Time-dependent risk of stroke following epilepsy: A nationwide cohort study in South Korea

Epilepsy(ICD-10 G40-G41) and stroke-including hemorrhagic stroke (HS: I60-I62) and ischemic stroke (IS: I63))-are major neurological disorders. Although epilepsy has been proposed as a risk factor for stroke, large-scale evidence from Asian populations and analyses of time-dependent risk remain limited. This study investigated long-term risks of HS and IS after epilepsy using a nationwide cohort in South Korea.

A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort (2002-2013). Newly diagnosed epilepsy cases were identified after a 2-year washout and matched 1:10 with controls. Incident HS and IS were evaluated using crude incidence rates (IRs), incidence rate ratios (IRRs), Kaplan-Meier analyses, and 2-year interval time-stratified Cox models.

Over 10 years of follow-up, epilepsy was associated with increased risks of HS (IRR 3.50, 95 % CI 2.50-4.91) and IS (IRR 2.52, 95 % CI 2.16-2.95). Risk elevations were more pronounced in males and individuals < 60 years. Time-dependent analyses revealed a biphasic pattern: HS risk peaked during the first 0-2 years (aHR 4.25, 95 % CI 2.68-6.74), while IS risk increased at 0-2 years (aHR 2.99, 95 % CI 2.41-3.71) and again at 6-8 years (aHR 3.00, 95 % CI 1.51-5.99).

Epilepsy was associated with substantial and time-varying risks of HS and IS. Although causal relationships cannot be confirmed, these findings highlight the need for vigilant early monitoring and sustained, individualized stroke prevention strategies in individuals with epilepsy.