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Background: The presence of mild traumatic brain injury (mTBI) increases post-traumatic stress disorder (PTSD) symptoms in the months following injury. However, factors that link mTBI and PTSD development are still unclear. Acute stress responses after trauma have been associated with PTSD development. mTBI may impair cognitive functions and increase anxiety immediately after trauma. Objective: This research aimed to test the possibility that mTBI increases acute stress symptoms rapidly, which in turn results in PTSD development in the subsequent months. Method: Fifty-nine patients were recruited from the emergency rooms of local hospitals. Post-mTBI, acute stress, and PTSD symptom severity were measured using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Acute Stress Disorder Scale (ASDS), and PTSD Checklist for DSM-5 (PCL-5), respectively. Results: Moderated mediation analysis indicated that ASDS, at 2 weeks post-trauma, mediated the relationship between RPQ scores at 2 weeks and PCL-5 scores at 3 months post-trauma, only for patients who met mTBI diagnostic criteria. Conclusions: These findings present preliminary evidence suggesting that acute stress disorder symptoms may be one of the mechanisms involved in the development of PTSD among trauma survivors who have experienced mTBI, which provides a theoretical basis for early intervention of PTSD prevention after mTBI.

Mild traumatic brain injury (mTBI), also referred to as concussion, remains a controversial diagnosis because the brain often appears quite normal on conventional computed tomography (CT) and magnetic resonance imaging (MRI) scans. Such conventional tools, however, do not adequately depict brain injury in mTBI because they are not sensitive to detecting diffuse axonal injuries (DAI), also described as traumatic axonal injuries (TAI), the major brain injuries in mTBI. Furthermore, for the 15 to 30 % of those diagnosed with mTBI on the basis of cognitive and clinical symptoms, i.e., the “miserable minority,” the cognitive and physical symptoms do not resolve following the first 3 months post-injury. Instead, they persist, and in some cases lead to long-term disability. The explanation given for these chronic symptoms, i.e., postconcussive syndrome, particularly in cases where there is no discernible radiological evidence for brain injury, has led some to posit a psychogenic origin. Such attributions are made all the easier since both posttraumatic stress disorder (PTSD) and depression are frequently co-morbid with mTBI. The challenge is thus to use neuroimaging tools that are sensitive to DAI/TAI, such as diffusion tensor imaging (DTI), in order to detect brain injuries in mTBI. Of note here, recent advances in neuroimaging techniques, such as DTI, make it possible to characterize better extant brain abnormalities in mTBI. These advances may lead to the development of biomarkers of injury, as well as to staging of reorganization and reversal of white matter changes following injury, and to the ability to track and to characterize changes in brain injury over time. Such tools will likely be used in future research to evaluate treatment efficacy, given their enhanced sensitivity to alterations in the brain. In this article we review the incidence of mTBI and the importance of characterizing this patient population using objective radiological measures . Evidence is presented for detecting brain abnormalities in mTBI based on studies that use advanced neuroimaging techniques. Taken together, these findings suggest that more sensitive neuroimaging tools improve the detection of brain abnormalities (i.e., diagnosis) in mTBI. These tools will likely also provide important information relevant to outcome (prognosis), as well as play an important role in longitudinal studies that are needed to understand the dynamic nature of brain injury in mTBI. Additionally, summary tables of MRI and DTI findings are included. We believe that the enhanced sensitivity of newer and more advanced neuroimaging techniques for identifying areas of brain damage in mTBI will be important for documenting the biological basis of postconcussive symptoms, which are likely associated with subtle brain alterations, alterations that have heretofore gone undetected due to the lack of sensitivity of earlier neuroimaging techniques. Nonetheless, it is noteworthy to point out that detecting brain abnormalities in mTBI does not mean that other disorders of a more psychogenic origin are not co-morbid with mTBI and equally important to treat. They arguably are. The controversy of psychogenic versus physiogenic, however, is not productive because the psychogenic view does not carefully consider the limitations of conventional neuroimaging techniques in detecting subtle brain injuries in mTBI, and the physiogenic view does not carefully consider the fact that PTSD and depression, and other co-morbid conditions, may be present in those suffering from mTBI. Finally, we end with a discussion of future directions in research that will lead to the improved care of patients diagnosed with mTBI.

To report the frequency of head impacts and associated visible signs of possible concussion, and their inter-rater reliability at the FIFA World Cup Qatar 2022™. Observational and inter-rater reliability study. Fifteen visible signs of potential sport-related concussion, grouped into “red flags”, “yellow flags”, and “other signs”, were recorded live by FIFA injury spotters during the tournament. Post-tournament all matches were reviewed for visible signs by independent injury spotters. Agreement was assessed using Fleiss kappa (κ) and Prevalence And Bias Adjusted Kappa. FIFA spotters registered 172 head impacts live, while the post-tournament independent spotters registered 206 (67 % positive agreement). Both groups observed five incidents with at least one “red flag”, though these were not identical, resulting in moderate agreement (Kappa (K) = 0.58, 0.41 to 0.76). Agreement for each “red flag” varied from poor to almost perfect (K = −0.01 to 1.00). Incidents with “yellow flags” showed poor agreement (K = −0.46, −0.64 to −0.29), primarily due to differences in scoring “slow to get up”, while signs “face or scalp injury” and “lying motionless” had moderate to substantial agreement (K = 0.58 to 0.66). Inter-rater reliability of each visible sign varied from poor to substantial (K = −0.01 to 0.75), with low prevalence of some signs directly influencing kappa values. For the majority of visible signs, results of the prevalence-adjusted-and-bias-adjusted kappa showed almost perfect (K = 0.81 to 1.00) agreement and inter-rater reliability. Visible signs of concussion categorized as “red flags” were infrequent, resulting in uncertain reliability. The frequency and reliability of visible signs categorized as “yellow flags” and “other signs” varied, with the visible signs “clutching of the head” and “slow to get up” occurring so frequently that their utility for identifying possible concussion in football is questionable. Further research should focus on investigating specificity of the visible signs in larger studies with surveillance and clinical follow-up from multiple competitions (seasons).

The pathological basis underlying mild traumatic brain injury (mTBI)-induced long-term cognitive impairment is not fully understood. It is supposed that mTBI induces residential microglia activation rather than peripheral leukocyte infiltration to promote neuroinflammation, thus triggering myelin damage as well as cognitive impairment. The transformation of microglia towards a pro-inflammatory (M1 type) or anti-inflammatory (M2 type) state is critical for restraining the cerebral inflammatory response to acute or chronic insults. In addition to classical M1- and M2-like phenotypes, a specific subgroup of microglia, which is referred to as disease-associated microglia (DAM), the transition of which is regulated by triggering receptor expressed on myeloid cells 2 (Trem2), is also demonstrated to play a critical role in neurodegenerative diseases sharing similar pathological procedures to mTBI. The expression and function of p75 neurotrophin receptor (p75NTR) in microglia vary depending on the type and severity of the specific pathological stimuli. In the current study, we investigated whether peripheral leukocytes infiltrated the brain following mild traumatic brain injury (mTBI) using a CX3CR1- and CCR2-double transgenic reporter mouse model. We also examined whether M1- or M2-like microglia exhibited a disease-associated microglia (DAM) phenotype after mTBI, as indicated by their Trem2 expression. Then we explored the expression of p75NTR in M1- and M2-like phenotype microglia after mTBI and its modulating effects on the activation of Trem2 positive M1- and M2-like phenotype microglia, neuroinflammatory reaction, myelin damage, and cognitive performance. We found that most of the activated residential microglia after mTBI were Trem2 positive and p75NTR expression was significantly elevated in Trem2-positive M1-type microglia post-mTBI, correlating with increased pro-inflammatory cytokine release, demyelination, and cognitive deficits. Pharmacological blockade of p75NTR using the antagonist TAT-Pep5 suppressed M1 microglial activation, reduced neuroinflammation, and restored myelin integrity, leading to marked improvements in cognitive function. Mechanistically, p75NTR exhibited a cell-type-specific regulatory role in neuroinflammatory responses, potentially through interacting with Trem2 to modulate DAM-like microglia activation. These findings highlight p75NTR as a key mediator of mTBI-induced neuropathology and propose its inhibition as a novel therapeutic strategy to mitigate secondary neuroinflammation and cognitive decline.

Background : Head trauma in children is a common cause for a visit to the A&E. Among the many children it is important to identify those at risk for developing a clinical important head injury (CITBI). The most important way of identifying the children at risk is to perform a CT scan of the head. There are reports indicating an induction of 1 cancer in children on 1000 – 5000 CT examinations. It is thus important to minimise the use of CT. In 2010 Osmond and co-workers introduced the Canadian Assessment of Tomography for Childhood Head injury: the CATCH rule (CATCH-R), with the aim of identifying those at most risk and to reduce the use of CT. The aim of this study is to validate the CATCH-R, using a large cohort of children. Material Methods : The study is a cohort study based on the data set from: ‘‘Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study’’(Kuppermanns et al 2009). It includes data from more than 43000 children. The cohort was identified using the basal criteria in the CATCH-R, i.e. children with a GCS of 13 – 15. The CATCH-R was then used to identify children who should perform a CT. Results : We identified 37277 children with a GCS of 13 – 15 of which 7774 fulfilled the criteria for MHI according to the CATCH-R. Of these 2699 had one or more risk factors, i.e. should perform a CT scan. In the CT group 117 children had a CITBI and in the non-CT group (n=5075) we identified 36 children with CITBI. At the division MHI and no-MHI according to the CATCH-R the NPV is 99.2 % (CI 99.1 – 99.2 %), and specificity 79.3% (CI 78.9 – 79.7). At the division MHI with risk factor/s and MHI without risk factor/s the NPV is 99.3% (CI 99.1 – 99.5 %), and specificity 66.1 % (CI 65.0 – 67.2 %). Conclusion : It seems that using the CATCH-R the risk of not detecting a child with a CITBI is very small.

Background : Head trauma in children is common, with a low rate of clinically-important traumatic brain injury (ciTBI). CT scan is the reference standard for diagnosis of traumatic brain injury, of which the increasing use is alarming because of the risk of induction of lethal malignancies. Recently, the Scandinavian Neurotrauma Committee (SNC) derived new guidelines for the initial management of minor and moderate head trauma (GCS 9-15) in children. Our aim was to validate the SNC guidelines by assessing the risk of a child being discharged with a ciTBI. A secondary aim was to assess the risk of a child being discharged with a TBI on CT. Methods : We applied the SNC guidelines to a population consisting of children with mild and moderate head trauma, enrolled in the dataset ‘‘Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study’’ (Kuppermanns et al 2009). We calculated the SNC guidelines negative predictive values to assess their ability to distinguish children without ciTBI and traumatic brain injuries on CT scans, for whom CT would be unnecessary. Results : We enrolled and analysed 43 025 children (mean age 7.0 years, range 0-17, 62.3% males). The prevalence of ciTBI were statistically significant lower in the group of minimal head injury as compared to the mild low-risk head injury group (p<0.001). The rate of ciTBI in the minimal head injury group was 0,15% and the negative predictive value was 99.8% for ciTBI (minimal vs mild-moderate head injury groups). Traumatic finding on CT was detected in 3.1% of the children in the minimal group who underwent a CT examination, which accounts for 0.45% of all children in the minimal head injury group. The negative predictive value was 96.9% for traumatic finding on CT. Conclusion : It is safe to discharge children with oral and written instructions and, according to the SNC guidelines, minimal head injury. Use of the SNC guidelines will potentially reduce the use of CT.

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26–62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm2) was applied for 10 min to each of 11 scalp placements (13 J/cm2). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1–5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.

Repetitive subconcussive head impacts (RSHI) are believed to induce sub‐clinical brain injuries, potentially resulting in cumulative, long‐term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI‐exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data. Four datasets were centrally pooled to perform uniform quality control and data preprocessing. A total of 131 non‐concussed active athletes (American football, rugby, ice hockey; mean age: 20.06 ± 2.06 years) with baseline and post‐season data were included. Nonparametric permutation inference (one‐sample t tests, one‐sided) was applied to analyze the difference maps of multiple diffusion parameters. The analyses revealed widespread lateralized patterns of sports‐season‐related increases and decreases in mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across spatially distinct white matter regions. Increases were shown across one MD‐cluster (3195 voxels; mean change: 2.34%), one AD‐cluster (5740 voxels; mean change: 1.75%), and three RD‐clusters (817 total voxels; mean change: 3.11 to 4.70%). Decreases were shown across two MD‐clusters (1637 total voxels; mean change: −1.43 to −1.48%), two RD‐clusters (1240 total voxels; mean change: −1.92 to −1.93%), and one AD‐cluster (724 voxels; mean change: −1.28%). The resulting pattern implies the presence of strain‐induced injuries in central and brainstem regions, with comparatively milder physical exercise‐induced effects across frontal and superior regions of the left hemisphere, which need further investigation. This article highlights key considerations that need to be addressed in future work to enhance our understanding of the nature of observed white matter changes, improve the comparability of findings across studies, and promote data pooling initiatives to allow more detailed investigations (e.g., exploring sex‐ and sport‐specific effects). The combined analysis of existing longitudinal repetitive subconcussive head impacts studies showed widespread seasonal white matter changes across multiple diffusion parameters (i.e., mean diffusivity, radial diffusivity, and axial diffusivity) showing probable strain‐induced injuries and potential physical exercise effects.

BACKGROUND:Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment. OBJECTIVE:To describe the current landscape of treatment for concussion and to provide summary agreements related to treatment to assist clinicians in the treatment of concussion. METHODS:On October 14 to 16, 2015, the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion meeting was convened in Pittsburgh, Pennsylvania. Thirty-seven concussion experts from neuropsychology, neurology, neurosurgery, sports medicine, physical medicine and rehabilitation, physical therapy, athletic training, and research and 12 individuals representing sport, military, and public health organizations attended the meeting. The 37 experts indicated their agreement on a series of statements using an audience response system clicker device. RESULTS:A total of 16 statements of agreement were supported covering (1) Summary of the Current Approach to Treating Concussion, (2) Heterogeneity and Evolving Clinical Profiles of Concussion, (3) TEAM Approach to Concussion TreatmentSpecific Strategies, and (4) Future DirectionsA Call to Research. Support (ie, response of agree or somewhat agree) for the statements ranged from to 97% to 100%. CONCLUSION:Concussions are characterized by diverse symptoms and impairments and evolving clinical profiles; recovery varies on the basis of modifying factors, injury severity, and treatments. Active and targeted treatments may enhance recovery after concussion. Research is needed on concussion clinical profiles, biomarkers, and the effectiveness and timing of treatments. ABBREVIATIONS:ARS, audience response systemCDC, Centers for Disease Control and PreventionDoD, Department of DefensemTBI, mild traumatic brain injuryNCAA, National Collegiate Athletic AssociationNFL, National Football LeagueNIH, National Institutes of HealthRCT, randomized controlled trialRTP, return to playSRC, sport- and recreation-related concussionTBI, traumatic brain injuryTEAM, Targeted Evaluation and Active Management

Because of the rigid coupling between the upper dentition and the skull, instrumented mouthguards have been shown to be a viable way of measuring head impact kinematics for assisting in understanding the underlying biomechanics of concussions. This has led various companies and institutions to further develop instrumented mouthguards. However, their use as a research tool for understanding concussive impacts makes quantification of their accuracy critical, especially given the conflicting results from various recent studies. Here we present a study that uses a pneumatic impactor to deliver impacts characteristic to football to a Hybrid III headform, in order to validate and compare five of the most commonly used instrumented mouthguards. We found that all tested mouthguards gave accurate measurements for the peak angular acceleration, the peak angular velocity, brain injury criteria values (mean average errors < 13, 8, 13%, respectively), and the mouthguards with long enough sampling time windows are suitable for a convolutional neural network-based brain model to calculate the brain strain (mean average errors < 9%). Finally, we found that the accuracy of the measurement varies with the impact locations yet is not sensitive to the impact velocity for the most part.