Recovery of Cerebral Blood Flow Following Sports-Related Concussion

Abstract

IMPORTANCE Animal models suggest that reduced cerebral blood flow (CBF) is one of the most enduring physiological deficits following concussion. Despite this, longitudinal studies documenting serial changes in regional CBF following human concussion have yet to be performed. OBJECTIVE To longitudinally assess the recovery of CBF in a carefully selected sample of collegiate athletes and compare time course of CBF recovery with that of cognitive and behavioral symptoms. DESIGN, SETTING, AND PARTICIPANTS A cohort of collegiate football athletes (N = 44) participated in this mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging between March 2012 and December 2013. Serial imaging occurred approximately 1 day, 1 week, and 1 month postconcussion for a subset of participants (n = 17). All athletes reported no premorbid mood disorders, anxiety disorders, substance abuse, or alcohol abuse. MAIN OUTCOMES AND MEASURES Arterial spin labeling magnetic resonance imaging was used to collect voxelwise relative CBF at each visit. Neuropsychiatric evaluations and a brief cognitive screen were also performed at all 3 points. Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome (ie, number of days withheld from competition). RESULTS The results indicated both cognitive (simple reaction time) and neuropsychiatric symptoms at 1 day postinjury that resolved at either 1 week (cognitive; P < .005) or 1 month (neuropsychiatric; P < .005) postinjury. Imaging data suggested both cross-sectional (ie, healthy vs concussed athletes; P < .05) and longitudinal (1 day and 1 week vs 1 month postinjury; P < .001) evidence of CBF recovery in the right insular and superior temporal cortex. Importantly, CBF in the dorsal midinsular cortex was both decreased at 1 month postconcussion in slower-to-recover athletes (t 11 = 3.45; P = .005) and was inversely related to the magnitude of initial psychiatric symptoms (Hamilton Depression Scale: r = −0.64, P = .02; Hamilton Anxiety Scale: r = −0.56, P = .046), suggesting a potential prognostic indication for CBF as a biomarker. CONCLUSIONS AND RELEVANCE To our knowledge, these results provide the first prospective evidence of reduced CBF in human concussion and subsequent recovery. The resolution of CBF abnormalities closely mirrors previous reports from the animal literature and show real-world validity for predicting outcome following concussion.

A Physiological Approach to Prolonged Recovery From Sport-Related Concussion

“…Concussion affects the autonomic nervous system (ANS) 27,28 and the control of both cerebral blood flow (CBF) [29][30][31][32] and cardiac rhythm. 33,34 The primary ANS control center may be damaged in concussion, particularly if a rotational force was applied to the upper cervical spine, 35 as supported by results from a diffusion tensor imaging study 36 that showed changes to brainstem white matter neurons after concussion.…”

“…24,37 For example, reduced resting CBF has been evident for up to a month postconcussion in some adolescents 31 and collegiate football players. 32 The resolution of this vulnerable period of brain metabolic imbalance after concussion does not necessarily coincide with the resolution of symptoms. Using proton magnetic resonance spectroscopy, Vagnozzi et al 38 showed that metabolic dysfunction can last up to 30 days after SRC and up to 45 days if a second injury occurs before the first has resolved.…”

The current state of biomarkers of mild traumatic brain injury

“…These results suggest that determination of regional CBF detection via neuroimaging has potential as an objective biomarker for tracking symptoms and recovery after concussion. A study of 44 collegiate football athletes showed decreased CBF in the dorsal midinsular cortex (dmIC) and superior temporal sulcus, both of which are important for higher cognitive functioning, as compared with healthy controls one week after injury (43). Furthermore, CBF in dmIC at one-month after injury inversely correlated with concussion severity and symptom resolution (43).…”

“…A study of 44 collegiate football athletes showed decreased CBF in the dorsal midinsular cortex (dmIC) and superior temporal sulcus, both of which are important for higher cognitive functioning, as compared with healthy controls one week after injury (43). Furthermore, CBF in dmIC at one-month after injury inversely correlated with concussion severity and symptom resolution (43). Future neuroimaging studies should examine not only functional activity after mTBI but also differences in functional connectivity as potential biomarker candidates (43).…”

Sports Concussion: A Clinical Overview

“…Altered functional connectivity has also been observed relative to executive function, visual, and motor networks [57][58][59][60]. Reduced cerebral blood flow (CBF) has been reported during the acute and sub-acute phases (days to weeks) post-concussion [61][62][63], as well as at more chronic time points (approximately 5 months) [64].…”