Examination of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in former elite American football players.

INTRODUCTION: Blood-based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players. METHODS: The sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45-74). Plasma assays were conducted for beta-amyloid (Aß) 40, Aß42, hyper-phosphorylated tau (p-tau) 181+231, total tau (t-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), Aß42/p-tau181 and Aß42/Aß40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES). RESULTS: P-tau181 and p-tau231(padj = 0.016) were higher and Aß42/p-tau181 was lower(padj = 0.004) in football players compared to controls. Discrimination accuracy for p-tau was modest (area under the curve [AUC] = 0.742). Effects were not attributable to AD-related pathology. Younger age of first exposure (AFE) correlated with higher NfL (padj = 0.03) and GFAP (padj = 0.033). Plasma GFAP was higher in TES-chronic traumatic encephalopathy (TES-CTE) Possible/Probable (padj = 0.008). DISCUSSION: Plasma p-tau181 and p-tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI-related neuropathologies. HIGHLIGHTS: Former football players had higher plasma p-tau181 and p-tau231 and lower Aß42/ptau-181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES-CTE possible/probable compared to TES-CTE no/suggestive.

Protocol for COACH, an evidence-based intervention for improved head impact safety in youth American football developed using a community-engaged approach.

Subconcussive, repetitive head impacts sustained in collision sports may negatively affect brain health. American football practices are controlled environments amenable to intervention. Engaging community members is essential for successful development, implementation, and sustainability of viable interventions. The objective of this study is to develop and pilot test an evidence-based intervention to reduce head impact exposure in youth American football (i.e., football), using a community-engaged approach. This manuscript describes the co-design of the intervention and associated implementation plan and the study protocol for evaluating the effectiveness and feasibility of the intervention and implementation plan. In the first part of this study, focus groups with parents and coaches, and individual interviews with organizational leaders associated with two teams at the middle school level were conducted. An anonymous survey assessing beliefs and perceptions of non-concussive head impacts was given to parents, coaches, and organizational leaders within the local youth football league. Following the football season, qualitative and quantitative data describing determinants of head acceleration events in football were shared with 12 stakeholders of coaches, league and school administrators, parents, an athletic trainer, and local university player development director. Together, we co-designed COACH (COmmunities Aligned to reduce Concussion and Head impact exposure) and implementation plan using a strategic planning approach. The preliminary effectiveness and feasibility were assessed in the second part of this study. Youth football players participating on the teams in year 1 (control teams) were fitted with mouthpiece-based head kinematic sensors which measure head acceleration events (HAEs). HAEs were collected and quantified during team activities. Preliminary effectiveness of the intervention to reduce HAEs was measured among two new teams pilot testing COACH with mouthpiece-based sensors, while simultaneously monitoring implementation of the intervention. We report our study design and evaluation, and opportunities and challenges with our approach. The results will inform a future full-scale pragmatic trial to assess the implementation and effectiveness of the intervention program. NCT04908930.

Understanding of head injury assessment and return to play processes and associated factors in United States Major League Rugby players.

OBJECTIVES: Evaluate professional rugby players' self-reported perceived understanding of the head injury assessment (HIA) and return to play (RTP) processes and determine factors related to understanding and trust pertaining to these processes. METHODS: An electronic survey measured concepts of interest. A thematic analysis of player understanding was performed, and player statements were coded. RESULTS: 207 U.S. Major League Rugby (MLR) players participated (26.7 ± 3.4 years). HIA and RTP protocol understanding was not correlated with concussion history (p = 0.41). International rugby experience and trust regarding MLR support of the following protocols and opposing team medical staff practices varied in their relationship to HIA understanding. Trust that all MLR teams follow the same protocols was positively correlated with all HIA questions (ps < 0.03). No HIA questions were correlated with trust in their own team's medical staff. All trust questions were significantly correlated with RTP process understanding. Qualitative analysis identified four HIA- and RTP-related themes: education needs, staffing needs, HIA criticisms, and importance of player safety. CONCLUSION: International playing experience and greater trust in the MLR and league stakeholders were associated with greater player understanding of the HIA and RTP protocols. These results provide insight into the importance of educating players on league-specific concussion protocols.

How Shell Add-On Products Influence Varsity Football Helmet Performance?

PURPOSE: The study purpose was to investigate the laboratory-based performance of three commercially available shell add-on products under varsity-level impact conditions. METHODS: Pendulum impact tests were conducted at multiple locations (front, front boss, rear, side) and speeds (3.1, 4.9, 6.4 m/s) using two helmet models. Tests were performed with a single add-on configuration for baseline comparisons and a double add-on configuration to simulate collisions with both players wearing shell add-ons. A linear mixed-effect model was used to evaluate peak linear acceleration (PLA), peak rotational acceleration (PRA), and concussion risk, which was calculated from a bivariate injury risk function, based on shell add-on and test configuration. RESULTS: All shell add-ons decreased peak head kinematics and injury risk compared to controls, with the Guardian NXT producing the largest reductions (PLA: 7.9%, PRA: 14.1%, Risk: 34.1%) compared to the SAFR Helmet Cover (PLA: 4.5%, PRA: 9.3%, Risk: 24.7%) and Guardian XT (PLA: 3.2%, PRA: 5.0%, Risk: 15.5%). The same trend was observed in the double add-on test configuration. However, the Guardian NXT (PLA: 17.1%; PRA: 11.5%; Risk: 62.8%) and SAFR Helmet Cover (PLA: 12.2%; PRA: 9.1%; Risk: 52.2%) produced larger reductions in peak head kinematics and injury risk than the Guardian XT (PLA: 5.7%, PRA: 2.2%, Risk: 21.8%). CONCLUSION: In laboratory-based assessments that simulated varsity-level impact conditions, the Guardian NXT was associated with larger reductions in PLA, PRA, and injury risk compared to the SAFR Helmet Cover and Guardian XT. Although shell add-ons can enhance head protection, helmet model selection should be prioritized.

Player and match characteristics associated with head acceleration events in elite-level men's and women's rugby union matches.

Objective: To examine the likelihood of head acceleration events (HAEs) as a function of previously identified risk factors: match time, player status (starter or substitute) and pitch location in elite-level men's and women's rugby union matches. Methods: Instrumented mouthguard data were collected from 179 and 107 players in the men's and women's games and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA) and peak resultant angular acceleration were extracted from each HAE. Field location was determined for HAEs linked to a tackle, carry or ruck. HAE incidence was calculated per player hour across PLA recording thresholds with 95% CIs estimated. Propensity was calculated as the percentage of contact events that caused HAEs across PLA recording thresholds, with a 95% CI estimated. Significance was assessed by non-overlapping 95% CIs. Results: 29 099 and 6277 HAEs were collected from 1214 and 577 player-matches in the men's and women's games. No significant differences in match quarter HAE incidence or propensity were found. Substitutes had higher HAE incidence than starters at lower PLA recording thresholds for men but similar HAE propensity. HAEs were more likely to occur in field locations with high contact event occurrence. Conclusion: Strategies to reduce HAE incidence need not consider match time or status as a substitute or starter as HAE rates are similar throughout matches, without differences in propensity between starters and substitutes. HAE incidence is proportional to contact frequency, and strategies that reduce either frequency or propensity for contact to cause head contact may be explored.

Fact or Fiction-Accelerometry Versus Self-Report in Adherence to Pediatric Concussion Protocols: Prospective Longitudinal Cohort Study.

Background: Concussion, or mild traumatic brain injury, is a growing public health concern, affecting approximately 1.2% of the population annually. Among children aged 1-17 years, concussion had the highest weighted prevalence compared to other injury types, highlighting the importance of addressing this issue among the youth population. Objective: This study aimed to assess adherence to Return to Activity (RTA) protocols among youth with concussion and to determine if better adherence affected time to recovery and the rate of reinjury. Methods: Children and youth (N=139) aged 5-18 years with concussion were recruited. Self-reported symptoms and protocol stage of recovery were monitored every 48 hours until symptom resolution was achieved. Daily accelerometry was assessed with the ActiGraph. Data were collected to evaluate adherence to the RTA protocol based on physical activity cutoff points corresponding to RTA stages. Participants were evaluated using a battery of physical, cognitive, and behavioral measures at recruitment, upon symptom resolution, and 3 months post symptom resolution. Results: For RTA stage 1, a total of 13% of participants were adherent based on accelerometry, whereas 11% and 34% of participants were adherent for stage 2 and 3, respectively. The median time to symptom resolution was 13 days for participants who were subjectively reported adherent to the RTA protocol and 20 days for those who were subjectively reported as nonadherent (P=.03). No significant agreement was found between self-report of adherence and objective actigraphy adherence to the RTA protocol as well as to other clinical outcomes, such as depression, quality of life, and balance. The rate of reinjury among the entire cohort was 2% (n=3). Conclusions: Overall, adherence to staged protocols post concussion was minimal when assessed with accelerometers, but adherence was higher by self-report. More physical activity restrictions, as specified in the RTA protocol, resulted in lower adherence. Although objective adherence was low, reinjury rate was lower than expected, suggesting a protective effect of being monitored and increased youth awareness of protocols. The results of this study support the move to less restrictive protocols and earlier resumption of daily activities that have since been implemented in more recent protocols.

Characterizing the Effects of Concussion and Head Impact Exposure: Design, Methods, and Participant Traits of the CARE 2.0 Study.

OBJECTIVE: This article describes the design, methods, and participant characteristics of the second phase of the Concussion Assessment, Research, and Education (CARE) Consortium study ("CARE 2.0") of the effects of concussion and repetitive head impact exposure on neuropsychiatric health. METHODS: The authors conducted a prospective multisite observational study of male and female collegiate athletes and military service academy cadets and midshipmen participating in the CARE study. Participants were assessed at three time points: undergraduate baseline (UB), before departure from university or service academy (exit), and up to 6 years following graduation (postgrad) via an online battery of brain health assessments. Participant characteristics were compared across the three time points and four levels of head impact exposure. RESULTS: A total of 4,643 participants completed the exit assessment, and 3,981 completed the postgrad assessment. Relative to the UB assessment cohort, the exit and postgrad assessment cohorts differed with respect to the percentage of women, baseline Wechsler Test of Adult Reading scores, National Collegiate Athletic Association division category, sport contact level, and number of previous concussions. The median standardized difference across balancing variables, assessment time points, and degree of head impact exposure was 0.12 (with 90% of effect sizes ≤0.29). CONCLUSIONS: Although there were some statistically significant differences between participants across assessments, the effect sizes were modest, and overall the data suggest that the exit and postgrad cohorts reflect the characteristics of the baseline cohort. The CARE study design and its large, richly characterized sample provide an opportunity to answer important questions about cumulative and persistent effects of concussion and repetitive head impact exposure on neuropsychiatric health.

Quality of Life in Adolescent Athletes With Sport-Related Concussion Prescribed Heart Rate-Targeted Aerobic Exercise Within 10 Days of Injury.

Individualized aerobic exercise treatment prescribed within 10 days of injury facilitates recovery in adolescents after sport-related concussion (SRC) and reduces incidence of persisting post-concussive symptoms (PPCSs) beyond 4 weeks. The effect of aerobic exercise treatment on quality of life symptoms is, however, unknown. This planned secondary aim of a published randomized controlled trial found that while adolescents prescribed aerobic exercise recovered faster, there was no difference on the Pediatric Quality of Life (PedsQL) questionnaire scores during the 4-week intervention period. Nevertheless, adolescents who experienced PPCS reported significantly worse initial visit (within 10 days of injury) symptoms on the PedsQL than those who recovered within 4 weeks. Higher scores on the PedsQL correlated with greater initial visit concussion symptom burden and more abnormalities on a concussion-relevant visio-vestibular examination. Thus, the PedsQL captures the clinical severity of concussion and is prognostic of risk for delayed recovery when administered early after SRC in adolescents.

Detecting a shadow pandemic: The current state and future direction of screening and assessment tools for intimate partner violence-related brain injury.

Intimate partner violence (IPV) is a major global concern, and IPV victim-survivors are at an increased risk of brain injury (BI) due to the physical assaults. IPV-BI can encompass both mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), but IPV-BI often goes undetected and untreated due to a number of complicating factors. Therefore, the clinical care and support of IPV victim-survivors could be enhanced by BI screening and assessment in various settings (e.g., first responders, emergency departments, primary care providers, rehabilitation, shelters, and research). Further, appropriate screening and assessment for IPV-BI will support more accurate identifications, and prevalence estimates, improve understanding of health implications, and have the potential to inform policy decisions. Here we overview the seven available tools that have been used for IPV-BI screening and assessment purposes, including the BISA, BISQ-IPV, BAT-L/IPV, OSU TBI-ID, the HELPS, and the CHATS, and outline the advantages and disadvantages of these screening tools in the clinical, community, and research settings. Recommendations for further research to enhance the validity and utility of these tools are also included.

Mass media guidelines for sports concussion: a scoping review protocol.

Sports concussion is a common and costly injury, and increased public injury awareness could help reduce costs. Many factors, including public messages about sports concussion by the sports media, shape public injury awareness. Empirical analyses show that this messaging can be poor. The proposed solutions include providing media guidance, but little is known about this topic. This scoping review will enable a systematic search and synthesis of guidance materials for improved health messaging of sports concussion by the mass media. The five review stages are (1) determining the research question, (2) identifying relevant materials, (3) selecting relevant information, (4) data extraction and (5) analysis and presentation of the results. A brief protocol will be registered on a recommended platform (Open Science Framework). The search strategy will access 20 databases, as well as Google and Google Scholar, and include hand searching. Selected materials must describe or provide mass media guidance for sports concussion by a health-affiliated authority. Eligibility will be confirmed via a two-stage screening process, including independent assessment. Data from eligible materials will be extracted and collated in tables. If sufficient or appropriate materials are identified, the synthesis will draw on key evaluative resources related to injury management and guideline development methodologies. The knowledge synthesis will use descriptive and narrative methods to determine what is known on this topic, including documenting existing guidance (content and properties) and using the extracted data to inform recommendations for future guidance.

Virtual Neuromuscular Training Among Physically Active Young Adults: A Feasibility Study.

CONTEXT: Evidence indicates a 2 to 3 times increased risk of musculoskeletal injury after return to play from concussion. Undetected neuromuscular control deficits at return to play may relate to increased musculoskeletal injury risk. Rehabilitation to improve neuromuscular control may benefit patients with concussion, but access to rehabilitation professionals and/or poor adherence may limit efficacy. Our purpose was to determine the feasibility of an 8-week virtual neuromuscular training (NMT) program administered through a novel smartphone application among physically active, uninjured adults. DESIGN: Feasibility trial. METHODS: Participants were instructed to complete an NMT program administered via a smartphone application and returned for follow-up questionnaires 8 weeks later. They were instructed to complete 3 asynchronous self-guided workouts per week during the 8-week intervention period. Workouts included balance, plyometrics, strengthening, and dual-task exercises. The application provided instructions for each exercise using video, text, and audio descriptions. Our primary feasibility measure was participant adherence, calculated as the percentage of workouts completed out of the total possible 24 workouts. We recorded the average duration of each workout using start/stop/advance features within the application. RESULTS: Twenty participants were enrolled, of which 15 (age = 26.3 [2.7] y, 67% female) returned for follow-up (75% retention). Participant adherence was 57.2% (25.0%; range: 16.7%-91.7%). Participants spent 17.3 (8.0) minutes per workout (range: 7.4-37.9 min). There were no adverse reactions or injuries. Most participants (60%) reported time availability as a primary barrier to intervention completion. CONCLUSIONS: Participants were moderately (>50%) adherent to a virtual NMT program, without any reported injuries. We identified several barriers to participation and pathways for improved adherence in the future. The virtual NMT program completed by uninjured adults provides evidence of its feasibility and future scalability to those with a recent concussion to address neuromuscular control deficits and reduce future injury risk.

'Their role has a lot of purpose beyond being just being about exercises': a qualitative study of patients' experiences of physiotherapy following a mild traumatic brain injury.

Following a mild traumatic brain injury (mTBI; also known as concussion), physiotherapists may be involved in injury identification, assessment and rehabilitation. However, how people perceive and experience the physiotherapist's role is not well understood. Semistructured interviews were undertaken with patients who saw a physiotherapist individually or as part of a multidisciplinary team following mTBI in New Zealand. Interviews were recorded, transcribed verbatim and analysed using the interpretive descriptive approach. A total of 12 interviews were held with participants aged 19-67 (50% female; mean age 37 (SD=14.8) years) who had a mTBI on average 9 (SD=8) months ago. Thematic coding of interviews generated four themes, each supported by three to five categories representing their experiences: (1) 'How physiotherapy could help me'-representing how the interventions were delivered; (2) 'Empower me to manage my mTBI'-representing participants learnings to self-manage; (3) 'Set me up to get the most out of treatment'-representing considerations needed before, during and after practice to maximise engagement and (4) 'Get to know me and what's important to me'-representing the importance of considering the person as a whole, and preferences for assessment, intervention, communication and culture throughout service delivery. Overall, participants reported variable mTBI care experiences yet perceived the physiotherapist as having a key role in supporting self-management and treating headaches, neck pain and balance issues. mTBI physiotherapy care needs to be more attuned to patients' preferences and circumstances and delivered in a way that maximises rehabilitation outcomes. Building effective therapeutic connections with patients may be key to addressing these concerns simultaneously in practice.

Mild traumatic brain injury gives rise to chronic depression-like behavior and associated alterations in glutamatergic protein expression.

Mild traumatic brain injury (mTBI) is known to result in chronic somatic, cognitive, and emotional symptoms. Depression is commonly reported among individuals suffering from persistent concussion symptoms; however, the underlying mechanisms are not understood. The glutamatergic system has recently been linked with mTBI and depression due to reports of similar changes in expression of glutamatergic proteins. Using a closed-head controlled cortical impact (cCCI) model in adult male rats (n = 8/group), this study investigated the emergence of self-care deficits and changes in social interaction behaviors at four, eight and twelve weeks post-injury. Western blotting was used to assess associated changes in expression of glutamate transporters and N-methyl-D-aspartate (NMDA) receptor subunits at twelve weeks. Splash test results revealed deficits in self-care behaviors beginning at eight weeks, which continued through twelve weeks in the injury group. Injured animals also exhibited decreased preference for social novelty at four weeks and loss of desire for social interaction as a whole by twelve weeks. GluN1 was increased in injured animals compared to shams in the frontal cortex and amygdala, while decreased GLT-1 was observed in the hippocampus. Linear regression was performed to evaluate relationships between behavioral and molecular variables; the results suggested that injury affects these relationships in a region-dependent manner. Together, these results suggest that the development of chronic depression-like behavior was associated with changes in glutamatergic protein expression. Deeper investigations into how injury influences glutamatergic synaptic protein expression are needed, as this has the potential to affect circuit-level neurotransmission that drives depression-like behavior following mTBI.

Exposure to Adverse Childhood Experiences Predicts Increased Neurobehavioral Symptom Reporting in Adults with Mild Traumatic Brain Injury.

The objective of this study was to understand whether exposure to adverse childhood experiences (ACEs) before 18 years of age predicts increased neurobehavioral symptom reporting in adults presenting for treatment secondary to persistent symptoms after mild traumatic brain injury (mTBI). This cross-sectional study identified 78 individuals with mTBI from 2014 to 2018 presenting for treatment to an outpatient multidisciplinary rehabilitation clinic. Neurobehavioral symptom inventory (NSI-22) scores were collected on admission, and ACEs for each patient were abstracted by medical record review. A linear regression model was used to assess if an individual who experienced at least one ACE before age 18 resulted in significantly different neurobehavioral scores compared with those not reporting any history of an ACE before age 18. Participants who reported at least one ACE before age 18 had significantly increased NSI-22 scores on admission to the rehabilitation clinic compared with patients without history of ACEs (mean difference 10.1, p = 0.011), adjusted for age and gender. For individuals presenting for treatment after mTBI, a history of ACEs before age 18 was associated with increased neurobehavioral symptoms.

Characteristics of potential head injury situations at the FIFA World Cup Qatar 2022TM.

This exploratory video analysis study aimed to review characteristics of potential head injury situations during a men's professional international football tournament. For 64 matches of the FIFA World Cup Qatar 2022™ FIFA analysts used match footage to record all potential head injury situations. A potential head injury situation was defined as a player staying down for more than 5 s and/or requesting medical attention, and where the body impact location included the player's head. Characteristics were further recorded for match, player (i.e. player action including aerial duels), medical assessment, and outcome (e.g. substitution). Descriptive statistics are reported as well as Pearson's Chi-squared test (or Fisher's exact test) to explore potential head injury situations more likely to result in medical attention. In total, 149 potential head injury situations occurred in 56 matches (mean 2.33/match, range 0-6) involving 117 players. Eight matches resulted in no incidents. Aerial duels were the most frequent match characteristic leading to a potential head injury situation. Injury stoppage with on-pitch medical assessment occurred in 35 of the 149 potential head injury situations (23%), with pitch-side assessment also occurring in 15 situations (10%), resulting in four concussion substitutions. Players were more likely to require medical attention for potential head injuries sustained when the ball was loose (χ2 = 6.88; p = 0.038) when the injured player was jumping (FET p = 0.044) and for head-to-head contact (FET p = <0.001). Further exploration of aerial duels during match play which do and do not lead to potential and actual head injuries is recommended.

Concussion Health Improvement Program (CHIP): study protocol for a randomized controlled optimization trial for youth with persistent post-concussive symptoms.

BACKGROUND: Up to 1.9 million youth in the USA sustain a concussion each year, and up to 30% experience persistent post-concussive symptoms (PPCS) lasting 1 month or more. PPCS can substantially interfere with social, emotional, and academic functioning. Despite these concerns, few evidence-based treatments are available for youth with PPCS. We previously found effectiveness in treating youth with concussion using a collaborative care intervention that integrates mental health care into a medical model, with improvements in concussive symptoms and quality of life at 1 year. Using the multiphase optimization strategy (MOST) framework, we now aim to assess the contribution of each of the three components that were part of collaborative care: concussion-focused cognitive behavioral therapy (cf-CBT), parenting skills training (PST), and care management (CM). METHODS: The MOST factorial design examines all three intervention components with two levels of each (present or absent), resulting in 8 possible treatment combinations. We will recruit 368 youth with PPCS from 2 geographic locations (Seattle and Dallas), randomizing them to 1 of 8 treatment groups. Youth and/or parents will attend treatment sessions via video conferencing software over 3 months, and complete surveys regarding primary outcomes (concussive symptoms and health-related quality of life) and secondary outcomes (sleep, pain, mood, and parental distress) at 6 weeks and 3, 6, and 12 months. We will also assess potential mediators and moderators to allow for future tailoring and refinement. DISCUSSION: The overarching goal of this investigation is to determine which collaborative care components (delivered individually or in combination) are most effective in treating PPCS in concussion-exposed youth. The investigation will inform mental health screening, intervention, and referral procedures for youth and families following concussion. At the completion of this study, we will have an optimized and refined intervention for youth with PPCS ready for large-scale implementation and dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT06036147. Registered on September 13, 2023.

Graded exposure therapy for adults with persistent symptoms after mTBI: A historical comparison study.

Fear avoidance behaviour is associated with slow recovery from mild traumatic brain injury (mTBI). This study is a preliminary evaluation of graded exposure therapy (GET), which directly targets fear avoidance behaviour, for reducing post-concussion symptoms (PCS) and disability following mTBI. In a historical comparison design, we compared two groups from independent randomized trials. The GET + UC group (N = 34) received GET (delivered over 16 videoconference sessions) in addition to usual care (UC). The historical comparison group (N = 71) received UC only. PCS severity (Rivermead Post Concussion Symptoms Questionnaire; RPQ) and disability (World Health Organization Disability Assessment Schedule; WHODAS 2.0 12-item) were measured at clinic intake (M = 2.7, SD = 1.1 months after injury) and again at M = 4.9 (SD = 1.1) months after injury. Between-group differences were estimated using linear mixed effects regression, with a sensitivity analysis controlling for injury-to-assessment intervals. The estimated average change on the RPQ was -14.3 in the GET + UC group and -5.3 in the UC group. The estimated average change on the WHODAS was -5.3 in the GET + UC group and -3.2 in the UC group. Between-group differences post-treatment were -5.3 on the RPQ and -1.5 on the WHODAS. Treatment effects were larger in sensitivity analyses. Findings suggest that a randomized controlled trial is warranted.

The beneficial effects of modafinil administration on repeat mild traumatic brain injury (RmTBI) pathology in adolescent male rats are not dependent upon the orexinergic system.

The sleep-wake cycle plays an influential role in the development and progression of repeat mild traumatic brain injury (RmTBI)-related pathology. Therefore, we first aimed to manipulate the sleep-wake cycle post-RmTBI using modafinil, a wake-promoting substance used for the treatment of narcolepsy. We hypothesized that modafinil would exacerbate RmTBI-induced deficits. Chronic behavioural analyses were completed along with a 27-plex serum cytokine array, metabolomic and proteomic analyses of cerebrospinal fluid (CSF), as well as immunohistochemical staining in structures important for sleep/wake cycles, to examine orexin, melanin-concentrating hormone, tyrosine hydroxylase, and choline acetyltransferase, in the lateral hypothalamus, locus coeruleus, and basal forebrain, respectively. Contrary to expectation, modafinil administration attenuated behavioural deficits, metabolomic changes, and neuropathological modifications. Therefore, the second aim was to determine if the beneficial effects of modafinil treatment were driven by the orexinergic system. The same experimental protocol was used; however, RmTBI rats received chronic orexin-A administration instead of modafinil. Orexin-A administration produced drastically different outcomes, exacerbating anxiety-related and motor deficits, while also significantly disrupting their metabolomic and neuropathological profiles. These results suggest that the beneficial effects of modafinil administration post-RmTBI, work independently of its wake-promoting properties, as activation of the orexinergic wake-promoting system with orexin-A was detrimental. Overall, these findings highlight the complexity of sleep-wake changes in the injured brain and showcase the potential of the arousal and sleep systems in its treatment.

Potential of Soft-Shelled Rugby Headgear to Lower Regional Brain Strain Metrics During Standard Drop Tests.

BACKGROUND: The growing concern for player safety in rugby has led to an increased focus on head impacts. Previous laboratory studies have shown that rugby headgear significantly reduces peak linear and rotational accelerations compared to no headgear. However, these metrics may have limited relevance in assessing the effectiveness of headgear in preventing strain-based brain injuries like concussions. This study used an instantaneous deep-learning brain injury model to quantify regional brain strain mitigation of rugby headgear during drop tests. Tests were conducted on flat and angled impact surfaces across different heights, using a Hybrid III headform and neck. RESULTS: Headgear presence generally reduced the peak rotational velocities, with some headgear outperforming others. However, the effect on peak regional brain strains was less consistent. Of the 5 headgear tested, only the newer models that use open cell foams at densities above 45 kg/m3 consistently reduced the peak strain in the cerebrum, corpus callosum, and brainstem. The 3 conventional headgear that use closed cell foams at or below 45 kg/m3 showed no consistent reduction in the peak strain in the cerebrum, corpus callosum, and brainstem. CONCLUSIONS: The presence of rugby headgear may be able to reduce the severity of head impact exposure during rugby. However, to understand how these findings relate to brain strain mitigation in the field, further investigation into the relationship between the impact conditions in this study and those encountered during actual gameplay is necessary.

Age-Related Variations in Clinical Profiles for Children with Sports- and Recreation-Related Concussions.

OBJECTIVE: The purpose was to examine clinical profiles in concussed children aged 5-9 and 10-12 years and compare them with those of adolescents >12 years. METHODS: This study included patients aged 5-18 years presenting to a specialty care concussion program with a sports- and recreation-related (SRR) concussion ≤28 days postinjury. Demographics, injury mechanisms, symptoms, and clinical features were assessed. Chi-squared tests, one-way ANOVA, and Kruskal-Wallis were used for comparisons across age groups. RESULTS: A total of 3280 patients with SRR concussion were included: 5.0% were 5-9 years, 18.4% were 10-12 years, and 76.6% were 13-18 years. Younger age groups had more males than females (5-9 years: 70.7% vs. 29.3%) and more commonly sustained their injury during limited- (28.7%), and non-contact (7.9%) activities compared to other age groups (p < 0.01). Younger children presented less symptoms frequently (p ≤ 0.042), but higher symptom severity in somatic and emotional domains (p ≤ 0.016). Fewer 5-9-year-olds reported changes in school (25.6%), sleep (46.3%), and daily habits (40.9%) than adolescents (p < 0.001). CONCLUSIONS: Among SRR-concussed children and adolescents, we found significant age-related variations in demographics, injury mechanism, symptoms, and clinical features. Recognizing these unique features in younger children may facilitate targeted management and treatment.