Search Results (189)

Concussions, classified as a type of mild traumatic brain injury (mTBI), are frequently underdiagnosed due to the subjective nature of symptoms and limitations in existing diagnostic methodologies. Current clinical evaluations, including tools such as the Sport Concussion Assessment Tool 5 (SCAT5), Balance Error Scoring System (BESS), and Vestibular Ocular Motor Screening (VOMS), demonstrate high sensitivity and specificity but often fail to capture the full complexity of concussive injuries. Emerging diagnostic approaches, such as blood biomarkers (for example, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), S100 calcium-binding protein B (S100B), and tau) and advanced neuroimaging techniques (for example, diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI)), show promise but remain impractical for routine clinical use due to accessibility and standardization challenges. This review examines objective markers, including neuroimaging, electrophysiological measures (for example, Electroencephalography (EEG), Magnetoencephalography (MEG)), and real-time diagnostic tools, as complementary strategies to enhance traditional clinical evaluations. Findings indicate that while clinical assessments remain central to concussion diagnosis, integrating them with advanced imaging and electrophysiological tools can provide more accurate diagnostics and recovery tracking. Biomarkers, although not yet ready for widespread use, hold significant potential for future applications. Further research is required to validate these methods and establish standardized protocols to facilitate their integration into clinical practice. Full article

Objectives: This in silico study sought to identify specific biomarkers for mild traumatic brain injury (mTBI) through the analysis of publicly available gene and miRNA databases, hypothesizing their influence on neuronal structure, axonal integrity, and regeneration. Methods: This study implemented a three-step process: (1) data searching for mTBI-related genes in Gene and MalaCard databases and literature review, (2) data analysis involved performing functional annotation through GO and KEGG, identifying hub genes using Cytoscape, mapping protein–protein interactions via DAVID and STRING, and predicting miRNA targets using miRSystem, miRWalk2.0, and mirDIP, and (3) RNA-sequencing analysis applied to the mTBI dataset GSE123336. Results: Eleven candidate hub genes associated with mTBI outcome were identified: APOE, S100B, GFAP, BDNF, AQP4, COMT, MBP, UCHL1, DRD2, ASIC1, and CACNA1A. Enrichment analysis linked these genes to neuron projection regeneration and synaptic plasticity. miRNAs linked to the mTBI candidate genes were hsa-miR-9-5p, hsa-miR-204-5p, hsa-miR-1908-5p, hsa-miR-16-5p, hsa-miR-10a-5p, has-miR-218-5p, has-miR-34a-5p, and has-miR-199b-5p. The RNA sequencing revealed 2664 differentially expressed miRNAs post-mTBI, with 17 showing significant changes at the time of injury and 48 h post-injury. Two miRNAs were positively correlated with direct head hits. Conclusions: Our bioinformatic analysis suggests that specific genes and miRNAs, particularly hsa-miR-10a-5p, may be involved in molecular pathways influencing mTBI outcomes. Our research may guide future mTBI diagnostics, emphasizing the need to measure and track these specific genes and miRNAs in diverse cohorts. Full article

New brain imaging modalities and neuropsychological testing tools are used to study neuronal changes in brain injuries such as mild traumatic brain injury (mTBI). Here we utilized diffusion tensor imaging (DTI) parameters and Wisconsin Card Sorting Test (WCST) variables to investigate patients with chronic mTBI. Neuropsychological assessments for mTBI evaluate impairments across a broad spectrum of executive functions. Our study aims to examine the relationship between fractional anisotropy (FA) and WCST covariates in patients with chronic mTBI. We hypothesize that patients who suffered chronic mTBI have significantly reduced FA in frontal white matter regions in association with significant deviation from standard percentile scores in WSCT. Utilizing multi-linear regression models alongside analyzing DTI scans, WCST covariates were linearly regressed to produce positive and negative contrasts to identify specific regions of interest (ROIs) with reduced FA. Results show that WCST covariates (such as percentile perseverative responses (Ep), non-perseverative responses (Enp), and conceptual response (CResp)) significantly deviate beyond standard percentile scores and correlate with lower FA in white matter regions in the frontal cortex, demonstrating executive function deficits. These frontal regions include the inferior frontal, superior frontal, and corpus callosum (CC), correlated with greater errors in WCST percentile scores. This study investigates the correlation between WCST covariates and DTI parameters as valuable tools in the diagnosis and prognosis of persistent cognitive impairment for patients with a history of chronic traumatic brain injury. Full article

Background: Post-traumatic epilepsy (PTE) is a recognized complication of traumatic brain injury (TBI), yet its risk following mild and moderate TBI remains underappreciated. Although mild TBI represents the majority of cases in clinical practice, a subset of patients develop unprovoked seizures months or even years post-injury. This review aims to synthesize current evidence on the incidence and predictors of PTE in mild and moderate TBI and to propose a clinically actionable decision-support tool for early risk stratification. Methods: We performed a narrative review of peer-reviewed studies published between 1985 and 2024 that reported on the incidence, risk factors and predictive models of PTE in patients with mild (Glasgow Coma Scale [GCS] 13–15) and moderate (GCS 9–12 or imaging-positive) TBI. Data from 24 studies were extracted, focusing on neuroimaging findings, early post-traumatic seizures, EEG abnormalities and clinical risk factors. These variables were integrated into a rule-based algorithm, which was implemented using Streamlit to enable real-time clinical decision-making. The decision-support tool incorporated five domains: injury severity, early post-traumatic seizures, neuroimaging findings (including contusion location and hematoma type), clinical and demographic variables (age, sex, psychiatric comorbidities, prior TBI, neurosurgical intervention) and EEG abnormalities. Results: PTE incidence following mild TBI ranged from <1% to 10%, with increased risk observed in patients presenting with intracranial hemorrhage or early seizures. From moderate TBI, incidence rates were consistently higher (6–12%). Key predictors included early seizures, frontal or temporal contusions, subdural hematoma, multiple contusions and midline shift. Additional risk-enhancing factors included prolonged loss of consciousness, male sex, psychiatric comorbidities and abnormal EEG patterns. Based on these features, we developed a decision-support tool that stratifies patients into low-, moderate- and high-risk categories for developing PTE. Conclusions: Even in non-severe cases, patients with mild and moderate TBI who exhibit high-risk features remain vulnerable to long-term epileptogenesis. Our proposed tool provides a pragmatic, evidence-based framework for early identification and follow-up planning. Prospective validation studies are needed to confirm its predictive accuracy and optimize its clinical utility. Full article

Background: The aim of this study was to systematically explore point-of-care biomarkers as diagnostic indicators for the detection and exclusion of mild traumatic brain injury (mTBI) in an emergency room (ER) setting using Eye-Tracking and Virtual Reality (ET/VR) technology. The primary target group included patients who had suffered an acute trauma to the head and presented within 24 h to the emergency department. Methods: The BG Unfallkrankenhaus Berlin and the BG Klinikum Hamburg participated in this explorative, prospective, single-arm accuracy study. This study included patients who presented to the emergency department with suspected mTBI and were examined using ET/VR glasses. All further steps corresponded to clinical routine (e.g., decision on hospital admission, imaging diagnostics). After the completion of treatment, the patients were divided into mTBI and non-TBI subgroups by consensus between two independent clinical experts, who were blinded to the results of the index test (examination using ET/VR glasses) in the form of a clinical synopsis. The diagnosis was based on all clinical, neurological, neurofunctional, neuropsychological, and imaging findings. Routine trauma and neurological history, examination, and diagnosis were performed in each case. All statistical analyses were performed with exploratory intent. Results: The use of ET/VR glasses was found to be predominantly unproblematic. Two of the fifty-two analyzed parameters can be statistically distinguished from a random decision. No difference in oculomotor function was found between the two subgroups, and no correlations between the parameters recorded by the VR goggles and the detection of mTBI were found. Conclusions: At present, the use of VR goggles for the diagnosis of mTBI in an ER setting cannot be recommended. Full article

Traumatic brain injury (TBI), even when mild, has been associated with the presence of depression. Depression is a mood disorder characterized by persistent negative thoughts and sadness and is challenging to treat due to the multiple mechanisms involved in its pathophysiology, including increased nitric oxide (NO) levels. There are no completely safe and effective pharmacological strategies to treat this disorder. Mucuna pruriens (MP) has been shown to possess neuroprotective properties by regulating inflammatory responses and nitric oxide synthase activity. In this study, we evaluated the antidepressant-like effect of MP in male Wistar rats with induced mild traumatic brain injury (mTBI). MP extract (50 mg/kg i.p.) was administered immediately after mTBI and every 24 h for five days. We used the rats’ preference for sucrose consumption to assess the presence of depression-like behavior and analyzed the nitrite and nitrate levels in their cerebral cortex, striatum, midbrain, and nucleus accumbens. Untreated animals with mTBI showed a reduced preference for sucrose than those treated with MP, whose preference for sucrose was similar to that of sham animals. Increased nitrite and nitrate levels were observed in different brain regions in the TBI subjects; however, this increase was not observed in MP-treated animals. MP reduces behavior associated with depression and the brain NO levels in rats with mTBI. Full article

Neurogranin (NRGN), a synaptic protein essential for plasticity and memory function, is gaining recognition as a promising biomarker for mild traumatic brain injury (mTBI). This systematic review brings together findings from six studies that measured neurogranin levels in biofluids—including serum, cerebrospinal fluid (CSF), plasma, and exosomes—during both the acute and chronic phases following injury. In the acute phase of mTBI, elevated levels of neurogranin were consistently observed in serum samples, suggesting its potential as a diagnostic marker. These increases appear to reflect immediate synaptic disturbances caused by injury. In contrast, studies focusing on the chronic phase reported a decrease in exosomal neurogranin levels, pointing to ongoing synaptic dysfunction well after the initial trauma. This temporal shift in neurogranin expression highlights its dual utility—both as an early indicator of injury and as a longer-term marker of synaptic integrity. However, interpreting these findings is not straightforward. The studies varied considerably in terms of sample type, timing of measurements, and control for potential confounding factors such as physical activity. Such variability makes direct comparisons difficult and may influence the outcomes observed. Additionally, none of the studies included proteoform-specific analyses of neurogranin, an omission that limits our understanding of the molecular changes underlying mTBI-related synaptic alterations. Due to heterogeneity across study designs and outcome measures, a meta-analysis could not be performed. Instead, a narrative synthesis was conducted, revealing consistent patterns in neurogranin dynamics over time and underscoring the influence of biofluid selection on measured outcomes. Overall, the current evidence supports neurogranin’s potential as both a diagnostic and mechanistic biomarker for mTBI. Yet, to fully realize its clinical utility, future research must prioritize standardized protocols, the inclusion of proteoform profiling, and rigorous longitudinal validation studies. Full article

Introduction: Mild traumatic brain injury (mTBI) in older adults (≥65 years) is often underestimated, despite being associated with significant morbidity. Age-related vulnerability, comorbidities, and medication use may exacerbate outcomes. This study aimed to identify predictors of brain health and functional recovery in older adults following mTBI, focusing on acute symptoms, CT imaging findings, and sociodemographic factors. Methods: We analyzed a cohort of 93 older adult patients with mTBI (GCS 13–15) who were prospectively enrolled at a tertiary neurosurgical center. All patients underwent baseline CT, structured clinical assessment, and follow-up at six months with standardized instruments (Glasgow Outcome Scale–Extended-GOSE, 12-Item Short Form Health Survey (quality-of-life measure)-SF-12, Rivermead Post-Concussion Symptoms Questionnaire-RPQ, Patient Health Questionnaire-9 (depression measure)-PHQ-9, PTSD (Post Traumatics Stress Disorder) Checklist for DSM (Diagnostic and Statistical Manual for Mental Disorders)-PCL-5, Timed up and Go Test (mobility measure-TUG test). Multivariate regression was performed to identify independent predictors of recovery. Results: At six months, 94.9% of older adults achieved functional independence (GOSE ≥ 5), though only 43% attained complete recovery (GOSE = 8). Patients with acute intracranial lesions on CT had worse physical outcomes, including slower mobility (mean TUG 17.6 vs. 16.3 s, p = 0.012). Severe acute headache independently predicted poorer recovery (lower GOSE and SF-12 PCS). Lower educational attainment correlated with worse functional and quality-of-life outcomes, consistent with reduced cognitive reserve. Psychological outcomes (PTSD and depression rates) were not associated with CT findings but were influenced by social support and sex. Prompt anticoagulation reversal in patients on anticoagulants markedly reduced hemorrhagic complications. Discussion: Older adults with mTBI generally maintain independence but experience reduced physical health and mobility compared to younger patients. Predictors of poorer outcomes include severe acute symptoms, CT-detected lesions, advanced age, and lower educational levels. Psychosocial support mitigated mental health complications. Conclusions: mTBI in older adults is not benign. Clinical, imaging, and sociodemographic factors collectively shape recovery. Early identification of high-risk patients and targeted interventions are essential to preserve brain health and independence in this growing population. Full article

Background: Amino acid biomarkers have a crucial influence on our understanding of brain injury mechanisms, and their plasma concentrations may indicate neurological damage and recovery patterns. Pediatric mild traumatic brain injury (mTBI) assessment particularly benefits from such molecular indicators, as clinical presentations can be subtle and variable. However, current diagnostic and prognostic tools lack reliable biochemical markers that can track the temporal evolution of injuries and recovery. Methods: We conducted a prospective longitudinal cohort study involving 36 pediatric mTBI patients and 44 controls to characterize the temporal evolution of key amino acids and their derived indices. Blood samples were collected at 3, 6, 12, and 24 h and at 7, 14, and 28 days post-injury, with amino acids quantified using high-performance liquid chromatography. Results: Our analysis revealed significant temporal changes in glutamate, glutamine, and glycine concentrations, with glutamate peaking at day 7 before declining, while glutamine showed steady increases throughout. The GLN/GLU ratio demonstrated an early excitatory imbalance followed by astrocytic compensation, and the GLX ratio indicated progressive recovery. Conclusions: These patterns represent continuous neurochemical processes involving excitotoxicity and glial regulation, suggesting potential utility as biomarkers for mTBI diagnosis and monitoring. While further validation using larger cohorts is needed, these findings provide compelling evidence of the efficacy of using amino acid profiles to track pediatric mTBI progression and recovery. Full article

Mild traumatic brain injury (mTBI) remains a clinical challenge, particularly in cases with normal computed tomography (CT) findings but persistent or evolving symptoms. Conventional diagnostic approaches relying solely on clinical criteria and neuroimaging often lack adequate sensitivity and may lead to unnecessary radiation exposure. Recent advances in biomarker research have identified several blood-based proteins such as glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), Tau protein, neuron-specific enolase (NSE), and neurofilament light chain (NFL) as potential tools for improving diagnostic precision and guiding clinical decisions. In this study, we synthesize current evidence evaluating the diagnostic and prognostic utility of these biomarkers using sensitivity, specificity, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). GFAP and UCH-L1 have shown high sensitivity in detecting intracranial lesions and are now FDA-cleared for emergency department triage within 12 h of injury. While S100B remains widely investigated, its low specificity limits its application beyond select clinical scenarios (i.e., in patients without polytrauma). Additionally, Tau, NSE, and NFL are emerging as prognostic markers, with studies suggesting associations with persistent symptoms and long-term neurocognitive outcomes. Overall, the integration of biomarker-based data into clinical workflows may enhance early mTBI diagnosis, reduce reliance on imaging, and enable individualized follow-up and prognostic stratification. Future research should refine optimal sampling windows and explore multimarker panels to maximize diagnostic and prognostic performance. Full article

Mild traumatic brain injury (mTBI) affects over 40 million people every year. One of its features includes the activation of microglia, the resident immune cells of the brain. Microglia assume different morphological states depending on their level of activation, such as surveilling ramified and activated hypertrophic, ameboid, and rod-like microglia. These states can be distinguished by multiple features, including the shape, span, and branching of microglia. Male Sprague–Dawley rats sustained mTBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) (3 times, 1.5 J per impact) or sham treatment. Four days after the injury, brains were collected and stained for microglia using the ionized calcium-binding adapter molecule-1 (Iba-1) antibody. Cortical injury sites were identified in a subset of CHIMERA animals. Using the MicrogliaMorphology ImageJ plugin and the MicrogliaMorphologyR package, 27 morphological features were quantified from individual microglia, and k-means clustering was used to classify microglia as ramified, rod-like, ameboid, and hypertrophic states. The CHIMERA injury altered microglia morphology features, which contributed to increased hypertrophic (activated) and decreased ramified (inactive) microglia compared to the sham controls. Combined with the clinically relevant mTBI paradigm and semi-automated/unbiased approach, the current findings may contribute to microglia morphology classification. Full article

Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Traumatic brain injury (TBI) is a major neurological condition affecting millions of individuals each year. Mild TBI (mTBI) manifests differently, with some individuals experiencing persistent, debilitating symptoms while others recover more rapidly. Despite its classification as “mild,” mTBI leads to both short- and long-term neurological effects, many of which occur due to functional changes in the brain. TBI-induced environmental changes within the brain play a critical role in shaping these functional outcomes. The importance of astrocytes in maintaining central nervous system (CNS) homeostasis has been increasingly recognized for their pivotal role in the brain’s response to TBI. Previous studies showed significant TBI-associated metabolic dysregulations. Therefore, we sought to analyze how astrocytes might adapt to persistent metabolic stressors in the post-injury microenvironment and identify injury-induced shifts occurring in vivo that may contribute to chronic metabolic dysfunction. We used an astrocyte-specific genome-scale metabolic model that allowed for the input of biologically relevant uptake rates corresponding to healthy astrocytes to analyze how the activity of metabolic pathways differed in hypoxic and acidic conditions. Additionally, these fluxes were integrated with mass spectrometry-based proteomics from male Sprague-Dawley rats subjected to mTBI to identify chronic adaptive neural responses post-injury. Comparison of modeled metabolic fluxes and experimental proteomic data demonstrated remarkable alignment, with both predicting significant changes in key metabolic processes including glycolysis, oxidative phosphorylation, the TCA cycle, and the Pentose Phosphate Pathway. These overlapping signatures may represent core survival strategies, offering insight into metabolic priorities and potentially serving as biomarkers of injury adaptation or recovery capacity. Full article

Background/Objectives: Mild traumatic brain injury (mTBI) presents with persistent, heterogeneous symptoms requiring multifaceted care. Although interdisciplinary rehabilitation is increasingly recommended, implementation remains inconsistent. This study aimed to synthesize existing literature and clinician perspectives to construct a practice-informed conceptual framework for interprofessional mTBI rehabilitation. Methods: Structured interviews were conducted with 94 clinicians—including neurologists, neuropsychologists, optometrists, occupational and physical therapists, speech-language pathologists, neurosurgeons, and case managers—across academic, private, and community settings in the United States. Interviews followed a semi-structured format adapted for the NIH I-Corps program and were analyzed thematically alongside existing rehabilitation literature. Results: Clinicians expressed strong consensus on the value of function-oriented, patient-centered care. Key themes included the prevalence of persistent cognitive and visual symptoms, emphasis on real-world goal setting, and barriers such as fragmented communication, reimbursement restrictions, and referral delays. Disciplinary differences were noted in perceptions of symptom persistence and professional roles. Rehabilitation technologies were inconsistently adopted due to financial, training, and interoperability barriers. Equity issues included geographic and insurance-based disparities. A four-domain conceptual framework emerged: discipline-specific expertise, coordinated training, technological integration, and care infrastructure, all shaped by systemic limitations. Conclusions: Despite widespread clinician endorsement of interprofessional mTBI care, structural barriers hinder consistent implementation. Targeted reforms—such as embedding interdisciplinary models in clinical education, expanding access to integrated technology, and improving reimbursement mechanisms—may enhance care delivery. The resulting framework provides a foundation for scalable, patient-centered rehabilitation models in diverse settings. Full article