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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Current Issues and Ongoing Challenges in Epilepsy


GOAL
To provide epileptologists and neurologists with information on the most recent developments regarding the treatment of epilepsy.

TARGET AUDIENCE
The activity is designed for epileptologists and neurologists. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content,
quality, and scientific integrity of this CME activity. At the conclusion of this activity,
participants should be able to:

  • Evaluate approaches to the treatment of patients with new-onset seizures.
  • Discuss the importance of presentation when determining treatment of epilepsy.
  • Identify patients and indications for which therapeutic drug monitoring is indicated.
  • Identify associated epilepsy and sleep disorders and ways to overcome the challenges presented in these patients.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education
for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for
a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award.
Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  2 hours.

Release date: August 15, 2004. Expiration date: August 15, 2006.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Ortho-McNeil Pharmaceutical, Inc.

Full Disclosure Policy Affecting CME Activities:
As a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

Peter Kaplan, MBBS, FRCP
Professor of Neurology
Johns Hopkins University
School of Medicine
Chair of Neurology
Johns Hopkins Bayview Medical Center
Baltimore, Maryland
Dr Kaplan reports receiving grants/research support from GlaxoSmithKline and Pfizer Inc; serving as a consultant to GlaxoSmithKline, Ortho-McNeil Pharmaceutical Inc, Pfizer Inc, and UCB Pharma; and serving on the speakers' bureau for GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer Inc, and UCB Pharma.

PARTICIPATING FACULTY

Lionel Carmant, MD, FRCP (C)
Director, Epilepsy Research Unit
Clinical Assistant Professor of Pediatrics
Department of Pediatrics
Neurology Division
Ste-Justine Hospital
University of Montreal
Montreal, Quebec, Canada
Dr Carmant reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Beth A. Malow, MD, MS
Associate Professor
Department of Neurology
University of Michigan School of Medicine
Ann Arbor, Michigan
Associate Professor
Department of Neurology
Medical Director
Sleep Disorders Program
Vanderbilt University Medical Center
Nashville, Tennessee
Dr Malow reports receiving grant/research support from Cyberonics, Inc and UCB Pharma; and serving as a consultant to Pfizer Inc.

Page B. Pennell, MD
Associate Professor of Neurology
Acting Director
Emory Epilepsy Center
Emory University School of Medicine
Atlanta, Georgia
Dr Pennell reports receiving grants/research support from GlaxoSmithKline, Pfizer Inc, and UCB Pharma; serving as a consultant to GlaxoSmithKline and Ortho-McNeil Pharmaceutical, Inc; and receiving honoraria from GlaxoSmithKline and UCB Pharma.

Notice: In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. The following faculty members have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs or devices:

Dr Malow—vagus nerve stimulator

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Seizures: To Treat Or Not To Treat
Peter Kaplan, MBBS, FRCP*

Epilepsy is a disease with enormous implications for the patient. Its consequences have ramifications in every aspect of life, and its duration can be from cradle to grave. The manifestations of epilepsy are often commingled with other disorders that the patient may have. Different treatments with differing adverse effect profiles may also complicate management. For these reasons, the clinician cannot consider the diagnosis and treatment of epilepsy in isolation, but in the setting of all the patient's conditions.

The complexity of the disease and its impact on the patient is demonstrated by the basic questions still to be answered, despite our growing knowledge. When should treatment begin? How should we monitor drug therapy? How can we distinguish between the effects of epilepsy and those of comorbidities that may be present? The importance of answering these questions correctly is underscored by the potential adverse effects of the surgeries and therapeutic agents with which epilepsy is treated. Against these are weighed the consequences of insufficient treatment. Decisions are influenced by the conflicting concurrent need to prevent or minimize seizure activity with the need to restrict interventions to the minimum required to produce the desired outcome.

In this issue of Advanced Studies in Medicine, several topics have been selected that illustrate the dilemmas, challenges, and opportunities that face the practitioner when treatment decisions are made in epilepsy. These papers were all presented at the 2003 Annual Meeting of the American Epilepsy Society, which was held on December 5-10 in Boston. Journal editors also attended platform and poster sessions that examined the implications to patients of several specific antiepileptic drugs (AEDs); much of these data are also included.

When should antiseizure treatment commence? Lionel Carmant, MD, FRCP (C), addresses this controversial topic on the use of AEDs throughout the life span of the patient. More than a century after the progressive nature of epilepsy was first noted, consensus on the initiation of AED treatment still evades the epilepsy research community. Dr Carmant reviews the basis of the American Academy of Neurology Practice Parameter concerning pediatric treatment after a single seizure, focusing particular attention on situations of which predisposing factors may increase the risk of subsequent seizures to the point at which early treatment may be indicated. He also discusses evidence that there are cases in which treatment with AEDs before a seizure occurs may have long-term benefits for the patient. He then reviews the rather discouraging long-term data for early treatment outcomes. Finally, he discusses future improvements that may arise from better modeling in drug research, and from improved electroclinical, genetic, and neuroimaging techniques.

Another article deals with the topic of therapeutic drug monitoring (TDM). Page B. Pennell, MD, gives a case-based presentation illustrating the patient groups, special situations, and specific drugs for which TDM may be beneficial. The poor dose-response relationship for many AEDs, together with a very wide variation in drug metabolism both between and within patients, depending on such factors as age, reproductive status, metabolic pathway, and concomitant medications, result in considerable difficulty in achieving and maintaining lowest effective dosages. Dr Pennell reviews the role that variations in physiology, compliance, and concomitant medications play in affecting AED concentrations. She shows that TDM can be a valuable tool in titrating appropriate doses and in establishing a reference against which future changes can be calibrated. She considers the basis for the measurement of peak, trough, free fraction, and metabolites. In her article, Dr Pennell also details situations in which TDM is unnecessary or even potentially deleterious.

Sleep disturbances in epilepsy present considerable challenges to the clinician, in both diagnosis and determination of appropriate treatment. In her presentation on sleep disorders and epilepsy, Beth A. Malow, MD, MS, clearly demonstrates the importance of the careful and complete history in determining the origins and best course of action for treatment of sleep concerns in the epileptic patient. In her article, she examines common causes of sleep difficulties in the epileptic patient and cautions against the tendency to assume that sleep problems and epilepsy are necessarily related. Using a series of cases, she shows how good clinical detective work can reveal the true causes of even cryptic and complex sleep disorders. She explains how treatment should be selected based on the etiology of the problem. She also suggests means by which antiepileptic therapies can in some cases be chosen to facilitate, rather than impede, the achievement of good sleep patterns.

The complex nature of epilepsy inevitably dictates that research will uncover new questions as it answers old ones. Not only that, but it is likely to require us to revisit some conclusions that we had previously believed to be correct. However, the re-examination of old and current beliefs, such as the role of epilepsy in sleep disturbance, the correct timing for the initiation of therapy, and the need, or lack of it, for drug monitoring, together with the continuing search for new answers to old questions, will eventually assist us in advancing our body of knowledge of epilepsy and thus help physicians to improve treatment.

*Professor of Neurology, Johns Hopkins University School of Medicine; Chair of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.

Address correspondence to: Peter Kaplan, MBBS, FRCP, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, B Building 1N, Room 122, Baltimore, MD 21224. E-mail: pkaplan@jhmi.edu.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.