The January 28, 2004, issue of the Journal of the American Medical Association (JAMA) included an article that captured the attention of the media and generated reports all over the Internet. The article, "Migraine as a Risk Factor for Subclinical Brain Lesions,"¹ reported on a study conducted in the Netherlands.

It has been suggested that Migraines may be an independent risk factor for stroke, but some in the medical community had considered consistent data lacking. I asked Terri Miller Burchfield, Co-Founder and Vice President of MAGNUM, why previous studies hadn't been given more in-depth consideration. She explained, "Although there have been many case studies and clinical studies, there always seemed to be issues regarding them that the medical community couldn't agree on.

Studies of patients with Migrainous stroke exist, but data regarding the prevalence of subclinical infarcts in Migraine patients has been lacking. The study was to investigate whether Migraineurs from the general population are at increased risk of brain infarcts and white matter lesions (WMLs) or whether this risk varies by Migraine subtype and attack frequency.

Some of the findings:

• A total of 60 brain infarcts were detected in 31 study participants. Proportionately more Migraineurs had at least one infarct compared with controls. "However, in the cerebellar region of the posterior circulation territory (PCT), patients with Migraine had a higher prevalence of infarct than controls [5.4 percent vs. 0.7 percent; more than seven times the risk],"
• The risk of posterior circulation territory infarcts was 7.1 times higher in the Migraineurs than the control patients.
• Migraine with aura was associated with significantly increased PCT infarcts, but not Migraine without aura.
• "The adjusted OR was 13.7 (95% CI, 1.7-112) for patients with migraine with aura compared with controls. In patients with migraine with a frequency of attacks of 1 or more per month, the adjusted OR was 9.3 (95% CI, 1.1-76). The highest risk was in patients with migraine with aura with 1 attack or more per month (OR, 15.8;95%CI, 1.8-140)."¹
• Among women, compared with controls, Migrainuers  had a significantly increased risk of high DWML (dense white matter lesion) load... that was similar for patients with migraine without aura... and patients with migraine with aura...This risk increased with increasing attack frequency...; compared with controls, female migraine patients with fewer than 1 attack per month had an OR (odds ratio) of 1.6 (95% CI, 0.8-3.5) and those with 1 or more attack per month had an OR of 2.6 (95% CI, 1.2-5.7)."¹
• The group with migraine with aura and 1 or more attack per month had the highest risk of PCT infarct.

Notable comments from the authors:

• "These results suggest that patients with migraine from the general population are at increased risk of subclinical cerebellar PCT infarcts and that the risk increases with increasing attack frequency. Patients with migraine with aura and a high attack frequency are at greatest risk. In addition, women, but not men, with migraine with and without aura are at increased risk of high DWML (dense white matter lesion) load, and this risk also increases with increasing attack frequency."¹
• "Our study confirms the vulnerability of the PCT, especially for the cerebellum in migraine patients with aura."³
• "Several hemodynamic features of migraine may contribute to the pathogenesis of both WMLs and infarcts in migraine. Repeated or prolonged reduced perfusion pressure, reduced blood flow, and oligemia in large and/or small arteries, combined with activation of the clotting system or vasoconstriction, possibly mediated or induced by endothelium perturbation (endothelin 1) could lead to arterial or venous (micro) embolism, thrombosis, or ischemia. Dehydration during migraine attacks might contribute to formation of local thromboses. It is also possible that local changes during migraine attacks, such as excessive neuronal activation, neurogenic inflammation, neuropeptide and cytokine release, or excitotoxity, directly lead to tissue damage. Cardiac abnormalities, such as patent foramen ovale or mitral valve prolapse, might also increase the risk of ischemic brain changes in patients with migraine."¹

Worthy of special notice:
If one paragraph of the JAMA article speaks to the importance of such research and the need for continuing research, it is the paragraph quoted below.

"MAGNUM has long held that Migraine Disease is a major public health issue," commented MAGNUM Executive Director Michael John Coleman. He "was encouraged by publication of the Dutch study as the authors addressed many concerns about biases and problems in the methodology of past studies of Migraine and stroke. The current JAMA article powerfully demonstrates the importance of such needed research and expanding the scientific dialogue on Migraine disease research." The study makes his his and my point very proficiently as follows.

"Based on the current evidence, further study into the possible etiologic mechanisms of brain lesions in migraine patients is required.

This will not only provide important clues about the pathophysiology of migraine but also contribute to management guidelines for migraine. Based on the finding of higher risks in those with higher migraine attack frequency, it is necessary to assess whether prevention or (early) abortion of migraine attacks will also decrease the risk for brain lesions and whether there is a subgroup most likely to benefit."

Other specialists comment on the study and article:
In an editorial also in JAMA, Dr. Richard B. Lipton and Dr. Julie Pan said that the Kruit et al article presented "important new data on the prevalence of brain infarction and white matter lesions in persons with migraine." Their editorial is very aptly titled, "Is Migraine a Progressive Brain Disease?"²

Lipton and Pan emphasize:

"These data have implications for current concepts of migraine as a disease; migraine should be conceptualized not just as an episodic disorder but as a chronic-episodic and sometimes chronic progressive disorder. With this shift in conceptualization, the goals of treatment may also shift. Preventing disease progression in migraine has already been added to the traditional goals of relieving pain and restoring patients' ability to function. If the brain lesions demonstrated by Kruit et al have a significant clinical correlate, preventing the accumulation of brain lesions may become an additional goal of treatment. Emerging treatment strategies to prevent disease progression, including risk factor modification, preventive therapies, and the early use of acute treatments, are an important focus for future investigation."²

Dr. Joel R. Saper, director of the Michigan Head Pain and Neurological Institute in Ann Arbor, told ABC News: "You might have a patient who says, 'I can live with three headaches per week.' This study, if validated, means maybe they shouldn't ... If we say that progressive changes are occurring in the brain from recurring and repetitive attacks … then there's a greater burden on preventing those attacks." 

Susan Moeller Denny, MAGNUM's Director of information, while quite pleased that the media attention to the JAMA article was getting Migraine disease and research the attention of the public, was concerned by some of the phone calls and emails pouring into their headquarters in Washington, DC. Along with a multitude of calls from the media, there were calls and emails from Migraineurs who were confused and upset, especially by the ABC News article. She commented, "While it's true that Migraine can cause damage to the brain, and people need to know that, the public perception of the phrase "brain damage" is a perception of cognitive damage . .. a perception of mental and/or emotional impairment."

Although coverage of this topic is important, ABC could have researched the basics of Migraine disease better and chosen a more accurate title than, "Migraine Maladies: Migraines May Starve Brain of Oxygen, Causing Lasting Damage." Dr. Fred Sheftell agrees:

"While I think well intentioned, the content of the article (ABC article) will serve more to frighten patients than to inform them.  As president of the American Council for Headache Education and chair of the World Headache Alliance I applaud exposure which highlights the need to take migraine seriously given its impact.  I would however, offer: The thrust of the article may be a little overkill in regard to the implications as there is no evidence to support that the lesions are either due to diminished blood supply, have clinical importance, or are diminished by acute or preventive medications.  We have been aware of the presence of these lesions for years. All we know is that they are there; the rest is a stretch and totally hypothetical . . . Since most researchers agree that blood vessel constriction is an unlikely mechanism in migraine, the "neurogenic" theory makes these lesions even more mysterious and difficult to explain."⁵

Summary:

MAGNUM, the National Migraine Association was the first nongovernmental organization (NGO) to address Migraine as a disease in the public forum. The editorial in this same JAMA issue supports addressing Migraine as a disease, and points out "With this shift in conceptualization, the goals of treatment may also shift." This study presents not only new information, but information that verifies and reinforces some previously published and taught philosophies of treatment. MAGNUM has recommended a "Multifactoral Approach" for over a decade now.

1. Trigger identification and management
2. Preventive treatment
3. Attack abortive treatment
4. Pain management as needed

As always, I encourage you to keep learning and to take charge of your health and your health care. Address the four aspects above, and work with your primary physician to manage your overall health in a way the reduces risk of stroke or cardiovascular disease. Keep working on Migraine prevention, and treat a Migraine attack as soon as possible. All of these will help keep you healthier longer.

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Resources:

¹ Mark C. Kruit, MD; Mark A. van Buchem, MD, PhD; Paul A. M. Hofman, MD, PhD; Jacobus T. N. Bakkers, MD; Gisela M. Terwindt, MD, PhD; Michel D. Ferrari, MD, PhD; Lenore J. Launer, PhD. "Migraine as a Risk Factor for Subclinical Brain Lesions." JAMA. 2004;291:427-434.

² Richard B. Lipton, MD; Julie Pan, MD, PhD. "Is Migraine a Progressive Brain Disease?" JAMA. 2004;291:493-494.

³ Joanna Schaffhausen. WHAT'S THE PROBLEM? "Migraine Maladies: Migraines May Starve Brain of Oxygen, Causing Lasting Damage." abcNEWS.com. January 27, 2004.

⁴ Michael John Coleman and Susan Moeller Denny of MAGNUM, the National Migraine Association. Personal interview with Teri Robert. January 31, 2004.

⁵ Dr. Fred Sheftell. Personal interview with Teri Robert. January 31, 2004.

Published February 1, 2004
© Teri Robert