Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

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.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

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.

Headaches in Traumatic Brain Injury: Improvement Over Time, Associations With Quality of Life, and Impact of Migraine-Type Headaches.

OBJECTIVE: To describe headache characteristics over time in patients with traumatic brain injury (TBI). SETTING: Patients enrolled and followed at the National Institutes of Health Clinical Center between 2011 and 2020. PARTICIPANTS: There were 147 patients with TBI, with 74 mild TBI (mTBI), 49 moderate (modTBI), 24 severe (sTBI), and 20 individuals without brain injury (IWBIs). DESIGN: Regular surveys of headache characteristics in patients with TBI were conducted. Patients were enrolled as early as 30 days post-injury and followed up to 5 years, for 419 total visits and 80 patients with multiple return visits. MAIN MEASURES: Surveys of headache characteristics, including headache severity, were measured on a 0- to 10-point Likert scale and headache frequency quantified as headaches per month. Patients with migraine-type headaches ( n = 39) were identified by a clinician-administered tool. Functional outcomes were measured using the Glasgow Outcome Scale-Extended (GOS-E) and quality of life by the Satisfaction with Life Scale (SWLS) and the 36-item Short Form Survey (SF-36). RESULTS: At their initial visit, patients with TBI had more severe and frequent headaches than IWBIs (median 5 vs 2.5, P < .001; median 2 vs 0.2, P < .001), as did patients with mTBI compared with modTBI/sTBI (all P ≤ .01). Migraines were associated with lower SWLS and SF-36 scores. Migraines and young age were associated with higher headache severity and frequency across time points. Longitudinally, time post-injury correlated with improvement in headache severity and frequency without differences by injury severity. However, time post-injury did not correlate with improvement in headache characteristics in a patient subgroup with moderate/severe headaches. CONCLUSION: Our findings suggest that patients with mild, moderate, or severe TBI see improvement in headaches over time. However, patients should be counseled that improvement is modest and seen more in patients with milder headache symptoms. Patients with migraine headaches in particular are at risk for worse headache characteristics with greater impact on quality of life.

Traumatic microbleeds persist for up to five years following traumatic brain injury despite resolution of other acute findings on MRI.

OBJECTIVE: The primary objective of this study was to track the incidence and progression of traumatic microbleeds (TMBs) for up to five years following traumatic brain injury (TBI). METHODS: Thirty patients with mild, moderate, or severe TBI received initial MRI within 48 h of injury and continued in a longitudinal study for up to five years. The incidence and progression of MRI findings was assessed across the five year period. In addition to TMBs, we noted the presence of other imaging findings including diffusion weighted imaging (DWI) lesions, extra-axial and intraventricular hemorrhage, hematoma, traumatic meningeal enhancement (TME), fluid-attenuated inversion recovery (FLAIR) hyperintensities, and encephalomalacia. RESULTS: TMBs were observed in 60% of patients at initial presentation. At one-year follow-up, TMBs were more persistent than other neuroimaging findings, with 83% remaining visible on MRI. In patients receiving serial MRI 2-5 years post-injury, acute TMBs were visible on all follow-up scans. In contrast, most other imaging markers of TBI had either resolved or evolved into ambiguous abnormalities on imaging by one year post-injury. CONCLUSIONS: These findings suggest that TMBs may serve as a uniquely persistent indicator of TBI and reinforce the importance of acute post-injury imaging for accurate characterization of persistent imaging findings.