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.

Characterizing upper limb function in the context of activities of daily living in CLN3 disease.

In CLN3 disease, impairments in motor function are frequently reported to have later onset compared to visual and cognitive decline, but upper limb motor function has yet to be explored in this population. In a cohort of 22 individuals with CLN3, we used a novel application of multiple measures to (1) characterize motor function, particularly of the upper limbs, in activities of daily living (ADLs), and (2) explore associations between motor function and age as well as visual ability, disease severity, and cognitive function, as evaluated by the Unified Batten Disease Rating Scale (UBDRS), a validated CLN3 disease measure. ADLs that required coordination, speed, and fine motor control were particularly challenging for children with CLN3 based on item-level performance across direct assessments (Jebsen-Taylor Hand Function Test [JTHFT] and MyoSet Tools) and caregiver reports (Pediatric Evaluation of Disability Inventory-Computer Adaptive Testing [PEDI-CAT] and Patient-Reported Outcomes Measurement Information System [PROMIS] Pediatric Upper Extremity). Poorer visual ability, disease severity, and cognitive function were associated with worse performance on these measures, whereas age had limited impact. These findings support the need for children with CLN3 to receive skilled clinical evaluation and treatment tailored to their individual needs, particularly in the context of ADLs, as their symptom profile progresses.

General and Specific Strategies Used to Facilitate Locomotor Maneuvers.

People make anticipatory changes in gait patterns prior to initiating a rapid change of direction. How they prepare will change based on their knowledge of the maneuver. To investigate specific and general strategies used to facilitate locomotor maneuvers, we manipulated subjects' ability to anticipate the direction of an upcoming lateral "lane-change" maneuver. To examine specific anticipatory adjustments, we observed the four steps immediately preceding a maneuver that subjects were instructed to perform at a known time in a known direction. We hypothesized that to facilitate a specific change of direction, subjects would proactively decrease margin of stability in the future direction of travel. Our results support this hypothesis: subjects significantly decreased lateral margin of stability by 69% on the side ipsilateral to the maneuver during only the step immediately preceding the maneuver. This gait adaptation may have improved energetic efficiency and simplified the control of the maneuver. To examine general anticipatory adjustments, we observed the two steps immediately preceding the instant when subjects received information about the direction of the maneuver. When the maneuver direction was unknown, we hypothesized that subjects would make general anticipatory adjustments that would improve their ability to actively initiate a maneuver in multiple directions. This second hypothesis was partially supported as subjects increased step width and stance phase hip flexion during these anticipatory steps. These modifications may have improved subjects' ability to generate forces in multiple directions and maintain equilibrium during the onset and execution of the rapid maneuver. However, adapting these general anticipatory strategies likely incurred an additional energetic cost.