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Patients with cervicogenic symptoms following a concussion have shown a disproportionate rate of delayed symptom resolution. However, the prevalence of cervicogenic symptoms in the acute stages following a concussion and the percentage of those patients who continue on to suffer delayed symptom resolution is poorly described in the literature. To provide a comprehensive report on the clinical prevalence, diagnostic methods, and potential treatment options for cervicogenic symptoms that are elicited during acute and chronic phases following a concussion. Electronic searches were conducted in PubMed, SPORTDiscus, ICL, CINAHL and PEDro, from inception to May 2020, to identify original research articles on concussion involving cervicogenic symptoms. We assessed each included article for risk of bias, methodological quality, level of evidence and evidence quality. The articles were categorized into three topics: (1) prevalence of post-concussion cervicogenic symptoms; (2) diagnostic testing for cervicogenic symptoms, and (3) treatment techniques for cervicogenic symptoms. The initial review resulted in 1443 abstracts, of which 103 abstracts met the inclusion criteria of our research. After the review of full text, 80 articles were excluded, which resulted in a total of 23 articles for this systematic review. Prevalence of cervicogenic symptoms in the acute stages ranged from 7 to 69% and increased to 90% in patients experiencing persistent post-concussive symptoms. Neck pain at initial evaluation increased risk of developing persistent post-concussive symptoms (PPCS) by 2.58–6.38 times. Patient-reported outcome measures (e.g., Neck Disability Index, Dizziness Handicap Inventory, and Rivermead Post-Concussion Questionnaire) can identify patients with cervicogenic symptoms that should be further differentiated by clinical testing. Lastly, treatment using graded cervical manual therapy has shown to reduce time to symptom resolution and medical clearance. Cervicogenic symptoms are prevalent in the acute and chronic stages following concussion, which if not diagnosed appropriately increase the likelihood of PPCS. Several clinical tests are available to help differentiate cervicogenic symptoms; however, lack of awareness and hesitation by practitioners limits their use. More randomized controlled trials are necessary to evaluate the effectiveness of cervical specific treatment programs for PPCS.

Context: Increased injury rates following concussive injury have been attributed to decreased neuromuscular coordination frequently documented following a concussion. However, altered integration between the vestibular system and oculomotor pathways following impacts at subconcussive thresholds implicate all sports-related impacts not just those at a concussive threshold in future musculoskeletal injury. While, several studies have explored the utility of vestibular and oculomotor clinical testing to detect altered neuromuscular control and then correlated those alterations to future injury risk, no research has explored the use of cervical clinical tests in the same capacity. Outcome Measures: Cervical joint position error test, Neck Disability Index and head acceleration. Interventions: Soccer headers, fatigue protocol, soccer headers + fatigue. Objective: To explore the clinical utility of a novel clinical approach to measuring changes in cervical neuromuscular control following subconcussive impacts in a controlled lab environment. Participants: 40 current female colligate club soccer athletes were recruited. Inclusion criteria included between the age of 18 and 25 and a minimum of 4-year soccer heading experience. Setting: Laboratory. Design: A repeated-measures design with 4 groups was utilized to test the hypothesis. Results: A 65%, 54%, and 49% increased error was observed following the soccer heading, fatigue only, and soccer heading + fatigue interventions, respectively. Meanwhile, the controls saw a 6% decrease in neck position error. Concussion: While, cervical joint position error testing was sensitive to decreased neuromuscular coordination following soccer heading, it was not specific enough to rule out an exercise effect in the absence of subconcussive impacts. Further research is warranted to explore the clinical utility and specificity of cervical joint position error testing to measured alterations in supraspinal processing following subconcussive impacts, and how these alterations may lead to decreased coordination and movement of the body during sports-related task.

Physical activity during adolescence is associated with positive health outcomes, yet only 26% of US middle and high school students report daily physical activity. Moreover, the number of high school students playing a sport is declining, with the largest decline in football. One reason for this decline in playing football may be increased attention to the risk of head injury. For public health, the decline is alarming because football offers a physical activity opportunity for millions of young people every year. In response, efforts have been made to institute measures to enhance the safety of football. The objective of this topical review was to review these measures and the data supporting their effectiveness. We conducted a search of scientific literature supplemented by a web search to identify safety measures. We used the Indiana University library electronic database, PubMed, and web browser searches with specific search terms. In addition to peer-reviewed studies, we searched news stories and reports from sport-related organizations. We summarized the measures and evaluations of effectiveness and categorized the measures by type (game rules, practice guidelines, equipment innovations, strategic initiatives) and target age group (elementary/middle school, high school, college, professional). We found that attempts are being made to improve the safety of football at all levels. However, many measures lack scientific evidence to support their effectiveness. Therefore, researchers need to systematically evaluate safety measures. By implementing evidence-based interventions, we can balance the public health risk of playing football versus the public health risk of continued declines in participation.

Understanding the impact of concussion history on mental health—mood disorders and substance use—is an essential step in characterizing the psychological and behavioral consequences of concussion and in developing effective treatments. The objective of this study was to examine the association between the history of concussion and substance abuse by investigating both its direct and indirect association via mood disorder. A secondary objective was to determine whether gender moderates the association. A comprehensive survey was administered to 4849 college-age adults that assessed history of concussion; depression, anxiety, and panic disorders using the Patient Health Questionnaire (PHQ); and substance use using the Alcohol Use Disorders Identification Test (AUDIT) (alcohol) and Cannabis Use Disorders Identification Test-Revised (CUDIT) (cannabis). Regression models were used to examine the association between concussion history and substance use. Mood disorders were entered into the model as mediators and gender as a moderator variable. Those with a history of concussion had higher panic, AUDIT, and CUDIT scores than those with no history of concussion, and AUDIT and CUDIT scores showed an interaction between concussion history and gender. The regression models revealed significant direct and indirect (via depression and panic disorder) effects of concussion history on alcohol and cannabis use, which was moderated by gender. Concussion can have long-term psychological consequences and appears to affect both mood and substance use. The results presented demonstrate that the relationship between concussion and substance use is complex with mood disorder mediating the effect.

ObjectivesTo gather the perspectives of collegiate instructors regarding how concussion is managed within the college classroom. To introduce the themes surrounding collegiate return-to-learn (RTL) and the classroom management of students with concussion.DesignQualitative grounded theory.SettingLarge, public university in the Midwest.ParticipantsTwenty-three college instructors participated in a private, semistructured, audio-recorded, one-on-one interview. Participants included 12 males and 11 females. Interview recordings were transcribed verbatim, followed by an iterative process of open-coding and axial-coding, performed by two researchers.ResultsThree themes emerged from the coded data: (1) awareness—external knowledge of concussion and previous experiences, (2) legitimacy—medical note provided and no note provided and (3) accommodating the student—instructor’s role and feasibility of the accommodation. Psychosocial factors such as small class sizes, graduate-level students and an instructor’s empathy appeared to influence an instructor’s decision making when accommodating a student recovering from concussion.ConclusionThese novel data provide foundational evidence regarding how college instructors perceive and subsequently manage concussion within the classroom, while also offering accuracy to aims of subsequent collegiate RTL investigationsArticle summaryRTL is an emerging field within concussion management, yet is grossly underexplored within the college setting. By utilising a grounded theory approach, this article introduces the themes that dictate the landscape of RTL for a college student.

Importance Symptom-based methods of concussion diagnosis in contact sports result in underdiagnosis and repeated head injury exposure, increasing the risk of long-term disability. Measures of neuro-ophthalmologic (NO) function have the potential to serve as objective aids, but their diagnostic utility is unknown. Objective To identify NO measures that accurately differentiate athletes with and without concussion. Design, setting, and participants This cohort study was conducted among athletes with and without concussion who were aged 17 to 22 years between 2016 and 2017. Eye movements and cognitive function were measured a median of 19 days after injury among patients who had an injury meeting the study definition of concussion while playing a sport (retrospectively selected from a concussion clinic), then compared with a control group of participants without concussion (enrolled from 104 noncontact collegiate athlete volunteers without prior head injury). Data analysis was conducted from November 2019 through May 2020. Exposure Concussion. Main outcomes and measures Classification accuracy of clinically important discriminator eye-tracking (ET) metrics. Participants' eye movements were evaluated with a 12-minute ET procedure, yielding 42 metrics related to smooth pursuit eye movement (SPEM), saccades, dynamic visual acuity, and reaction time. Clinically important discriminator metrics were defined as those with significantly different group differences and area under the receiver operator characteristic curves (AUROCs) of at least 0.70. Results A total of 34 participants with concussions (mean [SD] age, 19.7 [2.4] years; 20 [63%] men) and 54 participants without concussions (mean [SD] age, 20.8 [2.2] years; 31 [57%] men) completed the study. Six ET metrics (ie, simple reaction time, discriminate reaction time, discriminate visual reaction speed, choice visual reaction speed, and reaction time on 2 measures of dynamic visual acuity 2) were found to be clinically important; all were measures of reaction time, and none were related to SPEM. Combined, these 6 metrics had an AUROC of 0.90 (95% CI, 0.80-0.99), a sensitivity of 77.8%, and a specificity of 92.6%. The 6 metrics remained significant on sensitivity testing. Conclusions and relevance In this study, ET measures of slowed visual reaction time had high classification accuracy for concussion. Accurate, objective measures of NO function have the potential to improve concussion recognition and reduce the disability associated with underdiagnosis.

While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.

Objective: To test our hypothesis that individuals with ADHD would exhibit reduced resiliency to subconcussive head impacts induced by ten soccer headings. Method: We conducted a case-control intervention study in 51 adults (20.6 ± 1.7 years old). Cognitive assessment, using ImPACT, and plasma levels of neurofilament-light (NF-L), Tau, glial-fibrillary-acidic protein (GFAP), and ubiquitin-C-terminal hydrolase-L1 (UCH-L1) were measured. Results: Ten controlled soccer headings demonstrated ADHD-specific transient declines in verbal memory function. Ten headings also blunted learning effects in visual memory function in the ADHD group while the non-ADHD counterparts improved both verbal and visual memory functions even after ten headings. Blood biomarker levels of the ADHD group were sensitive to the stress induced by ten headings, where plasma GFAP and UCH-L1 levels acutely increased after 10 headings. Variance in ADHD-specific verbal memory decline was correlated with increased levels of plasma GFAP in the ADHD group. Conclusions: These data suggest that ADHD may reduce brain tolerance to repetitive subconcussive head impacts.

INTRODUCTION Repetitive subconcussive head impacts in contact/collision sports such as in US football are believed to contribute to long-term brain changes and chronic symptoms. However, the lack of tools to measure the effects of repeated subconcussion limits our understanding of potential contributions to neuropathological alterations including cellular damage. METHODS We examined subconcussive head impacts using an accelerometer-embedded mouthguard on changes in blood levels of neurofilament light (NFL) chain in 18 Division I college football players. Plasma levels of NFL and clinical symptoms were assessed at pre-post practices. The frequency and linear and rotational head accelerations recorded via the mouthguard were examined in relation to NFL plasma changes. RESULTS The frequency and magnitude of head impacts associated with increased NFL levels. The greater numbers of hits and head accelerations associated with greater pre- to post-practice NFL level increases (p

While awareness and understanding of concussion have improved drastically, post-concussion management in academic settings is still at its infancy. The aim of the study was to examine to what extent concussion influences academic performance and to whether there would be a difference in concussion effects on academic performance between high school and college students. This cross-sectional survey study included students, who were between 14 and 24 years old and sustained a sport-related concussion within the previous year. The study used a modified chain-referral sampling method, by distributing a questionnaire link to 3,000 randomly stratified athletic trainers, who worked in high school or college settings. These athletic trainers were then asked to forward the questionnaire link to students in their team, who have sustained a concussion within the previous year. The questionnaire recorded responses regarding demographics (age, sex, race/ethnicity, number of previous concussions); 22 concussion-related symptoms in a binary scale (presence/absence); perception of difficulties in math, reading, writing, computer use, and attention in a 5-point Likert scale; and asymptomatic duration of academic engagement in a 7-point Likert scale. There were 130 respondents with a history of concussion in the past year (n = 59 high school, n = 71 college). While recovering from concussion, significantly more college students (84.5%) reported “difficulty concentrating” than high school students (68.6%: p = 0.049). High -school students experienced more difficulty with math than college students (p = 0.002), whereas college students experienced more difficulty with reading (p = 0.013) and computer use (p = 0.026) than high school students. Asymptomatic duration of cognitive activity was influenced by age (p = 0.0004), where younger students were less tolerant in performing academic tasks after a concussion than older students. Our data indicate that concussions can induce negative symptoms in the academic setting regardless of age. The post-concussion difficulties in academic performance may be a grade-dependent manner, where concussions triggered difficulty in math among high school students and in reading and computer use among college students. It is clear that there is a need for guidelines and accommodations to support students with concussion in academic settings, and the guideline should reflect the age-dependent response to concussions.

The current study investigates whether repetitive subconcussive impacts cause changes in plasma S100β levels, and also tests the associations between S100β changes and frequency/magnitude of impacts sustained. This prospective study of 22 Division-I collegiate football players included baseline and pre-season practices (one helmet-only and four full-gear). Blood samples were obtained and assessed for S100β levels at baseline and pre- to post-practices; symptom scores were assessed at each time-point. An accelerometer-embedded mouthguard was employed to measure the number of impacts (hits), peak linear acceleration (PLA), and peak rotational acceleration (PRA). Because we observed a distinct gap in impact exposure (hits, PLA, and PRA), players were clustered into lower (n = 7) or higher (n = 15) impact groups based on the sum of impact kinematics from all five practices. S100β levels significantly changed across the study duration. Although S100β levels remained stable from baseline to all pre-practice values, statistically significant acute increases in S100β levels were observed in all post-practice measures compared with the respective pre-practice values (range: 133-246% in the overall sample). Greater number of hits, sum of PLA, and sum of PRA were significantly associated with greater acute increases in S100β levels. There were significant differences in head impact kinematics between lower and higher impact groups (hits, 6 vs. 43 [M

Subconcussive head impacts (SHI), defined as impacts to the cranium that do not result in concussion symptoms, are gaining traction as a major public health concern. The contribution of physiological factors such as physical exertion and muscle damage to SHI-dependent changes in neurological measures remains unknown. A prospective longitudinal study examined the association between physiological factors and SHI kinematics in 15 high school American football players over one season. Players wore a sensor-installed mouthguard for all practices and games, recording frequency and magnitude of all head impacts. Serum samples were collected at 12 time points (pre-season, pre- and post-game for five in-season games, and post-season) and were assessed for an isoenzyme of creatine kinase (CK-MM) primarily found in skeletal muscle. Physical exertion was estimated in the form of excess post-exercise oxygen consumption (EPOC) from heart rate data captured during the five games. Mixed-effect regression models indicated that head impact kinematics were significantly and positively associated with change in CK-MM but not EPOC. There was a significant and positive association between CK-MM and EPOC. These data suggest that when examining SHI, effects of skeletal muscle damage should be considered when using outcome measures that may have an interaction with muscle damage.

Aim: Students re-entering the academic setting after a concussion is commonly referred to as return-to-learn and, to date, very few studies have examined the return-to-learn aspect of concussion recovery. Methodology: Nine college-aged, full-time students who were diagnosed with concussions were monitored throughout their concussion recovery. The severity for five chief symptoms (headache, dizziness, difficulty concentrating, fatigue, anxiety) were recorded six-times per day through text messages, and daily phone calls recorded participant's behavioral traits. Results: We identified five behavioral variables which significantly influenced symptom resolution (music, sleep, physical activity, water and time) (p = 0.0004 to p = 0.036). Additionally, subjects reported math and computer-oriented courses as the most difficult (33 and 44%, respectively). Conclusion: We introduce a novel approach to monitor concussed students throughout their recovery, as well as factors that may influence concussion recovery process., Lay abstract Concussed students and student-athletes returning to the classroom is commonly referred as return-to-learn. To date, there are very few recommendations that can aid students’ concussion recovery in relation to their academic responsibilities. This is trouble giving that every student-athlete is first and foremost a ‘student’. In light of this, we sought to track behavioral factors that might influence the resolution of college students’ concussion symptoms as they recover from their injury and return to their coursework. Students also gave a perception of their recovery, including what types of activities and school accommodations appeared beneficial. In turn, behaviors such as minimizing music, getting more sleep, introducing more physical activity, drinking more water and overall time since injury appeared to help resolving the concussion symptoms. Additionally, students reported that math and computer-oriented courses were the most difficult, and that additional time on assignments/exams and reducing screen brightness were the most beneficial accommodations. These results are the first of their kind and will optimistically lead to recommendations utilized by healthcare professionals.

Astrocyte-enriched marker, S100B, shows promise for gauging the severity of acute brain trauma, and understanding subconcussive effects will advance its utility in tracking real-time acute brain damage. The aim of the study was to investigate whether serum S100B elevations were associated with frequency and magnitude of subconcussive head impacts in adolescents. This prospective cohort study of 17 high-school football players consisted of the following 12 time points: pre-season baseline, 5 in-season pre-post games, and post-season. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA) and peak rotational (PRA) head accelerations from every practice and game. During the 5 games, players wore chest-strap heart-rate monitors to estimate players' excess post-exercise oxygen consumption (EPOC), accounting for physical exertion effects. At each time point, blood samples were obtained and assessed for S100B and creatine kinase levels to account for astrocyte damage/activation and muscle damage, respectively. Using k-means clustering on the impact data, players were categorized into high- or low-impact group. Two players withdrew during the first month of the study. A total of 156 blood samples from 15 players were assessed for S100B and creatine kinase levels and included in the analysis. A median value of 596 head impacts from 15 players were recorded during all practices and games in a season. S100B levels were significantly elevated in all post-game measures compared with the respective pre-game values (median-increase, 0.022 μg/L; interquartile-range, 0.011–0.043 μg/L, p < 0.05 for all games). Greater acute S100B increases were significantly associated with greater impact frequency, sum of PLA and PRA, with negligible contributions from physical exertion and muscle damage effects. The high-impact group exhibited greater increases in serum S100B levels at post-games than the low-impact group (high vs. low, 0.043 ± 0.035 μg/L vs. 0.019 ± 0.017 μg/L, p = 0.002). The degree of acute S100B increases was correlated with subconcussive head impact exposure, suggesting that acute astrocyte damage may be induced in an impact-dependent manner. Acute changes in serum S100B levels may become a useful tool in monitoring real-time brain damage in sports.

Background: A concussion is a complex pathophysiologic process that is induced by biomechanical forces and affects the brain. Cervical injuries and concussion can share similar mechanisms and nearly identical symptoms or causes. Therefore, symptoms or causes alone may be insufficient to differentiate between patients with a concussion and patients with cervical injuries. Objective: To demonstrate the homogeneous causes and symptoms observed in patients with a concussion and patients with cervical injury and to provide information on clinical tests that can differentiate cervical injury from pathologic conditions of vestibular or central origin. Summary: Given that concussion and cervical injury share similar causes and symptoms, this information alone may be insufficient to diagnose a concussion. Clinical assessments, such as the cervical joint-reposition error test, smooth-pursuit neck-torsion test, head-neck differentiation test, cervical flexion-rotation test, and physical examination of the cervical spine, can be performed after a head and neck pathomechanical event to identify the presence of cervical injury. Differentiating between a concussion and cervical injury is clinically vital for timely and appropriate evidence-based treatment. Conclusions: Specific clinical tests should be used after a head and neck pathomechanical event to differentiate between symptoms due to a concussion and cervical injury. Continued research on the clinical utility of the 5 identified cervicogenic tests is also recommended.

Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury.

Subconcussive head impacts, defined as impacts to the cranium that do not result in clinical symptoms of concussion, are gaining traction as a major public health concern. Researchers begin to suggest subconcussive impact-dependent changes in various neurological measures. However, a contribution of physiological factors such as physical exertion and muscle damage has never been accounted. We conducted a prospective longitudinal study during a high school American football season to examine the association between physiological factors and subconcussive head impact kinematics. Fifteen high-school American football players volunteered in the study. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA:g) and peak rotational (PRA: rad/s2) head accelerations from every practice and game. Serum samples were collected at 12 time points (pre-season baseline, five in-season pre-post games, and post-season) and assessed for the creatine kinase skeletal muscle-specific isoenzyme (CK-MM), as a surrogate for skeletal muscle damage. Physical exertion was estimated in the form of excess post-exercise oxygen consumption (EPOC) from heart rate data captured during five games via a wireless heart rate monitor. A total of 9,700 hits, 214,492g, and 19,885,037 rad/s2were recorded from 15 players across the study period. Mixed-effect regression models indicated that head impact kinematics (frequency, PLA, and PRA) were significantly and positively associated with CK-MM increase, but not with EPOC. There was a significant and positive association between CK-MM and EPOC. These data suggest that skeletal muscle damage effects should be considered when using outcome measures that may have an interaction with muscle damage, including inflammatory biomarkers and vestibular/balance tests.

The purpose of the study was to examine an association of repetitive subconcussive head impacts with changes in plasma neurofilament light (NF-L) levels following 10 bouts of controlled soccer heading. In this randomized control trial, 37 healthy adult soccer players were randomly assigned into either a heading (n = 19) or kicking-control group (n = 18). The heading group executed 10 headers with soccer balls projected at a velocity of 25 mph over 10 min. Plasma samples were obtained at pre-heading baseline, 0 h, 2 h, and 24 h post-heading. The kicking-control group followed the same protocol with 10 kicks. Plasma NF-L was measured using ultrasensitive single-molecule array technology. Data from 34 subjects were eligible for analysis (heading n = 18 and kicking n = 16). Ten subconcussive head impacts induced a gradual increase in plasma NF-L expression for the heading group (β = 0.0297, standard error [SE] = 0.01, p = 0.0049), whereas there was no significant time effect for the kicking-control group. A follow-up analysis revealed that a significant difference appeared at 24 h post-heading (3.68 ± 0.30 pg/mL) compared with pre-heading (3.12 ± 0.29 pg/mL, p = 0.0013; Cohen's d = 1.898). At the 24 h post-heading time-point, the plasma NF-L level for the heading group was significantly higher than that of the kicking-control group with an estimated mean difference of 0.66 pg/mL (SE = 0.22, p = 0.0025). The data suggest that the increased level of plasma NF-L was driven by repetitive subconcussive head impacts and required longer than 2 h after the head impacts for the increase to be detected. Plasma NF-L levels may serve as an objective marker to monitor acute axonal burden from subconcussive head impacts.

The purpose of the study was to test the utility of unique panel of blood biomarkers as a means to reflect one’s recovery process after sport-related neurotrauma. We established a panel of biomarkers that reacted positive with CD81 (extracellular vesicle marker) and various neuron- and glia-specific antigens [e.g., neurofilament light polypeptide (NF-L), tau, synaptosome-associated protein 25 (SNAP25), glial fibrillary acidic protein, and myelin basic protein]. We first evaluated test–retest reliabilities of brain-derived exosome markers, followed by an application of these markers in eight professional ice hockey players to detect cumulative neuronal burden from a single ice hockey season. During the season, two players were diagnosed with concussions by team physician based on an exhibition of symptoms as well as abnormality in balance and ocular motor testing. One player reached symptom-free status 7 days after the concussion, while the other player required 36 days for symptoms to completely resolve. Blood samples and clinical assessments including balance error scoring system and near point of convergence throughout recovery process were obtained. Biomarkers indicative of axonal damage, neuronal inflammation, and glial activation showed excellent test–retest reliabilities (intraclass correlation coefficient: 0.713–0.998, p’s

Sports-related traumatic brain injuries (TBIs) range in severity from severe to subconcussive. Although technologies exist for clinical diagnosis of more severe injuries, methods for diagnosis of milder forms of brain injury are limited. Developing objective measures to indicate pathogenic processes after a suspected mild TBI is challenging for multiple reasons. The field of biomarker discovery for diagnosing TBI continues to expand, with newly identified candidate biomarkers being reported regularly. Brain-specific biomarkers include proteins derived from neurons and glia, and are often measured to assess neural injury and repair, and to predict outcomes. Ideally, changes in biomarker levels should indicate pathologic events and answer critical questions for accurate diagnosis and prognosis. For example, does the presence or a change in the biomarker level suggest greater vulnerability for sustaining a second concussion or show that the window of increased vulnerability has passed? Likewise, do changes in biomarker levels predict postconcussion syndrome or recovery/repair? Although there are numerous promising candidates for fluid biomarkers that may diagnose mild TBI or concussion, none has reached the clinic to date. In this chapter, we will define biomarkers, discuss the importance of understanding their normal and pathologic functions, and outline some considerations for interpreting detection assay results in TBI. We will then review five proposed blood and cerebrospinal fluid biomarkers (tau, neurofilament, ubiquitin carboxyl-terminal hydrolase L1, S100β, and glial fibrillary acidic protein) used currently to address TBI. Lastly, we will discuss a future trajectory for developing new, clinically useful fluid biomarkers.

ObjectiveInvestigate the potential factors influencing resolution of chief concussion symptoms in a longitudinal design. Second, assess subjects’ perception of their concussion recovery and what types of activities and accommodations appeared beneficial.BackgroundAthletes re-entering the academic setting after a concussion is commonly referred as return-to-learn (RTL), which has appeared secondary to the abundantly researched return-to-play protocols implemented ubiquitously. Importantly, every concussed collegiate, adolescent, and pediatric athlete is first and foremost a student-athlete, with “student” holding the emphasis. To date, very few studies have examined the RTL aspect of concussion recovery, and the effects premature classroom attendance may cause.Design/MethodsNine concussed, college aged (18-26 years), full-time students were monitored longitudinally throughout their recovery from diagnosis to full symptom-free academic participation. Symptom severity for five prevalent symptoms were recorded 4 times per day, along with a daily phone call to report participant’s diet, duration of screen-time usage and music listened to, physical activity participation, and types of classes attended.ResultsResponse rates to text messages and phone calls yielded a mean 92% and 93% respectively across the nine subjects. Additionally, five variables were significantly associated with symptom resolution (music, sleep, physical activity, water, and time) (p = 0.0004 to p = 0.036). Lastly, subjects reported math and computer-oriented courses as the most difficult (33% and 44% respectively). Additional time on assignments/exams and reducing screen brightness were the most beneficial accommodations (66% and 56% respectively).ConclusionsOur findings introduce a novel and robust approach to monitoring concussed students throughout their recovery. Furthermore, this methodology is the first to produce holistic evidence-based results concerning re-integrating students to the classroom. Lastly, it appears that dietary and social behaviors can indeed influence symptom resolution.

ObjectiveThe purpose of this investigation was to examine the relationships between subconcussive head impact frequency and magnitude and measures of physical exertion and muscle damage.BackgroundSubconcussive head impacts, or impacts that do not present with concussion symptoms, are gaining traction as a major public health concern. However, there is a gap in knowledge about the contribution of physiological variables, such as muscle damage and physical exertion, to neurological measures used to assess subconcussive impact-dependent changes. The unknown contribution of physical exertion and strenuous exercise is often listed as a limitation in field studies of subconcussive head impacts.Design/MethodsFifteen high school football players wore mouthguards installed with triaxial accelerometers and gyroscopes in order to quantify the linear and rotational accelerations of every head impact sustained throughout one season (practices and games). Additionally, serum samples were collected at twelve time points (pre-season, pre- and post-competition for five in-season games, and post-season) and assayed for CK-MM, the skeletal muscle-specific isoenzyme of creatine kinase. Subjects wore heart rate monitors during the five games, and heart rate data were used to estimate physical exertion in terms of excess post-exercise oxygen consumption (EPOC).ResultsMixed-effect regression modeling (MRM) showed significant and positive associations between CK-MM and subconcussive head impact kinematic variables, in addition to a significant and positive association between CK-MM and EPOC. The models were adjusted for cumulative head impact exposures up to each game and the pre-season serum CK-MM levels, when applicable.ConclusionsWhen investigating subconcussive head impacts, the effects of muscle damage should be considered when using correlated outcome measures, such as inflammatory biomarkers and vestibular assessments.

ObjectiveThe purpose of this study was to determine the subconcussive head impacts (SHI) effects on neurocognitive function in individuals diagnosed with attention-deficit/hyperactivity disorder (ADHD).BackgroundAthletes diagnosed with ADHD have a heightened risk (2 to 4-fold) for sustaining concussion. However, their response to repetitive SHI remain unclear.Design/MethodsIn this case-control intervention study, 17 soccer players clinically diagnosed with ADHD who take their prescribed medication daily, were assigned a heading intervention (ADHD-Heading group),individuals who met the ADHD criteria but were non-soccer players, were assigned into a kicking group, (ADHD-Kicking group, n = 15). Whereas 34 soccer players without ADHD diagnosis were randomized into either a heading or kicking intervention, yielding Non-ADHD-Heading group (n = 17) or Non-ADHD-Kicking group (n = 17). To implement SHI, the heading groups executed 10 headers with a standard soccer ball projected at a velocity of 25 mph (equivalent to a long throw-in) over 10 minutes by a JUGS soccer machine, while the kicking groups performed 10 kicks. Neurocognitive function was measured via the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) at pre-intervention baseline, 0h, 2h, and 24h post-intervention.ResultsThe vulnerability to SHI was notable in subjects diagnosed with ADHD particularly in memory, as illustrated by a significant group × time interaction, F(6,96) = 3.796, p = 0.002. Both Kicking groups improved verbal memory over time indicating the brain’s ability to learn, whereas the Non-ADHD-Heading group showed no improvement. The ADHD-Heading group showed a significant decline at 0h and 2h post-heading compared to other groups. As for visual memory, the ADHD-Heading group showed a significant decline at 24h post; however, all other groups displayed improvement. There were no group differences in remaining domains.ConclusionsData suggests neurocognitive vulnerability in athletes diagnosed with ADHD after experiencing SHI, specifically in memory performance. These outcomes can better inform clinicians; overall, promoting a better personalized care in athletes diagnosed with ADHD.