Search Results (1,416)

Persistent post-concussion syndrome (PPCS) develops in 10 to 30 percent of patients following mild traumatic brain injury (mTBI), yet the most effective management approach remains an open question. This report describes a 37-year-old female who sustained a motor vehicle collision and was followed prospectively over 27 months. Structured evaluation at baseline identified dysfunction across oculomotor, vestibular, autonomic, cognitive, and neurophysiological domains. An intensive multimodal rehabilitation programme was associated with an 86 percent reduction in symptom burden (Post-Concussion Symptom Scale: 80 to 11) by the six-month mark. Thereafter, symptoms gradually returned in spite of continued treatment, and at 27 months the patient still reported moderate-to-severe headache (6 to 7 out of 10), persistent dizziness (5 to 6 out of 10), and meaningful functional limitations. The trajectory observed here, marked by initial gains followed by progressive relapse, illustrates the fluctuating and often incomplete recovery seen in a subgroup of PPCS patients. Clinicians should anticipate this pattern and frame outcome expectations accordingly, while building sustained, adaptive management strategies into long-term care plans. Full article

Background: Traumatic brain injury (TBI) damages brain tissues and affects the ocular system. Ocular manifestations such as orbital fractures, ocular surface disease, photosensitivity, impaired pupillary response, and retinal damage often co-occur with TBI. Despite established diagnostic criteria, a gap remains, particularly in detection, monitoring, and recovery prediction. Since ocular manifestations co-occur with TBI, they may offer non-invasive means to address this gap. Accordingly, this review evaluates whether TBI-associated ocular manifestations can serve as biomarkers for TBI detection, monitoring, and recovery. Methods: A literature search was conducted across three databases for studies that address ocular manifestations of TBI listed above. Results: Orbital fractures occur in 69%, matching TBI severity. Occult fractures may indicate unseen mild TBI on advanced neuroimaging. Dry eye disease prevalence is inconsistent (15 and 37%). Tear film proteomics show altered inflammatory and repair proteins, though this area remains understudied. Vitreous total tau and neurofilament light chain correlate with brain levels in chronic traumatic encephalopathy. Photosensitivity affects approximately 50% of acute TBI and declines to 14% after three months. NPi-200 pupillometer shows high specificity in triaging acute injury but with low sensitivity. PLR-3000 pupillometer and smartphone applications require further validation. Retinal imaging shows biphasic thickening then progressive thinning, modulated by sex, severity and duration. Conclusions: No single ocular biomarker fulfills all roles. Instead, different markers map into distinct stages of the clinical course. Future research should prioritize molecular markers in the tear film, combined with changes in corneal nerves across different TBI severities. Full article

Background: Mild traumatic brain injury (mTBI) may rapidly alter neurocognitive function and has been associated with an increased risk for post-traumatic stress disorder (PTSD). However, neuroimaging investigations during the acute post-trauma phase remain sparse. We previously reported greater left anterior insular cortex (aIC) activation during the cognitive appraisal of fearful versus neutral emotional faces in survivors who did and did not exhibit probable PTSD at 3 months, but not at 2 weeks, after a motor vehicle collision (MVC). Given previous studies suggesting that mTBI may lead to increased cortical activation in the early post-trauma period, we hypothesize that aIC activation within 2 weeks post-MVC may be elevated among probable PTSD survivors who sustained an mTBI compared to those who did not sustain mTBI. Methods: In this secondary hypothesis-driven analysis, previously reported task-related activation at both 2 weeks and 3 months after trauma was extracted from the aIC region of interest and compared among groups of survivors diagnosed with probable PTSD at 3 months with (n = 5) and without (n = 11) mTBI in the emergency department. An exploratory analysis of change over time included two time points and additional groups of survivors without probable PTSD with (n = 10) and without (n = 12) mTBI. Results: At 2 weeks, aIC activation was significantly greater in the probable PTSD with mTBI group than in the probable PTSD without mTBI group (mean = 0.125, SD = 0.053 vs. 0.014, SD = 0.111) (Welch’s t (13.86) = 2.71, two-sided p = 0.017). aIC activation in probable PTSD survivors with and without mTBI was not significantly different at 3 months after MVC. The time and time × group interactions were not significant in brain activation and post-traumatic stress symptoms, but within-group tests suggest that decreases in post-traumatic stress symptoms over time were significant in groups without mTBI. Conclusions: These preliminary results are consistent with the hypothesized association between mTBI and greater aIC activation to negative emotional stimuli in the early post-trauma period among survivors with probable PTSD, but do not support post-trauma brain changes in survivors with mTBI, probable PTSD, both conditions, or neither condition. These preliminary findings warrant further investigation into the relationship between mTBI and probable PTSD-related cortical alterations during the acute post-trauma period. Full article

Background: Pediatric traumatic brain injury (TBI) is the leading cause of acquired disability in childhood and is associated with post-concussive symptoms (PCS) that may negatively impact recovery and long-term outcomes. Despite the importance of follow-up care after TBI, families from marginalized racial and ethnic backgrounds are less likely to receive follow-up care and rehabilitation. This study examined the association between PCS and follow-up care, as well as the types of follow-up care received, among young, racially and ethnically diverse children with TBI. Methods: Data were collected from 36 families of children ages 2–5 years with a confirmed TBI in the past 3–6 months who completed screening procedures as part of a larger study. Parents reported demographic and injury characteristics, PCS, and whether they sought follow-up care after their child’s emergency department visit. Regression analyses examined associations between PCS and follow-up care. Results: Participants were 55.6% female, with a mean age of 3.60 years (SD = 1.22). Most children sustained mild injuries due to falls (77.8%). Headaches, drowsiness, balance difficulties, feeling slowed down, and behavior changes were individually associated with seeking follow-up care. In a regression model including all significant main effects, balance difficulties (B = 0.46) and drowsiness (B = 0.42) remained significant [F(5,30) = 6.11, p < 0.001]. Only 44.4% of parents sought follow-up care, and 33.3% of them followed up with a TBI specialist. Conclusions: Findings highlight low rates of post-injury follow-up and specialty care among young children with TBI, underscoring the need for improved caregiver education and first-line provider training. Full article

Blast-induced traumatic brain injury is a prevalent and underreported condition, particularly among military service members, for whom effective prophylactic interventions are lacking. Nano-pulsed laser therapy (NPLT) is a non-invasive neuromodulatory approach that delivers short pulses of near-infrared light to generate optoacoustic effects within cerebral tissue and has previously demonstrated therapeutic benefit following TBI. In this study, we evaluated whether a single pre-exposure application of NPLT could confer protection against neurological, cognitive, and cellular sequelae of mild blast injury. Adult male Sprague-Dawley rats were randomized to receive NPLT or Sham treatment 24 h prior to either Sham or mild blast exposure using the Advanced Blast Simulator. Neurological reflexes and vestibulomotor function were assessed on post-injury days (PIDs) 1–5, while cognitive performance was evaluated using the Morris Water Maze on PIDs 13–17. Histological analyses of microglia, astrocytes, and myelination were performed on PID 17. A single mild blast did not significantly alter gross neurological function but was associated with deficits in fine motor coordination and cognitive performance. Pre-exposure NPLT modestly attenuated blast-associated fine motor dysfunction, with a significant improvement compared with TBI on PID 4. In the Morris Water Maze, TBI animals exhibited significantly increased latency compared with Sham on PIDs 13 and 17, whereas NPLT + TBI animals did not significantly differ from Sham across the testing period, consistent with preservation of cognitive performance. Histological responses were regionally heterogeneous: NPLT alone produced distinct glial alterations, while NPLT + TBI animals exhibited a mixture of treatment- and injury-associated responses rather than uniform normalization to uninjured controls. NPLT did not prevent localized blast-associated reductions in corpus callosum myelin staining. In naive animals, NPLT significantly increased hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression 24 h after treatment. A single pre-injury application of NPLT was associated with functional resilience following mild blast exposure despite persistent and regionally heterogeneous histopathological alterations. Increased hippocampal BDNF 24 h after NPLT, together with region-specific glial changes following NPLT in the absence of injury, demonstrates that a single treatment produces sustained molecular and cellular effects before blast exposure. These findings are consistent with the hypothesis that prophylactic NPLT establishes an altered pre-injury biological state that may modify the subsequent response to blast and support further investigation of NPLT as a prophylactic strategy and of the mechanisms underlying NPLT-associated preconditioning. Full article

In contrast to foreign nucleic acids, some of our own endogenously synthesized nucleic acids may become immunologically active without being considered “foreign”. For example, abnormalities in chromatin organization, transcription termination, ribonucleic acid (RNA) splicing, and RNA editing, together with damage to mitochondrial integrity, may render normally functional deoxyribonucleic acid (DNA) and RNA persistently available and aberrantly structured ligands for innate immunity. Z-DNA-binding protein 1 (ZBP1), recently identified as an important component of this innate immune system, recognizes both left-handed DNA (Z-DNA) and left-handed RNA (Z-RNA) using its tandem Z-alpha (Zα) domains and couples recognition of these conformational states to receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-, receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-, and mixed-lineage kinase domain-like pseudokinase (MLKL)-dependent inflammatory and cell-death pathways. More recent studies have also shown that ZBP1 plays a role in recognizing damaged self-nucleic acids associated with tauopathies, Alzheimer’s disease (AD), traumatic brain injury (TBI), and amyloid-associated neuroinflammation. The nucleic-acid forms associated with these conditions include transposable-element activation, extended repeat-containing transcripts, RNA–RNA duplexes or RNA:DNA hybrids, oxidized mitochondrial DNA (mtDNA), and intercellularly transferred nucleic acids, all of which may exhibit substrate structures compatible with Z-form formation. Signaling by ZBP1 does not occur simply based upon nucleic-acid abundance; rather, signaling occurs after prolonged exposure to a nucleic acid when it persists in a structurally competent state, sufficient receptors are present to bind its exposed regions, the receptor proteoforms are competent to participate in signaling, receptor-interacting protein homotypic interaction motif (RHIM)-dependent assembly occurs, and the appropriate adaptor molecules are present. Furthermore, the identity of the cell type expressing ZBP1 determines whether the response produces RIPK3–MLKL-dependent neuronal injury, microglia-mediated inflammation, apoptosis, or mixed cell death. Finally, competition with adenosine deaminase acting on RNA 1 (ADAR1), melanoma differentiation-associated protein 5 (MDA5), double-stranded RNA-dependent protein kinase (PKR), the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS–STING) pathway, and other nucleic-acid-sensing proteins divides the available pool of endogenous nucleic acids among the outcomes of immune tolerance, type I interferon (IFN-I) signaling, translational inhibition, neuroinflammation, and necroptosis. Full article

Background: The purpose of this paper is to describe lessons learned from a clinical program that was developed to serve adolescents who experienced ABI in childhood during their transition to adulthood by providing insights to achieve good health and assessment of needs in both healthcare and educational/career areas. Methods: Participatory Action Research methods were utilized for program development by collaborating with focus groups of teen participants and stakeholders following each year. Activities were devised based on best practices for cognitive rehabilitation, direct instruction, and practice of cognitive and metacognitive strategies, technology use, peer coaches and incorporation of multiple stakeholders, including family members. Results: We learned the importance of technology utilization, completing surveys of vocational interests, peer coaches, and post program follow-up to better understand both healthcare and career needs of adolescents who experienced TBI and are transitioning to adulthood. Conclusions: Adolescents who experience a childhood ABI benefit from education about the injury effects, technology use for self-management, peer coaches and connection to both healthcare and career opportunities following high school graduation. Full article

(1) Background: Traumatic brain injury (TBI) triggers synaptic loss, leading to long-term neurological deficits. Electroacupuncture (EA) benefits neurological conditions, but its mechanisms after TBI remain unclear. (2) Methods: We used a controlled cortical impact (CCI) mouse model. Behavioral outcomes were assessed using the modified neurological severity score (mNSS), rotarod, Y-maze, and novel object recognition test (NORT). Synaptic morphology was examined by transmission electron microscopy (TEM). Energy metabolism was assessed using biochemical assays, and mitochondrial function was assessed using flow cytometry. Quantitative real-time PCR (qPCR) and Western blotting (WB) were used to examine the underlying molecular mechanisms. (3) Results: We found that EA ameliorates TBI-induced motor and cognitive impairments by preserving synaptic and mitochondrial integrity. EA-treated mice showed improvements in mNSS, rotarod, NORT, and Y-maze performance, along with preserved synaptic ultrastructure and mitochondrial function. CaMKII overexpression abolished EA-induced neuroprotection, identifying the CaMKII/Drp1 axis as a key mediator. (4) Conclusions: Thus, EA limits TBI deficits by restraining CaMKII/Drp1-driven mitochondrial fission and subsequent synaptic loss. Full article

Background: Between 33% and 75% of women who experience intimate partner violence (IPV) sustain an IPV-related traumatic brain injury (TBI). Although IPV-related TBI is associated with adverse psychosocial outcomes, its impact on response to healthcare-based IPV interventions remains unclear. Methods: Using data from a randomized clinical trial within the Veterans Health Administration, we examined psychosocial outcomes among 60 woman veterans with past-year IPV experiences participating in two brief IPV interventions: Enhanced Care As Usual (ECAU) and Recovering from IPV through Strengths and Empowerment (RISE). Results: At pretreatment, 21 women (35%) reported a history of probable IPV-related TBI. Multilevel modeling revealed no significant main or interaction effects of TBI history for self-efficacy, empowerment, patient activation, depression, physical health symptoms, or resilience. However, there was a significant interaction of time and probable IPV-related TBI history for valued living, such that women with probable IPV-related TBI history demonstrated greater initial gains followed by slight posttreatment decline; F(2, 76.55) = 2.96, p = 0.049. There was also a significant interaction between probable IPV-related TBI history, treatment condition, and pretreatment anxiety symptoms for anxiety symptoms as an outcome, such that women with probable IPV-related TBI history in the RISE condition, who had more severe anxiety symptoms at pretreatment, reported higher anxiety symptoms on average across the study period than women without probable IPV-related TBI history in RISE; F(1, 48) = 5.04, p = 0.029. Furthermore, there was a significant interaction of probable IPV-related TBI history and pretreatment physical health symptoms for physical health symptoms as an outcome, such that women with probable IPV-related TBI histories maintained higher physical symptoms from pretreatment to the last follow-up assessment; F(1, 134) = 8.99, p = 0.004. Conclusions: No evidence of differential treatment response was detected for women with and without probable IPV-related TBI history. Findings related to valued living and anxiety suggest areas where additional support may improve implementation of brief healthcare-based IPV interventions. Full article

Traumatic brain injury (TBI) is associated with heterogeneous neurophysiological and behavioral outcomes that are not always captured by conventional clinical classifications. This study aimed to characterize electrophysiological patterns in individuals with TBI and examine their alignment with clinical groupings. EEG, event-related potentials (ERPs), spectral features, and behavioral performance were analyzed in 121 participants from a larger clinical cohort. Data were preprocessed using artifact subspace reconstruction (ASR), adaptive mixture independent component analysis (AMICA), and standardized quality control procedures. Spectral power, ERP components, and behavioral metrics were extracted and compared across clinical severity and OSU TBI-ID classifications, and unsupervised k-means clustering was applied to identify data-driven electrophysiological subgroups. Results demonstrated consistent ERP signal quality across participants, with all datasets meeting P300 global field power thresholds. While group-level comparisons revealed distributions of electrophysiological markers across clinical categories, clustering identified two electrophysiological subgroups characterized by differing spectral, connectivity, and ERP profiles that were not significantly associated with OSU TBI-ID classifications. Electrophysiological subgroup assignments were not significantly associated with OSU TBI-ID classifications. These findings suggest that data-driven electrophysiological subgrouping captures variability not reflected in traditional clinical groupings, highlighting the potential utility of electrophysiological measures for characterizing heterogeneity within chronic TBI populations. Full article

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability worldwide and is frequently associated with persistent impairments in consciousness, cognition, mood, and functional independence. Despite advances in acute neurocritical care, effective therapies that enhance neurological recovery remain limited. Neuromodulation has emerged as a promising strategy to augment neuroplasticity and improve recovery through both pharmacologic and non-pharmacologic approaches. This narrative review summarizes current evidence supporting pharmacologic neuromodulatory therapies, including central nervous system stimulants (methylphenidate and modafinil), dopaminergic agents (amantadine and bromocriptine), acetylcholinesterase inhibitors (donepezil and rivastigmine), and selective serotonin reuptake inhibitors (sertraline and fluoxetine). Mechanisms of action, clinical efficacy, adverse effects, and practical considerations across the acute, subacute, and chronic phases of TBI recovery are discussed. Emerging non-pharmacologic neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation, are also reviewed. Although amantadine remains the only neuromodulator supported by moderate-quality guideline recommendations for accelerating recovery in disorders of consciousness, accumulating evidence suggests that several additional pharmacologic and non-pharmacologic neuromodulation interventions may improve attention, executive function, fatigue, mood, and rehabilitation participation in carefully selected patients. However, current evidence is limited by heterogeneous study populations, small sample sizes, inconsistent outcome measures, and a paucity of long-term randomized controlled trials. Future research should prioritize adequately powered comparative studies, standardized outcome measures, biomarker-guided patient selection, and multimodal treatment strategies to optimize neurological recovery following TBI. Full article

Background: Non-missile penetrating traumatic brain injury (pTBI) is a rare but life-threatening condition. In self-inflicted cases involving the frontal sinus, a rigorous preoperative diagnostic workup is crucial to assess foreign body fragmentation, trajectory, and potential vascular compromise. The complexities of such cases demand a highly structured approach to prevent severe secondary brain injury and long-term infectious sequelae. Case Presentation: A 36-year-old male with schizophrenia presented after attempting suicide by stabbing a kitchen knife through his frontal sinus. Multimodal diagnostic imaging was immediately employed. Skull radiographs and computed tomography (CT) precisely delineated the blade traversing the frontal sinus and entering the anterior cranial fossa. Crucially, given the proximity to the skull base, digital subtraction angiography (DSA) was proactively performed, which confirmed the absence of major cerebrovascular injury and safely guided the surgical strategy. Based on these precise imaging findings, a bifrontal craniotomy was performed. During the procedure, the main blade was extracted, and a retained broken metallic tip—recognized upon close intraoperative inspection of the extracted blade—was successfully retrieved from the intracranial compartment. Postoperative wound infections (with causative pathogens isolated as Serratia odorifera and coagulase-negative Staphylococci) were effectively eradicated with targeted antibiotics. The patient achieved a favorable neurological recovery. Conclusions: Multimodal neuroimaging, particularly the combination of CT and DSA, can be highly beneficial in the diagnostic workup of complex pTBI. Precise preoperative imaging helps guide the optimal surgical approach, ensuring complete foreign body removal and minimizing severe secondary complications. Early intervention, guided by standardized imaging and followed by aggressive medical management, can yield positive outcomes even in severely morbid presentations. Full article

Mild traumatic brain injury (mTBI) is a common cause for pediatric emergency department visits and can impose substantial burdens on families, including missed work and childcare needs. Socioeconomic context may influence both healthcare use and these downstream impacts. This study examined the association between Child Opportunity Index (COI), a neighborhood-level measure of socioeconomic status, and healthcare utilization and indirect costs following pediatric concussion. In a secondary analysis of a multisite randomized controlled trial of patients with acute (<72 h) concussion, participants were categorized into high, middle, and low COI groups. Outcomes included follow-up care, caregiver missed workdays, childcare needs, and indirect costs, analyzed using multivariable regression models. Participants from lower COI neighborhoods were more likely to present to the emergency department, with 93.02% compared to 71.43% in higher COI groups (p = 0.005); had higher symptom scores at 14 days, 28.69 versus 16.64 (p = 0.03); and were less likely to be seen by concussion specialists, 6.98% versus 28.57% (p = 0.005). They also had lower odds of attending follow-up within 14 days (OR = 0.36, p = 0.015) and higher caregiver burden, including more missed workdays and childcare needs. Although total indirect costs did not differ significantly for low COI groups after adjustment, middle COI participants had lower costs than high COI ones. Overall, disparities were observed in care patterns and caregiver burden despite similar recovery outcomes. These findings suggest that expanding access to affordable concussion follow-up through school-based programs, telehealth services, transportation assistance, and flexible scheduling may help reduce caregiver burden and improve continuity of care for children from lower COI neighborhoods following pediatric mTBI. Full article

Background and Objectives: Traumatic brain injury (TBI) is one of the leading causes of long-term disability among adults, with consequences for balance, postural stability, and quality of life. Addressing balance disorders in TBI patients requires a tailored and continuous care approach; the existing literature underlines a general framework for physiotherapy treatments, but no clear profile of technique, dosage and timing of intervention emerges. The present scoping review, therefore, aimed at mapping physiotherapy approaches to balance in TBI population, highlighting their potential effects and role through care pathways. Materials and Methods: A scoping review was conducted, according to PRISMA Extension for Scoping Reviews, with the aim of mapping physical therapy approaches to treat balance disorders in adult patients with TBI. A specific search string for each database was formulated through a PCC (Population, Concept, Context) framework. The search, limited to articles in English and published between 2015 and 2025, was conducted across five databases (PubMed, PEDro, Scopus, Embase, and Web of Science), including experimental studies, observational designs, and `case reports. Results: From the initial selection of 1052 records, six studies were included: five randomized controlled trials and a case report, published between 2016 and 2022. Results presented high heterogeneity of physiotherapy programs and outcome variations; interventions identified included virtual reality, video game therapy, adapted physical exercise, ballistic training, rapid-resistance elliptical training, and rhythmic auditory stimulation. These studies reported variable improvements in balance and mobility, not even with significant inter-group differences. Conclusions: Several techniques showed preliminary evidence in pre/post improvements of balance for TBI patients, including strength exercise, aerobic training and virtual-mediated approaches such as video game therapy and virtual reality. Rhythmic auditory stimulation has unclear effects. Future studies are needed to define the impact of each balance recovery strategy according to the baseline characteristics of the patient. Full article