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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: Developmental Advances in Migraine Management


GOAL
To provide neurologists with the most current information available for the treatment and management of migraine and other headache disorders.

PROGRAM SERIES RATIONALE
This program is designed to provide neurologists with current and practical information for the diagnosis, acute treatment, and prevention of migraine as well as other headache disorders. In the past decade, advances have been made in the use of triptans and antiepileptic drugs for acute and preventive treatment. Advanced imaging techniques have shed light on pathophysiology, and improvements in diagnostic criteria have enhanced diagnostic accuracy. As with other areas of scientific research, recent and current investigations of migraine and other forms of headache continue to raise new issues. As these issues are explored, it is hoped that future investigations will provide answers that will improve treatment and quality of life.

TARGET AUDIENCE
This activity is designed for neurologists, particularly those who treat patients with migraine. 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:

  • Distinguish primary from secondary headache and differentiate types of primary headache disorders.
  • Discuss the challenges associated with diagnosing and managing headache disorders in the elderly.
  • Review the most common primary headache disorders in elderly patients.
  • Describe several therapies under investigation for the treatment and prevention of migraine.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor 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, 2003. Expiration date: June 15, 2005.

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 unrestricted educational grant from Ortho-McNeil Pharmaceutical, Inc.

Advanced Studies in Medicine (ISSN-1530-3004) is published by Galen Publishing, a division of Advanced Studies in Medicine, an HMG Company. PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2003 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. Advanced Studies in Medicine is a registered trademark of The Healthcare Media Group, LLC.

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. Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

    Brian E. Mondell, MD
    Medical Director
    Baltimore Headache Institute
    Johns Hopkins at Green Spring Station
    Lutherville, Maryland
    Assistant Professor of Neurology
    Johns Hopkins University School of Medicine
    Baltimore, Maryland
    • Dr Mondell reports receiving grants and/or research support from Abbott Laboratories, Allergan, Inc, AstraZeneca LP, Bristol-Myers Squibb Company, Elan Corporation, GlaxoSmithKline, Merck & Co, Inc, Novartis Corporation, Pfizer, Inc, Pozen, UCB Pharma, and Vernalis Group.

PARTICIPATING FACULTY

    David J. Capobianco, MD
    Assistant Professor
    Mayo Medical School
    Mayo Clinic
    Jacksonville, Florida
    • Dr Capobianco reports serving as a consultant to Ortho-McNeil Pharmaceutical, Inc.

    David W. Dodick, MD
    Associate Professor of Neurology
    Department of Neurology
    Mayo Clinic, Scottsdale
    Scottsdale, Arizona
    • Dr Dodick reports having no financial or advisory relationships with corporate organizations related to this activity.

    Frederick G. Freitag, DO
    Associate Director
    Diamond Headache Clinic
    Chicago, Illinois
    • Dr Freitag reports receiving grant and/or research support, serving on the speakers' bureau for, and/or serving as a consultant to Abbott Laboratories, Allergan, Inc, AstraZeneca LP, Bayer Corporation, Bristol-Myers Squibb Company, CAPNIA, Inc, Elan Corporation, Epicept Corporation, GlaxoSmithKline, Janssen Pharmaceutica, Merck & Co, Inc, Novartis Corporation, Pfizer, Inc, Pharmacia Corporation, Pozen, Winston, and Wyeth.

    Stephen D. Silberstein, MD, FACP
    Director, Jefferson Headache Center
    Professor of Neurology
    Thomas Jefferson University
    Clinical Professor of Neurology
    Temple University
    Philadelphia, Pennsylvania
    • Dr Silberstein reports receiving grants and/or research support from Abbott Laboratories, Allergan, Inc, AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutica, Merck & Co, Inc, Ortho-McNeil Pharmaceutical, Inc, and Pfizer, Inc; and serving on the advisory panel, speakers' bureau, or as a consultant for Abbott Laboratories, Allergan, Inc, AstraZeneca LP, Elan Corporation, Eli Lilly and Company, GlaxoSmithKline, Merck & Co, Inc, and Ortho-McNeil Pharmaceutical, Inc.

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 contains 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 products:

Botulinum toxin—Dr Mondell
Levetiracetam—Dr Mondell
Oxcarbazepine—Dr Mondell
Topiramate—Drs Freitag, Mondell, and Silberstein

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.

Concept to Practice: Developmental Advances in Migraine Management
Brian E. Mondell, MD*

This issue of Advanced Studies in Medicine explores emerging treatments for migraine and other headache disorders with special focus on specific headache patient populations such as the elderly and those otherwise difficult to diagnose or treat. The issue reports on presentations given during the 14th Migraine Trust International Symposium held in London, United Kingdom, September 23-26, 2002, and one presentation from the American Headache Society's Scottsdale Headache Symposium held in Scottsdale, Arizona, November 15-17, 2002. Also included are summaries of several poster presentations involving headache prevalence, impact, diagnosis, and treatment.

Migraine and other chronic headache disorders greatly impact work productivity and quality of life. New research summarized in this issue indicates that headaches cost employers an estimated $23.7 billion annually in lost productivity and that 75% of this cost is due to headaches occurring while employees are at work—not while out sick. Furthermore, a minority (28%) of workers report the most severe headaches, but these headaches account for 70% of the lost productivity time. In addition, another study used the Headache Impact Test (HIT-6) and a quality-of-life scale as well as a migraine severity scale to assess correlation.1 The researchers concluded that the HIT-6 scale was a worthwhile tool to determine the true impact of migraine—particularly in the functional dimension.

Migraine affects up to 8% of women and 18% of men, but most sufferers do not seek medical attention despite the availability of newer treatments with fewer side effects.2,3 In addition, almost half of migraine patients are underdiagnosed or misdiagnosed, creating another barrier to receiving effective treatment.4-6 Results from the Landmark Study using HIT-6 to assess migraine impact and diagnosis by primary care physicians showed that while primary care physicians correctly diagnosed migraine 87% of the time, about 49% of patients who received a diagnosis of nonmigraine headache actually had migraine.

Whereas migraine incidence peaks at age 40 years and declines thereafter, primary headache disorders, including tension-type headache, cluster headache, chronic daily headache, and, especially, hypnic headache, often occur in older individuals.7-9 However, accurate diagnosis and management in this patient population requires a thorough history and investigation so as not to miss any secondary headache disorders. Medication use, overuse, or rebound can influence the presence of headache in the elderly. Giant cell arteritis, lesional headache, and all other secondary headaches must be excluded in these patients. An appropriate treatment plan cannot be initiated without the correct diagnosis and an understanding of any coexisting medical issues.

Emerging Headache Treatments

Anticonvulsants
New research is providing strong evidence that antiepileptic drugs are the current growth industry for migraine prevention. For example, early pilot studies using topiramate showed that the agent is safe and effective in migraine treatment.10,11 The most recent work is a well-conceived and well-executed randomized, placebo-controlled, double-blind study using 1 of 3 doses of topiramate (50 mg, 100 mg, or 200 mg) or placebo for 26 weeks in patients with migraine and migraine with aura. This study showed that both 100- and 200-mg daily doses caused more than one half of the patients to have at least a 50% reduction in migraine periods. Migraine frequency and the number of migraine days were also significantly reduced with topiramate therapy. In a similarly designed trial, researchers found that patients having migraine with aura experienced a more marked reduction in migraine frequency, number of migraine days, and migraine severity with topiramate. In this study, topiramate was also associated with a 41% reduction in photophobia symptoms—an interesting finding. Although this difference was numerically significant, it was not statistically significant.

In smaller, open-label, uncontrolled studies, the anticonvulsants levetiracetam and oxcarbazepine appeared useful for treating refractory migraine, chronic migraine, and tension-type headache. In one study, intravenous levetiracetam was given to 21 patients with refractory migraine who had not responded to other acute treatments. All but 1 patient reported some response. An open-label study using oxcarbazepine as an add-on therapy to existing preventive therapy in patients with refractory migraine or tension-type headache caused a reduction in monthly migraine frequency in some participants. Of those participants who did respond, some were able to discontinue or reduce their prior preventive treatments.

Botulinum toxins
Researchers investigated an intradermal route of delivering botulinum toxins types A (BTX-A) and B (BTX-B) to treat cervicogenic migraine. Patients received either BTX-A or BTX-B intradermally at the site of greater and lesser occipital nerve inlets on the side of the migraine pain. Of those who responded, there was a reduction in migraine frequency, pain, and/or muscular spasm, and the average duration of effect was 12 to 16 weeks.

In another reported study—a retrospective analysis of charts reviewed—intramuscular injections of BTX-A in facial and cervical regions significantly reduced headache frequency and severity in almost two thirds of chronic daily headache patients during the month following injection. Although much more rigorous research is clearly needed, BTX (especially type A) may offer an important treatment option for chronic daily headache patients—particularly those treatment-resistant or narcotic-dependent chronic daily headache patients.

Occipital Nerve Stimulation
There has been increasing interest in occipital nerve blockade or stimulation, particularly for the treatment of refractory chronic cluster headache. Evidence from animal models and several small human trials shows that stimulation of the greater occipital nerve inhibits stimulus-evoked trigeminal activity and that an implantable stimulation device can provide long-lasting cluster pain resolution.12-15 A case study using this technique in refractory cluster headache is included in this issue. Occipital nerve stimulation has also been tried in patients with occipital neuralgia and chronic migraine with good results. Without doubt, further work will be done with this treatment modality, and, with additional quality data, the role of this procedure should become clear over time.

REFERENCES
1. Ware JE, Bjorner JB, Dahlof C, et al. Development for the headache impact test (HIT) using item response theory (IRT). Cephalalgia. 2000;20:309.
2. Stewart WF, Shecter A, Rasmussen BK. Migraine prevalence. A review of population-based studies. Neurology. 1994;44(suppl 4):S17-S23.
3. Lipton RB, Stewart WF, Simon D. Medical consultation for migraine: results from the American Migraine Study. Headache. 1998;38:87-96.
4. Diamond M. The role of concomitant headache types and non-headache comorbidities in the underdiagnosis of migraine. Neurology. 2002;58(suppl 6):S3-S9.
5. Lipton RB, Diamond S, Diamond M, Reed M, Stewart WF. Prevalence of migraine headache in the United States: results of two studies at a 10-year interval. Headache. 2001;41:646-656.
6. Lipton RB, Diamond S, Reed M. Migraine diagnosis and treatment: results from the American Migraine Study II. Headache. 2001;41:638-645.
7. Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States: relation to age, income, race, and other sociodemographic factors. JAMA. 1992;267(1):64-69.
8. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41(7):646-657.
9. Waters WF. The pontypridd headache survey. Headache. 1974;14(2):81-90.
10. Storey JR, Caldor CS, Hart DE, Potter DL. Topiramate in migraine prevention: a double-blind, placebo-controlled study. Headache. 2001;41(10):968-975.
11. Silberstein SD. Efficacy of topiramate in migraine prophylaxis: a randomized controlled study. Adv Stud Med. 2002; 2(21):758-761.
12. Vincent MB, Ekman R, Edvinsson L, Sand T, Sjaastad O. Reduction of calcitonin gene-related peptide in jugular blood following electrical stimulation of rat greater occipital nerve. Cephalalgia. 1992;12(5):275-279.
13. Bartsch T, Goadsby PJ. Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input. Brain. 2002;125(pt 7):1496-1509.
14. Leone M, Franzini D, D'Amico D, et al. Deep brain stimulation in posterior hypothalamic gray matter to relieve intractable chronic cluster headache. Cephalalgia. 2002;22:582.
15. Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation. 1999;2(3):217-221.

*Medical Director, Baltimore Headache Institute, Johns Hopkins at Green Spring Station, Lutherville, Maryland; Assistant Professor of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.





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.