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Sudden Unexpected Death in Epilepsy: A Personalized Prediction Tool

Jha, Ashwani1; Oh, Cheongeun2; Hesdorffer, Dale3; Diehl, Beate1; Devore, Sasha2; Brodie, Martin4; Tomson, Torbjörn5; Sander, Josemir W.1; Walczak, Thaddeus S.6; Devinsky, Orrin2

Published Jun 29, 2021 on Dryad. https://doi.org/10.5061/dryad.cfxpnvx4c

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Jun 29, 2021 version files 270.17 KB

Abstract

Objective: To develop and validate a tool for individualised prediction of Sudden Unexpected Death in Epilepsy (SUDEP) risk, we re-analysed data from one cohort and three case-control studies undertaken 1980-2005.

Methods: We entered 1273 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 generalised 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 to 0.74) for our model versus 0.38 (0.33 to 0.42) and 0.63 (0.59 to 0.67) for the baseline average and generalised tonic-clonic seizure frequency models respectively. Model performance was weaker when applied to non-represented populations. Prognostic factors included generalized tonic-clonic and focal-onset seizure frequency, alcohol excess, younger age of epilepsy onset and family history of epilepsy. Anti-seizure medication adherence was associated with lower risk.

Conclusions: Even when generalised 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 only focus on the frequency of convulsions.