Causes of Death in Veterans With Posttraumatic Epilepsy

Background and Objectives Veterans with posttraumatic epilepsy (PTE) experience higher rates of mortality compared to those with nontraumatic epilepsy (NTE). An understanding of the causes of death responsible for the difference in mortality would lay the groundwork for mortality-reducing interventions in individuals with PTE. Methods We analyzed a previously identified cohort of Veterans with epilepsy, initially diagnosed from 2005 to 2022. PTE was identified if there was a diagnosis code for traumatic brain injury (TBI) within the 5 years preceding epilepsy diagnosis. Causes of death were identified using the VA/DoD Mortality Data Repository and were classified using the Global Burden of Disease (GBD) hierarchy. NTE controls were matched with Veterans with PTE by 2:1 nearest-neighbor matching based on age at onset, sex, and year of diagnosis. Cause-specific hazard ratios were computed using univariate Cox proportional hazards regression. Results A cohort of 210,065 Veterans with epilepsy (median age at onset 61.5 years [IQR 49.4–71.7], 8.3% female) was identified. After matching, covariates were balanced between 28,815 Veterans with PTE (median age at onset 53.6 years [IQR 37.4–65.2], 7.4% female) and 57,630 NTE controls (median age at onset 53.6 years [IQR 37.8–65.2], 8.0% female). The causes of death that were more common in Veterans with PTE compared with NTE controls were injuries (hazard ratio [HR] = 1.84, 95% CI 1.68–2.02), self-harm and interpersonal violence (HR = 1.57, 95% CI 1.37–1.80), stroke (HR = 1.38, 95% CI 1.20–1.59), and dementia (HR = 1.44, 95% CI 1.32–1.58). In contrast, idiopathic epilepsy (HR = 0.60, 95% CI 0.44–0.82) and neoplasms (HR = 0.66, 95% CI 0.63–0.70) were more common among Veterans with NTE. Discussion Veterans with PTE experienced higher mortality due to injuries, stroke, and dementia. These are frequently overrepresented causes of death in epilepsy cohorts, and the present findings clarify that Veterans with PTE are even more vulnerable. The explanations for these findings are likely multifactorial, but the findings are consistent with previously reported associations. Idiopathic epilepsy and neoplasms were less common in PTE, possibly due to competing risks from other causes and because brain tumors are a cause of intractable NTE. Since a Veteran population was analyzed in this study, women and children were underrepresented; furthermore, these results cannot be generalized since the risk factors facing Veterans differ from those experienced by the general population.