Sudden Unexpected Death in Epilepsy: A Personalized Prediction Tool

Ashwani Jha, Cheongeun Oh, Dale Hesdorffer, Beate Diehl, Sasha Devore, Martin J. Brodie, Torbjörn Tomson, Josemir W. Sander, Thaddeus S. Walczak, Orrin Devinsky

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)e2627-e2638
JournalNeurology
Volume96
Issue number21
DOIs
StatePublished - May 25 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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