Sudden Unexpected Death in Epilepsy: A Personalized Prediction Tool. (25th May 2021)

• Record Type: Journal Article
• Authors: Jha, Ashwani; Oh, Cheongeun; Hesdorffer, Dale; Diehl, Beate; Devore, Sasha; Brodie, Martin J.; Tomson, Torbjörn; Sander, Josemir W.; Walczak, Thaddeus S.; Devinsky, Orrin
• Is Part Of: Neurology. Volume 96:Number 21(2021)
• Publication Date: 2021-05-25
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000011849
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To develop and validate a tool for individualized prediction of sudden unexpected death in epilepsy (SUDEP) risk, we reanalyzed data from 1 cohort and 3 case–control studies undertaken from 1980 through 2005. Methods: We entered 1, 273 epilepsy cases (287 SUDEP, 986 controls) and 22 clinical predictor variables into a Bayesian logistic regression model. Results: Cross-validated individualized model predictions were superior to baseline models developed from only average population risk or from generalized tonic-clonic seizure frequency (pairwise difference in leave-one-subject-out expected log posterior density = 35.9, SEM ± 12.5, and 22.9, SEM ± 11.0, respectively). The mean cross-validated (95% bootstrap confidence interval) area under the receiver operating curve was 0.71 (0.68–0.74) for our model vs 0.38 (0.33–0.42) and 0.63 (0.59–0.67) for the baseline average and generalized tonic-clonic seizure frequency models, respectively. Model performance was weaker when applied to nonrepresented populations. Prognostic factors included generalized tonic-clonic and focal-onset seizure frequency, alcohol excess, younger age at epilepsy onset, and family history of epilepsy. Antiseizure medication adherence was associated with lower risk. Conclusions: Even when generalized to unseen data, model predictions are more accurate than population-based estimates of SUDEP. Our tool can enable risk-based stratification for biomarker discovery and interventional trials. With further validation in unrepresented populations, it may be suitable for routine individualized clinical decision-making. Clinicians should consider assessment of multiple risk factors, and not focus only on the frequency of convulsions.