Persistent Impairment in Cerebral Vasoreactivity in Subacute Phase Following Concussion

Concussion diagnosis is characterized by a lack of objective markers, as there is a paucity of better understanding of the pathophysiology. Cerebral vasoreactivity (CVR), an important factor in cerebral blood flow (CBF) regulation with dynamic changes in metabolism can be assessed utilizing manipulation of arterial carbon dioxide. CVR utilizing transcranial Doppler ultrasonography may be a useful, objective vascular biomarker for physiological recovery. PURPOSE: To determine the link between clinical symptoms and CVR on Day-3, Day-21, and Day-90 following a concussion in comparison to the non-injured controls. METHODS: Twenty-seven male and female collegiate athletes (21 ±1years) sustaining a sports-related concussion were enrolled. Age and sports-matched non-injured controls were also enrolled. For the concussed athletes, data were obtained on Day-3, Day-21, and Day-90 (N= 17) following the head injury. Symptom severity and cognition were assessed using the Sports Concussion Assessment Tool-3rd Edition (SCAT-3). Depression was assessed utilizing the Patient Health Questionnaire (PHQ-9). Continuous middle cerebral artery blood flow velocity (MCAV) was obtained with transcranial Doppler ultrasonography (TCD) while subjects were seated in an upright position. End-tidal CO₂ (PetCO₂) was measured with an infrared CO₂ analyzer attached to a nasal cannula. MCAV was evaluated in response to changes in PetCO₂ for 2-minutes each during normal breathing (normocapnia), inspiring a gas mixture containing 8% CO₂, 21% oxygen (hypercapnia), and hyperventilating (hypocapnia). RESULTS: On Day-3 subsequent to the head injury, concussed athletes displayed higher symptom number (2.5±3 vs. 12.1±7; PCONCLUSION: Elevated symptoms and lower cognitive scores on Day-3 were resolved by Day-21 following a sports-related concussion. On the other hand, CVR remained impaired at 90 days following concussion suggesting persistent physiological impairment beyond symptom resolution, which could accentuate secondary injuries during this phase. Future studies with a large sample size and longer follow-up period are needed to validate the use of CVR as an objective marker

Cardiac Vagal Tone Impairment is Associated with Reduced Cerebral Blood Flow in Collegiate Athletes Following Concussion

Reduced cerebral blood flow (CBF) is linked to functional disturbances following concussion. Since cardiac vagal tone (an index of cardiac health) is associated with disturbances in the autonomic nervous system, deficits in CBF are likely associated with cardiac vagal tone impairment post-concussion. PURPOSE: The current study examined cardiac vagal tone and CBF on days 3, 21 and 90 following concussion in comparison to non-injured control athletes. The association between these two variables was also evaluated. METHODS: Concussed male and female collegiate athletes were evaluated day-3 (N=29), day-21 (N=25) and day-90 (N=17) post concussion and matched controls were enrolled (N=29). A 3-lead electrocardiogram was used to assess cardiac vagal tone in the high frequency domain (HF; 0.15-0.4 Hz). Beat-to-beat mean arterial pressure (MAP) was obtained via finger photoplethysmography and transcranial Doppler ultrasonography (TCD) was used to assess middle cerebral blood flow velocity (MCAV). To measure vascular tone, cerebrovascular conductance index (CVCi) was estimated by dividing MCAV with MAP. Symptom severity and cognition were assessed using the Sports Concussion Assessment Tool-3rd Edition (SCAT-3) and executive function was assessed with the Trails test A & B. RESULTS: On day-3, concussed athletes had lower cognition (SAC 28±1vs.26±2,P=0.0005; Trails B 48±8vs.58±15sec,P=0.006) and HF power (52±12vs.36±14,P=0.006) compared to controls. On days 21 and 90, values were comparable to the controls. However, concussed participants were also categorized based on day-3 MCAV (divided at the median), into low and high MCAV groups. On day-3, the group with lower MCAV exhibited lower HF power (29±13vs.42±11.P=0.006) and lower CVCi (0.60±0.13vs.0.88±0.13,PCONCLUSION:Cardiac vagal tone was impaired 3 days following concussion compared to controls. Lower CBF was also associated with higher cerebrovascular tone. Additionally, lower CBF was linked to blunted cardiac vagal tone and functional outcome on day-21. On day-90, CBF recovered with normalization of functional outcome. Future studies with large sample are recommended to validate these findings

Persistent Neurovascular Coupling Dysregulation During Subacute Recovery Phase Following Concussion

Concussion diagnosis is characterized by a lack of objective markers, as there is a paucity of better understanding of the pathophysiology. Neurovascular coupling (NVC), an important factor in cerebral blood flow (CBF) regulation, is a tight temporal relationship between neuronal activity and CBF in order to meet cerebral metabolism. PURPOSE: To examine NVC on Day-3, Day-21, and Day-90 following a concussion in comparison to the non-injured healthy controls. METHODS: Twenty-nine male and female collegiate athletes (20±1years) sustaining a sports-related concussion were enrolled in a longitudinal study. For the concussed athletes, data were obtained on Day-3 (N=29), Day-21 (N=26), and Day-90 (N= 21) following the head injury. Thirty-two sports-matched non-injured controls were also enrolled and data were obtained at a single time point. Symptom number and severity and cognition were assessed using the Sports Concussion Assessment Tool-3rd Edition (SCAT-3). To assess NVC, continuous middle cerebral artery blood flow velocity (MCAV) was obtained bilaterally with 2 MHz transcranial Doppler ultrasonography (TCD) while subjects were seated in an upright position. As a measure of working memory and executive function, the 0-Back (control task) and 2-Back (cognitive task) tasks were performed for 3 minutes each. NVC was estimated as the percentage change in MCAV between the 2-Back (MCAV2Bk) and 0-Back (MCAV0Bk) tasks for each subject. The equation used was NVC (%)=[(MCAV2Bk - MCAV0Bk)/ MCAV0Bk] X 100. A non-parametric Wilcoxon rank sum test was utilized to compare NVC means between the controls and concussed athletes at the three time points. RESULTS: On Day-3 subsequent to the head injury, concussed athletes, compared to the controls, displayed higher symptom number (12.2±6.8 vs. 2.4±3.4; p, lower NVC was observed on Day-3 (0.36±3.62 p=0.03) and Day-21 (0.18±3.31 p=0.01) with persistent decline observed on Day-90 (-0.5±2.9 p=0.003) following concussion. No difference in NVC was observed within the three points post-concussion. CONCLUSION: NVC remained dysregulated during the acute phase and worsened during subacute phases following concussion suggesting persistent physiological impairment beyond symptom resolution. Future studies with a large sample size and longer follow-up period are needed to track the physiological recovery trajectory and examine if there is an association between dysregulation of NVC and higher risk of secondary injuries post-concussion

Despite Symptom Resolution Dynamic Cerebral Autoregulation is Impaired in Collegiate Athletes Following Concussion

Concussions are among some of the most prevalent sports-related injuries, however, the pathophysiology of the injury is still poorly understood. Studies have consistently reported deficits in cerebral blood flow (CBF) following concussions, suggesting impairments in CBF regulation. PURPOSE: To examine dynamic cerebral autoregulation (dCA) in collegiate athletes on day-3, day-21, and day-90 following a concussion and compare them with non-injured controls. METHODS: Twenty-seven male and female athletes (20±1 years) diagnosed with a sports-related concussion were enrolled in the prospective cohort study. For the concussed athletes, data was collected on days 3, 21, and 90 following the injury. A cross-sectional design included twenty-five sports matched healthy controls (20±1 years) in the study. Concussion symptom number and severity was assessed using the Sports Concussion Assessment Tool (SCAT-3). Depression scores were quantified utilizing the Patient Health Questionnaire-9 (PHQ-9). Continuous mean arterial blood pressure (MAP) (finger photoplethysmography) and middle cerebral artery blood flow velocity (MCAV) (2 MHz transcranial Doppler ultrasonography) were attained while subjects were at rest seated in an upright position for 6 minutes and during a squatting exercise at 0.1Hz frequency for 5 minutes. Transfer function (Tf) analysis of beat-to-beat oscillations in MAP and MCAV in the low (LF, 0.07-0.20 Hz) and high (HF, 0.20-0.35 Hz) frequency ranges were utilized to assess dCA. Effective dCA reduces the fluctuations in MCAV in response to MAP oscillations, resulting in a low Tf gain value. Independent and paired t-tests were used to compare symptoms and dCA between days 3, 21, and 90 following concussion with the healthy controls. RESULTS: As anticipated, on day-3, concussed athletes exhibited greater symptom number (12.2±6.8 vs. 2.4±3.4; p\u3c0.001) and higher PHQ-9 score (8.7±5.6 vs. 2.1±2.1; p\u3c0.001) compared to the controls. Additionally, on day-3, LF Tf gain at rest was higher (1.26±0.34U vs. 1.04±0.28U; p=0.016) compared to the healthy athletes. Despite normalization of symptoms and depression scores, LF Tf gain continued to be higher on day-21 (1.30±0.45U p=0.025) compared to the controls. In addition, LF Tf gain during the squatting exercise was higher on day-3 (1.5±0.34 vs. 1.05±0.29U; p=0.001) and day-21 (1.47±0.22U p=0.0009) in the concussed athletes compared to the controls. LF Tf gain at rest and during squatting on day-90 was comparable to the controls. CONCLUSION: The study confirms that dCA is impaired during the subacute recovery phase despite improvements in clinical symptom and depression. Additionally, during this subacute phase, physical stressors following return-to-play may worsen cerebral autoregulation. CBF regulation estimated from transcranial Doppler ultrasonography may be useful in tracking physiological recovery and preventing the risk of second-impact syndrome in collegiate athletes