Abstracts

Rationale:
Sudden unexpected death in epilepsy (SUDEP) is a major cause of epilepsy-related mortality. The risk of SUDEP is higher in individuals with frequent, convulsive and nocturnal seizures. There is often evidence of a recent seizure at the time of death suggesting that seizures and their resulting systemic effects have a direct role in causing death.  Many SUDEP victims are found in bed, frequently in the prone position, suggesting that the etiologic mechanisms may increase during sleep. Seizures are most frequent in non-REM sleep, intermediate in wakefulness, and least frequent (1% of seizures) in REM sleep. In a mouse model, seizures induced during sleep, in particular REM sleep, are associated with greater respiratory dysfunction and higher fatality rate compared with seizures induced during wakefulness. In this study, we investigated patients with SUDEP who had previously undergone video-EEG monitoring to assess how frequently their seizures arose from sleep, and specifically REM sleep.
Method:
All patients who had undergone video-EEG monitoring between 1990 and 2018 at Jefferson Comprehensive Epilepsy Center and subsequently succumbed to SUDEP, were included. All available EEG data were reviewed. For each recorded seizure, the state during which it arose was documented.  
Results:
Twenty six patients were included. F: M rate was 1:1. Mean age at the time of monitoring and at the time of death was 31 (14-55) and 34 (18-57) respectively. Twenty two (85%) of patients had history of tonic-clonic seizure and 22 (85%) had history of nocturnal seizures. A total of 107 seizures were recorded. The mean number of seizures per patient was 4.1 (0-13). Figure 1 shows the distribution of seizure onset between wakefulness and different sleep stages. Two patients had seizures with onset during REM sleep. Each patient had a single seizure arising from REM sleep and both had additional seizures arising from other states. Figure 2 shows the fraction of patients who had seizures arising from different vigilance states.
Conclusion:
The frequency of seizures arising from REM sleep in our cohort of 26 patients who died of SUDEP was 1.9% (2/107), comparable to the 1% frequency previously reported. The lack of correlation between REM sleep onset seizures and SUDEP could reflect lack of association, but it is also possible that the cohort was too small to show such association. Though the percentage of total seizures arising from REM was low, it is notable that 2 out of 26 patients (7.7%) had REM-onset seizures. Similarly, in the MORTEMUS study, 12.5% of patients whose sleep stage was known at the time of terminal seizure was in REM sleep at the time of death. Study limitations: •The inpatient hospitalization and antiepileptic medication taper may alter the natural sleep pattern. Second, •Lack of control patients. In a power analysis, we calculated that several hundred control patients would be required to demonstrate a statistically significant difference, which was not feasible. Additional work in larger cohorts and utilization of ambulatory EEG data may be useful in further addressing the potential association of REM-onset seizures and SUDEP.
Funding:
:No funding was received.