Faculty Bibliography

PURPOSE/UNASSIGNED:Navigating urban environments poses significant challenges for individuals who are blind or have low vision, especially in areas affected by construction. Construction zones introduce hazards such as uneven surfaces, barriers, hazardous materials, excessive noise, and altered routes that obstruct familiar paths and compromise safety. Although navigation tools assist in trip planning, they often overlook these temporary obstacles. Existing hazard detection systems also struggle with the visual variability of construction sites. METHODS/UNASSIGNED:We developed a computer vision-based assistive system integrating three modules: an open-vocabulary object detector to identify diverse construction-related elements, a YOLO-based model specialised in detecting scaffolding and poles, and an optical character recognition module to interpret construction signage. RESULTS/UNASSIGNED:In static testing at seven construction sites using images from multiple stationary viewpoints, the system achieved 88.56% overall accuracy. It consistently identified relevant objects within 2-10 m and at approach angles up to 75°. At 2-4 m, detection was perfect (100%) across all angles. Even at 10 m, six of seven sites remained detectable within a 15° approach. In dynamic testing along a 0.5-mile urban route containing eight construction sites, the system analysed every frame of a first-person walking video. It achieved 87.26% accuracy in distinguishing construction from non-construction areas, rising to 92.0% with a 50-frame majority vote filter. CONCLUSION/UNASSIGNED:The system can reliably detect construction sites in real time and at sufficient distances to provide advance warnings, enabling individuals with visual impairments to make safer mobility decisions, such as proceeding with caution or rerouting.

IMPORTANCE/UNASSIGNED:Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are attributable to a pathogenic variant in the superoxide dismutase 1 (SOD1) gene. Tofersen, an intrathecal antisense oligonucleotide designed to reduce SOD1 protein synthesis, is the first and only approved therapy for the treatment of ALS in adults who have a variant in the SOD1 gene. OBJECTIVE/UNASSIGNED:To evaluate the long-term effects of tofersen in adults with SOD1-ALS. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The phase 3, randomized, double-blind, placebo-controlled VALOR trial (A Study to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tofersen in SOD1-ALS; conducted from March 2019 to July 2021) evaluated tofersen use over 28 weeks in adults (18 years and older) with weaknesses attributable to ALS and a confirmed SOD1 pathogenic variant at 32 sites in 10 countries; participants could then enroll in an open-label extension (OLE; completed August 2024). INTERVENTION AND EXPOSURE/UNASSIGNED:Adults with SOD1-ALS were randomly assigned 2:1 to receive tofersen (100 mg) or placebo over a 24-week period in the VALOR study. All participants in the OLE were treated with tofersen. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Integrated analysis of VALOR and the OLE study aimed to compare early start vs placebo/delayed start (approximately 6 months later) treatment with tofersen. Key efficacy end points included measures of axonal injury and neurodegeneration (neurofilament), function and strength, quality of life, and survival. RESULTS/UNASSIGNED:VALOR enrolled 108 participants with 42 unique SOD1 pathogenic variants (mean [SD] age: placebo/delayed-start group 51.2 [11.6] [n = 36]; early-start group: 48.1 [12.6] [n = 72]) with 19 (53%) and 43 (60%) of participants being male in the placebo/delayed- and early-start groups, respectively. Overall, 95/108 participants (88%) enrolled in the OLE, and 46 participants completed the OLE (early-start group, 34 [47%]; placebo/delayed-start group, 12 [33%]). At OLE completion, participants could have accumulated 3.5 years or more (range, 192-276 weeks) of follow-up from the start of VALOR. Over 148 weeks, earlier initiation of tofersen (compared to later initiation) was associated with numerically less decline in measures of clinical function (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, -9.9 vs -13.5 points), respiratory function (slow vital capacity, -13.8% vs -18.1%), muscle strength (handheld dynamometry megascore, -0.38 vs -0.43 points), and quality of life (Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 score, 17.0 vs 22.5 points; EuroQol 5 Dimension, 5 Level Questionnaire score, -0.1 vs -0.2 points). Tofersen prolonged survival relative to the expected natural history of SOD1-ALS. Most adverse events were consistent with ALS progression or known procedural adverse effects. All serious neurological adverse events were reversible; few led to tofersen discontinuation. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Final data from VALOR and the OLE demonstrated the benefit of tofersen in SOD1-ALS and provide clear rationale for its use in this population. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: VALOR NCT02623699; OLE NCT03070119.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Dural arteriovenous fistula (dAVF) surgery is a microsurgical procedure that requires confirmation of obliteration using formal cerebral angiography, but the lack of intraoperative angiogram or need for postoperative angiogram in some settings necessitates a search for alternative, less invasive methods to verify surgical success. This study evaluates the use of indocyanine green videoangiography FLOW 800 hemodynamic intraoperatively during cranial and spinal dAVF obliteration to confirm obliteration and predict surgical success. METHODS:A retrospective analysis was conducted using indocyanine green videoangiography FLOW 800 to intraoperatively measure 4 hemodynamic parameters-Delay Time, Speed, Time to Peak, and Rise Time-across venous drainage regions of interest pre/post-dAVF obliteration. Univariate and multivariate statistical analyses to evaluate and visualize presurgical vs postsurgical state hemodynamic changes included nonparametric statistical tests, logistic regression, and Bayesian analysis. RESULTS:A total of 14 venous drainage regions of interest from 8 patients who had successful spinal or cranial dAVF obliteration confirmed with intraoperative digital subtraction angiography were extracted. Significant hemodynamic changes were observed after dAVF obliteration, with median Speed decreasing from 13.5 to 5.5 s-1 (P = .029) and Delay Time increasing from 2.07 to 7.86 s (P = .020). Bayesian logistic regression identified Delay Time as the strongest predictor of postsurgical state, with a 50% increase associated with 2.16 times higher odds of achieving obliteration (odds ratio = 4.59, 95% highest density interval: 1.07-19.95). Speed exhibited a trend toward a negative association with postsurgical state (odds ratio = 0.62, 95% highest density interval: 0.26-1.42). Receiver operating characteristic-area under the curve analysis using logistic regression demonstrated a score of 0.760, highlighting Delay Time and Speed as key features distinguishing preobliteration and postobliteration states. CONCLUSION/CONCLUSIONS:Our findings demonstrate that intraoperative FLOW 800 analysis reliably quantifies and visualizes immediate hemodynamic changes consistent with dAVF obliteration. Speed and Delay Time emerged as key indicators of surgical success, highlighting the potential of FLOW 800 as a noninvasive adjunct to traditional imaging techniques for confirming dAVF obliteration intraoperatively.

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.

The convergence of artificial intelligence (AI) and neuroscience represents one of medicine's most profound intellectual partnerships. Neuronal architecture has inspired computational methods, while computational models, evolving from theoretical constructs to transformative clinical tools, are reshaping neurological practice. As AI systems attempt to augment diagnostic accuracy, treatment planning, and patient care, neurologists must develop fluency in these technologies to harness their potential while navigating their limitations and dangers. AI-related publications have exponentially increased in recent years, yet many neurologists lack the foundational computer science background needed to critically evaluate and most safely and effectively implement these tools in clinical practice. This article serves to outline the historical foundations linking neuroscience to computing, examine core concepts of the past and current AI landscape in neurology, and describe methodologies that aim to revolutionize neurological care.

INTRODUCTION/AIMS/OBJECTIVE:There is a lack of information about startle reflex (SR) in primary lateral sclerosis (PLS). This study examined the presence and prevalence of SR in PLS and compared findings with amyotrophic lateral sclerosis (ALS). METHODS:46 PLS and 54 ALS participants were assessed through structured interviews in this cross-sectional study. Fisher's exact test was used to compare reported SR prevalence. Multivariable linear regression was utilized to study associations between disease group and SR frequency in response to sudden stimuli. RESULTS:SR differed markedly between the two groups, with a higher prevalence in PLS (93.5%) than ALS (20.4%; p < 0.001). Among ALS patients, SR was present in all upper motor neuron (UMN)-predominant cases, which accounted for 54.5% of the SR-positive ALS group, but only 10.4% of probable/definite ALS cases. In SR-positive patients, response frequency to sudden stimuli exceeded 60% in both ALS and PLS, most often triggered by auditory stimuli. Younger age, shorter disease duration, and PLS diagnosis were associated with more frequent SR. DISCUSSION/CONCLUSIONS:SR is significantly more common in PLS than in ALS. Notably, UMN-predominant ALS, although limited in number, showed a higher prevalence of SR (6 out of 6, 100%), indicating that predominant UMN involvement may be a key determinant of SR across both conditions. These hypothesis-generating findings suggest that SR may serve as a novel clinical marker in PLS and UMN-predominant ALS, warranting further validation through prospective studies.

BACKGROUND:Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period. METHODS:This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching COVID to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching. FINDINGS/RESULTS:We identified 407 300 (87·5%) of 465 717 eligible children and adolescents with a first infection episode and 58 417 (12·5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233 842 (50·2%) patients were male and 231 875 (49·8%) were female. The mean age was 8·17 years (SD 6·58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903·7 (95% CI 780·9-1026·5) in the first infection group and 1883·7 (1565·1-2202·3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2·08 [1·68-2·59]) and a range of symptoms and conditions potentially related to PASC (RR range 1·15-3·60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms. INTERPRETATION/CONCLUSIONS:Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies. FUNDING/BACKGROUND:National Institutes of Health.

BACKGROUND:Optimal emergency contraception (EC) can prevent approximately 95% of rape-related pregnancies. However, time to presentation, weight, and BMI influence efficacy of EC, and disparities in access to care, race and ethnicity, language, and socioeconomic status may modify rape-related pregnancy risk. We aimed to increase effective EC administration and eliminate potential health disparities in all sexual assault (SA) survivors managed in the emergency department (ED). METHODS:We conducted a 5-year retrospective review evaluating race and ethnicity, language, selected socioeconomic indicators, and obesity factors in EC administration. We implemented a quality improvement (QI) initiative over 2 years across three urban EDs, with interventions focused on care standardization (e.g., pharmaceutical changes, electronic health record optimizations, and checklists), multimodal and inter-disciplinary education, and sustainability of change (e.g., quality assurance reviews and bi-directional feedback). Statistical process control charts (SPCs) were used to evaluate temporal changes in EC administration to SA survivors. The Pearson Chi-squared was used to analyze differences across race and ethnicity groups in pre- and post-intervention cohorts. We estimated rape-related pregnancy preventions based on estimated pharmaceutical efficacy and previously reported marginal risks of pregnancy. RESULTS:Through two QI improvement cycles, within a pre-initiative cohort of 291 patients and post-initiative cohort of 156 patients, we increased any EC administration from 73.7% to 100% and effective EC from 44.1% to 100%, both of which were sustained for 14 months. Differences in effective EC administration across race and ethnicity groups pre-initiative (p = 0.005) were eliminated post-initiative (p = 0.840). An estimated 2.7-9.1 rape-related pregnancies were prevented in our post-initiative cohort. CONCLUSIONS:We achieved sustained effective EC administration to SA survivors and eliminated race and ethnicity disparities. Multi-modal interventions focusing on care standardization, education, and sustainability demonstrated success in patient preventative health goals and health equity.

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.

Machine learning (ML) on structural MRI data shows high potential for classifying Alzheimer's disease (AD) progression, but the specific contribution of brain regions, demographics, and proteinopathy remains unclear. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) data, we applied an extreme gradient-boosting algorithm and SHAP (SHapley Additive exPlanations) values to classify cognitively normal (CN) older adults, those with mild cognitive impairment (MCI) and AD dementia patients. Features included structural MRI, CSF status, demographics, and genetic data. Analyses comprised one cross-sectional multi-class classification (CN vs. MCI vs. AD dementia, n = 568) and two longitudinal binary-class classifications (CN-to-MCI converters vs. CN stable, n = 92; MCI-to-AD converters vs. MCI stable, n = 378). All classifications achieved 70-77% accuracy and 61-83% precision. Key features were CSF status, hippocampal volume, entorhinal thickness, and amygdala volume, with a clear dissociation: hippocampal properties contributed to the conversion to MCI, while the entorhinal cortex characterized the conversion to AD dementia. The findings highlight explainable, trajectory-specific insights into AD progression.