Migraine with aura, thrombophilia, and the debate on white matter hyperintensities

White matter hyperintensities (WMHs) on brain magnetic resonance imaging (MRI) are a common finding in migraine with aura[1] whose nature remains debated as they may represent vascular or non-vascular phenomena.[2] The vascular hypothesis is supported by migraine, especially with aura, being a risk factor for ischemic stroke and other vascular events,[3] possibly due to prothrombotic factors, occult embolism, and/or endothelial dysfunction.[4]

In a study published in this issue of Arquivos de Neuropsiquiatria, Can investigated thrombophilia in individuals with migraine with aura. The author found an association between resistance to activated protein C and WMHs in this population.[5] Notably, thrombophilia was present in up to one third of subjects, a high prevalence consistent with previous literature.[6]

While the study found a link between WMHs and resistance to activated C protein, other thrombophilic factors might also influence WMH occurrence in migraine with aura. Clinically, these results suggest a comprehensive investigation of thrombophilia in individuals with migraine with aura and WMHs.

Pathophysiologically, the study does not definitively resolve the origin of WMHs in migraine with aura. Although WMHs were more prevalent in individuals with thrombophilia, they were also common in those without it. This suggests that WMHs may not be solely related to factors leading to thrombophilia in individuals with migraine. The increased risk for thrombotic events in individuals with migraine can be explained by several factors different from thrombophilia, such as microembolism or microvascular dysfunction.[4] [7] Besides, WMHs can have non-vascular causes such as inflammation.[2] The results of Can's study suggest that at least some WMHs in migraine with aura may have a vascular origin due to their association with thrombophilia.

Should individuals with migraine with aura and WMHs receive antithrombotic treatment given their high suspect for thrombophilia? Currently, there is no indication for universal antithrombotic therapy in individuals with migraine with aura, as its benefits for WMH progression or migraine management are unclear. Antithrombotic treatments should be prescribed only if some forms of thrombophilia are found. The study suggests screening for thrombophilia in individuals with migraine and WMHs, given its high prevalence, and treating accordingly if found.

As a further therapeutic implication, the study does not address patent foramen ovale, which has been associated with migraine, particularly with aura.[8] However, closure of patent foramen ovale is not generally indicated for migraine, even with aura, due to uncertain outcomes in available literature.[9] Thrombophilia might increase the susceptibility to paradoxical embolism in individuals with migraine and consequently contribute to triggering migraines; however, there is no study addressing the benefits of patent foramen ovale closure in individuals with migraine with aura and thrombophilia, likely because of the very low prevalence of those individuals.

In conclusion, this study highlights a potentially significant comorbidity in migraine with aura that may be associated with WMHs and requires attention to avoid missing treatable diagnoses. Questions remain regarding the role of various thrombophilia forms in migraine, the nature of WMHs, and the optimal management of individuals with comorbid migraine with aura, WMHs, and thrombophilia.

Authors' Contributions

RO: conceived the paper and drafted the manuscript; FdS, MF: revised the manuscript for intellectual content.

Publication History

Received: 14 August 2024

Accepted: 15 August 2024

Article published online:
24 September 2024

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