Pediatric Traumatic Brain Injury and Later Neurologic and Psychiatric Disorders

Pediatric traumatic brain injury (pTBI) is a significant cause of morbidity and mortality in children, with its incidence rising globally. The potential link between pTBI and the development of neurologic and psychiatric disorders such as attention- deficit/hyperactivity disorder (ADHD), epilepsy, multiple sclerosis, and psychotic syndromes remains significantly understudied. This dissertation aims to address this gap of knowledge by examining the association between pTBI and these neurologic/psychiatric conditions in a large, nationwide cohort.

Utilizing data from the Finnish Care Register and the Finnish Social Insurance Institution, we identified 137,794 pediatric trauma patients between 1998 and 2018. After excluding 969 patients due to insufficient data, 136,825 patients were analyzed, with 71,969 in the pTBI group and 64,856 in the control group hospitalized for distal extremity fractures. The incidence of ADHD, multiple sclerosis, psychotic syndromes, and post-traumatic epilepsy (PTE) was assessed through Kaplan-Meier (KM) survival analyses and Cox proportional hazards models.

Our findings indicate a significant association between pTBI and increased risk of post-traumatic ADHD medication usage, particularly after four years of follow-up (Hazard ratio (HR) 1.9, CI: 1.7–2.1). This risk was notably higher in patients who underwent operative treatment for pTBI (HR 6.3, CI: 2.8–14.2). Both male and female pTBI patients exhibited a higher risk of starting ADHD medication compared to their respective control groups.

The study also revealed an increased risk for epilepsy in pTBI patients, with the risk being 4.4 times higher within the first two years post-injury (HR 4.4, CI: 3.4–5.7) and nearly double over a 20-year period (HR 2.0, CI: 1.7–2.4). Those with operatively managed pTBI had a significantly higher risk of developing epilepsy, with a 14-fold increase in the first four years post-injury (HR 14.4, CI: 9.3–20.8), and a 3.7-fold increase between four, and twenty years post-injury (HR 3.7, CI: 1.6–8.2).
Conversely, this dissertation found no significant association between pTBI and multiple sclerosis (HR 1.1, CI: 0.6–1.5), likely due to the limited number of patients with multiple sclerosis in the cohort.

Additionally, pTBI was associated with a slightly increased risk of post-traumatic psychotic syndromes, particularly within the first ten years of follow-up (HR 1.3, CI: 1.2–1.6). Female pTBI patients demonstrated higher risk, with the hazard ratio decreasing over time (HR 2.0, CI: 1.2–3.2 in the first three years, and HR 1.1, CI: 0.9–1.3 from three to twenty years). Male pTBI patients did not demonstrate a significant increase in risk (HR 1.2, CI: 0.7–2.0 in the first three years, and HR 0.9, CI: 0.7–1.0 from three to twenty years). The overlapping confidence intervals and convergence of cumulative incidence curves at specific points indicate no meaningful difference in risk for males.

In conclusion, this dissertation identifies a significant elevation in the risk of ADHD medication use and epilepsy following pTBI compared to orthopedic references. While pTBI showed only a slight association with the development of psychotic syndromes, this was observed primarily in females, and no association was found with multiple sclerosis. Notably, patients who underwent surgical intervention for pTBI demonstrated a particularly heightened risk, significantly increasing their likelihood of developing ADHD or epilepsy.