Identifying the 'Miserable Minority' Among Pediatric Patients Following Concussion.

OBJECTIVES: To investigate whether there are empirically-detectable subgroups of concussion severity and recovery across three consecutive concussions, as well as to define risk factor and clinical assessment differences across subgroups. METHODS: The present study was a retrospective chart review of 202 adolescents 13.17 ± 1.99 years old who presented to a concussion specialty clinic within 30 days of injury for multiple injuries between 2019 and 2020. Participants included patients from a specialty clinic for two (n = 202) or three (n = 68) total concussions. Latent class analysis (LCA) was used to identify subgroups based upon concussion symptom severity and recovery time. Risk factors (sex, age at first injury, and histories of anxiety, depression, migraine, motion sickness, ocular dysfunction, and attention-deficit/hyperactivity disorder [ADHD] or learning disability [LD]) were compared across subgroups. RESULTS: A two-class solution yielded one group of 163 participants characterized by lower symptoms and shorter recovery times (80.7%, "normal") and 39 participants (19.3%, "miserable minority") characterized by higher symptoms and longer recovery times. Only female sex (OR = 4.91, p = 0.005) was a significant predictor of class membership. The miserable group presented for treatment nearly 4 days later (9.41 days) compared to the normal group (5.74 days) for the first injury, and almost 2 days later for the second injury (7.33 vs 5.26 days). CONCLUSIONS: Approximately 1 in 5 patients who presented to a concussion specialty clinic for a repeat concussion were classified in the miserable minority subgroup. This subgroup was characterized by markedly higher initial symptom burdens and over double the recovery time. LEVEL OF EVIDENCE: Retrospective cohort study, Level III evidence.

Predictive Blood Biomarkers of Targeted Intervention for Chronic Mental Health Symptoms following Traumatic Brain Injury.

The purpose of this study was to assess the performance of predictive blood biomarkers for responsiveness to targeted treatments for chronic psychological issues years after traumatic brain injury (TBI). Targeted Evaluation Action and Monitoring of TBI was a prospective 6-month interventional trial of participants with chronic TBI sequelae (n = 95). Plasma biomarkers were analyzed pre-intervention: glial fibrillary acidic protein (GFAP), tau, hyperphosphorylated tau Thr231 (p-Tau), von Willebrand factor (vWF), brain lipid-binding protein (BLBP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), vascular endothelial growth factor-a (VEGFa), and claudin-5 (CLDN5). Clinical outcomes included the Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) and Brief Symptom Inventory-18 (BSI-18). Regression models were built for change in PCL5/BSI-18. Biomarkers and covariates were included. Two models were built to identify responders (improved beyond the minimum clinically important difference). The model to predict change in PCL5 (R2=0.64; p < 0.001) included vWF (p = 0.032), BLBP (p = 0.001), tau (p = 0.002), VEGFa (p = 0.015), female sex (p = 0.06), and military status (p = 0.014). The model to predict change in BSI-18 (R2=0.42; p = 0.003) included vWF (p = 0.042), VEGFa (p = 0.09), BLBP (p = 0.01), CLDN5 (p < 0.001), female sex (p = 0.012), and military status (p = 0.004) as predictors. The model to differentiate participants who improved for PCL5 (R2=0.68; p < 0.001; AUC = 0.93) included vWF (p = 0.02), VEGFa (p = 0.008), and BLBP (p = 0.006). The model to differentiate participants who improved for BSI-18 (R2=0.25; p = 0.04; AUC = 0.75) included UCH-L1 (p = 0.03), GFAP (p = 0.06), and vWF (p = 0.03). Combinations of pre-intervention blood biomarkers were able to differentiate responders from nonresponders in both post-traumatic stress and overall psychological health domains.

Immediate post-concussion assessment and cognitive testing Pediatric (ImPACT Pediatric) change scores and factors associated with performance in patients aged 5-9 years following concussion: Preliminary findings.

BACKGROUND: Computerized neurocognitive testing is one component of a multidomain assessment of concussion. However, the use of computerized neurocognitive testing has been limited to patients aged 11 years and up, leaving clinicians with few options to evaluate younger children. PURPOSE: To examine the change in Immediate Post-concussion Assessment and Cognitive Testing Pediatric (ImPACT Pediatric) (ImPACT Applications, 2021) scores and factors associated with performance in children aged 5-9 years following a concussion. METHODS: Participants included 63 children (42% [n = 27] female) aged 5-9 (M = 7.5 ± 1.0) years within 30 (M = 8.5 ± 5.9) days of a concussion. All participants completed the ImPACT Pediatric at their initial visit and at medical clearance for their return to activity (RTA) visit. The ImPACT Pediatric test is a computerized neurocognitive battery that includes 5 tests that assess memory and visual processing speed. Multivariate and univariate analyses of variance and paired t-tests were used to compare ImPACT Pediatric scores from the initial visit to medical clearance. Multivariate and univariate analyses of covariance and multiple linear regression examined factors associated with ImPACT Pediatric performance. RESULTS: Participants demonstrated improved overall performance from the initial visit to the medical clearance visit (F(4, 59)=3.08, p = 0.02, Wilks' Λ = 0.83, ηp2=0.17), with significant improvement in Rapid Processing Speed (F(1, 62)=7.48, p < 0.01, ηp2=0.11). When controlling for age, sex, history of ADHD, and days to clinic, the improvement in overall performance remained significant (F(4, 51)=2.99, p = 0.03, Wilks' Λ = 0.81, ηp2=0.19). Older age was significantly associated with the Rapid Processing composite score at the initial visit (F(4, 59)=5.9, p < 0.001, Adj. R2=0.25) and medical clearance visit (F(4, 59)=3.8, p = 0.008, Adj. R2=0.16), with older children associated with better performance at both time points (Initial visit: B = 8.17, p < 0.001; Medical Clearance: B = 3.62, p = 0.03). CONCLUSION: Our main findings suggest that children aged 5-9 years improved significantly in Rapid Processing on the ImPACT Pediatric from the initial visit to medical clearance. However, no differences were found for the memory components of the ImPACT Pediatric. Older children also performed better on processing speed than younger children. The findings suggest that the processing speed components of ImPACT Pediatric are useful for monitoring improvements in neurocognitive functioning following concussion in children aged 5-9 years, but that age differences need to be considered when interpreting performance.

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.

Working Memory Recovery in Adolescents with Concussion: Longitudinal fMRI Study.

Background: Understanding the behavioral and neural underpinnings of the post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points. We aimed to examine working memory recovery during the first 6 months post-concussion in adolescents. Methods: We used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONCs] at baseline (<10 days post-concussion) and at 6 months post-concussion. Healthy control adolescents [HCs; n = 32] without a history of concussion were scanned once. During the scans, participants performed one-back and two-back working memory tasks with letters as the stimuli and angry, happy, neutral, and sad faces as distractors. Results: All affected adolescents were asymptomatic and cleared to return to activity 6 months after concussion. Working memory recovery was associated with faster and more accurate responses at 6 months vs. baseline (p-values < 0.05). It was also characterized by significant difficulty-related activation increases in the left inferior frontal gyrus (LIFG) and the left orbitofrontal cortex (LOFC) at 6 months vs. baseline. Although the activation differences between one-back and two-back were comparable between HCs and CONCs at 6 months, HCs had more pronounced activation in the LIFG than concussed adolescents. Conclusions: Post-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as the normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.

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.

Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes.

BACKGROUND: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. OBJECTIVE: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. STUDY DESIGN: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. LEVEL OF EVIDENCE: Level 3. RESULTS: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. CONCLUSION: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. CLINICAL RELEVANCE: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.

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.

Medical Conditions in Former Professional American-Style Football Players Are Associated With Self-Reported Clinical Features of Traumatic Encephalopathy Syndrome.

Consensus criteria for traumatic encephalopathy syndrome (TES) specify that at least one core clinical feature of cognitive impairment (CI; e.g., difficulties with memory, executive function) or neurobehavioral dysregulation (ND; e.g., explosiveness, rage, and mood lability) be present and not fully accounted for by other health disorders. Associations between self-reported symptoms that mirror the core clinical features of TES-and how they may be related to concomitant medical conditions-remain unclear. The purpose of this study was to evaluate the association of medical conditions and football exposures with TES clinical features (CI+/-, ND+/-) in 1741 former professional American-style football (ASF) players (age, 57.7 ± 13.9 years; professional seasons, 6.6 ± 3.9 years). Demographics (age, race/ethnicity, current body mass index, age of first football exposure, use of performance-enhancing drugs, position played, and past concussion symptoms), self-reported medical conditions (anxiety, depression, attention-deficit hyperactivity disorder [ADHD], sleep apnea, headache, stroke, hypertension, heart disease, high cholesterol, erectile dysfunction, and low testosterone) were collected. Of 1741 participants, 7.4% were CI+ and/or ND+ (n = 129). Participants who were CI+ or ND+ were more likely to report one or more coexisting medical conditions than participants who did not report CI or ND (odds ratio [OR] = 2.04; 95% confidence interval: 1.25-3.47; p = 0.003). Separate general linear models for each medical condition that adjusted for demographics and football-related factors identified significant associations between ADHD, diabetes, erectile dysfunction, headaches, sleep apnea, anxiety, and low testosterone and CI+ and/or ND+ (ORs = 1.8-6.0). Chi-square automatic interaction detection (CHAID) multi-variable decision tree models that incorporated medical conditions and football exposures accurately differentiated former players meeting either CI or ND clinical criteria from those meeting none (accuracy = 91.2-96.6%). CHAID identified combinations of depression, headache, sleep apnea, ADHD, and upper quartiles of concussion symptom history as most predictive of CI+ and/or ND+ status. CI+ and/or ND+ players were more likely to report medical conditions known to cause cognitive symptoms. Concussion exposure and medical conditions significantly increased the likelihood that a former ASF player would demonstrate cognitive or neurobehavioral dysfunction. Clinicians engaged with this population should consider whether treatable coexisting condition(s) could account for some portion of the clinical picture associated with TES presentation.

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.

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 role of concussion history and biological sex on baseline concussion clinical profile symptoms in adolescent rugby players.

BACKGROUND: Accurate concussion monitoring requires access to preinjury baseline data. This is particularly important in adolescent athletes who have a high risk of concussion and are prone to prolonged recovery. As Rugby Union is governed by similar laws for men and women, it is also an ideal population to rigorously examine the impact of biological sex on concussion symptoms. AIMS: To evaluate self-reported concussion symptoms at baseline in adolescent rugby union players, and examine if subtype-specific symptoms are affected by concussion history and biological sex. METHODS: Adolescent rugby union players aged 16-18 years were recruited during the 2022-2023 playing season. Participants completed a series of questionnaires covering post-concussion symptoms, concussion clinical profiles, anxiety, depression and fear avoidance behaviours. Independent variables of interest in analysis were biological sex and concussion history. RESULTS: 149 participants (75% male) were included. 42% (63/149) reported at least one previous concussion (average time since concussion: 18.7 months, range 1-72). Adolescents with a concussion history reported significantly higher scores than those with no history, across two clinical profiles (ocular and sleep), concussion symptom severity, and depression, all based on medium effect sizes (SMD 0.3-0.5). Females had significantly higher scores across cognitive/fatigue, ocular and sleep clinical profiles, concussion symptoms, anxiety and depression, each with large effect sizes (SMD > 0.5). CONCLUSIONS: Concussion history and sex are associated with higher baseline scores on specific concussion clinical profile, concussion symptom severity, and anxiety symptoms. These findings highlight the importance of considering baseline differences when interpreting post-injury clinical profile symptoms in adolescent rugby players. (Trial registration: ACTRN12622000931774).

Comparison of Vestibular/Ocular Motor Screening (VOMS) and Computerized Eye-tracking to Identify Exposure to Repetitive Head Impacts.

INTRODUCTION: Military service members (SMs) are exposed to repetitive head impacts (RHIs) in combat and training that are purported to adversely affect brain health, including cognition, behavior, and function. Researchers have reported that RHI from blast-related exposure may affect both vestibular and ocular function, which in turn may be related to symptomology. As such, an examination of the effects of RHI on exposed military SMs should incorporate these domains. To date, researchers have not compared groups of exposed special operations forces (SOF) operators on combined clinical vestibular/ocular and eye-tracker-based outcomes. Therefore, the primary purpose of this study was to compare participant-reported symptoms and performance on the Vestibular/Ocular Motor Screening (VOMS) tool with performance on the computerized RightEye tracking system between SOF operators exposed to blast-related RHI and healthy controls without blast-related exposure. In addition, the study aimed to compare subgroups of snipers and breachers exposed to RHI to controls on the preceding metrics, as well as identify a subset of individual (demographic) factors, participant-reported symptoms, and performance metrics on VOMS and RightEye that best identify SOF operators exposed to RHI from unexposed controls. MATERIALS AND METHODS: The study involved a cross-sectional design including 25 Canadian SOF SMs comprised of breachers (n = 9), snipers (n = 9), and healthy, unexposed controls (n = 7). The former 2 groups were combined into an RHI group (n = 18) and compared to controls (n = 7). Participants provided demographics and completed a self-reported concussion-related symptom report via the Military Acute Concussion Evaluation 2, the VOMS, and RightEye computerized eye-tracking assessments. Independent samples t-tests and ANOVAs were used to compare the groups on the outcomes, with receiver operating characteristic curve and area under the curve (AUC) analyses to identify predictors of blast exposure. This study was approved by the Defence Research Development Canada Human Research Ethics Committee and the Canadian Forces Surgeon General/Special Forces Command. RESULTS: The results from t-tests supported group differences for age (P = .012), participant-reported symptoms (P = .006), and all VOMS items (P range = <.001-.02), with the RHI group being higher than healthy controls on all variables. ANOVA results supported group differences among snipers, breachers, and controls for age (P = .01), RightEye saccades (P = .04), participant-reported total symptom severity (P = .03), and VOMS total scores (P = .003). The results of the receiver operating characteristic curve analyses supported age (AUC = 0.81), Military Acute Concussion Evaluation 2 participant-reported total symptom severity (AUC = 0.87), and VOMS total scores (AUC = 0.92) as significant predictors of prior blast exposure. CONCLUSIONS: Participant-reported concussion symptoms, VOMS scores, and age were useful in identifying SOF operators exposed to RHI from controls. RightEye metrics were not useful in differentiating RHI groups from controls. Differences between snipers and breachers warrant further research. Overall, the findings suggest that VOMS may be a useful tool for screening for the effects of exposure to RHI in SOF operators. Future investigations should be conducted on a larger sample of military SMs, consider additional factors (e.g., RHI exposure levels, medical history, and sex), and include additional assessment domains (e.g., balance, cognitive, and psychological).

Impact of Sex and Pubertal Development on Anxiety in Adolescents After Concussion.

Concussion often results in psychological symptoms, including anxiety. Post-concussion anxiety has been well documented, although much of this research has focused on collegiate athletes. The purpose of this study was to compare (1) anxiety symptoms in concussed and healthy controls over time and (2) to explore sex differences in post-concussion anxiety within the context of pubertal development. Participants (N = 126, mean age = 15.1 years old), including concussed (n = 86) and healthy adolescents (n = 40), completed the Pubertal Development Scale (PDS) and the Screen for Child Anxiety and Related Disorders (SCARED-C). The concussed groups completed SCARED-C at three visits (<10 days, 4 weeks, 3 months). Results of an analysis of covariance (ANCOVA) and multi-variate analysis of covariance (MANCOVA) found concussed adolescents reported higher SCARED-C total, generalized, and panic anxiety scores than healthy controls, after controlling for sex, age, and PDS score (PDSS). A three-way mixed ANCOVA examined the effects of sex, PDSS, time, and their interaction on SCARED-C total score in concussed adolescents while controlling for age. There was a significant three-way interaction between sex, age, and PDSS on SCARED-C total score while controlling for age. Overall, we observed increased anxiety in concussed adolescents, compared with controls, as well as greater post-concussion anxiety reported by females compared with males, including within PDSS groups. Concussion providers should be prepared to receive training to administer well-validated measures of psychopathology and should consider that female adolescents, compared with males, regardless of pubertal development, may be at greater risk for post-concussion anxiety.

Evaluating Recovery After Two and Three Repeated Concussions Using Growth Curves.

The results of prior research concerning the effects of repeated concussions have been mixed. The aim of this study was to evaluate how concussion outcomes and presentation changed within patients who were evaluated at a concussion specialty clinic multiple times with a concussion. Subjects included 202 patients (54% male) aged 10-21 years (M = 13.17) who presented to a specialty concussion clinic for two and three concussions (77% sport-related) and were followed through formal clearance. First, growth curve models were estimated to determine recovery time and initial symptom burden across the multiple injuries. Second, covariates were added to these models to evaluate which demographic, risk factor, or injury variables predicted any change that did occur in evaluation or outcome variables. Models indicated that each subsequent concussion linearly resulted in significantly fewer days to recovery (-4.62 days, p < 0.047) across three concussions, and significantly lower (and linear) symptom scores on the post-concussion symptom scale (PCSS) (-2.16, p = 0.05). More severe presentation (i.e., days to recovery; higher symptom score) was significantly associated (-.62, p = 0.005) with greater improvement in recovery time (-.62, p = 0.005) and symptom burden (-.56, p < 0.001) at subsequent injuries. No covariates were significantly associated with improvement (or lack thereof) at subsequent injuries. This study adds to evidence suggesting multiple injuries is not associated with protracted recovery at subsequent injuries, in the context of treatment and full clearance for each injury at a multi-disciplinary clinic.

Multidomain Predictors of Protracted Recovery following Concussion Among 5- to 9-Year-Old Patients: A Preliminary Study.

OBJECTIVE: To determine which components from a multidomain assessment best predict protracted recovery in pediatric patients with a concussion. STUDY DESIGN: A prospective cohort of patients aged 5-9 years who presented within 21 days of concussion to a specialty clinic were categorized into normal (≤30 days) and protracted (>30 days) recovery. Participants provided demographic and medical history information, and completed the Child Sport Concussion Assessment Tool-5 symptom report and balance assessment, the Vestibular/Ocular Motor Screen-Child (VOMS-C), and the Pediatric Immediate Post-concussion Assessment and Cognitive Testing. Univariate logistic regressions (LR) were used to inform a follow-up forward stepwise LR to identify the best predictors of protracted recovery. Receiver operating characteristic analysis of the area under the curve (AUC) was used to identify which predictors retained from the LR model best discriminated recovery. RESULTS: The final sample included 68 patients (7.52 ± 2.3 years; 56% male), 36 (52.9%) with normal and 32 (47.1%) with protracted recovery. Results of the LR to identify protracted recovery were significant (P < .001) and accounted for 39% of the variance. The model accurately classified 78% of patients, with days to first clinic visit (OR, 1.2; 95% CI, 1.1-1.4; P = .003) and positive VOMS-C findings (OR, 8.32; 95% CI, 2.4-28.8; P < .001) as significant predictors. A receiver operating characteristic analysis of the AUC of this 2-factor model discriminated protracted from normal recovery (AUC, 0.82; 95% CI, 0.71-0.92; P < .001). CONCLUSIONS: Days to first clinic visit and positive findings on the VOMS-C were the most robust predictors of protracted recovery after concussion in young pediatric patients.

Reliable Change Indices for the Serial Administration of the Concussion Clinical Profiles Screening Tool.

CONTEXT: The Concussion Clinical Profiles Screening Tool (CP Screen) self-report concussion symptom inventory is often administered at weekly intervals. However, 1-week reliable change indices (RCIs) for clinical cutoffs and the test-retest reliability of the CP Screen are unknown. OBJECTIVE: To document RCI cutoff scores and 1-week test-retest reliability for each profile and modifier of the CP Screen for men and women. DESIGN: Case series. SETTING: A large US university. PATIENTS OR OTHER PARTICIPANTS: One hundred seventy-three healthy college students. MAIN OUTCOME MEASURE(S): Participants completed 2 administrations of the CP Screen 7 days apart. The CP Screen items yielded 5 clinical profiles and 2 modifiers. Spearman ρ coefficients (rs), intraclass correlation coefficients (ICCs), single measures, and unbiased estimates of reliability (UERs) were used to assess test-retest reliability. Wilcoxon signed-rank tests assessed differences across time. Reliable change index values and cutoff scores are provided at 90%/95% CIs. All analyses were performed for the total sample and separately for men and women. RESULTS: Reliable change index cutoffs for clinically significant change (increase/decrease) at a 90% CI for men were as follows: ocular, vestibular >2/>4; anxiety/mood, cognitive/fatigue, and migraine >3/>3; sleep >4/>6; and neck >2/>2. Reliable change index cutoffs for clinically significant change (increase/decrease) at a 90% CI for women were as follows: anxiety/mood ≥2/≥4; cognitive/fatigue, migraine, ocular, vestibular, and sleep ≥3/≥3; and neck ≥1/≥1. Correlations for the CP Screen ranged from 0.51 (migraine) to 0.79 (anxiety/mood) for the total sample, from 0.48 (migraine) to 0.84 (vestibular) for men, and from 0.51 (migraine) to 0.77 (ocular) for women. Test-retest indices for each profile and modifier were moderate to good for the total sample (ICC, 0.64-0.82; UER, 0.79-0.90), men (ICC, 0.60-0.87; UER, 0.76-0.94), and women (ICC, 0.64-0.80; UER, 0.78-0.89). CONCLUSION: The CP Screen is reliable and stable across a 1-week interval, and established RCIs for men and women can help identify meaningful change throughout recovery.

Temporal Changes in Fixational Eye Movements After Concussion in Adolescents and Adults: Preliminary Findings.

Concussions often involve ocular impairment and symptoms such as convergence insufficiency, accommodative insufficiency, blurred vision, diplopia, eye strain, and pain. Current clinical assessments of ocular function and symptoms rely on subjective symptom reporting and/or involve lengthy administration time. More objective, brief assessments of ocular function following concussion are warranted. The purpose of this study was to evaluate changes in fixational eye movements (FEMs) and their association with clinical outcomes including recovery time, symptoms, cognitive and vestibular/ocular motor impairment. Thirty-three athletes (13-27 years of age; 54.5% female) within 21 days of a diagnosed concussion participated in the study. A tracking scanning laser ophthalmoscope (TSLO) evaluated FEMs metrics during fixation on a center and corner target. Participants completed symptom (Post-Concussion Symptom Scale [PCSS]), cognitive (Immediate Post-concussion Assessment and Cognitive Testing [ImPACT], and Vestibular/Ocular Motor Screening (VOMS) evaluations. All measures were administered at the initial visit and following medical clearance, which was defined as clinical recovery. Changes in FEMs were calculated using paired-samples t tests. Linear regression (LR) models were used to evaluate the association of FEMs with clinical recovery. Pearson product-moment correlations were used to evaluate the associations among FEMs and clinical outcomes. On the center task, changes across time were supported for average microsaccade amplitude (p = 0.005; Cohen's d = 0.53), peak velocity of microsaccades (p = 0.01; d = 0.48), peak acceleration of microsaccades (p = 0.02; d = 0.48), duration of microsaccade (p < 0.001; d = 0.72), and drift vertical (p = 0.017; d = -0.154). The LR model for clinical recovery was significant (R2 = 0.37; p = 0.023) and retained average instantaneous drift amplitude (ß = 0.547) and peak acceleration of microsaccade (ß = 0.414). On the corner task, changes across time were supported for drift proportion (p = 0.03; d = 0.43). The LR model to predict clinical recovery was significant (R2 = 0.85; p = 0.004) and retained average amplitude of microsaccades (ß = 2.66), peak velocity of microsaccades (ß = -15.11), peak acceleration of microsaccades (ß = 12.56), drift horizontal (ß = 7.95), drift vertical (ß = 1.29), drift amplitude (ß = -8.34), drift proportion (ß = 0.584), instantaneous drift direction (ß = -0.26), and instantaneous drift amplitude (ß = 0.819). FEMs metrics were also associated with reports of nausea and performance within the domain of visual memory. The FEMs metric were also associated with PCSS, ImPACT, and VOMS clinical concussion outcomes, with the highest magnitude correlations between average saccade amplitude and VOMS symptoms of nausea and average instantaneous drift speed and ImPACT visual memory, respectively. FEMs metrics changed across time following concussion, were useful in predicting clinical recovery, and were correlated with clinical outcomes. FEMs measurements may provide objective data to augment clinical assessments and inform prognosis following this injury.

A Common Data Element-Based Adjudication Process for mTBI Clinical Profiles: A Targeted Multidomain Clinical Trial Preliminary Study.

INTRODUCTION: The primary purpose of this study was to examine the prevalence and percent agreement of clinician-identified mild traumatic brain injury (mTBI) clinical profiles and cutoff scores for selected Federal Interagency Traumatic Brain Injury Research common data elements (CDEs). A secondary purpose was to investigate the predictive value of established CDE assessments in determining clinical profiles in adults with mTBI. MATERIALS AND METHODS: Seventy-one (23 males; 48 females) participants (M = 29.00, SD = 7.60, range 18-48 years) within 1-5 months (M = 24.20, SD = 25.30, range 8-154 days) of mTBI completed a clinical interview/exam and a multidomain assessment conducted by a licensed clinician with specialized training in concussion, and this information was used to identify mTBI clinical profile(s). A researcher administered CDE assessments to all participants, and scores exceeding CDE cutoffs were used to identify an mTBI clinical profile. The clinician- and CDE-identified clinical profiles were submitted to a multidisciplinary team for adjudication. The prevalence and percent agreement between clinician- and CDE-identified clinical profiles was documented, and a series of logistic regressions with adjusted odds ratios were performed to identify which CDE assessments best predicted clinician-identified mTBI clinical profiles. RESULTS: Migraine/headache, vestibular, and anxiety/mood mTBI clinical profiles exhibited the highest prevalence and overall percent agreement among CDE and clinician approaches. Participants exceeding cutoff scores for the Global Severity Index and Headache Impact Test-6 assessments were 3.90 and 8.81 times more likely to have anxiety/mood and migraine/headache profiles, respectively. The Vestibular/Ocular Motor Screening vestibular items and the Pittsburgh Sleep Quality Index total score were predictive of clinician-identified vestibular and sleep profiles, respectively. CONCLUSIONS: The CDEs from migraine/headache, vestibular, and anxiety/mood domains, and to a lesser extent the sleep modifier, may be clinically useful for identifying patients with these profiles following mTBI. However, CDEs for cognitive and ocular may have more limited clinical value for identifying mTBI profiles.

Comparison of physiological outcomes after dynamic exertion between athletes at return to sport from concussion and controls: Preliminary findings.

OBJECTIVES: Compare physiological (heart rate, heart rate variability, and blood pressure), performance (change-of-direction task completion time and errors), and clinical (symptoms and rating of perceived exertion) outcomes during dynamic exertion between athletes at return to sport after concussion to healthy athlete controls. DESIGN: Case control. METHODS: A sample of 23 (Female = 10; 43.5 %) athletes at medical clearance to play/activity from concussion (CONCUSS) and 23 sex-, age-, and sport-matched healthy athletes (CONTROLS) completed a 5-min seated rest before and after the dynamic exertion test. Independent sample t-tests were used to compare CONCUSS and CONTROLS for completion time, heart rate, and blood pressure; and Mann-Whitney U tests for symptoms, perceived exertion, and errors. A series of ANOVAs were conducted to compare heart rate variability between groups across pre- and post-exercise rest periods. RESULTS: There were no differences in heart rate, blood pressure, symptoms, perceived exertion, and errors. CONCUSS were faster on Zig Zag (p = .048) and Pro Agility (p = .018) tasks, reported lower symptom severity (p = .019), and had lower post-EXiT HRV (p < .049) than CONTROLS. CONCLUSIONS: Performance, symptoms, perceived exertion, and blood pressure outcomes from dynamic exertion were equivocal between athletes at medical clearance from concussion and healthy controls, which provide empirical support for dynamic exercise to inform medical clearance clinical decision making for sport-related concussion. However, differences in autonomic nervous system functioning indicate that additional research is needed to examine temporal changes in heart rate variability and other physiological outcomes following dynamic exertion.