Perspective:

The following are 10 points to remember regarding this review on patent foramen ovale (PFO) and migraine:

1. The estimated prevalence of migraine is 6% in men and 15-17% in women ages 20-62.

2. The mechanism linking PFO to migraine is unknown. One hypothesis suggests that metabolites and microemboli normally removed by passage through the lungs cross the PFO and enter the systemic circulation, with resultant irritation to the trigeminal nerve and vascular network. An additional hypothesis suggests that hypoxemia related to right-to-left shunting may increase plasminogen activator-1, which may suppress fibrinolysis and increase risk for paradoxical microembolism.

3. The current review identified a total of 41 manuscripts meeting eligibility criteria, of which 20 investigated the relationship between PFO and migraine, and 21 investigated the impact of PFO closure on migraine burden.

4. Case series and cohort studies report significant variability of prevalence of PFO in patients with migraine, ranging from 14.6-66.5%.

5. Case-control studies report a similarly broad prevalence of 26.8-96% of PFO in patients with migraine with aura, as compared with prevalence of 16.0-25.7% in controls.

6. Based on case series, migraine with aura resolution after PFO closure ranged from 28.6-92.3%, whereas migraine without aura resolution ranged from 13.6-82.9%.

7. Additional case series showed that improvement in migraine with aura ranged from 4.17-64.3% after PFO closure, whereas improvement in migraine without aura ranged from 0-68.2%.

8. The only randomized-controlled trial, MIST (Migraine Intervention with STARFlex Technology), published in 2008, compared device closure with a StarFlex device to sham procedure, demonstrating no difference in the primary endpoint of migraine cessation. There were methodological concerns with the MIST trial, including concerns about the screening process, complication rate, and uncertainty regarding residual shunts after device closure.

9. Interestingly, the MIST trial showed resolution rates of only 4% in both the device closure and sham procedure groups, as compared with the complete resolution rates of 13.6-82.9% in the case series.

10. In conclusion, the prevalence of PFO appears be higher in patients with migraine than the general population. While retrospective trials suggest significant benefit of device closure, the sole randomized trial did not reproduce this finding.