Faculty Bibliography

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD (n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data (n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI (n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

INTRODUCTION/BACKGROUND:Anti-amyloid antibody therapies such as lecanemab are increasingly being used to treat Alzheimer's disease (AD). These therapies are associated with a high rate of amyloid-related imaging abnormalities (ARIA). METHODS:We review the case history of a patient who developed ARIA associated with lecanemab treatment. RESULTS:In addition to microhemorrhages and cerebral edema that are recognized features of ARIA, the patient developed several ischemic strokes. The patient also experienced frequent electrographic seizures without overt clinical seizures. The patient demonstrated clinical and radiographic improvement after steroid treatment. DISCUSSION/CONCLUSIONS:Our case suggests that ischemic strokes may be a feature of ARIA and highlights the importance of having a high clinical suspicion for seizures in ARIA. As anti-amyloid therapies are likely going to be increasingly used to treat AD, it is important to appreciate the spectrum of clinical and radiographic findings that can result as side effects from this class of therapies. HIGHLIGHTS/CONCLUSIONS:We report a patient who developed severe amyloid-related imaging abnormalities (ARIA) after treatment with lecanemab. Our report suggests that ischemic strokes may be a novel imaging feature of ARIA. Our report highlights the need for high clinical suspicion for seizures in ARIA.

Over the last decade there has been tremendous growth in the development of accelerated MD pathways that allow medical students to graduate in three years. Developing an accelerated pathway program requires commitment from students and faculty with intensive re-thinking and altering of the curriculum to ensure adequate content to achieve competency in an accelerated timeline. A re-visioning of assessment and advising must follow and the application of AI and new technologies can be added to support teaching and learning. We describe the curricular revision to an accelerated pathway at NYU Grossman School of Medicine highlighting our thought process, conceptual framework, assessment methods and outcomes over the last ten years.

BACKGROUND:Aspiration thrombectomy is one of the mainstays for stroke interventions. The Zoom 71 (Z71) aspiration catheter is unique with its angled tip. This study describes the orientation of the angled tip as it is navigated around the carotid siphon in relation to trackability. METHOD/METHODS:Prospectively collected cases involving large vessel occlusions of the anterior circulation intervened upon using the Z71 were retrospectively analyzed. 71 passes in 50 patients were analyzed with respect to Z71 tip orientation. 3 anatomical "turns" were defined as follows: "1": proximal cavernous, "2"- ophthalmic turn, and "3"-ICA terminus to M1. The tip was described as "Toward" Vs "Away" with respect to the inner curve of each turn. The tip getting "caught" was also analyzed. RESULTS:There was no preferential angled tip orientation of the Z71 as it was navigated around "Turn 1", 51 % "Away" vs 44 % "Toward", p= 0.54; "2", 46.5 % "Away" vs 53.5 % "Toward", p= 0.55; and "3", 43.7 % "Away" vs 46.5 % "Toward", p=0.63. The tip was not caught in Turn 1. It was caught up in "2" in 15.5 % of passes. "Away" at "2" got caught up in 21 % of passes vs 10.5 % for "Toward", p= 0.22. Z71 got caught up in "3" in 4.7 % of passes. "Away" was associated with getting caught in 6.5 % of passes vs 3 % for "Toward", p=0.52. Zoom 88 (Z88) usage as guide catheter may be associated with Z71 getting caught less in "2" compared to "Others", 9.3 % for Z88 vs 25 %, p= 0.07. This also applied to Turn 3, 0 % for Z88 vs 11.1 %, p=0.038. CONCLUSION/CONCLUSIONS:There is no preferential angled tip orientation of the Z71 as it navigates around the carotid siphon. The tip orientation does not appear to significantly affect navigation. Usage of Z88 as guide catheter helps with Z71 trackability around the siphon.

Compartment-specific cellular membrane protein turnover is not well understood. We show that FBXO10, the interchangeable component of the cullin-RING-ligase 1 complex, undergoes lipid modification with geranylgeranyl isoprenoid at cysteine953, facilitating its dynamic trafficking to the outer mitochondrial membrane (OMM). FBXO10 polypeptide lacks a canonical mitochondrial targeting sequence (MTS); instead, its geranylgeranylation at C953 and interaction with two cytosolic factors, cytosolic factor-like δ subunit of type 6 phosphodiesterase (PDE6δ; a prenyl-group-binding protein) and heat shock protein 90 (HSP90; a chaperone), orchestrate specific OMM targeting of prenyl-FBXO10. The FBXO10(C953S) mutant redistributes away from the OMM, impairs mitochondrial ATP production and membrane potential, and increases fragmentation. Phosphoglycerate mutase-5 (PGAM5) was identified as a potential substrate of FBXO10 at the OMM using comparative quantitative proteomics of enriched mitochondria. FBXO10 loss or expression of prenylation-deficient FBXO10(C953S) inhibited PGAM5 degradation, disrupted mitochondrial homeostasis, and impaired myogenic differentiation of human induced pluripotent stem cells (iPSCs) and murine myoblasts. Our studies identify a mechanism for FBXO10-mediated regulation of selective mitochondrial proteostasis potentially amenable to therapeutic intervention.

Embryologically, the left brachiocephalic vein (LBV) originates as an anastomotic channel between the right and left anterior cardinal veins. This positions the LBV between the manubrium sterni anteriorly and the innominate artery posteriorly. This pattern of adjacency of the aorta to the LBV is unique to mammals and results from a quirk of evolution. With age, the ascending aorta unfolds, elongates and dilates. Simultaneously, there is a change in the thoracic geometry that reduces the thoracic volume primarily from disc height loss and kyphosis. These transitions progressively compress the LBV. Normally, this compression is circumvented via collateral pathways and "Blood finds a way". However, traversing these circuitous pathways comes at a cost and can result in delayed transit times and venous congestion. While it is possible that compression of the LBV in the setting of adequate collateral channels may fail to provoke any pathologic sequelae, we propose a phenomenon in which such compression in the setting of inadequate collateral circulation may lead to a state of pathologic venous congestion. This anatomic anomaly and its associated clinical features, if identified, can offer a new avenue for treatment options for some of the hitherto unexplained neurologic disorders.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Multiple preferences exist for embolic materials selection in middle meningeal artery embolization (MMAE) for chronic subdural hematoma with limited comparative literature data. Herein, we compare different embolic materials. METHODS:Consecutive patients undergoing MMAE for chronic subdural hematoma at 14 North-American centers (2018-2023) were classified into 3 groups: (a) particles, (b) Onyx, (c) n-butyl cyanoacrylate (n-BCA). The end points were unplanned rescue surgery, radiographic success (≥50% reduction in hematoma thickness at last imaging "minimum of 2 weeks"), and major complications. Initial unmatched analysis compared the 3 groups; subsequent propensity score matching (PSM) compared particles vs liquid embolics (groups b and c combined). Additional subgroup PSM analyses compared particles vs Onyx, particles vs n-BCA, and Onyx vs n-BCA. All matched analyses controlled for age, sex, concurrent surgery, previous surgery, hematoma thickness, midline shift, pretreatment antithrombotics, and baseline modified Rankin Scale. RESULTS:Eight hundred and seventy-two patients (median age 73 years, 72.9% males) underwent 1070 MMAE procedures. Onyx was most used (41.4%), then particles (40.3%) and n-BCA (15.5%). Surgical rescue rates were comparable between particles, Onyx, and n-BCA (9.8% vs 7% vs 11.7%, respectively, P = .14). Similarly, radiographic success (78.8% vs 79.3% vs 77.4%; P = .91) and major complications (2.4% vs 2.3% vs 2.5%; P = .83) were comparable. The PSM comparing particles vs liquid generated 128 matched pairs; general anesthesia and bilateral procedures were significantly higher in particles (37.8% vs 21.3%; P = .004 and 39.8% vs 27.3%; P = .034, respectively). No differences in surgical rescue, radiographic improvement, or major complications were noted (P > .05). Concurrently, PSM comparing particles vs Onyx, particles vs n-BCA, and Onyx vs n-BCA, resulted in 112, 42, and 40 matched pairs, respectively, without differences in surgical rescue, radiographic success, or major complications (P > .05). CONCLUSION/CONCLUSIONS:We found no differences in radiological improvement, surgical rescue, or major complications between embolic materials in MMAE. Current randomized trials are exclusively using liquid embolics, and these data suggest that future trials involving particles are likely to produce similar outcomes.

Recent research has used large language models (LLMs) to study the neural basis of naturalistic language processing in the human brain. LLMs have rapidly grown in complexity, leading to improved language processing capabilities. However, neuroscience researchers haven't kept up with the quick progress in LLM development. Here, we utilized several families of transformer-based LLMs to investigate the relationship between model size and their ability to capture linguistic information in the human brain. Crucially, a subset of LLMs were trained on a fixed training set, enabling us to dissociate model size from architecture and training set size. We used electrocorticography (ECoG) to measure neural activity in epilepsy patients while they listened to a 30-minute naturalistic audio story. We fit electrode-wise encoding models using contextual embeddings extracted from each hidden layer of the LLMs to predict word-level neural signals. In line with prior work, we found that larger LLMs better capture the structure of natural language and better predict neural activity. We also found a log-linear relationship where the encoding performance peaks in relatively earlier layers as model size increases. We also observed variations in the best-performing layer across different brain regions, corresponding to an organized language processing hierarchy.

BACKGROUND/UNASSIGNED:The burden of Alzheimer's disease and related dementias (AD/ADRD) in Costa Rica is expected to become one of the highest in the region. Early detection will help optimize resources and improve primary care interventions. The Montreal Cognitive Assessment (MoCA) has shown good sensitivity for detecting mild cognitive impairment (MCI), but specificity varies depending on the population. This motivated the analysis of different cutoffs to minimize false-positive classifications in a Costa Rican sample for its use in clinical settings. METHODS/UNASSIGNED:Data was analyzed from 516 memory clinic outpatients (148 cognitively normal, 260 MCI, 108 mild AD/ADRD; mean age 66.3 ± 10.8 years) who underwent complete neurological and neuropsychological assessment and were diagnosed by consensus. Optimal MoCA cutoff scores were identified using a multiple cutoff approach. RESULTS/UNASSIGNED:Overall, a cutoff score of ≥ 23 showed better accuracy to distinguish between normal cognition (NC) and MCI (sensitivity 73%, specificity 83%). When analyzed by educational levels, a cutoff score of ≥ 21 showed better accuracy for ≤ 6 years (sensitivity 80%, specificity 76%), ≥23 for 7-12 years (sensitivity 86%, specificity 76%) and ≥ 24 for > 12 years (sensitivity 70%, specificity 85%). For distinguishing MCI from mild AD/ADRD, the optimal overall cutoff score was ≥ 15 (sensitivity 66%, specificity 85%). When stratified by years of education, cutoff scores of ≥ 14 showed better accuracy for ≤ 6 years (sensitivity 70%, specificity 88%), ≥15 for 7-12 years (sensitivity 46%, specificity 95%) and ≥ 17 for > 12 years (sensitivity 67%, specificity 93%). CONCLUSIONS/UNASSIGNED:A MoCA cutoff score of ≥ 23 in the Costa Rican population showed better diagnostic accuracy for detecting MCI and may reduce the false positive rate. Our findings may be helpful for primary care clinical settings and further referral criteria.