Differences in Mortality Between Veterans With Posttraumatic and Nontraumatic Epilepsy

Higher mortality, relative to the general population, is associated with epilepsy and with particular types of traumatic brain injury (TBI). It is thus presumed that posttraumatic epilepsy (PTE), which indicates epilepsy after TBI, would have higher mortality relative to nontraumatic epilepsy (NTE). However, previous studies have not established a difference in mortality between PTE and NTE.

We analyzed administrative data in the Veterans Health Administration to identify US military veterans diagnosed with epilepsy from 2005 to 2022 using previously validated criteria. PTE was defined as TBI documented in the 5 years before the epilepsy index date. TBIs were classified as skull/facial fracture, diffuse cerebral, focal cerebral, extracerebral, or concussion, based on International Classification of Diseases codes. Adjusted Kaplan-Meier survival curves and multivariable Cox proportional hazards models were fitted to compare mortality between PTE and NTE.

Among 210,182 veterans with epilepsy, 28,832 had PTE (mean onset age 52.6 years, 7.4% female) and 181,350 had NTE (mean onset age 60.9 years, 8.5% female). Mortality rate in PTE was higher compared with NTE and varied with the underlying TBI, being the highest with underlying diffuse cerebral injury (hazard ratio [HR] 1.17, 95% CI 1.07-1.28, p < 0.001), focal cerebral injury (HR 1.16, 95% CI 1.07-1.26, p < 0.001), or skull/facial fracture (HR 1.18, 95% CI 1.09-1.28, p < 0.001). However, underlying concussion had a mortality rate lower than all NTE combined (HR 0.91, 95% CI 0.86-0.95, p < 0.001). The relative mortality rate also varied with age at PTE onset, being the highest among young-onset PTE with extracerebral injury (HR 2.02, 95% CI 1.47-2.78, p < 0.001).

This study demonstrates that PTE leads to higher mortality compared with other forms of epilepsy, being up to 2 times higher in selected subgroups. The mechanism of underlying TBI influenced mortality rate. PTE after diffuse cerebral TBI, focal cerebral TBI, or skull/facial fractures led to higher mortality relative to NTE. Relative to NTE, young-onset PTE had the greatest rate of mortality. These results show that the age of PTE onset and the TBI precipitating PTE influence mortality and are relevant to consider in clinical practice. Future work should explore the reasons underlying higher mortality in PTE and refine TBI classification using additional data sources.