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The objective was to clarify occurrence, phenomenology, and risk factors for novel psychiatric disorder (NPD) in the first 3 months after mild traumatic brain injury (mTBI) and orthopedic injury (OI). Children aged 8-15 years with mTBI (n = 220) and with OI but no TBI (n = 110) from consecutive admissions to an emergency department were followed prospectively at baseline and 3 months post-injury with semi-structured psychiatric interviews to document the number of NPDs that developed in each participant. Pre-injury child variables (adaptive, cognitive, and academic function, and psychiatric disorder), pre-injury family variables (socioeconomic status, family psychiatric history, and family function), and injury severity were assessed and analyzed as potential confounders and predictors of NPD. NPD occurred at a significantly higher frequency in children with mTBI versus OI in analyses unadjusted (mean ratio [MR] 3.647, 95% confidence interval [CI(95)] (1.264, 15.405), p = 0.014) and adjusted (MR = 3.724, CI(95) (1.264, 15.945), p = 0.015) for potential confounders. In multi-predictor analyses, the factors besides mTBI that were significantly associated with higher NPD frequency after adjustment for each other were pre-injury lifetime psychiatric disorder [MR = 2.284, CI(95) (1.026, 5.305), p = 0.043]; high versus low family psychiatric history [MR = 2.748, CI(95) (1.201, 6.839), p = 0.016], and worse socio-economic status [MR = 0.618 per additional unit, CI(95) (0.383, 0.973), p = 0.037]. These findings demonstrate that mild injury to the brain compared with an OI had a significantly greater deleterious effect on psychiatric outcome in the first 3 months post-injury. This effect was present even after accounting for specific child and family variables, which were themselves independently related to the adverse psychiatric outcome.

Background The use of blood biomarkers after mild traumatic brain injury (mTBI) has been widely studied. We have identified eight unresolved issues related to the use of five commonly investigated blood biomarkers: neurofilament light chain, ubiquitin carboxy-terminal hydrolase-L1, tau, S100B, and glial acidic fibrillary protein. We conducted a focused literature review of unresolved issues in three areas: mode of entry into and exit from the blood, kinetics of blood biomarkers in the blood, and predictive capacity of the blood biomarkers after mTBI. Findings Although a disruption of the blood brain barrier has been demonstrated in mild and severe traumatic brain injury, biomarkers can enter the blood through pathways that do not require a breach in this barrier. A definitive accounting for the pathways that biomarkers follow from the brain to the blood after mTBI has not been performed. Although preliminary investigations of blood biomarkers kinetics after TBI are available, our current knowledge is incomplete and definitive studies are needed. Optimal sampling times for biomarkers after mTBI have not been established. Kinetic models of blood biomarkers can be informative, but more precise estimates of kinetic parameters are needed. Confounding factors for blood biomarker levels have been identified, but corrections for these factors are not routinely made. Little evidence has emerged to date to suggest that blood biomarker levels correlate with clinical measures of mTBI severity. The significance of elevated biomarker levels thirty or more days following mTBI is uncertain. Blood biomarkers have shown a modest but not definitive ability to distinguish concussed from non-concussed subjects, to detect sub-concussive hits to the head, and to predict recovery from mTBI. Blood biomarkers have performed best at distinguishing CT scan positive from CT scan negative subjects after mTBI.

Background Headache is one of the most common symptoms after concussion, and mild traumatic brain injury (mTBI) is a risk factor for chronic migraine (CM). However, there remains a paucity of data regarding the impact of mTBI on migraine-related symptoms and clinical course. Methods Of 2161 migraine patients who participated in the American Registry for Migraine Research between February 2016 and March 2020, 1098 completed questions assessing history of TBI (50.8%). Forty-four patients reported a history of moderate to severe TBI, 413 patients reported a history of mTBI. Patients’ demographics, headache symptoms and triggers, history of physical abuse, allodynia symptoms (ASC-12), migraine disability (MIDAS), depression (PHQ-2), and anxiety (GAD-7) were compared between migraine groups with (n = 413) and without (n = 641) a history of mTBI. Either the chi-square-test or Fisher’s exact test, as appropriate, was used for the analyses of categorical variables. The Mann-Whitney test was used for the analyses of continuous variables. Logistic regression models were used to compare variables of interest while adjusting for age, gender, and CM. Results A significantly higher proportion of patients with mTBI had CM (74.3% [307/413] vs. 65.8% [422/641], P = 0.004), had never been married or were divorced (36.6% [147/402] vs. 29.4% [187/636], P = 0.007), self-reported a history of physical abuse (24.3% [84/345] vs. 14.3% [70/491], P P = 0.003), had headache-related vertigo (23.0% [95/413] vs. 15.9% [102/640], P = 0.009), and difficulty finding words (43.0% [174/405] vs. 32.9% [208/633], P P = 0.018) and reading (6.6% [26/393] vs. 3.0% [18/607], P = 0.016), compared to patients without mTBI. Patients with mTBI had significantly greater ASC-12 scores (median [interquartile range]; 5 [1–9] vs. 4 [1–7], P P = 0.034), and PHQ-2 scores (1 [0–2] vs. 1 [0–2], P = 0.012). Conclusion Patients with a history of mTBI are more likely to have a self-reported a history of physical abuse, vertigo, and allodynia during headache attacks, headaches triggered by lack of sleep and reading, greater headache burden and headache disability, and symptoms of anxiety and depression. This study suggests that a history of mTBI is associated with the phenotype, burden, clinical course, and associated comorbid diseases in patients with migraine, and highlights the importance of inquiring about a lifetime history of mTBI in patients being evaluated for migraine.

OBJECTIVE To examine perceived injustice and its associations with self-reported symptoms and return to work at 3 months after injury in a prospectively recruited sample of patients with mild traumatic brain injury (mTBI). DESIGN Observational study. SETTING TBI outpatient unit. PARTICIPANTS Adult patients aged 18 to 68 years with mTBI (n = 100) or orthopedic injury ([OI]; n = 34). MAIN MEASURES The Injustice Experience Questionnaire (IEQ) and its associations with the Rivermead Post Concussion Questionnaire (RPQ), Beck Depression Inventory-Second Edition (BDI-II), PTSD Checklist-Civilian Version (PCL-C), and Pain Visual Analog Scale (PVAS). Information on injury-related characteristics, compensation seeking and litigation, and return-to-work status was also collected. RESULTS Median IEQ total score was 3 (range, 0-23) in the mTBI group and 2.5 (range, 0-25) in the OI group. In the mTBI group, IEQ was significantly correlated with RPQ (rs = 0.638, P < .01), BDI-II (rs = 0.612, P < .01), PCL-C (rs = 0.679, P < .01), and PVAS (rs = 0.232, P < .05). The association between IEQ and PCL-C (rs =0.797, P < .01) and BDI-II (rs = 0.395, P < .05) was also found in the OI group. In both groups, patients who were still on sick leave at 3 months after injury tended to report higher perceived injustice (IEQ total score) than patients who had returned to work or studies. However, this difference did not reach statistical significance. CONCLUSIONS Perceived injustice is associated with self-reported symptoms in patients with mTBI. Our results suggest that perceived injustice could be a relevant construct to consider in clinical management of patients with mTBI. Also, perceived injustice could be a potential target for psychological interventions promoting recovery after mTBI.

Background Balance impairment and lack of postural orientation are serious problems in patients with repetitive mild traumatic brain injury (mTBI). Objective To investigate whether anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can improve balance control and gait in repetitive mTBI rat models. Methods In this prospective animal study, 65 repetitive mTBI rats were randomly assigned to two groups: the tDCS group and the control group. To create repetitive mTBI model rats, we induced mTBI in the rats for 3 consecutive days. The tDCS group received one session of anodal tDCS over the M1 area 24 h after the third induced mTBI, while the control group did not receive tDCS treatment. Motor-evoked potential (MEP), foot-fault test, and rotarod test were evaluated before mTBI, before tDCS and after tDCS. The Mann–Whitney U test and Wilcoxon signed rank test were used to assess the effects of variables between the two groups. Results Anodal tDCS over the M1 area significantly improved the amplitude of MEP in the tDCS group (p = 0.041). In addition, rotarod duration was significantly increased in the tDCS group (p = 0.001). The foot-fault ratio was slightly lower in the tDCS group, however, this was not statistically significant. Conclusion Anodal tDCS at the M1 area could significantly improve the amplitude of MEP and balance function in a repetitive mTBI rat model. We expect that anodal tDCS would have the potential to improve balance in patients with repetitive mTBI.

Background Mild traumatic brain injury is the leading cause of arrivals to emergency department due to trauma in the 65-year-old population and over. Recent studies conducted in ED suggested a low intracranial lesion prevalence. The objectives of this study were to assess the prevalence and risk factors of intracranial lesion in older patients admitted to emergency department for mild traumatic brain injury by reporting in the emergency department the precise anamnesis of injury and clinical findings. Methods Patients of 65 years old and over admitted in emergency department were prospectively included in this monocentric study. The primary outcome was the prevalence of intracranial lesion threw neuroimaging. Results Between January and June 2019, 365 patients were included and 66.8% were women. Mean age was 86.5 years old (SD = 8.5). Ground-level fall was the most common cause of mild traumatic brain injury and occurred in 335 patients (91.8%). Overall, 26 out of 365 (7.2%) patients had an intracranial lesion. Compared with cutaneous frontal impact (medium risk group), the relative risk of intracranial lesion was 2.54 (95% CI 1.20 to 5.42) for patients with temporoparietal or occipital impact (high risk group) and 0.12 (95% CI 0.01 to 0.93) for patients with facial impact or no cutaneous impact (low risk group). There was not statistical increase in risk of intracranial injury with patients receiving antiplatelets (RR = 1.43; 95% CI 0.68 to 2.99) or anticoagulants (RR = 0.98; 95% CI 0.45 to 2.14). Conclusion Among patients of 65 years old and over, the prevalence of intracranial lesion after a mild traumatic brain injury was similar to the younger adult population. The cutaneous impact location on clinical examination at the emergency department may identify older patients with low, medium and high risk for intracranial lesion.

Objective:To investigate whether the ‘Brains Ahead! Intervention for children and adolescents with mild traumatic brain injury’ was implemented as intended. In addition, involvement in and satisfaction with the intervention among patients, caregivers and professionals delivering the intervention were studied.Design:Mixed methods, prospective study.Participants:Children with mild traumatic brain injury and their caregivers, allocated to the intervention group of the randomized controlled trial in the ‘Brains Ahead!’ study, and the two professionals providing the intervention.Intervention:The intervention consists of a standardized and individualized psychoeducational session with written take-home information, and follow-up telephone call(s).Main measures:Registration forms, evaluation questionnaires for patients and caregivers and semi-structured interviews for professionals.Data analysis:Qualitative data were categorized based on content. Quantitative data were reported as descriptive statistics.Results:Fifty-five patients and caregivers out of 60 study-participants attended both sessions. All elements of the intervention were delivered to 53 study-participants. Evaluation questionnaires were completed by 21 of the 31 patients aged 12 years and older, and by 41 caregivers. Overall, the sessions were considered useful by 19 patients, 40 caregivers and both professionals. Reassurance, creating a better understanding and recognition of symptoms were rated as important aspects. On a scale from 1 to 10, the intervention was rated by children, caregivers and professionals with 7.6 (SD 1.2), 8.1 (SD .9) and 8.0 (SD .0), respectively.Conclusion:The ‘Brains Ahead!’ intervention was largely implemented as intended and the process evaluation revealed that it is considered feasible according to patients, caregivers and professionals.

Introduction: Headache is one of the most frequent reported symptom after mild traumatic brain injury and it affects normal functioning and life as a whole. The goal: The goal is the evaluation of access, the quality and characteristics of the headache which occurs after the mild traumatic brain injury. Material and methods: The research has been done as a study section in the clinical center of Vojvodina, in the neurosurgery section. A survey questionnaire constructed for the purposes of this research was used as a research instrument. The survey questionnaire included twenty-one questions.. The norm for including respondents in the research was for them to be hospitalized patients with mild traumatic brain injury and the norm for determining how bad the injury was Glazgow's coma score was used. For determining the intensity of the headache the numeric pain rate scale from zero to ten was used. Results: The posttraumatic headache was present in all patients. Most of the respondents described the headache as dull pain of high intensity, 50% of them said that the headache is disturbing them while doing everyday activities and that the intensity of the pain is worst in the morning than at night. Also, some reported that bright light, thinking and talking increase the pain level. Conclusion: The data from this study indicate that headaches in patients after mild TBI can be a major problem in terms of their functional abilities. Thus, the primary focus of nurses should be on early detection and relief of these symptoms. We can also view this study as an initial step, which can affect nurses' practice, and thus the well-being of patients and society as a whole.

Background Mild-traumatic brain injury (mTBI) and concussions cause significant morbidity. To date, synthesis of specific health care disparities and gaps in care for rural mTBI/concussion patients remains needed. Methods A comprehensive literature search was performed using PubMed database for English articles with keywords “rural” and (“concussion” or “mild traumatic brain injury”) from 1991 to 2019. Eighteen articles focusing on rural epidemiology (n = 5), management/cost (n = 5), military (n = 2), and concussion prevention/return to play (n = 6) were included. Results mTBI/concussion incidence was higher in rural compared with urban areas. Compared with urban patients, rural patients were at increased risk for vehicular injuries, lifetime number of concussions, admissions for observation without neuroimaging, and injury-related costs. Rural patients were less likely to utilize ambulatory and mental health services following mTBI/concussion. Rural secondary schools had decreased access to certified personnel for concussion evaluation, and decreased use of standardized assessment instruments/neurocognitive testing. While school coaches were aware of return-to-play laws, mTBI/concussion education rates for athletes and parents were suboptimal in both settings. Rural veterans were at increased risk for postconcussive symptoms and posttraumatic stress. Telemedicine in rural/low-resource areas is an emerging tool for rapid evaluation, triage, and follow-up. Conclusions Rural patients are at unique risk for mTBI/concussions and health care costs. Barriers to care include lower socioeconomic status, longer distances to regional medical center, and decreased availability of neuroimaging and consultants. Due to socioeconomic and distance barriers, rural schools are less able to recruit personnel certified for concussion evaluation. Telemedicine is an emerging tool for remote triage and evaluation.

Primary Objective: Visual photosensitivity following mild traumatic brain injury (mTBI) can cause mild discomfort to significant pain and can affect a person's ability to lead a regular life and perform normal activities. The purpose of the present study is twofold: (1) To determine the recovery pattern of visual photosensitivity following mTBI and (2) to find out whether the onset of visual photosensitivity and its recovery pattern is any different among habitual screen users (HSU) (chronic exposure to digital device screens). Materials and Methods: This study was a hospital-based prospective, analytical, observational study. The study period was from July 2017 to March 2019. All the mTBI patients with visual photosensitivity who fulfilled the inclusion Criteria were followed up for 1 year to capture their recovery profile. Results: In 60% of the patients, the time of appearance of visual photosensitivity was at around 3 month's post-mTBI. Nearly 66.6% of patients suffering from visual photosensitivity following mTBI recovered within 3 months following the onset of their symptoms. The symptoms of visual photosensitivity appeared earlier among the HSU as compared to nonscreen users (P = 0.0039). The recovery from the symptoms of visual photosensitivity following mTBI is delayed in HSU (P = 0.0028). The patients in whom the symptoms of visual photosensitivity persisted beyond a year were predominantly HSU (P = 0.0062). Conclusions: The present study has given a new insight on the timeline of recovery for the patients with visual photosensitivity following mTBI. To the best of our knowledge, this is the only study which has shown how chronic exposure to blue light from digital device screens can affect the recovery of visual symptoms such as visual photosensitivity following mTBI.

Despite the often seemingly innocuous nature of a mild traumatic brain injury (mTBI), its consequences can be devastating, comprising debilitating symptoms that interfere with daily functioning. Currently, it is still difficult to pinpoint the exact cause of adverse outcome after mTBI. In fact, extensive research suggests that the underlying etiology is multifactorial. In the acute and early sub-acute stages, the pathophysiology of mTBI is likely to be dominated by complex physiological alterations including cellular injury, inflammation, and the acute stress response, which could lead to neural network dysfunction. In this stage, patients often report symptoms such as fatigue, headache, unstable mood and poor concentration. When time passes, psychological processes, such as coping styles, personality and emotion regulation, become increasingly influential. Disadvantageous, maladaptive, psychological mechanisms likely result in chronic stress which facilitates the development of long-lasting symptoms, possibly via persistent neural network dysfunction. So far, a systemic understanding of the coupling between these physiological and psychological factors that in concert define outcome after mTBI is lacking. The purpose of this narrative review article is to address how psychophysiological interactions may lead to poor outcome after mTBI. In addition, a framework is presented that may serve as a template for future studies on this subject.

Background Acute neck pain (ANP) has recently been demonstrated to be a predictor of persistent posttraumatic complaints after mild traumatic brain injury (mTBI). The aim of this study was to determine specific characteristics of patients with ANP following mTBI, their posttraumatic complaints and relationship with functional outcome. Methods Data from a prospective follow-up study of 922 mTBI patients admitted to the emergency department (ED) in three level-one trauma centres were analysed. Patients were divided into two groups: 156 ANP patients and 766 no acute neck pain (nANP) patients. Posttraumatic complaints were evaluated 2 weeks and 6 months post-injury using standardized questionnaires and functional outcome was evaluated at 6 months with the Glasgow Outcome Scale Extended (GOSE). Results ANP patients were more often female (p p p p = 0.01) and less head wounds (58% vs. 73%, p p p = 0.01). Conclusions MTBI patients with acute neck pain at the ED constitute a distinct group within the mTBI spectrum with specific injury and demographic characteristics. Early identification of this at risk group already at the ED might allow specific and timely treatment to avoid development of incomplete recovery.

Deficits in information processing speed (IPS) are among the earliest and most prominent cognitive manifestations in mild traumatic brain injury (mTBI). We investigated the impact of white matter fiber location on IPS outcome in an individual basis assessment. A total of 112 acute mild TBI with all CT negative underwent brain DTI and blood sampling for inflammation cytokines within 7 days postinjury and 72 age‐ and sex matched healthy controls with same assessments were enrolled. IPS outcome was assessed by the trail making test at 6–12 month postinjury in mild TBI. Fractional anisotropy (FA) features were extracted using a novel lesion‐load analytical strategy to capture spatially heterogeneous white matter injuries and minimize implicit assumptions of uniform injury across diverse clinical presentations. Acute mild TBI exhibited a general pattern of increased and decreased FA in specific white matter tracts. The power of acute FA measures to identify patients developing IPS deficits with 92% accuracy and further improved to 96% accuracy by adding inflammation cytokines. The classifiers predicted individual's IPS and working memory ratings (r = .74 and .80, respectively, p, Combination of inflammation cytokine and fibers projecting to frontal cortex as predictors can identify long‐term information processing speed deficits in mild TBI patients with negative CT.

Background Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement. Methods Forty-four mTBI patients with PTH, 27 mTBI patients without PTH and 43 healthy controls who were well matched for age, gender, and years of education were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning as well as headache symptom measurement and cognitive assessment. Hypothalamic resting state networks were characterized by using a standard seed-based whole-brain correlation method. The bilateral hypothalamic FC was compared among the three groups. Furthermore, the correlations between hypothalamic resting state networks and headache frequency, headache intensity and MoCA scores was investigated in mTBI patients with PTH using Pearson rank correlation. Results Compared with mTBI patients without PTH, mTBI patients with PTH at the acute stage presented significantly decreased left hypothalamus-based FC with the right middle frontal gyrus (MFG) and right medial superior frontal gyrus (mSFG), and significantly decreased right hypothalamus-based FC with the right MFG. Decreased FC of the right MFG was significantly positively associated with headache frequency and headache intensity (r = 0.339, p = 0.024; r = 0.408, p = 0.006, respectively). Decreased FC of the right mSFG was significantly positively associated with headache frequency and headache intensity (r = 0.740, p r = 0.655, p Conclusion Our data provided evidence of disrupted hypothalamic FC in patients with acute mTBI with PTH, while abnormal FC significantly correlated with headache symptom measurement. Taken together, these changes may play an essential role in the neuropathological mechanism of mTBI patients with PTH.

OBJECTIVE: To investigate the natural course of activities and participation of children up to 6 months after a mild traumatic brain injury (mTBI).METHODS: A prospective longitudinal cohort study with complete data sets of 231 children diagnosed with mTBI and their caregivers.MAIN MEASURES: Activities and participation assessed with the Child and Adolescent Scale of Participation (CASP) and the Children's Assessment of Participation and Enjoyment (CAPE) measured at 2 weeks, 3 months, and 6 months post-mTBI. Because of a ceiling effect, the primary outcome measure (CASP) was divided into deviant (not maximum score) or full functioning.RESULTS: Friedman's, Cochran's Q, and McNemar's tests (CASP) and repeated-measures analyses of variance (CAPE) showed significant increases in activities and participation between 2 weeks and 3 and 6 months after mTBI. Based on the parents' perspective, 67% of the children returned to full functioning at 6 months postinjury, with only 38% of the children describing themselves as functioning at their premorbid level.DISCUSSION: Findings indicate that most children return to maximum level of activities and participation over time after mTBI. In a substantial number of children, however, the level of activities and participation at 6 months postinjury is evaluated as lower than that of peers. The importance of investigating predictors for child and caregiver perspectives is emphasized.

Background: In the past decade, accidents have been one of the top 10 causes of death in Taiwan. Head trauma caused by accidents has been an issue of concern in Taiwan. Although serious long-term effects have been documented, research on mild traumatic brain injury (mTBI) remains scarce. Thus, the main purpose of this study was to analyze post-concussion symptome (PCS) and the relevant impact on physical, emotional, and cognitive functions. Materials and Methods: During 2012–2013, 105 patients with mTBI in a single hospital were surveyed based on the Rivermead postconcussion symptoms questionnaire in 1 week, and their postinjury status was followed 1 month later. The collected data were analyzed using the paired t-test and descriptive statistics. Results: The collected data were included patient demographics and pretrauma risk factors. A total of 101 patients were subject to mTBI. The rate increased among males and the population aged from 21 to 44 years old. The most common cause of injury was the motorcycle accident, where half of the patients had an initial loss of consciousness and posttraumatic amnesia. Partial resolution of symptoms was noted within 1 month for all participants, but some symptoms persisted (P < 0.0001). In general, patients (especially females) recovered faster from physical impairment. The analysis provides information about the impacts and shows the increased risk of neurocranial traumas related to mTBI. Conclusion: This study presents patients' PCS symptoms in different periods. Those symptoms improved gradually in 1 month, but some symptoms persisted, especially those affecting emotional and cognitive functions. Most patients in this study were young, and the illness had impact on the patients' daily life. As shown by the results, the risk factors were associated with prolonged PCS among females. Aside from physical symptoms, special attention should be paid to mental care as well. More predictors for mTBI may improve medical care quality and reduce losses of medical resources.

OBJECTIVE: To examine the effectiveness of Brains Ahead!, a psychoeducational intervention aimed to prevent long-term problems with activities and participation in children after mild traumatic brain injury (mTBI).PARTICIPANTS: In total, 124 children, aged 6 to 18 years, diagnosed with mTBI and their caregivers.METHOD: After randomization, participants in the intervention group received a face-to-face psychoeducational session with written take-home information and follow-up telephone call(s). Participants in the control group received usual care, consisting of a concise information brochure.PRIMARY OUTCOME MEASURES: Activities and participation (Child and Adolescent Scale of Participation [CASP]).SECONDARY OUTCOMES: fatigue, postconcussive symptoms (PCSs), posttraumatic stress symptoms (PTSSs), and quality of life (QOL).RESULTS: Generalized Estimated Equation analyses showed that both groups improved over the first 6 months post-mTBI, but the intervention group did not differ significantly on the CASP. Mann-Whitney U tests showed that the intervention group reported significantly less fatigue, PCSs, and PTSSs and better QOL compared with the control group at 6 months post-MTBI.CONCLUSIONS: The Brains Ahead! intervention resulted in significant improvements compared with usual care in reducing fatigue, PCSs, and PTSSs and improving QOL. Lack of an effect on activities and participation may be due to the ceiling effect of the CASP.

Background: Mild traumatic brain injury (mTBI) often results in post-concussion symptoms, chronic pain, and sleepiness. Genetic factors are thought to play an important role in poor prognosis. Aims: The aims of this study are to (1) document the prevalence of pain and post-concussion symptoms in mTBI patients in acute and chronic phases (2) determine whether candidate genes predispose to post-concussive symptoms and pain. Methods: Posttraumatic symptoms, evaluated using the Rivermead Post-Concussion Symptoms Questionnaire, and pain were assessed in 94 mTBI patients in the acute phase as well as in 22 healthy controls. Assessment was repeated in 36 patients after one year who agreed to participate in the follow-up visit. Gene polymorphisms and expression were assessed in mTBI patients and healthy controls. Results: In the acute phase, mTBI patients with pain (69%) presented more psychological symptoms and sleepiness and were less able to return to work than those without pain. At one year, 19% of mTBI patients had persistent pain and psychological distress. Two haplotypes (H2 and H3) in the brain-derived neurotrophic factor (BDNF) gene were shown to be respectively deleterious and protective against post-concussion symptoms and pain in both acute and chronic phases. Protective haplotype H3 was associated with a decreased expression of the anti-sense of BDNF (BDNF-AS). Deleterious haplotype H2 predicted the development of chronic pain at one year, whereas H3 was protective. Conclusions: This pilot study suggests a protective mechanism of a multilocus effect in BDNF, through BDNF-AS, against post-concussion symptoms and pain in the acute phase and possibly chronic pain at one year post-mTBI. The role of antisense RNA should be validated in larger cohorts.

Lower levels of physical activity in the first month after mild TBI predicts decreased conditioned pain modulation and greater pain catastrophizing in patients with mild TBI., Objective: The purpose of this study was to determine whether self-reported physical activity (PA) in the first month after mild traumatic brain injury (mTBI) predicts endogenous pain modulatory function and pain catastrophizing at 1 to 2 weeks and 1 month after injury in patients with mTBI. Methods: Patients with mild traumatic brain injury completed study sessions at 1 to 2 weeks and 1 month after injury. Assessments included a headache survey, Pain Catastrophizing Scale, International Physical Activity Questionnaire-Short Form, and several quantitative sensory tests to measure endogenous pain modulatory function including conditioned pain modulation (CPM), temporal summation, and pressure pain thresholds of the head. Hierarchical linear regressions determined the relationship between the PA variables (predictors) and pain catastrophizing and pain modulation variables (dependent variables) cross-sectionally and longitudinally, while controlling for potential covariates. Results: In separate hierarchical regression models, moderate PA, walking, and total PA at 1 to 2 weeks after injury predicted pain inhibition on the CPM test at 1 month, after controlling for significant covariates. In addition, a separate regression revealed that minutes sitting at 1 month predicted CPM at 1 month. Regarding predicting pain catastrophizing, the regression results showed that sitting at 1 to 2 weeks after injury significantly predicted pain catastrophizing at 1 month after injury. Conclusion: Greater self-reported PA, especially moderate PA, 1 to 2 weeks after injury longitudinally predicted greater pain inhibitory capacity on the CPM test at 1 month after injury in patients with mTBI. In addition, greater sedentary behavior was associated with worse pain inhibition on the CPM test and greater pain catastrophizing at 1 month after injury.

Computed tomography (CT) scan is a standard for the diagnosis of intracranial pathology after traumatic brain injury (TBI). Hemorrhagic progression of contusion (HPC) is frequently seen on repeat CT, but its clinical and radiological significance in case of mild TBI is not well define. The aim of the study:to evaluate the result of routine repeat head CT in patients with mild TBI and brain contusions. Materials and methods:retrospective analysis of management of patients with mild TBI (Glasgow Coma Scale (GCS) score – 13 to 15) and cerebral contusion. All patients were treated at the Kyiv City Clinical Emergency Hospital between 2016 and 2017. Results:within 202 patients with mild TBI, 87 (43.1 %) met the inclusion criteria and were selected for detailed analysis. There were 69 (79.3 %) men and 18 (20.7 %) women. The mean age of the patients was 43.8±12.7 years (17–82 years). The average time between trauma and CT was 3.3 hours. The average volume of contusion on the initial CT was 1.9±0.6 cm3 (0.2–9.6 cm3). The average time of routine CT was 6.8 hours (range 4–24 hours) after the initial scans. HPC was found in 24 (30.7 %) of 87 cases. The average volume of brain contusion on the repeat CT was 2.3±0.5 cm3(0.2-17.1 cm3). In 3 (3.4 %) patients the size of the hematoma increased. Clinical deterioration occurred in 10 (11.5 %) patients. Six (6.9 %) patients were operated after a CT scan due to HPC with midline shift in 4 cases and increasing of subdural hematoma – 2 cases. Four of these patients had clinical deterioration, and 2 patients were neurological stable. Patients with HPC at admission had lower points of GCS, fractures of the skull (both p Conclusions:Routine repeat CT in patients with mild TBI with brain contusions is aimed to find a patients with s high risk for clinical deterioration. One third of patients with mild TBI and brain contusion experienced HPC. Patients with HPC often have unfavorable clinical course with higher average duration of treatment, delay surgical treatment and mortality rate.

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury.

Motor control deficits outlasting self-reported symptoms are often reported following mild traumatic brain injury (mTBI). The exact duration and nature of these deficits remains unknown. The current study aimed to compare postural responses to static or dynamic virtual visual inputs and during standard clinical tests of balance in 38 children between 9 and 18 years-of-age, at 2 weeks, 3 and 12 months post-concussion. Body sway amplitude (BSA) and postural instability (vRMS) were measured in a 3D virtual reality (VR) tunnel (i.e., optic flow) moving in the antero-posterior direction in different conditions. Measures derived from standard clinical balance evaluations (BOT-2, Timed tasks) and post-concussion symptoms (PCSS-R) were also assessed. Results were compared to those of 38 healthy non-injured children following a similar testing schedule and matched according to age, gender, and premorbid level of physical activity. Results highlighted greater postural response with BSA and vRMS measures at 3 months post-mTBI, but not at 12 months when compared to controls, whereas no differences were observed in post-concussion symptoms between mTBI and controls at 3 and 12 months. These deficits were specifically identified using measures of postural response in reaction to 3D dynamic visual inputs in the VR paradigm, while items from the BOT-2 and the 3 timed tasks did not reveal deficits at any of the test sessions. PCSS-R scores correlated between sessions and with the most challenging condition of the BOT-2 and as well as with the timed tasks, but not with BSA and vRMS. Scores obtained in the most challenging conditions of clinical balance tests also correlated weakly with BSA and vRMS measures in the dynamic conditions. These preliminary findings suggest that using 3D dynamic visual inputs such as optic flow in a controlled VR environment could help detect subtle postural impairments and inspire the development of clinical tools to guide rehabilitation and return to play recommendations.

To identify a screening tool for poor self-reported sleep quality at 12 weeks according to non-invasive measurements and patients’ characteristics in the first week after mild traumatic brain injury (mTBI), data from 473 mTBI participants were collected and follow-ups were performed at 12 weeks. Patients with previous poor self-reported sleep quality prior to the injury were excluded. Patients were then divided into two groups at 12 weeks according to the Pittsburgh Sleep Quality Index based on whether or not they experienced poor sleep quality. The analysis was performed on personal profiles and heart rate variability (HRV) for 1 week. After analyzing the non-invasive measurements and characteristics of mTBI patients who did not complain of poor sleep quality, several factors were found to be relevant to the delayed onset of poor sleep quality, including age, gender, and HRV measurements. The HRV–age–gender (HAG) index was proposed and found to have 100% sensitivity (cut-off, 7, specificity, 0.537) to predicting whether the patient will experience poor sleep quality after mTBI at the 12-week follow-up. The HAG index helps us to identify patients with mTBI who have no sleep quality complaints but are prone to developing poor self-reported sleep quality. Additional interventions to improve sleep quality would be important for these particular patients in the future.

Background: Clinical practice guidelines for mild traumatic brain injury (mTBI) management call on family physicians to proactively screen and initiate treatment for mental health complications, but evidence suggests that this does not happen consistently. The authors aimed to identify physician-perceived barriers and facilitators to early management of mental health complications following mTBI. Methods & results: Semi-structured interviews based on the Theoretical Domains Framework (TDF) were conducted with 11 family physicians. Interview transcripts were analyzed using directed content analysis. Factors influencing management of mental health post-mTBI were identified along five TDF domains. Conclusion: Family physicians could benefit from accessible and easily implemented resources to manage post-mTBI mental health conditions, having a better defined role in this process, and formalization of referrals to mental health specialists., Lay abstract Best practice recommendations call for family doctors to proactively screen for and treat mental health problems that might arise after a mild traumatic brain injury (mTBI) (also known as a concussion). However, previous studies show that these recommendations are not followed consistently. The authors aimed to find reasons why this is not happening by interviewing 11 family doctors. The authors found that family doctors are mostly unaware of resources to guide their practice, are unsure about their role in mental health management, and experience difficulties in referring their patients to specialists for mental health care. Actively providing family doctors with knowledge and tools that help them initiate mental health care, as well as a structure for mental health referrals after mild traumatic brain injury, would help doctors apply best practice recommendations., Graphical abstract

Introduction: Comorbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common in military service members. The aim of this study is to investigate brain metabolic i...

Objective: To compare healthcare and productivity costs between patients with mild traumatic brain injury (mTBI) who received verbal discharge instructions only and patients who received an additional flyer with or without video instructions. Setting: Emergency departments (EDs) of 6 hospitals in the Netherlands. Participants: In total, 1155 adult patients with mTBI (384 with verbal instructions; 771 with additional flyer with or without video instructions) were included. Design: Cost study with comparison between usual care and intervention. Methods: Medical and productivity costs up to 3 months after presentation at the ED were compared between mTBI patients with usual care and mTBI patients who received the intervention. Results: Mean medical costs per mTBI patient were slightly higher for the verbal instructions-only cohort (€337 vs €315), whereas mean productivity costs were significantly higher for the flyer/video cohort (€1625 vs €899). Higher productivity costs were associated with higher working age, injury severity, and postconcussion symptoms. Conclusion: This study showed that the implementation of flyer (and video) discharge instructions for patients with mTBI who present at the ED increased reports of postconcussion symptoms and reduced medical costs, whereas productivity costs were found to be higher for the working population in the first 3 months after the sustained head injury.

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.

The main objective of this prospective cohort study was to evaluate whether traumatic microbleeds (TMBs) are a significant prognostic factor of return to work (RTW), post-traumatic symptoms, and overall recovery in patients with mild traumatic brain injury (mTBI). One hundred and thirteen patients with mTBI were recruited from the Helsinki University Hospital emergency units. All patients underwent multi-contrast 3T magnetic resonance imaging (MRI) 3-17 days after mTBI. Patients were evaluated in the Traumatic Brain Injury Outpatient Clinic of Helsinki University Hospital 1 month after injury. Post-concussion symptoms were assessed with the Post-Concussion Symptom Questionnaire (RPQ) and overall recovery was assessed with the Glasgow Outcome Scale Extended (GOS-E). Their time to RTW was continuously measured up to 1 year after TBI. Median RTW was 9 days (interquartile range [IQR] 4-30) after mTBI and full RTW rate after 1 year was 98%. Patients with TMBs (n = 22) did not have more post-concussion symptoms (median RPQ 10.0 vs. 7.0, p = 0.217) or worse overall recovery (58% vs. 56% with GOS-E = 8, p = 0.853) than patients without TMBs (n = 91). There was no significant difference in time to RTW (13.5 vs. 7.0 days, p = 0.063). In this study, patients with TMBs did not have delayed RTW or more post-concussion symptoms than other patients with mTBI. TMBs in mTBI do not seem to be a significant prognostic factor of RTW.

Background and Purpose: Identification of changesin brain microstructure following mild traumatic brain injury (mTBI) could be instrumental in understanding the underlying pathophysiology. The purpose of this study was to apply neurite orientation dispersion and density imaging (NODDI) to a rodent model of mTBI to determine whether microstructural changes could be detected immediately following injury. Methods: Fifteen adult male Wistar rats were scanned on a Bruker 9.4 Tesla small animal MRI using a multi-shell acquisition (30 b = 1000 s/mm2 and 60 b = 2000 s/mm2). Nine animals experienced a single closed head controlled cortical impact followed by NODDI from 1 to 4 h post injury. Region of interest analysis focused on the corpus callosum and hippocampus. A mixed analysis of variance (ANOVA) was used to determine statistically significant interactions in neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity. Follow up repeated-measures ANOVAs were used to determine individual changes over time. Results: NDI showed a significant increase in the hippocampus and corpus callosum following injury, while ODI showed increases in the corpus callosum. No significant changes were observed in the sham control animals. No changes were found in FA, MD, AD, or RD. Histological analysis revealed increased glial fibrillary acidic protein staining relative to controls in both the hippocampus and corpus callosum, with evidence of activated astrocytes in these regions. Conclusions: Changes in NODDI metrics were detected as early as 1 h following mTBI. No changes were detected with conventional diffusion tensor imaging (DTI) metrics, suggesting that NODDI provides greater sensitivity to microstructural changes than conventional DTI.

Objective findings of brain injury or dysfunction are typically lacking in mild traumatic brain injury (MTBI) despite prolonged post-concussion symptoms in some patients. Thus, there is a need for objective biomarkers of MTBI that reflect altered brain physiology underlying subjective symptoms. We have previously reported increased attention to threat-related stimuli in subjects with MTBI, suggesting a physiological vulnerability to depression. Vulnerability to depression has been linked with relatively greater activity of the right than left frontal cortex reflected in inverse pattern in frontal alpha with greater power on the left than right. We investigated whether patients with previous MTBI show this pattern of frontal activity reflected in more negative frontal alpha asymmetry (FAA) scores. Furthermore, in search for potential biomarkers of MTBI, we created a novel index, emotional modulation of FAA (eFAA) and investigated whether it correlates with subjective symptoms. EEG was recorded while subjects with previous MTBI and controls performed a computer-based reaction time task integrating different cognitive executive functions and containing either threat-related or emotionally neutral visual stimuli. Post-concussion symptoms and depression were assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Beck’s depression inventory (BDI). Task-induced FAA was assessed and eFAA calculated by subtracting FAA in the context of neutral stimuli from FAA in the context of emotional stimuli. The MTBI group showed FAA scores reflecting relatively greater right-sided frontal activity compared to healthy controls. eFAA differentiated the symptomatic MTBI from non-symptomatic MTBI group and from healthy controls. eFAA also correlated with RPQ and BDI scores. In conclusion, FAA pattern previously linked with vulnerability to depression, was observed in patients with previous MTBI. Furthermore, eFAA has potential as a biomarker of altered affective brain functions in MTBI. publishedVersion

Sleep is commonly disrupted following mild traumatic brain injury (mTBI), however there is a lack of consensus in the existing literature regarding the prevalence of insomnia/insomnia symptoms after injury. The aim of this review was to conduct a systematic review and meta-analysis of insomnia and insomnia symptoms prevalence following mTBI.\ud \ud Full-text articles published in English in peer-reviewed journals including adults with a clinical or self-reported mild traumatic brain injury diagnosis, were eligible for inclusion. Studies that assessed insomnia/insomnia symptoms after injury were included.\ud \ud Of the 2091 records identified, 20 studies were included in the review. 19 of these were meta-analysed (n=95,195), indicating high heterogeneity among studies. Subgroup analyses indicated pooled prevalence estimates of post-mTBI insomnia disorder of 27.0% (95% CI 6.49-54.68) and insomnia symptoms of 71.7% (95% CI 60.31-81.85).\ud \ud The prevalence of insomnia is significantly higher in individuals who have sustained mild traumatic brain injury compared to prevalence estimates reported in the general population but high heterogeneity and methodological differences among studies make it difficult to provide reliable prevalence estimates. Future research should continue to advance our understanding of the onset, progression and impact of post-mild traumatic brain injury insomnia to promote the recovery and wellbeing of affected individuals.\ud \ud PROSPERO registration CRD42020168563.

Objectives This study aimed to investigate changes in three intrinsic functional connectivity networks (IFCNs; default mode network [DMN], salience network [SN], and task‐positive network [TPN]) in individuals who had sustained a mild traumatic brain injury (mTBI). Methods Resting‐state functional magnetic resonance imaging (rs‐fMRI) data were acquired from 27 mTBI patients with persistent postconcussive symptoms, along with 26 age‐ and sex‐matched controls. These individuals were recruited from a Level‐1 trauma center, at least 3 months after a traumatic episode. IFCNs were established based on seed‐to‐voxel, region‐of‐interest (ROI) to ROI, and independent component analyses (ICA). Subsequently, we analyzed the relationship between functional connectivity and postconcussive symptoms. Results Seed‐to‐voxel analysis of rs‐fMRI demonstrated decreased functional connectivity in the right lateral parietal lobe, part of the DMN, and increased functional connectivity in the supramarginal gyrus, part of the SN. Our TPN showed both hypo‐ and hyperconnectivity dependent on seed location. Within network hypoconnectivity was observed in the visual network also using group comparison. Using an ICA, we identified altered network functional connectivity in regions within four IFCNs (sensorimotor, visual, DMN, and dorsal attentional). A significant negative correlation between dorsal attentional network connectivity and behavioral symptoms score was also found. Conclusions Our findings indicate that rs‐fMRI may be of use clinically in order to assess disrupted functional connectivity among IFCNs in mTBI patients. Improved mTBI diagnostic and prognostic information could be especially relevant for athletes looking to safely return to play, as well for individuals from the general population with persistent postconcussive symptoms months after injury, who hope to resume activity., We found extensive functional connectivity changes in a group of mild traumatic brain injury patients who were still experiencing post‐concussive symptoms months after injury. These results suggest that resting state fMRI may help improve diagnosis, prognosis and overall management of mild traumatic brain injury in athletes as well as in the general population suffering from this prevalent, yet commonly overlooked condition.

The diffuse and continually evolving secondary changes after mild traumatic brain injury (mTBI) make it challenging to assess alterations in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic mTBI and persistent symptoms and measured their cognitive status using the NIH Toolbox Cognitive Battery. Fifteen adults with mTBI with persistent symptoms and twelve age, gender and education matched healthy controls took part in this study. We found a significant decrease in global white matter MWF in patients compared to the healthy controls. Significantly lower MWF was evident in most white matter region of interest (ROIs) examined including the corpus callosum (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. Although patients showed lower cognitive functioning, no significant correlations were found between MWF and cognitive measures. These results suggest that individuals with chronic mTBI who have persistent symptoms have reduced MWF., magnetic resonance imaging; mild traumatic brain injury; cognition; myelin water fraction; chronic injury

Despite the high prevalence of mild traumatic brain injury (mTBI), current diagnostic tools to objectively assess cognitive complaints after mTBI continue to be inadequate. Our aim was to identify neuronal correlates for cognitive difficulties in mTBI patients by evaluating the possible alterations in oscillatory brain activity during a behavioral task known to be sensitive to cognitive impairment after mTBI. We compared oscillatory brain activity during rest and cognitive tasks (Paced Auditory Serial Addition Test [PASAT] and a vigilance test [VT]) with magnetoencephalography between 25 mTBI patients and 20 healthy controls. Whereas VT induced no significant differences compared with resting state in either group, patients exhibited stronger attenuation of 8-to 14-Hz oscillatory activity during PASAT than healthy controls in the left parietotemporal cortex (p ≤ 0.05). Further, significant task-related modulation in the left superior frontal gyrus and right prefrontal cortex was detected only in patients. The∼10-Hz (alpha) peak frequency declined in frontal, temporal, and parietal regions during PASAT compared with rest (p < 0.016) in patients, whereas in controls it remained the same or showed a tendency to increase. In patients, the ∼10-Hz peak amplitude was negatively correlated with behavioral performance in the Trail Making Test. The observed alterations in the cortical oscillatory activity during cognitive load may provide measurable neurophysiological correlates of cognitive difficulties in mTBI patients, even at the individual level.

Previous work has shown that non-invasive optical measurement of low cerebral blood flow (CBF) is an acute biomarker of poor long-term cognitive outcome after repetitive mild traumatic brain injury (rmTBI). Herein, we explore the relationship between acute cerebral blood flow and underlying neuroinflammation. Specifically, because neuroinflammation is a driver of secondary injury after TBI, we hypothesized that both glial activation and inflammatory signaling are associated with acute CBF and, by extension, with long-term cognitive outcome after rmTBI. To test this hypothesis, cortical CBF was non-invasively measured in anesthetized mice 4 h after 3 repetitive closed head injuries spaced once-daily, at which time brains were collected. Right hemispheres were fixed for immunohistochemical staining for glial activation markers Iba1 and GFAP while left hemispheres were used to quantify Iba1 and GFAP expression via Western blot as well as 32 cytokines and 21 phospho-proteins in the MAPK, PI3K/Akt, and NF-κB pathways using a Luminex multiplexed immunoassay. N = 8/7 injured/sham C57/black-6 adult male mice were studied. Within the injured group, CBF inversely correlated with Iba1 expression (R = −0.86, p

Context: Postconcussion syndrome (PCS) is a set of symptoms occurred after a mild traumatic brain injury (MTBI). Aims: This study aims to determine the prevalence of PCS in a young adult population from a single Neurological Centre in Malaysia's East Coast and to evaluate the factors associated with PCS in MTBI patients. Settings and Design: This was a cross-sectional study conducted in a Neurological Centre at Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia, from January 2016 to December 2016. Subjects and Methods: A total of 209 patients; 133 males and 76 females, in the age range of 16–84 years, were randomly recruited for this study. All the selected patients were subjected to the checklist for diagnosis of PCS as per International Statistical Classification of Diseases and Related Health Problems 10th edition classification at a 2-week interval. Statistical Analysis Used: Descriptive statistic and Multivariable Logistic Regression Model were used for frequency and percentage analyses of categorical variables, using SPSS version 23.0. Results: Only 20 patients were identified with PCS. There were more female (70%) patients with PCS than the male (30%) patients. The prevalence of PCS for 2 weeks, 3 and 6 months since injuries were 9.6%, 8.1%, and 8.1% respectively. Majority (80%) of the patients were found to have PCS due to road traffic accidents, while the remaining were attributed to assault (15%), and falls (5%). Among the sample population, 25% were smokers, while 10% of them had either skull fracture or premorbidity. Conclusion: Less than 10% of patients with MTBI had PCS after 6 months' following trauma. None of the variables tested were significant factors for the development of PCS symptoms.

VISSER, K., M. Koggel, J. Blaauw, H.J.v.d. Horn, B. Jacobs, and J.v.d. Naalt. Blood based biomarkers of inflammation in mild traumatic brain injury: A systematic review. NEUROSCI BIOBEHAV REV XX(X) XXX-XXX, 2021. – Inflammation is an important secondary physiological response to traumatic brain injury (TBI). Most of the current knowledge on this response is derived from research in moderate and severe TBI. In this systematic review we summarize the literature on clinical studies measuring blood based inflammatory markers following mild traumatic brain injury (mTBI) and identify the value of inflammatory markers as biomarkers. Twenty-three studies were included. This review suggests a distinct systemic inflammatory response following mTBI, quantifiable within 6 hours up to 12 months post-injury. Interleukin-6 is the most promising biomarker for the clinical diagnosis of brain injury while interleukin-10 is a potential candidate for triaging CT scans. The diagnostic and prognostic utility of inflammatory markers may be more fully appreciated as a component of a panel of biomarkers. However, discrepancies in study design, analysis and reporting make it difficult to draw any definite conclusions. For the same reasons, a meta-analysis was not possible. We provide recommendations to follow standardized methodologies to allow for reproducibility of results in future studies.

Traumatic brain injury (TBI) imposes a significant economic and social burden. The diagnosis and prognosis of mild TBI, also called concussion, is challenging. Concussions are common among contact sport athletes. After a blow to the head, it is often difficult to determine who has had a concussion, who should be withheld from play, if a concussed athlete is ready to return to the field, and which concussed athlete will develop a post-concussion syndrome. Biomarkers can be detected in the cerebrospinal fluid and blood after traumatic brain injury and their levels may have prognostic value. Despite significant investigation, questions remain as to the trajectories of blood biomarker levels over time after mild TBI. Modeling the kinetic behavior of these biomarkers could be informative. We propose a one-compartment kinetic model for S100B, UCH-L1, NF-L, GFAP, and tau biomarker levels after mild TBI based on accepted pharmacokinetic models for oral drug absorption. We approximated model parameters using previously published studies. Since parameter estimates were approximate, we did uncertainty and sensitivity analyses. Using estimated kinetic parameters for each biomarker, we applied the model to an available post-concussion biomarker dataset of UCH-L1, GFAP, tau, and NF-L biomarkers levels. We have demonstrated the feasibility of modeling blood biomarker levels after mild TBI with a one compartment kinetic model. More work is needed to better establish model parameters and to understand the implications of the model for diagnostic use of these blood biomarkers for mild TBI.

Mild traumatic brain injury is highly prevalent in paediatric populations, and can result in chronic physical, cognitive and emotional impairment, known as persistent post-concussive symptoms. Magnetoencephalography has been used to investigate neurophysiological dysregulation in mild traumatic brain injury in adults; however, whether neural dysrhythmia persists in chronic mild traumatic brain injury in children and adolescents is largely unknown. We predicted that children and adolescents would show similar dysfunction as adults, including pathological slow-wave oscillations and maladaptive, frequency-specific, alterations to neural connectivity. Using magnetoencephalography, we investigated regional oscillatory power and distributed brain-wide networks in a cross-sectional sample of children and adolescents in the chronic stages of mild traumatic brain injury. Additionally, we used a machine learning pipeline to identify the most relevant magnetoencephalography features for classifying mild traumatic brain injury and to test the relative classification performance of regional power versus functional coupling. Results revealed that the majority of participants with chronic mild traumatic brain injury reported persistent post-concussive symptoms. For neurophysiological imaging, we found increased regional power in the delta band in chronic mild traumatic brain injury, predominantly in bilateral occipital cortices and in the right inferior temporal gyrus. Those with chronic mild traumatic brain injury also showed dysregulated neuronal coupling, including decreased connectivity in the delta range, as well as hyper-connectivity in the theta, low gamma and high gamma bands, primarily involving frontal, temporal and occipital brain areas. Furthermore, our multivariate classification approach combined with functional connectivity data outperformed regional power in terms of between-group classification accuracy. For the first time, we establish that local and large-scale neural activity are altered in youth in the chronic phase of mild traumatic brain injury, with the majority presenting persistent post-concussive symptoms, and that dysregulated interregional neural communication is a reliable marker of lingering paediatric ‘mild’ traumatic brain injury., Safar et al. show alterations in local and large-scale neural activity in children and adolescents with mild traumatic brain injury, with the majority experiencing long-term post-concussive symptoms, and establish that the functional connectome is a reliable and accurate classification marker for mild paediatric brain injury., Graphical Abstract Graphical Abstract

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients’ sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated., Gerhalter et al. report the in vivo detection of ionic imbalances in mild traumatic brain injury in the form of decreased total sodium concentrations in global grey and white matter compared to controls. These changes correlated with the degree of neuropsychological impairment and differentiated non-recovered patients from controls., Graphical Abstract Graphical Abstract

Highlights • Magnetoencephalography has higher sensitivity than clinical imaging to detect abnormalities in mild traumatic brain injury • Excess resting state low frequency power is consistently detected following mild traumatic brain injury. • There are widespread magnetoencephalography connectivity changes following mild traumatic brain injury. • Machine learning techniques generate high classification accuracy when analysing magnetoencephalography data. • Currently there is not enough evidence for routine clinical use of magnetoencephalography in mild traumatic brain injury, Background The global incidence of traumatic brain injuries is rising, with at least 80% being classified as mild. These mild injuries are not visible on routine clinical imaging. The potential clinical role of a specific imaging biomarker be it diagnostic, prognostic or directing and monitoring progress of personalised treatment and rehabilitation has driven the exploration of several new neuroimaging modalities. This systematic review examined the evidence for magnetoencephalography (MEG) to provide an imaging biomarker in mild traumatic brain injury (mTBI). Methods Our review was prospectively registered on PROSPERO: CRD42019151387. We searched EMBASE, MEDLINE, trial registers, PsycINFO, Cochrane Library and conference abstracts and identified 37 papers describing MEG changes in mTBI eligible for inclusion. Since meta-analysis was not possible, based on the heterogeneity of reported outcomes, we provide a narrative synthesis of results. Results The two most promising MEG biomarkers are excess resting state low frequency power, and widespread connectivity changes in all frequency bands. These may represent biomarkers with potential for diagnostic application, which reflect time sensitive changes, or may be capable of offering clinically relevant prognostic information. In addition, the rich data that MEG produces are well-suited to new methods of machine learning analysis, which is now being actively explored. Interpretation MEG reveals several promising biomarkers, in the absence of structural abnormalities demonstrable with either computerised tomography or magnetic resonance imaging. This review has not identified sufficient evidence to support routine clinical use of MEG in mTBI currently. However, verifying MEG’s potential would help meet an urgent clinical need within civilian, sports and military medicine.

OBJECTIVE: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. METHODS: Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13-15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. RESULTS: A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001). CONCLUSIONS: Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL., Funding Agencies: OneMind (USA) Hannelore Kohl Stiftung (Germany)

Mild traumatic brain injury (mTBI) has been defined as a transient (

Background: For measuring their impact in scientific research, the citation count of the publications is used in the bibliometric analysis, though still in the bibliometric analysis, there is no comprehensive summary of mild traumatic brain injury (mTBI) research. This article intends to provide the physicians and the neuroscientists with a reference guide to assess the most influential publications written on this subject through a macroscopic view of the research activities on mTBI.Methods: The database of the Web of Science was used to compile the 100 top-ranking publications on mTBI. The selected publications were evaluated on the basis of the several categorizations including the type of the publications, number of citations, country of origin, and year of publication.Results: Between 1946 and 2020, the 13,040 publications that were published were included in the database. The least cited publications received 274 citations, while the most cited received 1,748. Altogether, 71 publications were from the USA while 29 were from other countries. Among all the institutions, the University of Pittsburgh Medical Center led the list with six publications. Around 100 papers, mostly on the clinical studies in the categories of neurology and neurosciences, were published in 54 different journals.Conclusions: This study provides both a transverse section summary and historical retrospect for the clinical advances of mTBI, and the publications of important observations that contributed a significant impact on the treatment and prevention of mTBI had been identified.

Objective To investigate demographic and pre-injury factors in Finnish school-aged children admitted to pediatric neurology services after mild traumatic brain injury (mTBI). The relation of these factors to prolonged injury symptoms and later visits into psychiatric care was assessed. Methods Demographic information, pre-injury learning status, and neuropsychological test results of 120 patients aged 7-16 years were retrospectively collected from the hospital medical records. Data were compared with self- or parent-reported injury symptoms at 1-3 months post-injury and later visits to psychiatric care. Results According to medical records, 14.2% of the children with mTBI had a diagnosed neurobehavioral or psychiatric condition pre-injury. Additionally, 53.3% of the children had some neurobehavioral or psychiatric concerns or traits prior to the injury. Over half (56.7%) of the children studied were symptomatic at 1-3 months following the injury. Female gender and presence of prolonged symptoms were predictive for later visit into psychiatric care. Conclusions Pre-injury neurobehavioral or psychiatric problems may predict prolonged injury symptoms following pediatric mTBI. In this retrospective patient series, prolonged symptoms and female gender seem to predict the need for later psychiatric care. Monitoring the recovery of children with mTBI and pre-injury risk factors is important for timely interventions.

Mild traumatic brain injury (mTBI) is often characterized by deficits in response inhibition, which can contribute to marked social and occupational dysfunction. mTBI often occurs in the context of psychologically traumatic events. This can cause posttraumatic stress disorder (PTSD), which also impedes response inhibition. The overlap or distinction in these inhibitory deficits in mTBI and PTSD is unclear. This study aimed to assess behavioral, neurophysiological, and neuroimaging indices of response inhibition in mTBI by also assessing these parameters in healthy controls (HC) and PTSD participants. Participants with mTBI (without PTSD) (n = 46), PTSD (without mTBI) (n = 41), and HC (n = 40) were assessed during a response inhibition task (the Go/NoGo task) during neuropsychological testing and separate functional magnetic imaging and event-related potentials sessions. PTSD symptom severity was assessed with the Clinician-Administered PTSD Scale. Both mTBI and PTSD participants performed more omission errors on the Go/NoGo task and were associated with greater N2 amplitude, greater left inferior parietal activation and reduced connectivity of the left inferior parietal cluster and left angular gyrus compared to HC. There were no differences between mTBI and PTSD on any of these measures. These findings highlight that both mTBI and PTSD contribute to neural dysfunction during response inhibition, and arguably these occur due to distinct mechanisms. In the context of the common comorbidity between these two conditions, strategies to address response inhibition deficits in mTBI may need to consider causative factors underpinning neurological insult of mTBI and psychological effects associated with PTSD.

Introduction 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. Methods 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 Results In 152 patients aged 40.7 ± 15.0 years, 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]). Conclusions 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.

BackgroundMild traumatic brain injury (mTBI) is an acknowledged public health problem. Up to 25% of adult with mTBI present persistent symptoms. Headache, dizziness, nausea and neck pain are the most commonly reported symptoms and are frequently associated with cervical spine and vestibular impairments. The most recent international consensus statement (2017 Berlin consensus) recommends the addition of an individualized rehabilitation approach for mTBI with persistent symptoms. The addition of an individualized rehabilitation approach including the evaluation and treatment of cervical and vestibular impairments leading to symptoms such as neck pain, headache and dizziness is, however, recommended based only on limited scientific evidence. The benefit of such intervention should therefore be further investigated.ObjectiveTo compare the addition of a 6-week individualized cervicovestibular rehabilitation program to a conventional approach of gradual sub-threshold physical activation (SPA) alone in adults with persistent headache, neck pain and/or dizziness-related following a mTBI on the severity of symptoms and on other indicators of clinical recovery. We hypothesize that such a program will improve all outcomes faster than a conventional approach (between-group differences at 6-week and 12-week).MethodsIn this single-blind, parallel-group randomized controlled trial, 46 adults with subacute (3 to12 weeks post-injury) persistent mTBI symptoms will be randomly assigned to: 1) a 6-week SPA program or 2) SPA combined with a cervicovestibular rehabilitation program. The cervicovestibular rehabilitation program will include education, cervical spine manual therapy and exercises, vestibular rehabilitation and home exercises. All participants will take part in 4 evaluation sessions (baseline, week 6, 12 and 26) performed by a blinded evaluator. The primary outcome will be the Post-Concussion Symptoms Scale. The secondary outcomes will be time to clearance to return to function, number of recurrent episodes, Global Rating of Change, Numerical Pain Rating Scale, Neck Disability Index, Headache Disability Inventory and Dizziness Handicap Inventory. A 2-way ANOVA and an intention-to-treat analysis will be used.DiscussionControlled trials are needed to determine the best rehabilitation approach for mTBI with persistent symptoms such as neck pain, headache and dizziness. This RCT will be crucial to guide future clinical management recommendations.Trial registrationClinicalTrials.govIdentifier -NCT03677661, Registered on September, 15th 2018.

Traumatic brain injury (TBI) is a major cause of long-term cognitive deficits, even in mild TBI patients. Computerized cognitive training can help alleviate complaints and improve daily life functioning of TBI patients. However, the underlying biological mechanisms of cognitive training in TBI are not fully understood. In the present study, we utilised for the first time a touchscreen cognitive training system in a rat model of mild TBI. Moreover, we wanted to examine whether the beneficial effects of a cognitive training are task-dependent and selective in their target. Specifically, we examined the effect of two training tasks, i.e. the Paired Associate Learning (PAL) task targeting spatial memory functioning and 5-Choice Continuous Performance (5-CCP) task loading on attention and inhibition control, on the microstructural organization of the hippocampus and cingulum, respectively, using diffusion tensor imaging (DTI). Our findings revealed that the two training protocols induced similar effects on the diffusion MRI metrics. Further, in the TBI groups who received training microstructural organization in the hippocampus and cingulum improved (as denoted by increases in fractional anisotropy), while a worsening (i.e., increases in mean diffusivity and radial diffusivity) was found in the TBI control group. In addition, these alterations in diffusion MRI metrics coincided with improved performance on the training tasks in the TBI groups who received training. Our findings show the potential of DTI metrics as reliable measure to evaluate cognitive training in TBI patients and to facilitate future research investigating further improvement of cognitive training targeting deficits in spatial memory and attention.

IntroductionWorkplace violence carries a substantial economic loss burden. Up to 10% of all traumatic brain injury (TBI) admissions result from physical assault. There remains a paucity of research on assault as a mechanism of injury, taking into account sex, and its association with work re-entry.ObjectivesThe aim of this study was to characterise, by sex, the sample of workers who had sustained a work-related mild TBI (wr-mTBI) and to assess the independent influence of assault, as a mechanism of injury, on time away from work.MethodsA population-based retrospective cohort of workers’ compensation claimants in Australia (n=3129) who had sustained a wr-mTBI was used for this study. A multivariable logistic regression analysis assessed whether workers who had sustained wr-mTBI as a result of assault (wr-mTBI-assault) were more likely to claim time off work compared with workers who had sustained a wr-mTBI due to other mechanisms.ResultsAmong claimants who sustained a wr-mTBI, 9% were as a result of assault. The distribution of demographic and vocational variables differed between the wr-mTBI-assault, and not due to assault, both in the full sample, and separately for men and women. After controlling for potential confounding factors, workers who sustained wr-mTBI-assault, compared with other mechanisms, were more likely to take days off work (OR 2.14, 95% CI 1.53 to 2.99) within a 3-month timeframe.ConclusionThe results have policy-related implications. Sex-specific and workplace-specific prevention strategies need to be considered and provisions to support return-to-work and well-being within this vulnerable cohort should be examined.