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IntroductionEducation is strongly advocated as a key component of treatment for mild traumatic brain injury (mTBI) in clinical guidelines. However, there is mixed evidence on the benefit of education. This study aimed to evaluate a new education resource for mTBI. CLARITY is a freely available animated video based on a biopsychosocial conceptualization of mTBI, explaining the complex psychological, environmental and biological mechanisms behind symptoms and recovery.1Methods24 adults with a history of mTBI participated in this mixed method study to examine prior experience of mTBI education and to evaluate CLARITY. Following viewing of the education video participants’ were invited to engage in a semi-structured interview and to share their perceptions of it via an online anonymous questionnaire.ResultsThematic analysis of semi-structured interviews revealed one overarching theme: education is the foundation of recovery. Participants emphasised the critical role of coherent education in facilitating understanding, engagement in rehabilitation, and positive expectations during recovery. However, the first subtheme was that existing foundations are weak. Participants’ previous education was often limited in scope, inconsistent, and delivered in inaccessible ways. The second subtheme was that new foundations are stronger. Participants responded positively to CLARITY, highlighting its explanatory biopsychosocial approach, focus on mental health factors and accessible delivery methods as key strengths. Questionnaire responses revealed favourable endorsement of CLARITY’s utility, comprehensibility and accessibility.DiscussionRecommendations for minor refinements to CLARITY were provided and made, as well as for its use in health care services.

Clinical Scenario: As of 2020, the lifetime prevalence of at least one self-reported concussion is 24.6%. Athletic trainers in all settings work with patients who are at risk of sustaining a concussion or mild traumatic brain injury (mTBI) and developing persistent postconcussive symptoms. Aerobic exercise is emerging as an intervention for decreasing symptoms in patients who have sustained mTBI; however, the majority of research has been performed on pediatric patients. It is of interest whether aerobic exercise is an effective intervention for adult patients with mTBI. Focused Clinical Question: In adults who have sustained mTBI, does traditional therapy decrease symptoms more than aerobic exercise? Summary of Search: A systematic search of 4 databases was performed to answer this question. Three randomized controlled trials were identified that compared aerobic exercise to traditional therapy, which consists of physical and cognitive rest. Two studies found no significant differences in symptoms between the 2 groups while 1 study found decreased symptoms in the aerobic exercise group. Clinical Bottom Line: The current evidence is clear that there is no decrease in mTBI symptoms with traditional therapy as compared with aerobic exercise, with 1 study showing decreased symptoms with aerobic exercise. Strength of Evidence: Based on the Center for Evidence-Based Medicine grades of evidence, the clinical bottom line is based on grade A evidence. [ABSTRACT FROM AUTHOR]

We conducted a content analysis of the literature underlying the Centers for Disease Control and Prevention (CDC) Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children (i.e., the Guideline) to determine the extent to which social determinants of health (SDoH) were examined or addressed. The systematic review forming the basis for the Guideline included 37 studies addressing diagnosis, prognosis, and treatment/rehabilitation. We examined those studies to identify SDoH domains derived from the U.S. Department of Health and Human Services Healthy People 2020 and 2030 websites. No study explicitly mentioned social determinants of health, by name, and few studies addressed SDoH domains as a primary focus (ranging from 0% to 27% of studies across SDoH domains). The most frequently represented SDoH domains, described in an inferential or a descriptive manner, were Education Access and Quality (29.7% of studies), Social and Community Context (27.0% of studies), and Economic Stability (21.6% of studies). Health Care Access (13.5% of studies) was less well represented and no studies (0%) examined Neighborhood and Built Environment. In terms of the CDC clinical questions, SDoH were only examined as predictors of outcome (prognosis) and no studies examined SDoH in relation to diagnosis or treatment/rehabilitation. The Guideline includes some commentary on health literacy and socioeconomic status. Overall, social determinants of health are largely unrepresented as important or meaningful variables influencing the Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children, or in the studies that informed the Guideline.

Objectives: People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary aim to examine the relationship between symptom-based clinical profiles and recovery. Methods: Prospective observational study of adults aged 18 to 65 years who had sustained mTBI within the previous 7 days. Symptoms were assessed using the Post-Concussion Symptom Scale, HR was measured at rest, and exercise tolerance was assessed using the Buffalo Concussion Bike Test. Symptom burden and symptom-based clinical profiles were examined with respect to exercise tolerance and resting HR. Results: Data from 32 participants were assessed (mean age 36.5 ± 12.6 years, 41% female, 5.7 ± 1.1 days since injury). Symptom burden (number of symptoms and symptom severity) was significantly associated with exercise intolerance (P = .002 and P = .025, respectively). Physiological and vestibular-ocular clinical profile composite groups were associated with exercise tolerance (P = .001 and P = .014, respectively), with individuals who were exercise intolerant having a higher mean number of symptoms in each profile than those who were exercise tolerant. Mood-related and autonomic clinical profiles were associated with a higher resting HR (>80 bpm) (P = .048 and P = .028, respectively), suggesting altered autonomic response for participants with symptoms relating to this profile. After adjusting for age and mechanism of injury (sports- or non–sports-related), having a higher mood-related clinical profile was associated with persisting symptoms at 3 months postinjury (adjusted odds ratio = 2.08; 95% CI, 1.11-3.90; P = .013). Conclusion: Symptom-based clinical profiles, in conjunction with objective measures such as resting HR and exercise tolerance, are important components of clinical care for those having sustained mTBI. These results provide preliminary support for the concept that specific symptoms are indicative of autonomic dysfunction following mTBI. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the trajectory of parent-rated post-concussive symptoms (PCS), attentional performance and participation within 6 months in children after mild traumatic brain injury (mTBI). For this prospective longitudinal study, we included data on 64 children after mTBI and 57 healthy control children (age 8–16 years). Parents rated PCS using the Post-Concussion Symptom Inventory (PCSI) immediately (T0), 1 week (T1), and 3–6 months after injury (T2). Attentional performance (alertness, selective and divided attention) was measured using the Test of Attentional Performance (TAP) at T1 and T2 and participation was measured using the Child and Adolescent Scale of Participation (CASP) at T2. Friedman tests showed different trajectories of PCS subscales over time: Compared to pre-injury level, the amount of somatic and cognitive PCS was still elevated at T1, while emotional PCS at T1 were already comparable to pre-injury level. The rating of sleep-related PCS at T2 was significantly elevated compared to the pre-injury rating. Quade ANCOVAs indicated group differences in PCS subscales between patients and controls at T1, but not at T2. Patients and controls showed a similar performance in tests of attention at T1 and T2, but parental rating of participation at school was significantly reduced. Although cognitive PCS and attention were not correlated, there were significantly negative Spearman correlations between participation at home and pre-injury and concurrent PCS at T2. Our data imply that sleep-related PCS are still elevated weeks after injury and are thus a target for interventions after mTBI. [ABSTRACT FROM AUTHOR]

In this review, we provide an overview of the current research and treatment of all types of traumatic brain injury (TBI) before illustrating the need for improved care specific to mild TBI patients. Contemporary issues pertaining to acute care of mild TBI including prognostication, neurosurgical intervention, repeat radiographic imaging, reversal of antiplatelet and anticoagulation medications, and cost savings initiatives are reviewed. Lastly, the effect of COVID-19 on TBI is addressed.

Objective: The majority of traumatic brain injuries (TBIs) are classified as mild and occur in young individuals. The course of recovery varies but can result in chronic or troubling outcomes. The impact of age on TBI outcomes in young adults before complete brain maturation is not well studied. Methods: In this study, we compared the effects of mild TBI on cognitive performance and self-reported TBI symptoms and posttraumatic stress disorder (PTSD) in 903 soldiers in 3 different age groups: 24 years or younger, 25 to IT years, and 28 to 40 years. The soldiers had returned from war zones in Iraq and were screened for TBI within a few days of return. Cognitive performance was measured with the Automated Neuropsychological Assessment Metrics of Military TBI Version 4 (ANAM4). Symptoms associated with mild TBI were self-reported on the Neurobehavioral Symptom Inventory, and the PTSD Checklist--Civilian Version (PCL-C). Results: Soldiers with TBI in every age group had significantly higher prevalence of most symptoms than those with no TBI. Soldiers with TBI also reported more chronic pain sites, regardless of age. Soldiers aged 28 to 40 years with TBI had the lowest cognitive performance scores (ANAM) across several subtests, both unadjusted and adjusted. The Global Deficit Score was significantly higher for soldiers aged 28 to 40 years and 25 to 27 years with TBI than for soldiers younger than 24 years with no TBI. After adjusting for PTSD symptoms, education, and number of lifetime TBIs, the overall test battery mean for soldiers aged 28 to 40 years with TBI was significantly lower than for soldiers younger than 24 years with no TBI. Conclusion: Soldiers with mild TBI in the younger age group show more symptoms associated to frontal lobe function while soldiers in the older group suffer more cognitive impairment. This may warrant further study as it may indicate a propensity to later cognitive decline among soldiers who were older at the time of injury. [ABSTRACT FROM AUTHOR]

Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery. The objective of this study was to evaluate whether baseline clinical variables, three-month RTW, and three-month postconcussional symptoms (PCS) were associated with six-month RTW after mTBI. Adult subjects from the prospective multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with mTBI (Glasgow Coma Scale 13-15) who were employed at baseline, with completed three-and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extracted. Univariate and multivariable analyses were performed for six-month RTW, with focus on baseline employment, three-month RTW, and three-month ACE domains (physical, cognitive, sleep, and/or emotional postconcussional symptoms (PCS)). Odds ratios (OR) and 95% confidence intervals [CI] were reported. Significance was assessed at p < 0.05. In 152 patients aged 40.7 ± 15.0years, 72% were employed full-time at baseline. Three- and six-month RTW were 77.6% and 78.9%, respectively. At three months, 59.2%, 47.4%, 46.1% and 31.6% scored positive for ACE physical, cognitive, sleep, and emotional PCS domains, respectively. Three-month RTW predicted six-month RTW (OR = 19.80, 95% CI [7.61-51.52]). On univariate analysis, scoring positive in any three-month ACE domain predicted inability for six-month RTW (OR = 0.10-0.11). On multivariable analysis, emotional symptoms predicted inability to six-month RTW (OR = 0.19 [0.04-0.85]). Subjects who scored positive in all four ACE domains were more likely to be unable to RTW at six months (4 domains: 58.3%, vs. 0-to-3 domains: 9.5%; multivariable OR = 0.09 [0.02-0.33]). Three-month post-injury is an important time point at which RTW status and PCS should be assessed, as both are prognostic markers for six-month RTW. Clinicians should be particularly vigilant of patients who present with emotional symptoms, and patients with symptoms across multiple PCS categories, as these patients are at further risk of inability to RTW and may benefit from targeted evaluation and support.

Objective: To investigate whether involvement in litigation and performance validity test (PVT) failure predict adherence to treatment and treatment outcomes in adults with persistent symptoms after mild traumatic brain injury (mTBI). Setting: Outpatient concussion clinics in British Columbia, Canada. Participants were assessed at intake (average 12.9 weeks postinjury) and again following 3 to 4 months of rehabilitation. Participants: Adults who met the World Health Organization Neurotrauma Task Force definition of mTBI. Litigation status was known for 69 participants (n = 21 reported litigation), and 62 participants completed a PVT (n = 13 failed the Test of Memory Malingering) at clinic intake. Design: Secondary analysis of a clinical trial (ClinicalTrials.gov #NCT03972579). Main Measures: Outcomes included number of completed sessions, homework adherence, symptoms (Rivermead Post Concussion Symptoms Questionnaire), disability ratings (World Health Organization Disability Assessment Schedule 2.0), and patient-rated global impression of change. Results: We did not observe substantial differences in session and homework adherence associated with litigation or PVT failure. Disability and postconcussion symptoms generally improved with treatment. Involvement in litigation was associated with a smaller improvement in outcomes, particularly disability (B = 2.57, 95% confidence interval [CI] [0.25-4.89], P =.03) and patient-reported global impression of change (odds ratio [OR] = 4.19, 95% CI [1.40-12.57], P =.01). PVT failure was not associated with considerable differences in treatment outcomes. However, participants who failed the PVT had a higher rate of missing outcomes (31% vs 8%) and perceived somewhat less global improvement (OR = 3.47, 95% CI [0.86-14.04]; P =.08). Conclusion: Adults with mTBI who are in litigation or who failed PVTs tend to adhere to and improve following treatment. However, involvement in litigation may be associated with attenuated improvements, and pretreatment PVT failure may predict lower engagement in the treatment process. [ABSTRACT FROM AUTHOR]

Objective: The Common Sense Model (CSM) describes cognitive, emotional, and psychosocial factors that influence how health threats are processed and subsequently inform health-related decisions or actions. The purpose of this study was to examine psychosocial factors influencing coherence, or usefulness, of mild traumatic brain injury (mTBI) representations and their relationship to health-related decisions and actions. Setting: Public university. Participants: There were 458 graduate and undergraduate college students who participated in a web-based survey (mean age = 22 years; SD = 3.6). Design: A mixed-methods design randomized participants into 2 groups to examine perceptions of mTBI across differing injury mechanisms, or causes, by comparing actions recommended to a friend (Other; n = 214) with those generated for self (Self; n = 244). Main Measures: Seven common injury mechanisms representative of university student mTBI experiences were presented as vignettes (cause). Each vignette included open- and closed-ended questions framed from CSM constructs (identity, consequences, action plans, timeline, and social context). Data were analyzed using a series of chi-square tests and multiple analysis of variance. Post hoc analysis identified differences in the injury vignettes. Results: Students were more likely to identify the injury as mTBI (  χ 3 2 = 8.62, P =.035) and recommend immediate healthcare (F 1,415 = 316.89, P <.001) for all causes if the injury occurred to a friend as compared with themselves. Action plans also varied by cause, with post hoc analysis revealing a higher likelihood of healthcare seeking for motor vehicle crashes and assault and a lower likelihood for falls while intoxicated. Students were generally more likely to talk to closest confidants than doctors (F 8,398 = 33.66, P <.001). Conclusion: Cause appears to be a key construct in generating illness representations and associated action plans for seeking care, with lower perceived severity causes (eg, falls) resulting in little to no health-seeking action. In addition, social support appears to be important for college students when making decisions about their health. [ABSTRACT FROM AUTHOR]

Primary Objective: This is Part II of a four-part opinion review on traditional neuropsychological assessment methods and findings associated with mild traumatic brain injury (mTBI). This Part II review focuses on historical, psychometric and statistical issues involving traditional neuropsychological methods that have been used in neuropsychological outcome studies of mTBI, but demonstrates the critical limitations of traditional methods. Research Design: This is an opinion review. Methods and Procedures: Traditional neuropsychological tests are dated and lack specificity in evaluating such a heterogenous and complex injury as occurs with mTBI. Main Outcome and Results: In this review, we demonstrate traditional neuropsychological methods were never developed as standalone measures for detecting subtle changes in neurocognitive or neurobehavioral functioning and likewise, never designed to address the multifaceted issues related to underlying mTBI neuropathology symptom burden from having sustained a concussive brain injury. Conclusions: For neuropsychological assessment to continue to contribute to clinical practice and outcome literature involving mTBI, major innovative changes are needed that will likely require technological advances of novel assessment techniques more specifically directed to evaluating the mTBI patient. These will be discussed in Part IV. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE

BackgroundObjective(s)MethodsResultsConclusionsIndividuals with persistent symptoms following a mild traumatic brain injury (mTBI) demonstrate improved satisfaction with their performance of self-identified rehabilitation goals after completing a combined occupational therapy and physiotherapy group intervention. However, the relationship between factors associated with developing persistent symptoms following an mTBI and satisfaction with their performance of self-identified goals after completing an intervention are unknown.To evaluate whether factors associated with developing persistent symptoms influence satisfaction with the performance of self-identified goals after completing a combined occupational therapy and physiotherapy group intervention.During intake assessments, individuals with persistent mTBI symptoms completed the satisfaction section of the Canadian Occupational Performance Measure (COPM-S), the Rivermead Post-Concussion Symptom Questionnaire (RPQ), and the Generalized Anxiety Disorder Seven-Item Scale (GAD-7). Participants re-rated their satisfaction with performance of self-identified goals using the COPM-S during their discharge assessment. The influence of age, sex, days since injury, education, mechanism of injury, baseline COPM-S, GAD-7, and RPQ scores on goal satisfaction ratings were analyzed using a binomial logistic regression.One hundred and ninety-eight individuals (44.7 ± 13.6 years old) were included in this study, and 92% experienced a clinically important improvement in their goal satisfaction ratings after completing the intervention. Neither age, sex, days since injury, education, mechanism of injury, baseline COPM-S, GAD-7, or RPQ scores significantly influenced satisfaction with performance of self-identified goals.Factors associated with developing persistent symptoms following an mTBI did not influence goal satisfaction after completing a combined physiotherapy and occupational therapy group intervention. [ABSTRACT FROM AUTHOR]

Dizziness following mild traumatic brain injury (mTBI), or concussion, is common and can encompass multiple sensations reflecting diverse aetiologies. This exploratory study investigated the types of dizzy sensations experienced, their evolution, and relationship with other post-concussion symptoms. Thirty New Zealanders (24 female) aged 49 ± 16 years who experienced dizziness or imbalance following their injury completed the Dizziness Handicap Inventory, Visual Vertigo Analogue Scale, and the Hospital Anxiety and Depression Scale. Additional custom questionnaires probed subjective experiences of dizziness and balance, headaches, and difficulties with auditory processing and vision. Just over half the participants (56.7%) experienced a single mTBI. The median time interval since the injury was 16 months (IQR = 24 months). Participants usually reported multiple dizzy symptoms which developed within a week of the injury, although delays of up to six months were reported. Most participants (70%) felt their symptoms improved over time, while lack of improvement was associated with a history of multiple mTBI (P = 0.020). Moderate to strong correlations between questionnaire scores representing dizziness handicap, visual vertigo severity, and auditory processing difficulties (P < 0.001) suggest that dizziness and sensory impairment following mTBI are multi-modal and likely to benefit from holistic, multidisciplinary treatment. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes.MethodsThis pilot study comprised two independent cohorts. The first cohort—part of a Traumatic Head Injury Neuroimaging Classification (THINC) study—with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort—with a mean age of 19 years—comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay.ResultsConcentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690–0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT−/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT−/MRI−, n = 111) findings and UIC (P-values < 0.05).ConclusionThese findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.

ObjectiveA latent disease explanation cannot exclusively explain post-concussion symptoms after mild traumatic brain injury (mTBI). Network analysis offers an alternative form of explanation for relationships between symptoms. The study aimed to apply network analysis to post-concussion symptoms in two different mTBI cohorts; an acute treatment-seeking sample and a sample 10 years post-mTBI.MethodThe treatment-seeking sample (n = 258) were on average 6 weeks post-injury; the 10 year post mTBI sample (n = 193) was derived from a population-based incidence and outcomes study (BIONIC). Network analysis was completed on post-concussion symptoms measured using the Rivermead Post-Concussion Questionnaire.ResultsIn the treatment-seeking sample, frustration, blurred vision, and concentration difficulties were central to the network. These symptoms remained central in the 10 year post mTBI sample. A Network Comparison Test revealed evidence of a difference in network structure across the two samples (p = 0.045). However, the only symptoms that showed significant differences in strength centrality across samples were irritability and restlessness.ConclusionThe current findings suggest that frustration, blurred vision and concentration difficulties may have an influential role in the experience and maintenance of post-concussion symptoms. The impact of these symptoms may remain stable over time. Targeting and prioritising the management of these symptoms may be beneficial for mTBI rehabilitation.

To determine if there are longer-term effects on symptoms, health status, mood, and behavior 10 years after a mild traumatic brain injury (mTBI). Prospective cohort study. Community-based, civilian sample. Adults aged ≥16 years at follow-up who experienced an mTBI 10 years ago, and an age and sex-matched non-injured control group. Not applicable. mTBI cases and controls were asked to complete self-report assessments of functioning (WHO Disability Assessment Schedule Version 2), symptoms (Rivermead Post-Concussion Symptom Questionnaire), health status (100-point scale), alcohol (Alcohol Use Disorders Identification Test) and substance use (Alcohol, Smoking and Substance Involvement Screening Test), and whether they had engaged in any anti-social behaviors over the past 12 months. Data were analyzed for 368 participants (184 mTBI cases and 184 age-sex matched controls). Just over a third of mTBI cases (64, 34.8%) reported that they were still affected by their index mTBI 10 years later. After adjusting for education and ethnicity, the mTBI group had statistically higher overall symptom burden (F=22.32, P <.001, ηp2=0.07) compared with controls. This difference remained after excluding those who experienced a recurrent TBI. The mTBI group were more than 3 times as likely to have engaged in anti-social behavior during the previous 12 months (F=5.89, P =.02). There were no group differences in health status, functioning, or problematic alcohol or substance use 10 years post-injury. This study provides evidence of potential longer-term associations between mTBI, post-concussion symptoms, and anti-social behavior which warrants further evaluation. Future research should also examine if longer-term effects may be preventable with access to early rehabilitation post-injury. [ABSTRACT FROM AUTHOR]

Abstract Background Accurate data on the types of healthcare people seek in the early stages following mild traumatic brain injury (mTBI) in Australia is lacking. We sought to investigate the types of healthcare people seek following mTBI, including seeking no care at all; ascertain the demographic, pre- and peri-injury factors, and symptom characteristics associated with the care that people access; and examine whether choice of care is associated with symptomatic recovery and quality of life. Methods An online retrospective survey of Australians aged 18 to 65 years who had experienced a self-reported ‘concussion’ (mTBI) within the previous 18 months. Types of healthcare accessed were investigated, as well as those who did not seek any care. Data were analysed using frequency and percentages, chi-squared tests and logistic regression models. Results A total of 201 respondents had experienced a self-reported ‘concussion’ but 21.4% of the respondents did not seek any care. Of the 183 respondents who sought healthcare, 52.5% attended a hospital Emergency Department, 41.0% attended a general practitioner and 6.6% accessed sports-based care. Compared to their counterparts, those who had a lower level of education (p = 0.001), had experienced previous mTBI (p = 0.045) or previous mental health issues (p = 0.009) were less likely to seek healthcare, whilst those who had experienced loss of consciousness (p = 0.014), anterograde (p = 0.044) or retrograde (p = 0.009) amnesia, and symptoms including drowsiness (p = 0.005), nausea (p = 0.040), and feeling slow (p = 0.031) were more likely to seek care. Those who did not seek care were more likely to recover within one month (AOR 4.90, 95%CI 1.51 – 15.89, p = 0.008), albeit the relatively large 95%CI warrants careful interpretation. Compared to seeking care, not seeking care was not found to be significantly associated with symptom resolution nor quality of life (p > 0.05). Conclusions This study provides unique insight into factors associated with healthcare utilisation in the early stages following mTBI, as well as outcomes associated with choice of care, including not seeking care. Delivering targeted community education on the signs and symptoms of mTBI, and the advantages of seeking care following injury is an important step forward in the management of this challenging condition.

ObjectiveDescribe dementia cases identified through International Classification of Diseases (ICD) coding in the Long-term Impact of Military-relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) multicenter prospective longitudinal study (PLS) of mild traumatic brain injury (mTBI).DesignDescriptive case series using cross-sectional data.MethodsVeterans Affairs (VA) health system data including ICD codes were obtained for 1563 PLS participants through the VA Informatics and Computing Infrastructure (VINCI). Demographic, injury, and clinical characteristics of Dementia positive and negative cases are described.ResultsFive cases of dementia were identified, all under 65 years old. The dementia cases all had a history of blast-related mTBI and all had self-reported functional problems and four had PTSD symptomatology at the clinical disorder range. Cognitive testing revealed some deficits especially in the visual memory and verbal learning and memory domains, and that two of the cases might be false positives.ConclusionsICD codes for early dementia in the VA system have specificity concerns, but could be indicative of cognitive performance and self-reported cognitive function. Further research is needed to better determine links to blast exposure, blast-related mTBI, and PTSD to early dementia in the military population.

• Self-care deficits first emerged eight weeks after a single closed-head injury. • Injured animals lost social novelty preference within the first month post-injury. • Loss of desire for social interaction developed over a twelve week period. • GluN1 expression increased chronically in the injured frontal cortex and amygdala. • Hippocampal GLT-1 expression was decreased chronically following injury. Mild traumatic brain injury (mTBI) is known to result in chronic somatic, cognitive, and emotional symptoms. Depression is commonly reported among individuals suffering from persistent concussion symptoms; however, the underlying mechanisms are not understood. The glutamatergic system has recently been linked with mTBI and depression due to reports of similar changes in expression of glutamatergic proteins. Using a closed-head controlled cortical impact (cCCI) model in adult male rats (n = 8/group), this study investigated the emergence of self-care deficits and changes in social interaction behaviors at four, eight and twelve weeks post-injury. Western blotting was used to assess associated changes in expression of glutamate transporters and N-methyl-D-aspartate (NMDA) receptor subunits at twelve weeks. Splash test results revealed deficits in self-care behaviors beginning at eight weeks, which continued through twelve weeks in the injury group. Injured animals also exhibited decreased preference for social novelty at four weeks and loss of desire for social interaction as a whole by twelve weeks. GluN1 was increased in injured animals compared to shams in the frontal cortex and amygdala, while decreased GLT-1 was observed in the hippocampus. Linear regression was performed to evaluate relationships between behavioral and molecular variables; the results suggested that injury affects these relationships in a region-dependent manner. Together, these results suggest that the development of chronic depression-like behavior was associated with changes in glutamatergic protein expression. Deeper investigations into how injury influences glutamatergic synaptic protein expression are needed, as this has the potential to affect circuit-level neurotransmission that drives depression-like behavior following mTBI. [ABSTRACT FROM AUTHOR]

BACKGROUND: Veterans Affairs and the Department of Defense (DOD) acknowledge that nutrition may be a modifier of mild traumatic brain injury (TBI) sequelae. Military clinicians are considering nutritional supplements and dietary interventions when managing patients with mild TBI. Therefore, clinicians should be familiar with the current evidence for nutritional interventions in mild TBI and special considerations related to the military lifestyle. OBJECTIVE: This narrative review aims to summarize the existing evidence surrounding the role of special diets and select nutrients in mild TBI outcomes, gut microbiota changes, and special considerations for Service members and Veterans recovering from mild TBI. METHODS: We conducted a literature review in PubMed and Google Scholar limited to nutritional interventions and nine topics with primary focus on mild TBI, although we included some articles related to moderate-to-severe TBI where relevant: 1) ketogenic diet, 2) Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, 3) omega-3 fatty acids, 4) creatine, 5) vitamin D, 6) weight management, 7) gut microbiota, 8) caffeine, and 9) alcohol. We summarized key findings and safety factors where appropriate for each intervention. We also identified nutritional supplement safety and operational rations considerations and areas in need of further research. RESULTS: Preclinical studies and early human trials suggest that the specific nutrients and diets discussed in the current article may offer neuroprotection or benefit during mild TBI rehabilitation. Omega-3 fatty acids, creatine, and vitamin D are generally safe when taken within recommended guidelines. CONCLUSION: More evidence is needed to support nutritional recommendations for enhancing neuroprotection and mitigating mild TBI symptoms in humans. The DOD's Warfighter Nutrition Guide recommends a whole food diet rich in antioxidants, phytonutrients, omega-3 fatty acids, micronutrients, probiotics, and fiber to optimize long-term health and performance. [ABSTRACT FROM AUTHOR]

Objective: Memory and affective processing were compared in young adults with a remote mild traumatic brain injury (mTBI), to healthy younger and older adults. We evaluated memory performance when encoding was done under multi-tasking (divided attention) conditions, likely to exacerbate cognitive and psychological symptoms in mTBI. Methods: Participants studied pairs of unrelated words under either full or divided attention conditions. Memory for single words (item memory) and for pairs of words (associative memory) was then assessed in sequential independent recognition tests, under full attention. Results: Associative memory was poorer than item memory, and worse when encoding was done under divided than full attention. The decline in recognition accuracy from full to divided attention conditions on the associative memory test was significantly greater in mTBI compared to young adults and was similar in magnitude to that observed in older adults under full attention. Self-reported mental and total fatigue increased significantly as performance on the memory tests, following the divided attention condition, decreased, but only in the mTBI group. Conclusions: Results show lingering memory deficits, and suggest that cognitive tasks may be experienced as psychologically more demanding in those with a mTBI, even months or years after injury. [ABSTRACT FROM AUTHOR]

To investigate the long-term outcome of pediatric mild traumatic brain injury (mTBI) in terms of neurocognitive, behavioral, and school functioning and to identify clinical risk factors for adverse outcomes. This study describes the follow-up of a prospective multicenter sample of 89 children with mTBI 3.6 years postinjury and 89 neurologically healthy children matched for sex, age, and socioeconomic status. Neurodevelopmental outcomes were assessed using an intelligence test, behavioral questionnaires, computerized neurocognitive tests, and longitudinal (pre- and postinjury) standardized school performance data. Children with mTBI exhibited intelligence in the average range but had more behavioral problems related to inattentiveness (P = 0.004, d = 0.47) and hyperactive impulsivity (P = 0.01, d = 0.40) and showed poorer neurocognitive performance in information processing stability (P = 0.003, d = −0.55) and Visual Working Memory (P = 0.04, d = −0.39) compared with matched peers. Longitudinal school performance data revealed poorer performance in Technical Reading up to two years postinjury (P = 0.005, d = −0.42) when compared with normative data. Clinical risk factors did not reveal predictive value for adverse outcomes in children with mTBI. This study indicates that children with mTBI are at risk of long-term deficits in neurocognitive and behavioral functioning, with longitudinal evidence suggesting shortfalls in school performance up to two years postinjury. Clinical risk factors do not provide a solid basis for long-term neurodevelopmental prognosis. Findings emphasize the importance of, and challenges for, early identification of children at risk for adverse neurodevelopmental outcome after mTBI. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients (n = 192, age 16–60 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) <30 min, and post-traumatic amnesia (PTA) <24 h were included. Blood samples were collected at admission (within 72 h), 2 weeks, and 3 months. Concentrations of blood biomarkers associated with central nervous system (CNS) damage (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], and tau) and inflammation (interferon gamma [IFNγ], interleukin [IL]-8, eotaxin, macrophage inflammatory protein-1-beta [MIP]-1β, monocyte chemoattractant protein [MCP]-1, interferon-gamma-inducible protein [IP]-10, IL-17A, IL-9, tumor necrosis factor [TNF], basic fibroblast growth factor [FGF]-basic platelet-derived growth factor [PDGF], and IL-1 receptor antagonist [IL-1ra]) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on magnetic resonance imaging (MRI; within 72 h), and extracranial injuries. Delta values, that is, time-point differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multi-variable models, female sex, longer PTA duration, MRI findings, and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL, or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFNγ were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A, and FGF-basic at 2 weeks compared with admission, MCP-1 at 3 months compared with admission, and TNF at 2 weeks and 3 months compared with admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both time-point comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, whereas the optimal combination of biomarkers yielded areas under the curve (AUCs) between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling time-point after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS. [ABSTRACT FROM AUTHOR]

We examined the association between cognitive functioning and health-related quality of life (HR-QOL) in military veterans with a history of mild traumatic brain injury (mTBI) using two methods to assess cognition: mean performance on cognitive composite scores and across-test intraindividual variability (IIV). The sample included 73 veterans (84.9% male; age, mean = 32.47 years) who completed neuropsychological testing and self-report questionnaires ∼7 years post-injury. Three cognitive composite scores representing mean performance were computed, including memory, attention/processing speed (A/PS), and executive functioning (EF). Three IIV indices were also calculated reflecting degree of dispersion across the same cognitive domains: memory-IIV, A/PS-IIV, and EF-IIV. The Posttraumatic Stress Disorder (PTSD) Checklist-Military Version (PCL-M) was used to assess current PTSD symptoms, and the World Health Organization Quality of Life Short Version Physical Health domain was used to assess HR-QOL. Hierarchical linear regressions adjusting for PTSD symptoms demonstrated that IIV indices, but not mean cognitive composite scores, significantly predicted HR-QOL. Specifically, memory-IIV, A/PS-IIV, and EF-IIV, when taken together, made an independent and significant contribution to the prediction of HR-QOL. Examination of the standardized coefficients showed that the A/PS-IIV index was uniquely associated with HR-QOL, such that higher A/PS-IIV scores significantly predicted poorer HR-QOL. Our results are the first to show that, in veterans with remote mTBI histories, greater fluctuations in cognitive performance significantly contribute to poorer HR-QOL, even after accounting for PTSD symptom severity. Moreover, findings suggest that, compared to traditional mean cognitive performance scores, measures of IIV may represent more sensitive indicators of clinical outcome and better align with subjective experiences of distress.

Abstract Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated-mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long-Evans rats. We found that r-mTBI did not lead to cumulative neurological deficits with the model. R-mTBI animals exhibited an increase in BrdU + (bromodeoxyuridine positive) cells in the dentate gyrus (DG), and that this increase was more robust in male animals. This increase was not sustained, and cell proliferation returning to normal by PID3. A greater increase in BrdU + cells was observed in the dorsal DG in both male and female r-mTBI animals at PID1. Using Ki-67 expression as an endogenous marker of cellular proliferation, a robust proliferative response following r-mTBI was observed in male animals at PID1 that persisted until PID3, and was not constrained to the DG alone. Triple labeling experiments (Iba1+, GFAP+, Brdu+) revealed that a high proportion of these proliferating cells were microglia/macrophages, indicating there was a heightened inflammatory response. Overall, these findings suggest that rapid head acceleration with the ACHI model produces an mTBI, but that the acute neurological deficits do not increase in severity with repeated administration. R-mTBI transiently increases cellular proliferation in the hippocampus, particularly in male animals, and the pattern of cell proliferation suggests that this represents a neuroinflammatory response that is focused around the mid-brain rather than peripheral cortical regions. These results add to growing literature indicating sex differences in proliferative and inflammatory responses between females and males. Targeting proliferation as a therapeutic avenue may help reduce the short term impact of r-mTBI, but there may be sex-specific considerations.

Mild traumatic brain injury (mTBI) or concussion is prevalent among trauma patients, but symptoms vary. Assessing discharge safety is not standardized. At our institution, occupational therapy (OT) performs cognitive assessments for mTBI to determine discharge readiness, potentially increasing resource utilization. We aimed to describe characteristics and outcomes in mTBI trauma patients and hypothesized that OT consultation was associated with increased length of stay (LOS). This is a retrospective study at a level 1 trauma center over 17 mo. All patients with mTBI, without significant concomitant injuries, were included. We collected data regarding OT assessment, LOS, mechanism of injury, Glasgow coma score, injury severity score (ISS), concussion symptoms, and patient disposition. Statistical analysis was performed, and significance was determined when P < 0.05. Two hundred thirty three patients were included. Median LOS was 1 d and ISS 5. Ninety percent were discharged home. The most common presenting symptom was loss of consciousness (85%). No symptoms were associated with differences in LOS or discharge disposition (P > 0.05). OT consult (n = 114, 49%) was associated with longer LOS and higher ISS (P < 0.01). Representation with concussive symptoms, discharge disposition, mechanism of injury, and patient demographics were no different regardless of OT consultation (P > 0.05). mTBI is common and assessment for discharge safety is not standardized. OT cognitive assessment was associated with longer LOS and higher injury severity. Despite institutional culture, OT consultation was variable and not associated with improved concussion-related outcomes. Our data suggest that OT is not required for mTBI discharge readiness assessment. To improve resource utilization, more selective OT consultation should be considered. Further prospective data are needed to identify which patients would most benefit. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (TBI) and concussion can have serious consequences that develop over time with unpredictable levels of recovery. Millions of concussions occur yearly, and a substantial number result in lingering symptoms, loss of productivity, and lower quality of life. The diagnosis may not be made for multiple reasons, including due to patient hesitancy to undergo neuroimaging and inability of imaging to detect minimal damage. Biomarkers could fill this gap, but the time needed to send blood to a laboratory for analysis made this impractical until point-of-care measurement became available. A handheld blood test is now on the market for diagnosis of concussion based on the specific blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl terminal hydrolase L1 (UCH-L1). This paper discusses rapid blood biomarker assessment for mild TBI and its implications in improving prediction of TBI course, avoiding repeated head trauma, and its potential role in assessing new therapeutic options. Although we focus on the Abbott i-STAT TBI plasma test because it is the first to be FDA-cleared, our discussion applies to any comparable test systems that may become available in the future. The difficulties in changing emergency department protocols to include new technology are addressed.

We investigated whether clinically normal older adults with remote, mild traumatic brain injury (mTBI) show evidence of higher cortical Aβ burden. Our study included 134 clinically normal older adults (age 74.1 ± 6.8 years, 59.7% female, 85.8% white) who underwent Aβ positron emission tomography (Aβ-PET) and who completed the Ohio State University Traumatic Brain Injury Identification questionnaire. We limited participants to those reporting injuries classified as mTBI. A subset (N = 30) underwent a second Aβ-PET scan (mean 2.7 years later). We examined the effect of remote mTBI on Aβ-PET burden, interactions between remote mTBI and age, sex, and APOE status, longitudinal Aβ accumulation, and the interaction between remote mTBI and Aβ burden on memory and executive functioning. Of 134 participants, 48 (36%) reported remote mTBI (0, N = 86; 1, N = 31, 2+, N = 17; mean 37 ± 23 years since last mTBI). Effect size estimates were small to negligible for the association of remote mTBI with Aβ burden (p = .94, η2

Introduction. Loss of consciousness (LOC) is used as a diagnostic feature of mild traumatic brain injury (MTBI). However, only 10% of concussions result in LOC. There are only a limited number of in-vivo studies dealing with unconsciousness and structural and functional integrity of the brainstem in patients with MTBI. The aim of our pilot study was to assess the sensitivity of proton magnetic resonance spectroscopy (1H-MRS) to detect metabolic changes in the brainstem in patients after MTBI with unconscioussness. Methods. Twenty-four patients (12 with LOC, and 12 without LOC) within 3 days of MTBI and 19 healthy controls were examined. All subjects underwent single-voxel 1H-MRS examination of the upper brainstem. Spectra were evaluated using LCModel software. Ratios of total N-acetylaspartate (tNAA), total choline-containing compounds (tCho) and glutamate plus glutamine (Glx) to total creatine (tCre) were used for calculations. Results. We found a significant decrease in tNAA/tCre and tCho/tCre ratios in the patient group with LOC when compared with the control group of healthy volunteers (P=0.002 and P=0.041, respectively), and a significant decrease in the tNAA/tCre ratio in the LOC group when compared with patients without LOC (P=0.04). Other metabolite ratios in the brainstem did not show any significant group differences. Conclusion. Our findings indicate that decrease of tNAA/tCre ratio in the upper brainstem using single-voxel 1H-MRS may provide a potential biomarker for MTBI associated with LOC.

The main advantage of diffusion tensor tractography is that it allows the entire neural tract to be evaluated. In addition, configurational analysis of reconstructed neural tracts can indicate abnormalities such as tearing, narrowing, or discontinuations, which have been used to identify axonal injury of neural tracts in concussion patients. This review focuses on the characteristic features of axonal injury in concussion or mild traumatic brain injury (mTBI) patients through the use of diffusion tensor tractography. Axonal injury in concussion (mTBI) patients is characterized by their occurrence in long neural tracts and multiple injuries, and these characteristics are common in patients with diffuse axonal injury and in concussion (mTBI) patients with axonal injury. However, the discontinuation of the corticospinal tract is mostly observed in diffuse axonal injury, and partial tearing and narrowing in the subcortical white matter are frequently observed in concussion (mTBI) patients with axonal injury. This difference appears to be attributed to the observation that axonal injury in concussion (mTBI) patients is the result of weaker forces than those producing diffuse axonal injuries. In addition, regarding the fornix, in diffuse axonal injury, discontinuation of the fornical crus has been frequently reported, but in concussion (mTBI) patients, many collateral branches form in the fornix in addition to these findings in many case studies. It is presumed that the impact on the brain in TBI is relatively weaker than that in diffuse axonal injury, and that the formation of collateral branches occurs during the fornix recovery process. Although the occurrence of axonal injury in multiple areas of the brain is an important feature of diffuse axonal injury, case studies in concussion (mTBI) have shown that axonal injury occurs in multiple neural tracts. Because axonal injury lesions in mTBI patients may persist for approximately 10 years after injury onset, the characteristics of axonal injury in concussion (mTBI) patients, which are reviewed and categorized in this review, are expected to serve as useful supplementary information in the diagnosis of axonal injury in concussion (mTBI) patients.

The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10⁻15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors for CTE are challenging to identify because injury mechanisms of MTBI are heterogeneous, clinical manifestations and management vary, and CTE is a postmortem diagnosis, making prospective studies difficult. There is growing interest in the genetic influence on head trauma and development of CTE. Apolipoprotein epsilon 4 (APOE-ε4) associates with many neurologic diseases, and consensus on the ε4 allele as a risk factor is lacking. This review investigates the influence of APOE-ε4 on MTBI and CTE. A comprehensive PubMed literature search (1966 to 12 June 2018) identified 24 unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6 population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group). APOE-ε4 genotype is found to associate with outcomes in 4/8 athletic reports, 3/5 military reports, and 5/6 population-based reports following MTBI. Evidence on the association between APOE-ε4 and CTE from case series is equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed in MTBI.

Abstract Background Mild traumatic brain injury (mTBI) is an increasing public health problem, because of its persistent symptoms and several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help to guide the prevention of persistent symptoms following mTBI. The prognosis of mTBI has stimulated several empirical primary research papers and many systematic reviews leading to the identification of a wide range of factors. We aim to synthesize these factors to get a better understanding of their breadth and scope. Methods We conducted an overview of systematic reviews. We searched in databases systematic reviews synthesizing evidence about the prognosis of persistent symptoms after mTBI in the adult population. Two reviewers independently screened all references and selected eligible reviews based on eligibility criteria. They extracted relevant information using an extraction grid. They also rated independently the risk of bias using the ROBIS tool. We synthesized evidence into a comprehensive conceptual map to facilitate the understanding of prognostic factors that have an impact on persistent post-concussion symptoms. Results From the 3857 references retrieved in a database search, we included 25 systematic reviews integrating the results of 312 primary articles published between 1957 and 2019. We examined 35 prognostic factors from the systematics reviews. No single prognostic factor demonstrated convincing and conclusive results. However, age, sex, and multiple concussions showed an affirmatory association with persistent post-concussion outcomes in systematic reviews. Conclusion We highlighted the need for a comprehensive picture of prognostic factors related to persistent post-concussion symptoms. We believe that these prognostic factors would guide clinical decisions and research related to prevention and intervention regarding persistent post-concussion symptoms. Systematic review registration PROSPERO CRD42020176676

Mild traumatic brain injury (mTBI), often called concussion, is a prevalent condition that can have significant implications for people’s health, functioning and well-being. Current clinical practice relies on self-reported symptoms to guide decision-making regarding return to sport, employment, and education. Unfortunately, reliance on subjective evaluations may fail to accurately reflect the resolution of neuropathology, exposing individuals with mTBI to an increased risk of further head trauma. No objective technique currently exists to assess the microstructural alterations to brain tissue which characterise mTBI. MRI-based T2 relaxation is a quantitative imaging technique that is susceptible to detecting fluid properties in the brain and is hypothesised to indicate neuroinflammation. This study aimed to investigate the potential of individual-level T2 relaxometry to evaluate cellular damage from mTBI. 20 male participants with acute sports-related mTBI (within 14 days post-injury) and 44 healthy controls were recruited for this study. Each mTBI participant’s voxel-wise T2 relaxometry map was analysed against healthy control averages using a voxel-wise z-test with false discovery rate correction. Five participants were re-scanned after clinical recovery and results were compared to their acute T2 relaxometry maps to assess reduction in potential neuroinflammation. T2 relaxation times were significantly increased in 19/20 (95 %) mTBI participants compared to healthy controls, in regions including the hippocampus, frontal cortex, parietal cortex, insula, cingulate cortex and cerebellum. Results suggest the presence of increased cerebral fluid in individuals with mTBI. Longitudinal results indicated a reduction in T2 relaxation for all five participants, indicating a possible resolution over time. This research highlights the potential of individual-level T2 relaxometry MRI as a non-invasive method for assessing subtle brain pathology in mTBI. Identifying and monitoring changes in the fluid content in the brain could aid in predicting recovery and developing individualised treatment plans for individuals with mTBI. Future research should validate this measure with other markers of inflammation (e.g. from blood biomarkers) to test whether T2-relaxometry is related to subtle brain inflammation in mTBI. In addition, future research should utilise larger control groups to establish normative ranges and compute robust z-score analyses.

BackgroundBehavioral dyscontrol occurs commonly in the general population and in United States service members and Veterans (SM/V). This condition merits special attention in SM/V, particularly in the aftermath of deployments. Military deployments frequently give rise to posttraumatic stress disorder (PTSD) and deployment-related mild TBI traumatic brain injury (TBI), potentially leading to manifestations of behavioral dyscontrol.ObjectiveExamine associations among PTSD symptom severity, deployment-related mild traumatic brain injury, and behavioral dyscontrol among SM/V.DesignSecondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium – Chronic Effects of Neurotrauma Consortium prospective longitudinal study among SM/V (N = 1,808).MethodsUnivariable and multivariable linear regression models assessed the association and interaction effects between PTSD symptom severity, as assessed by the PTSD Checklist for the Diagnostic and Statistical Manual, 5th edition (PCL-5), and deployment-related mild TBI on behavioral dyscontrol, adjusting for demographics, pain, social support, resilience, and general self-efficacy.ResultsAmong the 1,808 individuals in our sample, PTSD symptom severity (B = 0.23, 95% CI: 0.22, 0.25, p 22.96.ConclusionResults indicated an association between PTSD symptom severity, deployment-related mild TBI, and behavioral dyscontrol among SM/V. Notably, the effect of deployment-related mild TBI was pronounced for individuals with lower PTSD symptom severity. Higher social support scores were associated with lower dyscontrol, emphasizing the potential for social support to be a protective factor. General self-efficacy was also associated with reduced behavioral dyscontrol.

Resting-state fMRI can be used to identify recurrent oscillatory patterns of functional connectivity within the human brain, also known as dynamic brain states. Alterations in dynamic brain states are highly likely to occur following pediatric mild traumatic brain injury (pmTBI) due to the active developmental changes. The current study used resting-state fMRI to investigate dynamic brain states in 200 patients with pmTBI (ages 8-18 years, median = 14 years) at the subacute (∼1-week post-injury) and early chronic (∼ 4 months post-injury) stages, and in 179 age- and sex-matched healthy controls (HC). A k-means clustering analysis was applied to the dominant time-varying phase coherence patterns to obtain dynamic brain states. In addition, correlations between brain signals were computed as measures of static functional connectivity. Dynamic connectivity analyses showed that patients with pmTBI spend less time in a frontotemporal default mode/limbic brain state, with no evidence of change as a function of recovery post-injury. Consistent with models showing traumatic strain convergence in deep grey matter and midline regions, static interhemispheric connectivity was affected between the left and right precuneus and thalamus, and between the right supplementary motor area and contralateral cerebellum. Changes in static or dynamic connectivity were not related to symptom burden or injury severity measures, such as loss of consciousness and post-traumatic amnesia. In aggregate, our study shows that brain dynamics are altered up to 4 months after pmTBI, in brain areas that are known to be vulnerable to TBI. Future longitudinal studies are warranted to examine the significance of our findings in terms of long-term neurodevelopment.

Background: Mild traumatic brain injury (mTBI) is common in children. Long-term cognitive and behavioral outcomes as well as underlying structural brain alterations following pediatric mTBI have yet to be determined. In addition, the effect of age-at-injury on long-term outcomes is largely unknown. Methods: Children with a history of mTBI (n = 406; M age = 10 years, SD age = 0.63 years) who participated in the Adolescent Brain Cognitive Development (ABCD) study were matched (1:2 ratio) with typically developing children (TDC; n = 812) and orthopedic injury (OI) controls (n = 812). Task-based executive functioning, parent-rated executive functioning and emotion-regulation, and self-reported impulsivity were assessed cross-sectionally. Regression models were used to examine the effect of mTBI on these domains. The effect of age-at-injury was assessed by comparing children with their first mTBI at either 0-3, 4-7, or 8-10 years to the respective matched TDC controls. Fractional anisotropy (FA) and mean diffusivity (MD), both MRI-based measures of white matter microstructure, were compared between children with mTBI and controls. Results: Children with a history of mTBI displayed higher parent-rated executive dysfunction, higher impulsivity, and poorer self-regulation compared to both control groups. At closer investigation, these differences to TDC were only present in one respective age-at-injury group. No alterations were found in task-based executive functioning or white matter microstructure. Conclusions: Findings suggest that everyday executive function, impulsivity, and emotion-regulation are affected years after pediatric mTBI. Outcomes were specific to the age at which the injury occurred, suggesting that functioning is differently affected by pediatric mTBI during vulnerable periods. Groups did not differ in white matter microstructure. [ABSTRACT FROM AUTHOR]

Mild traumatic brain injury (mTBI) is an important public health issue, as it can lead to long-term neurological symptoms and risk of neurodegenerative disease. The pathophysiological mechanisms driving this remain unclear, and currently there are no effective therapies for mTBI. In this study on repeated mTBI (rmTBI), we have induced three mild closed-skull injuries or sham procedures, separated by 24 h, in C57BL/6 mice. We show that rmTBI mice have prolonged righting reflexes and astrogliosis, with neurological impairment in the Morris water maze (MWM) and the light dark test. Cortical and hippocampal tissue analysis revealed DNA damage in the form of double-strand breaks, oxidative damage, and R-loops, markers of cellular senescence including p16 and p21, and signaling mediated by the cGAS-STING pathway. This study identified novel sex differences after rmTBI in mice. Although these markers were all increased by rmTBI in both sexes, females had higher levels of DNA damage, lower levels of the senescence protein p16, and lower levels of cGAS-STING signaling proteins compared to their male counterparts. Single-cell RNA sequencing of the male rmTBI mouse brain revealed activation of the DNA damage response, evidence of cellular senescence, and pro-inflammatory markers reminiscent of the senescence-associated secretory phenotype (SASP) in neurons and glial cells. Cell-type specific changes were also present with evidence of brain immune activation, neurotransmission alterations in both excitatory and inhibitory neurons, and vascular dysfunction. Treatment of injured mice with the senolytic drug ABT263 significantly reduced markers of senescence only in males, but was not therapeutic in females. The reduction of senescence by ABT263 in male mice was accompanied by significantly improved performance in the MWM. This study provides compelling evidence that senescence contributes to brain dysfunction after rmTBI, but may do so in a sex-dependent manner.