Review Explores Association Between Migraine and Patent Foramen Ovale

A “dose-response” relationship may exist between migraine and patent foramen ovale (PFO), according to a review published in Frontiers in Neurology.

A “dose-response” relationship may exist between migraine and patent foramen ovale (PFO), according to a review published in Frontiers in Neurology. However, authors cautioned more work needs to be done in terms of patient selection, in addition to the inclusion of an antiplatelet control group for PFO closure interventions, to uncover possible beneficial results for migraineurs in clinical trials.

According to the American Heart Association, a PFO is a hole in the wall of tissue (septum) between the left and right upper chambers of the heart (atria) that can only occur after birth when the foramen ovale does not close. “This hole allows blood to bypass the fetal lungs, which cannot work until they are exposed to air.” The foramen oval closes when a newborn takes its first breath and heals completely within a few months in about 75% of humans.

PFO is the most common congenital cardiac anomaly in adults and in 1998, one study found the incidence of PFO in migraineurs was significantly higher compared with healthy controls. Later studies also confirmed incidence of PFO among migraineurs ranged from 14.6% to 66.5% compared with 9% to 27.3% in the general population. Subsequent investigations concluded “in the population with PFO, the incidence of migraine was 9.13%-51.7%, which was also higher than the incidence of migraine in the general population,” authors wrote.

Explanations regarding the underlying pathophysiology of the 2 conditions are still based on hypotheses. One potential explanation involves the discharge or metabolization of vasoactive substances through pulmonary circulation. As venous blood can enter arterial blood by shunting without circulating in the lungs through the PFO channel, some chemicals and hormones—like serotonin—may bypass the pulmonary circulation, pass directly through the blood-brain barrier, and potentially cause migraine.

In addition, a small embolus in the systemic circulation can pass through the PFO and into the arterial system, which may lead to tiny brain infarctions triggering low perfusion or cortical spreading depression causing a migraine attack. “This hypothesis can also explain the use of antiplatelets or anticoagulants and atrial fibrillation ablation for relieving migraine attacks,” authors wrote.

Varying diagnostic methods for PFO contribute to the diversity in the relationship between PFO and migraine and future studies comparing individual methods ought to be carried out to better clarify the association.

Migraineurs with aura exhibit a stronger correlation with PFO as “incidence of PFO is 46.3%-88% in migraine patients with aura compared with 16.2%-34.9% in migraine patients without aura.” Incidence of PFO in migraine patients without aura is also similar to that of the general population, researchers explained.

The review yielded the additional findings:

  • Studies have shown that the incidence of PFO in chronic migraine, with aura or without aura, is higher
  • Migraineurs with frequent visual aura suffer a higher degree of right-to-left shunt (RLS), and symptoms improved after PFO closure
  • Attack frequency, Headache Impact Test (HIT)-6, and Migraine Disability Assessment Test (MIDAS) scores among migraine patients with moderate or large PFO were significantly higher than those of the mild PFO and non-PFO groups
  • After PFO closure, differences in VAS, HIT-6 and MIDAS scores as well as the headache duration were statistically significant
  • In migraine patients with aura especially, a greater proportion of permanent PFO and large PFO were found

“The frequency of headache onset, but not its clinical features, is also correlated with PFO, which seem to suggest that RLS may trigger the onset of migraine without directly affecting the migraine symptoms,” researchers wrote.

However, based on available evidence, PFO occlusion was not a satisfactory treatment for the improvement of headaches in migraine patients. “More accurate adequate patient recruitment may lead to greater postoperative benefit and more significant symptom improvement,” authors hypothesized.

In the future, randomized controlled studies should not be limited to patients with medication refractory migraineurs and investigations ought to identify migraineurs more likely to benefit from the closure of PFO. These may be migraineurs with more frequent aura attacks and PFO with a larger RLS shunt.

Importantly, “researchers should consider that the closure of PFO may carry a small but relevant risk of serious adverse events including stroke, pericardial tamponade, atrial fibrillation and death,” authors concluded.


Liu K, Wang BZ, Hao Y, Song S, and Pan M. The correlation between migraine and patent foramen ovale. Front Neurol. Published online December 1, 2020. doi:10.3389/fneur.2020.543485