Migraines and a shunt in the heart

Cardiologists around the world are eagerly awaiting the results of clinical trials testing an intriguing hypothesis: that many people who regularly suffer from migraine headaches may very well have a common defect of the heart.

The intriguing part is that the hypothesis was stumbled upon by accident by doctors testing whether the defect - known as a patent foramen ovale (PFO) or atrial septal defect (ASD) - was implicated in cryptogenic stroke.

Cryptogenic stroke particularly affects young people. In older people, a combination of age, diet and other environmental factors usually results in atherosclerosis, long implicated in stroke. Cryptogenic stroke, on the other hand, is a stroke with unknown aetiology that often affects young people out of the blue.

A link between cryptogenic stroke and a PFO was first mooted in the mid 1990s and many clinical studies are underway to discover whether closing the PFO with a medical device can make a difference in reducing recurrent stroke.

While the results of these studies aren't conclusive yet, the very act of closing the PFO to reduce stroke has led to a quite remarkable observation: more than 70 per cent of patients who have had the procedure also had a major reduction in incidents of migraine.

Dr Jonathan Tobis, a professor of medicine at UCLA, told an international cardiology conference in Sydney recently that based on results to date, he was optimistic that migraine sufferers will have a new treatment option in the future.

"We looked at young people who were developing strokes without a known cause, and found that 50 per cent had an open PFO - well above what we would expect across the community - and nearly half of those with an open PFO had migraines," Tobis said.

"When the passage was closed, 75 per cent of those people who had suffered from migraine found that their migraines went away or were significantly reduced."

An open PFO is thought to occur in one in four people and usually has no serious implications. A PFO is a passageway or shunt in the heart between the right and the left atrium and is required in utero, when a foetus gets its oxygen from the placenta.

"The amount of oxygen in the placenta is actually much lower than in normal arterial blood, so if blood moved from the right atrium to the pulmonary circulation and the back to the left side and up to the brain, it would lose even more oxygen," Tobis said.

"So by having this shunt you get that oxygenated blood going directly from the right to the left side and then up to the brain. When we are born and start breathing ... we don't need the shunt."

As the pressure in the left atrium increases after birth, it pushes the flap against the atrial septum and scar tissue develops, closing the passageway forever. In 25 per cent of people, however, this doesn't happen, he said.

"For a couple of hundred years no one thought this PFO caused any problems ... but it turns out that about 50 per cent of people who have a cryptogenic stroke have a PFO - twice the incidence than in the general population. That doesn't prove anything but it's an interesting association."

The hypothesis linking the open PFO to stroke is that blood clots are able to move directly from the right atrium to the left and straight to the brain. There are currently two ongoing studies to see if randomising patients between medical therapy and PFO closure can make a difference, and while the results aren't out yet there are a number of previous studies that suggest the recurrence of stroke is worse with medicine, he said.

(In the past, the PFO could only be closed by open heart surgery. These days, more than a dozen devices called septal occluders are being developed that work to close the PFO and are inserted percutaneously - placed through a catheter that is inserted by a needle.)

"Then the question is how does this relate to migraines," Tobis said. "It turns out that of the people who have cryptogenic stroke and an open PFO, about 50 per cent of them have migraines. The general incidence of migraine is 12 per cent of the population - 18 per cent of women and six per cent of men - and the incidence of PFO in people with migraine is higher than normal.

"In addition, in some of the earlier studies, when those people had their PFO closed to prevent cryptogenic stroke, the migraines went away in a high percentage of people - 71 per cent. Then also, we know that people who have migraines have a high incidence of abnormal MRIs - 13 times higher."

More intriguing questions have resulted from the massive American Physician's Health Survey, which has been ongoing for 20 years or so and has looked at about 20,000 men. Seven per cent of men have migraines, and according to Tobis those men also had a 24 per cent increased risk for cardio-vascular events, 40 per cent increase of heart attack, 12 per cent increase in stroke and seven per cent increase in cardio-vascular death.

"That's quite remarkable and the previously published women's health study had similar phenomena. And nobody knows what causes that.

"The neurologists treating the migraines don't have an explanation of why you should get these things. There are some theories but we don't really know. The assumption has been that maybe there is something biological or biochemical that is produced in migraines and also in these patients that produces atherosclerosis, the hardening of the arteries - and we have to figure out what that is biochemically.

"Another theory though, my theory, is that it is due to PFOs. We know that people who have migraines have a 50 per cent incidence of a PFO and if a blood clots goes it could cause a stroke, it could cause a heart attack, whether or not you had underlying atherosclerosis.

"When you close the PFO to prevent recurrent stroke, 78 per cent of those [patients] overall improved their migraines. For people who have migraine with aura, about 75 per cent of them have complete abolition of their migraines - gone completely."

(An 'aura' is a visual disturbance experienced in the hours before a migraine occurs, acting as a warning sign.)

"If you have migraines without aura it's not as dramatic but about 60 per cent of those have a significant reduction, and that's usually defined as a 50 per cent reduction in the amount of headache days. So these are the observations - it doesn't prove it, but it engenders enough interest that people are willing to spend millions of dollars to do these clinical trials."

A genetic link is definitely suspected, with one recent study looking at several generations of people with both open PFOs and migraines - "they run together, at least", Tobis said.

The next question is whether studies currently being carried out on people with severe migraines, defined as greater than six migraines a month, can prove that by closing the PFO the migraines go away, he said.

"If it shows that the migraines will go away, then we have to change our ideas on what migraine is. We believe that what is going on is that just as there are blood clots going across the PFO [causing stroke], there are chemicals that are going across the PFO that trigger the migraine.

"Of course, you can have migraine without a PFO - there are other triggers like sleep deprivation, lights, smoking cigarettes, but also drinking red wine, chocolate, nuts in some people - so there are chemicals that have been ingested that can induce the migraine.

"We believe they are absorbed and they go from the right atrium to the left atrium up to the brain. If you close the PFO and the migraines go away, then you've got to come up with an explanation as to why that should happen. If it's just a neurological phenomenon, PFOs shouldn't make a difference.

"Because of these observations, we believe that there is some connection, that it is because chemicals are moving across the PFO. By closing the PFO you'll prevent both the chemicals from going across [causing a migraine] and the increased risk of heart attacks and stroke in the migraine population."

Not only would closing the PFO rectify recurring stroke and migraine, but it might have an application in older people as well. "There are studies of people who have a PFO who have had strokes in the older age group, older than 65 ... and the incidence of PFO is actually three times greater. So as we get older, yes strokes are due atherosclerosis, but a number of them might be due to blood clots.

"As we get older we get more varicose veins, the pressures in the right side of the heart increase and there may be more shunting, and some of those strokes in elderly people might be due to PFO. One recommendation is that we would treat both - so you lower the cholesterol but you also close the PFO."

If all of the studies prove the PFO-stroke-migraine link is there, Tobis envisages a day in which people with PFOs suffering from migraine would have simple day surgery to close the flap. "In the future, millions could be treated for migraines in this way."