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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 Management of Comorbid Migraine and Epilepsy


GOAL
To provide neurologists and primary care physicians with up-to-date information on the connection between migraine and epilepsy, with focus on clinical implications and therapeutic strategies. 

TARGET AUDIENCE
This activity is designed for neurologists and primary care physicians. 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:

  • Describe the epidemiology and pathophysiology of migraine and epilepsy.
  • Understand the typical clinical presentation of migraine and epilepsy and the criteria to differentiate the 2 conditions.
  • Develop practical strategies for the care of patients with coexisting migraine and
    epilepsy.

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 The 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 provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the 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

Eric Kossoff, MD
Assistant Professor of Neurology and Pediatrics
Department of Neurology
Johns Hopkins Hospital
Baltimore, Maryland
Dr Kossoff reports receiving grants/research support from NeuroPace, Inc, the Robert C. Atkins Foundation, and UCB Pharma; and receiving honoraria from Novartis AG, Ortho-McNeil Pharmaceutical, Inc, and UCB Pharma.

PARTICIPATING FACULTY

Barry E. Gidal, PharmD, RPh
Professor of Pharmacy and Neurology
University of Wisconsin School of Pharmacy
Madison, Wisconsin
Dr Gidal reports receiving grants/research support from GlaxoSmithKline and UCB Pharma; serving as a consultant to GlaxoSmithKline, IVAX Corporation, UCB Pharma, and XenoPort, Inc; and receiving honoraria from GlaxoSmithKline, Novartis AG, and UCB Pharma.

Sheryl Haut, MD
Assistant Professor of Neurology
Director of Neurology Residency Training
Albert Einstein College of Medicine
Bronx, New York
Dr Haut reports receiving grants/research support from Pfizer Inc, and serving as a consultant to GlaxoSmithKline, Novartis AG, and UCB Pharma.

Allan Krumholz, MD
Professor of Neurology
University of Maryland School of Medicine
Director, University of Maryland Epilepsy Center
University of Maryland Medical Center
Baltimore, Maryland
Dr Krumholz reports receiving grants/research support from Pfizer Inc and the Schwartz Group, and serving as a consultant to GlaxoSmithKline and Ortho-McNeil Pharmacutical, Inc.

Donald Lewis, MD
Professor of Pediatrics and Neurology
Eastern Virginia Medical School
Children's Hospital of the King's Daughters
Norfolk, Virgina
Dr Lewis reports receiving grants/research support from AstraZeneca LP, GlaxoSmithKline, Merck & Co, Inc, Ortho-McNeil Pharmaceutical, Inc, Pfizer Inc, and Wyeth; and serving as a consultant to Abbott Laboratories, AstraZeneca LP, and Ortho-McNeil Pharmaceutical, Inc.

Richard B. Lipton, MD
Professor and Vice Chair of Neurology
Professor of Epidemiology and Population Health
Albert Einstein College of Medicine
Bronx, New York
Dr Lipton reports receiving grants/research support from, served as a consultant to, and received honoraria from Boehringer Ingelheim, Bristol-Myers Squibb Company, GlaxoSmithKline, Johnson & Johnson, Merck & Co, Inc, Pfizer Inc, and PR Osteo LLC.

Stephen D. Silberstein, MD
Director, Jefferson Headache Center
Thomas Jefferson University Hospital
Professor of Neurology
Thomas Jefferson University
Philadelphia, Pennsylvania
Dr Silberstein reports receiving grants/research support from Abbott Laboratories, Allergan Inc, AstraZeneca LP, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Medtronic, Inc, Merck & Co, Inc, NPS Pharmaceuticals, Pfizer Inc, Pozen, Inc, UCB Pharma, and Valeant Pharmaceuticals International; and is on the advisory panel, speakers' bureau, and serves as a consultant to Abbott Laboratories, AstraZeneca LP, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Merck & Co, Inc, Metis, NPS Pharmaceuticals, Ortho-McNeil Pharmaceutical, Inc, Pfizer Inc, Pozen, Inc, UCB Pharma, and Valeant Pharmaceuticals International.

Notice: The audience is advised that an article in this CME activity contains reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Silberstein—Acetylcholinesterase inhibitors, angiotensin-converting enzyme inhibitors, botulinum, CoQ10, feverfew, gabapentin, methysergide, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory drugs, riboflavin, selective serotonin reuptake inhibitors, tricyclic antidepressants, verapamil.
Dr Krumholz—aspirin, benzodiazepams, calcium channel blockers, carbamazepine, ergotamines, ethosuxamide, felbamate, gabapentin, lamotrigine, levetiracetam, nonsteroidal anti-inflammatory drugs, oxcarbazepine, phenobarbital, phenytoin, tiagabine, tricyclic antidepressants, vigabtrin, zonisamide.

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.

Current Management Of Comorbid Migraine And Epilepsy
Eric Kossoff, MD*

Both epilepsy and migraine can be difficult to diagnose and treat. The continuing efforts of the American Headache Society and the American Epilepsy Society in creating diagnostic criteria, classification systems, and practice parameters illuminate some of these challenges. For the patient, both migraine and epilepsy incur significant detriments to quality of life, and in the case of epilepsy, can occasionally cause serious injury or fatality.

As described by Dr Richard B. Lipton, comorbidity is the co-occurrence of 2 disorders more frequently than would be expected by chance alone. The presence of comorbid disorders with both migraine and epilepsy is well documented, and investigators are now realizing a possible comorbidity between migraine and epilepsy. Further investigation into the causes and presentation of both migraine and epilepsy reveals striking similarities, although the precise pathophysiologic processes of either disorder are not completely understood, particularly with migraine.

The use of antiepileptic drugs (AEDs) for migraine prevention is also well documented and has led to US Food and Drug Administration (FDA) approval of certain AEDs for this purpose. Other AEDs are frequently used off-label for migraine prevention and are now under investigation in treatment of acute migraine and other types of headache.1-8 Experience tells us that the use of AEDs in migraine is different from that in epilepsy—in titration schedules and therapeutic doses.

As we break new ground with different therapies for migraine and better treat epilepsy patients with comorbid conditions, the practicing neurologist is left with many questions about the patient who presents with confounding symptoms (eg, an epileptic patient with postictal headache [or migraine?], or the migraine patient who is experiencing "aura" [or a simple partial seizure?]). How does the answer affect treatment choice?

A roundtable of 7 opinion leaders in the fields of both migraine and epilepsy convened on February 5, 2005, in Philadelphia, Pa. The most recent advances in epidemiology, pathophysiology, presentation, diagnosis and classification, and treatment were presented and the panel members discussed numerous cases in order to best apply these findings. This monograph presents summaries of those presentations, as well as excerpts from the panel discussions, and a review of 5 cases. Dr Richard B. Lipton, past president of the American Headache Society and member of the executive committee of the International Headache Society, discusses his and others' research into the epidemiology of migraine and comorbid epilepsy. He also reviews how epidemiologic data can provide clues to causality of comorbidity, or at least rule out proposed theories. Dr Sheryl Haut, a clinical neurophysiologist and epileptologist, provides an in-depth comparison of the pathophysiology and presentation of both migraine and epilepsy—the commonalities as well as the differences—and provides an important focus of discussion for the subtle signs and symptoms that can complicate diagnosis. Dr Stephen D. Silberstein, current President of the American Headache Society and Director of the Jefferson Headache Center, describes the currently available treatments for migraine—both FDA-approved and common off-label uses—for both acute and preventive treatment. He compares the treatment goals for migraine and epilepsy, as well as the factors that affect drug choice. He discusses the potential therapeutic opportunity of treating both disorders with one drug, and the role of an individual patient profile in determining treatment success for both disorders. Dr Allan Krumholz, Director of the University of Maryland Comprehensive Epilepsy Center, continues that discussion with a review of treatment for comorbid migraine and epilepsy from an epileptologist's perspective and how the presence of comorbid migraine affects his treatment choices.

This panel of international opinion leaders acknowledges the difficulty with diagnosis and management of epilepsy and/or migraine and offer their expertise and practical advice in the uncharted waters of comorbidity and the therapeutic consequences—opportunities and limitations and the aspects of a patient's profile in determining best treatment strategies.

REFERENCES

1. Drake ME Jr, Greathouse NI, Renner JB, Armentbright AD. Open-label zonisamide for refractory migraine. Clin Neuropharmacol. 2004;27(6):278-280.
2. Stillman MJ, Zajac D, Rybicki LA. Treatment of primary headache disorders with intravenous valproate: initial outpatient experience. Headache. 2004;44(1):65-69.
3. Leone M, Dodick D, Rigamonti A, et al. Topiramate in cluster headache prophylaxis: an open trial. Cephalalgia. 2003;23(10):1001-1002.
4. Spira PJ, Beran RG; Australian Gabapentin Chronic Daily Headache Group. Gabapentin in the prophylaxis of chronic daily headache: a randomized, placebo-controlled study. Neurology. 2003;61(12):1753-1759.
5. Tanen DA, Miller S, French T, Riffenburgh RH. Intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headaches: a prospective, randomized, double-blind trial. Ann Emerg Med. 2003;41(6):847-853.
6. Leandri M, Luzzani M, Cruccu G, Gottlieb A. Drug-resistant cluster headache responding to gabapentin: a pilot study. Cephalalgia. 2001;21(7):744-746.
7. Delvaux V, Schoenen J. New generation anti-epileptics for facial pain and headache. Acta Neurol Belg. 2001;101(1):42-46.
8. Edwards KR, Norton J, Behnke M. Comparison of intravenous valproate versus intramuscular dihydroergotamine and metoclopramide for acute treatment of migraine headache. Headache. 2001;41(10):976-980.

*Assistant Professor of Neurology and Pediatrics, Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland.
Address correspondence to: Eric Kossoff, MD, 600 N Wolfe St, Jefferson 128, Baltimore, MD 21287.
E-mail: ekossoff@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.