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Neurometabolites and sport-related concussion: From acute injury to one year after medical clearance.

ABSTRACT: Sport-related concussion is associated with acute disturbances in neurometabolic function, with effects that may last weeks to months after injury. However, is presently unknown whether these disturbances resolve at medical clearance to return to play (RTP) or continue to evolve over longer time intervals. Moreover, little is known about how these neurometabolic changes correlate with other measures of brain physiology. In this study, these gaps were addressed by evaluating ninety-nine (99) university-level athletes, including 33 with sport-related concussion and 66 without recent injury, using multi-parameter magnetic resonance imaging (MRI), which included single-voxel spectroscopy (SVS), diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). The concussed athletes were scanned at the acute phase of injury (27/33 imaged), medical clearance to RTP (25/33 imaged), one month post-RTP (25/33 imaged) and one year post-RTP (13/33 imaged). We measured longitudinal changes in N-acetyl aspartate (NAA) and myo-inositol (Ins), over the course of concussion recovery. Concussed athletes showed no significant abnormalities or longitudinal change in NAA values, whereas Ins was significantly elevated at RTP and one month later. Interestingly, Ins response was attenuated by a prior history of concussion. Subsequent analyses identified significant associations between Ins values, DTI measures of white matter microstructure and fMRI measures of functional connectivity. These associations varied over the course of concussion recovery, suggesting that elevated Ins values at RTP and beyond reflect distinct changes in brain physiology, compared to acute injury. These findings provide novel information about neurometabolic recovery after a sport-related concussion, with evidence of disturbances that persist beyond medical clearance to RTP.

SUBMITTER: Churchill NW

PROVIDER: S-EPMC7215245 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neurometabolites and sport-related concussion: From acute injury to one year after medical clearance.

Churchill Nathan W NW Hutchison Michael G MG Graham Simon J SJ Schweizer Tom A TA

NeuroImage. Clinical 20200422

Sport-related concussion is associated with acute disturbances in neurometabolic function, with effects that may last weeks to months after injury. However, is presently unknown whether these disturbances resolve at medical clearance to return to play (RTP) or continue to evolve over longer time intervals. Moreover, little is known about how these neurometabolic changes correlate with other measures of brain physiology. In this study, these gaps were addressed by evaluating ninety-nine (99) univ ...[more]

PMID: 32388345

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Project description:CONTEXT:? Without a true criterion standard assessment, the sport-related concussion (SRC) diagnosis remains subjective. Inertial balance sensors have been proposed to improve acute SRC assessment, but few researchers have studied their clinical utility. OBJECTIVE:? To determine if group differences exist when using objective measures of balance in a sample of collegiate athletes with recent SRCs and participants serving as the control group and to calculate sensitivity and specificity to determine the diagnostic utility of the inertial balance sensor for acute SRC injuries. DESIGN:? Cross-sectional cohort study. SETTING:? Multicenter clinical trial. PATIENTS OR OTHER PARTICIPANTS:? We enrolled 48 participants with SRC (age = 20.62 ± 1.52 years, height = 179.76 ± 10.00 cm, mass = 83.92 ± 23.22 kg) and 45 control participants (age = 20.85 ± 1.42 years, height = 177.02 ± 9.59 cm, mass = 74.61 ± 14.92 kg) at 7 clinical sites in the United States. All were varsity or club collegiate athletes, and all participants with SRC were tested within 72 hours of SRC. MAIN OUTCOME MEASURE(S):? Balance performance was assessed using an inertial balance sensor. Two measures (root mean square sway and 95% ellipse sway area) were analyzed to represent a range of general balance measures. Balance assessments were conducted in double-legged, single-legged, and tandem stances. RESULTS:? A main effect for group was associated with the root mean square sway measure ( F1,91 = 11.75, P = .001), with the SRC group demonstrating balance deficits compared with the control group. We observed group differences in the 95% ellipse sway area measure for the double-legged ( F1,91 = 11.59, P = .001), single-legged ( F1,91 = 6.91, P = .01), and tandem ( F1,91 = 7.54, P = .007) stances. Sensitivity was greatest using a cutoff value of 0.5 standard deviations (54% [specificity = 71%]), whereas specificity was greatest using a cutoff value of 2 standard deviations (98% [sensitivity = 33%]). CONCLUSIONS:? Inertial balance sensors may be useful tools for objectively measuring balance during acute SRC evaluation. However, low sensitivity suggests that they may be best used in conjunction with other assessments to form a comprehensive screening that may improve sensitivity.

Project description:Sports-related concussion (SRC) is sustained by millions of people per year, yet the spatiotemporal patterns of white matter (WM) injury remain poorly understood. Several SRC studies have implemented the standardised approach Tract-Based Spatial Statistics (TBSS). The aim of this image-based meta-analysis was to identify consensus patterns of SRC-related WM injury across TBSS studies. We included studies comparing the diffusion MRI measurement fractional anisotropy (FA) in SRC or subconcussive injury vs. controls using TBSS, as FA is the most frequently examined diffusion tensor imaging metric. Authors of eligible studies were contacted to request unthresholded statistical map outputs from TBSS, and image-based meta-analyses were performed using Seed-Based d-Mapping. Eight studies contributed to our meta-analyses, comprising 174 SRC or subconcussive injury participants and 160 controls. Our primary meta-analysis (n = 8), encompassing subjects with acute SRC (n = 2), chronic SRC (n = 4) and subconcussive injuries (n = 2) revealed dominant bilateral increased FA in the superior longitudinal fasciculus (SLF) and internal capsule. Subconcussive injury was associated with small clusters of increased and decreased FA in the arcuate fasciculus compared to control. In acute SRC, we found diffuse foci of raised FA at WM/grey matter border-zone associated with the bilateral SLF and right inferior fronto-occipital fasciculus. In contrast, chronic SRC had a pattern of deep WM alteration, asymmetrically located in the right optic radiations and arcuate fasciculus. Our findings represent the most powerful analysis of TBSS data in SRC, supporting the use of this approach to analyse diffusion data. TBSS is sensitive to WM abnormalities resulting from SRC or subconcussive injury over a range of temporal and clinical scenarios. Our data show spatially concordant patterns of WM injury unique to subconcussive, acute and chronic phases, highlighting the future utility of diffusion MRI for concussion diagnosis.

Project description:Acute mood disturbance following sport-related concussion is common and is known to adversely affect post-concussion symptoms and recovery. The physiological underpinnings of depressive symptoms following concussion, however, are relatively understudied. We hypothesized that functional connectivity of the emotional processing network would be altered in concussed athletes and associated with the severity of depressive symptoms following concussion. Forty-three concussed collegiate athletes were assessed at approximately one day (N = 34), one week (N = 34), and one month post-concussion (N = 30). Fifty-one healthy contact-sport athletes served as controls and completed a single visit. The Hamilton Rating Scale for Depression (HAM-D) was used to measure depressive symptoms. Resting state fMRI data was collected on a 3 T scanner (TR = 2 s) and functional connectivity was calculated in a meta-analytically derived network of regions associated with emotional processing. Concussed athletes had elevated depressive symptoms across the first month post-concussion relative to control athletes, but showed partial recovery by one month relative to more acute visits (ps < 0.05). Concussed athletes had significantly different connectivity in regions associated with emotional processing at one month post-concussion relative to one day post-concussion (p = 0.002) and relative to controls (p = 0.003), with higher connectivity between default mode and attention regions being common across analyses. Additionally, depressive symptoms in concussed athletes at one day (p = 0.003) and one week post-concussion (p = 7 × 10-8) were inversely correlated with connectivity between attention (e.g., right anterior insula) and default mode regions (e.g., medial prefrontal cortex). Finally, the relationships with HAM-D scores were not driven by a general increase in somatic complaints captured by the HAM-D, but were strongly associated with mood-specific HAM-D items. These results suggest that connectivity of emotional processing regions is associated with acute mood disturbance following sport-related concussion. Increased connectivity between attention and default mode regions may reflect compensatory mechanisms.

Project description:BACKGROUND:Increasing evidence suggests inflammation is an important component of concussion pathophysiology. However, its etiology, restitution, and potential clinical repercussions remain unknown. The purpose of the current study was to compare the blood concentrations of interleukin (IL) -6, a prominent inflammatory cytokine, between healthy athletes and athletes with a sport-related concussion (SRC), while addressing the potential confounds of sex, recent physical activity, and the interacting effect of concussion history. METHOD:A prospective, observational cohort study was conducted on athletes at a single academic institute participating across 13 interuniversity sports. Follow-up of 96 athletes who agreed to provide a blood sample was completed: 41 athletes with a physician diagnosed SRC, and 55 healthy athletes. Ella™, the high sensitivity immunoassay system by ProteinSimple was used to measure peripheral plasma concentrations of IL-6 within the first week (median = 4 days, range = 2-7) following injury. A resampled ordinary least squares regression was used to evaluate the relationship between IL-6 concentrations and concussion status, while partial least squares regression was used to evaluate the relationship between IL-6 and both symptom burden and time to clinical recovery. RESULTS:Regression analysis identified a negative relationship between plasma IL-6 concentrations and the interaction between an acute SRC and a history of concussion (? = -0.29, p = 0.029). IL-6 did not differ between healthy athletes and those with an acute SRC independent of concussion history, and was not correlated with either recovery time or symptom burden in athletes with SRC. CONCLUSION:Perturbations to circulating IL-6 concentrations, a key inflammatory cytokine, may be more pronounced following SRC in athletes who have a history of concussion. These results add to a growing body of evidence supporting the involvement of inflammation at all phases of recovery following SRC, and potentially support a concomitant effect of prior concussion on acute SRC pathophysiology.

Project description:ObjectiveTo examine if self-reported dizziness is associated with concussion symptoms, depression and/or anxiety symptoms, or gait performance within 2 weeks of postconcussion.DesignCross-sectional study.SettingResearch laboratory.ParticipantsParticipants were diagnosed with a concussion within 14 days of initial testing (N = 40). Participants were divided into 2 groups based on their Dizziness Handicap Inventory (DHI) score: 36 to 100 = moderate/severe dizziness and 0 to 35 = mild/no dizziness.InterventionsParticipants were tested on a single occasion and completed the DHI, hospital anxiety and depression scale (HADS), Patient Health Questionnaire-9 (PHQ-9), and Post-Concussion Symptom Inventory (PCSI). Three different postural control tests were use: modified Balance Error Scoring System, single-/dual-task tandem gait, and a single-/dual-task instrumented steady-state gait analysis.Main outcome measuresComparison of patient-reported outcomes and postural control outcomes between moderate/severe (DHI ≥ 36) and mild/no (DHI < 36) dizziness groups.ResultsParticipants with moderate/severe dizziness (n = 19; age = 17.1 ± 2.4 years; 63% female) reported significantly higher symptom burden (PSCI: 43.0 ± 20.6 vs 22.8 ± 15.7; P = 0.001) and had higher median HADS anxiety (6 vs 2; P < 0.001) and depression (6 vs 1; P = 0.001) symptom severity than those with no/minimal dizziness (n = 21; age = 16.5 ± 1.9; 38% female). During steady-state gait, moderate/severe dizziness group walked with significantly slower single-task cadence (mean difference = 4.8 steps/minute; 95% confidence interval = 0.8, 8.8; P = 0.02) and dual-task cadence (mean difference = 7.4 steps/minute; 95% confidence interval = 0.7, 14.0; P = 0.04) than no/mild dizziness group.ConclusionParticipants who reported moderate/severe dizziness reported higher concussion symptom burden, higher anxiety scores, and higher depression scores than those with no/mild dizziness. Cadence during gait was also associated with the level of dizziness reported.

Dataset Information

Neurometabolites and sport-related concussion: From acute injury to one year after medical clearance.

Publications

Neurometabolites and sport-related concussion: From acute injury to one year after medical clearance.

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