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

BACKGROUND AND OBJECTIVES: After 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. METHODS: The 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. RESULTS: The 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. DISCUSSION: Utilizing 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.

Optimizing Concussion Care Seeking: Using Machine Learning to Predict Delayed Concussion Reporting.

BACKGROUND: Early medical attention after concussion may minimize symptom duration and burden; however, many concussions are undiagnosed or have a delay in diagnosis after injury. Many concussion symptoms (eg, headache, dizziness) are not visible, meaning that early identification is often contingent on individuals reporting their injury to medical staff. A fundamental understanding of the types and levels of factors that explain when concussions are reported can help identify promising directions for intervention. PURPOSE: To identify individual and institutional factors that predict immediate (vs delayed) injury reporting. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: This study was a secondary analysis of data from the Concussion Assessment, Research and Education (CARE) Consortium study. The sample included 3213 collegiate athletes and military service academy cadets who were diagnosed with a concussion during the study period. Participants were from 27 civilian institutions and 3 military institutions in the United States. Machine learning techniques were used to build models predicting who would report an injury immediately after a concussive event (measured by an athletic trainer denoting the injury as being reported "immediately" or "at a delay"), including both individual athlete/cadet and institutional characteristics. RESULTS: In the sample as a whole, combining individual factors enabled prediction of reporting immediacy, with mean accuracies between 55.8% and 62.6%, depending on classifier type and sample subset; adding institutional factors improved reporting prediction accuracies by 1 to 6 percentage points. At the individual level, injury-related altered mental status and loss of consciousness were most predictive of immediate reporting, which may be the result of observable signs leading to the injury report being externally mediated. At the institutional level, important attributes included athletic department annual revenue and ratio of athletes to athletic trainers. CONCLUSION: Further study is needed on the pathways through which institutional decisions about resource allocation, including decisions about sports medicine staffing, may contribute to reporting immediacy. More broadly, the relatively low accuracy of the machine learning models tested suggests the importance of continued expansion in how reporting is understood and facilitated.

Association of Sport Helmet Status on Concussion Presentation and Recovery in Male Collegiate Student-Athletes.

Sporting helmets contain force attenuating materials which reduce traumatic head injury risk and may influence sport-related concussion (SRC) sequelae. The purpose of this study was to examine the association of sport helmet status with SRC-clinical presentation and recovery trajectories in men's collegiate athletes. Sport helmet status was based on the nature of sports being either helmeted/non-helmeted. 1070 SRCs in helmeted (HELM) sports (Men's-Football, Ice Hockey, and Lacrosse), and 399 SRCs in non-helmeted (NOHELM) sports (Men's-Basketball, Cheerleading, Cross Country/Track & Field, Diving, Gymnastics, Soccer, Swimming, Tennis, and Volleyball) were analyzed. Multivariable negative binomial regression models analyzed associations between sport helmet status and post-injury cognition, balance, and symptom severity, adjusting for covariate effects (SRC history, loss of consciousness, anterograde/retrograde amnesia, event type). Kaplan-Meier curves evaluated median days to: initiation of return to play (iRTP) protocol, and unrestricted RTP (URTP) by sport helmet status. Log-rank tests were used to evaluate differential iRTP/URTP between groups. Two independent multivariable Weibull accelerated failure time models were used to examine differential iRTP and URTP between groups, after adjusting for aforementioned covariates and symptom severity score. Overall, the median days to iRTP and URTP was 6.3 and 12.0, respectively, and was comparable across NOHELM- and HELM-SRCs. Post-injury symptom severity was lower (Score Ratio 0.90, 95%CI 0.82, 0.98), and cognitive test performance was higher (Score Ratio 1.03, 95%CI 1.02, 1.05) in NOHELM-compared to HELM-SRCs. Estimated time spent recovering to iRTP/URTP was comparable between sport helmet status groups. Findings suggest that the grouping of sports into helmeted and non-helmeted show slight differences in clinical presentation but not recovery.

Association of Alzheimer's disease polygenic risk score with concussion severity and recovery metrics.

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six outcomes in 931 total participants. The outcomes were two concussion recovery measures (number of days to asymptomatic status, number of days to return to play (RTP)) and four concussion severity measures (scores on SAC and BESS, SCAT symptom severity, and total number of symptoms). We calculated PRS using a published score [1] and performed multiple linear regression (MLR) to assess the relationship of PRS with the outcomes. We also used t-tests and chi-square tests to examine outcomes by APOE genotype, and MLR to analyze outcomes in European and African genetic ancestry subgroups. Higher PRS was associated with longer injury to RTP in the normal RTP (<24 days) subgroup ( p = 0.024), and one standard deviation increase in PRS resulted in a 9.89 hour increase to the RTP interval. There were no other consistently significant effects, suggesting that high AD genetic risk is not strongly associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

Research Letter: Relationship of Blood Biomarkers of Inflammation With Acute Concussion Symptoms and Recovery in the CARE Consortium.

OBJECTIVE: Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion. SETTING: Multicenter study in National Collegiate Athletic Association member institutions including military service academies. PARTICIPANTS: Four hundred twenty-two participants with acute concussion. DESIGN: Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12 hours, 12-36 hours, and 36-60 hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12 hours; exploratory analyses were conducted with false discovery rate correction. RESULTS: For prespecified analyses, IL-1RA at 0 to 12 hours in female participants was positively associated with more errors on the SAC (B(standard error, SE) = 0.58(0.27), P < .05) and worse SCAT symptom severity (B(SE) = 0.96(0.44), P < .05). For exploratory analyses, higher levels of IL-1RA at 12 to 36 hours were associated with higher global (B(SE) = 0.55(0.14), q < 0.01), depression (B(SE) = 0.45(0.10), q < 0.005), and somatization scores on the BSI (B(SE) = 0.46(0.12), q < 0.01) in participants with concussion; Higher TNF at 12 to 36 hours was associated with fewer errors on the SAC (B(SE) = - 0.46(0.14), q < 0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12 hours was associated with slower RTP in female participants (OR = 14.47; 95% confidence interval, 2.96-70.66, q < 0.05); no other associations with recovery were observed. CONCLUSIONS: Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers.

Latent Profiles of Acute Symptoms, Cognitive Performance, and Balance in Sport-Related Concussions.

BACKGROUND: A sport-related concussion (SRC) is a common injury that affects multiple clinical domains such as cognition, balance, and nonspecific neurobehavioral symptoms. Although multidimensional clinical assessments of concussion are widely accepted, there remain limited empirical data on the nature and clinical utility of distinct clinical profiles identified by multimodal assessments. PURPOSE: Our objectives were to (1) identify distinct clinical profiles discernible from acute postinjury scores on the Sport Concussion Assessment Tool (SCAT), composed of a symptom checklist, a cognitive assessment (Standardized Assessment of Concussion), and a balance assessment (Balance Error Scoring System), and (2) evaluate the clinical utility of the identified profiles by examining their association with injury characteristics, neuropsychological outcomes, and clinical management-related outcomes. STUDY DESIGN: Cohort study (Prognosis); Level of evidence, 2. METHODS: Up to 7 latent profiles were modeled for 1885 collegiate athletes and/or military cadets who completed the SCAT at 0 to 12 hours after an injury. Chi-square tests and general linear models were used to compare identified profiles on outcomes at 12 to 72 hours after the injury. Kaplan-Meier analysis was used to investigate associations between clinical profiles and time to return to being asymptomatic and to return to play. RESULTS: There were 5 latent profiles retained: low impairment (65.8%), high cognitive impairment (5.4%), high balance impairment (5.8%), high symptom severity (16.4%), and global impairment (6.5%). The latent profile predicted outcomes at 12 to 72 hours in expectable ways (eg, the high balance impairment profile demonstrated worse balance at 12 to 72 hours after the injury). Time to return to being asymptomatic and to return to play were different across profiles, with the high symptom severity and global impairment profiles experiencing the longest recovery and the high balance impairment profile experiencing an intermediate-length recovery (vs low impairment profile). CONCLUSION: An SRC is a heterogeneous injury that presents in varying ways clinically in the acute injury period and results in different recovery patterns. These data support the clinical prognostic value of diverse profiles of impairment across symptom, cognitive, and balance domains. By identifying distinct profiles of an SRC and connecting them to differing outcomes, the findings support more evidence-based use of accepted multimodal clinical assessment strategies for SRCs.

The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium.

BACKGROUND: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes. HYPOTHESIS: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018. RESULTS: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without (P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days (P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) (P = .592). CONCLUSION: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery.

Head Impact Exposure in Hawaiian High School Football: Influence of Adherence Rates on a Helmetless Tackling and Blocking Training Intervention.

CONTEXT: High school football remains a popular, physically demanding sport despite the known risks for acute brain and neck injury. Impacts to the head also raise concerns about their cumulative effects and long-term health consequences. OBJECTIVE: To examine the effectiveness of a helmetless tackling training program to reduce head impact exposure in football participants. DESIGN: A three-year, quasi-experimental, prospective cohort (clinicaltrials.gov #NCTXXX) study. SETTING: Honolulu (XXX, XXX) area public and private secondary schools with varsity and junior varsity football. PATIENTS OR OTHER PARTICIPANTS: Football participants (n=496) ages 14 to 18 years old. Intervention(s) Participants wore new football helmets furnished with head impact sensor technology. Teams employed a season-long helmetless tackling and blocking intervention in Years 2 and 3 consisting of a 3-phase, systematic progression of 10 instructional drills. MAIN OUTCOME MEASURE(S): Head impact frequency per athlete exposure (ImpAE), location, and impact magnitude per participant intervention adherence levels (60% and 80%). RESULTS: An overall regression analysis revealed a significant negative association between ImpAE and adherence (p=0.003, beta=-1.21, SE=0.41). In year 3, a longitudinal data analysis of weekly ImpAE data resulted in an overall difference between the adherent and non-adherent groups (p=0.040 at 80%; p=0.004 at 60%), mainly due to decreases in top and side impacts. Mean cumulative impact burden for the adherent group (n=131: 2,105.84g ± 219.76,) was significantly (p=0.020) less than the non-adherent group (n=90: 3,158.25g ± 434.80) at the 60% adherence level. CONCLUSIONS: Participants adhering to the intervention on at least a 60% level experienced a 34% to 37% significant reduction in the number of head impacts (per exposure) through the season. These results provide additional evidence that a helmetless tackling and blocking training intervention (utilizing the HuTT® program) reduces head impact exposure in high school football players. Adherence to an intervention is crucial for achieving intended outcomes.

Mechanisms of Injury Leading to Concussions in Collegiate Soccer Players: A CARE Consortium Study.

BACKGROUND: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes. PURPOSE: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The Concussion Assessment, Research and Education (CARE) Consortium database was used. The mechanism of injury was categorized into head-to-ball, head-to-head, head-to-body, and head-to-ground/equipment. Baseline/acute injury characteristics-including Sports Concussion Assessment Tool-3 total symptom severity (TSS), loss of consciousness (LOC), and altered mental status (AMS); descriptive data; and recovery (RTP and URTP)-were compared. Multivariable regression and Weibull models were used to assess the predictive value of the mechanism of injury on TSS and RTP/URTP, respectively. RESULTS: Among 391 soccer SRCs, 32.7% were attributed to a head-to-ball mechanism, 27.9% to a head-to-body mechanism, 21.7% to a head-to-head mechanism, and 17.6% to a head-to-ground/equipment mechanism. Event type was significantly associated with injury mechanism [χ2(3) = 63; P < .001), such that more head-to-ball concussions occurred in practice sessions (n = 92 [51.1%] vs n = 36 [17.1%]) and more head-to-head (n = 65 [30.8%] vs n = 20 [11.1]) and head-to-body (n = 76 [36%] vs n = 33 [18.3%]) concussions occurred in competition. The primary position was significantly associated with injury mechanism [χ2(3) = 24; P < .004], with goalkeepers having no SRCs from the head-to-head mechanism (n = 0 [0%]) and forward players having the least head-to-body mechanism (n = 15 [19.2%]). LOC was also associated with injury mechanism (P = .034), with LOC being most prevalent in head-to-ground/equipment. Finally, AMS was most prevalent in head-to-ball (n = 54 [34.2%]) and head-to-body (n = 48 [30.4%]) mechanisms [χ2(3) = 9; P = .029]. In our multivariable models, the mechanism was not a predictor of TSS or RTP; however, it was associated with URTP (P = .044), with head-to-equipment/ground injuries resulting in the shortest mean number of days (14 ± 9.1 days) to URTP and the head-to-ball mechanism the longest (18.6 ± 21.6 days). CONCLUSION: The mechanism of injury differed by event type and primary position, and LOC and AMS were different across mechanisms. Even though the mechanism of injury was not a significant predictor of acute symptom burden or time until RTP initiation, those with head-to-equipment/ground injuries spent the shortest time until URTP, and those with head-to-ball injuries had the longest time until URTP.

The Interval Between Concussions Does Not Influence Time to Asymptomatic or Return to Play: A CARE Consortium Study.

INTRODUCTION: The purpose of this study was to determine if the time interval between two concussive events influences the number of days to asymptomatic status, days to return to play, or performance on common post-concussion assessments following the second concussion. METHODS: Data from 448 collegiate athletes and service academy cadets with two concussions (time between concussions: median 295.0 days [interquartile range: 125.0-438.2]), 40.0% female) were analyzed from Concussion Assessment Research and Education (CARE) Consortium institutions between 2014 and 2020. Days between concussions was the primary predictor variable. Primary outcome measures included time to asymptomatic and time to return to play following the second concussion. Secondary outcome measures included total number of symptoms, total symptom severity, Balance Error Scoring System total score, and Standardized Assessment of Concussion total score within 48 h of their second concussion. RESULTS: Time between concussions did not significantly contribute to the multivariate time to asymptomatic (p = 0.390), time to return to play (p = 0.859), or the secondary outcomes (p-range = 0.165-0.477) models. Time to asymptomatic (p = 0.619) or return to play (p = 0.524) did not differ between same-season and different-season concussions. Sex significantly contributed to the return to play (p = 0.005) multivariate model. Delayed symptom onset and immediate removal from play/competition significantly contributed to the total number of symptoms (p = 0.001, p = 0.014) and symptom severity (p = 0.011, p = 0.022) multivariate models. CONCLUSION: These results suggest that in a population with a large period between injuries, the time between concussions may not be relevant to clinical recovery.

National Athletic Trainers' Association Bridge Statement: Management of Sport-Related Concussion.

OBJECTIVE: To provide athletic trainers and team physicians with updated recommendations to the 2014 National Athletic Trainers' Association (NATA) concussion position statement regarding concussion management, specifically in the areas of education, assessment, prognostic factors, mental health, return to academics, physical activity, rest, treatment, and return to sport. BACKGROUND: Athletic trainers have benefited from the 2 previous NATA position statements on concussion management, and although the most recent NATA position statement is a decade old, knowledge gains in the medical literature warrant updating several (but not all) recommendations. Furthermore, in various areas of the body of literature, current evidence now exists to address items not adequately addressed in the 2014 statement, necessitating the new recommendations. This document therefore serves as a bridge from the 2014 position statement to the current state of concussion evidence, recommendations from other organizations, and discrepancies between policy and practice. RECOMMENDATIONS: These recommendations are intended to update the state of the evidence concerning the management of patients with sport-related concussion, specifically in the areas of education; assessment advances; prognostic recovery indicators; mental health considerations; academic considerations; and exercise, activity, and rehabilitation management strategies.

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.

Profile of brief symptom inventory-18 (BSI-18) scores in collegiate athletes: A CARE Consortium study.

Objective: The goal of this study was to characterize normative scores for the Brief Symptom Inventory (BSI-18) in collegiate athletes to inform decision making about the need for psychological health services in this group. Methods: Collegiate student-athletes (N = 20,034) from 25 universities completed the BSI-18 at their preseason baseline assessment. A subgroup (n = 5,387) underwent multiple baseline assessments. Global Severity Index (GSI) scores were compared to community norms and across multiple timepoints. Results: Collegiate athletes reported significantly lower GSI scores than published community norms (p<.001). Published GSI threshold scores for "caseness", identified only 2 per 100 athletes (≥ the 98th percentile) as needing further evaluation. Using a GSI score ≥ than the cohort's 90th percentile, 11.4 per 100 athletes would merit additional evaluation. These individuals were more likely to report a history of psychiatric diagnosis (Odds ratio [95% CI] 2.745 [2.480, 3.039]), as well as ≥ 2 prior concussions (p<.001). GSI scores were not highly correlated across timepoints. Suicidal ideation was rare (n = 230; 1.15%). Conclusions: For collegiate student-athletes, published BSI-18 threshold scores identify only extreme outliers who might benefit from additional behavioral health evaluation. Alternatively, use of threshold scores ≥ the 90th percentile identifies a more realistic 11.4% of the population, with higher likelihood of prior concussion and/or psychiatric disorders.

Factors Influencing Time to Return to Learn Among NCAA Student-Athletes Enrolled in the Concussion Assessment, Research, and Education (CARE) Study.

PURPOSE: The aim was to describe the demographic and post-injury factors that influence time to return to learn (RTL) among student-athletes enrolled in the Concussion Assessment, Research and Education (CARE) Consortium. METHODS: A total of 47,860 student-athletes enrolled in the National Collegiate Athletic Association-Department of Defense (NCAA-DoD) CARE Consortium study from 2014 to 2020, with 1485 sport-related concussions (SRCs) analyzed in the present dataset. Demographic and post-injury characteristics were calculated using descriptive statistics, followed by Kaplan-Meier estimates to examine median time to return to normal academic performance (i.e., RTL) by sex (male, female), baseline psychiatric conditions (depression, anxiety) and/or learning disorder, NCAA division (I, II, III), SRC history (0, 1, 2, 3+), NCAA sport category (contact, limited contact, non-contact sport), and median difference in baseline/post-injury symptom severity scores (< 21, ≥ 21). Further, a multivariable zero-inflated negative binomial (ZINB) regression model was used to examine their association with RTL. RESULTS: Overall, time to RTL (mean = 4.96 ± 8.24 days, median = 3.0 [interquartile range = 0.0, 6.0] days) was found to be influenced by several factors resulting in earlier trajectories. Notably, nearly 25% of the sample demonstrated immediate RTL (i.e., 0 days). Among student-athletes who did not immediately RTL, males demonstrated a decreased rate in RTL (rate = 0.79; 95% CI 0.66-0.96) compared to females. Further, student-athletes with a ≥ 21 change in symptom severity score (post-injury baseline) demonstrated a higher rate of RTL (rate = 1.47; 95% CI 1.21-1.79) compared to student-athletes with a symptom severity change score < 21. Lastly, male student-athletes demonstrated two times higher odds (odds ratio = 1.95; 95% CI 1.02-3.73) of immediate RTL compared to female student-athletes. No other covariates were associated with time to RTL. CONCLUSION: Collectively, the present findings suggest a rapid return to the classroom following concussion. Specifically, males demonstrated higher odds of time to RTL, whereas those with greater differences in symptom severity resulted in a higher rate of time to RTL among those who did not immediately RTL. Ultimately, these findings support prior work emphasizing an individualized approach to SRC management.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.

Postinjury Alcohol Use Is Associated With Prolonged Recovery After Concussion in NCAA Athletes.

OBJECTIVE: To determine whether alcohol use leads to prolonged clinical recovery or increased severity of concussion symptoms in National Collegiate Athletic Association (NCAA) athletes. DESIGN: Prospective observational study. SETTING: Clinical institutions. PARTICIPANTS: Athletes from the NCAA Concussion Assessment Research and Education consortium who sustained a concussion from 2014 to 2021. INTERVENTIONS: Athletes were divided into 2 groups, those reporting alcohol use postinjury and those reporting no alcohol use postinjury. MAIN OUTCOME MEASURES: Symptom recovery was evaluated as time (in days) from injury to clearance to return to unrestricted play (days until URTP). Severity of concussion symptoms was assessed using the Standardized Sport Concussion Assessment Tool (SCAT3) symptom severity, headache severity, difficulty concentrating, and difficulty remembering scores. These scores were taken a median of 6.6 [interquartile range (IQR) = 4.0-10] and 6 (IQR = 4.0-9.0) days after injury for those who did and did not consume alcohol postinjury respectively and compared with baseline SCAT3 scores. RESULTS: Four hundred eighty four athletes from the data set had complete data for exposure and outcome. The adjusted mean number of days until URTP for athletes reporting alcohol use postinjury [23.3; 95% confidence interval (CI), 20.0-27.2; days] was incidence rate ratio (IRR) 1.32 (95% CI, 1.12-1.55; P < 0.001) times higher than for athletes who reported no alcohol use postinjury [17.7 (95% CI, 16.1-19.3) days]. Postinjury alcohol was not associated with severity of concussion symptoms ( P 's < 0.05). CONCLUSION: Self-reported postinjury alcohol use is associated with prolonged recovery but not severity of concussion symptoms in collegiate athletes. This may inform future clinical recommendations regarding alcohol consumption after concussion.

Postinjury Outcomes After Non-Sport-Related Concussion: A CARE Consortium Study.

CONTEXT: Concussion research has primarily focused on sport-related mechanisms and excluded non-sport-related mechanisms. In adult populations, non-sport-related concussions (non-SRCs) demonstrated worse clinical outcomes compared with sport-related concussions (SRCs); however, investigations of non-SRCs in college-aged patients are limited. OBJECTIVES: To examine clinical outcomes in collegiate athletes with non-SRCs compared with SRCs and explore sex differences in outcomes among collegiate athletes with non-SRCs. DESIGN: Prospective cohort study. SETTING: Clinical setting. PATIENTS OR OTHER PARTICIPANTS: A total of 3500 athletes were included (n = 555 with non-SRCs, 42.5% female) from colleges or universities and service academies participating in the National Collegiate Athletic Association Department of Defense Concussion Assessment, Research and Education (CARE) Consortium. MAIN OUTCOME MEASURE(S): Dichotomous outcomes (yes or no) consisted of immediate reporting, mental status alterations, loss of consciousness, posttraumatic amnesia, retrograde amnesia, motor impairments, delayed symptom presentation, and required hospital transport. Continuous outcomes were symptom severity, days with concussion symptoms, and days lost to injury. Data were collected within 24 to 48 hours of injury and at return to play. Adjusted relative risks (ARRs) compared the likelihood of dichotomous outcomes by mechanism and by sex within patients with non-SRCs. Multivariate negative binomial regressions were used to assess group differences in continuous variables. RESULTS: Athletes with non-SRCs were less likely to report immediately (ARR = 0.73, 95% CI = 0.65, 0.81) and more likely to report delayed symptom presentation (ARR = 1.17, 95% CI = 1.03, 1.32), loss of consciousness (ARR = 3.15, 95% CI = 2.32, 4.28), retrograde amnesia (ARR = 1.77, 95% CI = 1.22, 2.57), and motor impairment (ARR = 1.45, 95% CI = 1.14, 1.84). Athletes with non-SRCs described greater symptom severity, more symptomatic days, and more days lost to injury (P < .001) compared with those who had SRCs. Within the non-SRC group, female athletes indicated greater symptom severity, more symptomatic days, and more days lost to injury (P < .03) than male athletes. CONCLUSIONS: Athletes with non-SRCs had worse postinjury outcomes compared with those who had SRCs, and female athletes with non-SRCs had worse recovery metrics than male athletes. Our findings suggest that further investigation of individuals with non-SRCs is needed to improve concussion reporting and management.

Pediatric Sport-Related Concussion: Recommendations From the Amsterdam Consensus Statement 2023.

The 6th International Consensus Conference on Concussion in Sport, Amsterdam 2022, addressed sport-related concussion (SRC) in adults, adolescents, and children. We highlight the updated evidence-base and recommendations regarding SRC in children (5-12 years) and adolescents (13-18 years). Prevention strategies demonstrate lower SRC rates with mouthguard use, policy disallowing bodychecking in ice hockey, and neuromuscular training in adolescent rugby. The Sport Concussion Assessment Tools (SCAT) demonstrate robustness with the parent and child symptom scales, with the best diagnostic discrimination within the first 72 hours postinjury. Subacute evaluation (>72 hours) requires a multimodal tool incorporating symptom scales, balance measures, cognitive, oculomotor and vestibular, mental health, and sleep assessment, to which end the Sport Concussion Office Assessment Tools (SCOAT6 [13+] and Child SCOAT6 [8-12]) were developed. Rather than strict rest, early return to light physical activity and reduced screen time facilitate recovery. Cervicovestibular rehabilitation is recommended for adolescents with dizziness, neck pain, and/or headaches for greater than 10 days. Active rehabilitation and collaborative care for adolescents with persisting symptoms for more than 30 days may decrease symptoms. No tests and measures other than standardized and validated symptom rating scales are valid for diagnosing persisting symptoms after concussion. Fluid and imaging biomarkers currently have limited clinical utility in diagnosing or assessing recovery from SRC. Improved paradigms for return to school were developed. The variable nature of disability and differences in evaluating para athletes and those of diverse ethnicity, sex, and gender are discussed, as are ethical considerations and future directions in pediatric SRC research.

Collegiate Athletes With Diabetes: Baseline Medical Comorbidities and Preseason Concussion Testing Performance.

CONTEXT: People with diabetes mellitus (DM) are at increased risk for adverse health events and complications throughout their lifetime. Whether DM significantly affects collegiate athletes' concussion baseline testing performance remains unclear. OBJECTIVES: To (1) describe the prevalence of DM and associated comorbidities and (2) compare concussion baseline testing performance between student-athletes with DM and student-athletes without DM (NoDM). DESIGN: Retrospective, cross-sectional study. SETTING: University. PATIENTS OR OTHER PARTICIPANTS: Using the Concussion, Assessment, Research and Education (CARE) Consortium research database, we matched athletes with self-reported DM (N = 229) by institution, sex, age, sport, position, testing year, and concussion history to athletes with NoDM (N = 229; total sample mean age = 19.6 ± 1.4 years, women = 42%). MAIN OUTCOME MEASURE(S): Descriptive statistics and χ2 tests of independence with subsequent odds ratios were calculated. Independent-samples t tests compared baseline symptoms, neurocognitive testing, and balance performance between athletes with DM and athletes with NoDM. Effect sizes were determined for significant group differences. RESULTS: At baseline, athletes with DM had higher rates of self-reported pre-existing balance disorders, sleep disorders, seizure disorders, motion sickness, learning disorders, vision and hearing problems, psychiatric disorders, depression, bipolar disorder, nonmigraine headaches, and meningitis than athletes with NoDM (P values < .05). We found balance differences between groups (P = .032, Cohen d = 0.17) such that, on average, athletes with DM had 1 additional error on the Balance Error Scoring System (DM = 13.4 ± 6.5; NoDM = 12.1 ± 5.9). No other comparisons yielded significant results. CONCLUSIONS: Although athletes with DM had high rates of self-reported balance disorders, sleep disorders, seizures, and meningitis, their baseline neurocognitive testing results were largely identical to those of athletes with NoDM. Our findings suggested that nonclinically meaningful differences were present in concussion baseline balance testing but no significant differences were noted in cognitive testing; however, the effect of DM on concussion recovery remains unknown.