Sudden unexplained death in individuals with and without epilepsy

Purpose

We aimed to compare demographics, circumstances, comorbidities, autopsy results, postmortem toxicology, and prescription claims between sudden unexplained deaths (SUD) without and with epilepsy, also known as sudden unexpected death in epilepsy (SUDEP).

Methods

SUD cases were identified from forensic autopsy and toxicology reports on a previously identified nationwide population of sudden deaths and sudden cardiac deaths in Denmark. SUD was defined as sudden cardiac death with no/subdiagnostic cardiac pathology and nonlethal toxicology. We included cases between 2000–2019 and 2007–2019 in deceased aged 1–35 years and 36–49 years. SUDEP cases, identified as SUD with epilepsy, were determined using Danish health registries with information on epilepsy-related hospitalizations and antiseizure medication (ASM) claims.

Results

We identified 477 SUDs, including 84 (18 %) SUDEP and 393 (82 %) SUDs without epilepsy. Compared with SUDs without epilepsy, SUDEP was significantly associated with unwitnessed death (93 % vs. 75 %, p < 0.001), solitary living (56 % vs. 42 %, p = 0.018), psychiatric comorbidity (36 % vs. 19 %, p < 0.001), and a lower prevalence of subdiagnostic cardiac hypertrophy (7.1 % vs. 22 %, p = 0.002). SUDEP cases exhibited a higher prevalence of proarrhythmic drug claims (88 % vs. 29 %, p < 0.001) and proarrhythmic drugs postmortem (77 % vs. 48 %, p < 0.001), which were attributable to ASM, compared to SUDs without epilepsy.

Conclusion

SUDEP cases are more frequently unwitnessed, involve individuals living alone, and are associated with psychiatric comorbidities than SUDs without epilepsy. Enhancing psychiatric care and supervision for individuals with epilepsy may reduce SUDEP incidence. Cardiac evaluations of arrhythmias are crucial before and during ASM administration.