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. 2023 Jun 1;80(6):605-613.
doi: 10.1001/jamaneurol.2023.0611.

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

Lucia Sinka  1 , Laura Abraira  2 , Lukas L Imbach  3 , Dominik Zieglgänsberger  4 , Estevo Santamarina  2 , José Álvarez-Sabín  2 , Carolina Ferreira-Atuesta  5   6   7 , Mira Katan  1   8 , Natalie Scherrer  1 , Giulio Bicciato  1 , Robert Terziev  1 , Cyril Simmen  1 , Kai Michael Schubert  1 , Adham Elshahabi  1 , Christian R Baumann  1 , Nico Döhler  4   9 , Barbara Erdélyi-Canavese  4 , Ansgar Felbecker  4 , Philip Siebel  4 , Michael Winklehner  10   11 , Tim J von Oertzen  10 , Judith N Wagner  10 , Gian Luigi Gigli  12 , Anna Serafini  12 , Annacarmen Nilo  12 , Francesco Janes  12 , Giovanni Merlino  12 , Mariarosaria Valente  12 , María Paula Zafra-Sierra  13 , Hernan Bayona-Ortiz  13 , Julian Conrad  14   15 , Stefan Evers  14   16 , Piergiorgio Lochner  17 , Frauke Roell  17 , Francesco Brigo  18 , Carla Bentes  19 , Ana Rita Peralta  19 , Teresa Pinho E Melo  19 , Mark R Keezer  20   21 , John S Duncan  5   7 , Josemir W Sander  5   7   20 , Barbara Tettenborn  4 , Matthias J Koepp  5   7 , Marian Galovic  1   5   7
Affiliations

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

Lucia Sinka et al. JAMA Neurol. .

Abstract

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk.

Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures.

Design, setting, and participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022.

Exposures: Type of acute symptomatic seizure.

Main outcomes and measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke).

Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy.

Conclusions and relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Abraira reported personal fees and/or travel support from UCB Pharma, Angelini Pharma, Eisai, Bial, GW Pharmaceuticals, Esteve Laboratories, and Sanofi outside the submitted work. Dr Santamarina reported grants and/or personal fees from UCB Pharma, Angelini Pharma, Esteve, Bial, and Eisai outside the submitted work. Dr Katan reported nonfinancial support from Roche and BRAHMS Thermo Fisher Scientific and grants from Swiss National Science Foundation during the conduct of the study. Dr von Oertzen reported personal fees from Angelini Pharma, Almirall, Arvelle Therapeutics, Arielle Pharma, Bayer, Indivior Austria, GW Pharma, Novartis, Philips, Zogenix, Jazz Pharma, LivaNova, Eisai, and UCB Pharma; grants from Merck; personal fees and nonfinancial support from g.tec; grants, personal fees, and nonfinancial support from Boehringer-Ingelheim; and grants and personal fees from Eisai outside the submitted work and serving as president/past-president of Österreichische Gesellschaft für Epileptology (Austrian ILAE chapter), co-chair of a scientific panel for epilepsy at European Academy of Neurology (EAN), and co-chair of the communication committee for EAN. Dr Wagner reported personal and/or other fees from UCB, Boehringer Ingelheim, and Roche outside the submitted work. Dr Evers reported consulting and lecture fees from Allergan/Abbvie, Lilly, Lundbeck, Novartis, Perfood, and Teva. Dr Brigo reported fees and travel support from Lusofarmaco outside the submitted work. Dr Bentes reported a grant from Sociedade Portuguesa do AVC (sponsored by Tecnifar) and honoraria for lectures and support for scientific events from Bial, Eisai, and Angelini outside the submitted work. Dr Keezer reported grants from UCB, Eisai, Canadian Institutes of Health Research, Fonds de Recherche Santé Québec, Quebec Bio-Imaging Network, Savoy Foundation, TSC Alliance, and Canadian Frailty Network outside the submitted work. Dr Sander reported grants from UCB (to his institution), Netherland Epilepsy Funds, and GW Pharma; speakers bureau fees from UCB; consulting fees from Angelini; and personal fees from Zogenix and Arvelle outside the submitted work. Dr Tettenborn reported personal fees from Biogen outside the submitted work. Dr Koepp reported personal fees from Bial outside the submitted work. Dr Galovic reported personal fees and/or travel support from Advisis, Arvelle, Bial, Eisai, Nestlé Health Science, and UCB outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Risk of Mortality or Remote Symptomatic Seizures Following Acute Symptomatic Seizures After Stroke
The data according to the type of acute symptomatic seizure in the derivation cohort (n = 4529) are displayed in panels A and C. The data after acute symptomatic status epilepticus in the replication cohort (n = 39 patients with acute symptomatic status epilepticus) are shown in panels B and D. The tables below each graph display the Kaplan-Meier estimates of the risk of remote symptomatic seizures 1 to 10 years after index stroke according to the type of acute symptomatic seizure. 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 acute symptomatic seizure). The dotted line denotes the 60% cutoff for the risk of unprovoked seizures used in the International League Against Epilepsy (ILAE) practical clinical definition of epilepsy. FA indicates focal aware seizure; FBTC, focal to bilateral tonic-clonic seizure; FIA, focal seizure with impaired awareness; no AS, no acute symptomatic seizures; SE, status epilepticus; and UD, undetermined or unknown seizure type.
Figure 2.
Figure 2.. Predicted Risk of Remote Symptomatic Seizures According to the Updated SeLECT 2.0 Score
Panel A shows the predicted risk of unprovoked remote symptomatic seizures 0-96 months after stroke. Each curve represents the estimates for a SeLECT 2.0 value ranging from 0 to 13. Risk estimate charts of late seizures 1 year and 5 years after stroke according to SeLECT 2.0 score values are displayed in panels B and C, respectively. Vertical lines indicate 95% CIs.
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