The subcortical basis of outcome and cognitive impairment in TBI

Objective To understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at 6 months after injury. Methods For this longitudinal analysis, clinical and MRI data were collected in a tertiary neurointensive care setting in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient, we collected T1- and T2-weighted MRI data acutely and at the 6-month follow-up, as well as acute measures of injury severity (Glasgow Coma Scale), follow-up measures of functional impairment (Glasgow Outcome Scale-extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory. Results In the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first 6 months after injury across the brain. However, only atrophy within subcortical regions, particularly in the left thalamus, was associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good from bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could achieve only 20% accuracy. Conclusion Despite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute event and the longer-term disease of traumatic brain injury.