Childhood TBI Causes Widespread and Persistent White Matter Disruption

Investigators assessed pediatric patients to determine the relationship between moderate to severe traumatic brain injury during childhood and white matter disruption.

Following moderate to severe traumatic brain injury (msTBI) in children, white matter disruption was widespread, persistent, and impacted by demographic and clinical factors, according to study findings published in Neurology.

Study researchers analyzed data from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Pediatric msTBI working group collaboration. At 7 sites in 3 countries, 10 cohorts of children and adolescents (n=244) with msTBI and controls (n=263) who were either healthy or had orthopedic injuries were assessed by diffusion magnetic resonance imaging (dMRI) and neurobehavioral instruments.

The msTBI and control groups had a mean age of 14.1 (standard deviation [SD], 3.0) and 13.6 (SD, 2.9) years and 170 and 150 were male, respectively. The participants were subdivided by severity, in which 38 TBI and 44 controls were in the acute/subacute, 78 TBI and 107 controls were in the post-acute, and 160 TBI and 190 controls were in the chronic phase cohorts.

The msTBI group exhibited lower fractional anisotropy and higher mean diffusivity, particularly in central white matter regions and tracts. Stratified by phase for group comparisons, central white matter regions of interest exhibited the most extensive disruptions, although, by the chronic phase, nearly every region of interest displayed significant group differences.

Findings indicated a group-by-sex interaction in the post-acute phase for fractional anisotropy and radial diffusivity in the uncinate fasciculus (b, 0.043; P =.0012; b, -3.1´10-5; P =.027, respectively).

Among the msTBI groups, an age-at-injury effect was observed for the post-acute phase in the posterior thalamic radiation (b, 0.20; P =.00023) and superior longitudinal fasciculus (b, 0.18; P =1.3´10-5), in which fractional anisotropy was positively related with age at injury. Regarding time since injury, study researchers observed a decrease in fractional anisotropy of the body (b, -0.0075; P =.0001) and genu (b, -0.0049; P =.0041) of the corpus coliseum.

Improved behavioral regulation was associated with higher skeletal fractional anisotropy (b, -0.0006; P =.0028) in the post-acute phase; in the chronic phase, there was a negative association between metacognition index and the fractional anisotropy of the uncinate fasciculus (b, -0.0028; P =8.6´10-5). Total problems were negatively associated with fractional anisotropy in the uncinate fasciculus (b, -0.0027; P =.0017) and sagittal stratum (b, -0.0014; P =.0024).

This study may have been limited by the various recruitment criteria, scan procedures, and measures collected across the research sites as well as the use of diffusion tension imaging which is less accurate in areas with crossing fibers.

These data indicated that msTBI injury during childhood generated widespread and persistent white matter disruption. Additional studies are needed to assess clinical subtypes of msTBI.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Dennis EL, Caeyenberghs K, Hoskinson KR, et al. White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury. Neurology. Published online May 28, 2021. doi:10.1212/WNL.0000000000012222