Temporal Profile of Cerebrovascular Reactivity Impairment, Gray Matter Volumes, and Persistent Symptoms after Mild Traumatic Head Injury

Leodante da Costa, Christiaan Bas van Niftrik, David Crane, Jorn Fierstra, Allison Bethune

Increased awareness around neurocognitive deficits after mild traumatic brain injury (mTBI) has progressed the search for objective, diagnostic, and monitoring tools, yet imaging biomarkers for mTBI and recovery are not established in clinical use. It has been suggested that mTBI impairs cerebrovascular reactivity (CVR) to CO2, which could be related to post-concussive syndrome (PCS). We investigate CVR evolution after mTBI using blood-oxygen-level dependent (BOLD) magnetic resonance imaging (MRI) and possible correlation with PCS. A prospective cohort of 25 mTBI patients and 18 matched controls underwent BOLD MRI CVR measurements. A subset of 19 mTBI patients underwent follow-up testing. Visits took place at a mean of 63 and 180 days after injury. Symptoms were assessed with the Sport Concussion Assessment Tool 2 (SCAT2). Symptoms, CVR and brain volume [gray matter (GM), white matter (WM), and whole brain (WB)], age, and sex, were examined between groups and longitudinally within traumatic brain injury (TBI) patients. Traumatic brain injury participants were 72% males, mean age being 42.7 years. Control participants were 61% with mean age of 38.7 years. SCAT2 scores tended to improve among those mTBI patients with follow-up visits (p = 0.07); however, they did not tend to recover to scores of the healthy controls. Brain volumes were not statistically different between groups at the first visit (WM p = 0.71; GM p = 0.36). In mTBI patients, there was a reduction in GM volume between visits 1 and 2 (p = 0.0046). Although mean CVR indexes were similar (WM p = 0.27; GM p = 0.36; and WB p = 0.35), the correlation between SCAT2 and CVR was negative in controls (WM-r = -0.59; p = 0.010; GM-r = -0.56; p = 0.016; brain-r = -0.58; p = 0.012) and weaker and positive in mTBI (brain-r = 0.4; p = 0.046; GM-r = 0.4; p = 0.048). SCAT2 correlated with GM volume (r = 0.5215, p = 0.0075) in mTBI but not in controls (r = 0.2945, p = 0.2355). There is a correlation between lower GM CVR indexes and lower performance on SCAT2 in patients with mTBI, which seems to be associated with more symptoms. This correlation seems to persist well beyond 120 days. mTBI may lead to a decrease in GM volume in these patients.