Burden of Headache Among People with Epilepsy: A Systematic Review and Meta-Analysis

<h2>Abstract</h2><h3>Background</h3> Headache and epilepsy frequently coexist, likely reflecting shared mechanisms such as cortical hyperexcitability and genetic susceptibility. However, the true burden of headache in people with epilepsy (PWE), particularly in children, remains uncertain. <h3>Methods</h3> We performed a systematic review and meta-analysis (PROSPERO: CRD420251000235) of observational studies reporting headache prevalence in PWE. MEDLINE, EMBASE, Scopus, and Web of Science were searched to January, 2026. Random-effects meta-analyses of proportions were conducted, with subgroup analyses by geography, age, and headache subtypes. Publication bias was assessed using Doi plots and the LFK index. <h3>Results</h3> Seventy-five studies including 105,586 PWE (2,067 children) were analyzed. The pooled prevalence of headache was 39.4% (95% CI: 35.5–43.4); in children, it was 27.5% (95% CI: 19.7–36.1). Prevalence varied significantly by geographic region (p < 0.0001), highest in Africa and lowest in North America. Among headaches temporally related to seizures, interictal headache was reported in 35.27% (95% CI: 26.65%–44.39%), and postictal headache in 29.28% (95% CI: 23.87%–35.00%), representing the most frequent subtypes. Patients receiving polytherapy had lower headache prevalence compared with those on monotherapy. Publication bias was evident for several outcomes. <h3>Conclusions</h3> Headache affects nearly two in five individuals with epilepsy and over one in four children, representing a substantial and underrecognized burden. Routine, standardized headache assessment should be integrated into epilepsy care. Future prospective, pediatric-inclusive studies using contemporary diagnostic criteria are needed to refine prevalence estimates and guide management.