What is the last word on migraine and PFOs?

This is surely one of neurology’s bug bears, the old chestnut. Just when one generation of neurologists thinks it has buried and sealed it in an impervious crypt, it resurrects to haunt the next breed. This cyclical and macabre dance of migraine and PFOs evokes a sense of deja vu every time it comes around. And each spawn of neurologists predictably picks up the gauntlet, answers the call to arms, and sets out to slaughter the ghost of migraines past.

By Lille1982 – Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9682382

But let’s take a step back to basics with some definitions. The foramen ovale is just a ‘hole in the heart‘ between the right and left atria, or upper heart chambers. It is essential in foetal life because it enables circulating blood to bypass the superfluous foetal lungs (apologies to readers across the Atlantic for the superfluous ‘o’!). However, after birth, when blood needs to circulate through the now indispensable lungs, the foramen ovale becomes irrelevant. In most people, the foramen ovale humbly accepts its fate, crawls to a corner, and closes shop. But foramen ovales in some people are recalcitrant; standing their ground, they endure and survive as PFOs.

By DrJanaOfficial – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50477765

It is not clear how the myth started, but stories of migraine cure following surgical closure of PFO spread rapidly and widely. Very soon, migraineurs where demanding echocardiograms to check if they have PFOs lurking in their tickers. Research trials investigating this issue started as a trickle, and very soon become a flood. But rather than shed light, the conflicting results intensified the darkness. That is, until some indignant and determined neurologists and cardiologists set out to settle the matter once and for all. And the onslaught came in three waves of studies.

MIGRAINE. aka Tman on Flickr. https://www.flickr.com/photos/rundwolf/331545021

The first wave in the attempt to slay the beast of migraine and PFO was a trial published in the journal Headache. Davinia Larrosa and colleagues studied 183 people with migraine and found that, whilst PFOs were larger and more permanent in people with migraine, there was no relationship between patent foramen ovale and migraine frequency.

Migraine spectrum. JoanDragonfly on Flickr. https://www.flickr.com/photos/joandragonfly/26221136058

The second wave was a study published in the European Heart Journal by Heinrich Mattle and colleagues. In their PRIMA trial (Percutaneous Closure of PFO in Migraine with Aura), they blindly allocated or randomized half of their subjects with refractory migraine and PFO to have PFO closure surgery. And their verdict was, PFO closure did nothing to reduce the frequency of migraine.

Open the key to your heart. Maria Eklind on Flickr. https://www.flickr.com/photos/mariaeklind/24659701809

The third wave, launched by Nauman Tariq and colleagues, took a different tack. They carried out a detailed review of practically all the studies that had addressed the subject. Their brilliantly titled paper, “Patent foramen ovale and migraine: closing the debate, reflected their ambition to settle the question once and for all. After an arduous trawl through the literature, and a mind-blowing crunching of statistics, the authors came to the conclusions that “there is no good quality evidence to support a link between migraine and PFO“, and “closure of PFO for migraine prevention does not significantly reduce the intensity and severity of migraine“.

By Patrick J. Lynch, medical illustrator – Patrick J. Lynch, medical illustrator, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1488277

The final word therefore is, leave PFOs alone! But there is a big caveat. There is one situation where PFO is associated with migraine, and that is when it is accompanied by another heart anomaly called an atrial septal aneurysm (ASA). The evidence for this comes from Roel Snijder and colleagues, and the title of their paper says it all: Patent foramen ovale with atrial septal aneurysm is strongly associated with migraine with aura: a large observational study. We already knew that PFO associated with ASA increases the risk of stroke; we can now add to this, the risk of migraine with aura.

By H. Airy – Flatau 1912 “Migrena” monograph after previous publication of H. Airy, Public Domain, https://commons.wikimedia.org/w/index.php?curid=7814450

The debate is now hopefully sealed and settled. But don’t hold your breath for too long: the phantom of migraine and PFO may just rear its hideous head again at a neuroscience centre near you.

 

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