Modeling Progressive Brain Volume Losses in Chronic Moderate Severe Traumatic Brain Injury: Extensive, but Attenuating.

OBJECTIVE

Progressive brain atrophy has now been widely observed in the chronic stages of moderate-severe traumatic brain injury (msTBI), but there is only coarse information regarding its prevalence and magnitude, and whether rate of atrophy accelerates or attenuates across time. We examined these questions in a Canadian inception cohort from the Toronto Rehab TBI Recovery Study.

METHODS

N = 123 patients with post-traumatic amnesia ranging from > 1 h to 10 weeks (70%, > 7 days) were administered up to three MRIs at approximately 5 months, 1 year, and 3 years post-injury. N = 32 healthy controls were scanned up to two times on average 14 months apart. Ventricle-to-brain ratio (VBR) was calculated and manual segmentation of the hippocampi (HPC), corpus callosum (CC), and substructures was employed. For each region, annualized rates of progressive atrophy were modeled from approximately 5 months to 1 year and 1 to 3 years post-TBI; proportions of patients with annualized volume losses of 2.5%-5%, 5%-10%, and > 10% were estimated.

RESULTS

Mixed-effects longitudinal models estimated robust progressive atrophy in both time windows in all regions compared to controls, but with significant attenuation across windows. In the earlier window, > 10% annualized loss was estimated in 76.2% of patients for VBR, 53.2% for CC, and 25.0% for HPC bilaterally. In the later window, at least 5%-10% annualized loss was estimated in 63.3% of patients for VBR, 49.4% for CC, and 17.7% for right HPC; for left HPC, 6.3% of patients showed at least 2.5%-5% annualized decline.

INTERPRETATION: Clinically concerning prevalence and degree of progressive volume losses were observed in the chronic stages of msTBI, with tapering of losses across time, and regional variations. Research is needed to understand and mitigate clinical impact of these declines.