Faculty Bibliography

BACKGROUND AND OBJECTIVES/UNASSIGNED:Burnout is a pervasive occupational hazard for neurologists-undermining their well-being, jeopardizing patient safety and satisfaction, limiting access to care, and inflating health care costs. Well-designed appreciation and recognition practices may help mitigate some of its key drivers. This pilot study evaluates faculty perspectives on appreciation strategies in an academic neurology department. We used the Moffitt Provider Appreciation Assessment (MPAA), which assesses the types of appreciation methods respondents value, regardless of whether those practices are currently implemented in their workplace. METHODS/UNASSIGNED:A cross-sectional survey was conducted among full-time clinical faculty in the Department of Neurology at NYU Grossman School of Medicine. The survey included demographics, the MPAA, the single-item Mini-Z burnout inventory to assess self-reported burnout levels, and an intent-to-leave question. MPAA responses were analyzed for frequencies, and the association between burnout and intent to leave was examined. RESULTS/UNASSIGNED:< 0.00001). Because the scores for self-reported burnout and intent to leave reflect current work conditions while MPAA scores capture enduring personal values, MPAA rankings cannot be compared directly with burnout or turnover metrics. DISCUSSION/UNASSIGNED:Neurology clinical faculty prioritized appreciation methods that directly address clinical work, underscoring the value of implementing tailored recognition practices that may reduce burnout. The methodology used in this pilot study can be adapted for broader application in other settings. After identifying faculty preferences, health care organizations can implement meaningful, transparent, and inclusive appreciation strategies that have the potential to strengthen physician relationships, promote well-being, and support a sustainable workforce.

BACKGROUND AND OBJECTIVES/UNASSIGNED:With more women entering the medical workforce, caregiving challenges and family-work conflicts are of growing importance to today's neurologists. The aim of this study was to assess the impact of caregiver (CG) status on academic achievements in neurology, analyze the division of labor and time devoted to domestic responsibilities, and measure family-work conflict in US academic neurology faculty. METHODS/UNASSIGNED:analyses as appropriate, with CGs vs noncaregivers (N-CGs) serving as the independent groups. RESULTS/UNASSIGNED:= 0.034). DISCUSSION/UNASSIGNED:Although the caregiving burden did not directly affect academic productivity, it significantly increased FWC in US academic neurology faculty surveyed. Female CG faculty disproportionately shouldered domestic and household responsibilities. Beyond recognizing CG challenges, advocating for a change in paradigm and providing solutions to these pervasive issues could be instrumental in preventing further attrition of professionals from our field, particularly women with caregiving roles.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of gray and white matter structures. Evidence supports a progressive condition, although the temporal evolution of TLE is poorly defined. In this ENIGMA-Epilepsy study, we aim to investigate structural alterations in gray and white matter across the adult lifespan in patients with TLE by charting both gray and white matter changes and explore the covariance of age-related alterations in both compartments. METHODS:scores of all patients. Covariance analyses examined the coupled correlations of gray and white matter lifespan curves for each region. RESULTS: DISCUSSION/CONCLUSIONS:This study highlights that patients with TLE exhibit more pronounced and widespread gray and white matter atrophy across the lifespan. The cross-sectional nature of our study limits definitive conclusions on whether the atrophy shown is progressive but emphasizes the importance of prompt diagnosis and intervention in patients. Collectively, our results motivate future longitudinal studies to clarify consequences of drug-resistant epilepsy.

Brain death, or death by neurologic criteria (BD/DNC), is the permanent loss of brain function, defined by coma with loss of capacity for consciousness and complete brainstem areflexia, including the inability to breathe spontaneously. The 2023 American Academy of Neurology/American Academy of Pediatrics/Child Neurology Society (CNS)/Society for Critical Care Medicine guidelines state that pregnancy is not a contraindication for BD/DNC evaluation. Clinical evaluation of BD/DNC includes an apnea test to demonstrate the absence of spontaneous respiratory effort in response to hypercapnia and acidosis. The safety of apnea testing to the fetus in pregnant patients remains uncertain.We convened a panel of experts in BD/DNC, neurocritical care, maternal-fetal medicine, neonatology, fetal/neonatal/child neurology, and pediatric/fetal anesthesiology to perform a scoping review of apnea testing in pregnant persons. We found no studies directly assessing safety of apnea testing on the fetus. Apnea testing consists of fetal exposure to parental hyperoxia and hypercapnia; therefore, we searched for evidence related to these conditions in pregnancy. Case reports, series, and literature on physiologic changes induced during apnea testing and their potential effects on placental, fetal systemic, and fetal cerebral circulations were identified. In reported cases of BD/DNC in pregnant persons, some authors described explicitly avoiding apnea testing because of safety concerns, but whether apnea testing was performed at all was inconsistently reported. Evidence from studies evaluating hyperoxia and hypercapnia in healthy pregnant persons and in other animal models suggested possible adverse effects caused by reduced uteroplacental blood flow, fetal metabolic acidosis, and hypercapnia-induced cerebral hyperperfusion. Further possible complications of apnea testing, such as hypotension or hypoxemia in pregnant persons, could also contribute to fetal injury. These potential detrimental risks to the fetus raise the question as to whether apnea testing should be deferred if a fetus may be viable. Ancillary tests, such as radionuclide cerebral blood flow imaging or transcranial Doppler ultrasonography, can be used if the remainder of the BD/DNC evaluation and neurologic examination is otherwise consistent with BD/DNC. Further research is essential to assess the physiologic consequences of apnea testing in pregnant persons and potential risks to the fetus.

Synaptic spine loss is an early pathophysiologic hallmark of Alzheimer disease (AD) that precedes overt loss of dendritic architecture and frank neurodegeneration. While spine loss signifies a decreased engagement of postsynaptic neurons by presynaptic targets, the degree to which loss of spines and their passive components impacts the excitability of postsynaptic neurons and responses to surviving synaptic inputs is unclear. Using passive multicompartmental models of CA1 pyramidal neurons (PNs), implicated in early AD, we find that spine loss alone drives a boosting of remaining inputs to their proximal and distal dendrites, targeted by CA3 and entorhinal cortex (EC), respectively. This boosting effect is higher in distal versus proximal dendrites and can be mediated by spine loss restricted to the distal compartment, enough to impact synaptic input integration, somatodendritic backpropagation, and plateau potential generation. This has particular relevance to very early stages of AD in which pathophysiology extends from EC to CA1.

Between 1919 and 1936, American physiologist Walter B. Cannon and Spanish physician Gregorio Marañón engaged in a sustained transatlantic correspondence that shed light on emerging ideas about the physiologic basis of emotion. Drawing on letters preserved at Harvard's Countway Library of Medicine and the Fundación Ortega-Marañón in Madrid, we examine how their dialogue bridged experimental physiology and clinical neuroendocrinology during a formative era in modern neuroscience. Cannon, widely known for introducing the concepts of "homeostasis" and the "fight-or-flight" response, saw in Marañón's clinical observations a compelling complement to his laboratory findings. In particular, Cannon repeatedly cited Marañón's work on the emotional effects of adrenaline, which distinguished between purely physiologic visceral reactions without subjective emotion ("cold emotion") and full subjective emotional states ("hot emotion"). This nuanced differentiation anticipated later cognitive and constructivist theories of emotion. Their exchange helped shape foundational concepts in affective and autonomic neuroscience by linking internal affective states to neuroendocrine mechanisms and observable bodily responses. These ideas would later cohere in Cannon's The Wisdom of the Body (1932), where traces of their correspondence are evident. Beyond their scientific importance, the Cannon-Marañón letters offer a rare window into the international and interdisciplinary networks that shaped biomedical thought in the early 20th century. It also reflects broader commitments because both men had a relevant political involvement. By recovering this epistolary exchange, we shed light on an overlooked chapter in the history of neuroscience and the enduring value of scientific dialogue.

IMPORTANCE/UNASSIGNED:Epilepsy affects approximately 65 million people worldwide, and 60% have focal seizures. Predicting seizure response and drug resistance to antiseizure medications (ASMs) in people with focal epilepsy remains difficult. OBJECTIVE/UNASSIGNED:To describe the expected short- and long-term response to treatment with ASMs in people with focal epilepsy using recognized definitions by the International League Against Epilepsy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Human Epilepsy Project is an international, prospective, observational cohort study that followed up people with newly diagnosed focal epilepsy for up to 6 years between 2012 and 2020. Data were analyzed from 2023 to 2024. The Human Epilepsy Project was conducted at 34 tertiary epilepsy centers across the US, Australia, and Europe. Participants with confirmed diagnosis of focal epilepsy aged 12 to 60 years were enrolled within 4 months of treatment initiation with ASM(s). Data were analyzed from February 2024 to July 2024. EXPOSURE/UNASSIGNED:ASM (variable). MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was seizure freedom, defined as a period without seizures for 12 months or 3 times the longest pretreatment seizure-free interval, whichever was longer. Treatment response was categorized as sensitive, meaning seizure free receiving 2 or fewer adequate ASM trials; resistant, meaning having 2 or more adequate ASM trials fail; or indeterminate (neither treatment sensitive nor resistant). RESULTS/UNASSIGNED:Among 448 enrolled participants, 267 (59.6%) were female, and median (IQR) participant age was 32 (21-44) years at treatment initiation. Median (IQR) follow-up duration was 3.13 (2.33-3.55) years. Most achieved seizure freedom (267 participants of 448 [59.6%]), largely without relapse (223 [83.5%]). There were 245 treatment-sensitive participants (54.7%), 102 treatment-resistant participants (22.8%), and 101 indeterminate participants (22.5%). Among treatment-sensitive participants, most (217 [89.3%]) responded to monotherapy and half (121 [49.4%], or 27% of total cohort) became seizure free while receiving their first ASM. In the first year of treatment, 251 participants (63%) had ongoing or worsening seizures. Median time to first seizure freedom was 12.1 months (95% CI, 9.7-16.1). This occurred earlier in those who never relapsed (median, 2.2 months; 95% CI, 0.8-3.2) than those who did (median, 7.4 months; 95% CI, 4.0-10.7). Those with infrequent pretreatment seizures were 0.41-fold more likely to be treatment resistant than those with very frequent seizures (relative risk [RR], 0.41; 95% CI, 0.18-0.89; P = .03; HB-corrected P = .02). Participants with self-reported comorbid psychological disorders were 1.78-fold more likely to be treatment resistant than those without (RR, 1.78; 95% CI, 1.26-2.52; P = .001). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In the Human Epilepsy Project multicenter prospective cohort study, most people with newly diagnosed focal epilepsy took more than a year and more than 1 ASM to become seizure free. Drug resistance can be identified earlier in those with frequent pretreatment seizures, and a history of psychiatric comorbidities at epilepsy diagnosis is an important prognostic factor. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02126774.

BACKGROUND:Identifying early neuropathological changes in Alzheimer's disease (AD) is important for improving treatment efficacy. Among quantitative MRI measures, transverse relaxation time (T2) has been shown to reflect tissue microstructure relevant in aging and neurodegeneration; however, findings regarding T2 changes in both normal aging and AD have been inconsistent. The association between T2 and amyloid-beta (Aβ) accumulation, a hallmark of AD pathology, is also unclear, particularly in cognitively normal individuals who may be in preclinical stages of the disease. PURPOSE/OBJECTIVE:To investigate longitudinal hippocampal T2 changes in a cognitively normal cohort of older adults and their association with global Aβ accumulation. STUDY TYPE/METHODS:Retrospective, longitudinal. SUBJECTS/METHODS:56 cognitively normal adults between 55 and 90 years of age (17 males and 39 females). FIELD STRENGTH/SEQUENCE/UNASSIGNED:3 Tesla; multi-echo spin echo sequence for T2 mapping; 18F-florbetaben positron emission tomography for Aβ measurement. ASSESSMENT/RESULTS:Bilateral hippocampal T2 and volume were extracted to relate to Aβ PET measurements. To understand variations in AD risk, participants were separated into Aβ-high and Aβ-low subgroups using a predetermined threshold. STATISTICAL TESTS/METHODS:Linear mixed-effect models and general linear models were used. A p-value < 0.025 was considered significant to account for bilateral comparisons. RESULTS:Older age was associated with increased T2 in the bilateral hippocampus (left: β = 0.30, right: β = 0.25) and smaller hippocampal volume on the left (β = -0.12). In the Aβ-low subgroup, both longitudinal T2 increase rates (β = 0.65) in the left hippocampus and bilateral cross-sectional T2 (left: β = 0.64, right: β = 0.46) were positively correlated with Aβ PET, independent of hippocampal volume. DATA CONCLUSION/CONCLUSIONS:This study provided in vivo evidence linking hippocampal T2 to Aβ accumulation in cognitively normal aging individuals, suggesting that quantitative T2 may be sensitive to microstructural changes accompanying early Aβ pathology, such as neuroinflammation, demyelination, and reduced tissue integrity. EVIDENCE LEVEL/METHODS:3. TECHNICAL EFFICACY/UNASSIGNED:Stage 2.

RATIONALE AND OBJECTIVES/OBJECTIVE:To evaluate the performance, stability, and decision-making behavior of large language models (LLMs) for title and abstract screening for radiology systematic reviews, with attention to prompt framing, confidence calibration, and model robustness under disagreement. MATERIALS AND METHODS/METHODS:We compared five LLMs (GPT-4o, GPT-4o mini, Gemini 1.5 Pro, Gemini 2.0 Flash, Llama 3.3 70B) on two imaging-focused systematic reviews (n = 5438 and n = 267 abstracts) using binary and ternary classification tasks, confidence scoring, and reclassification of true and synthetic disagreements. Disagreements were framed as either "LLM vs human" or "human vs human." We also piloted autonomous PubMed retrieval using OpenAI and Gemini Deep Research tools. RESULTS:LLMs achieved high specificity and variable sensitivity across reviews and tasks, with F1 scores ranging from 0.389 to 0.854. Ternary classification showed low abstention rates (<5%) and modest sensitivity gains. Confidence scores were significantly higher for correct predictions. In disagreement tasks, models more often selected the human label when disagreements were framed as "LLM vs human," consistent with authority bias. GPT-4o showed greater resistance to this effect, while others were more prone to defer to perceived human input. In the autonomous search task, OpenAI achieved moderate recall and high precision; Gemini's recall was poor but precision remained high. CONCLUSION/CONCLUSIONS:LLMs hold promise for systematic review screening tasks but require careful prompt design and circumspect human-in-the-loop oversight to ensure robust performance.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. METHODS:We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. RESULTS:Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). DISCUSSION/CONCLUSIONS:In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.