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Objective: Blood-based biomarkers have received considerable attention for their diagnostic and prognostic value in the acute and postacute period following traumatic brain injury (TBI). The purpose of this study was to examine whether blood-based biomarker concentrations within the first 12 months of TBI can predict neurobehavioral outcome in the chronic phase of the recovery trajectory. Setting: Inpatient and outpatient wards from 3 military medical treatment facilities. Participants: A total of 161 service members and veterans classified into 3 groups: (a) uncomplicated mild TBI (MTBI; n = 37), (b) complicated mild, moderate, severe, penetrating TBI combined (STBI; n = 46), and (c) controls (CTRL; n = 78). Design: Prospective longitudinal. Main Measures: Participants completed 6 scales from the Traumatic Brain Injury Quality of Life (ie, Anger, Anxiety, Depression, Fatigue, Headaches, and Cognitive Concerns) within 12 months (baseline) and at 2 or more years (follow-up) post-injury. Serum concentrations of tau, neurofilament light, glial fibrillary acidic protein, and UCHL-1 at baseline were measured using SIMOA. Results: Baseline tau was associated with worse anger, anxiety, and depression in the STBI group at follow-up (R 2 = 0.101-0.127), and worse anxiety in the MTBI group (R 2 = 0.210). Baseline ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) was associated with worse anxiety and depression at follow-up in both the MTBI and STBI groups (R 2Δ = 0.143-0.207), and worse cognitive concerns in the MTBI group (R 2Δ = 0.223). Conclusions: A blood-based panel including these biomarkers could be a useful tool for identifying individuals at risk of poor outcome following TBI. [ABSTRACT FROM AUTHOR]

Key Points: Question: Can a systematic evaluation using quantitative magnetic resonance imaging (MRI) metrics identify potential brain lesions in patients who have experienced anomalous health incidents (AHIs) compared with a well-matched control group? Findings: In this exploratory study that involved brain imaging of 81 participants who experienced AHIs and 48 matched control participants, there were no significant between-group differences in MRI measures of volume, diffusion MRI–derived metrics, or functional connectivity using functional MRI after adjustments for multiple comparisons. The MRI results were highly reproducible and stable at longitudinal follow-ups. No clear relationships between imaging and clinical variables emerged. Meaning: In this exploratory neuroimaging study, there was no significant MRI-detectable evidence of brain injury among the group of participants who experienced AHIs compared with a group of matched control participants. This finding has implications for future research efforts as well as for interventions aimed at improving clinical care for the participants who experienced AHIs. Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)–detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)–wise; (2) diffusion MRI–derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P <.05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons. This study assesses whether participants with anomalous health incidents (AHIs) differ significantly from US government control participants with respect to magnetic resonance imaging–detectable brain lesions. [ABSTRACT FROM AUTHOR]

Key Points: Questions: Do US government officials and their family members involved in anomalous health incidents (AHIs) differ from control participants with respect to clinical, biomarker, and research assessments? Findings: In this exploratory study that included 86 participants reporting AHIs and 30 vocationally matched control participants, there were no significant differences in most tests of auditory, vestibular, cognitive, visual function, or blood biomarkers between the groups. Participants with AHIs performed significantly worse on self-reported and objective measures of balance, and had significantly increased symptoms of fatigue, posttraumatic stress disorder, and depression compared with the control participants; 24 participants (28%) with AHIs presented with functional neurological disorders. Meaning: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for self-reported and objective measures of imbalance; symptoms of fatigue, posttraumatic stress, and depression; and the development of functional neurological disorders in some. Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons. This study assesses whether participants with anomalous health incidents (AHIs) differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. [ABSTRACT FROM AUTHOR]

AbstractObjective: The present study aimed to examine the impact of lifetime blast exposure (LBE) on neuropsychological functioning in service members and veterans (SMVs). Method: Participants were 282 SMVs, with and without history of traumatic brain injury (TBI), who were prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)-Traumatic Brain Injury Center of Excellence (TBICoE) Longitudinal TBI Study. A cross-sectional analysis of baseline data was conducted. LBE was based on two factors: Military Occupational Speciality (MOS) and SMV self-report. Participants were divided into three groups based on LBE: Blast Naive (n = 61), Blast + Low Risk MOS (n = 96), Blast + High Risk MOS (n = 125). Multivariate analysis of variance (MANOVA) was used to examine group differences on neurocognitive domains and the Minnesota Multiphasic Personality Inventory-2 Restructured Form. Results: There were no statistically significant differences in attention/working memory, processing speed, executive functioning, and memory (Fs < 1.75, ps > .1, ηp2s < .032) or in General Cognition (Fs < 0.95, ps > .3, ηp2s < .008). Prior to correction for covariates, lifetime blast exposure was related to Restructured Clinical (F(18,542) = 1.77, p = .026, ηp2 = .055), Somatic/Cognitive (F(10,550) = 1.99, p = .033, ηp2 = .035), and Externalizing Scales (F(8,552) = 2.17, p = .028, ηp2 = .030); however, these relationships did not remain significant after correction for covariates (Fs < 1.53, ps > .145, ηp2s < .032). Conclusions: We did not find evidence of a relationship between LBE and neurocognitive performance or psychiatric symptoms. This stands in contrast to prior studies demonstrating an association between lifetime blast exposure and highly sensitive blood biomarkers and/or neuroimaging. Overall, findings suggest the neuropsychological impact of lifetime blast exposure is minimal in individuals remaining in or recently retired from military service. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of this study were to (a) describe normative ranges-- expressed as reference intervals (RIs)--for vestibular and balance function tests in a cohort of Service Members and Veterans (SMVs) and (b) to describe the interrater reliability of these tests. Method: As part of the Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence 15-year Longitudinal Traumatic Brain Injury (TBI) Study, participants completed the following: vestibulo-ocular reflex suppression, visual-vestibular enhancement, subjective visual vertical, subjective visual horizontal, sinusoidal harmonic acceleration, the computerized rotational head impulse test (crHIT), and the sensory organization test. RIs were calculated using nonparametric methods and interrater reliability was assessed using intraclass correlation coefficients between three audiologists who independently reviewed and cleaned the data. Results: Reference populations for each outcome measure comprised 40 to 72 individuals, 19 to 61 years of age, who served either as noninjured controls (NIC) or injured controls (IC) in the 15-year study; none had a history of TBI or blast exposure. A subset of 15 SMVs from the NIC, IC, and TBI groups were included in the interrater reliability calculations. RIs are reported for 27 outcome measures from the seven rotational vestibular and balance tests. Interrater reliability was considered excellent for all tests except the crHIT, which was found to have good interrater reliability. Conclusion: This study provides clinicians and scientists with important information regarding normative ranges and interrater reliability for rotational vestibular and balance tests in SMVs. [ABSTRACT FROM AUTHOR]