Women With Multiple Sclerosis Have High Rate of Migraine

Allison Gandey

February 19, 2010

February 19, 2010 — A new analysis from the Nurses' Health Study shows that women with migraine have a nearly 50% increased relative risk of being diagnosed as having multiple sclerosis.

Headache is increased among multiple sclerosis patients in most clinic-based studies, report researchers, and this new study is questioning which comes first — the migraine or multiple sclerosis.

"It must be emphasized that over 99% of people with migraine will not develop multiple sclerosis since it is a rare disease," lead investigator Ilya Kister, MD, from New York University, New York City, told Medscape Neurology.

In contrast, migraine can be common — about 1 in 5 women in the United States will have migraine headaches over the course of a year.

The study will be presented in April at the American Academy of Neurology (AAN) 62nd Annual Meeting in Toronto, Ontario, Canada. First results were released February 16.

Researchers studied a cohort of more than 116,678 women. Of these, 375 were diagnosed as having multiple sclerosis during a follow-up of 16 years.

It must be emphasized that over 99% of people with migraine will not develop multiple sclerosis.

"Using Cox proportional hazards models, we estimated the relative risk of multiple sclerosis associated with having a preexisting history of physician-diagnosed migraine," Dr. Kister explained.

More than 7900 women in the study reported having a physician-diagnosed migraine at baseline in 1989. This represents 15% of the cohort. In all, 22% of the women who developed multiple sclerosis during follow-up reported ever having had a physician-diagnosed migraine.

After adjusting for potential confounders, such as age, latitude of residence, Scandinavian ancestry, vitamin D status, smoking status, and body mass index, investigators found that having a history of migraine at baseline was associated with an increased risk of multiple sclerosis.

Among the subset of women who experienced their first multiple sclerosis symptom after baseline, the relative increase in risk was a nonsignificant 30%.

Table. Risk of Multiple Sclerosis (MS) in Patients With a History of Migraine

History MS Risk, % Relative Risk (95% Confidence Interval) P Value
Migraine at baseline 47 1.47 (1.15 – 1.88) .002
MS symptoms after baseline


1.30 (0.94 – 1.80) .11


"A number of explanations for higher rates of migraine among multiple sclerosis patients are possible and will be discussed in more detail during the AAN presentation," Dr. Kister said. "One explanation is that migraine can, in some cases, be viewed as a symptom of multiple sclerosis."

Alternatively, Dr. Kister suggests, the higher frequency of migraine could be due to an intermediate variable such as depression or a medication such as interferon, which may have migraine as an adverse effect. Migraine may also be a factor that predisposes a patient to develop multiple sclerosis.

In a blog discussing the new study, Daniel Kantor, MD, argues that it is unlikely that migraine is prompting multiple sclerosis. Dr. Kantor is president-elect of the Florida Society of Neurology and medical director of Neurologique, an organization dedicated to patient care, research, and education.

The idea that migraine precedes the multiple sclerosis and not vice versa assumes the disease comes on at a certain defined point, like a car accident, Dr. Kantor said.

"Instead, we believe that multiple sclerosis is diagnosed well after the disease process starts — even prior to the initial symptoms — so it could be that the women who had migraines and then went on to be diagnosed with disease, actually had multiple sclerosis first."

Ask Patients About Migraine

Dr. Kantor told Medscape Neurology that this study highlights the need for neurologists to ask patients with multiple sclerosis about migraine.

"I think it would be very dangerous for us to do this the other way around and start scanning all patients with migraine. That is totally unnecessary," he emphasized.

Dr. Kantor says this study risks striking fear in the 18 million to 20 million American women with migraines. He also questions some of the numbers. If 375 of the more than 116,000 women had multiple sclerosis, this makes a prevalence of 321.397835 per 100,000, he explains. "This is extremely high and raises questions about the data."

In another study presented in September at the International Headache Congress, investigators reported an increased risk for ischemic brain and white matter lesions in patients with repeated migraine attacks.

Those results suggested that patients with migraine have more lesions, but the study authors pointed out at the time that this does not indicate that patients are at higher risk for multiple sclerosis or other diseases.

More White Matter Lesions

"The more attacks you have had, the more likely it is that you will have brain lesions," lead investigator Michel Ferrari, MD, from Leiden University Medical Center in the Netherlands, said at the meeting. "I think it's important to emphasize that just plain migraine can cause these effects and that you don't need to go through all kinds of investigations for diseases which are even more severe."

The study, known as Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA II), evaluated 286 patients. The 9-year magnetic resonance imaging follow-up study found that the risk of lesions is especially pronounced in migraine without aura.

Dr. Kister acknowledges that many questions remain. "We hope that our work serves as stimulus for closer study of the interrelationship between migraine and multiple sclerosis."

The researchers have disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 62nd Annual Meeting. Presented April 10-17, 2010.


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