Altered Blood Biomarker Profiles in Athletes with a History of Repetitive Head Impacts.
ABSTRACT: The long-term health effects of concussion and sub-concussive impacts in sport are unknown. Growing evidence suggests both inflammation and neurodegeneration are pivotal to secondary injury processes and the etiology of neurodegenerative diseases. In the present study we characterized circulating brain injury and inflammatory mediators in healthy male and female athletes according to concussion history and collision sport participation. Eighty-seven university level athletes (male, n = 60; female, n = 27) were recruited before the start of the competitive season. Athletes were healthy at the time of the study (no medications, illness, concussion or musculoskeletal injuries). Dependent variables included 29 inflammatory and 10 neurological injury analytes assessed in the peripheral blood by immunoassay. Biomarkers were statistically evaluated using partial least squares multivariate analysis to identify possible relationships to self-reported previous concussion history, number of previous concussions and collision sport participation in male and female athletes. Multiple concussions were associated with increases in peripheral MCP-1 in females, and MCP-4 in males. Collision sport participation was associated with increases in tau levels in males. These results are consistent with previous experimental and clinical findings that suggest ongoing inflammatory and cerebral injury processes after repetitive mild head trauma. However, further validation is needed to correlate systemic biomarkers to repetitive brain impacts, as opposed to the extracranial effects common to an athletic population such as exercise and muscle damage.
Project description:Studies have indicated that concussive and sub-concussive brain injuries that are frequent during collision sports may lead to long-term neurological abnormalities, however there is a knowledge gap on how biological sex modifies outcomes. Blood-based biomarkers can help to identify the molecular pathology induced by brain injuries and to better understand how biological sex affects the molecular changes. We therefore analyzed serum protein biomarkers in male (n = 50) and female (n = 33) amateur Australian rules footballers (i.e., Australia's most participated collision sport), both with a history of concussion (HoC) and without a history of concussion (NoHoC). These profiles were compared to those of age-matched control male (n = 24) and female (n = 20) athletes with no history of neurotrauma or participation in collision sports. Serum levels of protein markers indicative of neuronal, axonal and glial injury (UCH-L1, NfL, tau, p-tau, GFAP, BLBP, PEA15), metabolic (4-HNE) and vascular changes (VEGF-A, vWF, CLDN5), and inflammation (HMGB1) were assessed using reverse phase protein microarrays. Male, but not female, footballers had increased serum levels of VEGF-A compared to controls regardless of concussion history. In addition, only male footballers who had HoC had increased serum levels of 4-HNE. These findings being restricted to males may be related to shorter collision sport career lengths for females compared to males. In summary, these findings show that male Australian rules footballers have elevated levels of serum biomarkers indicative of vascular abnormalities (VEGF-A) and oxidative stress (4-HNE) in comparison to non-collision control athletes. While future studies are required to determine how these findings relate to neurological function, serum levels of VEGF-A and 4-HNE may be useful to monitor subclinical neurological injury in males participating in collision sports.
Project description:OBJECTIVE/BACKGROUND:Poor quality and inadequate sleep are associated with impaired cognitive, motor, and behavioral components of sport performance and increased injury risk. While prior work identifies sports-related concussions as predisposing factors for poor sleep, the role of sleep as a sports-related concussion risk factor is unknown. The purpose of this study was to quantify the effect of poor sleep quality and insomnia symptoms on future sports-related concussion risk. PATIENTS/METHODS:In this study, 190 NCAA Division-1 athletes completed a survey battery, including the Insomnia Severity Index (ISI) and National Health and Nutrition Examination Survey (NHANES) Sleep module. Univariate risk ratios for future sports-related concussions were computed with ISI and NHANES sleepiness scores as independent predictors. An additional multiple logistic regression model including sport, sports-related concussion history, and significant univariate predictors jointly assessed the odds of sustaining a concussion. RESULTS:Clinically moderate-to-severe insomnia severity (RR = 3.13, 95% CI: 1.320-7.424, p = 0.015) and excessive daytime sleepiness two or more times per month (RR = 2.856, 95% CI: 0.681-11.977, p = 0.037) increased concussion risk. These variables remained significant and comparable in magnitude in a multivariate model adjusted for sport participation. CONCLUSION:Insomnia and daytime sleepiness are independently associated with increased sports-related concussion risk. More completely identifying bidirectional relationships between concussions and sleep requires further research. Clinicians and athletes should be cognizant of this relationship and take proactive measures - including assessing and treating sleep-disordered breathing, limiting insomnia risk factors, improving sleep hygiene, and developing daytime sleepiness management strategies - to reduce sports-related concussion risk and support overall athletic performance.
Project description:BACKGROUND:Sport participation has many physical and psychosocial benefits, but there is also an inherent risk of injury, subsequent osteoarthritis and psychological challenges that can negatively impact quality of life (QOL). Considering the multifaceted impacts of sport participation on QOL across the lifespan, there is a need to consolidate and present the evidence on QOL in former sport participants. OBJECTIVE:To evaluate QOL and life satisfaction in former sport participants, and determine what factors are associated with QOL and life satisfaction in this population. METHODS:Eight electronic databases were systematically searched in July 2018 to retrieve all articles that evaluated QOL or life satisfaction in former sport participants. Two authors independently screened titles/abstracts and full texts, extracted data, and appraised methodological quality using a modified Downs and Black Checklist. Random-effects meta-analysis estimated pooled mean and 95% confidence intervals (Cis) for Mental Component Scores (MCS) and Physical Component Scores (PCS) derived from the SF-12, SF-36, VR-12 and VR-36 measures. MCS and PCS were pooled for all former sport participants, as well as professional- and collegiate-athlete subgroups. Data that were inappropriate for meta-analysis (i.e. EQ-5D, PROMIS and life-satisfaction outcomes) were collated and reported descriptively. RESULTS:Seventeen articles evaluated QOL or life satisfaction in a total of 6692 former athletes [eight studies (n?=?4255) former professional athletes; six studies (n?=?1946) former collegiate athletes; two studies (n?=?491) included both] with a mean age ranging from 21 to 66 years. Most studies were cross-sectional (15 of 17 articles) and 12 studies had a moderate risk of bias (n?=?1 high-risk, n?=?4 low-risk). Unpublished data were provided for five studies. Meta-analysis of seven studies resulted in a pooled PCS mean (95% CI) of 50.0 (46.6-53.3) [former professional athletes from two studies: 46.7 (42.1-51.2), former collegiate athletes from five studies: 51.2 (48.4-53.9)] and a pooled MCS of 51.4 (50.5-52.2) [former professional athletes: 52.7 (51.3-54.2), former collegiate athletes: 50.9 (50.0-51.8)]. Factors associated with worse QOL or life satisfaction in former athletes included involuntary retirement from sport (three studies), collision/high-contact sport compared with low/no-contact sport (three studies), three or more concussions compared with no/fewer concussions (two studies), increased body mass index (BMI) (worse PCS, three studies), and osteoarthritis or musculoskeletal issues (worse PCS and MCS, three studies; worse PCS but not MCS, two studies). CONCLUSIONS:Former athletes had similar PCS and better MCS, compared to general-population norms. Former athletes with impaired PCS reported better MCS than population norms, highlighting the need to use an instrument that differentiates between physical and mental components of QOL in former sport participants. Factors associated with worse QOL that may explain between-study variation include involuntary retirement, collision/high contact sports, concussion, BMI and osteoarthritis. PROSPERO:CRD42018104319.
Project description:Background: There is heterogeneity in neurosensory alterations following mild traumatic brain injury. Commonly assessed neurosensory symptoms following head injury include symptom reports and measures of oculomotor impairment, auditory changes, and vestibular impairment. Hypothesis/Purpose: Neurosensory alterations are prevalent acutely following mild traumatic brain injury secondary to blunt head trauma during collegiate varsity sports and may vary by sex and sport. Study Design: Retrospective study of a large collegiate athletic database. Methods: Analyses were performed using an established single University dataset of 177 male and female collegiate varsity athletes who were diagnosed with concussion/mild traumatic brain injury between September 2013 and October 2019. Descriptive and comparative analyses were performed on individual and grouped acute concussion assessments pertaining to neurosensory alterations obtained within 72 h of injury using components of the Sports Concussion Assessment Tool Version 5 and Vestibular/Ocular-Motor Screening. Results: Females had significantly more abnormal smooth pursuit (p-value: 0.045), convergence (p-value: 0.031), and visual motion sensitivity tests results (p-value: 0.023) than males. There were no differences in neurosensory alterations when grouped by overall auditory, vestibular, or oculomotor impairments. The majority of sports-related concussions occurred during football (50, 28.25%), wrestling (21, 11.86%), water polo (15, 8.47%), and basketball (14, 7.91%). Abnormal vestibular assessments were high in these top four sports categories, but statistically significant differences in overall auditory, vestibular, or oculomotor impairments were not reached by individual sport. However, water polo players had higher abnormal individual assessments related to balance reports on the sideline (60.00%, p-value: 0.045) and in the clinic setting (57.14%, p-value: 0.038) as compared to all other sports. Conclusion: While neurosensory alterations are prevalent in both male and female athletes acutely post-concussion, females have a higher incidence of abnormalities in smooth pursuit, convergence, and visual motion sensitivity and may benefit from early rehabilitation.
Project description:Concussions have been associated with elevated musculoskeletal injury risk; however, the influence of unreported and unrecognized concussions has not been investigated.The purpose of this study was to examine the association between concussion and lower extremity musculoskeletal injury rates across a diverse array of sports among collegiate student-athletes at the conclusion of their athletic career. The hypothesis was that there will be a positive association between athletes who reported a history of concussions and higher rates of lower extremity injuries.Cross-sectional study.Level 3.Student-athletes (N = 335; 62.1% women; mean age, 21.2 ± 1.4 years) from 13 sports completed a reliable injury history questionnaire. Respondents indicated the total number of reported, unreported, and potentially unrecognized concussions as well as lower extremity injuries including ankle sprains, knee injuries, and muscle strains. Chi-square analyses were performed to identify the association between concussion and lower extremity injuries.There were significant associations between concussion and lateral ankle sprain ( P = 0.012), knee injury ( P = 0.002), and lower extremity muscle strain ( P = 0.031). There were also significant associations between reported concussions and knee injury ( P = 0.003), unreported concussions and knee injury ( P = 0.002), and unrecognized concussions and lateral ankle sprain ( P = 0.001) and lower extremity muscle strains ( P = 0.006), with odds ratios ranging from 1.6 to 2.9.There was a positive association between concussion history and lower extremity injuries (odds ratios, 1.6-2.9 elevated risk) among student-athletes at the conclusion of their intercollegiate athletic careers.Clinicians should be aware of these elevated risks when making return-to-participation decisions and should incorporate injury prevention protocols.
Project description:OBJECTIVE:To examine the association between meeting physical activity (PA) volume recommendations and concussion rates in male ice hockey players aged 11-17 years. DESIGN:Pooled prospective injury surveillance cohort data from the 2011-2012, 2013-2014 and 2014-2015 youth ice hockey seasons. PARTICIPANTS:Male Alberta-based Pee Wee (aged 11-12?years), Bantam (aged 13-14?years) and Midget (aged 15-17?years) ice hockey players participating in any of the three cohorts were eligible (n=1726). A total of 1208 players were included after the exclusion criteria were applied (ie, players with new/unhealed injuries within 6?weeks of study entry, missing 6-week PA history questionnaires, missing game and/or practice participation exposure hours, players who sustained concussions when no participation exposure hours were collected). OUTCOME MEASURES:Dependent variable: medically diagnosed concussion. Independent variable: whether or not players' self-reported history of PA (ie, hours of physical education and extracurricular sport participation) met the Canadian Society of Exercise Physiology and Public Health Agency of Canada recommendation of one hour daily during the 6?weeks prior to study entry (ie, 42?hours or more). RESULTS:The PA volume recommendations were met by 65.05% of players who subsequently sustained concussions, and 75.34% of players who did not sustain concussions. The concussion incidence rate ratios (IRR) reflect higher concussion rates in players who did not meet the PA volume recommendations vs. players who met the PA volume recommendations among Pee Wee players (IRR 2.94 95% CI 1.30 to 6.64), Bantam players (IRR 2.18, 95% CI 1.21 to 3.93) and non-elite players aged 11-14 years (IRR 2.45, 95% CI 1.33 to 4.51). CONCLUSION AND RELEVANCE:The concussion rate of players who did not meet the Canadian PA volume recommendations was more than twice the concussion rate of players who met recommendations among male Pee Wee players, Bantam players and non-elite level players. Further exploration of the impact of public health PA recommendations in a sport injury prevention context is warranted.
Project description:Concussions from sport present a substantial public health burden given the number of youth, adolescent and emerging adult athletes that participate in contact or collision sports. Athletes who fail to report symptoms of a suspected concussion and continue play are at risk of worsened symptomatology and potentially catastrophic neurologic consequences if another impact is sustained during this vulnerable period. Understanding why athletes do or do not report their symptoms is critical for developing efficacious strategies for risk reduction. Psychosocial theories and frameworks that explicitly incorporate context, as a source of expectations about the outcomes of reporting and as a source of behavioral reinforcement, are useful in framing this problem. The present study quantifies the pressure that athletes experience to continue playing after a head impact--from coaches, teammates, parents, and fans--and assesses how this pressure, both independently and as a system, is related to future concussion reporting intention. Participants in the study were 328 male and female athletes from 19 teams competing in one of seven sports (soccer, lacrosse, basketball, softball, baseball, volleyball, field hockey) at four colleges in the northeast region of the United States. Results found that more than one-quarter of the sample had experienced pressure from at least one source to continue playing after a head impact during the previous year. Results of a latent profile mixture model indicated that athletes who experienced pressure from all four of the measured sources were significantly more likely to intend to continue playing in the future than were athletes who had not experienced pressure from all sources, or only pressure from coaches and teammates. These findings underscore the importance of designing interventions that address the system in which athletes make decisions about concussion reporting, including athletes' parents, rather than focusing solely on modifying the individual's reporting cognitions.
Project description:Despite the widespread awareness of concussion across all levels of sport, the management of concussion from youth to college is inconsistent and fragmented. A fundamental gap contributing to inconsistent care is the lack of a scalable, systematic approach to document initial injury characteristics following concussion. The purpose of this study was to determine differences in injury profiles and management of youth, high school, and college athletes using a mobile application for incident report documentation.A cohort study was conducted in which concussion electronic incident report data from 46 high schools and colleges, and Cleveland Clinic ambulatory concussion clinics were gathered and analyzed.In sum, 1421 (N?=?88 youth, N?=?1171 high school and N?=?162 college) athletes with sport-related concussions were included.Despite the relative absence of red flags, youth athletes had a greater probability of being sent to the emergency department than high school and collegiate athletes. Over 60% of athletes were removed from play immediately post-injury. Injury recognition was delayed in 25% of athletes due to delayed symptom reporting (20% of males, 16% of females) or delayed symptom onset (5% of males, 9% of females). A significantly greater incidence of red flags was evident in males, and in high school and collegiate athletes compared to youth athletes.The high frequency of youth athletes sent to the emergency department, despite the absence of red flags, may be a reflection of inadequate medical coverage at youth events, ultimately resulting in unnecessary utilization of emergency medicine services. The relatively high incidence of delayed injury reporting implies that additional educational efforts targeting student-athletes and the utilization of resources to improve injury detection are warranted. The systematic collection of injury-related demographics through the electronic mobile application facilitated interdisciplinary communication and improved the efficiency of managing athletes with concussion.
Project description:BACKGROUND:Inflammation appears to be an important component of concussion pathophysiology. However, its relationship to symptom burden is unclear. Therefore, the purpose of this study was to evaluate the relationship between symptoms and inflammatory biomarkers measured in the blood of male and female athletes following a sport-related concussion (SRC). RESULTS:Forty athletes (n =?20 male, n?=?20 female) from nine interuniversity sport teams at a single institution provided blood samples within one week of an SRC. Twenty inflammatory biomarkers were quantitated by immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms. Partial least squares (PLS) analyses were used to evaluate the relationship(s) between biomarkers and symptoms. In males, a positive correlation between interferon (IFN)-? and symptom severity was observed following SRC. The relationship between IFN-? and symptoms was significant among all symptom clusters, with cognitive symptoms displaying the largest effect. In females, a significant negative relationship was observed between symptom severity and cytokines IFN-?, tumor necrosis factor (TNF)-?, and myeloperoxidase (MPO); a positive relationship was observed between symptom severity and MCP-4. Inflammatory mediators were significantly associated with all symptom clusters in females; the somatic symptom cluster displayed the largest effect. CONCLUSION:These results provide supportive evidence of a divergent relationship between inflammation and symptom burden in male and female athletes following SRC. Future investigations should be cognizant of the potentially sex-specific pathophysiology underlying symptom presentation.
Project description:OBJECTIVE:To evaluate sex differences in incidence rates (IRs) of anterior cruciate ligament (ACL) injury by sport type (collision, contact, limited contact, and noncontact). DATA SOURCES:A systematic review was performed using the electronic databases PubMed (1969-January 20, 2017) and EBSCOhost (CINAHL, SPORTDiscus; 1969-January 20, 2017) and the search terms anterior cruciate ligament AND injury AND (incidence OR prevalence OR epidemiology). STUDY SELECTION:Studies were included if they provided the number of ACL injuries and the number of athlete-exposures (AEs) by sex or enough information to allow the number of ACL injuries by sex to be calculated. Studies were excluded if they were analyses of previously reported data or were not written in English. DATA EXTRACTION:Data on sport classification, number of ACL injuries by sex, person-time in AEs for each sex, year of publication, sport, sport type, and level of play were extracted for analysis. DATA SYNTHESIS:We conducted IR and IR ratio (IRR) meta-analyses, weighted for study size and calculated. Female and male athletes had similar ACL injury IRs for the following sport types: collision (2.10/10?000 versus 1.12/10?000 AEs, IRR = 1.14, P = .63), limited contact (0.71/10?000 versus 0.29/10?000 AEs, IRR = 1.21, P = .77), and noncontact (0.36/10?000 versus 0.21/10?000 AEs, IRR = 1.49, P = .22) sports. For contact sports, female athletes had a greater risk of injury than male athletes did (1.88/10?000 versus 0.87/10?000 AEs, IRR = 3.00, P < .001). Gymnastics and obstacle-course races were outliers with respect to IR, so we created a sport category of fixed-object, high-impact rotational landing (HIRL). For this sport type, female athletes had a greater risk of ACL injury than male athletes did (4.80/10?000 versus 1.75/10?000 AEs, IRR = 5.51, P < .001), and the overall IRs of ACL injury were greater than all IRs in all other sport categories. CONCLUSIONS:Fixed-object HIRL sports had the highest IRs of ACL injury for both sexes. Female athletes were at greater risk of ACL injury than male athletes in contact and fixed-object HIRL sports.