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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.

Peripheral injuries are common in patients who experience mild traumatic brain injury (mTBI). However, the additive or interactive effects of polytrauma on psychosocial adjustment, functional limitations, and clinical outcomes after head injury remain relatively unexamined. Using a recently developed structured injury symptom interview, we assessed the perception and relative importance of peripheral injuries at 3 months post-injury in patients with mTBI as defined by the American Congress of Rehabilitation Medicine. Our sample of Level 1 trauma patients (n = 74) included individuals who were treated and released from the emergency department (n = 43) and those admitted to an inpatient unit (n = 31). Across the sample, 91% of patients with mTBI experienced additional non-head injuries known to commonly impact recovery following mTBI, a majority of whom ranked pain as their worst peripheral injury symptom. Forty-nine percent of the mTBI sample (54% of the subsample with concurrent mTBI and peripheral injuries) reported being more bothered by peripheral injury symptoms than mTBI. Differences between patients with mTBI with worse mTBI symptoms versus those with worse peripheral injury symptoms are described. Conventional measures of injury severity do not capture patients' perceptions of the totality of their injuries, which limits the development of patient-centered treatments. Future research should enroll patients with mTBI diverse in peripheral injury severity and develop standardized assessments to characterize peripheral symptoms, enabling better characterization of the relevance of concurrent injuries in recovery and outcomes of patients with 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.

Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) demonstrate high prevalence and comorbidity among post-9/11 veterans. Veterans with this comorbidity often present with multiple co-occurring healthcare needs and increased clinical complexity. The current case report describes the clinical presentation of a veteran with mild TBI and PTSD, both before, during, and after treatment within a multidisciplinary 2-week intensive outpatient program involving prolonged exposure, evidence-based PTSD treatment, and Cognitive Symptom Management and Rehabilitation Therapy, evidence-based treatment for postconcussive symptoms. Mr. A was a 25-year-old White, transgender male who presented with a complex mental health history. At intake, presenting complaints included anxiety, panic attacks, nightmares, and depression secondary to military sexual trauma, as well as reported cognitive difficulties secondary to a concussion. He met current criteria for PTSD as well as panic disorder with agoraphobia. Head injury history consisted of a motor vehicle collision with less than 30 seconds loss of consciousness, brief posttraumatic amnesia, and alterations of consciousness. Mr. A demonstrated habituation during individual exposure sessions as assessed via skin conductance during imaginal exposures and decreased subjective ratings during in vivo exposures, as well as a decrease in trauma-potentiated startle response to trauma cues. Posttreatment data indicates significant reduction in neurobehavioral, posttraumatic stress, and depression symptoms and significant improvement in subjective cognitive functioning. The current findings support the feasibility and efficacy of short-term integrated treatment for complex clinical presentations and the need for larger scale research investigating combined PTSD and TBI intervention.

OBJECTIVE Somatic complaints are known to complicate recovery after mild traumatic brain injury (mTBI), but the construct is poorly understood due to evolving definitions of associated disorders and uncertainty related to its position within the broader construct network of psychopathology. Methods: To better understand measures of somatic symptom reporting widely used with mTBI patients, we examined relationships between the Brief Symptom Inventory-18 Somatization (SOM) scale, the Minnesota Multiple Personality Inventory-2-Restructured Form Somatic Complaints (RC1) scale, other measures of psychological and personality functioning, and mTBI in both athlete concussion (n = 100) and civilian trauma (n = 75 mTBI, n = 79 orthopedic injury) samples. Results: The association between post-injury SOM and RC1 was moderate (r=.37-.46) and similar to associations between these inventories and depression and anxiety symptoms. In civilians with mTBI, RC1 was more strongly associated with diverse personality dimensions than SOM. mTBI athletes reported increases in somatic symptoms from pre- to post-injury, with larger group effect sizes on SOM (ηp2 = 0.34, p < .001) than RC1 (ηp2 = 0.09, p = .003). Civilian mTBI patients showed a trend for somewhat higher post-injury RC1 scores than orthopedic trauma controls (ηp2 = 0.02, p = .068). Conclusions: Findings add to the current knowledge of the influence of somatic complaints in mTBI. BSI-18 SOM and MMPI-2-RF RC1 are not interchangeable, as they are only modestly correlated and demonstrate differing associations with other clinical outcomes and mTBI.

Background and purpose Mild traumatic brain injury (mTBI) in patients on antiplatelet (AP), anticoagulant (AC) or direct oral anticoagulant (DOAC) medication has become a systematic indication for head CT. However, the over-risk and impact of the intracranial hemorrhages (IH) detected with CT in this population remain unclear and need to be assessed. Materials and methods We prospectively assessed head CTs performed in adults taking AP/AC/DOAC referred after a mTBI to our Emergency Departments between September 2016 and January 2018. Frequency, type and severity of IH were described and frequency was analyzed as a function of treatment. Results 840 patients were prospectively included. 58.9% were treated with AP, 23.7% with AC, 11.7% with DOAC and 5.7% with a combination of antithrombotic agents. The rate of IH detected with head CT was 5.8% (n = 49), of which 81.6% (n = 40) and 18.4% (n = 9) with minor and intermediate severity respectively. No patient required surgical care and no death occurred. No statistically significant difference was found in treatment distribution between patients with or without IH (p = 0.98). Among the patients who discontinued their antithrombotic treatment after mTBI, three experienced thrombotic events during the hospitalization. Conclusions Our results showed a low frequency and severity of IH in mTBI patients indifferently treated with AP, AC or DOAC, without secondary neurological deterioration, death or need of surgical care. Our study suggests the limited benefit of systematic CT head scan as a standard practice for the management of mTBI patients under antithrombotic therapy.

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.

Post-traumatic movement disorder is one of the sequelae of traumatic brain injury. The dentatorubrothalamic tract (DRTT) is reported to be involved in the control of movement. Therefore, injury of the DRTT can be accompanied by abnormal movements, including ataxia, tremor, or dystonia. We investigated DRTT injuries in 27 patients who showed post-traumatic tremor in at least one of four extremities following mild traumatic brain injury. We classified DRTT injuries based on diffusion tensor tractography parameters and configuration: type A: the DRTT showed narrowing, type B: the DRTT showed partial tearing, and type C: the DRTT showed discontinuation. Fractional anisotropy and fiber number of the DRTT were significantly decreased in patients compared with the healthy controls. Based on our DRTT injury classification, among the 54 hemispheres of the 27 patients, type A injury occurred in 22 hemispheres (40.7%) of 17 patients, type B injury was present in 15 hemispheres (27.7%) of 10 patients, and type C injury was observed in 8 hemispheres (14.8%) of 6 patients. Our results suggest that diffusion tensor tractography-based evaluation of the DRTT would be useful when determining cause of post-traumatic tremor in patients with mild traumatic brain injury. The study protocol was approved by the Institutional Review Board of Yeungnam University Hospital (YUMC-2018-09-007) on September 5, 2018.

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.

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.

Mild traumatic brain injury (mTBI) is usually caused by a bump, blow, or jolt to the head or penetrating head injury, and carries the risk of inducing cognitive disorders. However, identifying the biomarkers for the diagnosis of mTBI is challenging as evident abnormalities in brain anatomy are rarely found in patients with mTBI. In this study, we tested whether the alteration of functional network dynamics could be used as potential biomarkers to better diagnose mTBI. We propose a sparse dictionary learning framework to delineate spontaneous fluctuation of functional connectivity into the subject‐specific time‐varying evolution of a set of overlapping group‐level sparse connectivity components (SCCs) based on the resting‐state functional magnetic resonance imaging (fMRI) data from 31 mTBI patients in the early acute phase (, We proposed a sparse dictionary learning framework to delineate spontaneous fluctuation of functional connectivity into the subject‐specific time‐varying evolvement of a set of overlapping group‐level sparse connectivity components (SCCs). The identified SCCs were consistently distributed in the cohort of subjects without significant inter‐group differences in connectivity patterns. Nevertheless, subject‐specific temporal expression of these SCCs could be used to effectively discriminate mTBI patients from healthy controls (HCs).

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.

Highlights • MTBI is poorly understood and lacks objective diagnostic and prognostic tools. • Abnormal neural oscillations are found in subjects with a history of mTBI. • We identify transient bursts in MEG data using a Hidden Markov Model. • We explain a deficit in beta connectivity and power in terms of transient bursts. • Data-driven feature selection identifies symptom-relevant functional connections., Mild traumatic brain injury (mTBI) poses a considerable burden on healthcare systems. Whilst most patients recover quickly, a significant number suffer from sequelae that are not accompanied by measurable structural damage. Understanding the neural underpinnings of these debilitating effects and developing a means to detect injury, would address an important unmet clinical need. It could inform interventions and help predict prognosis. Magnetoencephalography (MEG) affords excellent sensitivity in probing neural function and presents significant promise for assessing mTBI, with abnormal neural oscillations being a potential specific biomarker. However, growing evidence suggests that neural dynamics are (at least in part) driven by transient, pan-spectral bursting and in this paper, we employ this model to investigate mTBI. We applied a Hidden Markov Model to MEG data recorded during resting state and a motor task and show that previous findings of diminished intrinsic beta amplitude in individuals with mTBI are largely due to the reduced beta band spectral content of bursts, and that diminished beta connectivity results from a loss in the temporal coincidence of burst states. In a motor task, mTBI results in diminished burst amplitude, altered modulation of burst probability during movement, and a loss in connectivity in motor networks. These results suggest that, mechanistically, mTBI disrupts the structural framework underlying neural synchrony, which impairs network function. Whilst the damage may be too subtle for structural imaging to see, the functional consequences are detectable and persist after injury. Our work shows that mTBI impairs the dynamic coordination of neural network activity and proposes a potent new method for understanding mTBI.

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.

A major hurdle preventing effective interventions for patients with mild traumatic brain injury (mTBI) is the lack of known mechanisms for the long-term cognitive impairment that follows mTBI. The closed head impact model of repeated engineered rotational acceleration (rCHIMERA), a non-surgical animal model of repeated mTBI (rmTBI), mimics key features of rmTBI in humans. Using the rCHIMERA in rats, this study was designed to characterize rmTBI-induced behavioral disruption, underlying electrophysiological changes in the medial prefrontal cortex (mPFC), and associated mitochondrial dysfunction. Rats received 6 closed-head impacts over 2 days at 2 Joules of energy. Behavioral testing included automated analysis of behavior in open field and home-cage environments, rotarod test for motor skills, novel object recognition, and fear conditioning. Following rmTBI, rats spent less time grooming and less time in the center of the open field arena. Rats in their home cage had reduced inactivity time 1 week after mTBI and increased exploration time 1 month after injury. Impaired associative fear learning and memory in fear conditioning test, and reduced short-term memory in novel object recognition test were found 4 weeks after rmTBI. Single-unit in vivo recordings showed increased neuronal activity in the mPFC after rmTBI, partially attributable to neuronal disinhibition from reduced inhibitory synaptic transmission, possibly secondary to impaired mitochondrial function. These findings help validate this rat rmTBI model as replicating clinical features, and point to impaired mitochondrial functions after injury as causing imbalanced synaptic transmission and consequent impaired long-term cognitive dysfunction.

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.

Background: Increasing evidence suggests potential lifetime effects following mild traumatic brain injury (TBI) in childhood. Few studies have examined medium-term outcomes among hospitalized and non-hospitalized samples. Study aims were to describe children's behavioral and emotional adjustment, executive function (EF), quality of life, and participation at 7-years following mild TBI using parents' and teachers' reports.Methods: Nested case control study of 86 children (68% male, mean age at assessment = 11.27 years; range 7–17 years) who sustained a mild TBI 7-years previously, identified from a prospective, population-based study. They were compared to 69 children free from TBI (61% male, mean age at assessment = 11.12 years; range 5–17 years). In addition to parent-reported socio-demographic details, parents (mild TBI n = 86, non-TBI n = 69) completed age-appropriate standardized questionnaires about children's health-related quality of life, behavioral and emotional adjustment, EF, and social participation. Parents own mood was assessed using the Hospital Anxiety and Depression Scale. Teachers (mild TBI n = 53, non-TBI n = 42) completed questionnaires about children's behavioral and emotional adjustment, and EF.Results: Parent reports showed median group-level scores for cases were statistically significantly greater than controls for emotional symptoms, conduct problems, hyperactivity/inattention, total behavioral difficulties, inhibitory control, shifting, planning/organizing, and Global Executive Composite (total) EF difficulties (p-values 0.001–0.029). Parent reports of child quality of life and social participation were similar, as were teacher reports of child behavioral and emotional adjustment, and EF (p > 0.05). When examining clinical cut-offs, compared to controls, cases had a higher risk of parent-reported total EF difficulties (odds ratio = 3.00) and, to a lesser extent, total behavior problems (odds ratio = 2.51).Conclusions: As a group, children with a history of mild TBI may be at elevated risk for clinically significant everyday EF difficulties in the medium-term compared to non-TBI controls, as judged by their parents. Further multi-informant longitudinal research is required, following larger samples. Aspects requiring particular attention include pre-injury characteristics, such as sleep disturbances and comorbidities (e.g., headaches), that may act as potential confounders influencing the association between mild TBI and child behavioral problems.

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

There have been an increasing number of functional magnetic resonance imaging (fMRI) reports on brain abnormalities in mild traumatic brain injury (mTBI) at different phases. However, the neural bases and cognitive impairment after acute mTBI are unclear. This study aimed to identify brain functional hubs and connectivity abnormalities in acute mTBI patients and their correlations with deficits in cognitive performance. Within seven days after brain injury, mTBI patients (n=55) and age-, sex-, and educational -matched healthy controls (HCs) (n=41) underwent resting-state fMRI scans and cognitive assessments. We derived functional connectivity (FC) strength of the whole-brain network using degree centrality (DC) and performed Granger causality analysis (GCA) to analyze causal connectivity patterns in acute mTBI. Compared with HCs, acute mTBI patients had significantly decreased network centrality in the left middle frontal gyrus (MFG). Additionally, acute mTBI showed decreased inflows from the left MFG to bilateral middle temporal gyrus (MTG), left medial superior frontal gyrus (mSFG), and left anterior cingulate cortex (ACC). Correlation analyses revealed that changes in network centrality and causal connectivity were associated with deficits in cognitive performance in mTBI. Our findings may help to provide a new perspective for understanding the neuropathophysiological mechanism of acute cognitive impairment after mTBI.

Although much attention has been generated in popular media regarding the deleterious effects of pediatric mild traumatic brain injury (pmTBI), a paucity of empirical evidence exists regarding the natural course of biological recovery. Fifty pmTBI patients (12–18 years old) were consecutively recruited from Emergency Departments and seen approximately 1 week and 4 months post‐injury in this prospective cohort study. Data from 53 sex‐ and age‐matched healthy controls (HC) were also collected. Functional magnetic resonance imaging was obtained during proactive response inhibition and at rest, in conjunction with independent measures of resting cerebral blood flow. High temporal resolution imaging enabled separate modeling of neural responses for preparation and execution of proactive response inhibition. A priori predictions of failed inhibitory responses (i.e., hyperactivation) were observed in motor circuitry (pmTBI>HC) and sensory areas sub‐acutely and at 4 months post‐injury. Paradoxically, pmTBI demonstrated hypoactivation (HC>pmTBI) during target processing, along with decreased activation within prefrontal cognitive control areas. Functional connectivity within motor circuitry at rest suggested that deficits were limited to engagement during the inhibitory task, whereas normal resting cerebral perfusion ruled out deficits in basal perfusion. In conclusion, current results suggest blood oxygen‐level dependent deficits during inhibitory control may exceed commonly held beliefs about physiological recovery following pmTBI, potentially lasting up to 4 months post‐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

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.

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are pervasive consequences of the post-9/11 conflicts. Treatment of PTSD and mTBI has historically occurred separately and sequentially, which does not reflect the overlapping etiology of symptoms and may attenuate or delay recovery. This paper describes an integrated 2-week treatment program using prolonged exposure and cognitive symptom management and rehabilitation therapy to comprehensively treat PTSD and cognitive complaints attributed to mTBI, regardless of etiology. To minimize potential iatrogenic effects of treating presumed mTBI-related symptoms, a central focus of the program was to instill expectations of full recovery. Thirty patients with full or subclinical PTSD and self-reported TBI history completed the PTSD+TBI treatment program. Results indicated that self-reported PTSD, depression, and neurobehavioral symptoms significantly decreased following treatment, while satisfaction with participation in social roles increased. These preliminary effectiveness data indicate that PTSD complicated by mTBI history can be effectively treated within a 2-week intensive outpatient program.

Older age is associated with worsened outcome after mild traumatic brain injury (mTBI) and a higher risk of developing persistent post-traumatic complaints. However, the effects of mTBI sequelae on brain connectivity at older age and their association with post-traumatic complaints remain understudied.We analyzed multi-echo resting-state functional magnetic resonance imaging data from 25 older adults with mTBI (mean age: 68 years, SD: 5 years) in the subacute phase (mean injury to scan interval: 38 days, SD: 9 days) and 20 age-matched controls. Severity of complaints (e.g. fatigue, dizziness) was assessed using self-reported questionnaires. Group independent component analysis was used to identify intrinsic connectivity networks (ICNs). The effects of group and severity of complaints on ICNs were assessed using spatial maps intensity (SMI) as a measure of within-network connectivity, and (static) functional network connectivity (FNC) as a measure of between-network connectivity.Patients indicated a higher total severity of complaints than controls. Regarding SMI measures, we observed hyperconnectivity in left-mid temporal gyrus (cognitive-language network) and hypoconnectivity in the right-fusiform gyrus (visual-cerebellar network) that were associated with group. Additionally, we found interaction effects for SMI between severity of complaints and group in the visual(-cerebellar) domain. Regarding FNC measures, no significant effects were found.In older adults, changes in cognitive-language and visual(-cerebellar) networks are related to mTBI. Additionally, group-dependent associations between connectivity within visual(-cerebellar) networks and severity of complaints might indicate post-injury (mal)adaptive mechanisms, which could partly explain post-traumatic complaints (such as dizziness and balance disorders) that are common in older adults during the subacute phase.

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