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

Cerebral Vasoreactivity Is Impaired Beyond Symptom Resolution Following Concussion in Collegiate Athletes

Compromised cerebral blood flow (CBF) regulation is linked to impaired functional outcome following concussion. Cerebral vasoreactivity (CVR), an important mechanism in CBF regulation, is the ability of cerebral blood vessels to alter blood flow during dynamic changes in arterial carbon-dioxide (CO₂). PURPOSE: The purpose of this study was to examine CVR in an ongoing prospective cohort of collegiate athletes during acute (day-3) and sub-acute (day-21) phases following concussion and compare them with non-injured athletes. METHODS: Sixteen male and female collegiate athletes (21±1 years) with sports-related concussion and 16 sports matched non-injured controls (21±1 years) were enrolled in the study. For injured athletes, data was collected during the acute and sub-acute phase following concussion and for the controls data was collected at one time point. Symptom severity and cognition were assessed using the Sports Concussion Assessment Tool-3rd Edition. 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). CVR was analyzed as the slope of the linear relationship between PetCo₂ and MCAV, which was expressed as the percent change in CBF velocity per mmHg change in PetCo₂. Independent and paired t-tests were used to compare symptom severity, and CVR between acute and sub-acute phase following concussion with the controls. RESULTS: As anticipated, concussed athletes exhibited higher symptom severity (26.3±0.5 versus 5±7 P= 0.0007) and lower cognition (26.5±1.6 versus 28.3±2.4 P=0.03) during acute phase compared to the controls. Although symptoms and cognition were resolved during the sub-acute phase, CVR was lower in the acute phase compared to the non-injured controls (1.7±0.5U versus 2.3±0.3U, P=0.0006) and it continued to be blunted in the sub-acute phase following concussion (1.9±0.5U P=0.04). CONCLUSION: Despite improvements in symptom and cognition, cerebral vasoreactivity appears to be impaired in the sub-acute phase following concussion. Cerebral vasoreactivity utilizing TCD may be a useful vascular biomarker for physiological recovery and aid in accurate return-to play decision-making

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

Improvement in Heart Rate Variability during Mild Cognitive Task Following Concussion

Cognitive rest is widely recommended following concussion until symptoms resolve. Unlike return-to-play protocols, there is a lack of clear guideline for return-to-learn in student athletes. Heart rate variability (HRV) is an index of cardiac health and reduced HRV is associated with disturbances in the autonomic nervous system (ANS) following concussion. PURPOSE: Therefore, the purpose of our study was to examine ANS modulation utilizing HRV at rest and during mild cognitive task in concussed and non-injured control athletes. METHODS: Nineteen collegiate athletes (20 ± 1 years) with a physician-diagnosed sports-related concussion were enrolled in the study acutely (4 ± 1 days) following a concussion. Nineteen sports matched non-injured controls also participated. Continuous heart rate recording was obtained with a standard three-lead electrocardiogram at rest and during a mild cognitive task while subjects where seated upright. Resting data was collected for 6 minutes. A computer based cognitive test (2-Back) designed to assess sustained attention and executive function was administered for 3 minutes. Average response time and the percentage of correct responses were obtained from the 2-Back trial. HRV was analyzed with power spectral analysis within the low (LF, 0.04-0.15 Hz) and high (HF, 0.15-0.4 Hz) frequency domains. Normalized LF and HF power spectral densities (n.u.) and LF/HF ratio were obtained. Two-way repeated measures ANOVA {group (concussed, control) x condition (rest, 2-Back)} was used to examine the variables. RESULTS: Higher LF (61.1±15 vs. 45±12, P=0.007), lower HF (38.8±15 vs.54.4±12, P=0.008) variability and higher LF/HF ratio (2.2±2 vs. 0.92±0.4, P= 0.005) were observed in the concussed athletes compared to controls at rest indicating exaggeration of the sympathetic nervous system modulation. Conversely, lower LF (44.5±14, P=0.003), higher HF (55.4±14, P= 0.003) and lower LF/HF ratio (0.92±0.5, P=0.003) was observed with 2-Back cognitive tasks as opposed to rest in the concussed group. The control group showed no difference in HRV between rest and 2-back trials. Despite similar response times for the 2-Back cognitive task, the percentage of correct response was lower (79.9±14.2 vs. 89.9±4.6, P=0.008) in the concussed athletes compared to the non-injured athletes. CONCLUSION: Disturbances in ANS exist as early as 4 days following a concussion. Mild cognitive tasks during rehabilitation may be advantageous in improving cognitive function on and off the field and may expedite the return-to-learn phase in student athletes. Further studies in this field are needed to determine if current complete cognitive rest is possibly inhibitory to recovering in concussed athletes, as opposed to mild cognitive task to promote ANS function

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