Faculty Bibliography

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: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.

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.

Human pluripotent stem cells (hPSCs) are a valuable tool for disease modeling. Further stem cells can be reprogrammed from adult somatic cells, called induced pluripotent stem cells (iPSC). iPSC technology allows for the evaluation of specific study participants and populations and ventures into personalized medicine. Blood is routinely taken and cryopreserved for research purposes. These samples are processed either as buffy coats, a blood sample containing white blood cells and platelets, or as peripheral blood mononuclear cells (PBMCs), which represent a more purified population of white blood cells without eosinophils, basophils, platelets, or red blood cells. Both are a readily available and relatively non-invasive source for reprogrammable somatic cells. Several reports detail reprogramming from PBMCs, whereas only one describes this process from frozen buffy coats. Recent experience revealed PBMC reprogramming protocols available in the literature and from manufacturers to be unsuccessful when applied to frozen buffy coat samples, necessitating the adaptations and troubleshooting strategies described here. For many researchers, who employ iPSC technologies, it is imperative to have thorough protocols with a high success rate, especially in cases, where patient samples may contain only few cells, are obtained in wide time intervals, are from limited participant pool, or are otherwise highly valuable. Here, checkpoints and troubleshooting strategies are identified to increase the chance of reprogramming human frozen buffy coats or purified PBMCs. Ultimately, this protocol will allow researchers to identify predictors of reprogramming success and strategize alternative approaches to improve the chances of successful iPSC derivation.

Reliable structural brain measurements are essential for studying neurodegeneration and for designing adequately powered aging and Alzheimer's disease (AD) research. We evaluated the test-retest reliability of FreeSurfer 7.1 morphometric measures in 100 older adults (mean age 73.5 years) ranging from cognitively unimpaired to dementia. Each participant underwent two T1-weighted 3T MRI scans on the same scanner within a short interval (mean 5.5 weeks), minimizing biological change. Segmentation was performed in both standard cross-sectional and longitudinal FreeSurfer modes, focusing on AD-relevant volumes of entorhinal cortex, hippocampus, lateral ventricles, choroid plexus, and the AD cortical thickness signature. Reliability was quantified using absolute and root-mean-square test-retest differences, standard deviation of differences, and intraclass correlation coefficients. Longitudinal processing improved precision by 15-50% across most measures compared with cross-sectional processing, with the largest gain observed for entorhinal thickness. Larger, anatomically well-defined regions (e.g., hippocampus, AD signature) demonstrated higher reliability than small structures or those with complex geometry (e.g., entorhinal cortex, choroid plexus). Image quality, indexed by the Euler characteristic, was the only factor significantly associated with measurement variability; reliability was unrelated to age, sex, cognitive status, inter-scan interval, or amyloid/tau PET burden. Power analyses indicated that detecting a 1% within-individual change requires sample sizes ranging from 36 (AD signature) to >300 (entorhinal cortex). We observed low reliability of choroid plexus volumetry by FreeSurfer 7. These results provide practical benchmarks for expected FreeSurfer measurement variability in older adults. They highlight the advantages of longitudinal processing and rigorous quality control for research on brain aging and AD.

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.

OBJECTIVES/OBJECTIVE:The practice of limiting life-sustaining therapy (LST) at end-of-life is widespread globally. The goal of this study was to evaluate whether patient's age influences end-of-life limitations overall and of various LST in ICUs worldwide. DESIGN/METHODS:Multinational, multicenter, prospective observational study. SETTING/METHODS:One hundred ninety-nine ICUs in 36 countries worldwide. PATIENTS/METHODS:Consecutive adult patients admitted to ICUs who died and/or had LST limitations (withholding, withdrawing, or active shortening of the dying process) were included during a 6-month period between September 2015 and September 2016. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Patients were grouped: younger than 65 years, 65-79 years old, and 80 years old or older. A total of 12,200 patients were included. In multivariate logistic regression analysis, odds ratio (OR) for any LST limitation in the 80 years old or older group was higher than in younger than the 65 years old group (OR 1.47 [95% CI, 1.22-1.76], p < 0.001). When stratified by region, this association was significant in Central and Southern Europe (OR 1.56 [95% CI, 1.11-2.20], p = 0.037 and OR 2.23 [95% CI, 1.58-3.17], p < 0.001, respectively), but not in the other regions. The proportion of withholding therapy of each LST was highest in the group of individuals 80 years or older, whereas the proportion of withdrawing therapy was highest in the group younger than 65 years. The 80-year-old or older group also had a shorter time from ICU admission to first limitation. The predominant reason for any LST limitation in all age groups was unresponsiveness to maximal therapy, followed by neurologic and chronic diseases. Patient age was rarely the primary reason for limitations for all groups. CONCLUSIONS:End-of-life limitations were higher in patients 80 years or older compared to those 65 years old or younger, with regional variations. The main reasons for limitations were comparable across age groups, with age not being the primary reason.