Abstracts

Rationale: Dravet Syndrome (DS) is a rare, debilitating developmental and epileptic encephalopathy. DS has greatly increased mortality rates compared to other epilepsy populations, including higher rates of Sudden Unexpected Death in Epilepsy (SUDEP), the leading cause of epilepsy-related mortality. General risk factors for SUDEP have been identified among people with epilepsy but their importance may vary among epilepsy syndromes. We compiled a database of DS SUDEP cases to identify possible features associated with SUDEP risk in this syndrome.

Methods: SUDEP cases were collected from The Canadian Pediatric SUDEP Registry, North American SUDEP Registry and University of Melbourne Epilepsy Genetics database via referrals from health care providers, advocacy organizations and families between 1996-2020. Characteristics including demographics, clinical history, medical records, diagnostic exams, family history, seizure semiology, lifestyle factors, and genetic testing results were collected. Autopsy data was collected, when available, as well as family/witness statements regarding circumstances around death.

Results: 26 cases (12 female, 46%) of SUDEP in DS were identified. Classification of SUDEP is in Table 1. Median age at death was 8.58 years (IQR=12.63); 17 (65%) occurred before the age of 13. 18 (69%) deaths occurred in bed. 21 (81%) deaths were unwitnessed. 14 (54%) reported co-sleeping and room-sharing all or most of the time, 8 (57%) of whom died in bed, only 1 (14%) was witnessed. SCN1A pathogenic variants were confirmed in 22 (85%) cases, seizure onset was within the first year of life in 22 (85%) cases, and 22 (85%) cases had multiple seizure types. 9 cases (35%) reported a decrease in seizure frequency over the 6 months prior to death, and 9 (35%) reported no generalized tonic-clonic seizures (GTCs) in the month before death. 11/22 (50%) reported no evidence of a seizure immediately preceding death. 14 (54%) reported a recent illness, predominantly viral infections, with or without fever.

Conclusions: We identify clinical features that deviate from typical SUDEP characterizations in the general epilepsy population. Years living with epilepsy and frequent GTCs are common indicators of risk for SUDEP, however, our cohort tended toward early age of death, stable or improved seizure control prior to death, and few recent GTCs. Further, 50% of cases did not show evidence for a seizure immediately preceding death. A recent mild illness was noted prior to death in half the subjects. These findings suggest there may be additional or unique risk factors for SUDEP in DS, while common SUDEP risk factors may not be as significant. This is not a population-based cohort, as such, referral bias may limit interpretation. Expansion of this cohort is hoped to further elucidate the hypothesis that SUDEP in DS may involve factors unique to this disorder.

Funding: Please list any funding that was received in support of this abstract.: Michael Bahen Chair in Epilepsy Research at the University of Toronto; FACES (finding a cure for epilepsy/seizures), Lundbeck, AES;
National Health and Medical Research Council of Australia.