Patent Foramen Ovale and Migraine

What is a Patent Foramen Ovale (PFO)?

A PFO is a small opening between the right and left atria of the heart. While this opening is normal and necessary before birth, it typically closes shortly after. However, in about 25% of the general population, this opening remains patent (open) [1].

Key PFO Points:

• Present in approximately 1 in 4 people
• Usually asymptomatic
• Allows some blood to bypass the lungs

The PFO-migraine connection studies have shown a strong association between PFO and certain types of migraine:

• 46-88% of patients with migraine with aura have PFO (numbers differ depending on the study)
• 16-35% of patients with migraine without aura have PFO (very similar to those without migraine)
• 66% of chronic migraine patients have PFO [1]

This higher prevalence suggests a potential link between the two conditions, but it's important to note that correlation doesn't necessarily mean causation.

How Might PFO Trigger Migraine Attacks?

Several hypotheses attempt to explain the potential mechanisms by which PFO could lead to migraine attacks [1]:

1. Chemical Bypass: PFO might allow certain chemicals, like serotonin, to bypass lung filtration. This could result in higher concentrations reaching the brain, potentially triggering migraine attacks.
2. Microemboli and Cortical Spreading Depression: This complex process involves several steps:
   • Tiny blood clots (microemboli) pass through the PFO from the venous to the arterial system
   • These microemboli cause small areas of reduced blood flow in the brain
   • Reduced blood flow leads to localized brain tissue hypoxia (low oxygen)
   • Hypoxia triggers cortical spreading depression: a wave of neuronal and glial depolarization
   • Cortical spreading depression is believed to be the underlying mechanism of migraine aura
   • This phenomenon can activate the trigeminovascular system, leading to migraine pain
3. Chronic Hypoxemia: PFO can cause a general decrease in blood oxygen levels, potentially making the brain more susceptible to migraine triggers.
4. Genetic Factors: There may be shared genetic factors contributing to both PFO and migraine susceptibility, explaining their co-occurrence without a direct causal relationship.

The Discovery of the PFO-Migraine Link

The connection between PFO and migraine was first observed in divers with decompression sickness. Researchers noticed that when divers had their PFOs surgically closed to prevent decompression sickness, many experienced a reduction in migraine attacks as well [2]. This finding led to further investigation of the PFO-migraine connection.

PFO Closure for Migraine: Current Evidence

The potential link between PFO and migraine has led to studies investigating whether closing the PFO could reduce migraine frequency or severity. Here's what we know so far [2]:

• Clinical trials have NOT shown significant overall benefit for all migraine patients
• Some studies suggest potential effectiveness for patients with frequent aura
• PFO closure may reduce stroke risk in certain patients
• Further research is needed, especially for specific patient subgroups

A recent meta-analysis evaluated the effect of PFO closure on patients with migraine refractory to multiple medications. The primary outcome of reduction in monthly migraine attacks and complete resolution of migraine headache was higher in the PFO closure group compared with the control group. Similarly, reduction in monthly migraine days was significantly better in the PFO closure group [3].

Subgroup analysis found that patients with migraines with aura, particularly those with frequent aura, had a significantly greater reduction in migraine days and a higher incidence of complete migraine cessation following PFO closure. In patients with migraines without aura, PFO closure did not significantly reduce migraine days or improve complete headache cessation [3].

Safety and Adverse Events

While PFO closure appears to be generally safe, some adverse events have been reported in clinical trials. These include [4,5,6,7]:

• Device-related events (e.g., transient atrial fibrillation, general fatigue, syncope)
• Implant procedure-related events (e.g., access-site bleeding, retroperitoneal hematoma, arm phlebitis)
• Other events (e.g., muscle wasting, site bleeding, anemia, nosebleed)

Most adverse events resolved without sequelae, and no long-term device-related side effects were observed after at least one year of follow-up.

PFO, Migraine, and Stroke: A Complex Relationship

The connection between PFO, migraine, and stroke adds another layer of complexity [2]:

• Migraine patients, especially those with aura, have an increased stroke risk
• There's a high prevalence of PFO in patients with unexplained (cryptogenic) strokes
• Nearly 80% of cryptogenic stroke patients with migraine had PFO
• PFO may allow blood clots or air bubbles to travel directly to the brain, potentially increasing stroke risk

Final Thoughts

The relationship between patent foramen ovale and migraine is an evolving area of research. There are still many unanswered questions, and PFO closure is NOT currently recommended for migraine patients (outside of clinical trials, anyway). However, for certain subgroups, particularly those with frequent aura, PFO closure may offer potential benefits in reducing migraine frequency and severity.

If you suffer from migraine or have concerns about PFO, always consult with a healthcare professional for personalized advice and treatment options. As research in this field continues to advance, we may gain a better understanding of the complex relationship between PFO and migraine, potentially leading to more targeted and effective treatments in the future.

References:

1. Petrarca, K., Postalin, A., Calise, M., & Serth, L. (2024). Diving into the Connection Between Migraine and Patent Foramen Ovale.
2. Charles, A. (2024). PFO Closure for Migraine Prevention. American Headache Society.
3. Zhang, Y., Wang, H., & Liu, L. (2022). Patent Foramen Ovale Closure for Treating Migraine: A Meta-Analysis. Journal of Interventional Cardiology, 2022, Article ID 6456272.
4. Dowson, A., Mullen, M. J., Peatfield, R., et al. (2008). Migraine Intervention with STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation, 117(11), 1397-1404.
5. Tobis, J. M., Charles, A., Silberstein, S. D., et al. (2017). Percutaneous closure of patent foramen ovale in patients with migraine: the PREMIUM trial. Journal of the American College of Cardiology, 70(22), 2766-2774.
6. Mattle, H. P., Evers, S., Hildick-Smith, D., et al. (2016). Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial. European Heart Journal, 37(26), 2029-2036.
7. Mojadidi, M. K., Kumar, P., Mahmoud, A. N., et al. (2021). Pooled analysis of PFO occluder device trials in patients with PFO and migraine. Journal of the American College of Cardiology, 77(6), 667-676.