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Epilepsy and migraine: a diagnostic and therapeutic challenge

Angelo Pascarella, Oreste Marsico, Domenico Abelardo, Roberta Cutellè, Alessandro Bulgari, Cataldo Mummolo, Anna Mammì, Vittoria Cianci et al.

Frontiers in Pharmacology, 2025

10 citations

Abstract

Migraine and epilepsy are two common, chronic, disabling, paroxysmal neurological disorders. A growing body of evidence from epidemiological, genetic, neurophysiological, and clinical research suggests a complex, bidirectional association between them. Migraine prevalence in epilepsy patients ranges from 8% to 23%, while the reverse is noted at 1%-17%. Both disorders are underpinned by cortical hyperexcitability, dysfunctional neurotransmission, and impaired ion homeostasis. Shared genetic mutations, particularly in genes encoding ion channel subunits such as CACNA1A, SCN1A, and ATP1A2, further support a common channelopathy model. Cortical spreading depression, the electrophysiological substrate of migraine aura, and paroxysmal depolarization shift, a hallmark of epileptic activity, share converging features, including neuronal depolarization, potassium accumulation, glutamate release, and eventual firing suppression. Glial dysfunction, glutamatergic excitotoxicity, and mitochondrial deficits are additional unifying elements. Clinically, the differential diagnosis between migraine with aura and focal seizures remains challenging due to overlapping sensory, visual, and autonomic symptoms. Rare phenomena including ictal epileptic headache, postictal headache, and migraine-triggered seizures further complicate the clinical spectrum. Additionally, certain epilepsy syndromes, such as childhood epilepsy, are strongly associated with migraine. Early recognition of comorbidity is…

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