Diverging white matter trajectories in children after traumatic brain injury

Abstract

Objective: To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period.Methods: We studied 21 children (16 M/5 F) with msTBI, assessed 2-5 months postinjury and again 13-19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure. At the first time point, half of the patients with TBI had significantly slower IHTT (TBI-slow-IHTT, n 5 11) and half were in the normal range (TBI-normal-IHTT, n 5 10). Results:The TBI-normal-IHTT group did not differ significantly from healthy controls, either in WM organization in the chronic phase or in the longitudinal trajectory of WM organization between the 2 evaluations. In contrast, the WM organization of the TBI-slow-IHTT group was significantly lower than in healthy controls across a large portion of the WM. Longitudinal analyses showed that the TBI-slow-IHTT group experienced a progressive decline between the 2 evaluations in WM organization throughout the brain. Conclusions:We present preliminary evidence suggesting a potential biomarker that identifies a subset of patients with impaired callosal organization in the first months postinjury who subsequently experience widespread continuing and progressive degeneration in the first year postinjury. Neurology ® 2017;88:1392-1399 GLOSSARY AutoMATE 5 automated multi-atlas tract extraction; CC 5 corpus callosum; DWI 5 diffusion-weighted MRI; ERP 5 eventrelated potential; FA 5 fractional anisotropy; IHTT 5 interhemispheric transfer time; IRB 5 institutional review board; MD 5 mean diffusivity; msTBI 5 moderate/severe traumatic brain injury; PICU 5 pediatric intensive care unit; RD 5 radial diffusivity; TBI 5 traumatic brain injury; UCLA 5 University of California, Los Angeles; WM 5 white matter. Traumatic brain injury (TBI) is associated with substantial mortality and morbidity in children. Demyelination of white matter (WM) that is commonly found post-TBI 1,2 can have adverse cognitive repercussions. 3,4 In children, this disruption to myelin is compounded, as the brain is still maturing, and myelination continues well beyond age 30. 5,6 With diffusion-weighted MRI (DWI), we can identify WM disruptions postinjury. Prior work has shown lower WM organization in TBI, 7,8 suggesting disrupted myelin. Interhemispheric transfer time (IHTT) is the time required for signals to traverse the cerebral hemispheres through the corpus callosum (CC). It is an index of callosal functional organization; longer IHTT indicates slower information transfer. Both children and adults show slower IHTT following TBI.9,10 We measured IHTT using visual event-related potentials (ERPs), throughFrom the Imaging Genetics Center

Fronto‐temporal vulnerability to disconnection in paediatric moderate and severe traumatic brain injury

“…Overall, we observed decreased AD in acute patients versus controls, which we ascribed to acute axonal damage and cytotoxic oedema following inflammation [11]; we found increased AD in chronic patients, attributable to secondary degeneration [5]. Chronic patients showed decreased FA and increased diffusivities in the CC.…”

Magnetic resonance spectroscopy of fiber tracts in children with traumatic brain injury: A combined MRS – Diffusion MRI study

“…In prior papers we have shown that a subgroup of pediatric msTBI patients experiences a progressive decrease in WM organization (Dennis, 2017b). However, with only dMRI data, we were not able to determine whether these deficits were due to demyelination, inflammation, or other changes in neuronal organization.…”

“…In the first few months post-injury, some msTBI patients have significantly impaired callosal functional and structural integrity, and this affects cognitive performance as well. Additionally, these differences appear to be progressive, as one subgroup experiences expanding WM disruption and atrophy while the other subgroup of msTBI children appears to begin to return to a healthy trajectory (Dennis, 2017a; Dennis, 2017b). Importantly, the subgroup with impaired callosal function does not differ from the other msTBI patients in demographic or acute injury variables (including the incidence of lesions as detected by acute CT).…”

“…The msTBI group with slow IHTTs (TBI-slow) tended to have poor WM organization (Dennis, et al, 2015a), which progressively worsened. The msTBI group (TBI-normal) with normal IHTTs showed minimal disruptions to WM organization, which improved longitudinally (Dennis, 2017b). These groups did not significantly differ clinically or demographically so we sought to elucidate the processes underlying the WM disruption that some patients experience to better understand this divergence.…”

Diffusion MRI in pediatric brain injury

“…Dennis et al did not find a significant effect of age or severity, but found two subgroups of patients based on post-acute interhemispheric transfer time (IHTT). Those patients with significantly slower IHTT than healthy controls showed progressive decline in WM organization over time, while those with IHTTs within the healthy control range showed evidence of recovery [30]. Several studies have examined how dMRI measures in the acute or post-acute phase can predict chronic outcome.…”