An international team of scientists has identified critical risk factors that could help predict sudden unexpected death in epilepsy, according to a study published in The Lancet. 

The findings offer new hope for early intervention and improved monitoring strategies, said study co-author Stephan Schuele, MD, MPH, chief of Epilepsy and Clinical Neurophysiology in the Ken and Ruth Davee Department of Neurology. 

“This is the first prospective study of its kind in epileptic patients, and it has identified new risk biomarkers which we can use to help guide seizure monitoring and management,” Schuele said. 

Sudden Unexpected Death in Epilepsy (SUDEP) — the leading cause of epilepsy-related mortality — refers to the sudden, unexpected death of a person with epilepsy who was otherwise healthy and for which no other cause of death is found. It often occurs during or after a seizure and leaves no clear anatomical or toxicological explanation. Despite being the leading cause of epilepsy-related mortality, SUDEP remains poorly understood because it is unpredictable and challenging to study. 

Conducted across nine epilepsy centers in the U.S. and U.K., the current study followed 2,632 children and adults with epilepsy between 2011 and 2021. Participants underwent prolonged video electroencephalographic (EEG) monitoring and were tracked over time through clinic visits, electronic health records and interviews. 

Out of 2,468 participants with complete follow-up data, 38 died from SUDEP. Investigators analyzed demographic, electroclinical and cardiorespiratory data to identify risk factors. 

The study revealed four significant predictors of SUDEP: 

• Living alone: Individuals who lived alone had a 7.6 times higher risk of SUDEP. 

• Frequent convulsive seizures: Experiencing three or more generalized convulsive seizures in the previous year tripled the risk. 

• Prolonged breathing disruption: Longer episodes of breathing disruption during or after a seizure were strongly associated with an increased risk of sudden death. 

“Without measuring respiration, you don’t get a good sense about the severity of a patient’s seizure and the risk associated,” Schuele said. “We have long been committed to monitoring respiratory parameters in epilepsy, which really has changed the landscape of how we do things. This study validates that for us.” 

The findings pave the way for more personalized epilepsy care, especially for those with frequent seizures or who live alone. With further validation, the proposed risk index could become a vital tool in clinical decision-making and patient education, Schuele said. 

“This will allow us to have a more robust risk score for patients,” Schuele said. “This is helpful to counsel them on their risk and preventive measures. We believe that cessation of breathing may be a crucial step in a cascade that leads to SUDEP. Measuring respiration really should be the standard of practice.” 

The study was funded by the U.S. National Institutes of Health.