Growing evidence supports the potential of blood-based biomarkers for aiding in concussion diagnosis, though most work has focused on biomarker changes at the group level. Here, reliable change indices (RCI) identify individual athletes exhibiting meaningful elevations or decreases in biomarkers from baseline to multiple acute post-concussion timepoints. Baseline and post-injury blood (0-12, 12-36, and 36-60h) was prospectively collected from collegiate athletes in the Concussion Assessment, Research and Education Consortium. Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), tau, neurofilament light (NfL), and phosphorylated-tau181 (p-tau181) were measured in plasma; c-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, IL-receptor antagonist (RA), tumor necrosis factor, and vascular endothelial growth factor were measured in serum. Reliable change was calculated by dividing the difference between baseline and post-injury visits by the standard error of the difference from uninjured controls. Athletes with concussion with RCI > 1.65 (upper 5%) were classified as having 'elevated' biomarkers; those RCI < - 1.65 (lower 5%) were classified as 'decreased'. Binomial tests determined if the proportion of athletes with elevated/decreased biomarkers was different than 5%. Fisher's exact tests determined if presence of either loss of consciousness (LOC) and/or post-traumatic amnesia (PTA) impacted proportions of elevated or decreased biomarkers. A total of 521 participants (198 controls, 323 athletes with concussion) were included in this study. A significant proportion of athletes with concussion had elevated GFAP (16.0%), IL-1RA (16.4%), and IL-6 (15.9%) at 0-12h; a significant proportion had elevated GFAP at 12-36 (19.0%) and 36-60h (14.6%). Subsets of athletes with concussion had no elevations in any marker at 0-12 (37%), 12-36 (45%), and 36-60-h visits (63%). For decreased biomarkers (RCI < - 1.65), fewer participants with concussion had decreased NfL (0%) and GFAP (0%) at 12-36h, while a greater proportion had decreased p-tau181, NfL, UCH-L1, tau, IL-1RA, vascular endothelial growth factor (VEGF), and IL-10 at 36-60h (10.5-21.2%). Presence of LOC and/or PTA was associated with elevated GFAP at 12-36h (45% versus 15%; p = 0.004). Elevations in biomarkers were primarily observed in the early-acute window (0-12h); with only GFAP showing elevations at later visits and sensitivity to altered consciousness. Only a subset of athletes with concussion had meaningful elevations of any single blood-based biomarker, with elevations seen in single markers rather than a global increase across multiple markers. Any single marker has limited ability to capture the heterogenous physiological response to concussion and ultimately aid in concussion diagnosis.

Given the qualitative language differences observed during posttraumatic amnesia (PTA) after traumatic brain injury (TBI), along with the limited research base to guide clinical practice during PTA, this study aimed to (1) identify current speech-language pathologist (SLP) assessment and diagnostic practices for language dysfunction during PTA and (2) characterize the diagnostic terminology SLPs apply to PTA-associated language impairments. SLPs in the United States who provide clinical services to adults with neurologic communication impairments in hospital settings completed a cross-sectional online survey regarding their clinical practices and knowledge. Qualitative data were organized into broad categories using content analysis to summarize the common diagnostic themes applied by participants. Data were analyzed descriptively. Data from 83 SLPs revealed wide variability in reported knowledge and practice patterns for language and PTA assessment. Diagnostic terminology also varied considerably; for example, respondents reported using terminology for cognition (67%), language (47%), confusion (27%), and aphasia (18%) when labeling language impairments associated with transient confusion/PTA. These results expand on previous findings demonstrating inconsistencies in SLPs' knowledge and service delivery for individuals with TBI by examining diagnostic practices and terminology for language impairments during PTA. Specialized training in TBI is needed among SLPs, and guidelines need to be developed and disseminated to clinicians to support differential diagnosis and clinical decision making. Adoption of common diagnostic language to describe language impairments related to PTA is warranted. https://doi.org/10.23641/asha.32681088.

Hospitalized adults with traumatic brain injury (TBI) often experience acute confusional states. However, conceptual clarity remains limited because of overlapping terminology, which hinders assessment. This study aimed to map the terminology and assessment of acute confusional states in hospitalized TBI adults and examine their alignment with established definitions. We conducted a scoping review (2013-2025) in 4 databases (MEDLINE, PsycInfo, CINAHL, and Google Scholar) following the Arksey and O'Malley framework. Peer-reviewed studies and clinical guidelines addressing acute confusional states in hospitalized TBI adults were included. Data extraction focused on terminology, assessment practices, and correspondence with definitions. Thirty-four studies were included. The most frequently reported terms were post-traumatic amnesia (PTA; n = 18), agitation (n = 11), delirium (n = 5), and post-traumatic confusional state (PTCS; n = 2). PTA was described as a transient state, reflecting daily assessment using unimodal cognitive screening tools rather than a broader recovery phase. It was characterized by amnesia and disorientation after sedation, aligning with international cognitive rehabilitation guidelines (INCOG 2.0), although additional features were reported. Agitation, also described as a state, involved fluctuating motor restlessness, impulsivity, aggression, and intense emotions, often without significant cognitive impairment, partially aligning with Cohen-Mansfield definition. Delirium was conceptualized as a syndrome encompassing disturbances across cognitive, attentional, behavioral, psycho-affective, and perceptual domains, and was assessed using multicomponent instruments, consistent with Diagnostic & Statistical Manual of Mental Disorders (DSM-5). PTCS was described as a transitional period during early recovery of consciousness, assessed using a multidimensional observational tool, and characterized by attentional and executive disturbances, such as disorientation, slowed processing, attention deficits, as well as fluctuating emotional and behavioral responses, consistent with the case definition. Although overlapping features exist, PTA, agitation, delirium, and PTCS differ in underlying constructs and temporal framing. Refining definitions to better integrate behavioral and psycho-affective features and clarify transitional phases may improve conceptual and diagnostic clarity in acute TBI.

Long-term functional and vocational outcomes after traumatic brain injury (TBI) remain difficult to predict, limiting prognostic counselling and rehabilitation planning. We aimed to evaluate the Clinical-Biomarker-Imaging-Modifier (CBI-M) framework for predicting functional and employment outcomes up to 10 years following TBI. Retrospective cohort study of 2529 patients with TBI admitted for inpatient rehabilitation (1984-2024), contributing 5424 observations across 1, 2, 5 and 10 years post-injury. Prediction models used logistic regression with temporal validation, incorporating 21 CBI-M variables spanning clinical (post-traumatic amnesia (PTA), Glasgow Coma Scale (GCS)), imaging (9 CT variables) and modifier pillars (age, sex, pre-injury employment, mental health, extracranial injuries). Outcomes were Glasgow Outcome Scale-Extended (GOSE) functional outcomes (favourable outcome, return to participation, full recovery) and employment outcomes (any productive work, competitive work). Mean age was 38.7 years (SD=18.5); 705 (27.9%) were female. Models demonstrated good discrimination (mean area under the curve (AUC) 0.720; range 0.635-0.863), with 60% achieving AUC ≥0.70. Employment outcomes were slightly more predictable than GOSE outcomes (mean AUC 0.740 vs 0.70). PTA dominated prediction across both outcome types (GOSE: 28.8% variable importance; employment: 24%) versus GCS (GOSE: 3.9%; employment: 3.3%). Pre-injury employment was the second most important predictor for vocational outcomes (16.9%) after PTA. The clinical pillar was the dominant per-feature contributor to both GOSE (69.9%) and employment (64.5%) predictions, while the modifier pillar contributed most in absolute terms (41.6% and 50.8%, respectively). The CBI-M framework predicts functional and vocational outcomes up to 10 years post-TBI. PTA substantially outperforms GCS for long-term prognostication in TBI survivors, and vocational outcomes also depend on pre-injury social factors.

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Traditional classification based on the Glasgow Coma Scale (GCS) provides a shared clinical language but insufficiently captures the biological heterogeneity, imaging variability, and contextual modifiers that influence outcomes. In January 2024, the National Institute of Neurological Disorders and Stroke (NINDS) convened a multidisciplinary working group to propose the Clinical-Biomarkers-Imaging-Modifiers (CBI-M) framework. This review aims to summarize the rationale, structure, and potential clinical relevance of the CBI-M framework for trauma and acute care surgeons. A narrative literature review was conducted using PubMed and Scopus databases with the terms "traumatic brain injury," "classification," "biomarkers," "neuroimaging," and "personalized medicine." Articles published between 2000 and 2024 were prioritized, with emphasis on consensus statements, multicenter cohort studies (e.g.,TRACK-TBI, CENTER-TBI), and materials from the NINDS TBI Classification and Nomenclature Workshop. Reference lists were manually screened to identify additional relevant publications. The review synthesizes conceptual foundations, domain structure, and practical implementation considerations of the CBI-M model. The CBI-M framework introduces a multidimensional and dynamic approach to TBI characterization by integrating four domains: Clinical assessment (detailed GCS components, pupillary reactivity, post-traumatic amnesia, and structured symptom documentation); Biomarkers, including GFAP, UCH-L1, S100B, NfL, and pTau, which provide objective measures of neuronal and astroglial injury with defined temporal kinetics; Imaging, emphasizing standardized CT terminology within the first 24h and harmonized radiologic lexicons; and Modifiers, incorporating psychosocial, environmental, and comorbidity factors that influence outcomes. This integrated model may support more comprehensive characterization of TBI, facilitate interdisciplinary communication, and enable structured documentation across trauma systems. The CBI-M framework represents a conceptual shift from severity-based classification toward a multidomain approach to TBI characterization. For trauma surgeons, it offers a structured framework that may support more comprehensive documentation and facilitate integration with registry-based quality improvement and translational research. At present, its role is best understood as an evolving model with potential for future clinical applicability, pending prospective validation and assessment of feasibility across diverse trauma systems.

The post-traumatic confusional state (PTCS) is a period of recovery that follows traumatic brain injury (TBI), characterized by post-traumatic amnesia (PTA), impairments in attention, and behavioral dysregulation, among other clinical symptoms. The pathophysiology of PTCS is unknown, contributing to the absence of neurobiologically based diagnostic criteria, prognostic models, and treatments. The workgroup conducted a scoping review of the literature in MEDLINE/PubMed database and manual searches of references to synthesize the existing knowledge on structural, functional, electroencephalographic (EEG), molecular, and genetic biomarkers underlying PTCS diagnosis and prognosis through five Population, Intervention, Comparison, and Outcome (PICO) questions. The search yielded 3,333 abstracts of which 69 were retained and included. Teams of two workgroup members independently reviewed abstracts and articles. Most articles addressed whether biomarkers differentiated patients with PTCS/PTA from those not in PTCS/PTA, and whether biomarkers were associated with severity or duration of PTCS/PTA. Our findings suggest that transition through PTCS/PTA from lower to higher states of consciousness involves increased thalamic function, restoration of default mode network dynamics, and normalizing of excessive slow wave activity on quantitative EEG. For patients with mild TBI, PTCS/PTA was associated with greater TBI lesion burden on structural imaging. PTCS/PTA severity and duration were associated with lesion burden, reduced white matter integrity, and electrophysiological signatures. Results across studies were variable with many finding no relationship between PTCS/PTA and biomarkers. In summary, while it is premature to include biomarkers in the definition of PTCS/PTA, our findings provide avenues for future research that is designed specifically to address the pathophysiology of this condition.

While most people fully recover after mild traumatic brain injury (mTBI), a substantial minority experience persistent symptoms and incomplete recovery. This may be prevented by early interventions specifically targeting patients at risk of incomplete recovery. The UPFRONT-model was developed to identify patients at risk of poor functional outcome. This study aimed to externally validate the UPFRONT-model in an independent sample. A prospective, longitudinal, multicenter cohort study with 126 mTBI patients recruited from emergency and neurology departments (ED) of six hospitals in the Netherlands was performed. Predictors in the UPFRONT-model included educational level, Glasgow Coma Scale (GCS), neck pain at injury, alcohol intoxication, Post Traumatic Amnesia (PTA), pre-injury mental health, anxiety, depression, coping, and the number and severity of post-traumatic complaints. Functional recovery at 6 months was assessed using the Glasgow Outcome Scale Extended (GOS-E). The external validity of the UPRFONT model was assessed with measures of calibration and discrimination. The model showed acceptable discriminative ability (AUC = 0.74), comparable to the development sample (AUC = 0.77). However, calibration revealed systematic underestimation of recovery (predicted: 46%; observed: 75%), with a calibration intercept of 1.52 and a slope of 0.70. Despite differences in some predictor effects, psychological variables were robust and consistent across samples. The UPFRONT-model demonstrated solid discriminative performance in an external cohort, but tended to underestimate the likelihood of complete recovery. Further validation and optimization are needed before clinical implementation. The model holds promise for early identification of at-risk patients, enabling targeted interventions following mTBI.

This study compared the effects of 3 different approaches to handling missing data (listwise deletion of participants with missing data, mean imputation, and full information maximum likelihood [FIML]) when predicting functional independence trajectories over 10 years in older adults after traumatic brain injury (TBI). Twenty-three TBI Model Systems (TBIMS) inpatient rehabilitation facilities in the United States. Adults who sustained a complicated mild, moderate, or severe TBI at age 60 years or older and needed inpatient rehabilitation. They had to meet all eligibility criteria and have one or more functional independence measure (FIM) scores at 1, 2, 5, or 10 years post-TBI from the TBIMS national database. Retrospective analysis of observational data using hierarchical linear models. FIM total scores at 1, 2, 5, and 10 years post-TBI. Different missing data approaches led to drastically different findings. Model comparisons supported a quadratic effect of time only in the listwise deletion model and found no other significant predictors. Linear trajectories were found in the mean imputation and FIML models. For both these models, older age, underrepresented minority status, unemployment at injury, longer posttraumatic amnesia duration, and pre-injury limitations all predicted lower overall FIM trajectories. However, when compared with the mean imputation model, the FIML-estimated b-weights were larger with smaller P-values. Years of education significantly predicted higher overall FIM trajectories in the mean imputation model but not the FIML model, likely because of the artificial shrinking of the estimated b-weight standard errors in mean imputation. History of mental health treatment predicted lower FIM trajectories only in the FIML model. These findings show that it is critical to use appropriate modern methods to handle missing data because the method can affect outcome trajectory shape and identification of relevant predictor variables. Using older methods for handling missing data, such as listwise deletion, greatly reduces predictive ability, resulting in less generalizability and imprecision in longitudinal rehabilitation research.

The pattern of recovery from post-traumatic amnesia (PTA) is heterogeneous. This article aimed to: (1) identify possible groupings of patients with PTA based on the combination of relevant clinical variables; and (2) retrospectively analyze whether there were differences between these groups in terms of their response to a neuropsychological rehabilitation program. A retrospective observational study was conducted with 55 patients who had suffered a traumatic brain injury (TBI) and who had PTA at the time of admission to Guttmann—Hospital de Neurorrehabilitación. The presence of PTA was assessed using the Galveston Orientation and Amnesia Test (GOAT). Cluster analysis divided the sample into three groups. There were statistically significant differences between the three groups for the following variables: age (p < 0.001), Glasgow Coma Scale score (p < 0.001), PTA duration (p < 0.001), time elapsed between injury and admission to the neurorehabilitation center (p = 0.002), and duration of the neuropsychological rehabilitation program (p = 0.002). No differences were observed for the variables of sex, medical history, education level, TBI cause, number of medical complications associated with TBI, initial GOAT score, or geographical location of the referring hospital with respect to the neurorehabilitation center. These results suggest that there are distinct clinical courses and responses to treatment. In this context, the initial severity of the TBI appears to play a relevant role in the duration of the PTA phase. These findings, although preliminary, may help optimize the recovery process of patients with PTA.

Abstract Diffuse axonal injury (DAI) is a frequent and devastating form of traumatic brain injury (TBI) that requires prolonged intensive care and carries high morbidity and mortality. Early magnetic resonance imaging (MRI) lesion topography may offer crucial prognostic information to guide clinical management and family counseling. The objective of this is to evaluate the prognostic value of early MRI-based lesion location in DAI using the novel KASHI Classification and to correlate lesion topography with acute neurological severity, in-hospital mortality, and long-term functional recovery. In this single-center prospective cohort study, 91 patients with DAI (from 734 TBI admissions) underwent standardized MRI (T1, T2, FLAIR, diffusion-weighted imaging, gradient echo ± diffusion tensor imaging) on Day 1 postinjury. Lesions were graded 1–3C according to the KASHI schema based on their anatomical distribution. Clinical severity was assessed by the Glasgow Coma Scale (GCS) at admission, and outcomes included in-hospital mortality, duration of post-traumatic amnesia (PTA), and 6-month functional status measured by Glasgow Outcome Score and Rancho Los Amigos Scale. Higher KASHI grades were strongly associated with worse acute and long-term outcomes. Grade 3C lesions (pontine, medullary, cerebellar peduncle, or intraventricular hemorrhage) corresponded to the lowest mean GCS scores and a 68 % in-hospital mortality rate. Lesions of the thalamus and basal ganglia independently predicted prolonged PTA and poorer 6-month functional recovery. The KASHI Classification demonstrated high interrater reliability and outperformed total lesion volume models in early prognostication. Early MRI lesion topography, as stratified by the KASHI Classification, provides a simple, reliable framework for predicting neurological severity and recovery in DAI. Its application in acute TBI care can enhance prognostic accuracy and inform clinical decision-making. Further multicenter validation and integration with automated imaging analytics are warranted.

Traumatic brain injury (TBI) mechanisms are often grouped together in research. Differences in acute and long-term outcomes across mechanisms of injury (MOIs) remain unclear, partly because of confounding by age. Modeling MOI-specific effects can inform clinical triage and prognostication. We examined the relationship between motor vehicle accidents (MVAs) vs falls, the 2 most common MOIs, and acute and 1-year post-injury outcomes, after rigorous control of demographic and preinjury personal factors. Data were analyzed from individuals with moderate-to-severe TBI requiring inpatient rehabilitation from the TBI Model Systems National Database, a multicenter prospective longitudinal cohort study. The analytic sample was restricted to individuals aged 16-79 years with an MOI due to MVA or fall occurring between April 2010 and January 2023. We used inverse probability of treatment weighting, based on propensity scores, to adjust for 14 demographic and preinjury personal characteristics and estimate the causal effect of MOI on acute and 1-year outcomes after TBI. Acute hospital and rehabilitation outcomes included the following: Glasgow Coma Scale (GCS), sedation, intubation, post-traumatic amnesia duration, time to follow commands (TFC), length of hospital stay (LOS), and Functional Independence Measure (FIM) cognitive and motor scores. One-year outcomes included the following: Disability Rating Scale and Participation Assessment with Recombined Tools Objective. Among 5,181 participants (mean age 45.1 ± 19.5, 70% male), 48.4% sustained their injury from MVAs and 51.6% from falls. After weighting and multiple comparisons adjustment, the MVA group had lower GCS total scores by 1.27 points (95% CI -1.92 to -0.61; adjusted p = 0.001), greater odds of receiving sedation (odds ratio 1.43, 95% CI 1.11-1.85; adjusted p = 0.014), longer TFC by 1.64 days (95% CI 0.39-2.89; adjusted p = 0.017), and lower discharge FIM motor scores by 4.28 points (95% CI -7.50 to -1.26; adjusted p = 0.014). At 1 year after injury, disability levels and community participation did not differ. MVA-related TBI was associated with worse acute outcomes. However, by 1 year after injury, disability level and community participation do not differ. This work highlights novel findings in short-term and long-term outcomes after falls and MVAs, the leading TBI causes, which are not explained by confounders such as age. Findings may not generalize beyond patients receiving inpatient rehabilitation for TBI.

This study aimed to estimate the duration, of the posttraumatic confusional state (PTCS), and predictors of the duration after moderate and severe traumatic brain injury (TBI) in a prospective inception cohort. In 424 surviving neurosurgical patients with moderate [Glasgow Coma Scale (GCS) score 9-13] or severe TBI (GCS score ≤ 8), PTCS duration was estimated from sources documenting confusion or amnesia. Associations between PTCS duration and age, sex, indices of injury severity, and proxies of cognitive (education) and brain reserve (preinjury brain-related disability) were analyzed using binary logistic regression. The most common PTCS duration was ≤ 7 days in the moderate TBI group (58%) and >28 days in the severe TBI group (52%). In multivariable analyses, lower age (p < 0.001), higher education, higher GCS score (p < 0.001), lower Rotterdam CT score (p = 0.004-0.002) and no road traffic accident (p = 0.006) were associated with a PTCS duration ≤ 7 days. Higher age (p < 0.001), lower GCS score (p < 0.001), and higher Rotterdam CT score (p < 0.001) were associated with a PTCS duration >28 days. Proxies of brain reserve were not independently associated with PTCS duration. Cognitive reserve was associated with short, but not long, PTCS, while the proxy of brain reserve was not associated with PTCS. Age and injury-related variables were most consistently associated with PTCS duration. These results support the notion that PTCS is a foreseeable clinical phase after TBI, determined mainly by the brain injury itself.

Traumatic axonal injury is a common endophenotype of traumatic brain injury (TBI) in which injury to axons is a dominant component. In previous investigations, we identified a significant reduction of white matter (WM) volume from 3 to 12 months post-injury, an increased rate of atrophy during this period associated with a longer duration of post-traumatic amnesia (PTA), widespread reductions in white-matter fractional anisotropy (FA), and elevated free-water (FW) content in a cohort of moderate-to-severe TBI patients. To provide a more comprehensive characterization of the spatiotemporal trajectory of TBI-induced WM degeneration, we have estimated the spatial distribution of WM atrophy related to the duration of PTA in the first year following moderate-to-severe TBI (msTBI) (N = 33) and examined the degree to which baseline diffusion measures of WM integrity, FW and FW-corrected fractional anisotropy (F-FA), were each associated with subsequent WM atrophy. WM atrophy was observed diffusely across the brain, with the greatest effects in the splenium of the corpus callosum, corona radiata, and brainstem. Increased atrophy in the central WM was correlated with greater duration of PTA. Finally, elevated FW volume fraction at 3 months post-injury predicted greater subsequent WM atrophy, while F-FA did not show a significant relationship. These findings suggest that early FW elevation may serve as a biomarker of progressive WM neurodegeneration following TBI, and neuroinflammatory processes may underlie this relationship. Future research should directly investigate the underlying mechanisms of FW-related neuropathology and its role in progressive neurodegeneration following msTBI.

Previous studies have failed to determine whether acute neuroimaging findings after mild traumatic brain injury (mTBI) are associated with poor outcomes. We performed a systematic review and meta-analysis to determine whether such indicators are associated with health outcomes, recovery-related outcomes, or concurrent indicators of injury severity. We searched MEDLINE, PsycINFO, and Web of Science in April 2024. We extracted data from prospective studies or retrospective analyses of prospective data, where computed tomography scans were acquired within 1 week of mTBI or magnetic resonance imaging scans were acquired within 3 months of injury, according to PRISMA guidelines. The primary outcome measure was the Glasgow Outcome Scale. Secondary outcomes and indicators of injury severity included self-reported loss of consciousness, post-traumatic amnesia, and post-concussion symptom scores. The protocol for this study was pre-registered (PROSPERO #CRD42020190659). We included 64 studies in the review and 25 studies in the meta-analyses. The presence of acute neuroimaging findings after mTBI was associated with higher odds of poor outcome (OR = 2.04 [1.29-3.24], p = 0.0024, k = 7, n = 2,947) and loss of consciousness (OR = 1.42 [1.02-1.97], p = 0.039, k = 15, n = 3,912) compared to those without acute neuroimaging findings, but not post-traumatic amnesia (OR = 1.27 [0.65-2.49], p = 0.49, k = 10, n = 5,155) or post-concussion symptoms (Hedge's g = 0.00 [-0.17-0.17], p = 0.97, k = 9, n = 3,616). Results from qualitative analysis of outcome data that could not be synthesized quantitatively are congruent. Acute neuroimaging findings after mTBI are associated with poor functional outcome and may be clinically relevant for identifying patients at a higher risk for poor outcomes.

ABSTRACT Women with multi-gender attractions (i.e. bisexual+ women) experience alarmingly high rates of sexual violence (SV), which puts women at risk for posttraumatic stress disorder (PTSD). Bisexual+ women experience higher rates of PTSD compared to heterosexual and lesbian/gay people. The PTSD Checklist for DSM-5 (PCL-5) is a widely used self-report measure of PTSD symptoms. We conducted an item response theory (IRT) analysis to evaluate the item difficulty and discrimination of PCL-5 items in assessing PTSD symptoms related to adult SV among young bisexual+ women. We combined two samples of women: sample 1 participants were recruited via MTurk (N = 267; Mage = 25.9, range 18–35; 82.4% White) and sample 2 participants recruited via online ads (N = 133; Mage = 22.0, range 18–25, 85.0% White). Item difficulty and discrimination was evaluated using IRT with a graded response model. At clinically significant levels of PTSD, the most discriminating items were: flashbacks, nightmares, reckless behavior, inability to experience positive emotions, and intrusive memories, whereas the least discriminating items were: internal avoidance, hypervigilance, difficulty with sleep, external avoidance, and exaggerated startle response. The most difficult items were: reckless behavior, flashbacks, traumatic amnesia, nightmares, and irritability, whereas the least difficult items were: internal avoidance, cued emotional distress, external avoidance, hypervigilance, and strong negative emotions. Results suggest that symptoms related to flashbacks, nightmares, and reckless behavior are important for assessing clinically significant SV-related PTSD symptoms among young bisexual+ women, whereas symptoms related to internal and external avoidance and hypervigilance may be relatively less informative.

Post-traumatic confusional state (PTCS) frequently occurs during the recovery from disorders of consciousness (DoC) following severe traumatic brain injury (TBI). Confusional symptoms span multiple domains influencing consciousness, including impairments in the access and integration of mental contents, distortions in perceptual and emotional experiences, vigilance fluctuations, and deficits in memory, orientation, and executive control. While the clinical presentation can be systematically characterized using the Confusion Assessment Protocol (CAP), the underlying neurophysiological mechanisms remain poorly understood. Specifically, slowing of both periodic and aperiodic EEG activity is a consistent finding across multiple alterations of consciousness. We assessed whether recovery from PTCS involves a renormalization of EEG slowing. We recorded resting-state EEG from subacute severe TBI patients at admission (T0), comparing patients with PTCS (N=22) to TBI Controls who had already emerged (N = 19). Patients with PTCS were longitudinally monitored using CAP, and a follow-up EEG (T1) was acquired after rehabilitation either upon recovery (N=19) or at discharge (N=3). Recovery from PTCS was marked by partial normalization of the spectral profile-as indexed by the spectral exponent, and peak frequency-converging toward the profile of TBI Controls. However, marginal persistent elevations in power, indexed by spectral offset and delta power, indicated residual abnormalities. Spectral features, particularly spectral exponent and offset, correlated with CAP and robustly discriminated the presence of PTCS (bivariate model ROC AUC = 0.894). Results show that PTCS is marked by broadband EEG slowing affecting both periodic and aperiodic activity. Spectral reorganization over time provides insight into the mechanisms of recovery from PTCS and may inform rehabilitation pathways.

Background/Objectives: Mild traumatic brain injury (mTBI) is the most common subtype of traumatic brain injury, where patients experience a multitude of symptoms from headaches to memory loss and mood changes. Consequently, there are known poor prognostic factors for mTBI that can impede recovery and alter management courses. This narrative review aims to synthesize and provide a critical assessment of the current diagnostic criteria, management, and prognostic factors for mTBI to inform practice guidelines. Methods: This study adopts a patient-centered approach, focusing on treating presenting symptoms and referring patients to specialists for abnormal exam findings as needed. These findings are based on a narrative review of existing literature and the medical opinions of experts in neurology, physical medicine and rehabilitation, and pain medicine. The evidence supports that there are patient-related, injury-related, and contextual psychosocial factors that further complicate the long-term prognosis and management of mTBI. Conclusions: mTBI is defined by a set of diagnostic criteria: post-traumatic amnesia (PTA) lasting no longer than 24 h, loss of consciousness (LOC) not exceeding 30 min when present, and a Glasgow Coma Scale (GCS) score between 13 and 15. Current treatment options include prescribed rest followed by a gradual return to physical activity, medication management for symptoms with cognitive behavioral therapy, or vestibular physical therapy. Notably, several of these diagnostic criteria overlap with known poor prognostic indicators. These prognostic factors can be grouped into three categories: injury-related factors (LOC, positive imaging findings, history of prior concussions, and high symptom burden); patient-related factors (demographic characteristics and psychiatric history); and contextual psychosocial factors.

Mild traumatic brain injury (mTBI) is typically associated with transient cognitive disturbance, particularly involving attention and new learning, with most patients demonstrating full recovery within weeks. Memory impairment in uncomplicated mTBI generally reflects reversible neurometabolic dysfunction and is limited to a brief period of post-traumatic amnesia and restricted retrograde loss surrounding the injury. However, a subset of patients develop persistent and disproportionate autobiographical memory disturbance that exceeds expected neuroanatomical limits and lacks structural correlates on neuroimaging. In rare but clinically challenging cases, this presentation may resemble extensive retrograde or identity-related amnesia. This review examines functional (dissociative) amnesia emerging after mTBI and proposes that concussion may act as a gateway condition facilitating the development of Functional Cognitive Disorder (FCD) in vulnerable individuals. We differentiate expected post-traumatic memory patterns from atypical selective impairment of autobiographical retrieval and clarify how distinct memory systems-episodic, autobiographical, semantic, and procedural-are differentially affected. We expand the two-hit hypothesis by integrating contemporary neurobiological evidence. The first hit comprises concussion-induced neurometabolic disturbance, glial activation, oxidative imbalance, and transient fronto-limbic dysregulation. The second hit may involve psychological stress, identity threat, maladaptive metacognitive processes, or persistent neuroinflammatory signalling, collectively resulting in functional inhibition of autobiographical memory retrieval despite preserved memory storage. Functional amnesia is conceptualised as a severe phenotype within the spectrum of functional cognitive disorder. We introduce a structured clinician-administered interview (SIFRA) to operationalise diagnostic features and support systematic assessment. This integrative framework reconciles neurological vulnerability with functional network dysregulation and provides a coherent basis for diagnosis and multidisciplinary management of persistent memory disturbance after mTBI.

Repetitive mild traumatic brain injury (mTBI) may result in neurobiological changes that contribute to persistent symptoms of cognitive dysfunction. Elevations in plasma biomarkers (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL], total-tau [t-tau], and ubiquitin C-terminal hydrolase-L1 [UCH-L1]) have been reported acutely after mTBI, but few studies have assessed these biomarkers during the chronic phase of mTBI. To examine whether the associations among plasma biomarkers, brain volume, and cognition varied by mTBI among US active-duty service members and veterans. This cross-sectional study used data from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), a prospective, multicenter study of US active-duty service members and veterans (SMVs). Data collection began in January 2015, and only enrollment data (collected 2015 to September 2023) were analyzed. Recruitment occurred across several different VA medical centers and military sites across the United States. Participants were aged 18 years or older; had a history of deployment in Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn; and had combat exposure during deployment. Exclusion criteria were major neurologic or psychiatric disorder, history of moderate to severe TBI, coma lasting more than 30 minutes, posttraumatic amnesia lasting more than 24 hours, and intracranial lesion on computed tomography scan. History of blast- or combat-related mTBI. Plasma biomarkers were analyzed using Quanterix SIMOA assays. History of mTBI was ascertained using structured clinical interview. Regional brain volume was derived from T1-weighted magnetic resonance imaging scans. Cognitive performance was assessed using neuropsychological measures. Correlations were computed for associations between mTBI, brain volume, and cognition, and separate covariate-adjusted linear regression models we used to examine the association between each plasma biomarker and brain volume as well as cognition. Additional linear regression models were used to examine whether the number of combat-related and blast-related mTBIs moderated the association between each plasma biomarker, brain volume, and cognition. The cohort included 1160 participants (mean [SD] age, 41.9 [10.2] years; 1025 [88.4%] male; mean [SD] years since last mTBI, 12.1 [9.5]). Less than half of the sample was exposed to at least 1 blast-related (475 [40.9%]) or combat-related mTBI (490 [42.2%]). The association between enrollment biomarker concentration and brain volume and cognitive performance differed by the number of mTBIs. Among those with 2 mTBIs, higher UCH-L1 concentrations were associated with smaller anterior cingulate volume (blast-related mTBI: b = -0.08; 95% CI, -0.16 to -0.01; P = .04; combat-related mTBI: b = -0.09; 95% CI, -0.17 to -0.01; P = .03). Among those with 2 blast-related mTBIs, higher t-tau was associated with poorer performance on immediate and delayed visual memory (eg, performance on the Brief Visuospatial Memory Test-Revised, immediate recall: b = -0.11; 95% CI, -0.19 to -0.04; P = .003; delayed recall: b = -0.08; 95% CI, -0.16 to -0.01; P = .03), and higher GFAP and NfL concentration were associated with worse executive functioning (performance on Trail Making Testing B: GFAP concentration: b = 0.20; 95% CI, 0.03 to 0.37; P = .02; NfL concentration, b = 0.14; 95% CI, 0.01 to 0.26; P = .04), while no biomarker-cognition associations were observed for those with no mTBIs. However, most findings did not pass multiple comparison correction and should be interpreted with caution. In this cross-sectional study of 1160 SMVs, plasma biomarkers of neuronal injury and astrogliosis were associated with brain volume and cognitive performance based on mTBI.

Background/Objectives: Global disability scales such as the Glasgow Outcome Scale-Extended (GOS-E) may not fully capture real-life participation after traumatic brain injury (TBI). This secondary analysis quantified mismatch between global disability and participation 5 years after moderate-to-severe TBI and identified predictors of a "good recovery, poor participation" profile. Methods: We analysed the TBIMS National Database Public Use Data Set, including adults ≥ 16 years with moderate-to-severe TBI, 5-year follow-up, and valid GOS-E, PART-O, and employment data. High versus low global outcome was defined as GOS-E 7-8 versus 3-6; good versus poor participation was defined using PART-O total (≥median vs. ≤25th percentile) plus productive role engagement. Four outcome profiles were derived and compared using 2 × 2 factorial analyses and regression. Results: The analytic cohort included 6363 participants; among those with high GOS-E, 16.8% met criteria for poor participation. Profiles with poor participation showed lower participation and lower life satisfaction and higher mood symptoms than Group A (high GOS-E, good participation), whereas those with low GOS-E but good participation showed preserved participation with greater emotional burden. Older age, lower education, minority race/ethnicity, pre-injury unemployment or retirement, longer post-traumatic amnesia, and lower 2-year GOS-E independently predicted mismatch. Sensitivity analyses using alternative GOS-E and participation cut-offs and life-satisfaction outcomes yielded similar patterns. Conclusions: Five years after moderate-to-severe TBI, good global recovery does not guarantee successful reintegration, and some individuals maintain participation despite persisting disability. Routine assessment of participation and life satisfaction alongside global disability is needed to identify high-risk profiles and target vocational and psychosocial interventions.