Faculty Bibliography

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: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:The RESCUE-ICAS study (Registry of Emergent Large-Vessel Occlusion due to Intracranial Stenosis) demonstrated that patients undergoing acute stenting of intracranial atherosclerosis with large-vessel occlusion after mechanical thrombectomy had better outcomes than those undergoing mechanical thrombectomy alone. We present 2 secondary analyses of RESCUE-ICAS to evaluate intracranial stenting among patients who achieved successful reperfusion. METHODS:From a prospective observational cohort of 25 stroke centers (2022-2023), patients with acute intracranial occlusion, National Institutes of Health Stroke Scale score ≥6, and 50% to 99% residual stenosis or occlusion after endovascular thrombectomy were included. In the first analysis, we compared patients with stenting versus those without stenting from among those patients with a final modified Thrombolysis in Cerebral Infarction score of 2B-3. In the second analysis, we compared patients who underwent stenting with those who did not from among the patients with a Thrombolysis in Cerebral Infarction (TICI) score of 2B-3 before stenting. The odds of a favorable 90-day mRS (0-2) and 24-hour MRI infarct volume <30 mL were assessed using multivariable logistic regression. We also examined the rates of symptomatic ICH and death at 90 days in these cohorts. RESULTS:=0.480). CONCLUSIONS:Among both the cohort with final successful reperfusion and the cohort with initial successful reperfusion after mechanical thrombectomy alone, intracranial stenting was associated with better long-term clinical and radiographic outcomes, without higher morbidity and mortality. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05403593.

PURPOSE/OBJECTIVE:The Unified Multiple System Atrophy Rating Scale (UMSARS) is widely used as an outcome measure in MSA trials, but it has limitations for clinical trial use. To address these, we developed the Multiple System Atrophy Combined Outcome Assessment (MuSyCA), a comprehensive multimodal tool for disease-modifying MSA trials. The purpose of this manuscript is to describe the development and validation plan for MuSyCA, with emphasis on its structure, intended use, and assessment of reliability, validity, and sensitivity in tracking disease progression. METHODS:The development of MuSyCA followed a multistep process. Candidate outcome assessments were identified through systematic literature review and analysis of longitudinal data from large MSA cohorts. Content was refined through multiple Delphi-like consensus rounds involving MSA experts, patient advocacy groups representatives, and industry stakeholders. Cognitive interviews conducted in 20  patients with MSA evaluated the clarity and clinical relevance of patient- and clinician-reported outcomes; feedback was incorporated into a subsequent version of the MuSyCA. Validation is ongoing and includes assessment of construct validity, internal consistency, test-retest reliability, and responsiveness. Longitudinal analyses to determine sensitivity to change over time are ongoing. RESULTS:MuSyCA combines patient- and clinician-reported outcomes, biomarkers (neurofilament light chain, neuroimaging), and performance-based measures to capture subjective and objective aspects of MSA progression, enhancing its utility  to detect treatment effects in clinical trials. MuSyCa is not intended to be used in clinical practice. CONCLUSIONS:MuSyCA offers a multidimensional approach to MSA assessment, supporting precise, disease-relevant evaluations in trials of putative disease-modifying therapies. Its validation will provide a standardized multimodal outcome measure, advancing MSA therapeutic development.

OBJECTIVE:Interictal epileptiform discharges (IEDs) are transients observed on the electroencephalogram (EEG) of patients with epilepsy. IEDs have traditionally been recorded from scalp or intracranial EEG macrocontacts, which coarsely sample neural activity. Here, we investigated the use of flexible, high-resolution microelectrocorticographic (μECoG) arrays for measuring IEDs with greater spatiotemporal precision to test whether there exist microscale patterns of IED activity that may be missed on standard intracranial EEG. METHODS:) to record from seven patients undergoing surgical treatment of epilepsy. We identified IEDs by a combination of expert review and automated detection. We quantified the spatial extent of IEDs, mapped patterns of repeated IED activity, and quantified IED propagation direction using multilinear fit models. We also compared IED detection rates and propagation measurements between μECoG arrays and simulated macroarrays (10-mm spacing, 2.3-mm diameter). RESULTS:We demonstrated successful use of μECoG arrays to map intraoperative microscale patterns of IEDs. The majority of patients (5/7) exhibited elevated IED activity that was highly localized (subcentimeter localization). Across all patients, 40% of detected IEDs were observed within a 4-mm radius of cortex. μECoG arrays also mapped the direction of IED propagation. An average of 39% (range = 4.2%-96.5%, SD = ±36.8%) of the IED events captured by the μECoG arrays were not detectable by simulated macrocontacts. SIGNIFICANCE/CONCLUSIONS:These intraoperative data demonstrate that μECoG arrays can map the microscale spatiotemporal activity of IEDs. These patterns of IEDs may be poorly captured by standard, macroscale recording devices. Our findings support the use of high-resolution, large area coverage μECoG arrays for the presurgical and intraoperative mapping of epileptic cortex.

PURPOSE/OBJECTIVE:Responsive neurostimulation (RNS) is an effective therapeutic option for drug-resistant focal epilepsy, especially when the seizure onset zone lies in an eloquent cortex. However, the safety, tolerability, efficacy, as well as optimal stimulation and detection settings for RNS therapy in the primary motor cortex are poorly understood. METHODS:We performed a multi-center retrospective cohort study to assess the safety and efficacy of treatment with RNS targeting the primary motor cortex in patients with drug-resistant focal motor epilepsy. RESULTS:A total of 20 patients were included in the study. Overall, 79 % of the patients achieved ≥ 50 % seizure reduction at a mean follow-up time of 58.4 months, while 53 % of the patients achieved ≥ 90 % seizure reduction. None of the patients had any complications from the surgical implantation of the RNS device. There were no reported adverse side effects from neurostimulation therapy of the primary motor cortex. CONCLUSION/CONCLUSIONS:For individuals with drug-resistant focal motor epilepsy, treatment with RNS of the primary motor cortex is safe, effective, and well-tolerated.

OBJECTIVE:To assess whether object relations theory (ORT) formulations generated by large language models (LLMs) enhance resident education in psychodynamic psychiatry. METHODS:This institutional review board (IRB)-approved observational study was conducted at a single academic program from January to March 2025. Eleven postgraduate year (PGY) 3 and 4 residents submitted de-identified psychotherapy case narratives to a GPT-4 model using a standardized ORT prompt. Residents evaluated accuracy, clarity, and educational value using a 10-item, 5-point Likert scale and provided free-text feedback. Descriptive statistics were calculated. Thematic analysis was used to identify key perceptions. RESULTS:Ten residents completed the rating process. Mean scores ranged from 3.5 to 4.2 across all items, with the highest ratings for identification of objects, affective tone, and educational value. Qualitative analysis identified five themes: (1) improved clarity and structure, (2) stronger conceptual anchoring to ORT, (3) risk of overgeneralization, (4) maternal emphasis bias, and (5) importance of faculty oversight. Residents characterized the outputs as concise and clinically applicable, although they noted occasional factual inaccuracies and misalignments with specific case details. CONCLUSIONS:With appropriate supervision, AI-generated ORT formulations may serve as a valuable adjunct to psychodynamic education by standardizing terminology and supporting conceptual development. Future controlled studies are needed to evaluate effects on Milestone-aligned assessment and applicability to additional psychotherapy models.

OBJECTIVE:Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration. METHOD/METHODS:, t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC. RESULTS:ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests. CONCLUSIONS:SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.