Faculty Bibliography

BACKGROUND/UNASSIGNED:Outdoor navigation poses significant challenges for people with blindness or low vision, yet the role of gaze behaviour in supporting mobility remains underexplored. Fully sighted individuals typically adopt consistent scanning strategies, whereas those with visual impairments rely on heterogeneous adaptations shaped by residual vision and experience. METHODS/UNASSIGNED:We conducted a comparative eye-tracking study of fully sighted, low vision, blind, and fully blind participants navigating outdoor routes. Using a wearable eye tracker, we quantified fixation counts, fixation rate, fixation area, direction, peak fixation location, and walking speed. RESULTS/UNASSIGNED:Walking speed declined systematically with worsening vision. Fixation count increased with greater impairment, reflecting slower travel times and more frequent sampling. Fixation rate differed across groups, though between-group differences were generally not significant between most groups. Fixation spatial coverage decreased along the continuum of vision loss. Fixation patterns were most consistent in the fully sighted group. Peak fixation locations were centred in fully sighted participants but shifted outward and became more variable with impairment. CONCLUSION/UNASSIGNED:Gaze strategies during navigation form a graded continuum across vision groups, with fully sighted and fully blind participants at opposite poles and low vision and blind groups spanning the middle. Visual acuity alone does not predict functional gaze use, as rehabilitation experience and adaptive strategies strongly shape behaviour. These findings highlight the need for personalised rehabilitation and assistive technologies, with residual gaze patterns offering insight into mobility capacity and training opportunities for safer navigation.IMPLICATIONS FOR REHABILITATIONDistinct Residual Vision Patterns: This research reveals that residual vision patterns differ significantly, with fully sighted individuals exhibiting a consistent fixation pattern while low vision participants show more varied strategies during navigation.Highly Individualised Gaze Behaviours: Low vision participants demonstrate highly individualised gaze behaviours, indicating that a one-size-fits-all approach is inadequate for effective rehabilitation.Tailored Assistive Solutions: Assistive technologies and rehabilitation programs should be designed to address these unique, individualised needs, providing personalised feedback and training to enhance mobility and safety.

The ability to shift focus within three-dimensional space depends on vergence eye movements, which are impaired in ≤40% of individuals with neurodegenerative disorders. Although foundational studies in monkeys have identified neural correlates of vergence in the midbrain, a translational gap persists, leaving the neural basis of vergence dysfunction in humans poorly understood. Through voxel-wise analyses in 66 humans and 19 monkeys with midbrain lesions, we link vergence dysfunction causally to a region rostral to the superior colliculus and centred on the nucleus of the posterior commissure (NPC). Connectivity analyses across species identified a brain circuit linking the NPC to the visual pretectum and midbrain premotor hubs, regions capable of integrating the visual input and motor output necessary for vergence control. Collectively, these findings provide a neuroanatomical basis for vergence dysfunction and demonstrate how lesion mapping can bridge fundamental insights from animal models with clinical observations in humans.

OBJECTIVE:Cervical artery dissection (CeAD) may be limited to the extracranial extradural space or extend to the intradural space. Intradural extension can potentially increase the risk of stroke and subarachnoid hemorrhage. However, the factors associated with intradural extension and its impact on clinical outcome remain unclear. METHODS:This was a secondary analysis of the STOP-CAD observational, multi-center study. Patients with CeAD and intradural extension (CeADid) were compared with those with pure CeAD extradural dissections (CeADed) using multiple regression analyses. RESULTS:Of 4,023 patients with CeAD, 534 (13.3%) had CeADid. In comparison to patients with CeADed, those with CeADid more often had clinical overt stroke or transient ischemic attack (TIA) at presentation, acute infarcts on imaging, a vertebral artery affected, and severe stenosis of the involved vessel (p < 0.001 for all). In contrast, carotid involvement and complete occlusions were more frequent in patients with CeADed (p < 0.001 for both). CeADid was associated with a shift in the distribution of scores on the modified Rankin Scale (mRS) toward worse functional outcome (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.62-0.92) but the odds for favorable outcomes (mRS = 0-2) did not differ between the groups after appropriate adjustments on multivariate analysis. CeADid was independently associated with higher mortality at 180 days on multivariate analysis (adjusted OR = 2.84, 95% CI = 1.50-5.38). INTERPRETATION/CONCLUSIONS:CeADid is associated with more severe clinical presentation, a shift toward less favorable outcomes, and higher mortality rates. These findings suggest that CeADid may represent a high-risk type of CeAD. ANN NEUROL 2026.

BACKGROUND:Increased chronological age correlates with reduced relapse rates and increased disability in multiple sclerosis (MS). Biological age may better capture ageing's impact on MS and might accelerate due to MS itself. Establishing accelerated biological ageing in adults is complicated by normal ageing and comorbidities. Telomere length, a well-recognised biological ageing marker, is shortened in adults with MS and associated with disability. Demonstrating accelerated biological ageing in paediatric-onset MS (POMS) would strengthen the hypothesis that MS drives premature biological ageing. This study aimed to determine if telomere length differs in POMS compared to age-similar healthy controls. METHODS:We performed a cross-sectional case-control study of whole blood samples and clinical data from The US Network of Pediatric MS Centers. Real-time quantitative PCR measured telomere length, expressed as a telomere to somatic DNA ratio (T/S ratio). T/S ratio was compared between cases and age-similar healthy controls using multivariate regression analysis adjusting for chronological age, sex, race, ethnicity, tobacco exposure, socioeconomic status and body mass index. RESULTS:We analysed 300 POMS cases and 200 controls. The unadjusted mean T/S ratios were 1.66 (SD 0.32) for cases and 1.71 (SD 0.29) for controls (mean difference -0.05, 95% CI -0.10 to 0.01, p=0.08). After adjusting for key covariables with face validity, POMS participants had a mean 0.086 shorter T/S ratio than controls (95% CI 0.015 to 0.157, p=0.018). CONCLUSIONS:POMS participants demonstrated shorter telomeres than age-similar controls in a multivariable model adjusting for sociodemographic variables, suggesting that MS may contribute to accelerated biological ageing.

IMPORTANCE/UNASSIGNED:Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID. OBJECTIVE/UNASSIGNED:To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n = 903) and adolescents (12-17 years; n = 3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024. EXPOSURE/UNASSIGNED:Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices. RESULTS/UNASSIGNED:The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.

Antiretroviral therapies (ARTs) have reduced mortality among people living with HIV (PLWH) in Nigeria. Nonetheless, there is limited research on the impact of perceived helplessness on the wellbeing of PLWH in Nigeria. This study examined the effect of perceived helplessness on middle-age and older PLWH using health-related quality of life (HRQoL), subjective health (SH), and subjective cognitive decline (SCD) as outcomes related to wellbeing. We invited 150 participants, all of whom completed a self-administered questionnaire assessing the variables of interest and key sociodemographic characteristics. Multiple linear regression models were fit to examine the relationship between perceived helplessness and wellbeing, accounting for relevant covariates such as age, sex, relationship status etc. Results showed that higher perceived helplessness was associated with lower physical HRQoL (B = -0.275, p < 0.001), lower mental HRQoL (B = -0.18, p < 0.001), better SH (B = 0.010, p < 0.001) and higher reports of SCD (B = 0.443, p < 0.001). PLWH in Nigeria are exposed to stressors that diminish their sense of control and increase their risk for poor wellbeing. The findings underscore the need for interventions to ameliorate perceived helplessness, thereby improving health and wellbeing among aging adult PLWH in Nigeria.

IMPORTANCE/UNASSIGNED:Lyme disease (LD) is the most common vector-borne illness in the US. Given the increasing prevalence and expanding geographic bounds of LD, in-depth, up-to-date understanding of costs associated with an LD diagnosis, including patient out-of-pocket (OOP) costs, is needed. OBJECTIVE/UNASSIGNED:To assess health care costs in a broad US population diagnosed with LD, overall and stratified by localized disease vs disseminated disease. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study identified patients from Optum's deidentified Market Clarity Data (Optum Market Clarity) between December 2, 2014, and January 30, 2023 (study period), with an LD diagnosis between January 1, 2016, and December 31, 2022 (identification period), having at least 14 months of continuous health plan enrollment. Optum Market Clarity is an integrated, multisource medical claims, pharmacy claims, and electronic health records data set. Outpatients had a claim with an LD diagnosis plus relevant antibiotics within 30 days, and inpatients had a claim with LD as the primary diagnosis or as a secondary diagnosis with an LD-associated condition as the primary diagnosis. Data were analyzed from February 27, 2023, to October 20, 2025. EXPOSURE/UNASSIGNED:The main exposure was LD diagnosis. Case patients were classified as having disseminated, localized, or indeterminate LD based on diagnosis codes for LD and LD-associated conditions, inpatient vs outpatient services, or antibiotic treatment type. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Health care costs (reported in US dollars) for LD cases overall and stratified by localized disease vs disseminated disease were assessed 4 ways: (1) LD-specific costs per episode, (2) all-cause 6-month baseline vs follow-up costs for case patients with LD, (3) all-cause 6-month follow-up costs for case patients with LD compared with the control group, and (4) multivariable case-control analysis. Costs are reported as estimated direct (standardized) costs and patient OOP costs. Wald 95% CIs were used for means of cost measures. RESULTS/UNASSIGNED:A total of 70 531 case patients with LD were included. Their mean (SD) age was 44.8 (21.3) years; 51.3% were female. Estimated direct costs of LD were substantial across assessment methods, including episode cost (mean, $2227 [95% CI, $2111-$2342]), case patients as self-controls analysis (difference, $3304 [95% CI, $3117-$3491] in mean 6-month costs between baseline and follow-up), case-control analysis (difference, $4098 [95% CI, $3888-$4307] in mean 6-month follow-up costs), and multivariable-adjusted analysis (case-control difference, $5571 in projected mean 6-month follow-up costs; cost ratio, 1.96 [95% CI, 1.90-2.02]). OOP costs were available for 10 962 patients (15.5%) with LD. Mean OOP costs attributed to LD ranged from $188 to $399. Extrapolating to the US population in high-incidence states, annual costs of LD could range between $591 million and $1.05 billion (2022 dollars), with $411 to $771 million attributable to disseminated disease. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this retrospective cohort study, LD presented a large financial burden to the health care system and patients, especially for those with disseminated disease. These findings highlight the need for effective preventive measures to reduce costs for patients and the health care system.

IMPORTANCE/UNASSIGNED:Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. OBJECTIVE/UNASSIGNED:To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. INTERVENTIONS/UNASSIGNED:Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. RESULTS/UNASSIGNED:A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, -0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, -0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, -0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, -0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT05965739.

BACKGROUND AND IMPORTANCE/BACKGROUND:Rhino-orbital cerebral mucormycosis (ROCM) is an aggressive fungal infection involving the paranasal sinuses, orbit, and intracranial cavity, with a propensity for vascular invasion. This can lead to complications such as internal carotid artery (ICA) thrombosis and occlusion, presenting major neurosurgical challenges. Although surgical debridement and antifungal therapy are the mainstays of treatment, cases with significant neurovascular involvement require specialized intervention. We report a case of ROCM with severe flow-limiting ICA stenosis treated by direct extracranial-intracranial bypass. CLINICAL PRESENTATION/METHODS:tA 65-year-old man with diabetes presented with progressive left-sided blindness and facial numbness. Imaging revealed a left orbital mass extending into the paranasal sinuses and intracranially. Empiric antifungal therapy was started. Pathology confirmed Rhizopus species. Despite extensive surgical debridement and antifungal therapy, the patient developed progressive severe cavernous ICA stenosis, leading to watershed territory strokes. To restore cerebral perfusion, protect from distal emboli, and prepare for potential aggressive debridement, a flow-replacing direct (superficial temporal artery-middle cerebral artery (M2)) bypass was performed, and the supraclinoid carotid was trapped. Intraoperative angiography confirmed robust flow through the bypass. The patient was discharged on antifungal therapy and aspirin. At 6-month follow-up, the patient was neurologically intact with an modified Rankin Scale score of 1. Computed tomography angiography and transcranioplasty Doppler ultrasonography confirmed good flow through the bypass. CONCLUSION/CONCLUSIONS:In addition to antifungal therapy and surgical debridement, superficial temporal artery-middle cerebral artery bypass can be a lifesaving intervention in the management of ROCM with severe cerebrovascular compromise. This case highlights the critical role of cranial bypass in preserving cerebral perfusion in patients with flow-limiting ROCM-associated ICA invasion.