Prospective Study of Gray Matter Atrophy Following Pediatric Mild Traumatic Brain Injury

The clinical and physiological time-course for recovery following pediatric mild traumatic brain injury (pmTBI) remains actively debated. The primary objective of the current study was to prospectively examine structural brain changes (cortical thickness and subcortical volumes) and age-at-injury effects.A prioristudy hypotheses predicted reduced cortical thickness and hippocampal volumes up to 4 months post-injury, which would be inversely associated with age-at-injury.Prospective cohort study design with consecutive recruitment. Study inclusion adapted from American Congress of Rehabilitation Medicine (upper threshold) and Zurich Concussion in Sport Group (minimal threshold) and diagnosed by Emergency Department and Urgent Care clinicians. Major neurological, psychiatric or developmental disorders were exclusionary. Clinical (Common Data Element) and structural (3 Tesla MRI) evaluations within 11 days (sub-acute visit [SA]) and at 4 months (early chronic visit [EC]) post-injury. Age and sex-matched healthy children (HC) to control for repeat testing/neurodevelopment. Clinical outcomes based on self-report and cognitive testing. Structural images quantified with FreeSurfer (version 7.1.1).208 pmTBI (age=14.4±2.9; 40.4% female) and 176 HC (age=14.2±2.9; 42.0% female) included in final analyses (>80% retention). Reduced cortical thickness (right rostral middle frontal gyrus;d=−0.49) and hippocampal volumes (d=−0.24) observed for pmTBI, but not associated with age-at-injury. Hippocampal volume recovery was mediated by loss of consciousness/post-traumatic amnesia. Significantly greater post-concussive symptoms and cognitive deficits were observed at SA and EC visits, but were not associated with the structural abnormalities. Structural abnormalities slightly improved balanced classification accuracy above and beyond clinical gold standards (∆+3.9%), with a greater increase in specificity (∆+7.5%) relative to sensitivity (∆+0.3%).Current findings indicate structural brain abnormalities may persist up to four months post-pmTBI, and are partially mediated by initial markers of injury severity. These results contribute to a growing body of evidence suggesting prolonged physiological recovery post-pmTBI. In contrast, there was no evidence for age-of-injury effects or for physiological correlates of persistent symptoms in our sample.