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Multicenter Study
. 2025 Jul;56(7):1748-1757.
doi: 10.1161/STROKEAHA.124.050045. Epub 2025 Apr 24.

Association of the Timing and Type of Acute Symptomatic Seizures With Poststroke Epilepsy and Mortality

Kai Michael Schubert  1 , Dominik Zieglgänsberger  2 , Giulio Bicciato  1 , Laura Abraira  3 , Estevo Santamarina  3 , José Álvarez-Sabín  3   4   5 , Carolina Ferreira-Atuesta  6   7 , Mira Katan  1   8 , Lucia Sinka  1   9 , Robert Terziev  1   10 , Nico Deligas  2   11 , Barbara Erdélyi-Canavese  2 , Ansgar Felbecker  2 , Philip Siebel  2 , Michael Winklehner  12 , Tim J von Oertzen  12 , Judith N Wagner  12   13 , Gian Luigi Gigli  14 , Annacarmen Nilo  14 , Francesco Janes  14 , Giovanni Merlino  14 , Mariarosaria Valente  14 , María Paula Zafra-Sierra  15 , Luis Carlos Mayor-Romero  15 , Julian Conrad  4   5 , Stefan Evers  4   16 , Matias Alet  17 , Kazuki Fukuma  18 , Masafumi Ihara  18 , Benjamin Landau  19 , Piergiorgio Lochner  19 , Frauke Roell  19 , Francesco Brigo  20 , Carla Bentes  21 , Ana Rita Peralta  21 , Teresa Pinho E Melo  21 , Mark R Keezer  22   23 , John S Duncan  6 , Josemir W Sander  6   22   24 , Barbara Tettenborn  2 , Matthias J Koepp  6 , Marian Galovic  1   6
Affiliations
Multicenter Study

Association of the Timing and Type of Acute Symptomatic Seizures With Poststroke Epilepsy and Mortality

Kai Michael Schubert et al. Stroke. 2025 Jul.

Abstract

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.

Methods: This multicenter cohort study included data from 9 centers between 2002 and 2018, with a final analysis in February 2024. The study included 4552 adults (2005 female; median age, 73 years) with ischemic stroke and no seizure history. Seizures were classified using International League Against Epilepsy definitions. We examined ASyS occurring within 7 days after stroke. The main outcomes were all-cause mortality and epilepsy. Validation of the updated SeLECT score (SeLECT-ASyS) was performed in 3 independent cohorts (Switzerland, Argentina, and Japan) collected between 2012 and 2024, including 74 adults with ASyS.

Results: The 10-year risk of poststroke 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 (adjusted hazard ratio [aHR], 2.3 [95% CI, 1.3-4.0]; P=0.003) compared with 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 updated SeLECT-ASyS model, available as an application, outperformed a previous model in the derivation cohort (concordance statistics, 0.68 versus 0.58; P=0.02) and in the validation cohort (0.70 versus 0.50; P=0.18).

Conclusions: ASyS timing and type significantly affect epilepsy and mortality risk after stroke, improving epilepsy prediction and guiding patient counseling.

Keywords: epilepsy; ischemic stroke; seizures; status epilepticus; stroke.

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Conflict of interest statement

Dr Abraira reports travel support from Angelini Pharma; compensation from Union Chimique Belge for consultant services and Jazz Pharmaceuticals for other services; and travel support from Jazz Pharmaceuticals. Dr von Oertzen reports grants from the Austrian Science Fund; and compensation from UCB GmBH for other services. Dr Wagner reports compensation from Union Chimique Belge, Pfizer, and Janssen Cilag (Europe, Middle East, and Africa) for other services; compensation from Janssen Cilag EMEA for consultant services; compensation from Boehringer Ingelheim for other services; travel support from Boehringer Ingelheim, Novartis, and Janssen Cilag (Europe, Middle East and Africa); compensation from AstraZeneca for other services; and Novartis for consultant services. J.S. Duncan reports grants from Wellcome Trust. J.W. Sander reports compensation from The Lancet’s International Advisory Board for other services. Dr Koepp reports compensation from Matthias & Ronit Pressler-Koepp for consultant services and stock options in PrevEp. Dr Galovic reports compensation from Angelini Pharma, Eisai, and Union Chimique Belge for consultant services. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Characterization of acute symptomatic seizures (ASyS) timing and type. A and B, The distribution and stratification of the first ASyS occurring after ischemic stroke. A illustrates the timing of ASyS, while B combines the timing (day 0 vs other days) with the type of seizure (eg, focal to bilateral tonic-clonic seizure [FBTCS], status epilepticus [SE]). The color coding in B aligns with the stratification of ASyS shown in Figure 2. Due to the small number of cases, SE and UD (undetermined/unknown seizure timing) seizures were not further differentiated by timing. C and D, Kaplan-Meier estimates (n=4552) of the time to poststroke epilepsy stratified by ASyS timing (day 0 vs day≥1; B) and type (FBTCs vs other short seizure type; C). HR indicates hazard ratio.
Figure 2.
Figure 2.
Risk of poststroke epilepsy or mortality following acute symptomatic seizures (ASyS) after stroke. Data according to the type and timing of ASyS and association with remote symptomatic seizure (RSyS; n=4552; A) and mortality (n=3084; B). The tables below each graph display the Kaplan-Meier estimates of the risk of RSyS 1 to 10 years after index stroke according to the type of ASyS. All results were obtained after adjusting for covariates (age, sex, National Institutes of Health Stroke Scale score at admission, cortical involvement, involvement of the middle cerebral artery territory, stroke cause, reperfusion treatment, and antiseizure medication treatment after ASyS). The dotted line denotes the 60% cutoff for the risk of unprovoked seizures used in the International League Against Epilepsy practical clinical definition of epilepsy. FBTCS indicates focal to bilateral tonic-clonic seizure; and SE, status epilepticus.
Figure 3.
Figure 3.
Risk of epilepsy in individuals with or without acute symptomatic seizures (ASyS) having a similar SeLECT2.0 score. Kaplan-Meier estimates (n=4552) of the time to poststroke epilepsy in those with a SeLECT2.0 score of 3 to 4 (A) or 5 to 6 (B) points. Separate curves are shown for individuals with (red) or without (blue) ASyS. Those with a SeLECT2.0 score of 3 to 4 who suffered ASyS had a higher risk of poststroke epilepsy (higher risk of remote symptomatic seizures) compared with those without ASyS (P<0.001). There was a similar but nonsignificant trend in individuals with a SeLECT2.0 score of 5 to 6 who had ASyS compared with those without (P=0.096). ASyS is defined as seizures occurring within the first 7 days following ischemic stroke.
Figure 4.
Figure 4.
Predicted risk of poststroke epilepsy according to a new prognostic model in stroke survivors with acute symptomatic seizures. A, The predicted risk of poststroke epilepsy (unprovoked remote symptomatic seizures) is 0 to 120 months after stroke. Each curve represents the estimates for a SeLECT-ASyS value ranging from 0 to 6. Risk estimate charts of late seizures 1 year and 10 years after stroke according to SeLECT-ASyS score values are displayed in B and C, respectively. Vertical lines indicate 95% CIs.
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