Faculty Bibliography

OBJECTIVE:NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant genetic disorder characterized by the development of schwannomas, meningiomas, and spinal ependymomas. Treatment with bevacizumab, a monoclonal antibody against VEGF, has been shown to result in decreased vestibular schwannoma size and hearing improvement in ~50% of NF2-SWN patients. It is unknown whether the same degree of benefit is seen in younger patients compared with older patients. The objective of this study is to determine the association between age and bevacizumab treatment outcomes in NF2-SWN. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-seven patients with NF2-SWN. INTERVENTIONS/METHODS:Bevacizumab. MAIN OUTCOME MEASURES/METHODS:Change in tumor size of 20% or more. RESULTS:This study includes 37 patients with NF2-SWN who were treated with bevacizumab at our institution between 2014 and 2024. They were divided into 2 groups: 22 adults over the age of 25 (26 to 71 y) and 15 adolescent and young adult (AYA) patients under the age of 25 (12 to 24 y). The median treatment duration was 2.1 years. A significantly higher proportion of AYA schwannomas (37.5%, n=9) exhibited radiographic tumor progression during the treatment period compared with those of the older patient group (11.9%, n=5) (P=0.026), despite similar pre-treatment growth rates. There was no significant difference in the proportion of older and younger patients with hearing decline, improvement, or stability (P>0.05). CONCLUSIONS:AYA patients were significantly more likely to exhibit progression of tumor growth during bevacizumab treatment compared with older patients, though no significant differences were detected in hearing outcomes.

BACKGROUND:Multiple sclerosis (MS) and neurosarcoidosis (NS) can present as similar neuro-radiologic syndromes. Neither disease has pathognomonic clinical or laboratory findings and differentiating between them may be challenging. We hypothesized that cerebrospinal fluid (CSF) immune cell profiles, including CD4/CD8 cell ratio and proportion of B cells, might help to distinguish NS from MS. METHODS:Patients with probable or definite NS who were evaluated at the NYU MS Comprehensive Care Center (New York) and had CSF flow cytometry done as part of diagnostic workup were matched by age, sex, and race/ethnicity to MS patients with available CSF flow cytometry. All patients who received immunomodulatory therapy within 3 months of lumbar puncture were excluded. Flow cytometry was performed using BD FACSCanto™ and FACSCanto™ II Cell Analyzers (BDBiosciences, San Jose, CA) and manually verified by a hematopathologist. Group comparisons were made with an unpaired two-tailed Student's t-test, Chi-square test, or Wilcoxon rank sum test, as appropriate; p < 0.05 was considered significant. RESULTS:, p < 0.0001) and protein levels (101.2 ± 88.9 mg/dL vs. 35.7 ± 19.6, p = 0.003), while MS patients had more CSF-restricted oligoclonal bands (7.7 ± 5.3 vs. 1.7 ± 2.4, p < 0.00042). No differences were found in CSF glucose concentrations or IgG indices. Proportions of all immune cells in CSF were similar in NS and MS, including the CD4/CD8 ratio and percentages of B cells. CONCLUSION/CONCLUSIONS:Clinically available CSF flow cytometry immune profiles do not offer added discriminatory value for differentiating NS from MS. More granular immunophenotyping may be needed to improve diagnostic precision.

A transient ischemic attack is an acute neurologic event caused by focal ischemia affecting the brain, eye, or spinal cord, resolving quickly without infarction on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI). It is a tissue-based diagnosis, highlighting the need for prompt recognition and risk stratification. Evaluation in the emergency department includes detailed history, risk assessment, neurologic examination, and initial noncontrast computed tomography (CT) to rule out other conditions, with MRI DWI as the gold standard for confirming no infarction. Vascular imaging, echocardiography, electrocardiogram (ECG), and laboratories help identify underlying causes. Central retinal artery occlusion (CRAO) requires urgent diagnosis and ophthalmology consultation to prevent permanent vision loss.

BACKGROUND/UNASSIGNED:The potential for impaired sleep due to pain or discomfort can be a concern for adherence to nighttime bracing when treating clubfoot. The primary aim of our study was to compare sleep efficiency in young children wearing a nighttime foot abduction orthosis (FAO) to that of a matched control group. Secondary aims included the comparison of total sleep time, number of night wakings, and number of parental interventions between groups. METHODS/UNASSIGNED:< .05. RESULTS/UNASSIGNED:There were no significant differences in sleep efficiency, total sleep time, or number of night wakings. There were slightly more nighttime interventions for parents of children with clubfeet compared to controls. CONCLUSIONS/UNASSIGNED:Sleep metrics of young children undergoing Ponseti-style FAO bracing are not significantly different from those of matched controls. KEY CONCEPTS/UNASSIGNED:(1)Autovideosomnography using the Nanit infant monitor was utilized to measure sleep/wake patterns in 25 clubfoot patients undergoing Ponseti-style boots and bar treatment and 75 matched controls.(2)Clubfoot patients undergoing Ponseti-style boots and bar treatment did not have any significant differences across sleep efficiency, total sleep time, total time awake or number of night wakings compared to controls.(3)As brace tolerance and consistent adherence to a nighttime bracing regimen are essential to prevent recurrent clubfoot, caregivers and physicians may be reassured that clubfoot bracing will not significantly impact a child's sleep. LEVEL OF EVIDENCE/UNASSIGNED:Level II.

BACKGROUND:Depression, a debilitating mental disorder, has become the leading cause of disability worldwide. A growing body of evidence supports the feasibility and effectiveness of multicomponent lifestyle medicine programs for the treatment of depression, including the recent novel multicomponent Traditional Chinese Medicine Lifestyle Medicine (TCMLM) program (Registered at ClinicalTrials.Gov with registration number: NCT05799586). However, little is known about participants' experiences and perceptions of the program and the aspects that require improvement. This study aimed to explore the experiences and perceptions of participants attending the multicomponent TCMLM program and practicing the related lifestyle behaviors. METHODS:In this descriptive qualitative study, purposeful sampling was used to recruit Hong Kong Chinese adults who had participated in the multicomponent TCMLM program between August 2023 and January 2024. Face-to-face focus-group interviews and semi-structured interviews were conducted with audio recording, transcribed verbatim, and analyzed using conventional content analysis. All interviews were performed in classrooms in a university in Hong Kong. RESULTS:A total of 31 multicomponent TCMLM program attendees aged 20 to 65 years participated in the qualitative interviews. The content analysis identified three themes and 12 subthemes, namely, Theme 1: multicomponent TCMLM program originally being comprehensive and special (e.g., TCMLM program content originally being not unitary, increasing the number of methods for dealing with depressive symptoms); Theme 2: multicomponent TCMLM program being far more beneficial than expected (e.g., promoting diet, exercises, daily routine and sleep management based on TCMLM, improving physical functional status, improving one's personality); and Theme 3: practicing multicomponent TCMLM program having challenges (e.g., unsuitable conditions hindering some TCMLM practices in community). CONCLUSIONS:This study provides fresh in-depth insights into the perceptions and experiences of Hong Kong Chinese adults with depression who attended the multicomponent TCMLM program and engaged in the related lifestyle behaviors. Meanwhile, the challenges encountered while attending the program and practicing the related behaviors offer valuable information for further optimization of the program and expanding its application in Hong Kong or other regions.

OBJECTIVE:CDKL5 deficiency disorder (CDD) is a rare X-linked developmental and epileptic encephalopathy caused by loss-of-function variants in the CDKL5 gene. Preclinical experiments using enzyme replacement or gene therapies show promise and could be transformative therapies. This precompetitive consortium sought to harmonize nonseizure clinical endpoint selection for efficacy trials. Clinical Assessment of Neurodevelopmental Measures in CDD (CANDID) is an ongoing study evaluating the feasibility and suitability of neurocognitive tests and functioning scales in CDD patients. METHODS:CANDID is a 3-year, longitudinal, noninterventional global study involving children and adults with CDD. On-site and remote visits include clinical, behavioral, developmental, and quality of life assessments. RESULTS:We enrolled 112 patients (111 included in analyses); mean age = 8.3 years (range <1-28); 93% female; 10 participants were ≥18 years old. In the first 28 days, 82% had >16 seizures; six were seizure-free. Median seizure onset was at 1.5 months (range = 0-66). Patients used an average of 2.6 antiseizure medications at baseline. The most frequent comorbidities included gastrointestinal hypomotility, muscle tone abnormalities, and sleep disorders. Gross Motor Function Measure-88 (GMFM-88) scores indicated a floor effect in crawling, standing, and walking across all ages. Vineland-3 and Bayley-4 scores could be derived in most, with receptive language, interpersonal relationships, and fine and gross motor scores increasing with age. Bruni sleep questionnaire identified sleep initiation, sleep-awake transition, and excessive somnolence as the most disrupted components across all age groups. The mean Quality of Life Inventory-Disability total scores ranged from 53% to 64%, the independence domain being the most impacted. SIGNIFICANCE/CONCLUSIONS:The scales in the CANDID study capture disease-related deficits and phenotype variability in CDD. Floor effects in subdomains aligned with disease severity. The GMFM-88 lacks granularity, and its operational limitations make it unsuitable for CDD trials. Baseline analyses demonstrate the feasibility and potential value of most selected scales, supporting their use in optimizing trial design and endpoint selection for future CDD clinical trials.

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.

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.

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.