Blood Biomarkers of Sports-Related Concussion in Pediatric Athletes.

OBJECTIVE: To examine changes in blood biomarkers, serum neurofilament light (Nf-L), and plasma tau, as well as the relationship between blood biomarkers and symptom reports, in athletes with a sports-related concussion. DESIGN: Prospective cohort study. SETTING: Private community-based concussion clinic. PARTICIPANTS: Athletes aged 13 to 18 years old with a diagnosed sports-related concussion presenting to a concussion clinic within 7 days of injury and noninjured athletes with no history of concussion aged 13 to 23 years old. ASSESSMENT AND MAIN OUTCOME MEASURES: Injured athletes provided a blood sample at the initial clinical evaluation and again at least 6 months after injury. Noninjured athletes provided a single blood sample. All participants completed symptom reports during each visit. Statistical comparisons of biomarker concentrations and symptom reports were conducted. RESULTS: The mean rank for tau was significantly lower for concussed athletes compared with nonconcussed athletes. In contrast, the mean rank of Nf-L was higher for concussed athletes than for nonconcussed athletes, although the difference was nonsignificant. Plasma tau was significantly lower postinjury compared with 6 months after injury, whereas serum Nf-L was significantly higher postinjury. There was a weak but significant inverse relationship observed between tau and the number of symptoms reported, but no relationship was observed between Nf-L and the number of symptoms reported. CONCLUSIONS: These data indicate that in the days following a sports-related concussion, the blood biomarkers tau and Nf-L display contrasting patterns of change but may not be related to self-reported symptom scores.

Movement Patterns During a Jump-Landing Task in Athletes After Sport-Related Concussion and Healthy Control Individuals.

CONTEXT: A relationship between a history of sport-related concussion (SRC) and lower extremity injury has been well established in the literature. OBJECTIVE: To determine if biomechanical differences existed during a double-limb jump landing between athletes who had been released to return to play after SRC and healthy matched control individuals. DESIGN: Cross-sectional study. SETTING: Health system-based outpatient sports medicine center. PATIENTS OR OTHER PARTICIPANTS: A total of 21 participants with SRC (age = 15.38 ± 1.77 years, height = 169.23 ± 8.59 cm, mass = 63.43 ± 7.39 kg, time since release to return to sport after SRC = 16.33 ± 12.7 days) were compared with 21 age-, sex-, and activity-matched healthy participants serving as controls (age = 15.36 ± 1.73 years, height = 169.92 ± 11.1 cm, mass = 65.62 ± 12.08 kg). MAIN OUTCOME MEASURE(S): Biomechanical performance during the double-limb jump landing was assessed using a motion-capture system and force plates. The average of 3 consecutive trials was used to calculate lower extremity joint kinetics and kinematics. The variables of interest were internal knee-extension moment, internal varus moment, and total sagittal-plane knee displacement for the dominant and nondominant limbs. Independent t tests were performed to examine the differences between SRC and control groups for the variables of interest. RESULTS: No differences existed between groups for the descriptive data. The SRC group demonstrated greater internal knee-extension moments in the dominant (-0.028 ± 0.009 Nm/kg, P = .003) and nondominant (-0.018 ± 0.007, P = .02) limbs. The SRC group also exhibited greater internal varus moments in the dominant (0.012 ± 0.004 Nm/kg, P = .005) and nondominant (0.010 ± 0.003, P = .005) limbs. For sagittal-plane knee displacement, the SRC group displayed less knee-flexion displacement in the dominant (-12.56 ± 4.67°, P = .01) but not the nondominant (-8.30 ± 4.91°, P = .10) limb. CONCLUSIONS: Athletes who had been released for return to sport after SRC landed with greater knee valgus than healthy matched control participants.

Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season.

OBJECTIVERepetitive subconcussive head trauma is a consequence of participation in contact sports and may be linked to neurodegenerative diseases. The degree of neurological injury caused by subconcussive head trauma is not easily detectible, and this injury does not induce readily identifiable clinical signs or symptoms. Recent advancements in immunoassays make possible the detection and quantification of blood biomarkers linked to head trauma. Identification of a blood biomarker that can identify the extent of neurological injury associated with subconcussive head trauma may provide an objective measure for informed decisions concerning cumulative exposure to subconcussive head trauma. The purpose of the current study was to examine changes in the blood biomarkers of subconcussive head trauma over the course of an American football season.METHODSThirty-five National Collegiate Athletic Association (NCAA) American football athletes underwent blood sampling throughout the course of a football season. Serial samples were obtained throughout the 2016 season, during which the number and magnitude of head impacts changed. Blood samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light polypeptide (NF-L). Athletes were grouped based on their starter status, because athletes identified as starters are known to sustain a greater number of impacts. Between-group differences and time-course differences were assessed.RESULTSIn nonstarters, plasma concentrations of tau decreased over the course of the season, with lower values observed in starters; this resulted in a lower area under the curve (AUC) (starters: 416.78 ± 129.17 pg/ml/day; nonstarters: 520.84 ± 163.19 pg/ml/day; p = 0.050). Plasma concentrations of tau could not be used to discern between starters and nonstarters. In contrast, serum concentrations of NF-L increased throughout the season as head impacts accumulated, specifically in those athletes categorized as starters. The higher serum concentrations of NF-L observed in starters resulted in a larger AUC (starters: 1605.03 ± 655.09 pg/ml/day; nonstarters: 1067.29 ± 272.33 pg/ml/day; p = 0.007). The AUC of the receiver operating characteristic curve analyses displayed fair to modest accuracy to identify athletes who were starters with the use of serum NF-L following periods of repetitive impacts.CONCLUSIONSThe different patterns observed in serum NF-L and plasma tau concentrations provide preliminary evidence for the use of blood biomarkers to detect the neurological injury associated with repetitive subconcussive head trauma. Although further investigation is necessary, such findings might lay the foundation for the further development of an objective measure for the detection of neurological injury caused by subconcussive head trauma.

Sex Differences in Time to Return-to-Play Progression After Sport-Related Concussion.

BACKGROUND: Recently, female sports participation has increased, and there is a tendency for women to experience more symptoms and variable presentation after sport-related concussion (SRC). The purpose of this study was to determine whether sex differences exist in time to begin a return-to-play (RTP) progression after an initial SRC. HYPOTHESIS: After initial SRC, female athletes (11-20 years old) would take longer to begin an RTP progression compared with age-matched male athletes. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 579 participants (365 males [mean age, 15.0 ± 1.7 years], 214 females [mean age, 15.2 ± 1.5 years]), including middle school, high school, and collegiate athletes who participated in various sports and experienced an initial SRC were included and underwent retrospective chart review. The following information was collected: sex, age at injury, sport, history of prior concussion, date of injury, and date of initiation of RTP progression. Participants with a history of more than 1 concussion or injury sustained from non-sport-related activity were excluded. RESULTS: Despite American football having the greatest percentage (49.2%) of sport participation, female athletes took significantly longer to start an RTP progression after an initial SRC (29.1 ± 26.3 days) compared with age-matched male athletes (22.7 ± 18.3 days; P = 0.002). CONCLUSION: On average, female athletes took approximately 6 days longer to begin an RTP progression compared with age-matched male athletes. This suggests that sex differences exist between athletes, aged 11 to 20 years, with regard to initiation of an RTP progression after SRC. CLINICAL RELEVANCE: Female athletes may take longer to recover after an SRC, and therefore, may take longer to return to sport. Sex should be considered as part of the clinical decision-making process when determining plan of care for this population.

A Positive Vestibular/Ocular Motor Screening (VOMS) Is Associated With Increased Recovery Time After Sports-Related Concussion in Youth and Adolescent Athletes.

BACKGROUND: Vestibular and ocular motor impairments are routinely reported in patients with sports-related concussion (SRC) and may result in delayed return to play (RTP). The Vestibular/Ocular Motor Screening (VOMS) assessment has been shown to be consistent and sensitive in identifying concussion when used as part of a comprehensive examination. To what extent these impairments or symptoms are associated with length of recovery is unknown. PURPOSE: To examine whether symptom provocation or clinical abnormality in specific domains of the VOMS results in protracted recovery (time from SRC to commencement of RTP protocol). STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: A retrospective chart review was conducted of 167 patients (69 girls, 98 boys; mean ± SD age, 15 ± 2 years [range, 11-19 years]) presenting with SRC in 2014. During the initial visit, VOMS was performed in which symptom provocation or clinical abnormality (eg, unsmooth eye movements) was documented by use of a dichotomous scale (0 = not present, 1 = present). The VOMS used in this clinic consisted of smooth pursuits (SMO_PUR), horizontal and vertical saccades (HOR_SAC and VER_SAC), horizontal and vertical vestibular ocular reflex (HOR_VOR and VER_VOR), near point of convergence (NPC), and accommodation (ACCOM). Domains were also categorized into ocular motor (SMO_PUR, HOR_SAC, VER_SAC, NPC, ACCOM) and vestibular (HOR_VOR, VER_VOR). Cox proportional hazard models were used to explore the relationship between the domains and recovery. Alpha was set at P ≤ .05. RESULTS: Symptom provocation and/or clinical abnormality in all domains except NPC ( P = .107) and ACCOM ( P = .234) delayed recovery (domain, hazard ratio [95% CI]: SMO_PUR, 0.65 [0.47-0.90], P = .009; HOR_SAC, 0.68 [0.50-0.94], P = .018; VER_SAC, 0.55 [0.40-0.75], P < .001; HOR_VOR, 0.68 [0.49-0.94], P = .018; VER_VOR, 0.60 [0.44-0.83], P = .002). The lowest crude hazard ratio was for ocular motor category (0.45 [0.32-0.63], P < .001). CONCLUSION: These data suggest that symptom provocation/clinical abnormality associated with all domains except NPC and ACCOM can delay recovery after SRC in youth and adolescents. Thus, the VOMS not only may augment current diagnostic tools but also may serve as a predictor of recovery time in patients with SRC. The findings of this study may lead to more effective prognosis of concussion in youth and adolescents.

The sensitivity and specificity of clinical measures of sport concussion: three tests are better than one.

CONTEXT: A battery of clinical measures of neurocognition, balance and symptoms has been recommended for the management of sport concussion (SC) but is based on variable evidence. OBJECTIVE: To examine the sensitivity and specificity of a battery of tests to assess SC in college athletes. DESIGN: Cross-sectional. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Division 1 athletes diagnosed with a SC (n=40) who were 20.2±1.60 years of age and 180.5±11.12 cm tall and healthy athletes (n=40) who were 19.0±0.93 years of age and 179.1±11.39 cm tall were enrolled. INTERVENTIONS: Participants were administered Immediate Postconcussion Assessment and Cognitive Test (ImPACT), the Sensory Organization Test (SOT) and the Revised Head Injury Scale (HIS-r) prior to and up to 24 h following injury between the 2004 and 2014 sport seasons. Sensitivity and specificity were calculated using predictive discriminant analyses (PDA) and clinical interpretation guidelines. MAIN OUTCOME MEASURES: Outcome measures included baseline and postinjury ImPACT, SOT and HIS-r composite scores. RESULTS: Using PDA, each clinical measure's sensitivity ranged from 55.0% to 77.5% and specificity ranged from 52.5% to 100%. The test battery possessed a sensitivity and specificity of 80.0% and 100%, respectively. Using clinical interpretation guidelines, sensitivity ranged from 55% to 97.5% individually, and 100% when combined. CONCLUSIONS: Our results support a multidimensional approach to assess SC in college athletes which correctly identified 80-100% of concussed participants as injured. When each test was evaluated separately, up to 47.5% of our sample was misclassified. Caution is warranted when using singular measures to manage SC.

A Preliminary Formula to Predict Timing of Symptom Resolution for Collegiate Athletes Diagnosed With Sport Concussion.

CONTEXT: Symptom presentation and recovery after sport concussion (SC) are variable. Empirically based models documenting typical symptom duration would assist health care providers in managing return to play after SC. OBJECTIVE: To develop a prediction model for SC symptom duration. DESIGN: Cross-sectional study. SETTING: Two National Collegiate Athletic Association Division I university laboratories. PATIENTS OR OTHER PARTICIPANTS: Seventy-six (51 male and 25 female) concussed athletes with an average age of 19.5 ± 1.65 years who were evaluated within 24 hours of diagnosis. INTERVENTION(S): Participants completed the Revised Head Injury Scale (HIS-r), Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), and Sensory Organization Test within 24 hours of SC diagnosis. MAIN OUTCOME MEASURE(S): A stepwise multivariate regression incorporating ImPACT and Sensory Organization Test composites and HIS-r symptom severity-duration was used to predict the number of days athletes reported symptoms after SC. The resulting regression formula was cross-validated using the Stine cross-validation coefficient. RESULTS: The final formula consisted of the HIS-r's self-reported neck pain, drowsiness, tingling, and nervousness duration and ImPACT total symptom severity (R = 0.62, R(2) = 39%, R(2)(adj) = 34.2%, P < .001). Approximately 29% (R(2)(cv) = 29%) of the variance associated with total days symptomatic after SC was explained by our preliminary formula when cross-validated. The current formula correctly identified 76% of participants who recovered within 10 days of injury. CONCLUSIONS: Our results suggest that self-reported duration of 4 symptoms during the initial 24 hours after injury along with total symptom severity as measured by ImPACT accounted for a considerable amount of variance associated with days symptomatic after SC in collegiate athletes. Until the formula is cross-validated in a college-aged sample, caution is warranted in using it clinically.