Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Chronic subdural hematoma (cSDH) affects approximately 20 per 100,000 individuals annually, with surgical recurrence rates of 10-20%. Middle meningeal artery embolization (MMAE) has emerged as a promising minimally invasive treatment, but the optimal timing remains unclear. We evaluated the association between MMAE timing and radiological and functional outcomes in cSDH. METHODS:We conducted a retrospective multicenter international cohort study across 33 centres, including patients who underwent MMAE for cSDH between January 2018 and December 2024. Patients were stratified by timing from diagnosis: Q1 (≤1 day), Q2 (2 days), Q3 (3-6 days), and Q4 (>6 days). The primary composite endpoint required radiological success (hematoma thickness <5 mm at 1-3 months), absence of emergency surgical evacuation, and either functional improvement or good functional outcome (modified Rankin Scale 0-2). Propensity score matching compared Q1 and Q4. RESULTS:Of 1,781 patients screened, 908 met inclusion criteria. Mean age was 73.7 ± 12.2 years, and 70.9% were female. Early embolization (Q1) achieved the primary composite endpoint more frequently than delayed embolization (Q4), with concordant improvements in radiological and functional components and no difference in rescue surgery. Good functional outcome was achieved in 76.0% of Q1 patients versus 63.8% in Q4 (absolute difference, 12.2%; P=.003; number needed to treat approximately 8). Hospital length of stay was 21.0 days shorter in Q1 versus Q4 (P<.001), partly attributable to the timing definition. In 174 propensity score-matched pairs, early embolization was associated with higher odds of achieving the primary endpoint (odds ratio, 6.41; 95% confidence interval, 3.29-12.48; P<.001), with pronounced benefit among patients receiving antithrombotic therapy (odds ratio, 8.06; 95% confidence interval, 3.65-17.80). CONCLUSIONS:Early MMAE (≤1 day from diagnosis) was overall associated with better outcomes compared with delayed intervention, particularly among patients receiving antithrombotic therapy. Prospective confirmation is warranted.

BACKGROUND:People with multiple sclerosis (PwMS) frequently experience invisible symptoms, including cognitive impairment, fatigue, depression, anxiety, and psychosocial factors such as stigma, which can substantially affect social role participation (SRP). These factors are often under-recognized in clinical care despite their functional impact. OBJECTIVE:To examine the unique contributions of invisible MS-related symptoms to SRP after accounting for demographic characteristics and objective cognitive performance. METHODS:A cross-sectional sample of 434 PwMS was recruited from a large outpatient neurology clinic specializing in MS care. The sample was predominantly female (75%), largely white (85%), and middle-aged (M = 51.0, SD = 11.7), with mild-to-moderate disability. Participants completed a computerized cognitive battery and validated patient-reported outcome measures assessing disease impact, mood, fatigue, stigma, and SRP. Hierarchical regression models evaluated the variance explained by demographics, cognitive performance, and patient-reported symptoms. RESULTS:Demographic variables were not significant predictors of SRP. Cognitive performance accounted for 13.3% of the variance. Adding patient-reported outcomes increased explained variance to 70.6%. Depression, disease impact, fatigue, and executive functioning remained significant predictors, whereas stigma did not. CONCLUSIONS:Patient-reported symptom burden showed strong associations with SRP and explained more variance than demographic factors and most cognitive measures, while executive functioning also contributed independently.

OBJECTIVE:To evaluate the effectiveness and implementation of a multicomponent intervention to address the burden of drug use-related infectious diseases and overdose in rural settings. DESIGN/METHODS:Single-arm hybrid implementation-effectiveness design. SETTING/METHODS:Rural area comprising the Illinois counties of the Delta Regional Authority. PARTICIPANTS/METHODS:People who use opioids and/or stimulants nonmedically. INTERVENTION/METHODS:Expansion of community-based harm reduction services, capacity-building for opioid use disorder and hepatitis C treatment. MAIN OUTCOME MEASURES/METHODS:Harm reduction service expansion intervention Reach, Effectiveness (injection equipment sharing), Adoption and Cost (per participant and budget impact analysis). RESULTS:Three hundred six people who use drugs were enrolled. Of the 207 of who were not previously engaged in harm reduction services, 121 (59%) accepted referral and were retained in services at 6 months past study enrollment (intervention reach). In regards to intervention efficacy, among these individuals, 41 (35%) completed follow-up surveys; compared with their baseline self-report, there was a significant increase in obtaining sterile equipment from the harm reduction organization (43.9% vs. 68.3%, P = 0.03) and decrease in sharing injection equipment (46.3%-19.5%, P = .02). The harm reduction organization experienced an increase of approximately 100-550 program participants and an increase in service delivery area coverage from 1258 to 5509 square miles after intervention implementation (adoption). Cost per participant served by the harm reduction organization was $1486 per year, with annual budget impact to the program of $817 295. In regards to treatment capacity building, a total of 80 providers in the study area completed training in opioid use and/or hepatitis C management. CONCLUSION/CONCLUSIONS:The pragmatic evaluation of harm reduction service expansion supported by a suite of implementation strategies serves to inform the practical considerations and decision-making by community-based organizations seeking to increase services in rural areas heavily affected by substance use, overdose, and related infectious diseases.

INTRODUCTION AND PROBLEM STATEMENT/UNASSIGNED:Competency in brain death/death by neurologic criteria (BD/DNC) determination is an Accreditation Council for Graduate Medical Education (ACGME) milestone in neurology residency and neurocritical care fellowship; however, trainees have limited clinical exposure and receive inconsistent training across institutions. Simulation offers a standardized, safe environment to teach and assess BD/DNC, but multi-institutional implementation remains unstudied. The aim of this study was to evaluate the feasibility of implementing a consensus-based BD/DNC curriculum and to assess its impact on trainee confidence. LEARNING OBJECTIVES/UNASSIGNED:By the end of the curriculum, trainees will be confident in assessing BD/DNC prerequisites, performing a complete neurologic examination, safely conducting and interpreting apnea testing, and accurately declaring BD/DNC. METHODS AND CURRICULUM DESCRIPTION/UNASSIGNED:test. RESULTS/UNASSIGNED:Nineteen participants (9 female [47%]; predominantly PGY-4 trainees) were enrolled. Median [IQR] pre-post composite confidence scores improved significantly across all domains: "Setup and Family Counseling," 4 [3.5-4] to 4.5 [4-5]; "Prerequisites," 4 [4-5] to 4.5 [4-5]; "Neurologic Examination," 4 [4-4] to 4.5 [4-5]; and "Apnea Test and Declaration of BD/DNC," 3 [3-4] to 5 [4-5]. The effect sizes (Wilcoxon r) ranged from 0.79 to 0.88 across domains. There were no significant differences in the magnitude of improvement between high-fidelity and low-fidelity groups. After curriculum implementation, 13 of 19 participants (68%) self-assessed their ACGME BD/DNC milestone competency to be level 4 or 5. DISCUSSION AND LESSONS LEARNED/UNASSIGNED:This multi-institutional pilot demonstrated that a consensus-based BD/DNC simulation curriculum is feasible and improves trainee confidence despite limited previous clinical exposure. Key lessons include the feasibility of multicenter collaboration, standardizing core practices while accommodating local variability, and designing adaptable curricula that achieve similar outcomes across resource-diverse settings.

PURPOSE/OBJECTIVE:Pediatric low-grade gliomas (pLGGs) typically have excellent long-term outcomes; intratumoral hemorrhage is a rare, potentially dangerous complication. Hemorrhage risk in the context of molecular alterations and targeted therapies remains poorly characterized. We analyzed the incidence, timing, and independent risk factors for hemorrhage in a large contemporary pLGG cohort. METHODS:We conducted a retrospective cohort study of 236 children with pLGG treated at a single center (2011-2025). Clinical, radiographic, and molecular variables were abstracted. The primary endpoint was spontaneous tumoral hemorrhage. Time-to-event analyses utilized Kaplan-Meier methods and Cox proportional hazards modeling; penalized regression mitigated overfitting given the event rarity. RESULTS:Twelve patients (5.1%) experienced hemorrhage over 2,234 person-years (incidence: 0.54/100 person-years). Hemorrhage typically occurred years after initial tumor diagnosis (median 6.4 years). The presence of a KIAA1549::BRAF fusion in the tumor had the strongest association with hemorrhage, persisting across multivariable models (approximately sixfold increased risk), although estimates were limited by low event number. MAPK inhibitor exposure (specifically binimetinib and tovorafenib) was associated with hemorrhage in univariate analysis but partially confounded by fusion status. CSF diversion independently increased risk at brainstem, optic pathway, and hypothalamic locations. No hemorrhages occurred among patients with underlying genetic syndromes, including neurofibromatosis type 1 and tuberous sclerosis. CONCLUSION/CONCLUSIONS:Hemorrhage in pLGG is an infrequent late complication associated with tumor biology. KIAA1549::BRAF fusion may identify a higher-risk subgroup, with MAPK inhibitor exposure and CSF diversion further modifying risk. These findings support biology-informed surveillance and personalized management strategies for at-risk children.

BACKGROUND:Final infarct volume (FIV) on 24-hour magnetic resonance imaging is a well-established imaging biomarker linked to functional recovery after ischemic stroke, yet its prognostic value in intracranial atherosclerosis-related large vessel occlusion remains poorly explored. The impact of adjunct intracranial stenting on both infarct size and progression also remains unclear in this population. This study aimed to examine the association between FIV and clinical outcome, evaluate the effect of adjunct stenting on FIV and infarct progression, and assess the relationship between infarct progression and functional independence. METHODS:We conducted a post hoc secondary analysis of the RESCUE-ICAS registry (Registry of Emergent Large Vessel Occlusion due to Intracranial Stenosis); only patients with anterior circulation large vessel occlusion with magnetic resonance imaging after thrombectomy were included. FIV was measured on diffusion-weighted magnetic resonance imaging performed 24 to 36 hours postthrombectomy. Infarct progression was defined as the difference between baseline computed tomography perfusion infarct volume (cerebral blood flow <30%) on presentation and 24- to 36-hour FIV. The primary outcome was 90-day functional independence (modified Rankin Scale score 0-2). Additional analyses evaluated the association between adjunct intracranial stenting and FIV, and the association between infarct progression and 90-day functional outcome. Associations were analyzed using multivariable logistic regression and inverse probability of treatment weighting. RESULTS:=0.008). CONCLUSIONS:Among intracranial atherosclerosis-related large vessel occlusion patients, 24- to 36-hour FIV is a strong predictor of functional outcome. Adjunct stenting is associated with smaller FIV. Lower infarct progression was also associated with favorable outcome. These findings highlight FIV as a reliable imaging biomarker and potential surrogate end point in future trials.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Compartmentalized CNS inflammation involving B cells is implicated in gray matter injury and disease progression in multiple sclerosis (MS). Products secreted by B cells of patients with MS can kill oligodendrocytes and neurons, a cytotoxicity conferred by their exosome-enriched extracellular vesicle (Ex En) fraction. METHODS:To explore the potential molecular mediators of this cytotoxicity, we profiled proteomic and transcriptomic cargo of Ex En isolated from B cells of patients with treatment-naive MS and matched healthy controls. RESULTS:MS B-cell-derived Ex En appeared enriched in cell-death-associated proteins (including fibrinogen, complement C9, APP, and SPARC) and deficient in cell-survival-associated proteins (such as galectin-3). Abnormal enrichment for cell-death proteins was supported by gene set enrichment analysis. Protein pathway analysis revealed densely connected prodeath modules in the MS B-cell-derived Ex En, contrasting with homeostatic signatures in controls. Transcriptomic analysis further revealed that Ex En of MS B cells appeared to carry reduced levels of miRNAs (miR-182, miR-212, and miR-1270) known to inhibit apoptosis. DISCUSSION/CONCLUSIONS:Our findings indicate that B-cell-derived Ex En of patients with MS, previously shown to impair neuronal and glial survival, harbor an abnormal cytotoxic molecular profile that may contribute to CNS-compartmentalized injury and progressive MS biology.

Underdiagnosis of cardiometabolic risk factors (CMRFs) may represent an unrecognised biological pathway contributing to dementia risk; yet remains poorly characterised in African and African diaspora populations. We quantified the prevalence and determinants of underdiagnosed hypertension and abnormal glycaemia across four cohorts comprising up to 7000 adults aged ≥40 years from Nigeria, Kenya, and The United States: Indianapolis, and North Texas. Underdiagnosis was defined as absence of self-reported diagnosis despite elevated systolic blood pressure ( ≥130 mmHg) or fasting blood glucose ( ≥100 mg/dL). Cohort-stratified analyses examined demographic, socioeconomic, cognitive, Alzheimer's genetic, and blood-based biomarker correlates. Underdiagnosis was pervasive in African cohorts. Elevated fasting glucose was associated with cognitive impairment in Kenya and North Texas, while severe hypertension and diabetes were linked to Alzheimer's disease-related biomarkers [pTau217/181, NFL and Aβ42/40] in North Texas (all p ≤ 0.05). These findings identify context-specific diagnostic gaps in populations at high dementia risk and highlight cardiometabolic detection as a mechanistic target for prevention.