Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium

Importance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC

Head Impact Exposure in Youth Football: Elementary School Ages 9–12 Years and the Effect of Practice Structure

Head impact exposure in youth football has not been well-documented, despite children under the age of 14 accounting for 70% of all football players in the United States. The objective of this study was to quantify the head impact exposure of youth football players, age 9–12, for all practices and games over the course of single season. A total of 50 players (age = 11.0 ± 1.1 years) on three teams were equipped with helmet mounted accelerometer arrays, which monitored each impact players sustained during practices and games. During the season, 11,978 impacts were recorded for this age group. Players averaged 240 ± 147 impacts for the season with linear and rotational 95th percentile magnitudes of 43 ± 7 g and 2034 ± 361 rad/s(2). Overall, practice and game sessions involved similar impact frequencies and magnitudes. One of the three teams however, had substantially fewer impacts per practice and lower 95th percentile magnitudes in practices due to a concerted effort to limit contact in practices. The same team also participated in fewer practices, further reducing the number of impacts each player experienced in practice. Head impact exposures in games showed no statistical difference. While the acceleration magnitudes among 9–12 year old players tended to be lower than those reported for older players, some recorded high magnitude impacts were similar to those seen at the high school and college level. Head impact exposure in youth football may be appreciably reduced by limiting contact in practices. Further research is required to assess whether such a reduction in head impact exposure will result in a reduction in concussion incidence

HEAD IMPACT FREQUENCY IN YOUTH AMERICAN FOOTBALL, AGES 9-13

The objective of this study was to quantify head impact frequency in youth American football players, ages 9-13. Kinematic data from head impacts were collected from 25 players on two teams (11.7 ± 1.2 years) using a helmet-mounted accelerometer system. A total of 4432 head impacts were recorded, including 1800 during 265 practice sessions and 2632 during 175 game sessions. Most peak linear acceleration magnitudes were less than 20 g in practices (60%) and games (55%). For impacts greater than or equal to 60 g, players sustained 122% more in games than practices. Both teams played in leagues that limited full-contact practice time, which likely contributed to lower impact frequencies in practices. Interventions to further reduce head impact frequency in youth football should include measures which affect in-game exposure

Head Impact Exposure in Youth Football

The head impact exposure for athletes involved in football at the college and high school levels has been well documented; however, the head impact exposure of the youth population involved with football has yet to be investigated, despite its dramatically larger population. The objective of this study was to investigate the head impact exposure in youth football. Impacts were monitored using a custom 12 accelerometer array equipped inside the helmets of seven players aged 7–8 years old during each game and practice for an entire season. A total of 748 impacts were collected from the 7 participating players during the season, with an average of 107 impacts per player. Linear accelerations ranged from 10 to 100 g, and the rotational accelerations ranged from 52 to 7694 rad/s2. The majority of the high level impacts occurred during practices, with 29 of the 38 impacts above 40 g occurring in practices. Although less frequent, youth football can produce high head accelerations in the range of concussion causing impacts measured in adults. In order to minimize these most severe head impacts, youth football practices should be modified to eliminate high impact drills that do not replicate the game situations

Brain Injury Prediction: Assessing the Combined Probability of Concussion Using Linear and Rotational Head Acceleration

Recent research has suggested possible long term effects due to repetitive concussions, highlighting the importance of developing methods to accurately quantify concussion risk. This study introduces a new injury metric, the combined probability of concussion, which computes the overall risk of concussion based on the peak linear and rotational accelerations experienced by the head during impact. The combined probability of concussion is unique in that it determines the likelihood of sustaining a concussion for a given impact, regardless of whether the injury would be reported or not. The risk curve was derived from data collected from instrumented football players (63,011 impacts including 37 concussions), which was adjusted to account for the underreporting of concussion. The predictive capability of this new metric is compared to that of single biomechanical parameters. The capabilities of these parameters to accurately predict concussion incidence were evaluated using two separate datasets: the Head Impact Telemetry System (HITS) data and National Football League (NFL) data collected from impact reconstructions using dummies (58 impacts including 25 concussions). Receiver operating characteristic curves were generated, and all parameters were significantly better at predicting injury than random guessing. The combined probability of concussion had the greatest area under the curve for all datasets. In the HITS dataset, the combined probability of concussion and linear acceleration were significantly better predictors of concussion than rotational acceleration alone, but not different from each other. In the NFL dataset, there were no significant differences between parameters. The combined probability of concussion is a valuable method to assess concussion risk in a laboratory setting for evaluating product safety

Head Exposure to Acceleration Database in Sport (HEADSport): a kinematic signal processing method to enable instrumented mouthguard (iMG) field-based inter-study comparisons

Objective Instrumented mouthguard (iMG) systems use different signal processing approaches limiting field-based inter-study comparisons, especially when artefacts are present in the signal. The objective of this study was to assess the frequency content and characteristics of head kinematic signals from head impact reconstruction laboratory and field-based environments to develop an artefact attenuation filtering method (HEADSport filter method).Methods Laboratory impacts (n=72) on a test-dummy headform ranging from 25 to 150 g were conducted and 126 rugby union players were equipped with iMGs for 209 player-matches. Power spectral density (PSD) characteristics of the laboratory impacts and on-field head acceleration events (HAEs) (n=5694) such as the 95th percentile cumulative sum PSD frequency were used to develop the HEADSport method. The HEADSport filter method was compared with two other common filtering approaches (Butterworth-200Hz and CFC180 filter) through signal-to-noise ratio (SNR) and mixed linear effects models for laboratory and on-field events, respectively.Results The HEADSport filter method produced marginally higher SNR than the Butterworth-200Hz and CFC180 filter and on-field peak linear acceleration (PLA) and peak angular acceleration (PAA) values within the magnitude range tested in the laboratory. Median PLA and PAA (and outlier values) were higher for the CFC180 filter than the Butterworth-200Hz and HEADSport filter method (plt;0.01).Conclusion The HEADSport filter method could enable iMG field-based inter-study comparisons and is openly available at https://github.com/GTBiomech/HEADSport-Filter-Method.Data are available upon reasonable request. Anonymous data are available on reasonable request to the corresponding author

Rotational Head Kinematics in Football Impacts: An Injury Risk Function for Concussion

Recent research has suggested a possible link between sports-related concussions and neurodegen-erative processes, highlighting the importance of developing methods to accurately quantify head impact tolerance. The use of kinematic parameters of the head to predict brain injury has been sug-gested because they are indicative of the inertial response of the brain. The objective of this study is to characterize the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects. The helmets of 335 football players were instrumented with accelerometer arrays that measured head acceleration following head impacts sustained during play, resulting in data for 300,977 subconcussive and 57 concussive head impacts. The average subconcussive impact had a rotational acceleration of 1230 rad/s2 and a rotational ve-locity of 5.5 rad/s, while the average concussive impact had a rotational acceleration of 5022 rad/s2 and a rotational velocity of 22.3 rad/s. An injury risk curve was developed and a nominal injury value of 6383 rad/s2 associated with 28.3 rad/s represents 50% risk of concussion. These data provide an increased understanding of the biomechanics associated with concussion, and they provide critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention tech-niques

Ready for impact? A validity and feasibility study of instrumented mouthguards (iMGs)

Objectives Assess the validity and feasibility of current instrumented mouthguards (iMGs) and associated systems. Methods Phase I; four iMG systems (Biocore-Football Research Inc (FRI), HitIQ, ORB, Prevent) were compared against dummy headform laboratory criterion standards (25, 50, 75, 100 g). Phase II; four iMG systems were evaluated for on-field validity of iMG-triggered events against video-verification to determine true-positives, false-positives and false-negatives (20±9 player matches per iMG). Phase III; four iMG systems were evaluated by 18 rugby players, for perceptions of fit, comfort and function. Phase IV; three iMG systems (Biocore-FRI, HitIQ, Prevent) were evaluated for practical feasibility (System Usability Scale (SUS)) by four practitioners. Results Phase I; total concordance correlation coefficients were 0.986, 0.965, 0.525 and 0.984 for Biocore-FRI, HitIQ, ORB and Prevent. Phase II; different on-field kinematics were observed between iMGs. Positive predictive values were 0.98, 0.90, 0.53 and 0.94 for Biocore-FRI, HitIQ, ORB and Prevent. Sensitivity values were 0.51, 0.40, 0.71 and 0.75 for Biocore-FRI, HitIQ, ORB and Prevent. Phase III; player perceptions of fit, comfort and function were 77%, 6/10, 55% for Biocore-FRI, 88%, 8/10, 61% for HitIQ, 65%, 5/10, 43% for ORB and 85%, 8/10, 67% for Prevent. Phase IV; SUS (preparation-management) was 51.3-50.6/100, 71.3-78.8/100 and 83.8-80.0/100 for Biocore-FRI, HitIQ and Prevent. Conclusion This study shows differences between current iMG systems exist. Sporting organisations can use these findings when evaluating which iMG system is most appropriate to monitor head acceleration events in athletes, supporting player welfare initiatives related to concussion and head acceleration exposure.</p

Rotational Head Kinematics in Football Impacts: An Injury Risk Function for Concussion

Recent research has suggested a possible link between sports-related concussions and neurodegen-erative processes, highlighting the importance of developing methods to accurately quantify head impact tolerance. The use of kinematic parameters of the head to predict brain injury has been sug-gested because they are indicative of the inertial response of the brain. The objective of this study is to characterize the rotational kinematics of the head associated with concussive impacts using a large head acceleration dataset collected from human subjects. The helmets of 335 football players were instrumented with accelerometer arrays that measured head acceleration following head impacts sustained during play, resulting in data for 300,977 subconcussive and 57 concussive head impacts. The average subconcussive impact had a rotational acceleration of 1230 rad/s2 and a rotational ve-locity of 5.5 rad/s, while the average concussive impact had a rotational acceleration of 5022 rad/s2 and a rotational velocity of 22.3 rad/s. An injury risk curve was developed and a nominal injury value of 6383 rad/s2 associated with 28.3 rad/s represents 50% risk of concussion. These data provide an increased understanding of the biomechanics associated with concussion, and they provide critical insight into injury mechanisms, human tolerance to mechanical stimuli, and injury prevention tech-niques

Can helmet design reduce the risk of concussion in football?

Of all sports, football accounts for the highest incidence of concussion in the US due to the large number of athletes participating and the nature of the sport. While there is general agreement that concussion incidence can be reduced through rule changes and teaching proper tackling technique, there remains debate as to whether helmet design may also reduce the incidence of concussion. A retrospective analysis was performed of head impact data collected from 1833 collegiate football players who were instrumented with helmet-mounted accelerometer arrays for games and practices. Data were collected between 2005 and 2010 from 8 collegiate football teams: Virginia Tech, University of North Carolina, University of Oklahoma, Dartmouth College, Brown University, University of Minnesota, Indiana University, and University of Illinois. Concussion rates were compared between players wearing Riddell VSR4 and Riddell Revolution helmets while controlling for the head impact exposure of each player. A total of 1,281,444 head impacts were recorded, from which 64 concussions were diagnosed. The relative risk of sustaining a concussion in a Revolution helmet compared with a VSR4 helmet was 46.1% (95% CI 28.1%–75.8%). When controlling for each player’s exposure to head impact, a significant difference was found between concussion rates for players in VSR4 and Revolution helmets (χ2 = 4.68, p = 0.0305). This study illustrates that differences in the ability to reduce concussion risk exist between helmet models in football. Although helmet design may never prevent all concussions from occurring in football, evidence illustrates that it can reduce the incidence of this injury