Cerebral Vasoreactivity During Acute and Recovery Phase Post-Concussion: A Pilot Study

The diagnosis of sports-related concussion is based mostly on clinical symptoms. Return-to-play decisions are made when the athletes are symptom free; however, some metabolic and physiological impairments may persist such as impairments in cerebral blood flow regulation. The purpose of this study was to examine cerebral vasoreactivity from acute phase to recovery phase in athletes with a sports-related concussion. Eight NCAA Division I male athletes (21 ± 2 years) with a confirmed sports-related concussion participated in the study. Data was collected on day 3 (acute) and day 21 (recovery) following a concussion. Subjects also reported any incidences of previous concussions. Arterial blood pressure was obtained with finger photoplethysmography and middle cerebral artery blood flow velocity (MCAV) was collected using transcranial Doppler ultrasonography. Expired CO2 was continuously measured with an infrared CO2 analyzer attached to a nasal cannula. Data was collected while subjects breathed room air for 2 minutes, hyperventilated for 2 minutes, and then inspired a gas mixture of 8% CO2, 21% oxygen, and balanced nitrogen for 2 minutes. Cerebral vasoreactivity was analyzed as the slope of the linear relationship between end-tidal CO2 and MCAV and expressed as the change in cerebral blood flow per mmHg change in end-tidal CO2. Cerebral vasoreactivity improved from acute phase to recovery phase in 4 subjects, and worsened in 4 subjects. Subjects with no history of concussions had improved cerebral vasoreactivity (0.676 ± 0.11 to 1.218 ± 0.19 cm sec-1 mmHg-1). However, subjects with a history of concussions had poor outcome on cerebral vasoreactivity during recovery phase (1.154 ± 0.23 to 0.793 ± 0.15 cm sec-1 mmHg-1). These data provide evidence that athletes with a history of concussions may require a longer recovery period to prevent long-term complications

Impairments in Cerebral Autoregulation is Associated with Postural Control in Sports Related Concussion

Global and regional deficits in cerebral blood flow are reported with concussions, a major public health concern, with approximately 3.8 million incidences occurring annually in the United States alone. Recent studies have identified an increased risk of musculoskeletal injuries in athletes upon return-to-play. Complexity index is a sensitive marker of postural control, with low complexity index indicating a poor physiological adaptation to stress. PURPOSE: Twofold; 1. Examine complexity index and dynamic cerebral autoregulation (dCA) at rest and during physical stress (rhythmic squatting) in collegiate athletes following a concussion in comparison to non-injured controls. 2. Examine the association between complexity index and dCA. METHODS: Athletes (20±1 years) with sports-related concussions were tested on days 3 (N=33), 21 (N=29), and 90 (N=21) following the injury. Controls (N=27) were assessed at one time-point. Continuous mean arterial pressure (MAP) (finger photoplethysmography) and middle cerebral artery blood flow velocity (MCAV) (2 MHz transcranial Doppler ultrasonography) were obtained at rest for 6 minutes and during physical stress (squatting at 0.1Hz frequency) for 5 minutes. Transfer function analysis of beat-to-beat MAP and MCAV oscillations in the low frequency (LF, 0.07-0.20 Hz) range was utilized to assess dCA. Effective dCA dampens the fluctuations in MCAV in response to MAP oscillations, resulting in a low LF gain. Multiscale entropy analysis was used to determine complexity index from the center of pressure data obtained during quiet standing with eyes closed on a force platform. Two-sample Mann Whitney U test was used to compare data between control and concussed athletes at the three time points. Spearman correlation was used to examine the association between the variables. RESULTS: LF gain at rest was higher on day-3 (1.27±0.4U; p=0.007), and day-21 (1.27±0.5U; p=0.03) compared to the controls (1.03±0.2U). Similar findings were observed in LF gain with physical stress (day-3 p= 0.003; day-21 p=0.001). Postural complexity index was lower on day-3 (4.3±1.3U; p=0.004) and day-21 (4.5±1.1U; p=0.02) compared to the controls (5.4±1.4U). Moreover, a negative association was observed between complexity index and LF gain at rest (β= -0.66, p= 0.04) and during squatting (β= -1.53, p= 0.02). CONCLUSION: The findings confirm impairments in cerebral autoregulation and postural control during the acute and subacute recovery phases following a concussion despite symptom resolution. In addition, poor functional outcome, such as postural control, may be associated with alterations in cerebral blood flow regulation in this population. Tracking cerebral autoregulation during recovery phase may help in preventing musculoskeletal injuries in athletes after return-to-play following a concussion

King-Devick Test Score is Linked to Cerebral Vasoreactivity During Acute Recovery Phase Post-Concussion

The King-Devick (KD) test is a quick screening tool used to detect oculomotor and attention related brain function impairments following a concussion. Adequate cerebral blood flow (CBF) is an indicator of structural and functional integrity and impairments in CBF have been linked to cognitive deficits following concussion. Cerebral vasoreactivity (CVR), a key measure of hemodynamic reserve, is an important factor in CBFregulation. PURPOSE: To examine the association between CVR and oculomotor and attention function, using KD test scores, in collegiate athletes following a concussion. METHOD: Eighteen male and female athletes diagnosed with a sports-related concussion were enrolled in the prospective cohort study. Twenty-two non-injured athletes were enrolled as controls. Data was collected longitudinally on day-3, day-21, and day-90 following a concussion. Middle cerebral artery blood velocity (MCAV) was obtained using transcranial Doppler ultrasonography (TCD). CO2 was used as a stimulus to assess CVR. End-tidal CO2 (EtCO2) was monitored with an infrared CO2 analyzer attached to a nasal cannula. Continuous MCAV was obtained for 2-minutes each in response to three CO2 stimuli; normal room-air (normocapnia), inspiring 8% CO2 and 21% O2 gas mixture (hypercapnia), and during hyperventilation (hypocapnia). MCAV and EtCO2 data were plotted and CVR was estimated as the slope of the MCAV and EtCO2 relationship. For the KD test, subjects read aloud single-digit-numbers left to right from three test cards with progressive level of difficulty. Subjects were instructed to read as fast as possible without making errors. KD test score was determined as the sum of the total time required to complete the three test cards. Nonparametric Wilcoxon test was used to assess CVR and KD test scores between control and the concussed group at each of the three time points. Spearman rank order correlation was used to assess the association between CVR and KD scores at each time point. RESULTS: Compared to the control, CVR (1.33±0.31vs.1.14±0.43U; p=0.03) was blunted and KD score (44.4±7.7vs.48.1±6.9sec; p=0.04) was slower on day-3. CVR was comparable to the controls on days 21 and 90. However, a learning effect was observed in KD test score over time (42.1±8.9, p=0.02 [day-21]; 42.03±8.5, p=0.03 [day90]). In addition, a negative correlation between CVR and KD test was observed on day-3 (p= 0.04). CONCLUSION: The preliminary results indicate that deficits in oculomotor function and attention, as identified by KD test, may result from inadequate CBF regulation during the acute recovery phase post-concussion. Further studies should be done to evaluate the potential role of CVR in oculomotor function following concussion in collegiate athletes

Baroreflex Sensitivity is Impaired in Athletes Following a Sports-Related Concussion

Sport-related concussions are a major public health concern, with approximately 3.8 million incidences occurring annually in the United States alone. Autonomic nervous system (ANS) dysfunction is implicated in early and later stages of sports-related concussion recovery. Arterial baroreflex, a crucial mechanism by which the ANS controls short-term fluctuations in blood pressure, remains understudied in this population. PURPOSE: Examine baroreflex sensitivity (BRS) at rest during acute and sub-acute recovery phases following a sport-related concussion in collegiate athletes in comparison to non-injured athletes as controls. METHODS: Athletes (20±1 years) with sports-related concussions were tested on days 3 (N=13), 21 (N=13), and 90 (N=11) following the injury. Control athletes (N=12) were assessed at one time-point. Continuous arterial blood pressure (finger photoplethysmography) and R-R intervals (3-lead electrocardiogram) were obtained at rest for 6 minutes and while subjects were seated in an upright position. BRS was estimated with transfer function analysis to assess the fluctuations in systolic blood pressure and R-R intervals during the time period. Transfer gain in the low-frequency range (0.05– 0.15 Hz) quantified the magnitude of the relationship between changes in systolic blood pressure and R-R interval. Therefore, higher gain indicates higher BRS. A linear mixed model was used to examine symptoms and transfer function variables between the controls and the concussed athletes at the three time points. RESULTS: As anticipated, symptoms were worse on day-3 and resolved during the day-21 sub-acute phase. BRS was lower on day-3 (0.656±0.2U; p=0.003), day-21 (0.711±0.29U; p=0.013), and day-90 (0.77±0.27; p=0.04) following the injury compared to the controls (1.05±0.3U). CONCLUSION: The findings confirm impairments in baroreflex sensitivity during the acute and subacute recovery phases following a concussion despite symptom resolution. Blunted baroreflex sensitivity following injury may position athletes in a vulnerable situation while performing tasks that elicit sudden changes in blood pressure on and off the field

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

The functional role of the alpha-1 adrenergic receptors in cerebral blood flow regulation

Cerebral vasculature is richly innervated by the α-1 adrenergic receptors similar to that of the peripheral vasculature. However, the functional role of the α-1adrenergic receptors in cerebral blood flow (CBF) regulation is yet to be established. The traditional thinking being that during normotension and normocapnia sympathetic neural activity does not play a significant role in CBF regulation. Reports in the past have stated that catecholamines do not penetrate the blood brain barrier (BBB) and therefore only influence cerebral vessels from outside the BBB and hence, have a limited role in CBF regulation. However, with the advent of dynamic measurement techniques, beat-to-beat CBF assessment can be done during dynamic changes in arterial blood pressure. Several studies in the recent years have reported a functional role of the α-1adrenergic receptors in CBF regulation. This review focuses on the recent developments on the role of the sympathetic nervous system, specifically that of the α-1 adrenergic receptors in CBF regulation