Assessing Clinical Change in Individuals Exposed to Repetitive Head Impacts: The Repetitive Head Impact Composite Index.
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ABSTRACT:
SUBMITTER: Bernick C
PROVIDER: S-EPMC8290321 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo examine the characteristics of those who fulfil the recent National Institute of Neurological Disease and Stroke (NINDS) Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome (TES) and test whether they show differences in MRI-based regional brain volumes, cognitive domains, and certain plasma biomarkers.MethodsProfessional fighters 35 years of age or older and/or retired were included. Participants were categorised as either having TES (TES+) or not (non-TES). TES+ participants were further subtyped by their cognitive profile. Multiple linear regression models were used to compare MRI-based regional brain volumes, cognitive performance, plasma tau and neurofilament light levels between TES- and TES+ groups.Results176 participants (110 boxers and 66 MMA) were included in the analysis. 72 (41%)/176 were categorised as having TES, the likelihood of TES increasing with age. TES+ participants tended to be boxers, started fighting at a younger age, had more professional fights and knocked out more frequently. The TES+ group had lower regional brain volumes including both grey and white matter structures. TES+ also had lower scores on simple and choice reaction time, psychomotor speed and Trails A .ConclusionThe new TES criteria does distinguish a group of fighters with differences in regional brain volumes and reduced cognitive function. Our findings support the use of the NINDS criteria for TES in further research of the long-term effects of repetitive head impacts.
| S-EPMC10086298 | biostudies-literature
Project description:Repetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear. Further, the symptoms endorsed by young individuals with early disease are not fully explained by the extent of p-tau deposition, severely hampering development of therapeutic interventions. Here, we show that RHI exposure associates with a multicellular response in young individuals (<51 years old) prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure. Leveraging single nucleus RNA sequencing of tissue from 8 control, 9 RHI-exposed, and 11 low stage CTE individuals, we identify SPP1+ inflammatory microglia, angiogenic and inflamed endothelial cell profiles, reactive astrocytes, and altered synaptic gene expression in excitatory and inhibitory neurons in all individuals with exposure to RHI. Surprisingly, we also observe a significant loss of cortical sulcus layer 2/3 neurons in contact sport athletes compared to controls independent of p-tau pathology. These results provide robust evidence that multiple years of RHI exposure is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early clinical symptoms observed in young former contact sport athletes. Furthermore, these data identify specific cellular responses to repetitive head impacts that may direct future identification of diagnostic and therapeutic strategies for CTE.
| S-EPMC10996668 | biostudies-literature
Project description:ObjectivesThe purpose of our study was to investigate the association between repetitive head impact (RHI) exposure and postural control.DesignSystematic review.MethodsPubMed, Embase and PsycInfo were searched using a self-developed search term including the keywords balance OR postural control AND repetitive OR sub-concussive head impacts. Twenty-one studies excluding non-peer reviewed studies, secondary studies, cross-sectional studies, animal studies, and studies investigating concussion were included for further analyses. We rated Level of Evidence and quality using the Centre for Evidence-Based Medicine tool, the Quality Assessment for the Systematic Review of Effectiveness, and the Sub-concussion Specific Tool.ResultsAll included studies were grouped into Category I and II studies. Category I included trials investigating the effects of controlled soccer heading on postural control (n=8) and Category II studies were cohort studies investigating on-the-field changes between preseason and postseason assessments on postural control measures (n=13). Findings were heterogeneous, with a tendency towards no effects of RHI on clinical postural control measures. Most laboratory studies in Category I used instrumented assessments whereas on-the-field studies in Category II used both instrumented and non-instrumented assessments.ConclusionsDue to heterogeneous findings, future studies aiming to investigate the effects of RHI on different athlete populations are needed on other participant cohorts. Furthermore, the combination of objective clinical balance measures may be a promising approach to accurately measure how, and to what degree, postural control may be affected by RHI.
| S-EPMC7854930 | biostudies-literature
Project description:This was an exploratory study designed to evaluate the feasibility of a recently established imaging modality, quantitative ultrashort time-to-echo contrast enhanced (QUTE-CE), to follow the early pathology and vulnerability of the blood brain barrier in response to single and repetitive mild head impacts. A closed-head, momentum exchange model was used to produce three consecutive mild head impacts aimed at the forebrain separated by 24 h each. Animals were measured at baseline and within 1 h of impact. Anatomical images were collected to assess the extent of structural damage. QUTE-CE biomarkers for BBB permeability were calculated on 420,000 voxels in the brain and were registered to a bilateral 3D brain atlas providing site-specific information on 118 anatomical regions. Blood brain barrier permeability was confirmed by extravasation of labeled dextran. All head impacts occurred in the absence of any structural brain damage. A single mild head impact had measurable effects on blood brain barrier permeability and was more significant after the second and third impacts. Affected regions included the prefrontal ctx, basal ganglia, hippocampus, amygdala, and brainstem. Our findings support the concerns raised by the healthcare community regarding mild head injuries in participants in organized contact sports and military personnel in basic training and combat.
| S-EPMC8515019 | biostudies-literature
Project description:ImportanceSubconcussive head impacts have emerged as a complex public health concern. The oculomotor system is sensitive to brain trauma; however, neuro-ophthalmologic response to subconcussive head impacts remains unclear.ObjectiveTo examine whether subconcussive head impacts cause impairments in neuro-ophthalmologic function as measured by the King-Devick test (KDT) and oculomotor function as measured by the near point of convergence.Design, setting, and participantsIn this randomized clinical trial, adult soccer players were randomized into either a heading group or kicking (control) group. The heading group executed 10 headers with soccer balls projected at a speed of 25 mph. The kicking-control group followed the same protocol but with 10 kicks. Peak linear and rotational head accelerations were assessed with a triaxial accelerometer. The KDT speed and error and near point of convergence were assessed at baseline (preheading or prekicking) and at 0, 2, and 24 hours after heading or kicking.ExposuresTen soccer-ball headings or kicks.Main outcomes and measuresThe primary outcome was the group-by-time interaction of KDT speed at 0 hours after heading or kicking. The secondary outcomes included KDT speed at 2 hours and 24 hours after heading or kicking, KDT error, and near point of convergence.ResultsA total of 78 individuals enrolled (heading group, n = 40; kicking-control group, n = 38). Eleven individuals (heading group: 4 women; mean [SD] age, 22.5 [1.0] years; kicking-control group, 3 women and 4 men; mean [SD] age, 20.9 [1.1] years) voluntarily withdrew from the study. Data from 67 participants with a mean (SD) age of 20.6 (1.7) years were eligible for analysis (heading, n = 36; kicking-control, n = 31). Mean (SD) peak linear accelerations and peak rotational accelerations per impact for the heading group were 33.2 (6.8) g and 3.6 (1.4) krad/s2, respectively. Conversely, soccer kicking did not induce a detectable level of head acceleration. Both groups showed improvements in KDT speed (heading group: 0 hours, -1.2 [95% CI, -2.2 to -0.1] seconds; P = .03; 2 hours, -1.3 [95% CI, -2.6 to 0] seconds; P = .05; 24 hours, -3.2 [95% CI, -4.3 to -2.2] seconds; P < .001; kicking-control group: 0 hours, -3.3 [95% CI, -4.1 to -2.5] seconds; P < .001; 2 hours, -4.1 [95% CI, -5.1 to -3.1] seconds; P < .001; 24 hours, -5.2 [95% CI, -6.2 to -4.2] seconds; P < .001). Group differences occurred at all postintervention points; the kicking-control group performed KDT faster at 0 hours (-2.2 [95% CI, -0.8 to -3.5] seconds; P = .001), 2 hours (-2.8 [95% CI, -1.2 to -4.4] seconds; P < .001), and 24 hours after the intervention (-2.0 [95% CI, -0.5 to -3.4] seconds; P = .007) compared with those of the heading group.Conclusions and relevanceThese data support the hypothesis that neuro-ophthalmologic function is affected, at least in the short term, by subconcussive head impacts that may affect some individuals in some contact sports. Further studies may help determine if these measures can be a useful clinical tool in detecting acute subconcussive injury.Trial registrationClinicalTrials.gov Identifier: NCT03488381.
| S-EPMC7042902 | biostudies-literature
Project description: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.
| S-EPMC4961456 | biostudies-literature
Project description:BackgroundFew studies have examined white matter with diffusion tensor imaging in 8- to 12-year-old collision sport (CS) athletes.HypothesisYouth CS athletes will demonstrate change in brain fractional anisotropy (FA) after a season of CS compared with an age-matched noncollision sport (NCS) cohort, and the number, magnitude, and location of hits will correlate with changes in the brain determined via FA for CS athletes.Study designProspective cohort study.Level of evidenceLevel 3.MethodsThirty-five 8- to 12-year-old males in a youth tackle football league (CS) and 12 males from local swim teams (NCS) were recruited. Participants underwent brain magnetic resonance imaging with FA before and after the football season. Number, magnitude, and direction of head impacts were recorded for CS participants throughout the season.ResultsA total of 1905 hits were recorded in the CS group for the season, 341 (17.9%) collected during 7 games and 1564 (82.1%) observed during 31 practices. No significant interaction between group (CS and NCS) and time (pre- and postseason) was observed for FA (P > 0.05). Correlation analysis revealed a significantly positive and moderate relationship between increase of left cingulate cortex (CgC) FA from pre- to postseason and the total magnitude of lateral head impacts (r = 0.40; P = 0.03).ConclusionThere was no significant change in FA measurement of white matter integrity in a cohort of 8- to 12-year-old males after a season of youth football, nor was any difference detected in FA between youth football players and an age-matched cohort of swimmers. There was a significant correlation between total magnitude of hits sustained by youth football players and an increase in FA in the left CgC; whether this is adaptive or pathologic remains unknown.Clinical relevanceThese data can be used within the body of knowledge to counsel patients regarding the known risks of youth tackle football regarding brain health.
| S-EPMC6822208 | biostudies-literature
Project description:Ecotron facilities allow accurate control of many environmental variables coupled with extensive monitoring of ecosystem processes. They therefore require multivariate perturbation of climate variables, close to what is observed in the field and projections for the future. Here, we present a new method for creating realistic climate forcing for manipulation experiments and apply it to the UHasselt Ecotron experiment. The new methodology uses data derived from the best available regional climate model projection and consists of generating climate forcing along a gradient representative of increasingly high global mean air temperature anomalies. We first identified the best-performing regional climate model simulation for the ecotron site from the Coordinated Regional Downscaling Experiment in the European domain (EURO-CORDEX) ensemble based on two criteria: (i) highest skill compared to observations from a nearby weather station and (ii) representativeness of the multi-model mean in future projections. The time window is subsequently selected from the model projection for each ecotron unit based on the global mean air temperature of the driving global climate model. The ecotron units are forced with 3-hourly output from the projections of the 5-year period in which the global mean air temperature crosses the predefined values. With the new approach, Ecotron facilities become able to assess ecosystem responses on changing climatic conditions, while accounting for the co-variation between climatic variables and their projection in variability, well representing possible compound events. The presented methodology can also be applied to other manipulation experiments, aiming at investigating ecosystem responses to realistic future climate change.
| S-EPMC7481170 | biostudies-literature
Project description:IntroductionSport-related repetitive subconcussive head impacts (RSHIs) are increasingly thought to be associated with adverse long-term outcomes. However, owing to potentially subtle effects, accurate assessment of harm to the brain as a consequence of RSHI is a major challenge and an unmet need. Several studies suggest that biofluid markers can be valuable objective tools to aid the diagnosis and injury characterisation and help in medical decision-making. Still, by and large, the results have been limited, heterogeneous and inconsistent. The main aims of this scoping review are therefore (1) to systematically examine the extent, nature and quality of available evidence from studies investigating effects of RSHI on fluid biomarkers and (2) to formulate guidelines and identify gaps with the aim to inform future clinical studies and the development of research priorities.Methods and analysesWe will use a comprehensive search strategy to retrieve all available and relevant articles in the literature. The following electronic databases will be systematically searched: MEDLINE (EBSCO host; from 1809 to 2020); Scopus (from 1788 to 2020); SPORTDiscus (from 1892 to 2020); CINAHL Complete (from 1937 to 2020); PsycINFO (from 1887 to 2020); Cochrane Library (to 2020); OpenGrey (to 2020); ClinicalTrials.gov (to 2020) and WHO International Clinical Trials Registry Platform (to 2020). We will consider primarily biomedical studies evaluating the biofluid markers following RSHI. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria and extract data of retained articles. Disagreements will be resolved through consensus or arbitrated by a third reviewer if necessary. Data will be reported qualitatively given the heterogeneity of the included studies. In synthesising the evidence, we will structure results by markers, sample types, outcomes, sport and timepoints.Ethics and disseminationEthics approval is not required. We will submit results for peer-review publication, and present at relevant conferences.
| S-EPMC8240577 | biostudies-literature
Project description:Head injury is a known risk factor for Parkinson's disease. Disruption in the perivascular clearance of metabolic waste and unwanted proteins is thought to be a contributing factor to disease progression. We hypothesized that repetitive mild head impacts, without evidence of structural brain damage, would increase microgliosis and AQP4 expression and depolarization and alter perivascular flow in the midbrain dopaminergic system. Adult male rats were subjected to sham, or two mild head impacts separated by 48 h. Three weeks later, fully awake rats were imaged using dynamic, contrast-enhanced MRI to follow the distribution of intraventricular gadobenate dimeglumine contrast agent. Images were registered to and analysed using a 3D MRI rat atlas providing site-specific data on 171 different brain areas. Following imaging, rats were tested for cognitive function using the Barnes maze assay. Histological analyses of tyrosine hydroxylase, microglia activation and AQP4 expression and polarization were performed on a parallel cohort of head impacted rats at 20 days post insult to coordinate with the time of imaging. There was no change in the global flux of contrast agent between sham and head impacted rats. The midbrain dopaminergic system showed a significant decrease in the influx of contrast agent as compared to sham controls together with a significant increase in microgliosis, AQP4 expression and depolarization. There were no deficits in cognitive function. The histology showed a significant level of neuroinflammation in the midbrain dopaminergic system 3 weeks post mild repetitive head impact but no loss in tyrosine hydroxylase. MRI revealed no structural brain damage emphasizing the potential serious consequences of mild head impacts on sustained brain neuroinflammation in this area critical to the pathophysiology of Parkinson's.
| S-EPMC8600963 | biostudies-literature