr Kanner has long-standing research interests in the areas of pharmacology of epilepsy, psychiatric aspects of epilepsy and surgical treatment of temporal lobe epilepsy. He has authored or coauthored over 60 research publications, over 20 invited review articles and over 30 book chapters and has co-edited four textbooks. Dr Kanner is a regular reviewer for several professional journals of neurology and psychaitry, including Neurology, Epilepsy & Behavior and Epilepsia. He is also an ad hoc reviewer for a number of other journals, an editorial board member for Epilepsy & Behavior, and a contributing editor for Epilepsy Currents. Dr Kanner is a member of the American Epilepsy Society (AES), the American Academy of Neurology and the International Neuropsychiatric Association. He currently serves as chair of the practice guidelines committee of the American Epilepsy Society; he is serves in the Subcommittee of Education for Non-Neurologists of the American Academy of Neurology and is Chair of the Practice Committee of the Epilepsy Section of the American Academy of Neurology.
	Dr. Eric Kossoff is an Assistant Professor of Neurology and Pediatrics and a member of The John M. Freeman Pediatric Epilepsy Center, as well as the Division of Pediatric Neurology. His clinical practice specializes in the diagnosis and treatment of childhood seizures and epilepsy, especially approaches other than medications (e.g. diet, neurostimulation (VNS and NeuroPace), and surgery). Dr. Kossoff's clinical and research interests include the ketogenic diet, Atkins diet (for both children and adults), VNS, infantile spasms, hemispherectomy, migraine headaches (and their interaction with epilepsy), and Sturge-Weber syndrome. He is the Medical Director of the Ketogenic Diet program at Johns Hopkins and also the editor of epilepsy.com's "Keto News". Dr. Kossoff is also the Associate Director of the Pediatric Neurology Residency Program at Johns Hopkins Hospital. He is a coauthor of Treatment of Pediatric Neurologic Disorders and the current 4th edition of The Ketogenic Diet.
	Ruben Kuzniecky is Professor of Neurology, at NYU School of Medicine. He Co-directs the NYU Comprehensive Epilepsy Centers, and is Director of research at the NYU Epilepsy Center. He received his M.D. from Buenos Aires University in Argentina, followed by internship in Panama. He completed Medicine and Neurology training at the Montreal Neurological Institute, McGill University and his epilepsy fellowship at the MNI. He became Director of the UAB Epilepsy Center in 1995 and directed the Center until 2003 when he was recruited to NYU. Dr. Kuzniecky served as visiting professor in Radiology and Physics at the University College of London, UK in 1997-1998. His epilepsy research interests include: Imaging of epilepsy in particular MRI, MRS and MEG. He is also internationally recognized for his research in malformations of brain development and epilepsy. He has published widely in imaging, epilepsy, with more than 200 articles and chapters and is the author of 2 books and one monograph. He has chaired several committees of the American Epilepsy Society and served as a Board member and Treasurer. Dr Kuzniecky is a regular reviewer for several professional journals of neurology and epilepsy and he is in the editorial board for Epilepsy & Behavior, RIND, EpilepsyHypertex, etc. He serves as CME Chair for the SEEEG Society. Dr Kuzniecky has received multiple grants for his research from the NIH, Private foundations, AES, EFA and the Wellcome Fund and he is Co-PI of the Epilepsy Phenome/genome Project.
	Warren B. Lammert is Chairman and Co-Founder of the Epilepsy Therapy Development Project and Epilepsy.com. Mr. Lammert serves on the board of directors of the Epilepsy Foundation and of FACES (Finding a Cure for Epilepsy and Seizures) at New York University. Mr. Lammert is Founder, Principal and Chief Investment Officer of Granite Point Capital formed in January 2004 and has more than 18 years of investment industry experience. Prior to the formation of Granite Point Capital, he spent 14 years at Janus serving in several investment and senior management roles including most recently, Portfolio Manager of the Janus Mercury Fund from its inception in 1993 until March 2003. From July 1984 until joining Janus in 1987, Mr. Lammert served as Research Associate and then Associate Analyst at Fred Alger Management. Mr. Lammert received his B.A. in Economics from Yale University and graduated with Distinction from the London School of Economics with a M.Sc. in Economic History. He serves on the board of directors of Village Ventures and has also earned the right to use the Chartered Financial Analyst designation.
	Dr Mattson was born and raised in Connecticut, attended and received a BS degree from Yale University followed by his M.D. from Boston University. He did his neurology residency and a clinical neurophysiology fellowship at the Mayo Clinic. Following his formal training Dr Mattson spent five years with the USAF in San Antonio. During this time he and his colleagues did the initial studies on the effect of sleep deprivation on the occurrence of epileptic seizures and as an activating technique in EEG. After returning to Yale on the faculty at the Medical School in the late 1960’s he focused on development of the Yale/VA Epilepsy Center and has been active in this field since that time. Initially efforts were directed to developing one of the first Intensive Monitoring Units. The Unit evaluated diagnostic problems and increasingly focused on intractable epilepsy and intracranial recording for possible epilepsy surgery. His special area of interest increasingly turned toward antiepileptic drug therapy. He directed the two largest multi-center (VA Coop) studies that defined the effectiveness and adverse effects of the standard antiepileptic drugs. He continues to be active in development and evaluation the new AEDs. For the past decade and a half Dr. Mattson directed the Yale/NIH Program Project that has studied both clinical and basic aspects of the role of GABA in the pathophysiology and treatment of epilepsy using microdialysis and nuclear magnetic resonance spectroscopy in patients on various antiepileptic drugs. He has authored or co-authored more than 200 papers, most in the field of epilepsy and is co-editor of a number of books including the standard reference, Antiepileptic Drugs. Dr Mattson chaired the course on Clinical Epilepsy at the AAN for several years .In 1997 he became Chair of the Therapeutic Strategies Commissionof the International League Against Epilepsy, and continues to be especially active in development of the AED Guidelines for selection of therapy. Dr Mattson has been the President of the American Epilepsy Society. He has been recognized with a number of prizes and awards including The William Lennox Award of the American Epilepsy Society, the Novartis/ILAE Epileptology Prize, The Hans Berger Award, The Clinical Investigator Award of American Epilepsy Society/Milken Family Foundation, the Hans Berger Distinguished Scholar Award and Who’s Who in the World. In addition Dr Mattson has been active in education and was former director of the Yale Neurology Residency Program and the Director of the Medical Student Clinical Neuroscience Education at Yale Medical School. He has also been a member of the Yale Medical School Admissions and Faculty Promotions Committees. Although made Professor Emeritus in 2003, Dr Mattson continues an active research, educational and patient care role as Senior Research Scientist.
	Dr. Meador is Professor of Neurology and Director of Epilepsy Research at Emory University in Atlanta, Georgia. He was previously the Charbonnier Professor of Neurology at Medical College of Georgia, the Chair of Neurology at Georgetown University, and the Melvin Greer Professor of Neurology at the University of Florida. He has authored over 300 publications. Active areas of research include cerebral lateralization, dementia, epilepsy, mechanisms of attention and memory, neglect syndrome, neurodevelopmental effects of antiepileptic drugs, and the pharmacology and physiology of cognition.
	Ruth E. Nemire is the director of community engagement and an associate professor of pharmacy practice at Nova Southeastern University College of Pharmacy (www.nova.edu) and a voluntary assistant professor for the University Of Miami College Of Medicine (www.med.miami.edu). She graduated from Ohio Northern University with a baccalaureate degree in pharmacy and completed a doctor of pharmacy degree from the University Of Toledo College Of Pharmacy. She completed her formal training at the University Of Miami College Of Medicine with a fellowship in Epilepsy/Neurology. After completing the baccalaureate degree in pharmacy from Ohio Northern Ruth worked as a clinical pharmacist for the State of Ohio in a developmental center focusing on treatment for psychiatric and neurological disorders. She then worked as an ambulatory care pharmacist for the Veteran’s Administration. She returned to the academy to complete a doctor of pharmacy degree from the University of Toledo and then completed a fellowship in neurology from the University of Miami. Following that she was appointed as the director of research at the Center for Neurology Studies, and assistant professor of neurology at Texas Tech Medical School in Lubbock, Texas. During her tenure in Texas she participated as a principle investigator in multiple drug trials for treatment of alzheimer’s, parkinson’s, migraine and epilepsy. She mentored and trained neurology residents in good clinical practices for research and pharmacy issues in patient care. She returned to Florida for an appointment as an assistant professor at the Nova Southeastern University College of Pharmacy in the Department of Pharmacy Practice. Nemire served as the director of clinical education for 7 years. In 2005 she took on the role of Director of Community Engagement for the College of Pharmacy. As the Director of Community Engagement Nemire works with various community organizations and schools to increase partnerships that benefit faculty, students and members of the community. She has authored chapters on preceptor development, and articles relating to service-learning, intellectual property, and course development and is the co-editor of the book Pharmacy Clerkships: A Survival Manual for Students (McGraw-Hill 2002). She is the co-developer of a web based experiential education program for NSU preceptors and students. She has served as chair of the NSU College of Pharmacy technology committee. She has served in multiple elected leadership positions nationally for the American Epilepsy Society (www.aesnet.org) and American Association of Colleges of Pharmacy (aacp.org). She has been asked to develop learning communities within the AACP organization during the 2005-2006 school year. She is currently completing a doctorate in education with a specialty in higher education leadership at Nova Southeastern University College of Education.
	Chrysostomos P. Panayiotopoulos MD, PhD, FRCP is a renowned expert in the field of the epilepsies. He is now Consultant emeritus at St. Thomas’ hospital, London where he has served over the last 20 years as a Consultant in Clinical Neurophysiology and Epilepsies. Prior to this, he has been appointed Clinical Professor of Neurology, University of Colorado and Head and Professor of Neurology, University of Riyadh. He has also been an invited Associate Professor to Harvard University and Professor to the University of Western Australia. He has been one of the 12 members of the Task Force on Classification and Terminology of the International League Against Epilepsy. CP Panayiotopoulos has investigated the clinical and neurophysiological aspects of muscle and peripheral nerve function (he was first to describe F-chronodispersion) and is particularly known for his study of the epilepsies. CP Panayiotopoulos has written over 140 articles and editorials in prestigious journals including Brain, Neurology, Annals of Neurology, Archives of Disease in Childhood, Epilepsia, Journal of Child Neurology, Journal of Neurology, Neurosurgery and Psychiatry. He is the Editor of "The educational kit on epilepsies" and a member of the Editorial Board of Epilepsia, epilepsy.com, Epilepsy & Behavior, Epileptic Disorders, Medlink Neurology and serves as a reviewer for a number of journals including Lancet, Neurology, Epilepsia, and Epilepsy & Behavior. His books on epilepsies and particularly "A clinical guide to epileptic syndromes and their treatment" 2nd edition, Springer, 2007 are praised as landmarks in the epileptological literature. His work on establishing the syndromic diagnosis of epilepsies and the appropriate video-EEG methodology for their diagnosis has been regarded as ground breaking. "Panayiotopoulos syndrome" and autonomic status epilepticus specific to childhood are amongst his main contributions. His publications on idiopathic generalized epilepsies and absence seizures have shaped the current thought of their diagnosis and management. He is also the first to establish objective differential criteria between visual symptoms of occipital epilepsy and migraine.
	Steven Schachter, MD is president of the American Epilepsy Society and a member of the Scientific Advisory Board for the Epilepsy Therapy Project. Dr. Schachter is Professor of Neurology, Harvard Medical School; Director of Research Beth Israel Deaconess Medical Center Department of Neurology; Founding Editor and Editor-in-Chief, Epilepsy & Behavior, and a member of the Board of Directors of the Epilepsy Foundation.
	Joseph Sirven, is Editor-in-Chief of epilepsy.com/professionals. He obtained his undergraduate degree from Georgetown University in Washington DC. His Medical degree is from Louisiana State University in New Orleans followed by an internship in Internal medicine at Ochsner Medical Foundation. He completed his Neurology residency at the University of Minnesota. He completed an Epilepsy and Clinical Neurophysiology fellowship at the University of Pennsylvania. He is a Professor of Neurology at Mayo Clinic and is currently co director of the Epilepsy Program at Mayo Clinic Arizona as well as Chair of Medical Education for Mayo Clinic Arizona. Dr. Sirven has published extensively in the field of epilepsy and his works have appeared in numerous medical journals including Neurology, Annals of Neurology, Archives of Neurology, Mayo Clinic Proceedings, Epilepsia and Epilepsy & Behavior. He has published 2 books Clinical Neurology of the Older Adult and An Introduction to Epilepsy. He serves on the editorial Board of Mayo Clinic Proceedings and Epilepsy Currents. He is a tireless advocate for individuals with epilepsy and serves on the Professional Advisory Board of the Epilepsy Foundation of America where he chairs the Quality of Life Committee. His professional interests are Seizures in Older Adults and seizure Emergencies.
	Mark C. Spitz, MD. After receiving his medical degree from the University of Arizona College of Medicine in Tucson, Mark C. Spitz, MD, completed a 3-year residency in neurology at Baylor College of Medicine Affiliated Hospitals in Houston, Texas, and then a 2-year postdoctoral fellowship in clinical neurology and epilepsy at the Neurological Institute at the College of Physicians and Surgeons of Columbia University in New York City. Since 1985, he has been affiliated with the University of Colorado Health Sciences Center, where he is currently professor in the Department of Neurology. Dr. Spitz is board certified in neurology and clinical neurophysiology and is a fellow of the American Academy of Neurology. He is a member of several professional and scientific societies, including the American Clinical Neurophysiology Society and the American Epilepsy Society and serves on the Technology Committee of the latter. Dr. Spitz has received industry-sponsored grants to conduct drug treatment trials in different types of epilepsy. In 2003, he won the Commitment to Medical Excellence in Epilepsy Award from the Epilepsy Foundation of Colorado. He is an editor for Epilepsy.com , and has authored or coauthored 22 peer-reviewed publications, 52 abstracts, and 13 invited publications and book chapters largely concerning the diagnosis and treatment of various forms of epilepsy.
	Dr. Weiner, is an Associate Professor of Neurosurgery and Pediatrics at NYU School of Medicine, and is the youngest faculty member in his Department to have received tenure at the medical school. As a pediatric neurosurgeon with particular expertise in the surgical treatment of childhood epilepsy, he also treats pediatric brain and spinal tumors, craniofacial disorders, pediatric spasticity, hydrocephalus, spina bifida, Chiari malformations, syringomyelia, and tethered spinal cord. He works closely with the NYU Comprehensive Epilepsy Center as the pediatric epilepsy surgeon for the center. As a result, Dr. Weiner has developed one of the largest modern experiences in the surgical treatment of young children with medically refractory epilepsy, with a national and international referral base. Dr. Weiner has helped pioneer a novel epilepsy surgery approach in the treatment of children with Tuberous Sclerosis, work that has resulted in several publications as well as invited lectures at several international meetings. In the laboratory, he is studying brain development and, specifically, the role of the Sonic Hedgehog signaling pathway in formation of a childhood brain tumor, medulloblastoma. His work is funded by an NIH research grant. He has approximately 60 publications to date. He completed his neurosurgical training at NYU under Dr. Patrick Kelly, Chairman, and then completed a fellowship in Pediatric Neurosurgery at NYU. In addition, he was named the recipient of the 1996 Van Wagenen Fellowship by the AANS, the “Rhodes Scholarship” of neurosurgery, and the premier award granted to a graduating neurosurgery resident. Like Dr. Kelly, the 1976 Van Wagenen Fellow, Dr. Weiner chose to spend his fellowship in Paris, where he worked in the laboratory of Professor Nicole Le Douarin studying the biology of brain development. Dr. Weiner received his B.A. from the University of Pennsylvania, graduating Summa Cum Laude, Phi Beta Kappa in his junior year, and was one of three graduating seniors who received the Dean's Scholar Award for highest academic standing in his class. Dr. Weiner earned his M.D. from Cornell, where he received the John Metcalf Polk Prize for graduating with highest academic standing in his class, as well as Alpha Omega Alpha in his junior year.
	Dr. Wheless is Professor and Chief of Pediatric Neurology and the Le Bonheur Chair in Pediatric Neurology at the University of Tennessee Health Science Center in Memphis. He also serves as Director of the Neuroscience Institute and the Le Bonheur Comprehensive Epilepsy Program for the Le Bonheur Children’s Medical Center. He is Clinical Director and Chief of Pediatric Neurology at St. Jude Children’s Research Hospital. Dr. Wheless is a Diplomat of the American Board of Pediatrics, and the American Board of Psychiatry and Neurology with special qualifications in Child Neurology and in Clinical Neurophysiology. He is a fellow of the American Academy of Pediatrics. Dr. Wheless is a member of the Editorial Board of Journal of Child Neurology, Formulary, and Epilepsy.com and serves as reviewer of a number of journals including Neurology, Epilepsia, Pediatrics, and Epilepsy and Behavior. Dr. Wheless’s primary interests include child convulsive disorders. His research is focused on pediatric anti-epileptic drug development, the ketogenic diet, epilepsy surgery, and magnetoencephalography. Dr. Wheless is the author of more than 200 chapters, articles and abstracts on these subjects. He has lectured widely on pediatric epilepsy. He received his medical degree from the University of Oklahoma and completed residency training in pediatrics at the University of Oklahoma and then pediatric neurology at Northwestern University in Chicago at Children’s Memorial Hospital. His EEG/clinical epilepsy training was at the Medical College of Georgia in Augusta.

What's New on epilepsy.com/professionals?

The (Potential) Problems with Generics in Epilepsy Carl Bazil MD, PhD Associate Professor of Clinical Neurology College of Physicians and Surgeons Columbia University.

In the past year or so, new generic equivalents have been approved for lamotrigine, topiramate, oxcarbazepine, and levetiracetam. While this is good news in that cost consciousness is always an issue in medicine, and generic equivalents usually offer substantial savings, there is still concern that epilepsy is a condition where more caution should be exercised.

The American Food and Drug Administration sets strict standards for the approval of generic equivalents. Each must be compared to the approved brand-name drug in normal volunteers to ensure that two measures, Area Under the Curve (AUC, a measure of total drug absorbed) and Cmax (the peak concentration) are comparable. To do this, single doses of the proposed generic are tested against the brand name drug. The 95% confidence interval for each of these measures must fall between 80 and 125% of the branded drug. Usually, that translates into an average variability of 3-5%. For most conditions, this would be an insignificant amount. Think of a headache: if a 600 mg generic ibuprofen actually delivers only 570 mg, that probably doesn’t translate into a major problem for the patient. At worst, the headache may last a bit longer, or another dose would be needed.

In epilepsy, there is a relatively narrow therapeutic window that must be maintained for extended periods of time. Too much, and the patient experiences toxicity. Too little, and a seizure may occur. So the consequences of a slight fall in delivered dose may be severe: a patient who was seizure free may have a sudden seizure, potentially resulting in injury, loss of driver’s license, or even death. Under most circumstances we wouldn’t expect a 5% change to cause this. However, there are other, at least theoretical reasons that that variability could be greater. First, generic equivalents are tested in normal volunteers. Epilepsy patients may have greater differences in absorption or metabolism due to their condition or to concurrently administered drugs. Second, generic agents are not tested against each other (only to the brand). As there are multiple, sometimes dozens, of approved generic manufacturers for each epilepsy drug, this results in increased potential for variability; each time the patient returns to the pharmacy, a generic equivalent from a different manufacturer may be dispensed. The roughly 5% variability compared to the brand could then become a 10% swing from one generic to another. A handful of states (including Hawaii and North Carolina) have limited changes in generic manufacturers dispensed to a given epilepsy patient. Several others (Florida, Kentucky, Maine, Maryland, Minnesota, Missouri, and Rhode Island) limit substitution for drugs , however the practice of substitution is still the norm.

How often do problems occur? We really don’t know. While most neurologists have anecdotes of a problem resulting from a generic switch – a sudden seizure in a previously controlled patient being most common – it is often difficult to prove it is due to the generic substitution. We all certainly see patients with unexplained seizures without a change in brand. There are a few cases where the time course and documented changes in levels make generic change the likely culprit but these are rare.

"What’s New on Epilepsy.com Professionals in May?"

Medication Management Joyce Cramer President, Epilepsy Therapy Project Associate Research Scientist, Yale University School of Medicine

Do you take your medication the way you expect your patients to take theirs?
Doctors are notoriously unreliable in following medical instructions, particularly taking medication. Healthcare professionals have the knowledge to understand the importance of preventive and symptomatic treatment; they know what health behaviors should be accomplished regularly (e.g., diet, exercise, medication); they understand the mechanisms of action and pharmacology of medications; they have the intelligence to plan and the self-regimentation to maintain a pattern of personal healthcare. True, but unrelated to actual behaviors. Of course, some healthcare professionals do follow the advice they give to patients, but not all. The Doctors’ Health Study revealed that a large proportion of doctors who volunteered for the study were not eligible for randomization because they were so poorly compliant with the dosing during the placebo run-in phase.

Kastrissios et al.¹ asked medical students to take Tic Tac candy pills for two weeks, in a BID or TID regimen. They discovered that only 2/3 of “doses” were taken as agreed, 47% of doses were taken at the prescribed frequency (BID or TID), and 29% were taken at the prescribed intervals (hours apart). The Physicians’ Health Study II was designed to assess the efficacy of vitamin C, vitamin E, beta-carotene, and a multivitamin in reducing cardiovascular risk. Doctors who enrolled were sent calendar packs containing placebos of all four of the study drugs. Of the 11,128 willing to participate, only 7,001 (63%) took the pills regularly during the baseline (placebo run-in phase) and said they wanted to continue with the study².

I wrote an article for www.epilepsy.com geared toward patients called: "The Titanic Impact of Medication Compliance on Epilepsy"³ to explain that seizures may be related to missed doses, inadequate scheduling, and other remediable factors. Forgetfulness remains the main reason people report for missed doses, not unexpected for people commonly having memory difficulties. Rather than expecting patients to accommodate to know how to take their medication, or to use dosing schedules that are not convenient, try to adjust the medication to what the patient will be able to accomplish.

Of course, it’s difficult to counsel patients on medication management unless you know a few methods to impart to patients. Watch for a new CME program next month with tips on how to teach patients approaches to taking their (essential) antiepileptic drugs.

Transition and Transfer: the rocky road from pediatric to adult epilepsy care Peter Camfield MD, FRCP(C) Professor of Pediatrics Dalhousie University Halifax, Nova Scotia, Canada Carol Camfield MD, FRCP(C) Professor of Pediatrics Dalhousie University Halifax, Nova Scotia, Canada

A wise senior child neurologist suggested to us that if we did our job properly in pediatric epilepsy there would be no one to pass along to our adult colleagues. We wish it were so simple! About 50% of epilepsy that begins in childhood persists into the adult years. In our experience, the two biggest groups are patients with mental handicap (with a variety of epilepsy syndromes) and patients with idiopathic generalized epilepsy, especially Juvenile Myoclonic Epilepsy. There are others with cryptogenic or symptomatic partial epilepsies whose disorder resembles the partial epilepsies of adulthood.

1. Dealing with the adolescent/youth with relatively normal intelligence.

It is not easy to successfully navigate adolescence with persistent epilepsy. The epilepsy adds special restraints – regular sleep hours, regular medication, no alcohol, and some restrictions on activities, especially driving, uncertainty about contraceptive efficacy for girls. Epilepsy is a hidden handicap that can only be understood by others if they are told about it. Yet, we know that more that 50% of US teenagers would not date someone with epilepsy and view epilepsy as a mental illness. So how would you develop the courage to tell others?

Pediatric epilepsy care is family focused. Adult epilepsy care tends to be focused on the individual. When you are child, your parents make sure that you don’t forget your medication and direct you to go to bed early. Your doctor concurs with this approach. When you are an adult, you learn that all this is your choice, but you may not understand the consequences of poor compliance or poor lifestyle choices. Your adult doctor may not seem to care as long as you understand the facts and make your choices.

Simple transfer from pediatric to adult is potentially brutal (1). The child, now adult, does not understand his/her illness well – much of the family instruction was years ago and directed to the parents. The adult epileptologist only has a case summary and is unlikely to really understand how much of a burden epilepsy is to an adolescent, even if the seizures are well controlled.

Transition from pediatric to adult care is conceptually more attractive. Transition means that the adolescent, family and adult epileptologist all learn the critical steps to allow the youth with epilepsy to be treated in the adult world. Transition is a process that takes time and needs to begin in the pediatric setting. The adolescent learns what they need to know to explain their disorder. They learn the names of the drugs, the doses, the side effects and what needs to be done to fill a prescription. They understand that they have epilepsy but are not “epileptic”. Transition for epilepsy care can take many forms but is virtually undescribed in peer-reviewed literature. Without any data to support our contention, we think that a transition clinic that is staffed by both adult and pediatric epilepsy specialists is needed. A number of joint adult/pediatric visits should take place until transfer to adult care is deemed appropriate. The family needs to see that the pediatric team is still involved and that communication with the adult team is complete. The adult team needs to understand at what stage this particular adolescent is in the process of becoming an adult and design a therapeutic approach that is appropriate. If the adolescent is still in the “invulnerable stage” (nothing bad can happen to me), then more family involvement is needed. The pediatric team needs to “back off” to allow the adolescent to take responsibility.

2. Dealing with the adolescent/youth with mental handicap

The situation is quite different when the adolescent/youth has mental handicap. It is worth remembering that possibly 50% of epilepsy that starts in childhood and persists into adulthood is accompanied by mental handicap. Now parents and guardians must have an ongoing supervisory role. But, how much is too much and how much is too little?

Pediatric epilepsy specialists should have a fairly good understanding of how much independent judgment by these special adolescents is possible. This is likely more difficult for the adult neurologist. And where do the parents fit in? Suddenly, the individual focused adult health care system breaks down because the patients with mental handicap cannot represent themselves completely.

Parents have many years of trust in the pediatric system and need to be convinced that the adult system is equally nurturing, but it rarely is. They know when things are not going well but they may not know what to do about these issues in the adult system. Eventually the parents will need to surrender this responsibility to someone else – a guardian or an institution. So, the transition is more for the parents than the patient. The adult physician has few models and little experience in this arena. We often hear from our adult colleagues that they like children but could not deal with parents. If the child is mentally handicapped, there is no escape from the parents. In our experience, parents of a mentally handicapped adolescent with longstanding epilepsy are often very reluctant to take adult neurology advice – a new drug or consideration of an operation is threatening. They have come to accept a status quo that may not be acceptable in the eyes of the adult team.

Pediatric epileptologists also are giving up years of continual medical care for the patient and a long-standing friendship and bond with the family. Helping them cope over time is one of the main joys of pediatrics – and to lose this connection is hard. There is a transition for the pediatric epilepsy specialist also!

We are aware of few publications about transition and epilepsy. One paper describes a very personal transfer of care – the pediatric epileptologist and the adult epileptologist met together once with the family (2). There was no outcome measure – just a description of the process. Another paper describes an epilepsy adolescent clinic and some of the changes in medical prescriptions (3). Frankly, the literature in other chronic diseases of childhood is not much better. We know that in youth with diabetes and asthma often the transfer does not take place properly and the young adult may go without medical care for many critical years. Family physicians have not been very involved in the child’s care and in the eyes of the family are generally not significant contributors to ongoing care. For youth with epilepsy that persists into adulthood, we know that the social outcome, even for those with normal intelligence, is unsatisfactory in 30-50%. We know that for those with serious mental handicap and persistent seizures, adult neurology visits are relatively rare and newer medications are typically not prescribed. In summary, the epilepsy community handles transition or transfer of care poorly.

What needs to happen? Every centre needs to identify one or more adult epileptologists who are willing to participate in a structured transition clinic. Willingness must mean not just the prescription of medication but also major efforts at education, social integration and rehabilitation. Obviously, such an approach does not guarantee success, but it should be better than what we are currently doing.

References

1. Warnell P. The transition experience of epilepsy patients/families: results of a telephone survey. Axone. 1998;20:31-3.
2. Appleton RE. Appleton RE. Transition from paediatric clinic to the adult service. J R Soc Med. 2001;94:554.
3. Smith PE, Myson V, Gibbon F. A teenager epilepsy clinic: observational study. Eur J Neurol. 2002;9:373-6.

Epilepsy.com/Professionals Announcements from Joseph I. Sirven, MD, Editor-in-Chief

Happy Fourth of July!!

In the nonfiction book entitled, ”Mountains beyond Mountains,” Tracy Kidder tells the amazing story of Dr. Paul Farmer the famed infectious disease specialist from Harvard Medical School and his work in caring for the poor of Haiti. In a memorable aphorism, Dr. Farmer states that “medicine is a social science and politics is nothing but medicine on a larger scale. Medical education does not exist to provide students with a way of making a living but to ensure the health of the community. Physicians are the natural attorneys of the sick and social problems should largely be solved by them.” In the spirit of this message, during the month of March, epilepsy.com Professionals will focus on the concept of how the physician can best help our patients with psychosocial issues which are such a significant burden of disease. In four separate interviews on Hallway Conversations we explore the theme of how best to support our patients in dealing with the obstacles that epilepsy has placed in front of them.

"Thoughts of Spring"

Spring has begun as evident by longer days, warmer temperatures, and the desire to put the long cold winter behind us. Summer is drawing near. More people are outside playing, walking, driving and enjoying the best of the outdoors. Our thoughts often turn to spring cleaning and personal renewal. For some people, this time of year is marked by looking for a fresh start; finding a novel approach to dealing with situations at hand. In individuals with epilepsy or their families, their attention is diverted to “What can I do to improve my seizure control?” or “How can I join the rest of world in their pursuit of happiness?” At Epilepsy.com/Professionals, we have some answers to these questions.

As we start the year with a new US President, we now know that one of Mr. Obama’s main agenda items is healthcare reform. Thus, as we greet the month of February, a healthcare debate will begin in earnest on the many changes likely to occur in the coming months and years which may have a significant impact on the way in which healthcare is delivered. Regardless of whatever health system modifications are implemented, there will be an increased emphasis on quality and its measurement and how to deliver medical care at a lower cost.

Risks and Benefits of Epilepsy Surgery: Are We Missing A Boat?

Orrin Devinsky, MD
Dept of Neurology
NYU Langone School of Medicine

Medical disciplines are celebrated for their successes, defined by their challenges and haunted by their failures. Epilepsy surgery, a long and deep partnership between neurosurgery and neurology, has pockets of progress punctuating a field with little movement. Advances in neuroimaging and neurophysiology/invasive electrode monitoring have expanded the diagnostic arsenal. Novel stimulation and direct-to-brain drug delivery paradigms form an exciting pipeline to future therapies. Yet, it is frustrating to review Penfield’s outcomes from 50 years ago and wonder just how far we have come.

Unilateral temporal lobe epilepsy and extratemporal lobe epilepsy due to localized lesions are the success stories of epilepsy surgery, with seizure-free rates over 60%. In highly selected groups (e.g., patients with mesial temporal sclerosis on their non-dominant side and concordant seizure onsets), seizure-free rates exceed 80%. Among the estimated 500,000 US and 10,000,000 worldwide cases of medically refractory partial epilepsy, less than a third have unilateral temporal lobe epilepsy or extratemporal epilepsy with well-circumscribed lesions. What about the other two-thirds?

The past decade documents some improved outcomes that largely reflect improved patient selection. But improved outcome for who? And for the two-thirds who are not offered surgery, is it really better patient selection? Perhaps the goal should be to seek a lower percentage of seizure-free outcomes. Our target population should be widened, away from the “sweet center” of unilateral temporal lobe and extratemporal cases with localized lesions, to include those who are less likely to achieve seizure freedom.

The field of epilepsy surgery focuses on seizure-free outcome as the marker of success. But have we ignored palliation, the opportunity to improve quality of life through a reduction of seizure frequency and medication burden. For the approximately majority of patients with medically refractory partial epilepsy who are “not good candidates for epilepsy surgery”, we need to deeply reconsider our definition of “good candidate”. How did we come to decide that seizure freedom was synonymous with surgical success?

Epilepsy surgery shares with cerebral tumor and other neurosurgeries, a spectrum of disease substrates and a range of respective acceptable outcomes. These outcomes range from permanent alleviation of the disease to palliation or prolongation of the time to recurrence of the disease process. What all of these therapies share is the intention to improve the patient’s quality of life. Yet epilepsy surgery, unlike tumor surgery, is perceived as failing unless seizures are completely controlled. Our current demands for epilepsy surgery success restricts patient selection, being analogous to restricting tumor surgery to only benign or low-grade tumors. Evaluating success based solely on seizure resolution may deny therapy to patients who may gain worthwhile improvement otherwise. As epilepsy surgery becomes better refined are patients being excluded from consideration?

Who are these patients with refractory partial epilepsy whose seizures are frequent enough to restrict their lives, who have tried and failed multiple antiepileptic drugs and drug combinations; who live with ongoing seizures and side effects? For many, epilepsy is a progressive disorder, with deteriorating cognitive and behavioral function, increased rates of suicide and sudden unexplained death (SUDEP). Memory, attention, mental processing speed, executive and language functions, and social skills can all decline over the years of seizures pounding on the brain. Depression, anxiety disorders, psychosis all become more frequent with chronic epilepsy. Perhaps most startling are the rates of SUDEP. Among patients with refractory epilepsy who are considering surgery, the yearly rate of SUDEP is between 0.5 and .9%. Over a decade, that is a 5-9 rate. That does not include deaths from drowning, driving, accidents, and other causes. We need to re-examine the benefits as well as the risks of the status quo.

Epilepsy surgery is definitely not for everyone with refractory partial epilepsy. Many patients have multiple or widespread foci that overlap with functional cortex. Surgery could leave a permanent deficit without any benefit. Yet some patients with two or even three seizure foci can benefit when one or two main foci are resected. Seizure frequency and severity may be reduced by 50% or more. Hardly a cure, but a better place. And for some, potentially life-saving. Our challenge is to increase the frequency of seizure free outcomes, but also help patients who cannot currently achieve seizure freedom.

The field of epilepsy surgery needs to move beyond the myopic focus on seizures. Yes, well designed studies have examined deficits in naming and short-term verbal memory after dominant temporal resections. Yet, what do we know about real life executive and social functions after frontal lobe resections? Not much. More recent studies have addressed employment, quality of life, and mood. However, we have ignored or avoided questions that Penfield raised a half century ago concerning the epileptic substrate that he believed caused adverse inter ictal effects.

Nociferous cortex is defined as dysfunctional epileptogenic tissue that fails to perform its normal functions and impairs the function of other brain areas. Penfield and Jasper introduced the concept of nociferous cortex in describing the dramatic behavioral improvements after hemispherectomy in an aggressive boy: “Among patients who have large areas of abnormality in one hemisphere, abnormal behavior may appear, together with advancing mental retardation. The behavioral abnormality is often a more important complaint than the seizures themselves. Radical complete excision may correct the abnormal behavior, stop the seizures, and allow improvement in the patient’s mental state.” How do we systematically identify both deficits and improvements after epilepsy surgery? What can we do to predict postoperative cognitive and behavior changes before surgery? Restricted epileptogenic foci can be nociferous. For example, non-dominant anterior temporal lobectomy can improve verbal memory. Temporal lobectomy can improve metabolic functions ipsilateral and contralateral to the seizure focus, cortically and subcortically. Preoperative depression and anxiety often resolve after ATL.

Excellent surgical centers may improve outcomes through diagnostic and therapeutic advances as well as more restrictive patient selection. We must address the problems faced by those epilepsy patients who do not meet the more rigorous selection criteria. As epilepsy surgery becomes better refined are patients that would benefit from surgery being excluded from consideration?

Make sure to check out our other new offerings during the month of June on Epilepsy.com Professionals

Hallway Conversations will highlight new devices for epilepsy therapy during the month of June:

Medical Errors in Epilepsy — Redemption Joseph I. Sirven, M.D. Editor-in-Chief, Epilepsy.com/Professionals

Recently I had the opportunity of attending an institutional Medical Grand Rounds on a rather provocative topic. The lecture entitled” Medical Redemption” consisted primarily of physicians telling stories of medical errors that they had committed in the presence of patients who had been the subject of these errors. The point was to examine the issue of medical errors from two vantage points; physician and patient. If I had been a malpractice attorney, I would be in a state of disbelief and shock to witness an open discussion of one of the most emotionally fraught and legally complicated topics that can confront a medical professional. As I listened to their stories, I was struck by a few observations. Physicians who committed the errors were riddled with guilt out of proportion to the patients’ expressions of anger over the error. Patients seemed to be forgiving even when the consequences of the error were quite serious and long-lasting. Admitting the error appeared to relieve the patient and physician from the burden of anger and guilt respectively. It seemed that the old dictum that “It isn’t the crime that creates problems, but it’s the cover up” seemed to be a reality in the field of medical errors at least from my perspective as an attendee.

This led me to wonder about my own medical errors over time in the care of patients with epilepsy. I have personally never seen any literature or been privy to nonconfidential conversations of specific instances of medical errors as it pertains to epilepsy management. Attorneys often counsel that admitting a mistake publicly has legal implications and therefore the topic is somewhat taboo. However, we are certain that it occurs. Attendance at any hospital morbidity and mortality conference can confirm it. I too can profess to having committed a medical error which I have had to address with a patient and I have been personally forgiven by the patient. However, I was lucky as there were no long lasting untoward effects as the result of the error. Nevertheless, errors have consequences and oftentimes the patient will look for their care elsewhere after such an admission.

So how often do medical errors occur in the US? In November 1999, the Institute of Medicine issued a report entitled “To Err is Human; Building a Safer Health System” addressed this issue and the statistics were staggering. The authors found that as many as 44,000 to 98,000 people died in hospitals every year as a result of medical errors. By using the conservative estimate of the extent of the problem, medical errors would actually rank as the eighth leading cause of death in the United States, higher than motor vehicle accidents, breast cancer, and HIV. 7,000 people a year are estimated to die from medical errors. Errors are not restricted to hospitals but they occur in any healthcare settings such as physician offices, nursing homes, pharmacies, urgent care centers and care delivered in the home. The costs of these errors are in the billions of dollars.

To date there are no estimates that delineate the extent or cost of medical errors in the field of epilepsy. However, one can make an educated guess based on several papers that have courageously addressed the allied topic of complications as a result of specialized epilepsy care. Most notable are those from Noe and colleagues, reporting 21% of epilepsy monitoring units had some type of adverse event and from Hamer and colleagues, reporting the complication rate from invasive EEG monitoring. However these are complications that may be expected and would not be considered an error based on the definitions from the Institute of Medicine. Therefore the extent of the problem in epilepsy is not known.

So how should physicians address medical errors when caring for patients with epilepsy? If one accidentally overdoses a patient with extra anti-epileptic medication which results in toxicity or an unusual complication, does the physician or healthcare professional take the blame? Does one call the patient? How will the patient/physician relationship be altered as a result of this admission and can it ever really recover? The answers to these questions are not known, but intuitively honesty appears to be the best policy with regards to one’s admission of errors when they occur. More study is clearly needed for the best approach.

So as I sat in the audience anonymously in a cavernous auditorium listening to patient and physician stories, I was struck by how fragile the patient/physician relationship really is. The same trust issues that typify a partnership, a marriage, a friendship are the same ones involved in the relationship between physician and patient. One has to be honest, open and caring with regards to how information is presented. Communication is essential and yes legal counsel is sometimes needed. I suspect the issue of medical errors will remain an unspoken issue but it is important to understand how difficult the issue is for both patient and physician.

References:

1. Institute of Medicine. To err is Human, Building a safer Healthcare system. 1999. National Academy Press.
   http://books.nap.edu/html/to_err_is_human/reportbrief.pdf
   Accessed September 29. 2009.
2. Noe K, Drazkowski J. Safety of Long-Term Monitoring for Evaluation of Epilepsy. Mayo Clinic Proceedings 2009:84(6): 495-500.
3. Hamer H, Morris H, Mascha E, Karafa M, Bingaman W, Bej R and colleagues Complications of invasive video-EEG monitoring with subdural grid electrodes. Neurology 2002; 58; 97-103

My Epilepsy Diary - Why You Should Recommend it to Your Patients Joseph I. Sirven, M.D. Editor-in-Chief, Epilepsy.com/Professionals

Do your patients frequently forget to take their medications? When your patients recall past seizures, do you believe that critical details may be missing? Do you wish you could analyze the effectiveness of your patients’ treatment plans using trend data over the long term?