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


Concept to Practice: Advances in Epilepsy Management


GOAL
To provide neurologists, psychiatrists, OB/GYNs, and internists with up-to-date information on the treatment and management of patients with epilepsy.

TARGET AUDIENCE
This activity is designed for neurologists, psychiatrists, OB/GYNs, and internists.

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, the participant should be able to:

  • Better understand the major health outcomes associated with epilepsy.
  • Discuss the effects of certain antiepileptic drugs (AEDs) during pregnancy, using information from recent studies and national and international registries.
  • Recognize and manage AED-associated bone disease.
  • Identify and treat comorbid psychiatric disorders.
  • Ascertain the cognitive effects associated with epilepsy and its treatments.

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: June 15, 2005. Expiration date: June 15, 2007.

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 GlaxoSmithKline.

Full Disclosure Policy Affecting CME Activities:
As a provider 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
Chairman of Neurology
Director of Epilepsy and EEG
Department of Neurology
Johns Hopkins Bayview Medical Center
Baltimore, Maryland
Dr Kaplan reports receiving grants/research support from GlaxoSmithKline and Pfizer Inc/Parke-Davis; and serving as a consultant for GlaxoSmithKline.

PARTICIPATING FACULTY

John J. Barry, MD
Department of Psychiatry
Stanford University
Stanford, California
Dr Barry reports receiving grants/research support from Cyberonics, GlaxoSmithKline, and Stanford University; serving as a consultant for Cyberonics, GlaxoSmithKline, Neuropace, and Stanford University; and receiving honoraria from Cyberonics and GlaxoSmithKline.

John Craig, MD
Consultant Neurologist
Royal Group of Hospitals
Belfast, Ireland, United Kingdom
Dr Craig reports having no financial or advisory relationships with corporate organizations related to this activity.

Robert T. Fraser, PhD, CRC
Professor of Neurology, Neurological Surgery, and Rehabilitation Medicine
Director of Vocational Services
University of Washington Epilepsy Center
Seattle, Washington
Dr Fraser reports receiving honoraria from Galen Publishing.

Lewis B. Holmes, MD
Chief, Genetics and Teratology Unit
Massachusetts General Hospital for Children
Boston, Massachusetts
Dr Holmes reports receiving grants/research support from Abbott Laboratories, Eisai, GlaxoSmithKline, Ortho-McNeil Pharmaceuticals, Novartis, and Pfizer Inc.

Cecilie Lander, MD
Department of Medicine
The Australian Centre for Neuropharmacology
Raoul Wallenberg Centre
St. Vincent’s Hospital
Fitzroy, Melbourne, Australia
Dr Lander reports receiving grants from GlaxoSmithKline.

Kimford J. Meador, MD
Melvin Greer Professor of Neurology
Department of Neurology
University of Florida
Gainesville, Florida
Dr Meador reports receiving grants/research support from GlaxoSmithKline, Ortho-McNeil Pharmaceuticals, Pfizer Inc, SAM Technology, Shire, and UCB Pharma; serving as a consultant for Abbott Laboratories, Cyberonics, GlaxoSmithKline, Neuropace, Novartis, Ortho-McNeil Pharmaceuticals, and UCB Pharma; and receiving honoraria from GlaxoSmithKline, Ortho-McNeil Pharmaceuticals, and UCB Pharma.

Alison M. Pack, MD
Assistant Professor of Clinical Neurology
Columbia University
New York, New York
Dr Pack reports receiving grants/research support and honoraria from GlaxoSmithKline and Novartis.

Torbjörn Tomson, MD
EURAP Study Group
Chairman of the Central Project
Department of Neurology
Karolinska Hospital
Stockholm, Sweden
Dr Tomson reports receiving grants/research support from GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB Pharma; and being a shareholder in Pfizer Inc.

Notice: The authors have indicated that this CME activity contains no mention of 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.

Concept to Practice: Advances in Epilepsy Management
Peter Kaplan, MBBS, FRCP*

The US Congress declared the 1990s as the “Decade of the Brain,” resulting in increased appropriations for research in brain diseases—including epilepsy. As of 2005, significant clinical advances have been achieved in treatment options (drugs and devices) for seizure disorders, with more than 10 US Food and Drug Administration-approved antiepileptic drugs (AEDs). However, despite the expanded therapeutic options, a significant portion of patients with epilepsy not only are unable to achieve complete seizure control but also continue to struggle with other health-related outcomes that often may be overlooked or not extensively considered by the healthcare community.

This issue of Advanced Studies in Medicine explores the other negative outcomes of epilepsy and its treatments so that epileptologists and neurologists who treat patients with epilepsy can provide more comprehensive care to achieve “no seizures, no side effects.” The articles in this monograph are based on a symposium held during the 2004 Annual Meeting of the American Epilepsy Society in New Orleans, Louisiana. Also included is an update on the international pregnancy registries, which were discussed at a forum during the conference, in addition to selected posters covering similar topics.

In an effort to encourage the diagnosis and treatment of epilepsy, and because of the American culture of promoting parity for those people with disabilities, this monograph tends to focus on the retained abilities and possible positive outcomes for those patients with epilepsy. Nonetheless, there are more negative consequences, such as depression and anxiety, unintentional injury or death, suicide, lifestyle limitations, and social isolation. Patients with epilepsy can sustain serious physical injury during an epileptic seizure, and those patients with refractory epilepsy may have more hospitalizations, higher healthcare utilization, and higher mortality and suicide rates than matched control populations. The loss of activity because of injury or revocation of driving privileges can lead to a sense of isolation and depression.

Less clear is the quantified loss of a patient’s activity because of epilepsy. Clinicians know anecdotally that epilepsy prevents their patients from participating in certain activities and results in lost workdays. Driving is one of the most prominent concerns of patients with epilepsy, along with independence and the ability to work (Figure).1 In 13 states, persons with epilepsy are restricted from driving up to 12 months after diagnosis; most other states require 6 months of prohibited driving.2 Given Americans’ reliance on the automobile, it is not hard to imagine the limitation and isolation when driving privileges are revoked. Patients may not always report epilepsy symptoms to their physician, in part because of the driving restrictions. In a cross-sectional study in the United Kingdom, 122 patients completed anonymous questionnaires about their health. Approximately 16% of the study participants reported seizures in the past year in the questionnaire, but they did not report these episodes to their physician. Of the patients who anonymously reported a seizure in the questionnaire, 40% held a driver’s license, but only 25% of these patients admitted this to their physician.3

Dr Allison M. Pack has done extensive research on the effects of AEDs on bone health and provides an update on what is known about the influence of AED use on fracture risk. Most of the data are from the older AEDs, and data for the newer drugs from the 1990s are more limited. Dr Pack provides important recommendations for monitoring and preventing osteoporosis to avoid further injury and potential compliance failures with AED use.

Depression is a common comorbidity of epilepsy and often is automatically regarded as an emotional response to the disorder. Several studies have shown a strong relationship between mood and anxiety disorders and epilepsy, and evidence shows that these psychiatric comorbid illnesses affect a patient’s quality of life. In epilepsy, the prevalence of depression ranges from 20% to 55% in those patients with recurrent seizures, and from 3% to 9% in those patients with controlled seizures.4 These rates are significantly higher than in matched-control populations. Depression is an important comorbidity to detect and to address for several reasons. Evidence from studies of other chronic illnesses suggests that mood is an important factor in compliance.5-10 Also, major depression in patients with epilepsy is associated with significantly decreased self-reported quality of life, increased disability and missed work, and increased medication and medical costs.11-13 Although the negative outcomes in patients with epilepsy significantly impair quality of life, there is emerging evidence to suggest a causal link between depression and epilepsy. Dr John J. Barry reviews this evidence and provides recommendations for diagnosing depressive disorders in patients with epilepsy—quickly and reliably—in addition to treatment strategies in the context of concomitant AED treatment.

Employment challenges are often daily concerns for people with epilepsy because of the public’s and employers’ misinformation and potential stigma about epilepsy, which contributes to significant underemployment in these patients.14,15 Dr Robert T. Fraser discusses this important subject and clarifies myths and realities of job functioning among patients with epilepsy. He also provides useful information for physicians and employers to learn about epilepsy and its effect in the workplace. As Dr Fraser notes, the onus also is on physicians to become familiar with some of these resources for their patients because underemployment is not only a continual struggle but “risks overshadowing other achievements in patients’ lives.”

There has been recent intense focus on specific issues for women with epilepsy, most notably the potential teratogenic effects of some AEDs. AED registries have been under way for several years in an international effort. A forum to present the current status of these registries—regarding initial results and challenges in recruitment—included investigators from registries of several major countries or regions, including the United States, the United Kingdom, Europe, and Australia. Data from another registry that tracks cognitive and behavioral outcomes of AEDs (the neurodevelopmental effects of AEDs registry) also is presented. The results of these registries will be published soon. This monograph provides a review of the data collected, methods of enrollment, and the contact information for enrollment.

In addition to physical risks, epilepsy incurs mental challenges, such as cognitive decline. This monograph also includes an interview with Dr Kimford J. Meador, whose research focuses on mechanisms of attention and memory and the pharmacology and physiology of cognition. He describes not only the prevalence of cognitive impairment associated with epilepsy but also how it varies with the type of epilepsy and the long-term outcomes. Dr Meador also discusses his approaches to detecting and managing cognitive impairment in patients with epilepsy, when to initiate cognitive testing, and his approach to counseling patients with epilepsy on this sensitive topic.

A significant stigma remains attached to epilepsy in our society, much of it because of misunderstanding about the disease. The goal of this monograph is to reintroduce a discussion of the challenging and even negative outcomes of epilepsy, provide the basis for improved research funding for these problems, and advance the treatment goal of no seizures and minimal, if any, side effects.

REFERENCES
1. Gilliam F, Kuzniecky R, Faught E, et al. Patient-validated content of epilepsy-specific quality-of-life measurement. Epilepsia. 1997;38:233-236.
2. Gumnit RJ. Living Well with Epilepsy. 2nd ed. New York, NY: Demos Vermande; 1997.
3. Dalrymple J, Appleby J. Cross sectional study of reporting of epileptic seizures to general practitioners. BMJ. 2000;320:94-97.
4. Jacoby A, Baker GA, Steen N, et al. The clinical course of epilepsy and its psychosocial correlates: findings from a UK Community study. Epilepsia. 1996;37:148-161.
5. Ayres A, Hoon PW, Franzoni JB, et al. Influence of mood and adjustment to cancer on compliance with chemotherapy among breast cancer patients. J Psychosom Res. 1994;38:393-402.
6. Bosley CM, Fosbury JA, Cochrane GM. The psychological factors associated with poor compliance with treatment in asthma. Eur Respir J. 1995;8:899-904.
7. Edinger JD, Carwile S, Miller P, et al. Psychological status, syndromatic measures, and compliance with nasal CPAP therapy for sleep apnea. Percept Mot Skills. 1994;78:1116-1118.
8. Frazier PA, Davis-Ali SH, Dahl KE. Correlates of noncompliance among renal transplant recipients. Clin Transplant. 1994;8:550-557.
9. McDonough EM, Boyd JH, Varvares MA, Maves MD. Relationship between psychological status and compliance in a sample of patients treated for cancer of the head and neck. Head Neck. 1996;18:269-276.
10. Singh N, Squier C, Sivek C, et al. Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance. AIDS Care. 1996;8:261-269.
11. Gaitatzis A, Sander JW. The mortality of epilepsy. Epileptic Disord. 2004;6:3-13.
12. Hermann BP, Seidenberg M, Bell B. Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression. Epilepsia. 2000;41(suppl 2):S31-S41.
13. Kanner AM, Balabanov A. Depression and epilepsy: how closely related are they? Neurology. 2002;58(suppl 5):S27-S39.
14. Jacoby A, Snape D, Baker GA. Epilepsy and social identity: the stigma of a chronic neurological disorder. Lancet Neurol. 2005;4:171-178.
15. Jacoby A, Gorry J, Gamble C, Baker GA. Public knowledge, private grief: a study of public attitudes to epilepsy in the United Kingdom and implications for stigma. Epilepsia. 2004;45:1405-1415.

*Professor of Neurology, Chairman of Neurology, Director of Epilepsy and EEG, Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
Address correspondence to: Peter Kaplan, MBBS, FRCP, Professor of Neurology, Chairman of Neurology, Director of Epilepsy and EEG, Department of Neurology, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, 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.