An electroclinical case‐control study of sudden unexpected death in epilepsy

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 1 in 5 deaths in patients with epilepsy, but its cause remains unexplained. A recorded seizure resulting in death in our center appeared to suggest that postictal generalized electroencephalographic (EEG) suppression (PGES) and apnea are implicated in SUDEP. Our objective was to determine the association between PGES, as a possible identifiable EEG marker of profound postictal cerebral dysfunction, and SUDEP. METHODS: We studied 10 adult patients from our video-telemetry database who had 30 documented epileptic seizures during video-EEG recording and who later died of SUDEP. They were compared with 30 matching live controls with 92 epileptic seizures taken from the same database. Clinical and EEG findings were analyzed. RESULTS: PGES was seen in 15/30 (50%) case and 35/92 (38%) control seizures. A Mann-Whitney U test showed that PGES was significantly longer in the generalized motor seizures of the SUDEP group (p < 0.001). After adjustment for variables, odds ratio analysis of all seizures indicated significantly elevated odds of SUDEP with PGES durations of >50 seconds (p < 0.05). Beyond 80 seconds, the odds were quadrupled (p < 0.005). After adjustment for variables, for each 1-second increase in duration of PGES, the odds of SUDEP increased by a factor of 1.7%(p < 0.005). INTERPRETATION: Prolonged PGES (>50 seconds) appears to identify refractory epilepsy patients who are at risk of SUDEP. Risk of SUDEP may be increased in direct proportion to duration of PGES. Profound postictal cerebral dysfunction, possibly leading to central apnea, may be a pathogenetic mechanism for SUDEP.