Concussion Research Research Articles

Optimizing Concussion Care Seeking: Connecting Care-Seeking Behaviors and Neurophysiological States Through Blood Biomarkers

Background: Timely and appropriate medical care after concussion presents a difficult public health problem. Concussion identification and treatment rely heavily on self-report, but more than half of concussions go unreported or are reported after a delay. If incomplete self-report increases exposure to harm, blood biomarkers may objectively indicate this neurobiological dysfunction. Purpose/Hypothesis: The purpose of this study was to compare postconcussion biomarker levels between individuals with different previous concussion diagnosis statuses and care-seeking statuses. It was hypothesized that individuals with undiagnosed concussions and poorer care seeking would show altered biomarker profiles. Study Design: Cohort study; Level of evidence, 3. Methods: Blood samples were collected from 287 military academy cadets and collegiate athletes diagnosed with concussion in the Advanced Research Core of the Concussion Assessment, Research and Education Consortium. The authors extracted each participant’s self-reported previous concussion diagnosis status (no history, all diagnosed, ≥1 undiagnosed) and whether they had delayed or immediate symptom onset, symptom reporting, and removal from activity after the incident concussion. The authors compared the following blood biomarkers associated with neural injury between previous concussion diagnosis status groups and care-seeking groups: glial fibrillary acidic protein, ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light chain (NF-L), and tau protein, captured at baseline, 24 to 48 hours, asymptomatic, and 7 days after unrestricted return to activity using tests of parallel profiles. Results: The undiagnosed previous concussion group (n = 21) had higher levels of NF-L at 24- to 48-hour and asymptomatic time points relative to all diagnosed (n = 72) or no previous concussion (n = 194) groups. For those with delayed removal from activity (n = 127), UCH-L1 was lower at 7 days after return to activity than that for athletes immediately removed from activity (n = 131). No other biomarker differences were observed. Conclusion: Individuals with previous undiagnosed concussions or delayed removal from activity showed some different biomarker levels after concussion and after clinical recovery, despite a lack of baseline differences. This may indicate that poorer care seeking can create neurobiological differences in the concussed brain.

Publicly available data sources in sport-related concussion research: a caution for missing data

Publicly available data sources in sport-related concussion research: a caution for missing data

Publicly available data sources in sport-related concussion research: a caution for missing data

BackgroundResearchers often use publicly available data sources to describe injuries occurring in professional athletes, developing and testing hypotheses regarding athletic-related injury. It is reasonable to question whether publicly available data sources accurately indicate athletic-related injuries resulting from professional sport participation. We compared sport-related concussion (SRC) clinical incidence using data from publicly available sources to a recent publication reporting SRC using electronic health records (EHR) from the National Football League (NFL). We hypothesize publicly available data sources will underrepresent SRC in the NFL. We obtained SRCs reported from two publicly available data sources (NFL.com, pro-football-reference.com) and data reported from the NFL’s published EHR. We computed SRC per 100 unique player signings from 2015–2019 and compared the clinical incidence from publicly available data sources to EHR rates using clinical incidence ratios (CIR) and 95% confidence intervals (CI).FindingsFrom 2015–2019, SRC counts from published EHR record data ranged from 135–192 during the regular season, whereas SRC counts ranged from 102–194 and 69–202 depending on the publicly available data source. In NFL.com the SRC clinical incidence was significantly and progressively lower in 2017 (CIR: 0.73, 95% CI: 0.58–0.91), 2018 (CIR: 0.66, 95% CI: 0.50–0.87), and 2019 (CIR: 0.48, 95% CI: 0.35–0.64) relative to the gold-standard EHR. In the pro-football-reference.com data, the documented SRCs in publicly available data sources for other years were ~ 20–30% lower than the gold-standard EHR numbers (CIRs 0.70–0.81).ConclusionsPublicly available data for SRCs per 100 unique player signings did not match published data from the NFL’s EHR and in several years were significantly lower. Researchers should use caution before using publicly available data sources for injury research.

Association of Blood Biomarkers of Inflammation With Acute Concussion in Collegiate Athletes and Military Service Academy Cadets.

The objective was to characterize the acute effects of concussion (a subset of mild traumatic brain injury) on serum interleukin (IL)-6 and IL-1 receptor antagonist (RA) and 5 additional inflammatory markers in athletes and military service academy members from the Concussion Assessment, Research, and Education Consortium and to determine whether these markers aid in discrimination of concussed participants from controls. Athletes and cadets with concussion and matched controls provided blood at baseline and postinjury visits between January 2015 and March 2020. Linear models investigated changes in inflammatory markers measured using Meso Scale Discovery assays across time points (baseline and 0-12, 12-36, 36-60 hours). Subanalyses were conducted in participants split by sex and injury population. Logistic regression analyses tested whether acute levels of IL-6 and IL-1RA improved discrimination of concussed participants relative to brain injury markers (glial fibrillary acidic protein, tau, neurofilament light, ubiquitin c-terminal hydrolase-L1) or clinical data (Sport Concussion Assessment Tool-Third Edition, Standardized Assessment of Concussion, Balance Error Scoring System). Participants with concussion (total, N = 422) had elevated IL-6 and IL-1RA at 0-12 hours vs controls (n = 345; IL-6: mean difference [MD] (standard error) = 0.701 (0.091), p < 0.0001; IL-1RA: MD = 0.283 (0.042), p < 0.0001) and relative to baseline (IL-6: MD = 0.656 (0.078), p < 0.0001; IL-1RA: MD = 0.242 (0.038), p < 0.0001), 12-36 hours (IL-6: MD = 0.609 (0.086), p < 0.0001; IL-1RA: MD = 0.322 (0.041), p < 0.0001), and 36-60 hours (IL-6: MD = 0.818 (0.084), p < 0.0001; IL-1RA: MD = 0.317 (0.040), p < 0.0001). IL-6 and IL-1RA were elevated in participants with sport (IL-6: MD = 0.748 (0.115), p < 0.0001; IL-1RA: MD = 0.304 (0.055), p < 0.0001) and combative-related concussions (IL-6: MD = 0.583 (0.178), p = 0.001; IL-1RA: MD = 0.312 (0.081), p = 0.0001). IL-6 was elevated in male (MD = 0.734 (0.105), p < 0.0001) and female participants (MD = 0.600 (0.177), p = 0.0008); IL-1RA was only elevated in male participants (MD = 0.356 (0.047), p < 0.0001). Logistic regression showed the inclusion of IL-6 and IL-1RA at 0-12 hours improved the discrimination of participants with concussion from controls relative to brain injury markers (χ2(2) = 17.855, p = 0.0001; area under the receiver operating characteristic curve [AUC] 0.73 [0.66-0.80] to 0.78 [0.71-0.84]), objective clinical measures (balance and cognition; χ2(2) = 40.661, p < 0.0001; AUC 0.81 [0.76-0.86] to 0.87 [0.83-0.91]), and objective and subjective measures combined (χ2(2) = 13.456, p = 0.001; AUC 0.97 [0.95-0.99] to 0.98 [0.96-0.99]), although improvement in AUC was only significantly relative to objective clinical measures. IL-6 and IL-1RA (male participants only) are elevated in the early-acute window postconcussion and may aid in diagnostic decisions beyond traditional blood markers and common clinical measures. IL-1RA results highlight sex differences in the immune response to concussion which should be considered in future biomarker work.

Concussion-Related Disruptions to Hub Connectivity in the Default Mode Network Are Related to Symptoms and Cognition.

Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes (n = 44) at three time points: baseline (before beginning their athletic season), acute post-injury (approximately 48h after a diagnosed concussion), and recovery (after starting return-to-play progression, but before returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar time points to link these functional connectivity changes to clinical outcomes. Concussion resulted in increased connectivity between regions within the DMN compared with baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared with baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared with baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery. These results highlight a unique relationship between self-reported symptoms, visual memory performance, and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.

Diffusion tensor analysis of white matter tracts is prognostic of persisting post-concussion symptoms in collegiate athletes

Background and objectivesAfter a concussion diagnosis, the most important issue for patients and loved ones is how long it will take them to recover. The main objective of this study is to develop a prognostic model of concussion recovery. This model would benefit many patients worldwide, allowing for early treatment intervention. MethodsThe Concussion Assessment, Research and Education (CARE) consortium study enrolled collegiate athletes from 30 sites (NCAA athletic departments and US Department of Defense service academies), 4 of which participated in the Advanced Research Core, which included diffusion-weighted MRI (dMRI) data collection. We analyzed the dMRI data of 51 injuries of concussed athletes scanned within 48 h of injury. All athletes were cleared to return-to-play by the local medical staff following a standardized, graduated protocol. The primary outcome measure is days to clearance of unrestricted return-to-play. Injuries were divided into early (return-to-play < 28 days) and late (return-to-play >= 28 days) recovery based on the return-to-play clinical records. The late recovery group meets the standard definition of Persisting Post-Concussion Symptoms (PPCS). Data were processed using automated, state-of-the-art, rigorous methods for reproducible data processing using brainlife.io. All processed data derivatives are made available at https://brainlife.io/project/63b2ecb0daffe2c2407ee3c5/dataset. The microstructural properties of 47 major white matter tracts, 5 callosal, 15 subcortical, and 148 cortical structures were mapped. Fractional Anisotropy (FA) and Mean Diffusivity (MD) were estimated for each tract and structure. Correlation analysis and Receiver Operator Characteristic (ROC) analysis were then performed to assess the association between the microstructural properties and return-to-play. Finally, a Logistic Regression binary classifier (LR-BC) was used to classify the injuries between the two recovery groups. ResultsThe mean FA across all white matter volume was negatively correlated with return-to-play (r = −0.38, p = 0.00001). No significant association between mean MD and return-to-play was found, neither for FA nor MD for any other structure. The mean FA of 47 white matter tracts was negatively correlated with return-to-play (rμ = −0.27; rσ = 0.08; rmin = −0.1; rmax = −0.43). Across all tracts, a large mean ROC Area Under the Curve (AUCFA) of 0.71 ± 0.09 SD was found. The top classification performance of the LR-BC was AUC = 0.90 obtained using the 16 statistically significant white matter tracts. DiscussionUtilizing a free, open-source, and automated cloud-based neuroimaging pipeline and app (https://brainlife.io/docs/tutorial/using-clairvoy/), a prognostic model has been developed, which predicts athletes at risk for slow recovery (PPCS) with an AUC=0.90, balanced accuracy = 0.89, sensitivity = 1.0, and specificity = 0.79. The small number of participants in this study (51 injuries) is a significant limitation and supports the need for future large concussion dMRI studies and focused on recovery.

Sex Differences in Recovery Trajectories of Assessments for Sport-Related Concussion Among NCAA Athletes: A CARE Consortium Study.

The purpose of this study was to determine sex differences in recovery trajectories of assessments for sport-related concussion using Concussion Assessment, Research and Education (CARE) Consortium data. National Collegiate Athletic Association athletes (N = 906; 61% female) from sex-comparable sports completed a pre-season baseline assessment and post-sport-related concussion assessments within 6h of injury, 24-48h, when they initiated their return to play progression, when they were cleared for unrestricted return to play, and 6months post-injury. Assessments included the Standardized Assessment of Concussion, Balance Error Scoring System, Brief Symptom Inventory-18, Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), Sport Concussion Assessment Tool-3 symptom evaluation, Clinical Reaction Time, King-Devick test, Vestibular Ocular Motor Screen, 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale. Only the Vestibular Ocular Motor Screen Total Symptom Score at the 24-48h timepoint (p = 0.005) was statistically significantly different between sexes. Specifically, female athletes (mean = 60.2, 95% confidence interval [CI] 51.5-70.4) had higher Vestibular Ocular Motor Screen Total Symptom Scores than male athletes (mean = 36.9, 95% CI 27.6-49.3), but this difference resolved by the time of return-to-play initiation (female athletes, mean = 1.8, 95% CI 1.1-2.9; male athletes, mean = 4.1, 95% CI 1.5-10.9). Sport-related concussion recovery trajectories for most assessments were similar for female and male National Collegiate Athletic Association athletes except for Vestibular Ocular Motor Screen symptoms within 48h of sport-related concussion, which was greater in female athletes. Female athletes had a greater symptom burden across all timepoints, suggesting that cross-sectional observations may indicate sex differences despite similar recovery trajectories.

Neurosurgery and Sport-Related Concussion at the Amsterdam Consensus Meeting

The 6th International Conference on Concussion in Sport held in Amsterdam in October 2022 was a scientifically rigorous process that included international experts in sport-related concussion (SRC) from many medical and allied health disciplines. The scientific process included 10 systematic reviews that addressed SRC prevention, diagnosis, management, and potential long-term sequelae. The definition of SRC was revised to include contemporary neurophysiological and neuroimaging findings. Outputs from the meeting included the updated Concussion Recognition Tool 6, Sport Concussion Assessment Tool 6 and Child Sport Concussion Assessment Tool 6, and the introduction of new tools, the Sport Concussion Office Assessment Tool 6 and Child Sport Concussion Office Assessment Tool 6. The consensus statement included prevention strategies, the importance of physical activity and aerobic exercise in SRC management, rehabilitation strategies, the role of advanced neuroimaging and biomarkers in SRC research, management of retirement issues, analysis of potential long-term effects of SRC, pediatric recommendations, para athlete management, and ethical considerations. This review also discusses the important role of the neurosurgeon in concussion management, research, and advocacy.

Match official experiences with the Blue Card protocol in amateur rugby: implementing Rowan’s Law for concussion management

ABSTRACT The Blue Card protocol was introduced to domestic amateur rugby competitions to bring Rugby Canada into compliance with provincial concussion legislation. The Blue Card protocol formalises how match officials can remove an athlete with a suspected concussion from play and prevents athletes from returning to sport without medical clearance. This exploratory study examined the experiences of Canadian rugby match officials with the novel Blue Card process. Semi-structured interviews conducted with six Canadian rugby match officials were subjected to Interpretive Phenomenological Analysis. Findings revealed interpersonal (e.g. stakeholder collaboration and peer support) and intrapersonal (e.g. concerns about personal liability and comfort with the administration of the Blue Card) factors related to the successful implementation of concussion management protocols. Match officials distinguished actions from members of the rugby community as either supporting (e.g. information sharing) or actively resisting (e.g. questioning match official decisions regarding the Blue Card) efforts to implement the Blue Card protocol. Those who had personal experience removing an athlete from play due to a suspected concussion or who administered a Blue Card during the 2019 season reported feeling more comfortable with the process than less experienced peers. However, in this early policy implementation phase, 50% of participants expressed concerns about their personal liability associated with the Blue Card process. Implications for the design and implementation of sport-related concussion research and policy at the amateur level are discussed.

Concussion Risk and Recovery in Athletes With Psychostimulant-Treated Attention-Deficit/Hyperactivity Disorder: Findings From the NCAA-DOD CARE Consortium

The aim of the present study was to examine the effects of attention–deficit/hyperactivity disorder (ADHD) –related psychostimulant use in the context of concussion risk and symptom recovery. Data were obtained from the National Collegiate Athletic Association Department of Defense Grand Alliance Concussion Assessment, Research, and Education (NCAA-DOD CARE) Consortium from 2014 to 2017. Relative to individuals without diagnosed ADHD (i.e., control), both ADHD diagnosis and the combination of ADHD diagnosis and psychostimulant use were associated with a greater risk of incurring a concussive injury. Following a concussive injury, ADHD diagnosis was associated with longer symptom recovery time relative to the control group. However, individuals with ADHD who use psychostimulants did not take longer to resolve symptoms than controls, suggesting that psychostimulants may have a positive influence on recovery. Regardless of time point, ADHD diagnosis was associated with an elevated number of concussion-related symptoms; however, this effect appears mitigated by having used ADHD-related psychostimulants.

Sport-Specific Recovery Trajectories for NCAA Collegiate Athletes Following Concussion.

The recovery trajectories of collegiate athletes with sport-related concussion (SRC) are well characterized in contact/collision sports but are less well understood in limited contact sports with lower risk, reducing the ability of clinicians to effectively manage the return-to-play (RTP) process. The current study investigated the time to asymptomatic and RTP across a broad range of male and female collegiate sports and sought to group sports by recovery intervals. Data from the Concussion Assessment, Research and Education (CARE) Consortium included 1049 collegiate athletes who sustained a SRC while participating in game or practice/training of their primary sport. Injury setting and subsequent clinical presentation data were obtained. Survival analysis using the Cox Proportional Hazard model estimated the median recovery times for each sport. Optimal univariate K-means clustering grouped sports into recovery categories. Across all sports, median time to asymptomatic following SRC ranged from 5.9 (female basketball) to 8.6days (male wrestling). Median RTP protocol duration ranged from 4.9days (female volleyball) to 6.3days (male wrestling). Median total RTP days ranged from 11.2days (female lacrosse) to 16.9days (male wrestling). Sport clusters based on recovery differences in time to asymptomatic (3) and RTP protocol duration (2) were identified. The findings from this study of a large sample of more than 1000 NCAA collegiate athletes with SRC show there exists ranges in recovery trajectories. Clinicians can thus manage athletes with similar guidelines, with individualized treatment and recovery plans.

Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study

BackgroundMolecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury.ObjectiveThe aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery.MethodsWe analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline.ResultsCytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion.ConclusionsTranscriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

4 Women and Concussion Outcomes: What We Know and How We Can Do Better

Objective:The vast majority of existing research on outcomes following concussion is androcentric with women notably understudied in all settings where concussion commonly occurs, including sport, military, and civilian domains. Clinical care for concussed women is, by extension, far less evidenced-based as it is largely extrapolated from male-dominated studies. We therefore sought to center concussion outcomes of women in big data sources in this investigation to capitalize on both sample size and breadth of setting in which concussion occurs.Participants and Methods:We identified all studies with publicly released data as of 4/7/21 that included both male and female adults, enough information to determine severity of injury consistent with concussion/mild traumatic brain injury (TBI), a measure of postconcussive symptoms (PCS), and objective measures of neurocognitive functioning from the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System. FITBIR is a collaborative effort of the National Institutes of Health (NIH) and the Department of Defense (DoD), developed to share data across the entire TBI research community. This resulted in inclusion of six studies with a total of 9370 participants, 32% female. PCS data was drawn from the Neurobehavioral Symptom Inventory (NSI), the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), and the Sport Concussion Assessment Tool - 3rd Edition (SCAT 3), specifically the 22-item participant symptom evaluation rated on a 7-point scale. The questionnaires were harmonized and the following symptom domains emerged: Somatic, Cognitive, and Affective. Data were analyzed using linear mixed-effects models.Results:We found a small to medium sized significant effect of sex, with women reporting higher symptoms overall. Mean symptom endorsement scores were higher overall on the NSI in comparison to the RPSQ and SCAT (ps &lt; .001). Follow-up analyses revealed sex differences were largest for cognitive symptoms, followed by somatic symptoms, then affective symptoms. We also found significant main effects of population (military&gt;sport/civilian, p = .003) and sex (women&gt;males, p &lt; .001) on the overall composite, as well as a significant population-by-sex interaction such that female service members/veterans endorsed the highest rates of symptoms (p &lt; .001). Similar patterns of significance and effect sizes were observed for the somatic and affective composites. Cognitive symptom composites showed a similar pattern, but with smaller effect sizes overall. Racial and ethnic diversity was also limited in the sample.Conclusions:In one of the largest samples of women to date, we found a small to medium effect of sex on symptom reporting such that women reported higher levels of postconcussive symptoms than males. Notably, however, the women in military/Veteran samples endorsed the highest levels of symptoms. Despite using a large publicly available dataset to maximize the representation of women, the current sample was still predominantly male and racial and ethnic diversity among the sample was not consistent with expected broader population demographics. Dramatically more concerted efforts need to be made to engage women in all spheres of concussion research (military, civilian, and sport). Strategies to be more inclusive in concussion research will be highlighted.

73 Sex and Race/Ethnicity in Reporting of Lingering Concussion Symptoms by Adolescents

Objective:Consideration of individual differences in recovery after concussion has become a focus of concussion research. Sex and racial/ethnic identity as they may affect reporting of concussion symptoms have been studied at single time points but not over time. Our objective was to investigate the factors of self-defined sex and race/ethnicity in reporting of lingering concussion symptoms in a large sample of adolescents.Participants and Methods:Concussed, symptomatic adolescents (n=849; Female=464, Male=385) aged 13-18 years were evaluated within 30 days of injury at a North Texas Concussion Registry (ConTex) clinic. Participants were grouped by self-defined race/ethnicity into three groups: Non-Hispanic Caucasian (n=570), Hispanic Caucasian (n=157), and African American (n=122). Measures collected at the initial visit included medical history, injury related information, and the Sport Concussion Assessment Tool-5 Symptom Evaluation (SCAT-5SE). At a three-month follow-up, participants completed the SCAT-5SE. Pearson’s Chi-Square analyses examined differences in categorical measures of demographics, medical history, and injury characteristics. Prior to analysis, statistical assumptions were examined, and log base 10 transformations were performed to address issues of unequal group variances and nonnormal distributions. A three-way repeated measures ANOVA (Sex x Race/Ethnicity x Time) was conducted to examine total severity scores on the SCAT-5SE. Bonferroni post-hoc tests were performed to determine specific group differences. SPSS V28 was used for analysis with p&lt;0.05 for significance. Data reported below has been back transformed.Results:A significant interaction of Time by Race/Ethnicity was found for SCAT-5SE scores reported at initial visit and three-month follow-up (F(2, 843)=7.362, p&lt;0.001). To understand this interaction, at initial visit, Race/Ethnicity groups reported similar levels of severity for concussion symptoms. At three month follow-up, African Americans reported the highest level of severity of lingering symptoms (M= 3.925, 95% CIs [2.938-5.158]) followed by Hispanic Caucasians(M= 2.978, 95% CIs [2.2663.845]) and Non-Hispanic Caucasians who were the lowest(M= 1.915, 95% CIs [1.6262.237]). There were significant main effects for Time, Sex, and Race/Ethnicity. Average symptom levels were higher at initial visit compared to three-month follow-up (F(1, 843)=1531.526, p&lt;0.001). Females had higher average symptom levels compared to males (F(1, 843)=35.58, p&lt;0.001). For Race/Ethnicity (F(2, 843)=9.236, p&lt;0.001), Non-Hispanic Caucasians were significantly different than African Americans (p&lt;0.001) and Hispanic Caucasians (p=0.021) in reported levels of concussion symptom severity.Conclusions:Data from a large sample of concussed adolescents supported a higher level of reported symptoms by females, but there were no significant differences in symptom reporting between sexes across racial/ethnic groups. Overall, at three-months, the African American and Hispanic Caucasians participants reported a higher level of lingering symptoms than Non-Hispanic Caucasians. In order to improve care, the difference between specific racial/ethnic groups during recovery merits exploration into the factors that may influence symptom reporting.

A - 144 Prior Concussions and Symptom Elevation Rates in Collegiate Student-Athletes at Preseason Baseline.

Assess how prior concussions are related to baseline symptom endorsement using a four-factor model of post-concussion symptoms (i.e., cognitive, sleep-arousal, physical, and affective). Athletes from the Concussion Assessment, Research, and Education consortium (N&#3f7,370; 64% Male; 62% White; 36% Freshmen; 15% Football players) with at least one prior concussion were administered the Sport Concussion Assessment Tool-3 Symptom Evaluation at baseline. Subscale and total scores ≥84th percentile were considered elevated based on normative reference data from uninjured participants matched on gender and number of preexisting conditions. The symptoms of Headache, Pressure in head, Sensitivity to light, and Difficulty remembering were endorsed at a significantly higher rate (ps < 0.001, OR range = 1.35 to 1.40) by those with two or more prior concussions compared to those with one prior concussion. Approximately 22% of athletes had an elevated subscale score without an elevated total score. In contrast, no athletes were elevated on the total score without also being elevated on a subscale score, and 18% of athletes were elevated on both a subscale and the total score. The physical subscale was consistently the most frequent exclusively elevated subscale in the full sample (cognitive = 4%; physical = 10%, sleep-arousal = 6%, affective = 7%). Prior concussion status is related to item-level symptom endorsement among collegiate athletes at preseason baseline. A multidimensional approach to symptom interpretation identified a sizeable number of athletes (i.e., 22%) with significant symptoms that were not captured by a total score elevation. Most athletes with an elevated subscale score (i.e., 55%) were experiencing physical symptoms.

A - 145 Using a Multidimensional Symptom Model to Identify Persistent Post-Concussion Symptoms in Collegiate Athletes.

Determine if a multidimensional (i.e., four-factor model) approach to post-concussion symptoms identifies more participants with persistent post-concussion symptoms after a sport-related concussion than a standard total score approach. Student-athletes (N = 1097; 61% Male; 59% White; 35% Freshmen; 14% Football athletes) from the Concussion Assessment, Research, and Education consortium completed the Sport Concussion Assessment Tool-3 Symptom Evaluation six months after a concussion. Scores ≥84th percentile compared to normative data were considered elevated. Elevation rates for total and subscale scores were compared to examine the utility of a multidimensional interpretation in identifying persistent symptoms. Six months after injury, 9.9% of athletes had symptom elevations on the total or subscale score. Overall, 8.1% of athletes were elevated on a subscale (i.e., physical = 3.9%, cognitive = 1.9%, affective = 2.3%, sleep-arousal = 1.7%) but not the total score, whereas just 1.8% were elevated on both a subscale and the total score. No athletes were elevated on the total score without being concurrently elevated on a subscale. Multidimensional symptom interpretations may aid in identifying cases of persistent post-concussion symptoms, detecting up to 8.1% of athletes with elevated symptoms that would not be detected by focusing on a total score alone. This study did not assess for daily symptoms, which is one of the consensus criteria for persistent post-concussion symptoms. Future research should evaluate whether specific subscale elevations correspond to functional deficits or adverse health outcomes in these athletes.

Estimating the Relationship Between the Symptom-Free Waiting Period and Injury Rates After Return-to-Play from Concussion: A Simulation Analysis Using CARE Consortium Data.

A key component of return-to-play (RTP) from sport-related concussion is the symptom-free waiting period (SFWP), i.e., the period during which athletes must remain symptom-free before permitting RTP. Yet, the exact relationship between SFWP and post-RTP injury rates is unclear. We design computational simulations to estimate the relationship between the SFWP and rates of repeat concussion and non-concussion time-loss injury up to 30 days post-RTP for male and female collegiate athletes across 13 sports. We leverage N = 735 female and N = 1,094 male post-injury trajectories from the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium. With a 6-day SFWP, the mean [95% CI] rate of repeat concussion per 1,000 simulations was greatest in ice hockey for females (20.31, [20.16, 20.46]) and American football for males (24.16, [24.05, 24.28]). Non-concussion time-loss injury rates were greatest in field hockey for females (153.66, [152.59, 154.74]) and wrestling for males (247.34, [246.20, 248.48]). Increasing to a 13-day SFWP, ice hockey for females (18.88, [18.79, 18.98]) and American football for males (23.16, [23.09, 24.22]) exhibit the greatest decrease in repeat concussion rates across all sports within their respective sexes. Field hockey for females (143.24, [142.53, 143.94]) and wrestling for males (237.73, [236.67, 237.90]) exhibit the greatest decrease in non-concussion time-loss injury rates. Males receive marginally smaller reductions in injury rates for increased SFWP compared to females (OR=1.003, p ≤0.002). Longer SFWPs lead to greater reductions in post-RTP injury rates for athletes in higher risk sports. Moreover, SFWPs should be tailored to sport-specific post-RTP injury risks.

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts.

The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes. This pilot study comprised two independent cohorts. The first cohort-part of a Traumatic Head Injury Neuroimaging Classification (THINC) study-with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort-with a mean age of 19 years-comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay. Concentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690-0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT-/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT-/MRI-, n = 111) findings and UIC (P-values < 0.05). These findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

Intersection of Race and Socioeconomic Status on Concussion Recovery among NCAA Student-Athletes: A CARE Consortium Study.

The objectives of this study are to 1) describe collegiate student-athlete (SA) race and household income and 2) evaluate time to normal academic performance (i.e., return to learn (RTL)), initiation of the return to play (iRTP) protocol, RTP protocol duration, and time to unrestricted RTP (URTP) after sustaining sport-related concussion (SRC). Data were collected between 2014 and 2020 by the Concussion Assessment, Research, and Education Consortium. Baseline data were used to characterize participant demographics ( N = 22,819) and post-SRC outcomes ( n = 5485 SRC) in time to RTL ( n = 1724) and RTP outcomes ( n = 2646) by race. Descriptive statistics and nonparametric tests examined differences across race by demographic and injury characteristics. Kaplan-Meier curves estimated median days to RTL, iRTP protocol, RTP protocol completion, and URTP by race and covariate measures. Multivariable Cox proportional hazards regression assessed the effect of race on risk of RTL and RTP recovery time points. SA largely identified as White (75%) followed by Black (14%), multiracial (7%), and Asian (3%). More than half (53%) of all SA reported a household income of >$120,000, whereas 41% of Black SA reported a household income <$60,000. Race was not associated with relative risk of RTL or iRTP but was associated with RTP protocol completion and URTP. Non-Black/non-White SA were 17% less likely (adjusted hazard ratio = 0.83; 95% confidence interval = 0.71, 0.97) to complete the RTP protocol, and Black SA were 17% more likely (adjusted hazard ratio = 1.17; 95% confidence interval = 1.05, 1.31) to reach the URTP time point compared with White SA. The present findings suggest collegiate SA enrolled in the Concussion Assessment, Research, and Education Consortium are primarily White and come from household incomes well above the US median. Race was not associated with RTL or iRTP but was associated with RTP protocol duration and total time to URTP. Clinicians should be conscientious of how their implicit or preconceived biases may influence SRC management among National Collegiate Athletic Association SA.

Incidence of concussion and associated risk factors in collegiate soccer: findings from the NCAA-DoD CARE consortium

ABSTRACT This retrospective cohort study aims to examine concussion incidence rates (IR) in collegiate soccer players and compare IRs based on risk factors including sex, competition level, games/practices, history of concussion, and playing position. Collegiate soccer players were recruited (n = 2,471) from 23 institutions from the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium. Incidence rates for concussion per 1000 athlete exposures (AEs) were calculated across the 2015–16/2016–17 seasons. Incidence rates (IR) comparing risk factor groups were also calculated. A total of 162 concussions occurred during the study, for an IR of 0.08/1000 AEs. Females were more likely to have a concussion than males overall (IR = 1.47) and were more likely to have a concussion in games (IR = 1.42) and practices (IR = 2.91). Concussions were more likely during competition compared to practice (IR = 2.53), and less likely in Division III, compared to Divisions I and II, χ2 = 6.5, p > .05. In the concussed group, male sex was associated with 2.47 times higher odds of playing defender and 2.29 times higher odds of a collision mechanism. Results confirm previous findings that females and game exposures have higher concussion IR than males and practice exposures. Findings also supported sex differences in IRs based on exposure type, position, and mechanism.