ARTICLE IN BRIEF
Researchers reported an association between migraine and cervical artery dissection, mostly driven by the migraine subtype without aura.
Migraine — especially migraine without aura — is consistently associated with cerebral artery dissection (CEAD) in young stroke patients, according to the results of a large new study from Italian researchers published in the March 6 online edition of JAMA Neurology.
“Our findings, as well as those of others, point toward the apparently paradoxical conclusion that, at least for CEAD, the most frequent cause of early-onset brain ischemia, this risk is mainly driven by the migraine subtype without aura,” wrote the lead author Valeria DiGiuli, MD, and colleagues, of the neurology department at the University of Brescia in Italy.
“However, for complex diseases, such as migraine, identification of the phenotype is challenging due to the lack of objective markers and uncertainty about the cause of the disease,” they wrote. “Furthermore, as the recent large genetic studies on migraine have suggested, the phenotypes commonly used (migraine without aura and migraine with aura) are probably not the most adequate to capture the heterogeneity of the many disease subtypes.”
The 15-year prospective cohort study included 2,485 patients aged 18 to 45 years with first-ever acute ischemic stroke who were enrolled in the multicenter Italian Project on Stroke in Young Adults. The study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differed between patients whose stroke was due to CEAD, and those whose stroke was due to other causes.
After adjusting for other vascular risk factors, migraine without aura was significantly associated with the subgroup of strokes resulting from CEAD (OR, 1.74; 95%CI, 1.30-2.33), but the researchers detected no significant association between migraine with aura and CEAD strokes (OR, 0.80; 95%CI, 0.49-1.29).
“It has been known for a long time that people with migraine are at risk for CEAD, but the sort of subgroup analysis available when you have 2,500 participants hasn't been available in the smaller studies to date,” said Richard B. Lipton, MD, FAAN, Edwin S. Lowe Professor and vice chair of neurology, professor of epidemiology and population health and professor of psychiatry and behavioral sciences at the Albert Einstein College of Medicine in New York, who was not involved with the study. “This is an interesting confirmation of what we have long believed to be true based on smaller studies.”
Gretchen E. Tietjen, MD, Distinguished Professor and Clair Martig Chair of Neurology and director of the Headache Treatment and Research Program at the University of Toledo in Ohio, agreed. “When looking at causes of stroke in young people, we always focus on the more unusual things: heart-related problems like patent foramen ovale, and vascular problems that are non-atherosclerotic, like dissections. Even before we had these findings, for example, I would tell my patients with migraines not to go to chiropractors and get neck manipulation, because of reports that dissection had been associated with chiropractic cervical manipulation.”
But one key finding of the Italian study is likely to raise eyebrows, as it is contradictory with previous research in the field, the experts said. While a number of other case-control studies have linked migraine with CEAD, most epidemiological studies have found an association between young-age stroke and migraine with aura — not migraine without aura, as reported in this paper.
“There's a large literature on migraine and stroke, and for most stroke causes, the migraine with aura group is at increased risk,” observed Dr. Lipton. “In a whole series of papers from the Women's Health Study, migraine with aura doubled the risk of a variety of vascular events, including ischemic stroke, myocardial infarction, and claudication. But this appears to be the exception to that link, suggesting that CEAD appears to be different from those other cerebrovascular phenomena.”
Dr. Lipton praised the study's thorough methodology. “The impressive thing here is that the patients received very thorough workups. Everybody received an MR angiogram, which is a great way of diagnosing dissection; everybody received a transesophageal echocardiography and a bubble study [saline contrast study] to exclude patent foramen ovale,” he said.. “The real strength of study is the high level of diagnostic confidence that these young people had cervical artery dissection as an important cause of stroke.”
On the other hand, he noted, a key limitation of the study is that patients were enrolled because they had had a stroke. “You're taking young people 18 to 45 years old who've had an ischemic stroke and working them up to try to identify an etiology. They found that something like 14 percent of young stroke in this study is due to CEAD, and that migraine without aura is over-represented in this group. Obviously, though, not all CEAD leads to stroke, and those people are missing from the sample. We don't know how the magnitude of risk for CEAD-associated strokes for people who have migraine without aura, because part of the pie is missing.”
Dr. Tietjen added that a significant number of CEADs that do not lead to stroke likely go undiagnosed. “Dissection often presents with a headache or neck pain on one side, and the patient just thinks it's a migraine. Most of the time, it heals on its own.”
As an example, she described a patient she had recently seen — a medical student — who came in after a headache that started with a strange pulling in her neck. “She had a history of migraine, but this felt different. Her symptoms had gotten better, but she was worried. I thought I'd be careful and check things out with a CT angiogram, and sure enough, she had a vertebral artery dissection.”
Dr. Tietjen placed this particular patient on an antiplatelet agent for several months, and cautioned her to avoid chiropractic manipulation and generally be careful of her neck (no bumper cars at the amusement park, for example). “These are young people, they're active, and you don't want to require them to make huge lifestyle changes,” she said. “On the other hand, it is something that gives you pause, because we know it can recur.”
Dr. Lipton noted that the study's most important immediate clinical implication is diagnostic. “We know that migraine is one of the things we should search for as a factor in stroke, especially among young people,” he said. “This study suggests that looking for a migraine with aura isn't enough; you have to assess for migraine without aura too. If you find that in a young person with unexplained ischemic stroke and migraine without aura, it is reasonable to suspect cervical dissection.”
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