The Epidemiology of post-traumatic seizures following moderate to severe traumatic brain injury

Though death rates due to traumatic brain injury (TBI) are decreasing in the United Statues, TBI remains a significant public health problem. Individuals who survive moderate and severe TBI become at risk of developing secondary complications, including post-traumatic seizures (PTS). PTS are well-recognized sequelae of TBI. Despite previous research, there remains a high degree of variability in who will develop PTS and no approved prophylactic medications to prevent late PTS exist. Late PTS is associated with significant morbidity and worse outcomes following TBI. Therefore, it is of public health importance to understand the characteristics of individuals with PTS, identify factors to improve prognostication, and explore novel risk factors to support a personalized medicine approach. Using the Traumatic Brain Injury Model Systems, we examined the incidence of immediate (7 days post-injury) PTS. Incidence of new onset seizures was highest immediately (8.9%) and one-year (9.2%) post-injury. Late PTS prevalence surpassed 20% at five-years post-injury. Incidence was stratified by potential risk factors and relative risk calculated. Individuals with immediate but not early seizures had a significantly greater incidence of late PTS compared to individuals not seizing during acute hospitalization. We then developed and internally validated prognostic models for PTS during acute hospitalization, at one-year, and two-years post-TBI. We identified multiple variables, including novel factors such as pre-injury mental health conditions, predictive of PTS. Year one and two models showed fair-to-good ability to discriminate PTS, supporting the idea that more accurate prognostication of late PTS can be accomplished. Lastly, we examined genetic variation in neuronal glutamate transporter genes as risk factors for PTS. We identified genetic variants significantly associated with increased PTS risk, after controlling for known risk factors. The relative effect size of the genetic markers suggests these variants may be significant predictors of PTS and may improve prognostic model reliability and validity. Classifying subpopulations at high-risk for PTS could facilitate research regarding the effectiveness of tiered prophylaxis and novel pharmacological interventions, improving prevention and treatment. Together, findings from the current work may affect future research and programmatic decisions, positively impacting those at risk for PTS