ENIGMA Pediatric msTBI diffusion MRI supplemental data

Objective: Our study addressed aims: (1) test the hypothesis that
moderate-severe TBI in pediatric patients is associated with widespread
white matter (WM) disruption; (2) test the hypothesis that age and sex
impact WM organization after injury; and (3) examine associations between
WM organization and neurobehavioral outcomes. Methods: Data from ten
previously enrolled, existing cohorts recruited from local hospitals and
clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics
through Meta-Analysis) Pediatric msTBI working group. We conducted a
coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI
processing pipeline. Results: Five hundred and seven children and
adolescents (244 with complicated mild to severe TBI [msTBI] and 263
controls) were included. Patients were clustered into three post-injury
intervals: acute/subacute - <2 months, post-acute - 2-6 months,
chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral
problems as indexed by the Child Behavior Checklist (CBCL). Our analyses
revealed altered WM diffusion metrics across multiple tracts and all
post-injury intervals (effect sizes ranging between d=-0.5 to -1.3).
Injury severity is a significant contributor to the extent of WM
alterations but explained less variance in dMRI measures with increasing
time post-injury. We observed a sex-by-group interaction: females with TBI
had significantly lower fractional anisotropy in the uncinate fasciculus
than controls (?=0.043), which coincided with more parent-reported
behavioral problems (?=-0.0027). Conclusions: WM disruption after msTBI is
widespread, persistent, and influenced by demographic and clinical
variables. Future work will test techniques for harmonizing neurocognitive
data, enabling more advanced analyses to identify symptom clusters and
clinically-meaningful patient subtypes.