Women with a history of migraine headache with aura (transient neurological symptoms, mostly visual impairments) are at increased risk of stroke. However, according to new research reported in Circulation: Journal of the American Heart Association stroke events in women with migraine with aura are more likely to have mild or no disability compared to those without migraine.

In a new analysis of the Women's Health Study involving 27,852 women over 13.5 years, researchers found those who have migraine with aura and who experience an ischemic stroke were twice as likely to have no significant disability from stroke.

"The message from this study should be reassuring for migraineurs," said Tobias Kurth, M.D., Sc.D., the study's principal author and associate epidemiologist at Brigham and Women's Hospital in Boston, Mass.

"It is important for women who have migraine with aura to know that their risk of stroke is considerably low and there is high likelihood of a migraine-associated stroke being mild."

The reason for these results is unclear. But Kurth, who is also director of research at INSERM in Paris, France, speculated that mechanisms, perhaps involving smaller vessels - not the traditional mechanisms for stroke, lead to a smaller size stroke.

Compared to those without migraine history, women with migraine and aura were more likely to have a good to excellent functional outcome - defined as having no symptoms and no significant disability, researchers said.

Women participating in the study were divided into four groups: 22,723 who reported no migraine history; 5,129 who reported a migraine history; 3,612 who had active migraine; and of those who reported active migraine, 1,435 reported active migraine with aura.

Researchers evaluated functional ability after stroke at hospital discharge using the modified Rankin Scale, a seven-point scale that measures degree of impairment.

At the onset of the study, women completed a questionnaire about their headaches that allowed classification into the groups of migraine with and without aura, history of migraine or no history of migraine. Each following year, the women reported new medical conditions, including transient ischemic attack (TIA) or stroke, which were confirmed after medical record review.

During 13.5 years of follow-up, 398 TIAs and 345 ischemic strokes occurred.

Women in the study were primarily Caucasian, average age 55, healthy and working in the healthcare field.

There is currently little reason to believe that the association differs for women with other characteristics or men, Kurth said.

The first author is Pamela M. Rist, M.Sc., a doctoral student at the Harvard School of Public Health and research fellow at Brigham and Women's Hospital. Other co-authors are: Julie E. Buring, Sc.D.; Carlos S. Kase, M.D.; Markus Schurks, M.D., M.Sc. Author disclosures are on the manuscript.

The Women's Health Study is supported by grants from the National Heart, Lung, and Blood Institute and the National Cancer Institute. Grants from the Donald W. Reynolds, Leducq and Doris Duke Charitable foundations funded part of the study.

An international study led by scientists at Universite de Montreal and University of Oxford, has identified a gene associated with common migraines. Their findings show that a mutation in the KCNK18 gene inhibits the function of a protein called TRESK. TRESK normally plays a key role in nerve cell communication. Published in Nature Medicine, this study may have implications for people who suffer from recurrent headaches, which include more than six million Canadians.

Previously, genes for migraine have been found only in a rare form involving headaches combined with limb weakness limited to one side of the body. "We focused on the more common types of migraine, without this muscle weakness, in our study, and looked at genes controlling brain excitability," says lead author Ron Lafreniere, Associate Director of the Centre of Excellence in Neuromics of the Université de Montréal (CENUM).

The researchers compared the DNA from migraine sufferers to that of non-sufferers. "We found a mutation in the KCNK18 gene that interrupts TRESK function in one large family suffering from migraine with aura," say Lafreniere. "When we tested everyone in the family, all those who suffered from migraine also had the mutation."

Aura migraines are those that are preceded or accompanied by sensory warning symptoms or signs (auras), such as flashes of light, blind spots or tingling in an arm or leg. The ensuing headache can be associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting.

Mutation results in incomplete TRESK protein

The mutation causes production of an incomplete form of TRESK which disrupt the normal functioning of this protein. The end result is an alteration in the electrical activity (excitability) of cells. "We now have direct evidence that migraine is a nerve excitability problem and have highlighted a key causal pathway in migraine' says the joint lead author, Dr Zameel Cader from the MRC Functional Genomics Unit at Oxford.

TRESK present in migraine-relevant areas

Cell culture and in vitro experiments revealed that TRESK is present in certain neurons of the brain. "We showed that TRESK is in specific neuronal structures (trigeminal ganglia and dorsal root ganglia) that have been linked to migraine and pain pathways," says Lafreniere.

"This is a highly significant finding because activation of trigeminal ganglion neurons is central to migraine development and increased activation of these neurons could very plausibly increase the risk for developing a migraine attack," explains senior author Guy Rouleau, a Université de Montréal professor and Director of the Sainte-Justine University Hospital Research Center. "While TRESK mutations are present only in a small number of migraine sufferers, because we believe that TRESK helps control the excitability of nerve cells, our results suggest that increasing TRESK activity pharmacologically may help reduce the frequency or severity of migraine episodes, irrespective of their origin."

About migraines

Migraines are debilitating chronic headaches that can cause pain for hours or days. They can begin in the early teen years and may be triggered by many things, including stress, odors, certain foods, alcohol, etc.