Mild Traumatic Brain Injury Group Research Articles

Clinical value of serum LINC02446 and S100B in early diagnosis and prognosis assessment of traumatic brain injury

Objective To detect the expression levels of LINC02446 and S100B in serum of patients with traumatic brain injury (TBI) and explore their values as diagnostic and prognostic indicators for TBI. Method Abnormal expressed RNAs in brain injury were screened from the dataset GSE1131475. Serums were collected from moderate to severe TBI patients at 1–3 and 4–12 h post injury. Quantitative polymerase chain reaction was used to detect the expression levels of LINC02446 and S100B in serum. The Glasgow Outcome Scale was used for prognostic evaluation. The diagnostic and prognostic efficacy of LINC02446 and S100B in TBI was evaluated using the receiver operating characteristic (ROC) curve. Result The serum expression levels of LINC02446 and S100B in the TBI group were significantly increased. The expression levels of LINC02446 and S100B in the severe TBI group were significantly higher than those in the mild TBI group. ROC curve analysis showed that the combination of LINC02446 and S100B can distinguish TBI patients from healthy controls, as well as mild TBI from moderate to severe TBI. At the 6-month follow-up, the expression levels of LINC02446 and S100B in TBI patients with poor prognosis were significantly higher than those in patients with good prognosis, and ROC results showed their differentiation value. Moreover, the expression level of LINC02446 at 0–3 h can serve as an independent prognostic factor for poor prognosis. Conclusion Serum LINC02446 and S100B hold clinical application value in the diagnosis and prognosis of TBI and are expected to become new potential biomarkers.

Women Report Worse Neurobehavioral Symptoms than Men following Mild Traumatic Brain Injury in U.S. Military Service Members.

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the US military. However, women continue to be underrepresented in military research. Studies which do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms compared to men. Conclusions for true gender differences related to TBI is hard to make without controlling for non-TBI factors. The objective of this study was to examine the effects of gender specific to mild TBI (MTBI) sequelae from injured and non-injured control groups and investigate the role of PTSD in symptom reporting. It should be noted that the terms gender and men/women are used in this paper in place of sex or males/females given we are not discussing biological attributes. A total of 966 U.S. military service members and veterans where include in the study. Of the total sample, 455 men and 46 women where in the MTBI group, 285 men and 31 women in the Injured Controls group (IC), 111 men and 38 women in the Non-injured Controls group (NIC). Postconcussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the MTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters; and the TBI-QOL Anxiety, Fatigue, and Headache scales (n2=.018 to .032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n2=.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales compared to men (n2=.032 to .063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n2=.024 to .042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for all analyses. We were able to identify symptoms unique to women recovering from MTBI which were not present following other forms of physical injury or healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with MTBI equates most of the noted gender differences.

Associations Between Auditory Working Memory, Self-Perceived Listening Effort, and Hearing Difficulty in Adults With Mild Traumatic Brain Injury.

Mild traumatic brain injury (TBI) can have persistent effects in the auditory domain (e.g., difficulty listening in noise), despite individuals having normal pure-tone auditory sensitivity. Individuals with a history of mild TBI often perceive hearing difficulty and greater listening effort in complex listening situations. The purpose of the present study was to examine self-perceived hearing difficulty, listening effort, and performance on an auditory processing test battery in adults with a history of mild TBI compared with a control group. Twenty adults ages 20 to 53 years old participated divided into a mild TBI (n = 10) and control group (n = 10). Perceived hearing difficulties were measured using the Adult Auditory Processing Scale and the Hearing Handicap Inventory for Adults. Listening effort was measured using the National Aeronautics and Space Administration-Task Load Index. Listening effort ratings were obtained at baseline, after each auditory processing test, and at the completion of the test battery. The auditory processing test battery included (1) dichotic word recognition, (2) the 500-Hz masking level difference, (3) the Listening in Spatialized Noise-Sentences test, and (4) the Word Auditory Recognition and Recall Measure (WARRM). Results indicated that individuals with a history of mild TBI perceived significantly greater degrees of hearing difficulty and listening effort than the control group. There were no significant group differences on two of the auditory processing tasks (dichotic word recognition or Listening in Spatialized Noise-Sentences). The mild TBI group exhibited significantly poorer performance on the 500-Hz MLD and the WARRM, a measure of auditory working memory, than the control group. Greater degrees of self-perceived hearing difficulty were significantly associated with greater listening effort and poorer auditory working memory. Greater listening effort was also significantly associated with poorer auditory working memory. Results demonstrate that adults with a history of mild TBI may experience subjective hearing difficulty and listening effort when listening in challenging acoustic environments. Poorer auditory working memory on the WARRM task was observed for the adults with mild TBI and was associated with greater hearing difficulty and listening effort. Taken together, the present study suggests that conventional clinical audiometric battery alone may not provide enough information about auditory processing deficits in individuals with a history of mild TBI. The results support the use of a multifaceted battery of auditory processing tasks and subjective measures when evaluating individuals with a history of mild TBI.

Concomitant severe traumatic brain injury is not associated with increased red blood cell transfusion volumes in patients with pelvic fractures: A retrospective observational study

IntroductionTraumatic brain injury (TBI)-associated coagulopathy significantly influences survival outcomes in patients with multiple injuries. Severe TBI can potentially affect systemic hemostasis due to coagulopathy; however, there is limited evidence regarding whether the risk of hemorrhage increases in patients with pelvic fractures complicated with TBI. Therefore, through multivariable analysis, we aimed to examine the association between severe TBI and increased blood transfusion requirements in patients with pelvic fractures. Materials and methodsThis retrospective observational study was conducted at a tertiary care facility in Japan. Patients aged 16 years or older with pelvic fractures who were admitted to our intensive care unit between April 2014 and December 2021 were included in the analysis. The patients were categorized into no to mild and severe TBI groups according to whether the Head Abbreviated Injury Scale (AIS) score was 3 or higher. The primary outcome was the number of red blood cell (RBC) units transfused within 24 h after arrival at the hospital. The primary outcome was analyzed using univariable and multivariable linear regression analyses. The covariates used for the multivariable linear regression analysis were age, sex, antithrombotic therapy, mechanism of injury, Pelvic AIS score, and extravasation on contrast-enhanced computed tomography on admission. ResultsWe identified 315 eligible patients (221 and 94 in the no to mild and severe TBI groups, respectively). In the univariable analysis, the RBC transfusion volume within 24 h after arrival was significantly higher in the severe TBI group than in the no to mild TBI group (2.53-unit increase; 95 % confidence interval [CI]: 0.46–4.61). However, in the multivariable analysis, no statistically significant association was detected between severe TBI and the RBC transfusion volume within 24 h after arrival at the hospital (0.87-unit increase; 95 % CI: −1.11–2.85). ConclusionsConcomitant severe TBI was not associated with increased RBC transfusion volumes in patients with pelvic fractures on multivariable analysis.

Subcortical functional connectivity and its association with walking performance following deployment related mild TBI.

The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred. In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, Service Members and Veterans whose mild TBI occurred outside of deployment, and Service Members and Veterans who had no lifetime history of TBI. FC patterns differed for the two contextual types of mild TBI. Service Members and Veterans with deployment-related mild TBI demonstrated increased FC between the right caudate and lateral occipital regions relative to both the non-deployment mild TBI and TBI-negative groups. When evaluating the association between FC from the caudate and gait, the non-deployment mild TBI group showed a significant positive relationship between walking time and FC with the frontal pole, implicated in navigational planning, whereas the deployment-related mild TBI group trended towards a greater negative association between walking time and FC within the occipital lobes, associated with visuo-spatial processing during navigation. These findings have implications for elucidating subtle motor disruption in Service Members and Veterans with deployment-related mild TBI. Possible implications for future walking performance are discussed.

White Matter Organization and Cortical Thickness Differ Among Active Duty Service Members With Chronic Mild, Moderate, and Severe Traumatic Brain Injury.

Abstract This study compared findings from whole-brain diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) among 90 Active Duty Service Members with chronic mild traumatic brain injury (TBI; n = 52), chronic moderate-to-severe TBI (n = 17), and TBI-negative controls (n = 21). Data were collected on a Philips Ingenia 3T MRI with DTI in 32 directions. Results demonstrated that history of TBI was associated with differences in white matter microstructure, white matter volume, and cortical thickness in both mild TBI and moderate-to-severe TBI groups relative to controls. However, the presence, pattern, and distribution of these findings varied substantially depending on the injury severity. Spatially-defined forms of DTI fractional anisotropy (FA) analyses identified altered white matter organization within the chronic moderate-to-severe TBI group, but they did not provide clear evidence of abnormalities within the chronic mild TBI group. In contrast, DTI FA "pothole" analyses identified widely distributed areas of decreased FA throughout the white matter in both the chronic mild TBI and chronic moderate-to-severe TBI groups. Additionally, decreased white matter volume was found in several brain regions for the chronic moderate-to-severe TBI group compared with the other groups. Greater number of DTI FA potholes and reduced cortical thickness were also related to greater severity of self-reported symptoms. In sum, this study expands upon a growing body of literature using advanced imaging techniques to identify potential effects of brain injury in military Service Members. These findings may differ from work in other TBI populations due to varying mechanisms and frequency of injury, as well as a potentially higher level of functioning in the current sample related to the ability to maintain continued Active Duty status after injury. In conclusion, this study provides DTI and volumetric MRI findings across the spectrum of TBI severity. These results provide support for the use of DTI and volumetric MRI to identify differences in white matter microstructure and volume related to TBI. In particular, DTI FA pothole analysis may provide greater sensitivity for detecting subtle forms of white matter injury than conventional DTI FA analyses.

Research Letter: TBI Severity Moderates the Association Between Subjective and Objective Attention in Older Veterans.

This study examined the moderating effect of traumatic brain injury (TBI) history on subjective and objective cognition across multiple cognitive domains. Participants included 242 Vietnam-era veterans with a history of no TBI (n = 86), mild TBI (n = 74), or moderate-to-severe TBI (n = 82) from the observational Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) study. Objective cognition was the outcome and was measured using neuropsychological measures in the domains of memory, attention/executive functioning, and language. Subjective cognition was measured using the memory, divided attention, and language subscales from the Everyday Cognition (ECog) measure. TBI severity status was the moderating variable. Veterans with a history of moderate-to-severe TBI had a stronger negative association between subjective and objective attention relative to participants without a TBI ( P = .002). Although this association did not differ between mild TBI and no TBI history groups ( P = .100), the association between subjective and objective attention for the mild TBI group was intermediate to the no TBI and moderate-to-severe TBI history groups. TBI status did not moderate associations between subjective and objective memory or language. Results highlight the importance of assessing subjective and objective cognition in older veterans and the relevance of attention in the context of TBI history. More work is needed to better understand the intersection of TBI and aging and how these factors may be used to guide individualized assessment and treatment approaches for older veterans.

0080 TBI Time Since Injury: A Comparison Model Between Sleep Efficiency and Neurocognitive Performance

Abstract Introduction MTBI remains on one of the most prevalently reported brain injuries. Previous studies have shown an association between sleep efficiency, performance, and neurocognitive outcome. Reported time-since-injury (TSI) has also shown an association with neurocognitive outcome measures, with some evidence suggesting neurocognitive status is significantly worse at 2 weeks post-injury. Here, we examined differences in self-reported sleep efficiency at various time points since injury among individuals who had sustained an mTBI in the preceding year. Methods 190 Participants [71 male, 119 female], age M=24.48, SD=6.80 (HC, n=39) and five mild TBI groups based on time post-injury, 2-weeks (2W, n=12), 1-month (1M, n=30), 3-months (3M, n=34), 6-months (6M, n=33), and 12-months (12M, n=40) post-injury. Participants completed a cross-sectional study at specific post-injury time points ranging from (2W, 1M, 3M, 6M, 12M). Participants completed comprehensive Repeatable Battery for Neuropsychological Status (RBANS) and were administered the Pittsburg Sleep Quality Index (PSQI) at the time of assessment. Here we analyzed the sleep efficiency subscale of the PSQI. Separate correlation analysis examined the association between sleep efficiency and the attention index for each TSI group. Results The ANOVA showed a main effect of TSI group, F(5,182) = 2.83, p=.017. Post Hoc comparisons with the LSD test showed that the 12M group had worse sleep ­efficiency than HC and 2W, 1M, and 3M but did not differ from 6M (p<.05). Separate correlations between sleep efficiency and the attention index of the RBANS for each TSI group showed a marginally significant association at 2W (r(10)=-.467, p=.063, one tailed), and statistically significant at 12M (r(38)=-.266, p=.049, one tailed), suggesting that worse sleep efficiency was associated with worse attention performance at those time points. Conclusion Sleep efficiency differs across the first year of recovery from mTBI. Notably, individuals in the 12M TSI group appear to have worse sleep efficiency than any other TSI group but did not differ from the 6M group. Sleep efficiency appears to be associated with attentional capacity at 2W and 12M timeframes. This suggests that interventions that focus on enhancing sleep in patients with mTBI may prove promising for facilitating recovery. Support (if any) W81XWH-12-1-0386

Chronic frontal neurobehavioural symptoms in combat-deployed military personnel with and without a history of blast-related mild traumatic brain injury

ABSTRACT Objective This study evaluated frontal behavioural symptoms, via the FrSBe self-report, in military personnel with and without a history of blast-related mild traumatic brain injury (mild TBI). Methods Prospective observational cohort study of combat-deployed service members leveraging 1-year and 5-year demographic and follow up clinical outcome data. Results The blast mild TBI group (n = 164) showed greater frontal behavioural symptoms, including clinically elevated apathy, disinhibition, and executive dysfunction, during a 5-year follow-up, compared to a group of combat-deployed controls (n = 107) without mild TBI history or history of blast exposure. We also explored changes inbehaviourall symptoms over a 4-year span, which showed clinically significant increases in disinhibition in the blast mild TBI group, whereas the control group did not show significant increases in symptoms over time. Conclusion Our findings add to the growing evidence that a proportion of individuals who sustain mild TBI experience persistent behavioural symptoms. We also offer a demonstration of a novel use of the FrSBe as a tool for longitudinal symptom monitoring in a military mild TBI population.

Diffusion Tensor and Kurtosis Imaging Findings the First Year following Mild Traumatic Brain Injury.

Despite enormous research interest in diffusion tensor imaging and diffusion kurtosis imaging (DTI; DKI) following mild traumatic brain injury (MTBI), it remains unknown how diffusion in white matter evolves post-injury and relates to acute MTBI characteristics. This prospective cohort study aimed to characterize diffusion changes in white matter the first year after MTBI. Patients with MTBI (n = 193) and matched controls (n = 83) underwent 3T magnetic resonance imaging (MRI) within 72 h and 3- and 12-months post-injury. Diffusion data were analyzed in three steps: 1) voxel-wise comparisons between the MTBI and control group were performed with tract-based spatial statistics at each time-point; 2) clusters of significant voxels identified in step 1 above were evaluated longitudinally with mixed-effect models; 3) the MTBI group was divided into: (A) complicated (with macrostructural findings on MRI) and uncomplicated MTBI; (B) long (1-24 h) and short (< 1 h) post-traumatic amnesia (PTA); and (C) other and no other concurrent injuries to investigate if findings in step 1 were driven mainly by aberrant diffusion in patients with a more severe injury. At 72 h, voxel-wise comparisons revealed significantly lower fractional anisotropy (FA) in one tract and significantly lower mean kurtosis (Kmean) in 11 tracts in the MTBI compared with control group. At 3 months, the MTBI group had significantly higher mean diffusivity in eight tracts compared with controls. At 12 months, FA was significantly lower in four tracts and Kmean in 10 tracts in patients with MTBI compared with controls. There was considerable overlap in affected tracts across time, including the corpus callosum, corona radiata, internal and external capsule, and cerebellar peduncles. Longitudinal analyses revealed that the diffusion metrics remained relatively stable throughout the first year after MTBI. The significant group*time interactions identified were driven by changes in the control rather than the MTBI group. Further, differences identified in step 1 did not result from greater diffusion abnormalities in patients with complicated MTBI, long PTA, or other concurrent injuries, as standardized mean differences in diffusion metrics between the groups were small (0.07 ± 0.11) and non-significant. However, follow-up voxel-wise analyses revealed that other concurrent injuries had effects on diffusion metrics, but predominantly in other metrics and at other time-points than the effects observed in the MTBI versus control group analysis. In conclusion, patients with MTBI differed from controls in white matter integrity already 72 h after injury. Diffusion metrics remained relatively stable throughout the first year after MTBI and were not driven by deviating diffusion in patients with a more severe MTBI.

Subdural haematoma in the elderly: management and outcomes of a UK Major Trauma Centre

Background An estimated 40% of all traumatic brain injury (TBI) occurs in ≥70-year-olds with a high prevalence of traumatic subdural haematoma (tSDH). It is anticipated that an expanding elderly population will lead to a proportional increase in the incidence of patients with tSDH presenting to UK trauma centres, but the long-term clinical outcomes and factors influencing functional outcomes in this patient group remain poorly understood. Aim To examine the management and clinical outcomes for elderly (≥70 years) patients diagnosed with tSDH. Methods Patient data for this single-centre, retrospective cohort study were analysed from a Major Trauma Centre (MTC) electronic patient records between January 2013 and December 2019. Results Two hundred and eighty patients were included, 43% aged 70–79, 42% aged 80–89 and 15% >90. In total, 37% underwent a surgical intervention. The 6-month survival in the severe, moderate, and mild TBI groups was 14%, 43%, and 67%, respectively. The 6-month survival in the surgical group was 58%, vs. 60% in the conservatively managed group. Surgical intervention did not significantly impact Extended Glasgow Coma Score (GOS-E) at 6 months, regardless of injury severity. Advanced age (p = 0.04), mixed intracranial injuries (p < 0.0001), craniotomies (p = 0.03), and poor premorbid performance status (p = 0.02) were associated with worse survival and functional outcomes. Conclusions Our study demonstrated that increasing age, increasing severity of TBI and poorer premorbid performance status were associated with significantly poorer 6-month survival and functional outcomes in elderly patients with tSDH. Burr hole evacuation was associated with better functional outcomes compared to craniotomy, but overall, there was no significant difference in the outcomes of the surgical and non-surgical groups. We identified strong risk factors for death and poor functional outcomes at 6-months which are important to consider when counselling patients and families about the long-term prognosis of elderly patients with tSDH and can help guide clinical decision-making.

MILD TRAUMATIC BRAIN INJURY ATTENUATES PNEUMONIA-INDUCED LUNG INJURY BY MODULATIONS OF ALVEOLAR MACROPHAGE BACTERICIDAL ACTIVITY AND M1 POLARIZATION.

Traumatic brain injury is one of the main causes of death and disability worldwide, and results in multisystem complications. However, the mechanism of mild traumatic brain injury (MTBI) on lung injury remains unclear. In this study, we used a murine model of MTBI and pneumonia ( Pseudomonas aeruginosa ;) to explore the relationship between these conditions and the underlying mechanism. Methods: Mice (n = 104) were divided into control, MTBI, pneumonia, and MTBI + pneumonia groups. MTBI was induced by the weight-drop method. Pneumonia was induced by intratracheal injection with P. aeruginosa Xen5 strain. Animals were killed 24 h after bacterial challenging. Histological, cellular, and molecular indices of brain and lung injury were assessed using various methods. Results: Mice in both the MTBI and pneumonia groups had more Fluoro-Jade C-positive neurons than did the controls ( P < 0.01), but mice in the MTBI + pneumonia group had fewer Fluoro-Jade C-positive cells than did the pneumonia group ( P < 0.01). The MTBI + pneumonia mice showed decreased bacterial load ( P < 0.05), reduced lung injury score and pulmonary permeability ( P < 0.01), less inflammatory cells, and lower levels of proinflammatory cytokines (TNF-α and IL-1β; P < 0.01) when compared with the pneumonia group. Molecular analysis indicated lower levels of phosphorylated nuclear factor-κB in the lung of MTBI + pneumonia mice compared with the pneumonia group ( P < 0.01). Furthermore, alveolar macrophages from MTBI mice exhibited enhanced bactericidal capacity compared with those from controls ( P < 0.01). Moreover, MTBI + pneumonia mice exhibited less CD86-positive M1 macrophages compared with the pneumonia group ( P < 0.01). Conclusions: MTBI attenuates pneumonia-induced acute lung injury through the modulation of alveolar macrophage bactericidal capacity and M1 polarization in bacterial pneumonia model.

White matter abnormalities characterize the acute stage of sports-related mild traumatic brain injury.

Sports-related concussion, a form of mild traumatic brain injury, is characterized by transient disturbances of brain function. There is increasing evidence that functional brain changes may be driven by subtle abnormalities in white matter microstructure, and diffusion MRI has been instrumental in demonstrating these white matter abnormalities in vivo. However, the reported location and direction of the observed white matter changes in mild traumatic brain injury are variable, likely attributable to the inherent limitations of the white matter models used. This cross-sectional study applies an advanced and robust technique known as fixel-based analysis to investigate fibre tract-specific abnormalities in professional Australian Football League players with a recent mild traumatic brain injury. We used the fixel-based analysis framework to identify common abnormalities found in specific fibre tracts in participants with an acute injury (≤12 days after injury; n = 14). We then assessed whether similar changes exist in subacute injury (>12 days and <3 months after injury; n = 15). The control group was 29 neurologically healthy control participants. We assessed microstructural differences in fibre density and fibre bundle morphology and performed whole-brain fixel-based analysis to compare groups. Subsequent tract-of-interest analyses were performed within five selected white matter tracts to investigate the relationship between the observed tract-specific abnormalities and days since injury and the relationship between these tract-specific changes with cognitive abnormalities. Our whole-brain analyses revealed significant increases in fibre density and bundle cross-section in the acute mild traumatic brain injury group when compared with controls. The acute mild traumatic brain injury group showed even more extensive differences when compared with the subacute injury group than with controls. The fibre structures affected in acute concussion included the corpus callosum, left prefrontal and left parahippocampal white matter. The fibre density and cross-sectional increases were independent of time since injury in the acute injury group, and were not associated with cognitive deficits. Overall, this study demonstrates that acute mild traumatic brain injury is characterized by specific white matter abnormalities, which are compatible with tract-specific cytotoxic oedema. These potential oedematous changes were absent in our subacute mild traumatic brain injury participants, suggesting that they may normalize within 12 days after injury, although subtle abnormalities may persist in the subacute stage. Future longitudinal studies are needed to elucidate individualized recovery after brain injury.

Return to work after mild traumatic brain injury: association with positive CT and MRI findings

BackgroundReturn to work (RTW) might be delayed in patients with complicated mild traumatic brain injury (MTBI), i.e., MTBI patients with associated traumatic intracranial lesions. However, the effect of different types of lesions on RTW has not studied before. We investigated whether traumatic intracranial lesions detected by CT and MRI are associated with return to work and post-concussion symptoms in patients with MTBI.MethodsWe prospectively followed up 113 adult patients with MTBI that underwent a brain MRI within 3–17 days after injury. Return to work was assessed with one-day accuracy up to one year after injury. Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and Glasgow Outcome Scale Extended (GOS-E) were conducted one month after injury. A Kaplan–Meier log-rank analysis was performed to analyze the differences in RTW.ResultsFull RTW-% one year after injury was 98%. There were 38 patients with complicated MTBI, who had delayed median RTW compared to uncomplicated MTBI group (17 vs. 6 days), and more post-concussion symptoms (median RPQ 12.0 vs. 6.5). Further, RTW was more delayed in patients with multiple types of traumatic intracranial lesions visible in MRI (31 days, n = 19) and when lesions were detected in the primary CT (31 days, n = 24). There were no significant differences in GOS-E.ConclusionsThe imaging results that were most clearly associated with delayed RTW were positive primary CT and multiple types of lesions in MRI. RTW-% of patients with MTBI was excellent and a single intracranial lesion does not seem to be a predictive factor of disability to work.

Blood Biomarkers Predict Future Cognitive Decline after Military-Related Traumatic Brain Injury.

Traumatic brain injury (TBI) has been associated with an increased likelihood of late-life dementia; however, the mechanisms driving this relationship are elusive. Bloodbased biomarkers may provide insight into these mechanisms and serve as useful prognostic indicators of cognitive recovery or decline following a TBI. The aim of this study was to examine blood biomarkers within one year of TBI and explore their relationship with cognitive decline. Service members and veterans (n=224) without injury (n=77), or with a history of bodily injury (n=37), uncomplicated mild TBI (n=55), or more severe TBI (n=55), underwent a blood draw and neuropsychological assessment within one year of their injury as part of a case-control study. A subsample (n=87) completed a follow-up cognitive assessment. In the more severe TBI group, baseline glial fibrillary acidic protein (p=.008) and ubiquitin C-terminal hydrolase-L1 (p=.026) were associated with processing speed at baseline, and baseline ubiquitin C-terminal hydrolase-L1 predicted change in immediate (R2Δ=.244, p=.005) and delayed memory (R2Δ=.390, p=.003) over time. In the mild TBI group, higher baseline tau predicted greater negative change in perceptual reasoning (R2Δ=.188, p=.033) and executive functioning (R2Δ=.298, p=.007); higher baseline neurofilament light predicted greater negative change in perceptual reasoning (R2Δ=.211, p=.012). Baseline ubiquitin C-terminal hydrolase-L1 strongly predicted memory decline in the more severe TBI group, while tau and neurofilament light strongly predicted decline in the mild TBI group. A panel including these biomarkers could be particularly helpful in identifying those at risk for future cognitive decline following TBI.

Cingulo-Opercular and Frontoparietal Network Control of Effort and Fatigue in Mild Traumatic Brain Injury.

Neural substrates of fatigue in traumatic brain injury (TBI) are not well understood despite the considerable burden of fatigue on return to productivity. Fatigue is associated with diminishing performance under conditions of high cognitive demand, sense of effort, or need for motivation, all of which are associated with cognitive control brain network integrity. We hypothesize that the pathophysiology of TBI results in damage to diffuse cognitive control networks, disrupting coordination of moment-to-moment monitoring, prediction, and regulation of behavior. We investigate the cingulo-opercular (CO) and frontoparietal (FP) networks, which are engaged to sustain attention for task and maintain performance. A total of 61 individuals with mild TBI and 42 orthopedic control subjects participated in functional MRI during performance of a constant effort task requiring altering the amount of effort (25, 50, or 75% of maximum effort) utilized to manually squeeze a pneumostatic bulb across six 30-s trials. Network-based statistics assessed within-network organization and fluctuation with task manipulations by group. Results demonstrate small group differences in network organization, but considerable group differences in the evolution of task-related modulation of connectivity. The mild TBI group demonstrated elevated CO connectivity throughout the task with little variation in effort level or time on task (TOT), while CO connectivity diminished over time in controls. Several interregional CO connections were predictive of fatigue in the TBI group. In contrast, FP connectivity fluctuated with task manipulations and predicted fatigue in the controls, but connectivity fluctuations were delayed in the mild traumatic brain injury (mTBI) group and did not relate to fatigue. Thus, the mTBI group’s hyper-connectivity of the CO irrespective of task demands, along with hypo-connectivity and delayed peak connectivity of the FP, may allow for attainment of task goals, but also contributes to fatigue. Findings are discussed in relation to performance monitoring of prediction error that relies on internal cues from sensorimotor feedback during task performance. Delay or inability to detect and respond to prediction errors in TBI, particularly evident in bilateral insula-temporal CO connectivity, corresponds to day-to-day fatigue and fatigue during task performance.

The requirement of propofol for induction of anesthesia in patients with traumatic brain injury determined using bilateral bispectral index and target controlled infusion - An observational cohort study.

Patients with traumatic brain injury (TBI) frequently require emergency surgery. There is a paucity of literature with regard to anesthetic requirements in these patients. The aim of the study was to compare the dose of propofol required for induction of anesthesia in patients with different grades of TBI. This prospective, observational study included patients with mild, moderate, and severe grades of TBI undergoing emergency surgery within 48 h of injury. Bispectral Index (BIS) values were recorded using a bilateral BIS sensor. Anesthesia was induced with a target controlled infusion (TCI) pump. Once BIS reached 40, plasma (Cp) and effect-site (Ce) concentration and total dose of propofol required were noted from the TCI pump. Of the 96 patients recruited, 27, 36, and 33 patients belonged to mild, moderate, and severe TBI (sTBI) groups, respectively. The Ce of propofol in mild, moderate, and sTBI groups was 6 ± 0.9, 5.82 ± 0.98, and 4.48 ± 1.5 μg/mL (P < 0.001), and the dose of propofol required was 1.9 ± 0.2, 1.8 ± 0.4, 1.41 ± 0.5 mg/kg, respectively (P < 0.001). Baseline BIS on the injured side was 80 ± 7.8, 71 ± 9.4, 55 ± 11.6, and on the uninjured side was 89 ± 5.5, 81 ± 8.4, and 65 ± 12 in mild, moderate, and sTBI groups, respectively. The requirement of propofol was reduced in patients with sTBI. The dose of propofol required for induction of anesthesia as determined using Ce was significantly lower only between sTBI and mild TBI and not between patients with sTBI and moderate TBI or between mild and moderate head injury. BIS values were significantly different between the groups (highest in mild TBI and lowest in sTBI) and between normal and injured sides within each group.

Trajectories of Persistent Postconcussion Symptoms and Factors Associated With Symptom Reporting After Mild Traumatic Brain Injury

ObjectiveTo examine the trajectories of persistent postconcussion symptoms (PPCS) after mild traumatic brain injury (MTBI) and to investigate which injury-related and personal factors are associated with symptom reporting. DesignProspective longitudinal cohort study. Follow-up at 3 and 12 months postinjury. SettingA level 1 trauma center and an emergency outpatient clinic. ParticipantsPatients with MTBI (n=358), trauma controls (n=75), and community controls (n=78). Main outcome measuresSymptoms were assessed with the British Columbia Postconcussion Symptom Inventory (BC-PSI). Participants were categorized as having moderate to severe PPCS (msPPCS) when reporting ≥3 moderate/severe symptoms or a BC-PSI total score of ≥13. BC-PSI total scores were compared between the groups and were further used to create cutoffs for reliable change by identifying uncommon and very uncommon change in symptoms in the community control group. Associations between symptom reporting and 25 injury-related and personal factors were examined. ResultsThe MTBI group had a similar prevalence of msPPCS at 3 and 12 months (21%) and reported more symptoms than the control groups. Analyses of individual trajectories, however, revealed considerable change in both msPPCS and BC-PSI total scores in the MTBI group, where both worsening and improvement was common. Intracranial lesions on computed tomography were associated with a greater likelihood of improving from 3 to 12 months. Those with msPPCS at both assessments were more likely to be women and to have these personal preinjury factors: reduced employment, pain, poor sleep, low resilience, high neuroticism and pessimism, and a psychiatric history. ConclusionsGroup analyses suggest a stable prevalence of msPPCS the first year postinjury. However, there was considerable intraindividual change. Several personal factors were associated with maintaining symptoms throughout the first year.

A Novel Histological Technique to Assess Severity of Traumatic Brain Injury in Rodents: Comparisons to Neuroimaging and Neurological Outcomes.

Here we evaluate an alternative protocol to histologically examine blood-brain barrier (BBB) breakdown, brain edema, and lesion volume following traumatic brain injury (TBI) in the same set of rodent brain samples. We further compare this novel histological technique to measurements determined by magnetic resonance imaging (MRI) and a neurological severity score (NSS). Sixty-six rats were randomly assigned to a sham-operated, mild TBI, moderate TBI, or severe TBI group. 48 h after TBI, NSS, MRI and histological techniques were performed to measure TBI severity outcome. Both the histological and MRI techniques were able to detect measurements of severity outcome, but histologically determined outcomes were more sensitive. The two most sensitive techniques for determining the degree of injury following TBI were NSS and histologically determined BBB breakdown. Our results demonstrate that BBB breakdown, brain edema, and lesion volume following TBI can be accurately measured by histological evaluation of the same set of brain samples.

Apolipoprotein e (APOE) ε4 genotype influences memory performance following remote traumatic brain injury in U.S. military service members and veterans

The purpose of this study was to examine the association between the apolipoprotein E (APOE) ε4 allele and neurocognitive functioning following traumatic brain injury (TBI) in military service members and veterans (SMVs). Participants included 176 SMVs with a history of remote TBI (≥1 year post-injury), categorized into mild (n = 100), moderate (n = 40), and severe (n = 36) TBI groups. Participants completed a neuropsychological assessment and APOE genotyping (n = 46 ε4+, n = 130 ε4-). Neurocognitive composite scores representing memory, executive functioning, and visual processing speed were computed. ANCOVAs adjusting for race, education, combat exposure, and PTSD symptom severity showed a significant main effect of ε4 on the memory composite, such that ε4+ SMVs exhibited poorer memory performance than ε4- SMVs. When ε2 allele carriers were removed from the analyses, associations with memory were strengthened, demonstrating a possible protective effect of the ε2 allele. No main effect of TBI group was identified on any cognitive composite, nor were there any significant TBI group × ε4 status interactions for any cognitive composite. Future studies with larger samples are needed to verify these findings, but our results suggest an important relationship between ε4 status and memory functioning following remote TBI of all severities.