Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: a systematic review

Gardner, Andrew J.; Tan, Can Ozan; Ainslie, Philip N.; Donkelaar, Paul; Stanwell, Peter; Levi, Christopher

doi:10.1136/bjsports-2014-093901

Cited by 45 publications

(35 citation statements)

References 49 publications

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“…In professional boxers, CVR is decreased in the first week after a fight, and correlates with cumulative lifetime concussions 24. A meta‐analysis of CVR after sports concussion concluded that CVR is decreased acutely 25. Our group has found that MRI measures of CVR reliably distinguishes chronic TBI from HC with the greatest effect size in the gray matter 26.…”

Section: Introductionmentioning

confidence: 79%

Phosphodiesterase‐5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Kenney

Amyot

Moore

et al. 2018

Ann Clin Transl Neurol

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BackgroundTraumatic cerebrovascular injury (TCVI), a common consequence of traumatic brain injury (TBI), presents an attractive therapeutic target. Because phosphodiesterase‐5 (PDE5) inhibitors potentiate the action of nitric oxide (NO) produced by endothelial cells, they are candidate therapies for TCVI. This study aims to: (1) measure cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and change in CVR after a single dose of sildenafil (ΔCVR) in chronic TBI compared to uninjured controls; (2) examine the safety and tolerability of 8‐week sildenafil administration in chronic symptomatic moderate/severe TBI patients; and as an exploratory aim, (3) assess the effect of an 8‐week course of sildenafil on chronic TBI symptoms.MethodsForty‐six subjects (31 chronic TBI, 15 matched healthy volunteers) were enrolled. Baseline CBF and CVR before and after administration of sildenafil were measured. Symptomatic TBI subjects then completed an 8‐week double‐blind, placebo‐controlled, crossover trial of sildenafil. A neuropsychological battery and neurobehavioral symptom questionnaires were administered at each study visit.ResultsAfter a single dose of sildenafil, TBI subjects showed a significant increase in global CVR compared to healthy controls (P < 0.001, d = 0.9). Post‐sildenafil CVR maps showed near‐normalization of CVR in many regions where baseline CVR was low, predominantly within areas without structural abnormalities. Sildenafil was well tolerated. Clinical Global Impression (CGI) scale showed a trend toward clinical improvement while on sildenafil treatment.FindingsSingle‐dose sildenafil improves regional CVR deficits in chronic TBI patients. CVR and ΔCVR are potential predictive and pharmacodynamic biomarkers of PDE5 inhibitor therapy for TCVI. Sildenafil is a potential therapy for TCVI.

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Section: Introductionmentioning

confidence: 79%

Phosphodiesterase‐5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Kenney

Amyot

Moore

et al. 2018

Ann Clin Transl Neurol

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“…Indeed, a prospective study in a cohort of healthy controls, utilizing the same MRI technique described here but with different image data analysis, demonstrated excellent within-day measures of gray and white matter cerebrovascular reactivity (CVR), excellent between-day measures of gray matter CVR, and good between-day reproducibility of white matter CVR. 27 In comparison with other imaging modalities that can be used to estimate CVR, such as transcranial Doppler ultrasonography, 20 our technique provides qualitative and quantitative assessment of whole-brain cerebrovascular physiology that is not limited to only 1 or 2 vascular territories (for example, the middle cerebral artery) and is not dependent on the skill or interpretation of the examiner.…”

Section: Discussionmentioning

confidence: 99%

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome

Mutch

Ellis

Ryner

et al. 2016

JNS

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abbreviatioNs ASL = arterial spin labeling; AUC = area under the curve; BOLD = blood oxygen level-dependent; CBF = cerebral blood flow; CVR = cerebrovascular reactivity; dmIC = dorsal mid-insular cortex; DTI = diffusion tensor imaging; ET = end-tidal; GRE = gradient recalled echo planar; fMRI = functional MRI; MNI = Montreal Neurological Institute; MPET = model-based prospective end-tidal; MPRAGE = magnetization-prepared rapid gradient-echo; PaCO 2 = arterial partial pressure of carbon dioxide; pCASL= pseudo-continuous arterial spin labeling; PCD = postconcussion disorder; PCS = postconcussion syndrome; PCSS = Post-Concussion Symptom Scale; ROC = receiver operating characteristic; SPM = statistical parametric mapping; SRC = sports-related concussion; TBI = traumatic brain injury. obJective A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO 2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. methods This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO 2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO 2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). results Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO 2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO 2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. coNclusioNs Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO 2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

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“…11,13,[16][17][18][19][20][21][22] Although the pathogenesis of concussion has yet to be fully elucidated, it is becoming increasingly clear that cerebrovascular alterations play a significant role in the evolution of injury sequelae, as well as in the process of post-traumatic brain repair. 4,11,[22][23][24] Reduced cerebral blood flow (CBF) signifies one of the most lasting markers of concussion in animal models of traumatic brain injury (TBI), 14,25,26 while CBF has been shown to be decreased immediately after injury in an animal model 27,28 and decreased regional CBF persisted after injury. 29 Reduced CBF during the acute and subacute phases of mTBI has been detected using imaging methods such as single-photon emission computed tomography 30,31 and perfusion computed tomography, 32 which have several disadvantages, including financial cost, ionizing radiation, and limited repetition of acquisitions.…”

Section: Introductionmentioning

confidence: 99%

Cerebral Blood Flow Alterations in Acute Sport-Related Concussion

Wang

Nelson

LaRoche

et al. 2016

Journal of Neurotrauma

151

117

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Sport-related concussion (SRC) is a major health problem, affecting millions of athletes each year. While the clinical effects of SRC (e.g., symptoms and functional impairments) typically resolve within several days, increasing evidence suggests persistent neurophysiological abnormalities beyond the point of clinical recovery after injury. This study aimed to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared CBF maps assessed in 18 concussed football players (age, 17.8 -1.5 years) obtained within 24 h and at 8 days after injury with a control group of 19 matched non-concussed football players. While the control group did not show any changes in CBF between the two time-points, concussed athletes demonstrated a significant decrease in CBF at 8 days relative to within 24 h. Scores on the clinical symptom (Sport Concussion Assessment Tool 3, SCAT3) and cognitive measures (Standardized Assessment of Concussion [SAC]) demonstrated significant impairment (vs. pre-season baseline levels) at 24 h (SCAT, p < 0.0001; SAC, p < 0.01) but returned to baseline levels at 8 days. Two additional computerized neurocognitive tests, the Automated Neuropsychological Assessment Metrics and Immediate Post-Concussion and Cognitive Testing, showed a similar pattern of changes. These data support the hypothesis that physiological changes persist beyond the point of clinical recovery after SRC. Our results also indicate that advanced ASL MRI methods might be useful for detecting and tracking the longitudinal course of underlying neurophysiological recovery from concussion.

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Cerebrovascular reactivity assessed by transcranial Doppler ultrasound in sport-related concussion: a systematic review

Cited by 45 publications

References 49 publications

Phosphodiesterase‐5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Phosphodiesterase‐5 inhibition potentiates cerebrovascular reactivity in chronic traumatic brain injury

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome

Cerebral Blood Flow Alterations in Acute Sport-Related Concussion

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