Faculty Bibliography

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 METHODS/UNASSIGNED:To counter this misconception, we reviewed the evolution of treatment for significant CES from the outdated dominant protocols of 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.

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.

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.

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.

OBJECTIVE:Cenobamate has been shown to be an effective antiseizure medication for some patients with drug-resistant focal epilepsy being considered for epilepsy surgery. This retrospective single-center study evaluated whether surgery was obtained within 12 months for patients who received cenobamate as a treatment during the presurgical evaluation and those who did not, comparing across years before and after cenobamate approval. METHODS:Patients undergoing surgical evaluation for drug-resistant focal epilepsy at the University of Colorado during 2018 and 2023 who had 12 months of follow-up data were analyzed. Comparison years were also chosen to avoid the confounding effect of the COVID-19 pandemic on surgical volume (2020-2021). This allowed for comparison times before and after cenobamate's US Food and Drug Administration approval. The primary outcome (surgery within 12 months) was modeled with potential explanatory variables using multiple logistic regression. A p-value of <.05 was considered significant. RESULTS:After controlling for potentially confounding clinical and demographic variables, cenobamate use during the presurgical evaluation period was associated with .13 lower odds of surgery within 12 months compared to not being prescribed this medication (95% confidence interval [CI] = .04-.42, p < .001). Being Hispanic or Latino was significantly associated with .23 lower odds of surgery within 12 months compared to patients who did not report being Hispanic or Latino (95% CI = .09-.61, p = .003). Year of evaluation (2023 vs. 2018), education level, age, and sex did not have significant associations with undergoing surgery within 12 months. SIGNIFICANCE/CONCLUSIONS:Patients with drug-resistant focal epilepsy undergoing evaluation for epilepsy surgery may benefit from cenobamate. In this study, patients who received cenobamate during the presurgical evaluation were less likely to undergo surgery within 12 months. The delay to surgery identified among Hispanic and Latino patients suggests potential barriers to care in this patient population warranting further investigation.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Carotid webs are an underrecognized cause of ischemic stroke in young adults and are associated with a high risk of recurrence when managed with medical therapy alone. Although carotid endarterectomy (CEA) is increasingly performed, histopathological confirmation remains infrequently reported, and the underlying pathological substrate of symptomatic carotid webs is not well defined. In this study, we present the largest pathologically confirmed series of symptomatic carotid webs treated with CEA, providing a comprehensive clinicopathological characterization and evaluation of long-term surgical outcomes. METHODS:Patients with symptomatic carotid webs were retrospectively identified from institutional databases encompassing both inpatient and outpatient encounters. Clinical features, imaging characteristics, surgical findings, and histopathological results from CEA specimens are presented. RESULTS:Among 39 patients with symptomatic carotid web, 34 underwent CEA with histopathological confirmation of the diagnosis, characterized by focal eccentric intimal fibromyxoid tissue, fibromuscular dysplasia, hyperplasia, or thickening. Notably, concurrent atheromatous changes were noted in 6 patients. All webs were located within 3 cm of the carotid bifurcation, and most (76%) were localized on the posterior wall. Competing stroke mechanisms were identified in 15% of patients. Two-thirds of patients presented with a large or medium vessel occlusion and over half received acute reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy). Two patients experienced transient, minor cranial nerves injuries (hypoglossal nerve and marginal mandibular branch) after CEA. At a median follow-up of 29 months, no patients experienced recurrent stroke (95% CI: 0%-10%), and the median modified Rankin Scale score was 1 (0-1). CONCLUSION/CONCLUSIONS:This study supports CEA as a safe and effective therapeutic option for patients with symptomatic carotid webs and demonstrates its diagnostic value through direct histopathological confirmation. By presenting the largest pathologically validated series to date, our findings further define the vascular pathology underlying carotid webs and underscore the diagnostic value of surgical resection for definitive diagnosis.

BackgroundMisalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD).ObjectiveDetermine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition.MethodsActual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes were quality of life and cognitive domains frequently altered in people with PD (global cognition & executive function). Secondary cognitive domains assessed were attention, memory, visuo-spatial, verbal function, and information processing. Linear and non-linear models assessed the relationship between discordance, quality of life, and cognition.ResultsDiscordance related to mobility-related quality of life, such that under-confidence was related to poorer quality of life. Non-linear (quadratic) models were shown to fit the discordance-Global cognition (p = 0.02) data better than linear models such that over- and under-confidence related to poorer cognition. Secondary cognitive domains were not robustly related to discordance.ConclusionsIn a clinical sample of people with PD, discordance was related to mobility-related quality of life and global cognition. Global cognition further exhibited a possible non-linear relationship to discordance indicating that over- or under-confidence may relate to poorer cognition. This work underscores the functional relevance of misalignment of actual and balance abilities.