Dataset Information

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome.

ABSTRACT: Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological processes and disease mechanisms. Such knowledge will help improve diagnosis, clinical management, and prognosis. Total-tau (t-tau) has recently emerged as a promising blood marker showing sex-associated differences in neurodegenerative diseases. Nonetheless, to date, little is known about the potential influence of sex on its injury-related concentration and dynamics after SRC. We hypothesized that measurements of circulating levels of t-tau over time would reflect a differential vulnerability signature, providing insights into the sex-related phenotypes and their relationship with clinical outcomes. To test this hypothesis, plasma levels of t-tau were measured using an ultrasensitive immunoassay up to 7 days after injury, in 46 concussed athletes (20 males, 26 females). We used trajectory analysis to generate two distinct temporal profiles of t-tau, which were then compared with gender and return to play (RTP). The majority of subjects (~63%) started with low t-tau concentrations that further declined within the first 48 h; while the remaining ("maximal decliners") started with concentrations comparable to the baseline levels that also fell over time, but persisting markedly higher compared with the first profile. The maximal decliner group was primarily composed of female subjects (p = 0.007) and was significantly associated with poor outcome (RTP ? 10 days after concussion) (p = 0.011). Taken together, our data provide evidence for the existence of sex-related biosignatures following sports-related concussions, possibly indicating a differential effect as a result of distinct brain vulnerability and inherent injury response. Future studies will be required to further elucidate underlying sex-based biological and pathophysiological mechanisms, and determine the value of t-tau signatures for management and therapeutic decision-making in sports-related concussions.

SUBMITTER: Mondello S

PROVIDER: S-EPMC7358531 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome.

Mondello Stefania S Guedes Vivian A VA Lai Chen C Jeromin Andreas A Bazarian Jeffrey J JJ Gill Jessica M JM

Frontiers in neurology 20200707

Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological processes and disease mechanisms. Such knowledge will help improve diagnosis, clinical management, and prognosis. Total-tau (t-tau) has recently emerged as a promising blood marker showing sex-associated differences in neurodegenerative diseases. Noneth ...[more]

PMID: 32733367

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Project description:Background and purposeQuantitative susceptibility mapping using MR imaging can assess changes in brain tissue structure and composition. This report presents preliminary results demonstrating changes in tissue magnetic susceptibility after sports-related concussion.Materials and methodsLongitudinal quantitative susceptibility mapping metrics were produced from imaging data acquired from cohorts of concussed and control football athletes. One hundred thirty-six quantitative susceptibility mapping datasets were analyzed across 3 separate visits (24 hours after injury, 8 days postinjury, and 6 months postinjury). Longitudinal quantitative susceptibility mapping group analyses were performed on stability-thresholded brain tissue compartments and selected subregions. Clinical concussion metrics were also measured longitudinally in both cohorts and compared with the measured quantitative susceptibility mapping.ResultsStatistically significant increases in white matter susceptibility were identified in the concussed athlete group during the acute (24 hour) and subacute (day 8) period. These effects were most prominent at the 8-day visit but recovered and showed no significant difference from controls at the 6-month visit. The subcortical gray matter showed no statistically significant group differences. Observed susceptibility changes after concussion appeared to outlast self-reported clinical recovery metrics at a group level. At an individual subject level, susceptibility increases within the white matter showed statistically significant correlations with return-to-play durations.ConclusionsThe results of this preliminary investigation suggest that sports-related concussion can induce physiologic changes to brain tissue that can be detected using MR imaging-based magnetic susceptibility estimates. In group analyses, the observed tissue changes appear to persist beyond those detected on clinical outcome assessments and were associated with return-to-play duration after sports-related concussion.

Project description:Pediatric concussion has a rising incidence and can lead to long-term symptoms in nearly 30% of children. Resting state functional magnetic resonance imaging (rs-fMRI) disturbances are a common pathological feature of pediatric concussion, though no studies have explicitly examined sex-differences with respect to this outcome, precluding a sex-specific understanding of the functional neuropathology of pediatric concussion. Therefore, we performed a secondary data analysis of rs-fMRI data collected on children with concussion (n = 29) recruited from in a pediatric hospital setting, with greater than 12:1 matched control data accessed from the open-source ABIDE-II database. Seed-based and region of interest (ROI) analyses were used to examine sex-based rs-fMRI differences; threshold-free cluster enhancement (TFCE) and a family-wise error (FWE) corrected p-values were used to identify significantly different clusters. In comparing females with concussion to healthy females, groupwise differences were observed irrespective of seed selected. Notably, we observed (in order of largest effect) hypo-connectivity between the anterior cingulate cortex of the salience network and the thalamus and precuneus (TFCE = 1473.5, p-FWE < 0.001) and the cingulate gyrus (TFCE = 769.3, p-FWE = 0.009), and the seed (posterior cingulate cortex (PCC)) of the default mode network and the paracingulate gyrus (TFCE = 1275.7, p-FWE < 0.001), occipital pole right (TFCE = 1045.0, p-FWE = 0.001), and sub-callosal cortex (TFCE = 844.9, p-FWE = 0.005). Hyper-connectivity was observed between the salience network seed and the cerebellum (TFCE = 1719.3, p-FWE < 0.001) and the PCC and the thalamus (TFCE = 1198.3, p-FWE < 0.001), cuneal cortex (1070.9, p-FWE = 0.001), and lateral occipital cortex left (TFCE = 832.8, p-FWE = 0.006). ROI analyses showed 10 and 5 significant clusters of hypo- and hyper-connectivity in females, respectively. Only one cluster of difference was found between males with concussion and healthy males on seed-based analyses, and 3 clusters on ROI analyses. There are alterations in rs-fMRI in females with concussion at one-month post-injury that are minimally present in males, which provides further evidence that recovery timelines in pediatric concussion may differ by sex.

Project description:BackgroundGaelic games are some of the most popular sports played by Irish adolescents, and the Gaelic Athletic Association has undertaken educational initiatives to improve awareness of a sports-related concussion (SRC). However, SRC underreporting is common among adolescent athletes internationally, potentially due to poor knowledge or attitudes toward SRC. This study aimed to examine previous experiences with, knowledge of, and attitudes toward reporting SRCs, as well as views on future education in adolescent Gaelic games players and their parents.HypothesesThe hypotheses were as follows: (1) A significant number of adolescent Gaelic games players will have experienced an SRC, (2) nondisclosure of SRCs will be common, and (3) adolescents will display poorer attitudes toward reporting than parents.Study designCross-sectional study.Level of evidenceLevel 3.MethodsAdolescent male and female Gaelic games players (n = 113) and parents (n = 151) completed an anonymous questionnaire examining previous experiences with, knowledge of, and attitudes toward reporting SRCs, as well as views on future SRC education initiatives.ResultsOverall, 57.5% of adolescent Gaelic games players suspected they had suffered an SRC previously, and a greater number of suspected SRCs were reported than were medically diagnosed. Adolescent players (mean score, 11.4/14) and their parents (mean score, 11.8) displayed good knowledge of SRC signs and symptoms. However, adolescents were less likely to report an SRC during an important game or if an important game was coming up. Both adolescents and their parents would like more SRC education, particularly in the format of online videos or medical professional-led workshops.ConclusionUnderreporting of SRC occurs in adolescent players, despite good knowledge of SRC signs and symptoms. Education is required to highlight the importance of completing a return-to-play program after an SRC regardless of match importance.Clinical relevanceA multifaceted educational strategy that targets the wider Gaelic games community in the preferred formats identified by key stakeholders is required.

Project description:Traumatic brain injury (TBI) affects millions of Americans each year and has been shown to disproportionately impact those subject to greater disparities in health. Female sex is one factor that has been associated with disparities in health outcomes, including in TBI, but sex differences in biomarker levels and behavioral outcomes after TBI are underexplored. This study included participants with both blunt and blast TBI with majority rating their TBI as mild. Time since injury was 5.4 (2.0, 15.5) years for females and 6.8 (2.4, 11.3) years for males. The aim of this cross sectional study is to investigate the relationship between postconcussive, depression, and post-traumatic stress disorder (PTSD) symptoms, as well as health related quality of life (HRQOL), and the levels of glial fibrillary acidic protein (GFAP), total tau (t-tau), neurofilament light chain (NfL), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). Behavioral outcomes were evaluated with the Neurobehavioral Symptom Inventory (NSI), Patient Health Questionnaire-9 (PHQ-9), PTSD Checklist- Civilian Version (PCL-C), short form (SF)-36, and plasma levels of total tau, GFAP, NfL, and UCHL-1 measured with the Simoa-HDX. We observed that females had significantly higher levels of GFAP and tau (ps < 0.05), and higher PHQ-9 scores, NSI total scores, NSI- vestibular, NSI-somatosensory, NSI-affective sub-scale scores (ps < 0.05)), than males. In addition, females had lower scores in HRQOL outcomes of role limitations due to emotional problems, vitality, emotional well-being, social functioning, and pain compared to males (ps < 0.05). Correlation analysis showed positive associations between levels of tau and the NSI-total and NSI-cognitive sub-scale scores (ps < 0.05) in females. No significant associations were found for NfL or GFAP with NSI scores. For female participants, negative correlations were observed between tau and NfL concentrations and the SF-36 physical function subscale (ps < 0.05), as well as tau and the social function subscale (p < 0.001), while GFAP levels positively correlated with role limitations due to emotional problems (p = 0.004). No significant associations were observed in males. Our findings suggest that sex differences exist in TBI-related behavioral outcomes, as well as levels of biomarkers associated with brain injury, and that the relationship between biomarker levels and behavioral outcomes is more evident in females than males. Future studies are warranted to corroborate these results, and to determine the implications for prognosis and treatment. The identification of candidate TBI biomarkers may lead to development of individualized treatment guidelines.

Dataset Information

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome.

Publications

Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome.

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