Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury

To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury.

Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI.

Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest.

(1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time.

Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.