Quantitative pupillometry as a biomarker for prediction of return to play in mild traumatic brain injury: a Military Traumatic Brain Injury Initiative study.

OBJECTIVE: This study aimed to determine the validity of quantitative pupillometry to predict the length of time for return to full activity/duty after a mild traumatic brain injury (mTBI) in a cohort of injured cadets at West Point. METHODS: Each subject received baseline (T0) quantitative pupillometry, in addition to evaluation with the Balance Error Scoring System (BESS), Standardized Assessment of Concussion (SAC), and Sport Concussion Assessment Tool 5th Edition Symptom Survey (SCAT5). Repeat assessments using the same parameters were conducted within 48 hours of injury (T1), at the beginning of progressive return to activity (T2), and at the completion of progressive return to activity protocols (T3). Pupillary metrics were compared on the basis of length of time to return to full play/duty and the clinical scores. RESULTS: The authors' statistical analyses found correlations between pupillometry measures at T1, including end-initial diameter and maximum constriction velocity, with larger change and faster constriction predicting earlier return to play. There was also an association with maximum constriction velocity at baseline (T0), predicting faster return to play. CONCLUSIONS: The authors conclude that that pupillometry may be a valuable tool for assessing time to return to duty from mTBI by providing a measure of baseline resiliency to mTBI and/or autonomic dysfunction in the acute phase after mTBI.

Reference Values for the Headache Impact Test-6 Questionnaire.

OBJECTIVE: To determine reference values for the Headache Impact Test-6 (HIT-6) in a young, physically active cohort and to examine the influence of sex, concussion history, headache history, and competitive sport level on HIT-6 scores. DESIGN: Cross-sectional. SETTING: United States Service Academy. PARTICIPANTS: United States Service Academy cadets (N=2678) completed an HIT-6 questionnaire as part of their annual concussion baseline assessment. Cadets with a recent concussion were excluded from baseline testing. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Reference values were calculated and stratified by sex, concussion history, headache history, and competitive sport level. Mann-Whitney U and Kruskal-Wallis tests were used to examine the effect of sex, concussion history, headache history, and competitive sport level on HIT-6 scores (P<.05). RESULTS: Of the 3599 cadets baselined, 2687 cadets (23% female) agreed to participate in the study and completed the HIT-6. Female participants reported significantly worse HIT-6 scores compared with male participants both with (P<.001) and without (P<.001) a concussion history. In both sexes, participants with a headache history reported worse scores than those with no headache/concussion history and a concussion history (all P<.005). Female cadets who participated in intramural athletics reported worse HIT-6 scores at baseline than female intercollegiate athletes (P=.003). CONCLUSIONS: This is the first study to stratify HIT-6 data by sex, concussion history, headache history, and sport level in a collegiate population at risk for concussions. Sex and headache history appear to influence HIT-6 scores and should be given special consideration when interpreting health-related quality of life deficits due to headache.

Reference values for the Balance Error Scoring System as measured by the Tekscan MobileMat™ in a physically active population.

OBJECTIVES: The Balance Error Scoring System (BESS) is commonly used to measure postural stability; however, it has demonstrated inconsistent reliability values when administered by humans. The Tekscan MobileMat™ was developed to automate the assessment of BESS errors and eliminate rater subjectivity. The objective of this study was to report reference values for the BESS, as measured by the MobileMat™, and examine the effect of sex, concussion history, and competitive sport level on BESS performance. METHODS: Four hundred and forty participants performed the BESS on the MobileMat™. Participants were asked to maintain each stance with their eyes closed for 20 s. The MobileMat™ was used to quantify the number of errors. RESULTS: Concussion history (p = 0.279-0.979) and competitive sport level (p = 0.422-0.979) did not affect BESS performance. Males performed significantly better than females for the single-limb foam stance (p = 0.032). No sex differences were detected for the other BESS stances or BESS total score (p = 0.067-0.744). CONCLUSIONS: Previously reported reference values in collegiate athletes and adolescents were slightly higher thus highlighting the value in establishing population norms and in developing new technologies to objectively quantify BESS performance. Furthermore, sex, concussion history, and competitive sport level do not appear to influence BESS performance as measured by the MobileMat™.

Quantitative Pupillometry Predicts Return to Play and Tracks the Clinical Evolution of Mild Traumatic Brain Injury in US Military Academy Cadets: A Military Traumatic Brain Injury Initiative Study.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine the utility of the pupillary light reflex use as a biomarker of mild traumatic brain injury (mTBI). METHODS: This prospective cohort study was conducted at The US Military Academy at West Point. Cadets underwent a standard battery of tests including Balance Error Scoring System, Sports Concussion Assessment Tool Fifth Edition Symptom Survey, Standard Assessment of Concussion, and measure of pupillary responses. Cadets who sustained an mTBI during training events or sports were evaluated with the same battery of tests and pupillometry within 48 hours of the injury (T1), at the initiation of a graded return to activity protocol (T2), and at unrestricted return to activity (T3). RESULTS: Pupillary light reflex metrics were obtained in 1300 cadets at baseline. During the study period, 68 cadets sustained mTBIs. At T1 (<48 hours), cadets manifested significant postconcussion symptoms (Sports Concussion Assessment Tool Fifth Edition P < .001), and they had decreased cognitive performance (Standardized Assessment of Concussion P < .001) and higher balance error scores (Balance Error Scoring System P < .001) in comparison with their baseline assessment (T0). The clinical parameters showed normalization at time points T2 and T3. The pupillary responses demonstrated a pattern of significant change that returned to normal for several measures, including the difference between the constricted and initial pupillary diameter (T1 P < .001, T2 P < .05), dilation velocity (T1 P < .01, T2 P < .001), and percent of pupillary constriction (T1 P < .05). In addition, a combination of dilation velocity and maximum constriction velocity demonstrates moderate prediction ability regarding who can return to duty before or after 21 days (area under the curve = 0.71, 95% CI [0.56-0.86]). CONCLUSION: This study's findings indicate that quantitative pupillometry has the potential to assist with injury identification and prediction of symptom severity and duration.

The Relationship Between Human-rated Errors and Tablet-based Postural Sway During the Balance Error Scoring System in Military Cadets.

BACKGROUND: The Balance Error Scoring System (BESS) is commonly accepted as a valid measure of postural stability. However, reliability values have varied, and subtle changes undetectable with the human eye may exist postinjury. The inertial measurement unit in commercially available tablets has been used to quantify postural sway (instrumented Balance Error Scoring System [iBESS] volume). However, iBESS has not been validated in a military population, and the stability of the tests beyond 1 week is unknown. HYPOTHESIS: iBESS volume is capable of objectively measuring postural sway during the traditional BESS. STUDY DESIGN: Prospective repeated-measures study. LEVEL OF EVIDENCE: Level 3. METHODS: Eighty-three cadets (40.96% women; age 20.0 ± 1.44 years; height 68.7 ± 4.1 inches; weight 166.7 ± 30.2 lb) with no history of concussion or lower extremity injury agreed to participate. All participants completed the BESS at baseline and 6 months post baseline. During testing, a tablet equipped with an inertial measurement unit was positioned on the participant's sacrum to capture postural sway. RESULTS: Moderate to strong correlations were exhibited between baseline measurements for single-limb (SL)-firm (r = 0.84; P < 0.01), tandem (TAN)-firm (r = 0.85; P < 0.01), double-limb (DL)-foam (r = 0.50; P < 0.01), SL-foam (r = 0.59; P < 0.01), and TAN-foam (r = 0.79; P < 0.01). Balance improved significantly at 6 months for SL-firm human-rated errors (Effect Size [ES] = 0.32) and for SL-firm (ES = 0.38), DL-foam (ES = 0.21), and SL-foam iBESS volume (ES = 0.35). Moderate to strong correlations were exhibited between human-rated and iBESS change scores for SL-firm (r = 0.71; P < 0.01), TAN-firm (r = 0.75; P < 0.01), and TAN-foam (r = 0.71; P < 0.01), and a weak correlation was exhibited for DL-foam (r = 0.29; P < 0.01) and SL-foam (r = 0.40; P < 0.01). CONCLUSION: Moderate to strong correlations existed between human-rated BESS errors and iBESS volume at baseline and between change scores. In addition, iBESS volume may be more sensitive to balance changes than the human-rated BESS. CLINICAL RELEVANCE: This evidence supports the use of iBESS volume as a valid measure of postural stability in military cadets. iBESS volume may provide clinicians with an objective and more sensitive measure of postural stability than the traditional human-rated BESS.

Normative Values for Pupillary Light Reflex Metrics Among Healthy Service Academy Cadets.

INTRODUCTION: Assessments of the pupil's response to light have long been an integral part of neurologic examinations. More recently, the pupillary light reflex (PLR) has shown promise as a potential biomarker for the diagnosis of mild traumatic brain injury. However, to date, few large-scale normative data are available for comparison and reference, particularly, in military service members. The purpose of this study was to report normative values for eight PLR measurements among healthy service academy cadets based on sex, age, sleep, race, ethnicity, anisocoria, and concussion history. METHODS: Freshmen entering a U.S. Service Academy completed a quantitative pupillometric assessment in conjunction with baseline concussion testing. PLR measurements were conducted using a Neuroptics PLR-3000 with a 121 µW light stimulus. The device measured maximum and minimum pupil diameter (mm), latency (time to maximum pupil constriction post-light stimulus [s]), peak and average constriction velocity (mm/s), average dilation velocity (mm/s), percentage pupil constriction, and T75 (time for pupil re-dilation from minimum pupil diameter to 75% maximum diameter [s]). During baseline testing, cadets also reported concussion history (yes and no) and hours slept the night before (<5.5 and ≥5.5). Normative values for each PLR measurement were calculated as mean ± SD, percentiles, and interquartile range. Mann-Whitney U tests were used to assess differences based on sex, concussion history, ethnicity, and hours slept for each PLR measurement. Kruskall-Wallis testing was used to assess differences based on age, race, and anisocoria. Alpha was set at .05 and nonparametric effect sizes (r) were calculated for statistically significant results. Effect sizes were interpreted as no effect (r < .1), small (r ≥.1-<.3), medium (r ≥.3-<.5), or large (r ≥ .5). All procedures were reviewed and approved by the local institutional review board and the U.S. Army Human Research Protection Office before the study was conducted. Each subject provided informed consent to participate in the study before data collection. RESULTS: Of the 1,197 participants baselined, 514 cadets (131 female; 18.91 ± 0.96 years) consented and completed a valid baseline pupillometric assessment. Eighty participants reported at least one previous concussion and participants reported an average of 5.88 ± 1.63 h slept the previous night. Mann-Whitney U results suggest females had larger initial (z = -3.240; P = .001; r = .10) and end pupil diameter (z = -3.080; P = .002; r = .10), slower average dilation velocity (z = 3.254; P = .001; r = .11) and faster T75 values (z = -3.342; P = .001; r = .11). Age, sleep, and race stratified by sex, also displayed a significant impact on specific PLR metrics with effect sizes ranging from small to medium, while ethnicity, anisocoria, and concussion history did not display an impact on PLR metrics. CONCLUSION: This study provides the largest population-specific normative values for eight PLR measurements. Initial and end pupil diameter, dilation velocity, and the T75 metrics differed by sex; however, these differences may not be clinically significant as small effect size was detected for all metrics. Sex, age, sleep, and race may impact specific PLR metrics and are worth consideration when performing PLR assessments for mild traumatic brain injury management.

Measurement of Head Kinematics Using Instrumented Mouthguards During Introductory Boxing Courses in U.S. Military Academy Cadets.

INTRODUCTION: Use of wearable impact sensor devices to quantitatively measure head impact exposure remains largely unstudied in military-style martial arts training and combat sports, particularly at the beginner levels. The baseline frequency and severity of head impact exposure during introductory military-style martial arts trainings, such as combatives training, is valuable information for developing future programs of instruction and exposure monitoring programs. The purpose of this study was to describe head impact exposures experienced during introductory combatives training (a boxing course) at U.S. Military Academy. METHODS: This study used instrumented mouthguards to measure head impact exposure in U.S. Military Academy cadets during a compulsory boxing course. Summary exposures from a preliminary dataset are presented. RESULTS: Twenty-two male subjects (19.9 ± 1.1 years, 86.6 ± 11.7 kg) participated in 205 analyzed player-bouts (full contact sparring sessions) with 809 video verified impacts (average 3.9 impacts per player-bout). The mean peak linear acceleration was 16.5 ±7.1 G, with a maximum of 70.8 G. There was a right-skewed distribution, with 640/809 (79.1%) events falling between 10 and 20 G. The mean peak angular acceleration was 1.52 ± 0.96 krad/s2, with a maximum of 8.85 krad/s2. CONCLUSIONS: Compared to other high-risk sports at Service Academies, head impacts from beginner boxing were of similar magnitude to those reported for Service Academy football and slightly lower than those reported for Service Academy rugby. Based on these preliminary data, the risk profile for introductory military-style martial arts training, such as boxing or combatives, may be similar to other contact sports like football and rugby, but further research is required to confirm these findings and understand the effects of the exposures in a shorter duration.

Risk of Upper Extremity Musculoskeletal Injury Within the First Year After a Concussion.

Background: Emerging evidence suggests that athletes and military personnel are at increased risk for lower extremity musculoskeletal injury after a concussion; however, the association between concussion and subsequent upper extremity (UE) musculoskeletal injury is unknown. Purpose: To prospectively examine the association between concussion and UE musculoskeletal injury risk within the first year after returning to unrestricted activity. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 316 cases of concussion 42% (132/316 women) were observed among 5660 Concussion Assessment, Research and Education Consortium participants at the United States Military Academy from May 2015 to June 2018. Active injury surveillance within the cohort was conducted for 12 months after unrestricted return to activity to identify any incident cases of acute UE musculoskeletal injury. Injury surveillance during the follow-up period was also conducted for nonconcussed controls who were matched by sex and competitive sport level. Univariate and multivariable Cox proportional hazards regression models were used to estimate hazard ratios between concussed cases and nonconcussed controls for time to UE musculoskeletal injury. Results: During the surveillance period, 19.3% of concussed cases and 9.2% of nonconcussed controls sustained a UE injury. In the univariate model, concussed cases were 2.25 times (95% CI, 1.45-3.51) more likely to sustain a UE injury during the 12-month follow-up period when compared with the nonconcussed controls. In the multivariable model, adjusted for history of concussion, sport level, somatization, and history of UE injury, concussed cases were 1.84 times (95% CI, 1.10-3.07) more likely to sustain a UE injury during the surveillance period compared with nonconcussed controls. Sport level remained an independent risk factor for UE musculoskeletal injury; however, concussion history, somatization, and history of UE injury were not independent risk factors. Conclusion: Concussed cases were more than twice as likely to sustain an acute UE musculoskeletal injury within the first 12 months after unrestricted return to activity when compared with nonconcussed controls. The higher hazard of injury remained in the concussed group after adjusting for other potential risk factors.

Association Between Symptom Cluster Endorsement at Initiation of a Graduated Return-to-Activity Protocol and Time to Return to Unrestricted Activity After Concussion in United States Service Academy Cadets.

BACKGROUND: The endorsement of symptoms upon initiation of a graduated return-to-activity (GRTA) protocol has been associated with prolonged protocols. It is unclear whether there are specific symptom clusters affecting protocol durations. PURPOSE: To describe the endorsement of specific concussion symptom clusters at GRTA protocol initiation and examine the association between symptom cluster endorsement and GRTA protocol duration. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This study was conducted among cadets enrolled at 3 US service academies. Participants completed an evaluation upon GRTA protocol initiation. Participants endorsing symptoms were binarized based on 6 symptom clusters (cognitive, emotional, insomnia, physical, sensitivity, and ungrouped). The primary outcome of interest was GRTA protocol duration based on symptom cluster endorsement severity. Prevalence rates were calculated to describe symptom cluster endorsement. Kaplan-Meier survival estimates and univariate and multivariable Cox proportional hazards regression models were calculated for all 6 symptom clusters to estimate GRTA protocol duration while controlling for significant covariates. RESULTS: Data from 961 concussed participants were analyzed. Of these, 636 participants were asymptomatic upon GRTA protocol initiation. Among the 325 symptomatic participants, the physical symptom cluster (80%) was most endorsed, followed by the cognitive (29%), insomnia (23%), ungrouped (19%), sensitivity (15%), and emotional (9%) clusters. Univariate results revealed a significant association between endorsing cognitive (hazard ratio [HR], 0.79; p = .001), physical (HR, 0.84; p < .001), insomnia (HR, 0.83; p = .013), sensitivity (HR, 0.70; p < .001), and ungrouped (HR, 0.75; p = .005) symptom clusters and GRTA protocol duration. Endorsing physical (HR, 0.84; p < .001) and sensitivity (HR, 0.81; p = .036) clusters maintained a significant association with GRTA protocol duration in the multivariable models. CONCLUSION: Participants endorsing physical or sensitivity symptom clusters displayed GRTA protocols prolonged by 16% to 19% compared with participants not endorsing that respective cluster after controlling for significant covariates.

Association Between Symptom Burden at Initiation of a Graduated Return to Activity Protocol and Time to Return to Unrestricted Activity After Concussion in Service Academy Cadets.

BACKGROUND: Current consensus and position statements recommend that concussed patients be asymptomatic upon the initiation of the graduated return to activity (RTA) protocol. However, a significant number of concussed patients are beginning their RTA protocols while endorsing symptoms. PURPOSE: To characterize symptom endorsement at the beginning of the RTA protocol and examine the association between symptom endorsement and RTA protocol duration in service academy cadets. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective cohort study was conducted with cadets at 3 US service academies. Postconcussion symptom inventories were recorded upon the initiation of an RTA protocol. The Sport Concussion Assessment Tool Symptom Inventory was used to classify participants into 3 groups (0 symptoms, 1 symptom, and ≥2 symptoms) upon the initiation of the RTA protocol. The primary outcome of interest was RTA protocol duration. Kaplan-Meier survival estimates were calculated to estimate RTA protocol duration by symptom endorsement, sex, varsity status, academic break, and time to graduated RTA initiation. Univariate and multivariable Cox proportional hazards models were used to estimate the association between symptom endorsement at the initiation of the RTA protocol and RTA protocol duration (α < .05). RESULTS: Data were analyzed from 966 concussed cadets (36% women). Headache (42%) and faintness/dizziness (44%) were the most commonly endorsed symptoms on the Sport Concussion Assessment Tool-Third Edition and the Brief Symptom Inventory-18, respectively. Univariate results revealed a significant association between endorsing ≥2 symptoms and RTA protocol duration. In the multivariable model, endorsing ≥2 symptoms maintained a statistically significant association with RTA protocol duration. Significant associations were observed between RTA protocol duration and nonvarsity status (27% longer), women (15% longer), academic breaks (70% longer), and time to the initiation of the RTA protocol (1.1% longer daily incremental increase) after controlling for covariates. CONCLUSION: Symptom endorsement at the initiation of an RTA protocol was associated with RTA protocol duration. Cadets who had returned to preinjury baseline symptom burden or improved from baseline symptom burden and endorsed ≥2 symptoms at the initiation of the RTA protocol took longer to RTA.

The Influence of Self-Reported Tobacco Use on Baseline Concussion Assessments.

INTRODUCTION: Baseline symptom, balance, and neurocognitive scores have become an integral piece of the concussion management process. Factors such as sleep, learning disorders, fitness level, and sex have been linked to differences in performance on baseline assessments; however, it is unclear how tobacco use may affect these scores. The objective of this study was to compare baseline concussion assessment scores between service academy cadets who use and do not use tobacco. METHODS: Cadets completed a standard battery of concussion baseline assessments per standard of care and were classified into two groups: tobacco users (n = 1,232) and nonusers (n = 5,922). Dependent variables included scores on the Balance Error Scoring System, Standardized Assessment of Concussion, Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Brief Symptom Inventory-18, and Brief Sensation Seeking Scale (BSSS). Separate Mann-Whitney U-tests were used to compare all baseline assessment scores between groups with an adjusted P-value < 0.004. RESULTS: Cadets that used tobacco performed significantly worse on the impulse control (P < 0.001) section of the ImPACT, reported greater ImPACT symptom severity scores (P < 0.001), and were more likely to take risks as measured by the BSSS (P < 0.001). No differences were detected for Balance Error Scoring System, Standardized Assessment of Concussion, Brief Symptom Inventory-18, and Sport Concussion Assessment Tool-3 symptom scores, verbal memory, visual memory, visual-motor speed, or reaction time on the ImPACT (P > 0.004). CONCLUSIONS: Tobacco users performed significantly worse than tobacco nonusers on the impulse control section of the ImPACT, reported greater symptom severity scores on the ImPACT, and were more likely to take risks as measured by the BSSS. Despite statistical significance, these results should be interpreted with caution, as the overall effect sizes were very small. Future research should examine the influence of tobacco use on recovery post-concussion.

Factors Associated With Delayed Concussion Reporting by United States Service Academy Cadets.

CONTEXT: Approximately half of individuals who sustain a concussion do not immediately report their injuries. Motivators for not reporting include thinking the suspected concussion was not a serious injury and wanting to continue participating in activity. Additionally, military personnel have concerns about how concussions may affect their careers. However, delayed reporting can prolong neurobehavioral recovery. Understanding the frequency of delayed reporting and contributing factors will aid in identifying individuals who may be more likely to delay reporting. OBJECTIVE: To describe the frequency of delayed concussion reporting by service academy cadets and determine if sex, injury setting, sport level, or medical history is capable of predicting delayed reporting. DESIGN: Cohort study. SETTING: Service academies. PATIENTS OR OTHER PARTICIPANTS: A total of 316 patients with concussions were observed from January 2014 to August 2016. MAIN OUTCOME MEASURE(S): All cadets completed an annual concussion baseline collection of demographic, medical history, and sports participation information. Delayed concussion reporting served as the outcome variable. Predictor variables were sex, injury setting, and sport level, as well as concussion, headache, and learning disorder history. Frequencies were calculated to describe the proportion of participants who delayed reporting. Univariable and multivariable logistic regression models were used to assess if the predictor variables were associated with delayed concussion reporting. Odds ratios (ORs) and 95% confidence intervals were calculated for all variables included in the final model. RESULTS: Of the patients with concussion, 51% were classified as delayed reporting. In univariable models, females (OR = 1.70) and National Collegiate Athletic Association cadet-athletes (OR = 1.98) were more likely to delay reporting than males and intramural cadet-athletes, respectively. The multivariable model yielded similar findings. CONCLUSIONS: Roughly half of the cadets who sustained a concussion failed to immediately report their injury. Specifically, our data suggested that female cadets, cadets injured outside of competition, and highly competitive cadet-athletes were almost twice as likely to delay reporting as others.

Level of Agreement Between Human-Rated and Instrumented Balance Error Scoring System Scores.

Clinicians have used the Balance Error Scoring System (BESS) to quantify postural control for concussion management. However, the reliability of the human rated BESS has varied prompting the development of instrumented BESSs. A cross-sectional design was used to determine the level of agreement (LOA) between human rated and instrumented BESS scores. Sixty participants completed the BESS on video. An instrumented mat was used to quantify BESS errors while a live human rater simultaneously scored the BESS. A second human rated BESS performance via video. Bland-Altman LOA analyses evaluated agreement between scoring methods (Mat-Human, Mat-Video, Video-Live) for each stance. Mean biases between scores, for each stance, with 95% confidence intervals (95%CIs) were calculated. Agreement between scoring methods was not assessed for the Firm-Double-Limb stance because very few errors were recorded. Agreement between both human raters and the mat was poor based on mean bias estimates > ± 1 and/or wide 95%CIs for all stances including BESS-Total. Agreement between the human raters was better, having displayed consistently smaller mean bias estimates and tighter 95%CIs for all stances and BESS Total. As a result, human rated and instrumented BESS scores may not be comparable. One method should be used to measure BESS errors for consistency.