Selective association and familial aggregation of migraine in epilepsy: evidence from a dual-control study

Headache, particularly migraine, is frequently reported in people with epilepsy, but the specificity of this association and the contribution of familial susceptibility is not well defined. We evaluated headache prevalence in patients with epilepsy, their first-degree relatives, and unrelated controls.

In this prospective case-control study conducted at a tertiary epilepsy centre, we enrolled 120 consecutive patients with epilepsy, 120 first-degree relatives (one per patient), and 120 age- and sex-matched unrelated controls. Epilepsy was classified according to the International League Against Epilepsy 2017 criteria. Headache diagnoses were established using the International Classification of Headache Disorders, 3rd edition, through structured neurologist-conducted interviews. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Overall headache prevalence was higher in patients with epilepsy (81.7%) than in relatives (51.7%) and controls (42.5%; p < 0.001). Migraine was diagnosed in 25.8% of patients and 23.3% of relatives, compared with 10.8% of controls. Patients had significantly higher odds of migraine than controls (OR 2.87, 95% CI 1.42-5.81, p = 0.008). Migraine prevalence did not differ between patients and relatives but was significantly higher in both compared with controls. In contrast, tension-type headache did not show a statistically significant association with epilepsy. Headache prevalence was not associated with epilepsy duration, seizure frequency, or antiseizure medication use.

Migraine, but not tension-type headache, is selectively associated with epilepsy and demonstrates familial aggregation. These findings support shared biological susceptibility between epilepsy and migraine and warrant further longitudinal and genetic investigation.