Patients who have migraines may be at an increased risk for developing subclinical lesions in certain areas of the brain, according to Mark C. Kruit, MD, and colleagues. The overall prevalence of brain infarcts in patients with migraine was not significantly different from that of controls, but the presence of infarcts in the cerebellar region of the posterior circulation territory was significantly higher, the researchers found. Those patients who had both migraine with aura and a high attack frequency had the greatest risk.

As reported in the January 28 JAMA, the investigators analyzed data from a sample of randomly selected Dutch adults, ages 30 to 60, from the Genetic Epidemiology of Migraine study. The trial included 161 patients who experienced migraine with aura, 134 patients who had migraine without aura, and 140 controls who were matched to cases for age, gender, and place of residence. About half the cases had not been previously diagnosed by a physician, and no patients had reported a history of stroke or transient ischemic attack or had relevant abnormalities at standard neurologic examination.

Because of the high prevalence of migraine in the general population, Dr. Kruit’s team wanted to establish whether migraine was an independent risk factor for subclinical infarcts and white matter lesions. Both types of brain lesions have previously been shown to increase the risk of adverse sequelae, including clinical stroke events, physical limitations, and cognitive impairment, including dementia.

MIGRAINE AND LESIONS

Dr. Kruit’s team found that patients with migraine had an overall infarct prevalence rate of 8.1%, compared with 5% for that of controls. In the cerebellar region of the posterior circulation territory, patients with migraine had a significantly higher prevalence of infarct than did controls (5.4% versus 0.7%). In addition, patients with migraine with aura had 13.7 times the risk for infarct than did controls. In patients with migraine with a frequency of attacks of one or more per month, there was a 9.3-times increased risk. The highest risk for infarct occurred in patients with migraine with aura with one attack or more per month (15.8-times increased risk).

The investigators also found that women with migraine had twice the risk for deep white matter lesions, compared with controls. This risk increased with attack frequency (highest in those with one or more attacks per month, 2.6-times increased risk) but was similar in patients with migraine with or without aura. Male controls and patients with migraine did not differ in the prevalence of deep white matter lesions. Furthermore, no association was found between severity of periventricular white matter lesions and migraine, irrespective of gender or migraine frequency or subtype.

“Based on the current evidence, further study into the possible etiologic mechanisms of brain lesions in migraine patients is required,” reported Dr. Kruit, of the Leiden University Medical Center in the Netherlands, and colleagues. “This will not only provide important clues about the pathophysiology of migraine but also contribute to management guidelines for migraine.”

Dr. Kruit’s team believes that several hemodynamic features of migraine may contribute to the pathogenesis of white matter lesions 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,” the investigators wrote. They also noted that dehydration during migraine attacks might contribute to formation of local thromboses.

Although their results suggested that the risk for both cerebellar infarcts and high deep white matter lesion load was slightly mediated by the use of ergotamines, the researchers stated that the numbers were “too small to separate the effects of the medication per se and attack frequency.” Therefore, they could not exclude that using ergotamines was a marker of disease severity. They added that although ergotamines are known to cause vasoconstriction in the extracranial circulation, it is not known what effect they have in the brain.

“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,” Dr. Kruit’s team stated.

IS MIGRAINE A PROGRESSIVE BRAIN DISEASE?

In an accompanying editorial, Richard B. Lipton, MD, and Jullie Pan, MD, PhD, both of the Albert Einstein College of Medicine, Bronx, New York, commented, “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.… 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.”

NR

—Colby Stong

Suggested Reading
Kruit MC, van Buchem MA, Hofman PAM, et al. Migraine as a risk factor for subclinical brain lesions. JAMA. 2004;291:427-434.
Lipton RB, Pan J. Is migraine a progressive brain disease? JAMA. 2004;291:493-494.

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