In Traumatic Brain Injury, White Matter Diffusivity May Predict Long Term Outcomes

The biomarker has the potential to identify patients who may face prolonged cognitive impairments after TBI.
The biomarker has the potential to identify patients who may face prolonged cognitive impairments after TBI.

A study reported in a recent issue of Neurology shows that measurement of interhemispheric transfer time (IHTT) provides a potential biomarker of continued cognitive impairment in pediatric patients in the year following traumatic brain injury (TBI).1

Electroencephalographic (EEG) scalp recordings of the time it took for neurological signals to cross from one side of the brain to the other through the corpus collosum indicated widespread continuing structural white matter (WM) disorganization resulting in cognitive deficits in 21 pediatric patients 2 to 5 months after moderate to severe TBI, compared with 20 age-matched controls.

The aim of the current investigation was to identify patterns that could identify patients at risk for progressive damage based on previous studies showing slower IHTT following TBI.2-4 The children were selected for 2 periods of follow-up from 4 pediatric intensive care units in Los Angeles County in California. The study cohort was then split into 2 groups according to post-acute IHTT magnetic resonance images (MRI) at the first assessment following the initial trauma, designated as either “TBI-slow,” indicting continued progressive WM disorganization (n=11) or “TBI-normal,” indicating recovery  (n=10). White matter was reevaluated at 13 to 19 months post injury to identify the persistence of chronic degenerative damage.

The trajectories between the initial and chronic phases post-TBI were then plotted for comparison, with several interesting patterns revealed. The longitudinal trajectories for the patients in the TBI-slow group diverged from the normal group with widespread increases in mean, radial, and axial diffusivity (13 of 18 tracts measured on MRI), compared with decreases in those same tracks in the TBI-normal group for the same time segments, indicative of the recovery of myelin. The TBI-normal group followed a pattern very similar to that in healthy, unaffected participants.

The investigators found that the TBI-slow group had significantly poorer cognitive outcomes as far out as 18 months post-injury, while the TBI-normal group did not show significant WM changes compared with healthy controls, and did not show persistent signs of cognitive impairment. This differentiation of the 2 IHTT patterns expanded on previous research that showed post-TBI cognitive performance in both groups was greatly altered compared with normal controls.3,4

In an accompanying editorial, Rejean Guerriero, DO and Bradley Schlaggar, MD, PhD suggested that, “A key question, then, is the extent to which the postacute measurements can be used to predict, at an individual patient level, not only whether a patient is at risk for a poorer outcome, but also whether that poorer outcome will manifest.”5

The investigators found that injury severity had little bearing on individual outcomes. Progressive decline over the longer-range chronic period (1 year post-injury) was strongly predicted by slow IHTT in the initial TBI post-acute phase of 2 to 5 months, suggesting a potential biomarker for future morbidity, they concluded.


  1. Dennis EL, Rashid F, Ellis MU, et al. Diverging white matter trajectories in children after traumatic brain injury: the RAPBI study. Neurology. 2017;88:1392-1399.
  2.  Dennis EL, Jin Y, Villalon-Reina J, et al. White matter disruption in moderate/severe pediatric traumatic brain injury: advanced tract-based analyses. Neuroimage Clin. 2015;7:493-505.
  3.  Ellis MU, Marion SD, McArthur DL, et al. The UCLA study of children with moderate-to-severe traumatic brain injury: event-related potential measure of interhemispheric transfer time. J Neurotrauma. 2016;33:990-996.
  4.  Mathias JL, Bigler ED, Jones NR, et al. Neuropsychological and information processing performance and its relationship to white matter changes following moderate and severe traumatic brain injury: a preliminary study. Appl Neuropsychol. 2004;11:134-152.
  5.  Guerriero RM. Schlaggar BI. An important step toward a functional biomarker in pediatric TBI recovery and outcome. Neurology. 2017;88:1-2.
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