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.

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.

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.

PURPOSE OF REVIEW/OBJECTIVE:This review discusses the current state of the evidence related to the relationship between the cerebellum and epilepsy, highlighting evidence on neurostimulation of the cerebellum for treatment of epilepsy, and placing current knowledge into historical context. RECENT FINDINGS/RESULTS:The cerebellum plays an important role in certain epilepsy types, both as a key part of epileptic networks and an area that can give rise to seizures. Cerebellar stimulation as a potential treatment for drug-resistant epilepsy is a recurring, albeit niche, topic of interest. Over decades of intermittent, often highly limited investigations into this area of research, there are still more questions than answers. However, more recent preclinical insights point the way towards leveraging modern surgical techniques and technology in investigating cerebellar stimulation as a potential viable treatment approach to select types of epilepsy. SUMMARY/CONCLUSIONS:Cerebellar stimulation holds promise for improving seizure control in people with specific types of drug-resistant epilepsy. Future studies should leverage new preclinical data, along with modern technology, neurosurgical techniques, and clinical trial design, to help determine the optimal stimulation parameters, optimal stimulation targets, and optimal patient-selection for this promising area of investigation.

Health equity research in neurology and neuroscience faces a unique challenge in the current United States climate of funding scarcity and prioritization of other research topics. The low funding contrasts with rising interest and scholarship in the field. Neuroscientists in the early phases of their career are particularly vulnerable to the detrimental effects of reduced funding due to their relatively lower publication history and established sources of support for projects. Here, we introduce the Early Career Network within the Society of Equity Neuroscience (SEQUINS). The group is dedicated to the support of early-career neurologists and neuroscientists who pursue health equity neuroscience research. We will accomplish this via a combination of virtual and in-person events as well as the establishment of a robust community of scientists. Together, we will foster camaraderie, solidarity, and shared interests to propel the field of health equity neuroscience forward.

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.

PURPOSE OF REVIEW/UNASSIGNED:Alzheimer disease (AD) and epilepsy are major causes of neurologic disability and are reciprocally related: epileptiform discharges, subclinical seizures, and epilepsy are more prevalent in patients with AD compared with controls; progressive cognitive impairment commonly afflicts epilepsy patients; and late-onset epilepsy patients have higher rates of new-onset dementia. RECENT FINDINGS/UNASSIGNED:Epidemiologic studies support shared risk factors (e.g., genetic variants, vascular disease, sleep disorders, microbiome) with notable divergences. AD and epilepsy have some overlapping anatomic (e.g., hippocampus, entorhinal, and association cortex), clinical (e.g., memory, attentional, and executive) impairments, and neuropathologic (e.g., amyloid, tau, neurofibrillary tangles) features. Shared clinical and translational challenges include underlying mechanisms (e.g., genetic variants, neuroinflammation, metabolic and mitochondrial dysfunction, excitatory/inhibitory imbalance, microbiome, and sociodemographic factors) and identifying valid and reliable biomarkers (e.g., total tau and phosphorylated tau (p-tau), amyloid deposition, Aβ42/Aβ40 ratio) to assess disease progression, predict outcomes, and assess potentially disease-modifying interventions. SUMMARY/UNASSIGNED:Identifying convergences and divergences between epilepsy and AD may inform our understanding. The clinical, neurophysiologic, neuropathologic, and molecular pathologic changes in AD and epilepsy may reveal pathophysiologic insights and therapeutic opportunities.