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Observational Study
. 2025 Oct 4;406(10511):1497-1507.
doi: 10.1016/S0140-6736(25)01636-8. Epub 2025 Sep 17.

Risk markers for sudden unexpected death in epilepsy: an observational, prospective, multicentre cohort study

Manuela Ochoa-Urrea  1 , Xi Luo  2 , Laura Vilella  1 , Nuria Lacuey  1 , Shirin Jamal Omidi  1 , Norma J Hupp  1 , Blanca Talavera  1 , Johnson P Hampson  1 , M R Sandhya Rani  1 , Shiqiang Tao  1 , Xiaojin Li  1 , Christina Y Miyake  3 , Licong Cui  1 , Jaison S Hampson  1 , Ganne Chaitanya  4 , Yash Shashank Vakilna  4 , Rup K Sainju  5 , Daniel Friedman  6 , Maromi Nei  7 , Luke Allen  8 , Catherine A Scott  8 , Joana Oliveira  8 , Brian Gehlbach  5 , Stephan U Schuele  9 , Jennifer A Ogren  10 , Ronald M Harper  10 , Beate Diehl  8 , Lisa M Bateman  11 , George B Richerson  5 , Jose-Miguel Yamal  2 , Guo-Qiang Zhang  1 , Orrin Devinsky  6 , Samden D Lhatoo  12
Affiliations
Observational Study

Risk markers for sudden unexpected death in epilepsy: an observational, prospective, multicentre cohort study

Manuela Ochoa-Urrea et al. Lancet. .

Erratum in

  • Department of Error.
    [No authors listed] [No authors listed] Lancet. 2025 Oct 4;406(10511):1472. doi: 10.1016/S0140-6736(25)01970-1. Lancet. 2025. PMID: 41046147 No abstract available.

Abstract

Background: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Generalised-particularly nocturnal-convulsive seizures, longstanding epilepsy, and solitary living have been identified retrospectively as risk factors. No definitive electroclinical biomarkers have been prospectively ascertained. This study aimed to identify SUDEP risk markers using multimodality data with long-term follow-up.

Methods: This prospective, multicentre, observational cohort study, conducted at nine centres (eight in the USA and one in the UK), recruited children and adults with epilepsy who were undergoing prolonged video-electroencephalographic (EEG) monitoring. Inclusion criteria were diagnosis of epilepsy by an epilepsy specialist, with or without drug resistance; age older than 2 months; admission to the epilepsy monitoring unit of a participating centre, with video-EEG monitoring; and completion of at least one 6-month follow-up. Demographic, electroclinical, and cardiorespiratory data were collected at baseline. Participants were followed up long term through routine clinic visits, review of electronic health records, and telephone interviews to collect information about seizure frequency, medication status, and mortality. The primary endpoint was time to SUDEP. Cox proportional hazards models were used to assess significant risk factors.

Findings: Between Sept 17, 2011, and Dec, 30, 2021, 2632 children and adults with epilepsy were enrolled in this study; 164 were lost to follow-up. 38 (1·54%) of 2468 participants died from SUDEP (12 definite, 18 probable, and eight possible SUDEP cases) and two had near-SUDEP events. Incident SUDEP mortality rate was 4·76 (95% CI 3·37-6·53) cases per 1000 person-years, from a cohort of 7982 person-years. Living alone (hazard ratio 7·62, 95% CI 3·94-14·71), three or more generalised convulsive seizures in the previous year (3·1, 1·64-5·87]), longer ictal central apnoea (1·11, 1·05-1·18), and longer postictal central apnoea (1·32, 1·14-1·54]) were significant predictors of increased SUDEP risk. In a subanalysis excluding possible and near-SUDEP cases, longer ictal central apnoea was not significant.

Interpretation: This study shows an association between premortem peri-ictal apnoea and increased SUDEP risk. Cardiorespiratory monitoring during seizures might benefit assessments of epilepsy mortality risk. Together with solitary living and convulsive seizure frequency, peri-ictal apnoea (>14 s for postictal central apnoea and >17 s for ictal central apnoea) could inform the development of a validatable SUDEP risk index.

Funding: US National Institutes of Health.

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Conflict of interest statement

Declaration of interests LV received payment for lectures and presentations/educational events from Eisai, UCB, Jazz Pharmaceuticals, and Angellini. NL reports funding from the US National Institutes of Health (NIH). GC reports grant NIH R-25 (NS113757). MN reports grant NIH R-25 (NS113757). LMB reports payments to their institution from NIH/National Institute of Neurological Disorders and Stroke (NINDS) U01NS090407, NIH/NINDS R01NS130838, NIH/NINDS R56NS1277891, New York University (re NIH R01NS123928), and Dartmouth Health; payment for educational activities from Stanford University, Darthmouth Hitchcock Medical Center, and American Epilepsy Society; support for travel from the American Board of Psychiatry and Neurology, Stanford University, and Darthmouth Hitchcock Medical Center. SUS discloses royalties with Springer Publishing; receives consulting fees from UCB Pharma; payment or honoraria from SKLife Science, Neurelis and Jazz Pharmaceuticals; payment for expert testimony from Marcus Mays vs. Wellpath and Will County; and is Editor in Chief, of Journal of Clinical Neurophysiology. BG and RKS report grants from NINDS NIH grant R01NS113764 for SUDEP research and Neurava. BKG received travel expenses to participate in the 2024 SUDEP Risk Assessment and Prevention Workshop sponsored by CURE Epilepsy and reports use of transcutaneous CO2 monitors provided by Sentec. DF reports payments to their institution from NINDS, the US Centers for Disease Control and Prevention, Rapport Therapeutics, Epitel (via NIH), and Neuropace (via NIH); receives royalties or licenses from Oxford University Press and Neuroview Technoloyg; and salary support for consulting and clinical trial-related activities on behalf of The Epilepsy Study Consortium, a non-profit organization for which he is an Executive Vice President; DF does not receive personal income for these activities. NYU receives a fixed amount from the Epilepsy Study Consortium towards DF's salary and over the past 2 years, the Consortium received payments for research services performed by DF from Biogen, Biohaven, Cerberal Therapeutics, Cerevel, Encoded, Epalex, Equilibre, Jazz Pharmaceuticals, Janssen, Longboard, Ludbeck, Marinus, Modulite, Neurocrine, Ono, Praxis, PureTech, Rapport Therapeutics, SK Lifescience, Supernus, UCB, and Xenon. DF also received payment to self from the American Academy of Neurology and support for attending meetings from the Epilepsy Foundation; has a patent US 20180117331 issued for Minimally Invasive Subgaleal Extra-Cranial Electroencephalography EEG Monitoring Device and a pending patent electroencephalography electrode arrays and related methods of use; reports leadership as Executive Vice President for Epilepsy Study Consortium; and has equity interest in Neuroview Technology. SDL reports funding from the National Institutes of Health; receives consulting fees from UCB, LivaNova, and Neuropace; payment or honoraria from UCB; and participates on an Advisory Board for LivaNova. All other authors declare no competing interests.

References

    1. Sudden Devinsky O., unexpected death in epilepsy. N Engl J Med 2011;365(19):1801–1811. doi: 10.1056/NEJMra1010481 - DOI - PubMed
    1. Devinsky O, Hesdorffer DC, Thurman DJ, Lhatoo S, Richerson G. Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol 2016;15(10):1075–1088. doi: 10.1016/S1474-4422(16)30158-2 - DOI - PubMed
    1. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: current knowledge and future directions. Lancet Neurol. 2008;7(11):1021–1031. doi: 10.1016/S1474-4422(08)70202-3 - DOI - PubMed
    1. Sillanpaa M, Shinnar S. Long-term mortality in childhood-onset epilepsy. N Engl J Med 2010;363(26):2522–2529. doi: 10.1056/NEJMoa0911610 - DOI - PubMed
    1. Hesdorffer DC, Tomson T, Benn E, et al. Combined analysis of risk factors for SUDEP. Epilepsia 2011;52(6):1150–1159. doi: 10.1111/j.1528-1167.2010.02952.x - DOI - PubMed

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