Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Implementation of telemedicine expanded options for outpatient neurology care. It remains uncertain which new neurology patients can be appropriately evaluated virtually. We compared subsequent health care utilization after virtual vs in-person new patient neurology visits across 3 academic medical centers. METHODS:We conducted a retrospective multicenter cohort study of adults with a new outpatient neurology visit from September 2020 through December 2021 using the Vizient Clinical Data Base and Clinical Practice Solutions Center databases. Virtual and in-person patients were matched 1:1 using propensity scores incorporating demographics, clinical characteristics, time period, and previous health care utilization. Outcomes were analyzed overall and stratified by neurologic chief complaint category and institution. We compared rates of subsequent neurologic clinic follow-up, emergency department (ED) visits, and hospitalizations after virtual and in-person encounters. Testing and all-cause ED visits/hospitalizations were also assessed. RESULTS:= 0.13, respectively). Analyses by chief complaint found that 90-day follow-up was higher after in-person visits for dementia, whereas 30- and 90-day follow-up was higher after virtual visits for Parkinson disease and multiple sclerosis, and 90-day follow-up was higher after virtual visits for headache. Testing was more frequent after in-person visits for certain chief complaints. DISCUSSION/CONCLUSIONS:In this propensity score-matched multicenter cohort, new neurology patients seen virtually had similar downstream utilization as those seen in-person, including comparable 90-day follow-up and similar neurologic and all-cause ED visits and hospitalizations. Although follow-up varied modestly by chief complaint and testing was more frequent after some in-person visits, no major differences emerged overall.

BACKGROUND:Since 2018, the Geriatric Emergency Department (GED) Accreditation Program has recognized Emergency Departments (EDs) that provide high-quality care tailored to older adults. GEDs have expanded rapidly across the United States in recent years, but little is known about how GED care is associated with patient outcomes, including hospital admissions and subsequent mortality. METHODS:We used the 2018-2021 Health and Retirement Study (HRS)-Medicare linked data of adults aged ≥ 65 years. We supplemented these data with the American College of Emergency Physicians (ACEP) GED accreditation list and American Hospital Association (AHA) data. Receipt of acute care in a GED was defined as having an ED visit at a GED. Patient-level analyses were conducted using each individual's most recent ED visit. Multivariable logistic regression models were used to estimate associations between receipt of acute care in a GED and outcomes of hospital admission and 30-day mortality, adjusting for patient demographics, socioeconomic status, health conditions, ED visit severity, and hospital-level characteristics. RESULTS:Among 4563 older adults who had an ED visit, 270 (5.9%) received acute care in GEDs and 4293 (94.1%) received non-GED care. Compared with those treated in non-GEDs, patients treated in GEDs had significantly lower odds of hospital admission (OR, 0.61; 95% CI, 0.42-0.87; p < 0.01) and 30-day mortality (OR, 0.62; 95% CI, 0.40-0.96; p < 0.05). Subgroup analyses showed that the association with admission was more pronounced among adults aged 65-80 years (OR, 0.43; 95% CI, 0.24-0.76; p < 0.01) and non-Hispanic White individuals (OR, 0.51; 95% CI, 0.34-0.78). An association with lower mortality was observed among non-Hispanic White individuals (OR, 0.51; 95% CI, 0.30-0.87; p < 0.05). CONCLUSIONS:GED care was associated with lower odds of hospital admissions and 30-day mortality among older adults. Broader implementation may expand the reach of GED programs across diverse populations.

We report a 71-year-old woman who developed disabling orthostatic tremor and severe orthostatic hypertension following cosmetic neck lift surgery. Autonomic testing demonstrated exaggerated pressor responses and excessive orthostatic catecholamine release, consistent with sympathoadrenal overactivation due to impaired carotid baroreflex function. This case highlights a potential autonomic complication of aesthetic neck surgery.

Historically hindered by a lack of access to academic, political, financial, technological, scientific, and social resources, most people living with disability have been unable to successfully merge their lived experience with the traditional research process. The lack of this community's perspective has been an ongoing missed opportunity for the broadening and relevance of research around disability. Patient-scientists, however, bridge the gap. They are individuals who act as patient research partners (PRPs) with the valuable addition of a research and/or medical degree. Their embodied expertise, combined with their academic accreditation, seamlessly positions them to work within the academic system. With a foot in both worlds, they are equipped to generate real change for themselves and others living with their condition. Patients are encouraged to participate in their own clinical care, although PRPs remain relatively uncommon. Even more scarce are patient-scientists, who serve as intellectual peers with expertise in technical and experiential domains. Their research training gives them an invaluable role: to act as both scientist and patient at once. This special communication builds on ongoing efforts to bolster patient participation in rehabilitation research by focusing on patient-scientists and highlighting their potential to enhance rehabilitation research processes.

The formation of a stable antigenic peptide-HLA II (p-HLA class II) complex is a critical early step in the adaptive immune response. In this work, we identify the residue-residue contacts that 'anchor' the peptide between the alpha and beta chains of HLA II and examine whether the anchoring residue-residue contacts are shared among different p-HLA II complexes. We hypothesize that there are similarities between the contact map of the alpha and beta chains of HLA II with CLIP (the fragment of the invariant gamma chain that binds to newly synthesized HLA II molecules) and the contact maps between the different alpha and beta chains of HLA II molecules with various antigenic peptides. To test the hypothesis, 81 diverse peptide-HLA II DR and DQ complexes, including CLIP-HLA II complex, were selected from the PDB database, and 'Unified Residue Numbering' was introduced for all complexes. The Unified Residue Numbering enables us to compare residue contacts across complexes for each position, e.g., to identify the position in peptides occupied by residues with the highest number of contacts with HLA II similar to CLIP position with the highest number of contacts in all structures, and to define characteristics of residues for each position. We also identified all 'similar contacts' in the analyzed structures. 'Similar contacts' are defined as contacts between same-numbered residues in the peptide and HLA II and CLIP with HLA II structure independent of physicochemical properties of residues involved in the contact. We found that in the 81 analyzed structures, 90% of contacts between peptide and the alpha chains were 'similar contacts', as were 80% of contacts between peptides and the beta chains. Thus, our approach to sequence alignment, which is based on alignment of similar contacts rather than similar residues, allows one to define the common network of residues that underlies the interactions between peptide and HLA II. We also consider several criteria for the specificity of antigen peptide loading into HLA II based on the structural and physicochemical characteristics of the residues involved in the 'anchoring' contacts. These data may be useful for refining existing computational algorithms that predict peptide interactions with HLA II complexes.

BACKGROUND/UNASSIGNED:For over a decade, STAT surgery has been the standard of care (SOC) for treating significant cauda equina syndromes (CES). Nevertheless, too many spinal surgeons, physician extenders, and other medical professionals still wrongly believe they have up to 24-48 hours to treat CES. METHODS/UNASSIGNED:To counter this misconception, we reviewed the evolution of treatment for significant CES from the outdated dominant protocols of < 48 h, to 24 - < 48 h, to < 24 h, to 0-< 24 h, to the present SOC; STAT, "prompt", surgery performed "the sooner the better". RESULTS/UNASSIGNED:A 2014 study found that there is no support in the literature for delaying CES surgery for up to 48 h, and further; "... the earlier the surgical intervention, the more beneficial the effect for compressed nerves." Subsequent studies advocated for < 24 h for early CES, finding they resulted in improved outcomes including bladder function especially for those with incomplete/partial (ICES) vs. total/retention CES (RCES). One study, involving 20,924 CES patients, showed the best improvement for surgery performed within 0 - < 24 h, leading to the present SOC for treating significant CES, as STAT or "the sooner the better". CONCLUSION/UNASSIGNED:Based on the up-to-date literature, the present SOC for managing significant CES is STAT surgery. Notably, the American Association of Neurological Surgeons (AANS) "guidelines" (published 4/5/24 on (www. aans.org)) cited the present treatment for CES; "Prompt surgery is the best treatment for patients with CES;" with the Merriam-Webster definition of prompt as "immediate" or "without delay". We agree that the present SOC for treating significant CES is STAT or "prompt" surgery.

BACKGROUND:Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an established treatment for medication-refractory tremor with limited evidence in patients aged >80 years. OBJECTIVE:To retrospectively compare safety and efficacy of MRgFUS in under-80 versus over-80 patients without prior balance disturbances or unstable comorbidities. METHODS:One hundred thirty five consecutive patients with essential tremor or tremor-predominant Parkinson's disease underwent unilateral MRgFUS thalamotomy. Patients were stratified into under-80 (n: 97, median age 71 years) and over-80 (n: 38, median age 82 years). Tremor severity was scored with the Fahn-Tolosa-Marin Clinical Rating Scale. Outcomes included intraoperative tremor suppression and SE occurrence, resolution, and improvement. RESULTS:Older patients showed higher baseline tremor severity (U: 383.5; p: 0.02). Tremor reduction >50% occurred in 95.6% of cases, with complete resolution in 77.0%. Higher target temperature predicted better tremor control (OR [95% CI]: 4.03 [1.39-11.65]; p: 0.01), whereas greater baseline tremor (OR [95% CI]: 0.90 [0.83-0.99]; p: 0.02) and SDR <0.4 (OR [95% CI]: 0.14 [0.02-0.85]; p: 0.03) predicted poorer outcomes. Age ≥ 80 did not affect intraprocedural tremor control (OR [95% CI]: 0.83 [0.15-4.70]; p: 0.83) and longitudinal mixed-effects analysis confirmed sustained 1-year tremor control, unaffected by advanced age. SEs occurred in 71.1%, mostly balance disturbances. After a mean follow-up of 43.7 weeks, 60.4% improved and 46.9% fully resolved, with only 1.5% severe persistent SEs. Age ≥ 80 did not influence SE rates (OR [95% CI]: 0.60 [0.27-1.33]; p: 0.20), resolution (OR [95% CI]: 0.56 [0.25-1.26]; p: 0.16), or improvement (OR [95% CI]: 0.60 [0.28-1.30]; p: 0.19). CONCLUSIONS:MRgFUS thalamotomy yields comparable outcomes in carefully selected patients aged >80 years and in younger individuals.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Interactions between cancer cells and their microenvironment are central to tumor formation. Regional microenvironmental variability in the brain may offer insights into essential factors in tumorigenesis. Surprisingly, a granular assessment of regional patterns of gliomagenesis has not been undertaken in the molecular era. The aim of this study was to quantitatively establish the anatomic distribution of the major molecular subtypes of adult diffuse glioma. METHODS:We retrospectively analyzed 204 isocitrate dehydrogenase (IDH)-mutant and 200 IDH-wildtype gliomas. Reproducibility was assessed in an external cohort (190 IDH-mutant, 227 IDH-wildtype), and microarray expressions from Allen Human Brain Atlas were used to compare transcriptomic profiles between IDH-mutant hotspots and coldspots. RESULTS:A total of 50.5% (103/204) of IDH-mutant tumors arose with the superior and middle frontal gyri, indicating a 3.1-fold regional enrichment relative to the volume of these gyri (P < .001). Totally, 9.5% (19/200) of IDH-wildtype tumors arose in the superior temporal gyrus with a 2.1-fold enrichment (P = .01). IDH-mutant and wildtype tumors were enriched by 4 and 4.5-fold, respectively, in the insula (both P < .001). Overall, 23.3% (24/103) of astrocytomas occurred disproportionately higher in the insula compared with oligodendrogliomas (P < .001). Transcriptomic analysis comparing the lobar hotspot (frontal lobe) to the coldspot (occipital lobe) revealed frontal enrichment of cholesterol (normalized enrichment score = 1.78) and fatty acid (normalized enrichment score = 1.94) metabolism pathways, paralleling the observed regional enrichment of IDH-mutant gliomas. CONCLUSION/CONCLUSIONS:This study identifies molecular subtype-specific glioma hotspots and may suggest that regional metabolic differences may underlie the brain's variable vulnerability to gliomagenesis. These findings provide a framework for investigating additional microenvironmental factors that drive human glioma formation.

INTRODUCTION/BACKGROUND:Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been linked to dementia risk, but prior studies were limited by small sample sizes. METHODS:We assessed the association between baseline NLR and incident Alzheimer's disease (AD) and Alzeimer's disease and related dementias (AD/ADRD) using electronic health records from New York University (NYU) (n = 284,530) and the Veterans Health Administration [VA] (n = 85,836) Hospitals from 2011 to 2023. AD/ADRD diagnoses were identified via International Classification of Diseases (ICD) codes ≥6 months post-baseline. Cox models and cumulative incidence functions (CIFs) adjusted for demographic and clinical variables, with death as a competing risk. RESULTS:Higher NLR was associated significantly with increased AD/ADRD risk in both cohorts (NYU hazard ratio [HR] = 1.07, 95% confidence interval [CI] 1.02-1.15; VA HR = 1.21, 95% CI 1.10-1.34). Spline analysis further confirmed a continuous dose-response relationship, and subgroup analyses showed higher risk among female and Hispanic patients. DISCUSSION/CONCLUSIONS:Elevated NLR is independently associated with higher AD/ADRD risk across diverse populations, highlighting the role of systemic inflammation and neutrophil-mediated pathways in neurodegeneration.