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 six months post-injury. Methods: Longitudinal analysis of clinical and MRI data 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 a six-months follow-up, as well as acute measures of injury severity (Glasgow Coma Scale) and 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 six months post-injury across the brain. Nonetheless, only atrophy within subcortical regions, particularly in left thalamus, were 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 versus bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could only achieve 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 TBI.

These materials are a supplement to the text in the manuscript "The subcortical basis of outcome and cognitive impairment in TBI: a longitudinal cohort study" by Evan S. Lutkenhoff, PhD, Matthew J. Wright, PhD, Vikesh Shrestha, BS, Courtney Real, MSN, David L. McArthur, PhD, MPH, Manuel Buitrago-Blanco, MD, PhD, Paul M. Vespa, MD, Martin M. Monti, PhD.

This supplement includes the following content:

Table S1. Shape analysis results (Time).

Table S2. Shape analysis results (Outcome).

Table S3. Shape analysis results (Cognitive impairment analysis: Attention).  

Table S4. Shape analysis results (Cognitive impairment analysis: Executive Functions).  

Table S5. Shape analysis results (Cognitive impairment analysis: Episodic Memory).

Table S6. Modeling analysis results (Outcome).

Table S7. Modeling analysis results (Cognitive impairment).