LOS ANGELES—Studying migraine with aura and migraine without aura separately will aid the clinical management of these conditions by enabling neurologists to develop increasingly targeted and focused approaches, according to Jes Olesen, MD, Professor of Neurology at the University of Copenhagen.
Defining the similarities and differences between migraine with and without aura will improve researchers’ understanding of migraine mechanisms and could assist drug development, he added. At the 54th Annual Scientific Meeting of the American Headache Society, Dr. Olesen summarized decades of research that has uncovered various distinctions between the two conditions.
Changes in Blood Flow Characterize Migraine With Aura
In the early 1980s, Dr. Olesen and his colleagues used the xenon 133 intra-arterial injection method to study cerebral blood flow in patients with migraine. The researchers observed spreading oligemia in patients with migraine with aura, but no such phenomenon in patients with migraine without aura. “That was one of the key findings suggesting that some sort of distinction should be made between migraine with aura and migraine without aura,” said Dr. Olesen.
The results suggested that the underlying mechanism of migraine with aura was a cortical spreading depression that moved gradually across the brain. This hypothesis was confirmed by several subsequent studies that used perfusion-weighted imaging, which had a higher spatial resolution than the technique that Dr. Olesen had used.
No Blood Flow Changes in Migraine Without Aura
Dr. Olesen subsequently analyzed migraineurs without aura to determine whether they experienced changes in cerebral blood flow. He and his colleagues identified patients in whom migraine attacks could be provoked by red wine. The investigators gave the patients red wine and used the xenon inhalation technique to measure changes in blood flow but found no major changes. Other researchers duplicated these findings using PET.
In a subsequent PET study, Marie Denuelle, MD, a neurologist at the University Hospital Center of Toulouse, France, and colleagues found a mild reduction of blood flow in the posterior of the brain in migraineurs without aura. Peter Goadsby, MD, Professor of Neurology and Director of the Headache Center at the University of California, San Francisco, described changes in the brainstem in migraineurs without aura, but found no posterior hypoperfusion, which was consistent with Dr. Olesen’s findings. If posterior hypoperfusion is confirmed in migraineurs without aura, it may be related to autonomic reflexes rather than migraine, said Dr. Olesen.
Drug Effective for Only One Type of Migraine
The drug tonabersat was found to inhibit cortical spreading depression efficiently, and investigators soon began to study it as a potential treatment for migraine with aura. Dr. Olesen found that, given as a prophylactic drug, tonabersat reduced the number of auras by 70% in migraine patients with aura. A bigger study, primarily of patients with migraine without aura, found that tonabersat had no effect on migraine attacks. Combined, the results provided “the first example of a drug that works in migraine with aura, but not in migraine without aura,” noted Dr. Olesen.
Genotype May Affect Migraine Type
Other studies revealed that migraine with aura and migraine without aura are associated with different genotypes. Dr. Olesen found that first-degree relatives of a migraineur with aura have a risk of developing migraine with aura that is four times greater than people who are not first-degree relatives of a migraineur with aura. Having a first-degree relative who has migraine with aura does not affect one’s risk for having migraine without aura, however.
In addition, three gene mutations have been determined to cause familial hemiplegic migraine, a form of migraine with aura. But these gene mutations do not cause migraine without aura, according to Dr. Olesen.
Other researchers, such as Daniel Chasman, PhD, associate geneticist at Brigham and Women’s Hospital in Boston, identified genome variants associated with an increased risk of migraine, but they found that the genes were not associated more strongly with migraine with aura or migraine without aura. “It is likely that a number of variants predispose us for migraine of any kind, and other variants predispose us for having a specific form of migraine,” said Dr. Olesen.
Migraine With Aura Is Associated With More Comorbidities
Subsequent investigations showed that migraine with aura is associated with 23 comorbidities, while migraine without aura is associated with 12 comorbidities. The difference in comorbidities was more evident among female migraineurs than among males, said Dr. Olesen.
Migraine with aura doubles a patient’s risk of stroke, but migraine without aura does not affect this risk. Scoliosis, hypothyroidism, Ménière’s disease, tinnitus, and epilepsy are among the other comorbidities associated with migraine with aura, but not with migraine without aura.