Extratemporal Epileptogenic Zones Linked to Increased SUDEP Risk in Focal Epilepsy

Localization of the epileptogenic zone to extratemporal regions—specifically perisylvian and frontal lobes—is strongly associated with an increased risk for sudden unexpected death in epilepsy.

Extratemporal epileptogenic zones are strongly associated with an increased risk for sudden unexpected death in epilepsy (SUDEP) among adults with drug-resistant focal epilepsy, according to findings published in The Lancet Neurology.

Researchers conducted a prospective cohort study with a nested case-control design to identify novel seizure-related risk factors for SUDEP.

The researchers enrolled adults with drug-resistant focal epilepsy undergoing long-term in-hospital video electroencephalography. Within the cohort of 1074 individuals, 18 patients with definite or probable SUDEP were identified and matched to 72 control individuals by study center and date of inclusion.

During 6828 patient-years of follow-up, the overall SUDEP rate was 2.64 per 1000 patient-years (95% CI, 1.36-3.92). At baseline, compared with the control cohort, participants who died of SUDEP were more likely to be men (72% vs 53%), have obesity (22% vs 3%), have a longer duration of epilepsy (19.5 [IQR, 7.1-31.9] years vs 12.6 [IQR, 6.8-22.3] years), and were more likely to experience predominantly nocturnal seizures (50% vs 18%). The majority of participants in both groups were treated with multiple antiseizure medications.

“This finding warrants confirmation in larger cohorts and underscores the need to improve the diagnosis and surgical management of extratemporal epilepsies, which might contribute to improved SUDEP risk stratification and prevention.”

Localization of the epileptogenic zone emerged as the strongest risk factor for SUDEP. An extratemporal epileptogenic zone was identified in 83% of those who died of SUDEP compared with 33% of control individuals. In multivariable analyses, the presence of an extratemporal epileptogenic zone was associated with a significantly increased risk for SUDEP (odds ratio [OR], 37.8; 95% CI, 3.2-446.2; P =0.0039).

This association appeared to be driven primarily by a higher proportion of perisylvian epileptic zones among those with SUDEP compared with control individuals (56% vs 10%). Frontal lobe epileptogenic zones were also more common among those with SUDEP (28% vs 14%). In contrast, posterior extratemporal epileptogenic zones were not observed among participants who died of SUDEP but were present in 10% of control individuals.

Other independent risk factors independently associated with SUDEP included male sex (OR, 12.6; 95% CI, 1.5-106.8; P =0.0201), predominantly nocturnal seizures (OR, 6.0; 95% CI, 1.2-28.7; P =0.026), and obesity (OR, 26.0; 95% CI, 2.0-339.6; P =0.013).

Study limitations include the relatively small number of patients with SUDEP, resulting in wide confidence intervals, and the restricted generalizability to individuals with drug-resistant focal epilepsy.

“This finding warrants confirmation in larger cohorts and underscores the need to improve the diagnosis and surgical management of extratemporal epilepsies, which might contribute to improved SUDEP risk stratification and prevention,” the study authors concluded.

Disclosures: This research was supported by the French Ministry of Health. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References:

Ryvlin P, Huot M, Valton L, et al. Seizure-related biomarkers of sudden unexpected death in epilepsy (SUDEP) in drug-resistant focal epilepsy (REPO2MSE): a prospective, multicentre case-control study. Lancet Neurol. 2026;25(1):50-60. doi:10.1016/S1474-4422(25)00379-5