# Current perspectives in sudden unexpected death in epilepsy (SUDEP): epidemiology, research approaches and pathways to prevention

## TL;DR

SUDEP is a major cause of death in epilepsy patients, with risk factors like frequent seizures and living alone, and research is ongoing to understand and prevent it.

## Contribution

This review summarizes current SUDEP research, identifies risk factors, and highlights recent insights into potential mechanisms and biomarkers.

## Key findings

- SUDEP affects approximately 1 in 1,000 epilepsy patients annually, with higher rates in those with severe epilepsy.
- Frequent bilateral tonic–clonic seizures, living alone, and drug-resistant epilepsy are established risk factors.
- Recent studies suggest brainstem dysfunction and sleep disruption may contribute to SUDEP mechanisms.

## Abstract

People with epilepsy (PWE) are affected not only by the unpredictability of seizures, the risk of accidents, stigma, and comorbidities, but also by increased mortality. The most common directly epilepsy‑associated cause of death is sudden unexpected death in epilepsy patients (SUDEP). Across all PWE, SUDEP affects approximately 1 in 1,000 patients per year; depending on epilepsy severity, the annual SUDEP rate can exceed 10 per 1,000 patient years. Because many PWE live with the disorder for several decades, the cumulative SUDEP risk amounts to an average lifetime risk of 5–20%, rendering SUDEP a relevant contributor to mortality in PWE; however, considering its comparatively low annual incidence, SUDEP research remains challenging. Established risk factors and associated patient characteristics include frequent bilateral tonic–clonic seizures (BTCS) -especially when nocturnal-, living alone, long duration of epilepsy, and drug-resistant epilepsy. There are few observations in humans regarding the pathophysiological mechanisms underlying SUDEP, supplemented by findings from registries, animal models, and theoretical considerations. In the typical SUDEP cascade, a pathologically impaired arousal following a preceding, often nocturnal, BTCS appears to precipitate apnea and consequent bradycardia, progressing to fatal asystole. Various individual vulnerability factors contribute to this cascade. However, many aspects remain poorly understood. Two large, recently published prospective cohort studies have contributed valuable insights into biomarkers of SUDEP. Perisylvian epilepsies were identified as risk factors; furthermore, findings suggest dysfunctional brainstem respiratory regulation and impaired sleep homeostasis as potential mechanisms contributing to SUDEP. Nevertheless, on an individual level, it remains poorly understood why some patients die in the context of their first ever epileptic seizure, while others survive hundreds of BTCS. This narrative review provides an overview of the current state of SUDEP research and information on preventive measures used today, and delineates prospective directions for future investigation and prevention.