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The high incidence of mild traumatic brain injury (mTBI) and the associated post-concussion symptoms, such as headache and cognitive deficits, have captured the significant attention from researchers globally. Magnetic resonance spectroscopy (MRS), a non-invasively technique derived from Magnetic Resonance Imaging (MRI), provides a complement approach to investigating brain metabolites as biomarkers for in vivo pathophysiological changes following mTBI, which are not evident in traditional MRI or CT scans. However, the separate review of MRS in mTBI patients has been limited, given the myriad factors involved and wide spectrum of TBI severity. In this review, we first delve into metabolite changes after mTBI, highlighting a reduction in N-acetyl-aspartate (NAA) as a relatively stable marker associated with neuronal loss or disfunction following mTBI. We then discuss the varying results observed for different metabolites and enumerate possible factors contributing to these inconsistent findings. These factors include variations in experimental methods, such as scanner types, acquisition methods, and region of interest. Additionally, we address subjects-specific factors, such as occupation, cause of injury, control group selection, injury stage, severity, the number of traumatic events, and the assessment of clinical features. Finally, we discuss the trend for future research in this field.

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and improves classification performance. Additionally, a novel data interpretation approach was utilized to identify top-performing features learned by the AEs. Our method delivered a classification accuracy within the range of 79–91.67% for single neuroimaging modalities. However, the performance of classification improved to 95.83%, thereby employing the multimodality model. The models have identified several brain regions located in the default mode network, sensorimotor network, visual cortex, cerebellum, and limbic system as the most discriminative features. We suggest that this approach could be extended to the objective biomarkers predicting mTBI in clinical settings.

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups including controls (CN, n = 25), and patients receiving treatment with N-acetyl cysteine (NAC, n = 25). NAC group received 50 mg/kg intravenous (IV) medication once a day per week. In the rest of the week, they took one 500 mg NAC tablet twice per day. Each patient underwent rs-fMRI scanning at two timepoints including the baseline and 3 months later at follow-up, while the NAC group received a combination of oral and IV NAC over that time. Three rs-fMRI metrics were measured including fractional amplitude of low frequency fluctuations (fALFF), degree centrality (DC), and functional connectivity strength (FCS). Neuropsychological tests were also assessed at the same day of scanning for each patient. The alteration of rs-fMRI metrics and cognitive scores were measured over 3 months treatment with NAC. Then, the correlation analysis was executed to estimate the association of rs-fMRI measurements and cognitive performance over 3 months (p

Objective: The objective of this study was to examine the association between white matter hyperintensities and migraine-like headache in United States military veterans with a history of mild traumatic brain injury., Background: White matter hyperintensities on magnetic resonance imaging (MRI) may be associated with migraine; however, little is currently known about the relationship between white matter hyperintensities and headache following mild traumatic brain injury in military veterans., Methods: This cross-sectional study consisted of a retrospective chart review of veterans from a Southeastern Department of Veterans Affairs polytrauma clinic who had a verified history of mild traumatic brain injury. Participants were included if they had undergone an MRI of the brain. Images were reviewed for the presence and severity of periventricular and deep white matter hyperintensities. Headache and migraine-like headache were defined based on responses from the Neurobehavioral Symptom Inventory., Results: This cohort included 83 veterans, mostly consisting of males (78/83 [94%]) with a median (interquartile range [IQR]) age of 36 (13) years, who were a median (IQR) of 9 (8) years since their most recent mild traumatic brain injury. Most of the veterans reported experiencing migraine-like headache (67/83 [81%]). Periventricular white matter hyperintensities were identified on MRI among 35% (29/83) of the cohort, and deep white matter hyperintensities were identified on MRI of 25% (21/83) of the cohort. There was no association between the odds of displaying white matter hyperintensities and the presence of migraine-like headache (periventricular: unadjusted odds ratio [OR] 2.75, 95% confidence interval [CI] 0.71-10.6; deep white matter: OR 0.69, 95% CI 0.208-2.29; all p > 0.05), nor headache severity (periventricular: moderate headache OR 2.92, 95% CI 0.67-12.8; severe headache OR 3.11, 95% CI 0.77-12.6; deep white matter: moderate headache OR 1.44, 95% CI 0.358-5.8; severe headache OR 0.94, 95% CI 0.246-3.62; all p > 0.05)., Conclusions: Our findings suggest that neither migraine-like headache nor severity of headache is associated with increased prevalence of white matter hyperintensities in veterans with a history of mild traumatic brain injury., (© 2024 American Headache Society.)

Structural vulnerability of the thalamus remains underinvestigated in mild traumatic brain injury (mTBI), and few studies have addressed its constituent nuclei using robust segmentation methods. This study aimed to investigate thalamic subnuclei volume in the subacute period following mTBI. Trauma control (TC) and mTBI patients aged 18-60 years old completed a magnetic resonance imaging (MRI) protocol including both high resolution structural (T1w) and diffusion-weighted sequences at 6-12 weeks following injury (mean: 57 days; SD 11). Each thalamus was segmented into its constituent subnuclei, which were grouped into eight lateralized subregions. Volumes of the subregions were calculated. Neurite Orientation Dispersion and Density (NODDI) maps with parameters optimized for gray matter were computed for the same subregions. Group differences in subregion volumes and NODDI parameters were investigated using Bayesian linear modeling, with age, sex, and estimated intracranial volume included as covariates. Comparisons of mTBI (n = 39) and TC (n = 28) groups revealed evidence of relatively increased gray matter volume in the mTBI group for the bilateral medial and right intralaminar subregions (BF 10  > 3). Of the subregions which showed volume differences, there was no evidence for differences in NODDI metrics between groups. This study demonstrates that in the subacute period following mTBI, there is evidence of increased volume in specific thalamic subregions. Putative mechanisms underpinning the increased volume observed here are disordered remyelination or myelin debris yet to be cleared., (© 2024 Wiley Periodicals LLC.)

Magnetic resonance imaging (MRI) and cognitive profiles in patients with mild traumatic brain injury (mTBI) are often discordant. Conventional MRI seldom captures the full extent of pathological changes in the normal-appearing white matter (NAWM). The divided subtracted inversion recovery (dSIR) technique may enhance T1 differences in NAWM, making them easily visible. We aimed to implement dSIR on a clinical scanner and tested results in mTBI patients. To produce dSIR images, Inversion Recovery-Turbo Spin Echo sequences were modified using six different inversion times (TI) on a 3-T scanner in healthy participants and patients with mTBI. The multiple TIs determined normal white (TI short ) and gray matter (TI long ) nulling points in healthy subjects, which were used to create dSIR images. In one patient, the protocol was repeated at 3 months to identify changes after rehabilitation. Diffusion tensor imaging (DTI)-derived mean diffusivity (MD) and fractional anisotropy (FA) maps were aligned to dSIR images to ensure that signal was not artefactual. Ten healthy participants (five females; age 24 ± 3 [95% CI: 21, 26] years) were included. TI short and TI long were set at 450 and 750 ms, respectively. In both patients (one male, age 17 years; one female, age 14 years), dSIR images revealed areas with increased T1 in the NAWM not visible on conventional MRI. dSIR-based hyperintensities corresponded to elevated MD and reduced FA. Substantial changes were found at follow-up with improvement in DTI-based parameters. dSIR images enhance subtle changes in the NAWM of patients with mTBI by amplifying their intrinsic T1 signal., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

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

The US population suffers 1.5 million head injuries annually, of which mild traumatic brain injuries (mTBI) comprise 75%. Many individuals subsequently experience long-lasting negative symptoms, including anxiety. Previous rat-based work in our laboratory has shown that mTBI changes neuronal counts in the hippocampus and amygdala, regions associated with anxiety. Specifically, mTBI increased neuronal death in the dorsal CA1 sub-region of the hippocampus, but attenuated it in the medial (MeA) and the basolateral nuclei of the amygdala nine days following injury, which was associated with greater anxiety. We have also shown that glucocorticoid receptor (GR) antagonism prior to concomitant stress and mTBI extinguishes anxiety-like behaviors. Using immunohistochemistry, this study examines the expression of brain-derived neurotrophic factor (BDNF) following social defeat and mTBI, and whether this is affected by prior glucocorticoid receptor antagonism as a potential mechanism behind these anxiety and neuronal differences. Here, stress and mTBI upregulate BDNF in the MeA, and both GR and mineralocorticoid receptor antagonism downregulate BDNF in the dorsal hippocampal CA1 and dentate gyrus, as well as the central nucleus of the amygdala. These findings suggest BDNF plays a role in the mechanism underlying neuronal changes following mTBI in amygdalar and hippocampal subregions, and may participate in stress elicited changes to neural plasticity in these regions. Taken together, these results suggest an essential role for BDNF in the development of anxiety behaviors following concurrent stress and mTBI.

Abstract Accurate, and objective diagnosis of brain injury remains challenging. This study evaluated useability and reliability of computerized eye-tracker assessments (CEAs) designed to assess oculomotor function, visual attention/processing, and selective attention in recent mild traumatic brain injury (mTBI), persistent post-concussion syndrome (PPCS), and controls. Tests included egocentric localisation, fixation-stability, smooth-pursuit, saccades, Stroop, and the vestibulo-ocular reflex (VOR). Thirty-five healthy adults performed the CEA battery twice to assess useability and test–retest reliability. In separate experiments, CEA data from 55 healthy, 20 mTBI, and 40 PPCS adults were used to train a machine learning model to categorize participants into control, mTBI, or PPCS classes. Intraclass correlation coefficients demonstrated moderate (ICC > .50) to excellent (ICC > .98) reliability (p

Reported changes in electroencephalography (EEG)-derived spectral power after mild traumatic brain injury (mTBI) remains inconsistent across existing literature. However, this may be a result of previous analyses depending solely on observing spectral power within traditional canonical frequency bands rather than accounting for the aperiodic activity within the collected neural signal. Therefore, the aim of this study was to test for differences in rhythmic and arrhythmic time series across the brain, and in the cognitively relevant frontoparietal (FP) network, and observe whether those differences were associated with cognitive recovery post-mTBI. Resting-state electroencephalography (rs-EEG) was collected from 88 participants (56 mTBI and 32 age- and sex-matched healthy controls) within 14 days of injury for the mTBI participants. A battery of executive function (EF) tests was collected at the first session with follow-up metrics collected approximately 2 and 4 months after the initial visit. After spectral parameterization, a significant between-group difference in aperiodic-adjusted alpha center peak frequency within the FP network was observed, where a slowing of alpha peak frequency was found in the mTBI group in comparison to the healthy controls. This slowing of week 2 (collected within 2 weeks of injury) aperiodic-adjusted alpha center peak frequency within the FP network was associated with increased EF over time (evaluated using executive composite scores) post-mTBI. These findings suggest alpha center peak frequency within the FP network as a candidate prognostic marker of EF recovery and may inform clinical rehabilitative methods post-mTBI.

Abstract Background Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the diagnosis and treatment of rmTBI are quite limited. Methods We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery efficiency and specific target of IgG while reducing the effective therapeutic dose of the drug. Results Our results demonstrated that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also effectively inhibit the activation of microglia and the release of inflammatory factors. Conclusions In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG.

Sleep disturbances occur in up to 70% of patients with mild traumatic brain injury (mTBI). Modern mTBI management recommends targeted treatment for the patient's unique clinical manifestations (i.e., obstructive sleep apnea, insomnia). The purpose of this study was to evaluate the association of plasma biomarkers with symptom reports, overnight sleep evaluations, and response to treatment for sleep disturbances secondary to mTBI. This study is a secondary analysis of a prospective multiple interventional trial of patients with chronic issues related to mTBI. Pre- and post-intervention assessments were conducted, including overnight sleep apnea evaluation, the Pittsburgh Sleep Quality Index (PSQI), and blinded analysis of blood biomarkers. Bivariate Spearman correlations were conducted for pre-intervention plasma biomarker concentrations and 1) PSQI change scores and 2) pre-intervention sleep apnea outcomes (i.e., oxygen saturation measures). A backward logistic regression model was built to evaluate the association of pre-intervention plasma biomarkers with improvement in PSQI over the treatment period (p?0.05). Participants were 36.3???8.6 years old and 6.1???3.8 years from their index mTBI. Participants reported subjective improvements (PSQI?=??3.7???3.8), whereas 39.3% (n?=?11) had improved PSQI scores beyond the minimum clinically important difference (MCID). PSQI change scores correlated with von Willebrand factor (vWF; ??=??0.50; p?=?0.02) and tau (??=??0.53; p?=?0.01). Hyperphosphorylated tau correlated with average saturation (??=??0.29; p?=?0.03), lowest desaturation (??=??0.27; p?=?0.048), and baseline saturation (??=??0.31; p?=?0.02). The multi-variate model (R2?=?0.33; p?=?0.001) retained only pre-intervention vWF as a predictor (odds ratio?=?3.41; 95% confidence interval, 1.44?8.08; p?=?0.005) of improving PSQI scores beyond the MCID. vWF had good discrimination (area under the curve?=?0.83; p?=?0.01), with an overall accuracy of 77%, sensitivity of 46.2%, and specificity of 90.0%. Validation of vWF as a potential predictive biomarker of sleep improvement post-mTBI could optimize personalized management and healthcare utilization.

Abstract Background Neuroanatomical alterations have been associated with cognitive deficits in mild traumatic brain injury (MTBI). However, most studies have focused on the abnormal gray matter volume in widespread brain regions using a cross-sectional design in MTBI. This study investigated the neuroanatomical restoration of key regions in salience network and the outcomes in MTBI. Methods Thirty-six MTBI patients with posttraumatic headache (PTH) and 34 matched healthy controls were enrolled in this study. All participants underwent magnetic resonance imaging scans and were assessed with clinical measures during the acute and subacute phases. Surface-based morphometry was conducted to get cortical thickness (CT) and cortical surface area (CSA) of neuroanatomical regions which were defined by the Desikan atlas. Then mixed analysis of variance models were performed to examine CT and CSA restoration in patients from acute to subacute phase related to controls. Finally, mediation effects models were built to explore the relationships between neuroanatomical restoration and symptomatic improvement in patients. Results MTBI patients with PTH showed reduced headache impact and improved cognitive function from the acute to subacute phase. Moreover, patients experienced restoration of CT of the left caudal anterior cingulate cortex (ACC) and left insula and cortical surface area of the right superior frontal gyrus from acute to subacute phase. Further mediation analysis found that CT restoration of the ACC and insula mediated the relationship between reduced headache impact and improved cognitive function in patients. Conclusions These results showed that neuroanatomical restoration of key regions in salience network correlated reduced headache impact with cognitive function improvement in MTBI with PTH, which further substantiated the vital role of salience network and provided an alternative clinical target for cognitive improvement in MTBI patients with PTH. Graphical Abstract

Background: Return to learn (RTL) after mild traumatic brain injury (mTBI) presents unique challenges for school professionals. A multidisciplinary team approach is necessary yet training school professionals is logistically difficult. This paper describes an innovative pilot RTL program and its evaluation. Methods: Utilizing the telehealth/telementoring program Project ECHO® (Extension for Community Healthcare Outcomes), this study utilized a multidisciplinary team of subject matter experts to deliver five 1-hour sessions across 5 cohorts of school-based professionals (total of 133 participants). The evaluation used a mixed-methods approach of post-session and post-program participant surveys and post-program participant focus groups. Results: Participants who completed a post-program survey reported statistically significant improvements in essential aspects of RTL knowledge and self-efficacy. This included improvements in how to manage a student with an mTBI (44.8% to 86.9%), benefits of early return to school for students following mTBI (31.8% to 86.9%), and the importance of written RTL policies/procedures (55.1% to 97.1%). Conclusions: This study demonstrates that RTL training via a telementoring approach may be a positive and effective way to train school-based professionals and improve knowledge and self-efficacy, especially when attending face-to-face trainings are difficult. This model has the potential to produce programmatic and systematic improvements for RTL education.

Objective: To examine the persistence of visual symptoms in mild traumatic brain injury (MTBI) during the first months after injury. It is important to recognize visual disturbances because they can delay return to normal activities, while they might be simultaneously treated by visual therapy. Here we describe the results from a 1-year follow-up study of visual disturbances after MTBI., Participants and Measures: The study group comprised 26 patients from the Brain Injury Clinic of the Helsinki University Hospital. Inclusion criterion was a high score (≥21p) on the Convergence Insufficiency Symptom Survey (CISS) at an appointment with a neurologist within 6 months after injury. The patients underwent baseline vision evaluation at 4 months on average and follow-up at 14 months after injury. The evaluation included tests for visual acuity, near point of convergence, convergence facility, near point of accommodation, accommodative facility, motility, heterophoria, binocular vision, dynamic visual acuity, and fusional vergence width at near and far distances. Further assessments included the Rivermead Post Concussion Questionnaire for posttraumatic symptoms, a visual analog scale for visual fatigue, and the Developmental Eye Movement Test for saccadic eye movements., Results: Both CISS and Rivermead Post Concussion Questionnaire scores improved significantly from baseline to follow-up. The overall level of visual fatigue according to visual analog scale score was lower at follow-up, but the increase in visual fatigue (comparing fatigue before and after assessment session) was significant both at baseline and follow-up. In visual function assessments, spontaneous recovery from baseline to follow-up could be seen in vergence facility and pursuit eye movement but not in near point of convergence, near fusion, distance fusion, heterophoria, and dynamic visual acuity., Conclusion: The results point out the importance of evaluation of visual disturbances after MTBI. Early detection of these disturbances may provide an opportunity to provide visual therapy., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Importance: Traumatic brain injury (TBI) in patients on vitamin K antagonists (VKAs) is linked to a high rate of intracranial hemorrhage (ICH). Rapid reversal can reduce ICH progression and mortality, but its effectiveness depends on the time between bleeding onset and coagulation normalization., Objective: The PREVACT study aimed to assess the efficacy and safety of prompt systematic reversal of anticoagulation in patients presenting to emergency departments (EDs) for recent mild-TBI while receiving a VKA., Intervention: A randomized, open-label, blinded-endpoint clinical trial was conducted in 21 French EDs. Patients receiving a VKA, having experienced a TBI within the last 6 h, and presenting a Glasgow Coma Score ≥13 were included. Patients were randomized to systematic immediate VKA reversal with 25 IU/kg of four-factor prothrombin complex concentrate (4f-PCC) before any investigation (intervention group) or standard-of-care signifying reversal only if the initial cranial computed tomography (CT) scan indicated ICH (control group). The primary outcome was the rate of ICH detected on a cranial CT scan 24 h post-inclusion., Results: The study was prematurely stopped for logistic reasons after the randomization of 202 patients (101 and 101 in the intervention and control groups, respectively, mean age 90; 51.8% female). On the 24-h cranial CT scan, 6 of 98 patients (6.1%) in the intervention group manifested ICH vs. 12 of 99 patients (12.1%) in the control group [odds ratio: 0.47 (95% confidence interval: 0.14-1.44); P = 0.215]., Conclusion: In patients with recent mild-TBI receiving a VKA, systematic prompt reversal with 4f-PCC did not statistically significantly reduce ICH rate at 24 h. However, the study was prematurely stopped and does not exclude a clinically relevant benefit of the strategy tested., Trial Registration: Clinicaltrials.gov (NCT01961804)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study examines the diagnostic accuracy of brain perfusion SPECT for mild traumatic brain injury (mTBI)., Patients and Methods: A systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO: CRD42023484636). Five databases were searched for studies evaluating brain perfusion SPECT in adult patients with mTBI (GCS 13-15). Study quality was assessed using a modified QUADAS-2 tool. A meta-analysis was performed to pool proportions of hypoperfusion abnormalities across brain lobes., Results: Of 4735 records, 22 studies (5 longitudinal [40% high quality], 17 cross-sectional [24% high quality]) were included totaling 800 patients (mean age, 37.4 ± 12.6 years; 36.4% female). Meta-analysis of proportions indicated that the frontal lobe most frequently showed hypoperfusion on brain perfusion SPECT (pooled proportion 40.1% [95% confidence interval, 31.2% to 49.8%], 99/254, I2 = 54.5%), followed by the temporal lobe (26.1% [95% confidence interval, 19.9% to 33.6%], 68/254, I2 = 30.7%). Several studies found that hypoperfusion abnormalities were associated with neuropsychological findings. Also, brain perfusion SPECT could detect abnormalities not seen on MRI. Abnormalities in perfusion on brain perfusion SPECT may be more readily detected with a quantitative assessment compared with a visual assessment alone, although there appears to be no consensus on the optimal method for image interpretation. Evidence evaluating the sensitivity and specificity of brain perfusion SPECT for mTBI was limited. Using the GRADE framework, the evidence was rated as low., Conclusions: Although perfusion abnormalities can be seen in patients with mTBI, commonly in the frontal and temporal lobes, the findings are nonspecific and may derive from various factors. Ultimately, brain perfusion SPECT provides additional information for mTBI, but the final added value for the detection of mTBI is unknown., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Backgroung: Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines suggest that patients with mTBI can be safely discharged from the emergency department. Although half of patients with mTBI with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients' ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up., Study Design: A single-center prospective cohort study including adult trauma patients with ICH or skull fracture and a Glasgow Coma Scale of 13 to 15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as an RLA less than 8. We compared ECI and non-ECI groups for demographics, injury profile, CT imaging (eg Rotterdam CT score) and outcomes with bivariate analysis. Thirty-day follow-up telephone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms., Results: From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% vs 46.3%, p = 0.003) and higher Rotterdam CT score (p = 0.004) compared with those without ECI. On 30-day follow-up, 6 of 21 (26.6%) patients had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms., Conclusions: More than one-third of mTBI patients with ICH had ECI. At 30-day postdischarge follow-up, more than one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI before discharge as a significant portion may have ongoing difficulties reintegrating into work and society., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Abstract Background Traumatic brain injury (TBI) causes neuroinflammation and can lead to long-term neurological dysfunction, even in cases of mild TBI (mTBI). Despite the substantial burden of this disease, the management of TBI is precluded by an incomplete understanding of its cellular mechanisms. Sphingolipids (SPL) and their metabolites have emerged as key orchestrators of biological processes related to tissue injury, neuroinflammation, and inflammation resolution. No study so far has investigated comprehensive sphingolipid profile changes immediately following TBI in animal models or human cases. In this study, sphingolipid metabolite composition was examined during the acute phases in brain tissue and plasma of mice following mTBI. Methods Wildtype mice were exposed to air-blast-mediated mTBI, with blast exposure set at 50-psi on the left cranium and 0-psi designated as Sham. Sphingolipid profile was analyzed in brain tissue and plasma during the acute phases of 1, 3, and 7 days post-TBI via liquid-chromatography-mass spectrometry. Simultaneously, gene expression of sphingolipid metabolic markers within brain tissue was analyzed using quantitative reverse transcription-polymerase chain reaction. Significance (P-values) was determined by non-parametric t-test (Mann–Whitney test) and by Tukey’s correction for multiple comparisons. Results In post-TBI brain tissue, there was a significant elevation of 1) acid sphingomyelinase (aSMase) at 1- and 3-days, 2) neutral sphingomyelinase (nSMase) at 7-days, 3) ceramide-1-phosphate levels at 1 day, and 4) monohexosylceramide (MHC) and sphingosine at 7-days. Among individual species, the study found an increase in C18:0 and a decrease in C24:1 ceramides (Cer) at 1 day; an increase in C20:0 MHC at 3 days; decrease in MHC C18:0 and increase in MHC C24:1, sphingomyelins (SM) C18:0, and C24:0 at 7 days. Moreover, many sphingolipid metabolic genes were elevated at 1 day, followed by a reduction at 3 days and an absence at 7-days post-TBI. In post-TBI plasma, there was 1) a significant reduction in Cer and MHC C22:0, and an increase in MHC C16:0 at 1 day; 2) a very significant increase in long-chain Cer C24:1 accompanied by significant decreases in Cer C24:0 and C22:0 in MHC and SM at 3 days; and 3) a significant increase of C22:0 in all classes of SPL (Cer, MHC and SM) as well as a decrease in Cer C24:1, MHC C24:1 and MHC C24:0 at 7 days. Conclusions Alterations in sphingolipid metabolite composition, particularly sphingomyelinases and short-chain ceramides, may contribute to the induction and regulation of neuroinflammatory events in the early stages of TBI, suggesting potential targets for novel diagnostic, prognostic, and therapeutic strategies in the future.

Introduction: In low resource settings (LRS), utilization of Computed Tomography scan (CTS) for mild traumatic brain injuries (mTBIs) presents unique challenges and considerations given the limited infrastructure, financial resources, and trained personnel. The Theoretical Domains Framework (TDF) offers a comprehensive theoretical lens to explore factors influencing the decision-making to order CTS for mTBI by imaging referrers (IRs). Objectives: The primary objective was to explore IRs’ beliefs about factors influencing CT utilization in mTBIs using TDF in Uganda.Differences in the factors influencing CTS ordering behavior across specialties, levels of experience, and hospital category were also explored. Materials and Methods: In-depth semi-structured interviews guided by TDF were conducted among purposively selected IRs from 6 tertiary public and private hospitals with functional CTS services. A thematic analysis was performed with codes and emerging themes developed based on the TDF. Results: Eleven IRs including medical officers, non-neurosurgeon specialists and neurosurgeons aged on average 42 years (SD+/-12.3 years) participated.Identified factors within skills domain involved IRs’ clinical assessment and decision-making abilities, while beliefs about capabilities and consequences encompassed their confidence in diagnostic abilities and perceptions of CTS risks and benefits. The environmental context and resources domain addressed the availability of CT scanners and financial constraints. The knowledge domain elicited IRs’ understanding of clinical guidelines and evidence-based practices while social influences considered peer influence and institutional culture. For memory, attention & decision processes domain, IRs adherence to guidelines and intentions to order CT scans were cited. Conclusion: Using TDF, IRs identified several factors believed to influence decision making to order CTS in mTBI in a LRS. The findings can inform stakeholders to develop targeted strategies and evidence-based interventions to optimize CT utilization in mTBI such as; educational programs, workflow modifications, decision support tools, and infrastructure improvements, among others.

Abstract The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p

Background: Repetitive mild traumatic brain injury (rmTBI) often occurs in individuals engaged in contact sports, particularly boxing. This study aimed to elucidate the effects of rmTBI on phase-locking value (PLV)-based graph theory and functional network architecture in individuals with boxing-related injuries in five frequency bands by employing resting-state electroencephalography (EEG). Methods: Twenty-fore professional boxers and 25 matched healthy controls were recruited to perform a resting-state task, and their noninvasive scalp EEG data were collected simultaneously. Based on the construction of PLV matrices for boxers and controls, phase synchronization and graph-theoretic characteristics were identified in each frequency band. The significance of the calculated functional brain networks between the two populations was analyzed using a network-based statistical (NBS) approach. Results: Compared to controls, boxers exhibited an increasing trend in PLV synchronization and notable differences in the distribution of functional centers, especially in the gamma frequency band. Additionally, attenuated nodal network parameters and decreased small-world measures were observed in the theta, beta, and gamma bands, suggesting that the functional network efficiency and small-world characteristics were significantly weakened in boxers. NBS analysis revealed that boxers exhibited a significant increase in network connectivity strength compared to controls in the theta, beta, and gamma frequency bands. The functional connectivity of the significance subnetworks exhibited an asymmetric distribution between the bilateral hemispheres, indicating that the optimized organization of information integration and segregation for the resting-state networks was imbalanced and disarranged for boxers. Conclusions: This is the first study to investigate the underlying deficits in PLV-based graph-theoretic characteristics and NBS-based functional networks in patients with rmTBI from the perspective of whole-brain resting-state EEG. Joint analyses of distinctive graph-theoretic representations and asymmetrically hyperconnected subnetworks in specific frequency bands may serve as an effective method to assess the underlying deficiencies in resting-state network processing in patients with sports-related rmTBI.