BACKGROUND AND OBJECTIVES: Mortality is increased in epilepsy, but the important issue is that a proportion of epilepsy-related death is potentially preventable by optimized therapy and needs therefore to be identified. A new systematic classification of epilepsy-related mortality has been suggested by Devinsky et al. in 2016 to identify these preventable deaths. We applied this classification to an analysis of premature mortality in persons with epilepsy younger than 50 years.

METHODS: The study was a population-based retrospective cohort of all Danish citizens with and without epilepsy aged 1-49 years during 2007-2009. Information on all deaths was retrieved from the Danish Cause of Death Registry, autopsy reports, death certificates, and the Danish National Patient Registry. The primary cause of death in persons with epilepsy was evaluated independently by three neurologist, one neuro-pediatrician, and two cardiologists. In case of uncertainty a pathologist was consulted. All deaths were classified as either epilepsy- or not-epilepsy-related, and the underlying causes or modes of death were compared between persons with and without epilepsy.

RESULTS: During the study period 700 deaths were identified in persons with epilepsy, and 440 (62.9%) of these were epilepsy-related, hereof, 169 (38%) directly related to seizures and 181 (41%) due to an underlying neurological disease. SUDEP accounted for 80% of deaths directly related to epilepsy. Aspiration pneumonia was the cause of death in 80% of cases indirectly related to epilepsy.Compared with the background population, persons with epilepsy had a nearly four-fold increased all-cause mortality (adjusted mortality hazard ratio of 3.95 [95% CI 3.64-4.27], p<0.0001) and a higher risk of dying from various underlying causes including alcohol-related conditions (hazard ratio of 2.91 [95% CI 2.23-3.80], p<0.0001) and suicide (hazard ratio of 2.10 [95% CI 1.18-3.73], p=0.01).

DISCUSSION: The newly proposed classification for mortality in persons with epilepsy was useful in an unselected nationwide cohort. It helped classifying unnatural causes of death as epilepsy-related or not, and it helped identifying potentially preventable deaths. The leading causes of premature mortality in persons younger than 50 years were related to epilepsy and were thus potentially preventable by good seizure control.