The Mysterious Link Between Migraine Aura and Headache

A new brain imaging study finds no evidence for breakdown of the blood-brain barrier in the wake of migraine aura. Image: Artist’s depiction of a zigzag visual disturbance experienced during a migraine aura. Credit: Wikimedia Commons.

A migraine attack is more than a debilitating headache. Before the throbbing pain begins, some individuals experience strange sensations collectively known as an “aura.”

These patients can partially lose their vision, or see zigzag lines that aren’t really there, or more rarely, feel a tingling sensation, among other things. But the relationship between migraine aura and headache has long been a mystery.

According to one long-standing hypothesis, a wave of decreased nerve cell activity in the brain not only causes an aura but also leads to a breakdown of the so-called “blood-brain barrier,” or BBB, formed by cells that line the inside of the brain’s blood vessels. That would allow inflammatory proteins in the body’s circulatory system to slip inside the brain—something that the BBB normally protects against—and rouse the neurons there that trigger a migraine headache.

A new brain imaging study in 19 migraine with aura patients, however, finds no evidence for that hypothesis. Messoud Ashina, University of Copenhagen, Denmark, and colleagues now report that in the wake of migraine aura, the BBB remains intact.

The results have important implications for an understanding of how migraine medications work. These drugs reportedly can’t get across the BBB, and are usually taken around the time when Ashina and his colleagues scanned patients’ brains.

“What’s nice about the authors catching patients during the early phase of the migraine headache is that it’s probably not the case that these drugs are gaining access to the brain,” says Gregory Dussor, University of Texas at Dallas, US. Dussor is a migraine researcher but was not involved in the study.

The findings were published online April 18 in the journal Brain.

No evidence for a weakened blood-brain barrier
The idea that migraine patients might have a leaky BBB dates back to the 1970s. In the decades after it was first proposed, the idea evolved into more specific hypotheses.

One theory has maintained that a dip in activity in the cerebral cortex, which patients perceive as an aura, somehow causes a breach in the BBB. “The hypothesis was based on preclinical science,” explains Ashina, referring to animal studies.

So, to test that possibility in migraine with aura patients, first author Anders Hougaard and colleagues used a brain imaging technique that can measure the integrity of the BBB. Once patients had an aura, they telephoned the researchers and then came in to be scanned (that is, during their headache).

Patients were asked to return on a day without a migraine attack for a second scanning session so that the researchers could look for changes in the BBB. Altogether, 19 men and women, aged 22- to 59-years- old, completed the study.

When the researchers compared the scans from days with and without migraine attacks, they saw no differences. Even when comparing patients who reported visual disturbances—the most common set of aura symptoms—with those who did not, there was no observable leak in the visual cortex, the area of the brain responsible for seeing.

To Ashina, the new study provides the strongest evidence to date against the hypothesis linking migraine aura to headache via a weakened BBB. Still, the investigators can’t exclude the possibility that “other [experimental] methods, or methods used during the aura phenomenon, will show something different,” he says.

Perhaps the BBB only breaks down during an aura, which lasts on average for about 20 minutes, and at most for an hour. “That’s certainly a caveat,” says Dussor.

But if these patients really do have an intact BBB, then it seems that migraine medications work by acting outside of the brain.

To read about the research in more detail, see the related Pain Research Forum news story here.

Matthew Soleiman is a science writer currently residing in Nashville, Tennessee. Follow him on Twitter @MatthewSoleiman