White Matter Disruption in Pediatric Traumatic Brain Injury

Abstract

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 (𝞫=0.043), which coincided with more parent-reported behavioral problems (𝞫=-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.

Early recovery of cognition and brain plasticity after surgery in children with low-grade frontal lobe tumors

“…The major affected WM tracts were the corticospinal tracts, cingulum, internal capsule, and external capsule (Figure 2). Our results were similar with those of Dennis et al (41), indicating that tumor resection is a special form of TBI.…”

“…Dennis et al have investigated WM tract integrity in over 500 children and adolescents with traumatic brain injury (TBI) during acute/subacute (<2 months), post-acute (2-6 months), and chronic post-injury periods (!6 months). They found significantly lower FA and higher MD in those with TBI compared to the controls during all three periods (41). In our DTI analysis, LGFLT resection led to extensively decreased FA and AD in WH tracts from 0 to 6 months after surgery.…”

Multimodal Analysis of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury

“…4,45 DTI data for 28 ROIs were processed as detailed in our previous publication. 27 Briefly, we used the ENIGMA-DTI pipeline 46 , a modified tract-based spatial statistics approach 47 resulting in FA and other metrics averaged within ROIs from the Johns Hopkins University atlas. Of the 12 cohorts, 10 collected DTI data (parameters in eTable 4 in Supplement 1).…”

“…Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) is a global research consortium achieving greater statistical power through coordinated processing of legacy data. Combining 12 cohorts from the ENIGMA Pediatric msTBI working group, [27][28][29][30][31][32][33][34][35][36][37][38][39] we measured regional cerebellar volume in children and adolescents. A priori hypotheses were as follows: (1) cerebellar volume would be lower in individuals with msTBI vs non-TBI, (2) these disruptions would be most prominent furthest from the time of injury, and (3) smaller cerebellar volume would be associated with poorer executive functioning.…”

Towards PErsonalised PRognosis for children with traumatic brain injury: the PEPR study protocol

“…Second, existing models have almost exclusively been developed in adult patients, thereby not accounting for the developmental aspects of brain functioning that are crucial for outcome prediction in children 20. Third, advanced multimodal MRI (ie, targeting brain volume, white matter integrity, structural and functional connectivity and neurometabolites) has not been integrated in the existing prediction models, while each of these MRI techniques has shown promising prognostic potential when studied in isolation 17 21–23. More specifically, measures of fractional anisotropy and resting-state network connectivity are considered to be strongly implicated in the neurocognitive and behavioural impairments of children with TBI 21 23 24…”