Faculty Bibliography

OBJECTIVES/OBJECTIVE:Anti-amyloid-beta immunotherapy requires frequent MRI screening for amyloid-related imaging abnormalities-hemorrhage subtype (ARIA-H), consisting of cerebral microbleeds (CMB) and/or superficial siderosis (SS), using gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI). Screening MRI sequences for ARIA-H may benefit from acceleration to maximize patient enrollment by increased throughput and reduced motion degradation. This study assessed the diagnostic performance of standard GRE and SWI to echo-planar imaging (EPI) accelerated substitutions for detecting CMB and SS. MATERIALS AND METHODS/METHODS:This retrospective single-center rater study included 50 patients, 25 with CMB and 25 patients without CMB (median age 77 y, IQR: 70 to 82 y; 30 of 50 female) who were imaged with FDG PET-3T MRI from April to July 2023. Standard GRE (90 s) and SWI (192 s) were compared with an EPI-accelerated GRE (aGRE; 13 s, 86% time reduction) and an EPI-accelerated SWI substitution (aSWI; 33 s, 83% time reduction). Three board-certified neuroradiologists independently reported CMB and SS (per ARIA-H monitoring guidelines), perceived image quality and motion for each sequence. There were 240 total assessments per rater (the 4 different sequences for the 50 patients plus 10 duplicated patients). Sensitivity, specificity, positive and negative predictive values, area under the curve (AUC), inter-rater and intrarater agreement were determined for each sequence and rater. RESULTS:The aggregate AUCs for the 4 individual sequences were excellent for detecting CMB (0.84 to 0.94) and SS (0.89 to 1.00) without statistical differences observed between standard and EPI-accelerated substitutions. Both aGRE and aSWI had high negative predictive values (96.5% to 100%). There were modest quantitative correlations between standard and accelerated sequences (0.606 and 0.391 for GRE and SWI, respectively), no differences in CMB count for aGRE (bias 0.01, P=0.895), but reduced CMB count with aSWI (bias -1.12, P=0.014). Inter-rater agreements were mildly reduced for both GRE versus aGRE (eg, 0.757 to 0.622 for CMB detection) and SWI versus aSWI (eg, 0.834 to 0.649 for SS detection). Perceived image quality for accelerated sequences was reduced, but with less motion observed with aSWI. CONCLUSIONS:The aGRE and aSWI sequences shorten scan times 86% and 83%, respectively, with similar diagnostic performance for ARIA-H screening, but reduced rater agreement and perceived image quality.

Polyaminopathies are a recently described family of rare genetic neurodevelopmental disorders. Polyaminopathies disrupt the biosynthesis of the primary polyamines: putrescine, spermidine, and spermine. Snyder-Robinson syndrome results from hemizygous loss-of-function variants in the spermine synthase (SMS) gene, resulting in decreased or complete loss of spermine synthase enzyme activity. Bachmann-Bupp syndrome results from heterozygous gain-of-function variants in the ornithine decarboxylase 1 (ODC1) gene, resulting in increased ornithine decarboxylase enzyme activity. Faundes-Banka syndrome results from heterozygous loss-of-function variants in the eukaryotic translation initiation factor 5A (EIF5A) gene, impairing eIF5A protein function. DHPS (deoxyhypusine synthase) deficiency is an autosomal recessive disease and results from bi-allelic hypomorphic variants in the deoxyhypusine synthase (DHPS) gene, which results in reduced deoxyhypusine synthase enzyme activity. Finally, DOHH (deoxyhypusine hydroxylase) disorder is an autosomal recessive disorder caused by bi-allelic loss-of-function variants in the deoxyhypusine hydroxylase (DOHH) gene, which causes decreased deoxyhypusine hydroxylase enzyme activity. Snyder-Robinson syndrome was first described in 1969, while the other four syndromes have only been identified in the past 7 years. A comprehensive phenotypic and genotypic description of these five syndromes is needed. We review the clinical and genetic features of these five polyaminopathies to create an inclusive clinical resource. A systematic keyword search strategy was used to identify all published cases in PubMed, Web of Science, and Scopus databases. The five known syndromes associated with the polyamine pathway share many similar clinical phenotypes, and yet patients with each syndrome present with distinctive syndromic features. This review will serve as a valuable resource for clinicians diagnosing and caring for patients with these rare polyaminopathies.

OBJECTIVE:To validate the carotid web (CW) risk stratification assessment described in previous works within a larger cohort of patients with symptomatic and incidentally found asymptomatic CWs. METHODS:A retrospective analysis of our institution's electronic medical records identified all patients with a diagnosis of CW from 2017 to 2024. We included symptomatic patients and those with asymptomatic CWs, that is, incidentally found webs without history of stroke or transient ischemic attack. Patient charts were reviewed for demographics, imaging, comorbidities, and a diagnosis of stroke after diagnosis of asymptomatic CW. All angles were measured as described in previous work on a sagittal reconstruction of neck CT angiography in which the common carotid artery (CCA), external carotid artery, and internal carotid artery (ICA) were well visualized, together with the CW itself. Principal component analysis and logistic regression were performed to evaluate the association between high-risk angles and stroke risk.  RESULTS: Twenty-six symptomatic and 26 asymptomatic patients were identified. Of note, the number of patients with hypertension, hyperlipidemia, and smoking history was 17 (65.0%), 16 (62.0%), and 8 (31.0%) for symptomatic patients and 18 (69.0%), 17 (65.0%), and 15 (58.0%) for asymptomatic patients. All angular measurements showed statistically significant associations with stroke status. The CCA-web-pouch angle showed the strongest association (p=2.07×10⁻⁴), followed by the CCA-pouch-tip angle (p=3.23×10⁻⁴), ICA-web-pouch angle (p=0.004), and ICA-pouch-tip angle (p=0.005). Each additional high-risk angle increased the odds of stroke by 9.47-fold (p<0.0001). The associated probability of stroke increased from 6.3% with no high-risk angles to 39.1% with one high-risk angle and further to 85.9% with two high-risk angles. The model demonstrated high sensitivity, correctly identifying 84.6% of positive cases, and high specificity, correctly identifying 88.5% of negative cases. The F1 score was 0.863, indicating good overall model performance.  CONCLUSION: Given this successful stratification of CWs into high- and low-risk groups, the utilization of geometric CW parameters may play a role in improving patient selection for intervention in the setting of incidentally diagnosed CW. .

BACKGROUND AND OBJECTIVES/OBJECTIVE:Severe hypoxemia after generalized convulsive seizures (GCSs) can trigger neural injury and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP). Some degree of variability in interbreath interval is normal, but increased variability may suggest dysfunctional breathing control and may be associated with severe postictal hypoxemia. We evaluated the relationship between interictal breathing variability and severity and duration of hypoxemia after GCS. METHODS:nadir), and secondary outcome: occurrence of combined prolonged and pronounced hypoxemia. Univariable and multivariable models were created for primary outcomes, but only univariable analyses were performed for the secondary outcome. RESULTS:= 0.002) was the only variable significantly associated with hypoxemia severity after controlling for duration of postictal generalized EEG suppression, SD-2 of the awake interbreath interval, and body mass index. Univariable analyses for combined prolonged and pronounced hypoxemia showed SD-2 of the awake interbreath interval, temporal lobe epilepsy, ictal central apnea, and a shorter tonic phase duration were significantly associated. DISCUSSION/CONCLUSIONS:Measures of interictal respiratory variability are associated with severe and prolonged hypoxemia after GCS. Increased interictal respiratory variability suggests baseline respiratory dysregulation in some PWE and may be a surrogate for SUDEP risk.

Consumer wearable devices are commonly used by patients and consumers for several reasons with increasing application as new technologies are developed. Use of these devices is an emerging issue in Neurology because of increased adoption and the additional data reported to providers by patients. Understanding of possible functions, limitations, and effect on patients of non-US Food and Drug Administration (FDA)-cleared wearable technology to inform neurologic care is needed. A common theme in people with neurologic conditions regarding consumer wearables and associated tracking applications is that there is significant promise in these tools, but adherence (days per use/per week), continued engagement (attrition), and unintended consequences such as heightened anxiety remain important issues. Further understanding and validation of these devices is needed within the field of Neurology before full use and confidence can be achieved. Below, we provide examples of non-FDA-cleared wearable devices used in Neurology in the areas of epilepsy, headache, cardiac monitoring, and sleep.

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: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: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.

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.

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.