Abstracts

Rationale: Dravet Syndrome is a catastrophic childhood-onset epilepsy syndrome characterized by drug-resistant seizures, cognitive impairment and motor deficits. High rates of sudden unexpected death in epilepsy (SUDEP) have been reported in Dravet Syndrome. The identification of clinical risk factors for SUDEP in Dravet Syndrome may allow for the application of potential preventative strategies in those at highest risk. We present a case-control study of SUDEP in Dravet Syndrome. Methods: Cases of SUDEP among people with Dravet Syndrome and controls living with Dravet Syndrome were recruited from Dravet.org, a non-profit advocacy group. The study was advertised to Dravet.org members online and interested families were referred to the study coordinator. Data was collected by phone from family members by the study staff. Genetic and autopsy studies were obtained, when available. Results: Three cases of autopsy-confirmed SUDEP and 3 cases of probable SUDEP, without autopsy, were identified among individuals with Dravet Syndrome (4 female, 66.7%). Five cases had mutations of the SCN1A gene, 1 had a mutation of the SCN8A gene and 1 did not undergo genetic testing. Data was collected on 28 controls living with Dravet Syndrome (15 female, 51.7%), 22 with mutations of the SCN1A gene. Median age at death for the SUDEP cases was 17 years (IQR 9.75-20.5), median age at time of interview for the control cases was 13 years (IQR 5.5 -15.25). Eighty-four percent of the individuals who died of SUDEP were reported to have had more than 100 generalized tonic-clonic seizures (GTC) in their lifetime, in contrast to 56% of controls, however this difference did not reach statistical significance. The groups did not differ with regards to history of seizure freedom or history of nocturnal GTC in the 6 months prior to death or interview. With regards to sleep environment, the groups did not differ in the use of pillows, baby/video monitors, or room and bed sharing. Some form of nocturnal surveillance was common among both SUDEP cases and controls; 70% of controls and 83% of SUDEP cases reported ‘always, almost always or often' room sharing. Conclusions: Median age at death in these 6 cases of SUDEP in Dravet Syndrome was younger than the typically reported age associated with the highest risk of SUDEP. The limited sample size does not allow for the identification of significant differences between cases of SUDEP and living controls. Power is a limitation as 41 cases and 41 controls would be needed to detect a difference in having more than 100 lifetime GTC. However, differences in lifetime GTC frequency may emerge as an important predictor of SUDEP in a larger study. High rates of nocturnal surveillance were seen in both groups and the lack of difference between SUDEP cases and controls with regards to sleep environment suggests that these factors may not play a large role in SUDEP in Dravet Syndrome. Data collection is ongoing and data sources are expanding to improve case ascertainment. The North American SUDEP Registry has received support from Finding A Cure for Epilepsy and Seizures, AES Infrastructure Grant, and Lundbeck Pharmaceuticals.