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Updated: Jun 1, 2025
Closure of a Patent Foramen Ovale PFO: An Intervention Sequence
Published on: December 23, 2022
Effects of patent foramen ovale in migraine: a metabolomics-based study
Bosi Dong1, Xin Li2, Lu Zhang2,3
1Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Patent foramen ovale (PFO), a cardiac anatomical anomaly inducing abnormal haemodynamics, leads to a paradoxical bypass of the pulmonary circulation. PFO closure might alleviate migraines; however, clinical evidence and basic experiments for the relationship are lacking. To explore the effect of PFO on migraine, 371 migraineurs finishing blood tests and contrast transthoracic echocardiography for the detection of PFO were prospectively included. Multivariate regression analysis revealed that PFO was independently associated with aura, and lower cystatin-C (cys-C) and calcium levels. Among them, patients with PFO who underwent percutaneous PFO closure were continuously followed up 1 year after the operation. The intensity of migraine was significantly relieved and the levels of cys-C and calcium increased after PFO closure. Untargeted and targeted metabolomics of plasma from migraineurs before and after PFO closure revealed that 5-HT and glutathione (GSH) metabolites were differentially expressed after PFO closure. The differential metabolites were then validated in the plasma and brain tissues of PFO mouse models by LC-MS/MS analysis. Desorption electrospray ionization mass imaging demonstrated that these metabolic alterations occurred mainly in the posterior cerebral cortex. Collectively, aura, cys-C and calcium could be biomarkers of migraineurs with PFO. PFO might have an impact on the posterior head associated with the regulation of 5-HT and GSH. PFO closure might relieve migraine by improving 5-HT clearance metabolism and ameliorating redox reactions. Our results may provide evidence for an indication of PFO closure in migraine and support the related potential mechanism. KEY POINTS: Aura, and levels of cystatin-C and calcium are biomarkers of migraineurs with a patent foramen ovale (PFO). The clearance of pulmonary metabolism of 5-HT and deoxygenated blood might be the reason for the improvement of migraine symptoms in patients with PFO. The posterior region of the brain is the main area responsible for PFO-induced migraine.
Insights
Patent foramen ovale (PFO) is linked to migraines, with aura, cystatin-C, and calcium as potential biomarkers. PFO closure may relieve migraine symptoms by improving serotonin metabolism and brain redox balance.
Area of Science:
- Cardiology
- Neurology
- Metabolomics
Background:
- Patent foramen ovale (PFO) is a cardiac anomaly affecting blood flow.
- The link between PFO and migraines is not well-established.
- Investigating PFO's role in migraine pathophysiology is crucial.
Purpose of the Study:
- To explore the association between PFO and migraine characteristics.
- To investigate the impact of PFO closure on migraine intensity and biomarkers.
- To elucidate the underlying metabolic mechanisms of PFO-related migraines.
Main Methods:
- Prospective study of 371 migraineurs with PFO detection via echocardiography.
- Multivariate regression analysis to identify PFO-associated factors.
- Analysis of plasma metabolites (5-HT, GSH) and brain tissue in PFO models before and after PFO closure.
Main Results:
- PFO was independently associated with migraine aura, lower cystatin-C, and calcium levels.
- PFO closure significantly reduced migraine intensity and increased cystatin-C and calcium levels.
- Metabolomic analysis revealed differential expression of 5-HT and GSH metabolites, primarily in the posterior cerebral cortex.
Conclusions:
- Aura, cystatin-C, and calcium are potential biomarkers for migraineurs with PFO.
- PFO closure may alleviate migraines by enhancing 5-HT clearance and improving redox balance.
- The posterior brain region is implicated in PFO-associated migraine mechanisms.
