Association of the timing and type of acute symptomatic seizures with post-stroke epilepsy and mortality

Background Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear.

This multicenter cohort study included data from nine centers between 2002 and 2018, with final analysis in February 2024. The study included 4,552 adults (2,005 female; median age 73 years) with ischemic stroke and no seizure history. We examined ASyS occurring within seven days after stroke. Main outcomes were all-cause mortality and epilepsy. Validation in three separate cohorts included 74 adults with ASyS.

The ten-year risk of post-stroke epilepsy ranged from 41% to 94%, and mortality from 36% to 100%, depending on ASyS type and timing. ASyS on stroke onset day had a higher epilepsy risk (aHR 2.3, 95% CI 1.3-4.0, p=0.003) compared to later ASyS. Status epilepticus had the highest epilepsy risk (aHR 9.6, 95% CI 3.5-26.7, p<0.001), followed by focal to bilateral tonic-clonic seizures (aHR 3.4, 95% CI 1.9-6.3, p<0.001). Mortality was higher in those with ASyS presenting as focal to bilateral tonic-clonic seizures on day 0 (aHR 2.8, 95% CI 1.4-5.6, p=0.004) and status epilepticus (aHR 14.2, 95% CI 3.5-58.8, p<0.001). The novel SeLECT-ASyS model, available as an app, outperformed a previous model in the derivation cohort (concordance statistic 0.68 vs. 0.58, p=0.02) and in the validation cohort (0.70 vs. 0.50, p=0.18).

ASyS timing and type significantly affect epilepsy and mortality risk after stroke, improving epilepsy prediction and guiding patient counseling. Competing Interest Statement LA has received personal fees and travel support from UCB Pharma, Eisai, Esteve and Bial and personal fees from Sanofi outside the submitted work. ES has received grants and personal fees from UCB Pharma, personal fees from Eisai, personal fees from Esteve, and grants and personal fees from Bial, outside the submitted work. SE received honoraria for consulting and for lectures from from Allergan/Abbvie, Lilly, Lundbeck, Novartis, Perfood, Teva (past 3 years). FB received fees and travel support from Lusofarmaco, outside the submitted work. CB received a Grant from Sociedade Portuguesa do AVC (sponsor by Tecnifar), honoraria for lectures and support for scientific events from Bial, outside the submitted work. MK receives research support of the SNF( (182267), (213471), DISTAL (198783) and (204977)); grants from the Swiss Heart Foundation; participation on advisory boards and/or speaker honoraria for Medtronic, BMS Pfizer/Jansen and Astra Zeneca; in kind Contributions from Roche Diagnostics and Brahms Thermofisher Scientific.. MRK reports grants from UCB and Eisai, outside of the submitted work. BT reports personal fees from Biogen outside the submitted work. JWS reports grants and personal fees from UCB, grants from Netherland Epilepsy Funds; and personal fees from UCB and Angelini outside the submitted work. MG received fees and travel support from Arvelle, Advisis, Bial and Nestle Health Science outside the submitted work. JNW received fees from Boehringer Ingelheim and UCB as well as travel grants from ROCHE, outside the submitted work. TJO reports personal fees from Angelini Pharma Oesterreich GmbH; Arvelle Therapeutics, Argenx, Biogen, Eisai GesmbH, GW Pharma, Jazz Pharmaceuticals, LivaNova, und von Zogenix GmbH, grants from Boehringer-Ingelheim, outside the submitted work. All other authors declare no competing interests. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All subjects in the Italian, Spanish, Swiss (2) and Portuguese cohort and those having a face-to-face interview in the Swiss (1) cohort gave written informed consent. All subjects evaluated by telephone in the Swiss (1) and German (2) cohorts gave verbal informed consent. According to Swiss and German law the regional ethical committees exempted these cohorts from requiring written informed consent. The Austrian and German (1) case-control studies were classified as retrospective service evaluation by the regional ethical committee and informed consent was not required. The retrospective Colombian cohort did not require informed consent by the regional ethical committee. The use and analysis of patient data from the Zurich arm of the BIOSIGNAL study was done based on the project approval with BASEC- ID PB_2016-00672. that was approved by the Cantonal Ethics Commission of Zurich. All other cohorts received approval from their local ethical committees. The datasets used in our study were de-identified individual-level data. According to the Zurich Ethics Commission, the sharing and analysis of de-identified data of this nature does not require additional ethical approvals or adaptations. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors