The Toronto traumatic brain injury study

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Abstract
Objective: To assess the relationship between regional brain volume changes and traumatic brain injury (TBI) severity in patients with and without focal lesions. Methods: Sixty-nine chronic-phase TBI patients spanning the full range of severity were recruited from consecutive hospital admissions. Patients received high-resolution structural MRI a minimum of 1 year after injury. Multivariate statistical analyses assessed covariance patterns between volumes of gray matter, white matter, and sulcal/subdural and ventricular CSF across 38 brain regions and TBI severity as assessed by depth of coma at the time of injury. Patients with diffuse and diffuse plus focal injury were analyzed both separately and together. Results: There was a stepwise, dose–response relationship between parenchymal volume loss and TBI severity. Patients with moderate and severe TBI were differentiated from those with mild TBI, who were in turn differentiated from noninjured control subjects. A spatially extensive pattern of volume loss covaried with TBI severity, with particularly widespread effects in white matter volume and sulcal/subdural CSF. The most reliable effects were observed in the frontal, temporal, and cingulate regions, although effects were observed to varying degrees in nearly every brain region. Focal lesions were associated with greater volume loss in frontal and temporal regions, but volume loss remained marked even when analyses were restricted to patients with diffuse injury. Conclusions: Patterns of parenchymal volumetric changes can differentiate among levels of traumatic brain injury (TBI) severity, even in mild TBI. TBI causes a spatially extensive pattern of volume loss that reflects independent but overlapping contributions of focal and diffuse injury.