Premature mortality risk in individuals with convulsive epilepsy: Results from a longitudinal, prospective, population-based study

Objective: To assess premature mortality and identify associated risk factors among individuals with convulsive epilepsy in resource-poor settings using a longitudinal, prospective, population-based approach.Method: The study recruited people with convulsive epilepsy who underwent assessment and management of epilepsy at primary healthcare centers in rural Northwest China, including newly diagnosed individuals and previously identified prevalent cases. All participants were confirmed to have epilepsy by neurologists according to strict criteria and were followed up monthly by primary care physicians. Demographic data and cause of death (COD) were obtained from death certificates or verbal autopsies conducted by neurologists, following the International Classification of Diseases, 10th Edition. The standardized mortality ratio (SMR) and proportionate mortality ratio (PMR) for each cause of death were estimated using the Cause-Of-Death Surveillance Dataset of China (2020). Survival analysis was used to identify risk factors associated with all-cause mortality and death directly due to epilepsy.Results: During 5.9 years of follow-up with 40,947 person-years, there were 781 (11.2%) deaths among 6967 participants. The risk of premature death in people with convulsive epilepsy was 2.7-fold higher than that in the general population. Young participants had a significantly higher risk (standardized mortality ratio 26.5-52.5) of premature death. The proportionate mortality ratio was higher for cerebrovascular disease (15%), sudden unexpected death in epilepsy (SUDEP) (13.4%), cardiovascular disease (11.7%), status epilepsy (SE) (11.3%), and epilepsy-related accidents (14.0%) than other premature mortality cause of deaths. Additionally, the highest standardized proportional mortality ratio (SPMR) was observed from drowning in all cause of death (10.4, 95% confidence interval [CI]: 7.6-13.8), followed by burning (9.0, 95% CI: 3.7-18.9). Factors that increased the risk of all-cause mortality included male sex, late age of onset, short disease duration, high body mass index, monotherapy, and the frequency of generalized tonic-clonic seizures (GTCS). High frequency of generalized tonicclonic seizures (> 3 attacks in the last year) was an independent risk factor for premature death directly due to epilepsy (including sudden unexpected death in epilepsy, status epilepsy, and epilepsy-related accidents), while early age of onset (< 14 years) and long duration of epilepsy (> 20 years) were independent risk factors for sudden unexpected death in epilepsy. In addition, short duration of epilepsy (< 20 years) was an independent risk factor for status epilepsy.Conclusions: This study demonstrated that individuals with poorly controlled seizures are more likely to experience premature death, with most deaths being epilepsy-related and preventable. These findings underline the importance of effective seizure treatment and the potential impact on reducing premature mortality among people with convulsive epilepsy.