Faculty Bibliography

BACKGROUND:Glioblastoma intramedullary spinal cord metastasis (GISCM) is a rare sequela of high-grade astrocytoma and glioblastoma multiforme (GBM). Discrete intramedullary spinal cord metastases are less common than spinal leptomeningeal spread and may follow a more indolent course. Once identified as GISCM, palliative maximal safe resection of the tumor may be considered to alleviate neurological symptoms. Reports describing the surgical management of these rare lesions, including the use of emerging technologies that may aid in maximal safe resection, are sparse. A further understanding is also required regarding the course of disease and factors contributing to mortality in GISCM. METHODS:We reviewed the intraoperative management and clinical course of three patients treated for GISCM at our institution between 2015 and 2024. We additionally conducted a PRISMA-guided systematic literature review of PubMed Central, MEDLINE, and Bookshelf databases through May 26th, 2025, including original patient reports of GISCM from cranial astrocytoma or GBM. The disease course, management strategies, and causes of mortality in previously reported cases were analyzed. RESULTS:Our institutional cohort had a mean time to spinal metastasis of 26.2 months from diagnosis of cranial disease (range 17.5-40.5 months), with a mean survival of 9.2 months following maximal safe resection of extramedullary components (range 7-12 months). In two cases, intraoperative Stimulated Raman Histology (SRH) was employed to facilitate the rapid identification of metastatic GBM, thereby influencing surgical strategy. In one case, 5-aminolevulinic acid (5-ALA) was used to differentiate between tumor and spinal cord parenchyma, facilitating maximal safe debulking without neurological injury. Literature review identified 38 prior reported cases of GISCM, with a median time to spinal diagnosis of 11.0 months and a median survival of 3.5 months thereafter. The cause of death in the review cohort often involved multiple factors, and when analyzed for contributing factors to death, 38.7% involved cranial progression, 38.7% involved progression of spinal disease, and 29.0% involved medical complications. Gait ataxia at presentation was associated with shorter survival in review patients, potentially reflecting advanced disease with extramedullary cord compression. CONCLUSION/CONCLUSIONS:GISCM represents an entity distinct from leptomeningeal disease and may be managed in conjunction with recurrent cranial disease. Surgical debulking is a technically feasible strategy that can be safely facilitated using tools employed in the management of intracranial GBM, facilitating maximal safe resection without compromising survival.

PURPOSE/OBJECTIVE:Traditionally treated with microsurgical clipping, the treatment preference for intracranial aneurysms has shifted towards endovascular coiling. However, the choice between endovascular coiling and microsurgical clipping as the primary treatment strategy for ruptured middle cerebral artery (MCA) aneurysms remains disputed. We conducted a systematic review and meta-analysis to compare the radiological and clinical outcomes of ruptured MCA aneurysms treated with primary coiling and microsurgical clipping. METHODS:An extensive literature search was performed across PubMed, Embase, and Cochrane databases through August 2025. The primary outcomes of our study include the mRS scores at discharge and at long-term follow-up. Secondary outcomes include aneurysm occlusion post-procedurally or at discharge, and at long-term follow-up. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS:A total of 5 studies, involving 984 patients (coiling = 449, clipping = 535) were included. There are no significant differences in good functional outcome (mRS 0-2) among ruptured MCA aneurysms treated with either endovascular coiling or microsurgical clipping at discharge (RR: 1.04; CI: 0.93-1.18; p = 0.473) and long-term follow-up (RR: 1.07; CI: 0.95-1.20; p = 0.245), even though endovascular coiling is associated with lower rates of complete aneurysm occlusion at discharge (RR: 0.66; CI: 0.54-0.82; p < 0.001) and long-term follow-up (RR: 0.76; CI: 0.66-0.89; p < 0.001). CONCLUSION/CONCLUSIONS:Our meta-analysis suggests that while microsurgical clipping and primary coiling of ruptured MCA aneurysms had similar functional outcomes, clipping is associated with higher rates of complete aneurysm occlusion. Future studies with larger cohorts with prospective data, as well as studies that include more contemporary endovascular technologies and techniques, are warranted.

IMPORTANCE/UNASSIGNED:Asian language speakers with limited English proficiency (LEP) face significant barriers to accessing adequate mental health care. Despite worsening mental health outcomes for this population, there is limited research examining the availability of Asian language mental health treatment in the US. OBJECTIVE/UNASSIGNED:To quantify trends and analyze disparities in the geographic availability of Asian language mental health treatment from 2015 to 2024. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study of US mental health facilities from April 30, 2015, to December 9, 2024, used longitudinal data from the nationally representative Mental Health and Addiction Treatment Tracking Repository linked with county-level demographic data from the 2023 American Community Survey. Facilities were included if they completed the National Mental Health Services Survey or the National Substance Use and Mental Health Services Survey. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes included the annual proportion of mental health facilities offering Asian language services and the proportion of counties with at least 1 such facility. For 2024, facility-level characteristics associated with Asian language services were assessed and geographic mismatches between service availability and the proportion of Asian language-speaking individuals with LEP were mapped. RESULTS/UNASSIGNED:The study included 3847 mental health facilities. Of these, 214 facilities (5.6%) offered services in at least 1 Asian language in 2024 (including Arabic, Chinese, Farsi, Hindi, Hmong, Japanese, Korean, Tagolog, and Vietnamese). The proportion peaked at 265 facilities (6.9%) in 2021, then declined from 2022 to 2024. The number of counties with at least 1 facility with Asian language services was 98 (6.3%) in 2024. Facilities offering Asian language services were concentrated in metropolitan areas (208 [97.2%]), particularly in California (57 [26.6%]) and the Northeast (52 [24.3%]). Rural areas lacked such services (3 of 485 rural facilities [0.6%] in 2024), even in counties with substantial populations of Asian language-speaking individuals with LEP (0 of 5 facilities). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cross-sectional study found a persistent geographic mismatch between the mental health needs of Asian language-speaking individuals with LEP and the availability of appropriate linguistic services. The gap was pronounced in rural areas. The findings suggest that policies aimed at expanding the behavioral health workforce and increasing access to culturally and linguistically competent services to reduce ongoing disparities in mental health outcomes and access to care are urgently needed.

PURPOSE OF REVIEW/OBJECTIVE:This review discusses the current state of the evidence related to the relationship between the cerebellum and epilepsy, highlighting evidence on neurostimulation of the cerebellum for treatment of epilepsy, and placing current knowledge into historical context. RECENT FINDINGS/RESULTS:The cerebellum plays an important role in certain epilepsy types, both as a key part of epileptic networks and an area that can give rise to seizures. Cerebellar stimulation as a potential treatment for drug-resistant epilepsy is a recurring, albeit niche, topic of interest. Over decades of intermittent, often highly limited investigations into this area of research, there are still more questions than answers. However, more recent preclinical insights point the way towards leveraging modern surgical techniques and technology in investigating cerebellar stimulation as a potential viable treatment approach to select types of epilepsy. SUMMARY/CONCLUSIONS:Cerebellar stimulation holds promise for improving seizure control in people with specific types of drug-resistant epilepsy. Future studies should leverage new preclinical data, along with modern technology, neurosurgical techniques, and clinical trial design, to help determine the optimal stimulation parameters, optimal stimulation targets, and optimal patient-selection for this promising area of investigation.

Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.

Chromosomal rearrangements on the short arm of Chromosome 8 cause 8p syndrome, a rare developmental disorder characterized by neurodevelopmental delays, epilepsy, and cardiac abnormalities. Although significant progress has been made in managing the symptoms of 8p syndrome and other conditions caused by large-scale chromosomal aneuploidies, no therapeutic approach has yet been demonstrated to target the underlying disease-causing chromosome. Here, we establish a two-step approach to eliminate the abnormal copy of Chromosome 8 and restore euploidy in cells derived from an individual with a complex rearrangement of Chromosome 8p. Transcriptomic analysis revealed 361 differentially expressed genes between the proband and the euploid revertant, highlighting genes both within and outside the 8p region that may contribute to 8p syndrome pathology. Furthermore, we demonstrate that the proband exhibits a significant defect in neural differentiation that could be partially rescued by treatment with small-molecule inhibitors of cell death. Our work demonstrates the feasibility of using chromosome engineering to correct complex aneuploidies in vitro and establishes a platform to further dissect the pathophysiology of 8p syndrome and other conditions caused by chromosomal rearrangements.

IMPORTANCE/UNASSIGNED:Overdose prevention centers (OPCs) are interventions to reduce overdose mortality and support health care engagement. In the US, concerns have been raised that OPCs may be associated with reduced economic activity in their surrounding neighborhoods. OBJECTIVE/UNASSIGNED:To evaluate changes in the local economic activity in New York City (NYC), measured by neighborhood-level foot traffic and consumer spending, following the opening of the first 2 publicly recognized OPCs in the US. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used anonymized mobility and spending data from June 1, 2021, to June 13, 2022, for the areas surrounding the East Harlem and Washington Heights OPCs in NYC. These neighborhoods were defined using 5-minute and 10-minute walking buffers and Business Improvement Districts (BIDs). Synthetic control donors included walking buffers and BIDs around syringe service programs without OPCs and opioid treatment programs that were operational as of OPCs' opening. Analyses were conducted from February to July 2025. EXPOSURES/UNASSIGNED:Opening of the 2 NYC OPCs on November 30, 2021. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were foot traffic and in-person consumer spending within 10-minute walking buffers. Secondary analyses considered 5-minute walking buffers and BIDs. Augmented synthetic control models were adjusted for neighborhood-level demographic and socioeconomic features, with fit assessed using root mean squared error before OPC opening. Permutation tests and conformal inference were used to assess significance. RESULTS/UNASSIGNED:A total of 27 biweekly observations (13 in pre-OPC and 14 in post-OPC periods) were analyzed. The 10-minute walking buffer analyses captured 1259 consumer spending sites and 7816 foot traffic sites across 2 treated buffers and 56 donor buffers. In East Harlem, the average treatment effect on the treated (ATT) estimate (SE) was -$21.96 ($40.53) for consumer spending (P = .16) and 1.28 (5.40) visits for foot traffic (P = .19). In Washington Heights, ATT (SE) estimates were $14.94 ($37.38) for consumer spending (P = .13) and 0.44 (3.54) visits for foot traffic (P = .97). Secondary analyses produced consistent results. No statistically significant results were observed at any post-OPC time point. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study found that OPC opening was not associated with significant changes in local economic activity. Given the absence of observed economic harms, policy debates should instead focus on the public health implications of OPCs.

Difference-in-differences (DID) is popular because it can allow for unmeasured confounding when the key assumption of parallel trends holds. However, there exists little guidance on how to decide a priori whether this assumption is reasonable. We attempt to develop such guidance by considering the relationship between a causal diagram and the parallel trends assumption. This is challenging because parallel trends is scale-dependent and causal diagrams are generally scale-independent. We develop conditions under which, given a nonparametric causal diagram, one can reject or fail to reject parallel trends. In particular, we adopt a linear faithfulness assumption, which states that all graphically connected variables are correlated, and which is often reasonable in practice. We show that parallel trends can be rejected if either (i) the treatment is affected by pre-treatment outcomes, or (ii) there exist unmeasured confounders for the effect of treatment on pre-treatment outcomes that are not confounders for the post-treatment outcome, or vice versa. We also argue that parallel trends should be strongly questioned if (iii) the pre-treatment outcomes causally affect the post-treatment outcomes, since there exist reasonable semiparametric models in which such an effect violates parallel trends. When (i-iii) are absent, a necessary and sufficient condition for parallel trends is that the association between unmeasured confounders and potential outcomes is constant on an additive scale, pre- and post-treatment. We discuss our approach in the context of the effect of Medicaid expansion under the US Affordable Care Act on health insurance coverage rates.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation's biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.

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.