Faculty Bibliography

Health equity research in neurology and neuroscience faces a unique challenge in the current United States climate of funding scarcity and prioritization of other research topics. The low funding contrasts with rising interest and scholarship in the field. Neuroscientists in the early phases of their career are particularly vulnerable to the detrimental effects of reduced funding due to their relatively lower publication history and established sources of support for projects. Here, we introduce the Early Career Network within the Society of Equity Neuroscience (SEQUINS). The group is dedicated to the support of early-career neurologists and neuroscientists who pursue health equity neuroscience research. We will accomplish this via a combination of virtual and in-person events as well as the establishment of a robust community of scientists. Together, we will foster camaraderie, solidarity, and shared interests to propel the field of health equity neuroscience forward.

BACKGROUND:Spinocerebellar ataxia type 27 B (SCA27B) caused by GAA trinucleotide repeats in the fibroblast growth factor 14 gene is emerging as a common cause of late-onset ataxia. Oscillopsia due to downbeat nystagmus (DBN) and diplopia are common symptoms, yet the causes of diplopia and strabismus patterns are poorly defined. METHODS:Retrospective chart review of 18 patients diagnosed with SCA27B over the past year. RESULTS:Ten of 18 patients had episodic or persistent oscillopsia or diplopia at disease onset, neurologically isolated in 4. Seventeen had detectable DBN, although it was often delayed in onset and was clinically obvious in only 5. Diplopia was present in 14 patients: vertical due to skew deviation (static and or alternating on lateral gaze) (n = 8) and/or horizontal due to vergence dysfunction (n = 11). Symptomatic vergence dysfunction included convergence insufficiency (CI) (n = 4) and divergence insufficiency (n = 5). Thirteen of 16 patients experienced improvement in oscillopsia or imbalance on 4-aminopyridine (4-AP). CONCLUSIONS:Strabismus patterns causing diplopia in patients with SCA27B are, not unexpectedly, largely attributable to cerebellar dysfunction and are not unique to SCA27B. The exceptions to cerebellar localization were CI, sixth nerve palsy, and slow saccades. Careful assessment for DBN in patients presenting with episodic or persistent diplopia from skew deviation or vergence disorders is important, as this may be key to confirming a cerebellar localization, subtle on examination, and guide toward genetic testing and 4-AP treatment.

BACKGROUND:While immune checkpoint inhibitors (ICI) induce potent responses against several systemic malignancies, clinical efficacy against high-grade glioma has been limited by immunosuppression, low mutational burden and limited lymphocyte infiltration into tumors. Laser interstitial thermal therapy (LITT) induces coagulative necrosis and disrupts the peritumoral blood-brain barrier (BBB), creating a potentially antigenic milieu. We hypothesized that neoadjuvant and adjuvant ICI would synergize with LITT to potentiate antitumor immune responses and enhance survival. METHODS:This retrospective study is an exploratory case series that includes 9 adult patients with recurrent IDH wild-type glioblastoma (GBM, n = 6), IDH mutant high-grade astrocytoma (n = 2) and H3K27M mutant diffuse midline glioma (n = 1). All patients received neoadjuvant anti-PD1 ICI prior to LITT and most received adjuvant ICI (8/9). Disease burden was followed through radiographic volume segmentation of gadolinium-enhancing disease. Patients were followed for progression-free (PFS) and overall survival (OS). RESULTS:). There were no perioperative complications. All patients showed an initial increase in gadolinium-enhancing volume after LITT. Seven of 9 (78 %) patients demonstrated subsequent regression in total gadolinium-enhancing volume. Three non-contiguous satellite lesions naïve to laser ablation exhibited complete or near-complete regression in 2 patients. Median PFS was 5.90 months (range 1.00-41.23), and median OS was 9.97 months (range 1.20-41.23). CONCLUSIONS:Combination therapy with neoadjuvant and adjuvant pembrolizumab and LITT is feasible and safe in recurrent high-grade glioma. Responses may be more robust in certain molecular subtypes of glioma. Further studies are needed to investigate this potential synergy.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Double seronegative NMOSD (DS-NMOSD) lacks approved disease-modifying treatments, and limited data exist on optimal relapse-prevention strategies. In this multicenter, international, retrospective cohort study, we sought to compare the real-world effectiveness of anti-CD20 agents vs nonspecific immunosuppressants as disease-modifying strategies for relapse prevention in DS-NMOSD. METHODS:A retrospective cohort database was constructed using standardized data collection from medical records across collaborating centers in the United States, Brazil, the United Kingdom, Thailand, Turkiye, and China. Patients meeting IPND-2015 NMOSD criteria with negative serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibody testing via cell-based assays and at least 12 months of follow-up were reviewed. The primary outcome was the incidence rate ratio (IRR) of relapses; secondary outcomes included the annualized relapse rate (ARR) and time to relapse. RESULTS:A total of 103 patients with DS-NMOSD met study criteria, with a median follow-up of 6 years. Anti-CD20 therapy was associated with a significantly lower IRR (0.02, 95% CI 0.01-0.04) and ARR (0.17, 95% CI 0.07-0.40) compared with nonspecific immunosuppressants (0.76, 95% CI 0.40-1.43) after adjusting for covariates. Survival analysis demonstrated a prolonged relapse-free interval with anti-CD20 agents. DISCUSSION/CONCLUSIONS:Our findings support the use of B-cell depletion as a potentially superior relapse-prevention strategy in DS-NMOSD, highlighting its potential as a first-line therapy. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class IV evidence that, in patients with DS-NMOSD, treatment with a DMT reduces relapse incidence rate ratio compared with no treatment and anti-CD20 DMTs are associated with a lower relapse incidence rate ratio compared with nonspecific immunosuppressants.

BACKGROUND AND OBJECTIVES/UNASSIGNED:The aim of this study was to assess the limitations of a traditional twice-daily lecture format and evaluate the feasibility and impact of implementing an academic half-day (AHD) for neurology residents at a multisite academic institution. AHD has the potential to improve attendance, satisfaction, and clinical competency compared with traditional didactics in graduate medical education. However, its feasibility and impact within neurology residency programs remain underexplored, with few adopting this model to date. Coverage logistics, faculty availability, and neurologic emergencies continue to pose challenges, particularly in large, multisite institutions. METHODS/UNASSIGNED:A needs assessment survey was administered to 36 neurology residents (postgraduate year [PGY]2-PGY4) in spring 2024 to evaluate attendance, satisfaction, and suggestions for improvement. Attendance was recorded over 1 month (August 2024). Based on survey feedback, a new 3.5-hour AHD curriculum was developed collaboratively by residents and faculty, held Tuesday mornings every week with varied lecture formats. One resident per class covered urgent clinical duties at each of 3 sites, while faculty and advanced practice providers (APPs) independently conducted rounds. Attendance was recorded for one month after implementation (September 2024), and surveys were distributed to assess satisfaction with both the curriculum and the coverage model. Residency In-Training Examination (RITE) scores were compared between the 2022 and 2024 cohorts (before AHD) and the 2025 cohort (after AHD implementation). RESULTS/UNASSIGNED:= 0.0013). Faculty and APPs reported positive or neutral effects on workflow (82.6% and 100%, respectively) and patient safety (95.6% and 100%, respectively). DISCUSSION/UNASSIGNED:Implementation of AHD across a large, multisite neurology residency program was feasible and associated with higher attendance, improved resident satisfaction, and enhanced RITE performance, without adverse effects on workflow or patient safety. Key factors for success included resident involvement, a targeted needs assessment, and strong coverage support from faculty and APPs.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Multiple sclerosis (MS) exhibits racially disparate rates of disease progression. Black people with MS (B-PwMS) experience a more severe disease course than non-Hispanic White people with MS (NHW-PwMS). Here we investigated structural and functional connectivity as well as structure-function decoupling in the sensorimotor and default mode networks (SMN and DMN, respectively), which play a key role in determining physical and cognitive disability in people with MS. METHODS:A total of 176 participants (50 B-PwMS, 50 NHW-PwMS, 41 Black healthy controls (B-HCs), and 35 NHW-HCs) underwent 3T-MRI with T1, resting-state functional, & diffusion imaging, and clinical assessment with Expanded-Disability-Status-Scale (EDSS) & Symbol-Digit-Modalities-Test (SDMT). T1-weighted images were lesion-filled and segmented to obtain cortical, subcortical, and cerebellar structures. Diffusion and functional MRI datasets were preprocessed, and structural and functional connectivity were extracted between regions defined by the AAL3 atlas. Global and local network measures were extracted for both structural and functional connectivity, and structure-function decoupling was quantified by calculating the correlation between the strengths of the two networks, considering only edges with non-zero structural connectivity. Network measures were compared between subgroups, accounting for the impact of demographics and social determinants of health, with correction for multiple comparisons. RESULTS:Despite similar disease duration, treatment exposure, lesion load and brain volumes, B-PwMS exhibited higher EDSS and lower SDMT scores compared to NHW-PwMS, which were influenced by total income and body mass index. In both B- and NHW-PwMS, structural global efficiency and streamline density were lower in the SMN and DMN compared to their respective HCs. Structural characteristic path length in SMN was significantly higher in B-PwMS versus B-HCs, whereas no significant differences were observed in NHW groups. Extensive local rearrangements of structural and functional hubs were observed in the SMN and DMN of B-PwMS compared to B-HCs and NHW-PwMS. B-PwMS showed greater structure-function decoupling in the SMN as compared to the other groups. There was a trend towards a higher decoupling in the DMN with lower SDMT scores (ρ = -0.20, p = 0.05), and higher decoupling in the SMN with higher EDSS scores (ρ = 0.20, p = 0.06). DISCUSSION/CONCLUSIONS:Despite similar brain volumes and lesion load, B-PwMS showed a greater rearrangement of brain structural and functional connectivity within the SMN and DMN when compared with NHW-PwMS. Moreover, B-PwMS showed a higher degree of structure-function decoupling in the SMN, with a trend towards association with increased physical disability.

OBJECTIVE/UNASSIGNED:Carotid webs, first described in 1968, are increasingly recognized as a surgically treatable cause of ischemic stroke, particularly in young patients. Despite growing attention, the literature remains fragmented. We conducted the first advanced bibliometric analysis of carotid web research to map its historical foundations, identify key contributors, and illustrate emerging trends. METHODS/UNASSIGNED:The Web of Science database (inception-2025) was queried for carotid web publications. Articles and metadata were analyzed using Bibliometrix (R) and Python libraries. Reference publication year spectroscopy (RPYS) was employed to analyze the field's roots by analyzing citation frequency by publication year. RESULTS/UNASSIGNED:A total of 281 publications from 109 sources and 1,129 authors were identified. Annual publication growth averaged 6.15%, with 90% published after 2016. International collaboration was modest (9-11%), led by the U.S., China, France, and Canada. Shifts in keyword frequency reflected the field's evolution from early nosological uncertainty toward recognition of carotid webs as a distinct, high-risk lesion underlying ischemic stroke. Stroke and Journal of Vascular Surgery emerged as early key sources. Author analysis identified the most prolific contributors, though coauthorship networks remained small. RPYS revealed 19 seminal studies (1968-2021) that shaped the field's progression from early pathology descriptions to recognition of carotid webs as high-risk lesions for stroke. CONCLUSIONS/UNASSIGNED:Carotid web research has rapidly expanded, evolving into a multidisciplinary field. RPYS identified 19 seminal publications tracing the intellectual trajectory of the field. Ongoing challenges include limited collaboration, unresolved questions of pathogenesis, and variability in terminology and diagnostic criteria.

The frequency and nature of neurological exams (neuro-checks) in patients with severe acquired brain injury resulting in coma or disorders of consciousness (DoC) remain variable, with limited evidence guiding practice and poor understanding of their role in predicting and preventing neurological deterioration, functional recovery and adverse effects such as delirium. This scoping review aims to explore the frequency of bedside neurological exams within the first 7 days of injury impact on clinical outcomes in adult patients with severe acquired brain injury including mortality, neurological deterioration, long-term function, and delirium. METHODS: A comprehensive literature search was conducted using the PubMed, CINAHL, Medline and EMBASE databases from 2003 to 2023. Search terms captured a range of acute brain injuries and neuro-assessment tools. Eligible studies included adult patients with severe traumatic or non-traumatic brain injury or stroke that addressed frequency of bedside neurological exams within the first 7 days of admission. RESULTS: Of 1327 studies screened, 20 met inclusion criteria, representing over 16,000 patients across 14 countries. Assessment tools varied, but use of the Glasgow Coma Scale was prevalent. Frequency of neuro-checks ranged from hourly to daily. Multiple outcome measures were utilized. Some studies found that continuing hourly neuro-checks beyond the first 48 hours did not provide additional clinical benefit. Others associated excessive assessment with increased stress or delirium. CONCLUSION: There is very low evidence supporting an association between the frequency of neuro-checks and functional outcomes, mortality, length of stay, or delirium. Although early assessments may aid prognostication, excessive exams may not improve outcomes and may contribute to harm. The heterogeneity, lack of evidence, and limited standardization of neuro-check frequency highlight the need for clinical research to guide future practice.

OBJECTIVES/OBJECTIVE:Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems, but the role of preinfectional body mass index (BMI) in these outcomes among children and young adults remains unclear. We aimed to evaluate the association between pre-COVID-19 BMI status and post-acute cardiovascular, gastrointestinal, and neuropsychiatric outcomes in children and young adults. METHODS:We conducted a retrospective cohort study using data from 139320 individuals aged 5 to 20 years with confirmed SARS-CoV-2 infection between March 2020 and September 2023 across 20 U.S. pediatric health systems participating in the RECOVER initiative. Pre-infection BMI was defined using measurements obtained within 18 months before the index date and categorized as healthy weight, overweight, obesity, or severe obesity; when multiple values were available, the most recent measurement was selected. We assessed incident postacute cardiovascular, gastrointestinal, and neuropsychiatric symptoms and conditions occurring 28 to 179 days post-infection. Adjusted relative risks (RRs) were estimated using modified Poisson regression models, comparing elevated BMI categories to the healthy weight. FINDINGS/RESULTS:Among 139320 participants (mean [SD] age, 13.0 [4.3] years; 51.6% female), severe obesity was associated with a higher risk of cardiovascular disorders (adjusted RR 2.56; 95% CI 1.93-3.41), particularly hypertension (adjusted RR 3.68; 95% CI 2.65-5.11). Severe obesity was also linked with increased risks of diarrhea (adjusted RR 1.34; 95% CI 1.10-1.64) and gastroesophageal reflux disease (adjusted RR 1.29; 95% CI 1.06-1.58). Associations between BMI and neuropsychiatric outcomes were heterogeneous, with inverse associations observed for some conditions, including anxiety and major depression. INTERPRETATION/CONCLUSIONS:In this cohort study, pre-COVID-19 BMI status was associated with the risk and pattern of postacute cardiovascular and gastrointestinal outcomes among children and young adults. Association between pre-infection BMI and neuropsychiatric outcomes was more variable and should be interpreted with caution. These findings suggest BMI-stratified post-COVID-19 monitoring strategies may help inform long-term care in youth.