# Advancing SUDEP risk prediction using a multicenter case-control approach

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $683,618

## Abstract

Project Summary
Patients with epilepsy have a 25-fold elevated risk of sudden death. Sudden Unexpected Death in Epilepsy
(SUDEP) is the most common disease-related cause of premature mortality in people with seizure disorders,
affecting 1 of every 1000 patients annually. Despite this, mechanisms and risk factors of SUDEP remain largely
unknown. Having ongoing generalized tonic-clonic seizures (GTCS) and no nocturnal supervision are the only
definite risk factors, and reducing seizures is the only currently available preventive strategy. Several other
clinical factors and potential biomarkers such as prolonged post-ictal generalized EEG suppression (PGES) that
follows GTCS, abnormal inter-ictal ECG, and structural brain MRI abnormalities were associated with increased
SUDEP risk, but none were rigorously confirmed in a large case-control study. While limitations of single-center
studies in accumulating a sufficient number of cases are well recognized, prospective multicenter studies are
also severely limited by the time, expense, and loss of follow-up constraining sample size and power. To sidestep
these limitations, we propose a retrospective multisite case-control study that will screen >40,000 patients from
86 epilepsy monitoring centers worldwide, with a conservative expected total of >185 SUDEP cases and 370
age/sex-matched controls. Employing our comprehensive approaches to identify SUDEP cases combined with
novel data harmonization techniques will allow us to: 1) provide an unprecedentedly large curated dataset of
SUDEP, 2) identify clinical, electrophysiological, and imaging predictors of SUDEP using advanced machine
learning methods, and 3) develop an individualized model to predict SUDEP risk that can be used in clinic.
The proposed study will test the hypothesis that SUDEP cases exhibit different electroclinical and imaging
characteristics that can provide an individualized prediction model. We will identify ictal electroclinical and
interictal electrophysiological and neuroimaging biomarkers of SUDEP. We will compare markers of seizure
severity between SUDEP cases and age/sex-matched living epilepsy patients, including decerebrate or
decorticate posturing during GTCS, PGES duration, postictal bradycardia + asystole and post-convulsive central
apnea. Additionally, we will assess putative interictal biomarkers including decreased low frequency power in
ECG heart rate variability and decreased MRI-derived volumes in the right hippocampus/amygdala and
brainstem. We will also employ machine-learning techniques to uncover novel biomarkers from interictal
electrophysiological data. Finally, using a Bayesian framework, we will develop an individualized SUDEP risk
prediction tool that combines clinical features with measures derived from routine EEG, ECG, and MRI.
Our goal is to create a SUDEP case-control dataset to identify clinical risk factors and biomarkers that will help
to create a robust model of an individual’s SUDEP risk based on meas...

## Key facts

- **NIH application ID:** 10290017
- **Project number:** 1R01NS123928-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Orrin Devinsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $683,618
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10290017

## Citation

> US National Institutes of Health, RePORTER application 10290017, Advancing SUDEP risk prediction using a multicenter case-control approach (1R01NS123928-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10290017. Licensed CC0.

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