Repeated traumatic brain injury and risk of epilepsy: a Danish nationwide cohort study

Traumatic brain injury is associated with increased risk of epilepsy, but the importance of repeated traumatic brain injuries has not yet been established. We performed a nationwide population-based cohort study of 2 476 905 individuals born in Denmark between 1977 and 2016. We estimated hazard ratios (HRs) and the cumulative incidence of epilepsy following traumatic brain injury using Cox and competing risk regression, respectively. To estimate the cumulative incidence of epilepsy in the population without traumatic brain injury, we matched 10 controls for each subject with traumatic brain injury on year of birth, sex, and date of brain insult in the index person. In the cohort, traumatic brain injury was sustained by 167 051 subjects (71 162 females and 95 889 males), and 37 200 individuals developed epilepsy (17 905 females and 19 295 males). Compared with subjects without traumatic brain injury, the relative risk of epilepsy increased after a first traumatic brain injury [HR 2.04, 95% confidence interval (CI) 1.96-2.13] and even more after a second traumatic brain injury (HR 4.45, 95% CI 4.09-4.84). The risk increased with the severity of the first and the second traumatic brain injury, most notably after severe traumatic brain injuries. Females were more likely than males to develop epilepsy after mild traumatic brain injury (HR 2.13, 95% CI 2.00-2.28 versus HR 1.77, 95% CI 1.66-1.88; P < 0.0001); in contrast, males were more likely than females to develop epilepsy after severe traumatic brain injury (HR 5.00, 95% CI 4.31-5.80 versus 3.21, 95% CI 2.56-4.03; P = 0.0012). The risk remained increased for decades after the traumatic brain injury. This knowledge may inform efforts to prevent the development of post-traumatic epilepsy.