Diving into the Connection Between Migraine and Patent Foramen Ovale

Written by: Kylie Petrarca RN, BSN

Medically reviewed by: Dr. Alexander Postalin

Edited by: Melissa Calise and Leigh Serth

What is Patent Foramen Ovale? 

The foramen ovale is a “hole” between the top two chambers of the heart (atria) in fetuses that is necessary for blood to bypass the lungs while the lungs are not functioning. Normally, the hole closes shortly after birth, but in some individuals it stays open and is known as patent (open) foramen ovale (PFO). This occurs in approximately 25% of the general population. This hole between the atria may result in abnormal blood flow from the right side of the heart to the left. 

The Relationship Between Patent Foramen Ovale and Migraine

Interestingly, the presence of a PFO is strongly associated with migraine with aura, migraine aura without headache, and chronic migraine. 

Typical Aura vs. Atypical Aura

A typical aura is defined as an aura that is fully reversible with visual, sensory and/or speech/language symptoms without motor, brainstem or retinal symptoms.¹ An atypical aura is defined as a prolonged aura that lasts more than 60 minutes but less than 7 days without evidence of another disorder.² One study found the prevalence of PFO in those with atypical aura was 79.2% compared to 46.3% in those with typical aura.² Another study found that 67% of those who had migraine aura without headache also had PFO.³

Migraine With Aura vs. Migraine Without Aura

A review of several studies found that, “among migraine patients, the incidence of PFO is 46.3-88% in migraine patients with aura compared with 16.2-34.9% in migraine patients without aura.”³ Those who have migraine without aura do not appear to have a significantly higher prevalence of PFO in comparison to the general population.³ 

Chronic Migraine vs. Episodic Migraine

Lastly, chronic migraine (with or without aura) is more prevalent among those with PFO (66%) compared to the general population and those with episodic migraine.⁴

Hypotheses on How Patent Foramen Ovale May Lead to Migraine:³

• Patent Foramen Ovale can cause some chemicals and hormones such as serotonin to bypass the pulmonary circulation, where they would normally be metabolized, and move through the blood brain barrier to cause migraine. 
• Tiny emboli (small clots and debris) can pass through the PFO from the venous system into the arterial system. If these emboli travel to the central nervous system, they can cause small areas of the brain to have decreased blood flow, and thus low oxygenation. This may trigger a phenomenon called cortical spreading depression, which results in a migraine attack (with aura). 
• Due to the abnormal flow of blood, PFO can result in decreased blood oxygen saturation and hypoxia which can negatively affect the brain. Decreased oxygen to the brain can trigger cortical spreading depression resulting in migraine.
• Genetic factors may lead to development of both diseases simultaneously, without one causing the other.

Diagnosis of Patent Foramen Ovale

Most of the time, many people are unaware they have patent foramen ovale. It is usually discovered during testing for another condition, as it is very common and it usually does not cause symptoms. An echocardiogram (ultrasound of the heart) is used to diagnose a PFO. A bubble study can be added to the echocardiogram when the heart is imaged. Microbubbles are injected into a peripheral vein and if there is a hole, the bubbles would be seen moving from one side of the heart to the other. This injection of microbubbles is harmless. If better anatomic detail is required, then a transesophageal echocardiogram (TEE) can be pursued. In this test, the physician will place a probe with an ultrasound transducer down the esophagus to get a clearer visual of the heart which lies in front of the esophagus. 

Patent Foramen Ovale Treatment and Closure

Treatment may be initiated if someone has a history of blood clots or stroke. Medication regimen typically includes antiplatelet or anticoagulant medications which both help to prevent blood clots. Depending on the circumstances, doctors can close the PFO during open heart surgery or via minimally invasive cardiac catheterization using a closing device.

Closure of a PFO remains controversial for migraine and at this time it is not recommended to close a PFO for this reason outside of a clinical trial. Typically, a PFO would only be surgically closed if a patient develops a stroke where no other cause than the PFO can be identified. This is called a cryptogenic stroke. The minimally invasive approach via heart catheterization is preferred in most cases. The hole is closed using a self-expanding double disk occluder device. Two types of occluders are FDA approved, “to reduce the risk of recurrent ischemic stroke in patients, predominantly between the ages of 18 and 60 years, who have had a cryptogenic stroke due to a presumed paradoxical embolism, as determined by a neurologist and cardiologist following an evaluation to exclude known causes of ischemic stroke.”⁵  

Multiple clinical trials have been conducted to assess the efficacy of closing a PFO to treat migraine, comparing the use of a closure device against medical treatment. A pooled analysis of two of the most prominent trials was published in the Journal of the American Academy of Cardiology in 2021. The study assessed the efficacy of PFO closure after 1 year and found a reduction of monthly migraine days (3.1 vs 1.9 days), a mean reduction of monthly migraine attacks (2 vs 1.4 days) and complete cessation of migraine (14 subjects vs 1 subject) which were all statistically significant.⁶ The efficacy was more notable in patients with aura. Separately, these trials did not meet the primary endpoint, failing to definitively prove benefit, but when analyzed together, three of the four endpoints did achieve statistical significance.⁶ It appears that PFO closure may be better than medical therapy, but more evidence is needed prior to making this a standard recommendation as other studies have not shown benefit from PFO closure in migraine patients.

Stroke, Patent Foramen Ovale and Migraine

Migraine, auras, PFO, and strokes appear to share an association. As mentioned, PFO can allow tiny emboli to travel from the venous system into the arterial system. This is called “paradoxical embolism”. If these emboli travel to the central nervous system, they can lead to small areas of the brain receiving low blood flow, and thus low oxygenation. If this low oxygenation persists, that area of brain tissue can die, which is a stroke. 

A study showed that of 712 patients with ischemic stroke, 127 of the cases were diagnosed as cryptogenic stroke. Of those individuals, 68 (59%) had PFO.⁷  Patients with both cryptogenic stroke and migraine had a higher prevalence of PFO (79%).⁷  In patients with cryptogenic stroke who had migraine with frequent aura, the prevalence of PFO was very high at 93%.⁷ 

To learn more about migraine and stroke click here.

What Type of Doctor Should I See For Patent Foramen Ovale and Migraine?

Patent Foramen Ovale is best treated by a cardiologist. For surgical placement of an occluder device, an interventional cardiologist is needed. Migraine is best treated by a clinician that specializes in headache medicine. Due to the high incidence of PFO in migraine patients, multidisciplinary care among cardiology and neurology is recommended. 

A Note to Patients and Providers 

Cardiologists should be aware of the comorbidity between migraine and patent foramen ovale. In addition, neurologists should also be aware of this comorbidity due to the frequent co-occurrence of cryptogenic stroke, migraine with aura and PFO. Those who have a stroke of unknown origin should be asked if they have a history of migraine with aura and PFO. It is interesting that migraine and migraine aura without headache are both strongly associated with PFO and suggests aura or cortical spreading depression may lead to more answers about the comorbidity between the two conditions. If you already know you live with PFO, be sure to let your migraine doctor know so they can choose the best migraine medications for you. More research is needed for patent foramen ovale, therefore those with the condition are encouraged to enroll in clinical trials by routinely checking clinicaltrials.gov.

Recruiting Study

1. View a recruiting study on PFO and migraine

Patient Resources 

1. Patent Foramen Ovale and Migraine Headaches: Where Do We Stand Today? By Alexander Postalian, MD 
2. Educational Handout by the Patent Foramen Ovale Research Foundation
3. Educational Videos by the Patent Foramen Ovale Research Foundation 
4. Research from the Patent Foramen Ovale Research Foundation

References 

1. https://ichd-3.org/1-migraine/1-2-migraine-with-aura/1-2-1-migraine-with-typical-aura/
2. Marchione P, Ghiotto N, Sances G, Guaschino E, Bosone D, Nappi G, Giacomini P. Clinical implications of patent foramen ovale in migraine with aura. Funct Neurol. 2008 Oct-Dec;23(4):201-5. PMID: 19331783. https://pubmed.ncbi.nlm.nih.gov/19331783/
3. Liu, K., Wang, B. Z., Hao, Y., Song, S., & Pan, M. (2020). The Correlation Between Migraine and Patent Foramen Ovale. Frontiers in neurology, 11, 543485. https://doi.org/10.3389/fneur.2020.543485 
4. Nahas SJ, Young WB, Terry R, Kim A, Van Dell T, Guarino AJ, Silberstein SD. Right-to-left shunt is common in chronic migraine. Cephalalgia. 2010 May;30(5):535-42. doi: 10.1111/j.1468-2982.2009.02002.x. Epub 2010 Feb 11. PMID: 19732069. 
5. https://www.ahajournals.org/doi/10.1161/JAHA.117.007146
6. https://www.jacc.org/doi/abs/10.1016/j.jacc.2020.11.068
7. https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.117.020160

*The contents of this blog are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The writer does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.