A Stroke of Insight? Possible Bidirectional Relationship Between Stroke and Epilepsy
Year: 2026
Type: editorial
Study design: Observational Study
Abstract: Epilepsy and Stroke: A Mendelian Randomization Study Chen S, Crago M, Lekoubou A. Epilepsy Res . 2026;220:107714. doi:10.1016/j.eplepsyres.2025.107714 Background: Observational studies have established a relationship between stroke and epilepsy. While most studies have reported an increased risk of epilepsy following a stroke, fewer have concluded that a diagnosis of epilepsy increases the risk of future strokes. Precisely describing the causal relationship between epilepsy and stroke has clinical and public health implications. Methods: We performed a two-sample Mendelian Randomization (MR) to analyze the relationship between epilepsy and stroke. We identified genetic instruments from the Stroke Multiancestry Genome-Wide Association Study [GCST005838 (67,162 cases and 454,450 controls)] and the International League Against Epilepsy Consortium on Complex Epilepsies [Generalized epilepsy (GE): GCST007343 (n_case=3769, n_control=29677), Focal epilepsy (FE): GCST007352 (n_case=9671, n_control=29677)]. We used a significance threshold of p -value <5 × 10 (−5) for genetic instrument identification. We included the following epilepsy phenotypes: GE, FE, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy, GE with tonic-clonic seizures, FE with hippocampal sclerosis (focal HS), and focal lesion-negative epilepsy. Linkage disequilibrium reference panel of 1000 Genome Project pruning with Pearson correlation r 2 < 0.2 was applied to ensure that the analysis is restricted to independent variants. We used Steiger filtering for reverse causality and Z -scores for GE and FE. We employed the following methods for causal effect estimation: Inverse-variance weighted (IVW), MR-Egger, MR-RAPS, and MRPRESSO. Results: For the association between GE and stroke (GE > stroke), stroke and GE (stroke > GE), FE and stroke (FE > stroke), and stroke and FE (stroke > FE), the number of single nucleotide polymorphisms was respectively 253, 213, 187, and 210. GE was associated with an increased risk of stroke [IVW, 95% confidence interval: 0.058 (0.028-0.088)], and stroke was also associated with an increased risk of GE [IVW: 0.059 (0.026-0.092)]. FE was associated with an increased risk of stroke [IVW: 0.066 (0.029-0.102)] and stroke was associated with an increased risk of FE [IVW: 0.037(0.005-0.068)]. The analysis by epilepsy subtypes revealed an increased risk only among patients with stroke and for the following epilepsy subtypes: JAE, CAE, Focal HS, and Focal lesion negative epilepsy. Conclusion: Our findings support a bidirectional relationship between stroke and epilepsy. Studies on post-stroke epilepsy should account for this bidirectional relationship.
Author: Samuel W Terman
Institution: University of Michigan
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7141137349