A Stroke of Insight? Possible Bidirectional Relationship Between Stroke and Epilepsy

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 (ncase=3769, ncontrol=29677), Focal epilepsy (FE): GCST007352 (ncase=9671, ncontrol=29677). We used a significance threshold of p -value 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.