Evidence Suggesting Prolonged Neuroinflammation in a Subset of Children after Moderate/Severe TBI: A UCLA RAPBI Study

Traumatic brain injury (TBI) presents a public health concern as a leading cause of death and disability in children. Pediatric populations are particularly vulnerable to adverse outcomes following TBI due to periods of rapid growth, synaptic pruning, and myelination. Pediatric patients with moderate-severe TBI (msTBI) and healthy controls were evaluated from the post-acute (2-5 months) to chronic phase (13-19 months) of recovery using diffusion magnetic resonance imaging (dMRI) and interhemispheric transfer time (IHTT), which is an event-related potential measure the speed of information transfer across the corpus callosum. We previously identified two subgroups of patients based on IHTT, with one group showing a significantly slower IHTT (TBI-slow), poorer cognitive performance, and progressive structural damage. In contrast, the other group (TBI-normal) did not differ from controls on IHTT or cognitive performance and showed relative structural recovery over time. Here, we examined group differences in restricted diffusion imaging (RDI), which is a dMRI metric sensitive to inflammation. Comparing TBI-slow, TBI-normal, and controls on RDI cross-sectionally, dMRI connectometry analysis revealed higher RDI across the white matter in the TBI-slow group compared to both the control and TBI-normal groups.

Longitudinal analyses indicated that while both TBI groups exhibited a decrease in RDI over time, suggesting resolution of neuroinflammation and recovery, the decreases in the TBI-slow group were smaller. The differences in RDI between TBI-slow and TBI-normal suggest that inflammation may play a key role in the prolonged recovery, including brain structure, cognitive performance, and symptom reports, of pediatric patients with msTBI.