Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
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23427
A Direct Comparison of 10 WAIS-IV Digit Span Embedded Validity Indicators among a Mixed Neuropsychiatric Sample with Varying Degrees of Cognitive Impairment
OBJECTIVE:Reliable Digit Span (RDS), RDS-Revised (RDS-R), and age-corrected scaled score (ACSS) have been previously validated as embedded performance validity tests (PVTs) from the Wechsler Adult Intelligence Scale-IV Digit Span subtest (WAIS-IV DS). However, few studies have directly compared the relative utility of these and other proposed WAIS-IV DS validity indicators within a single sample. METHOD/METHODS:This study compared classification accuracies of 10 WAIS-IV DS indices in a mixed neuropsychiatric sample of 227 outpatients who completed a standardized neuropsychological battery. Participants with ≤1 PVT failures of the four, freestanding criterion PVTs constituted the valid group (n = 181), whereas those with ≥2 PVT failures formed the invalid group (n = 46). Among the valid group, 113 met criteria for mild cognitive impairment (MCI). RESULTS:Classification accuracies for all DS indicators were statistically significant across the overall sample and subsamples with and without MCI, apart from indices derived from the Forward trial in the MCI sample. DS Sequencing ACSS, working memory RDS (wmRDS), and DS ACSS emerged as the most effective predictors of validity status, with acceptable to excellent classification accuracy for the overall sample (AUCs = 0.792-0.816; 35%-50% sensitivity/88%-96% specificity). CONCLUSIONS:Although most DS indices demonstrated clinical utility as embedded PVTs, DS Sequencing ACSS, wmRDS, and DS ACSS may be particularly robust to cognitive impairment, minimizing risk of false positive errors while identifying noncredible performance. Moreover, DS indices incorporating data from multiple trials (i.e., wmRDS, DS ACSS) also generally yielded greater classification accuracy than those derived from a single trial.
PMID: 36244241
ISSN: 1873-5843
CID: 5593102
Brain Calcifications: Genetic, Molecular, and Clinical Aspects
Many conditions can present with accumulation of calcium in the brain and manifest with a variety of neurological symptoms. Brain calcifications can be primary (idiopathic or genetic) or secondary to various pathological conditions (e.g., calcium-phosphate metabolism derangement, autoimmune disorders and infections, among others). A set of causative genes associated with primary familial brain calcification (PFBC) has now been identified, and include genes such as SLC20A2, PDGFB, PDGFRB, XPR1, MYORG, and JAM2. However, many more genes are known to be linked with complex syndromes characterized by brain calcifications and additional neurologic and systemic manifestations. Of note, many of these genes encode for proteins involved in cerebrovascular and blood-brain barrier functions, which both represent key anatomical structures related to these pathological phenomena. As a growing number of genes associated with brain calcifications is identified, pathways involved in these conditions are beginning to be understood. Our comprehensive review of the genetic, molecular, and clinical aspects of brain calcifications offers a framework for clinicians and researchers in the field.
PMCID:10218793
PMID: 37240341
ISSN: 1422-0067
CID: 5508762
The advent of epilepsy directed neurosurgery: The early pioneers and who was first
Efforts to treat epileptic seizures likely date back to primitive, manmade skull openings or trephinations at the site of previous scalp or skull injuries. The purpose may have been the release of "evil spirits," removal of "cerebral excitement," and "restoral of bodily and intellectual functions." With progressive discoveries in brain function over the past 100 to 300 years, the cerebral cortical locations enabling voluntary movements, sensation, and speech have been well delineated. The locations of these functions have become surgical targets for the amelioration of disease processes. Disease entities in particular cerebral-cortical areas may predispose to the onset of focal and or generalized seizures, which secondarily interfere with normal cortical functioning. Modern neuroimaging and electroencephalography usually delineate the location of seizures and often the type of structural pathology. If noneloquent brain regions are involved, open surgical biopsy or removal of only abnormal tissue may be undertaken successfully. A number of the early neurosurgical pioneers in the development of epilepsy surgery are credited and discussed in this article.
PMID: 37199685
ISSN: 1744-5213
CID: 5508092
Clinical Validation of Stimulated Raman Histology for Rapid Intraoperative Diagnosis of Central Nervous System Tumors
Stimulated Raman histology (SRH) is an ex vivo optical imaging method that enables microscopic examination of fresh tissue intraoperatively. The conventional intraoperative method uses frozen section analysis, which is labor and time intensive, introduces artifacts that limit diagnostic accuracy, and consumes tissue. SRH imaging allows rapid microscopic imaging of fresh tissue, avoids tissue loss, and enables remote telepathology review. This improves access to expert neuropathology consultation in both low- and high-resource practices. We clinically validated SRH by performing a blinded, retrospective two-arm telepathology study to clinically validate SRH for telepathology at our institution. Using surgical specimens from 47 subjects, we generated a data set composed of 47 SRH images and 47 matched whole slide images (WSIs) of formalin-fixed, paraffin-embedded tissue stained with hematoxylin and eosin, with associated intraoperative clinicoradiologic information and structured diagnostic questions. We compared diagnostic concordance between WSI and SRH-rendered diagnoses. Also, we compared the 1-year median turnaround time (TAT) of intraoperative conventional neuropathology frozen sections with prospectively rendered SRH-telepathology TAT. All SRH images were of sufficient quality for diagnostic review. A review of SRH images showed high accuracy in distinguishing glial from nonglial tumors (96.5% SRH vs 98% WSIs) and predicting final diagnosis (85.9% SRH vs 93.1% WSIs). SRH-based diagnosis and WSI-permanent section diagnosis had high concordance (κ = 0.76). The median TAT for prospectively SRH-rendered diagnosis was 3.7 minutes, approximately 10-fold shorter than the median frozen section TAT (31 minutes). The SRH-imaging procedure did not affect ancillary studies. SRH generates diagnostic virtual histologic images with accuracy comparable to conventional hematoxylin and eosin-based methods in a rapid manner. Our study represents the largest and most rigorous clinical validation of SRH to date. It supports the feasibility of implementing SRH as a rapid method for intraoperative diagnosis complementary to conventional pathology laboratory methods.
PMID: 37201685
ISSN: 1530-0285
CID: 5508102
Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke
BACKGROUND AND OBJECTIVES:Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS:We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS:= 0.004). DISCUSSION:We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.
PMCID:10186236
PMID: 37015818
ISSN: 1526-632x
CID: 5507842
Spatiotemporal neural dynamics of object recognition under uncertainty in humans
While there is a wealth of knowledge about core object recognition-our ability to recognize clear, high-contrast object images-how the brain accomplishes object recognition tasks under increased uncertainty remains poorly understood. We investigated the spatiotemporal neural dynamics underlying object recognition under increased uncertainty by combining MEG and 7 Tesla (7T) fMRI in humans during a threshold-level object recognition task. We observed an early, parallel rise of recognition-related signals across ventral visual and frontoparietal regions that preceded the emergence of category-related information. Recognition-related signals in ventral visual regions were best explained by a two-state representational format whereby brain activity bifurcated for recognized and unrecognized images. By contrast, recognition-related signals in frontoparietal regions exhibited a reduced representational space for recognized images, yet with sharper category information. These results provide a spatiotemporally resolved view of neural activity supporting object recognition under uncertainty, revealing a pattern distinct from that underlying core object recognition.
PMID: 37184213
ISSN: 2050-084x
CID: 5541732
The distribution of transcallosal inhibition to upper extremity muscles is altered in chronic stroke
OBJECTIVE:To determine if the distribution of transcallosal inhibition (TI) acting on proximal and distal upper extremity muscles is altered in chronic stroke. METHODS:We examined thirteen healthy controls and sixteen mildly to moderately impaired chronic stroke patients. We used transcranial magnetic stimulation (TMS) to probe TI from the contralesional onto ipsilesional hemisphere (assigned in controls). We recorded the ipsilateral silent period in the paretic biceps (BIC) and first dorsal interosseous (FDI). We measured TI strength, distribution gradient (TI difference between muscles), and motor impairment (Fugl-Meyer Assessment). RESULTS:Both groups had stronger TI acting on their FDIs than BICs (p < 0.001). However, stroke patients also had stronger TI acting on their BICs than controls (p = 0.034), resulting in a flatter distribution of inhibition (p = 0.028). In patients, stronger FDI inhibition correlated with less hand impairment (p = 0.031); BIC inhibition was not correlated to impairment. CONCLUSION/CONCLUSIONS:TI is more evenly distributed to the paretic FDI and BIC in chronic stroke. The relative increase in proximal inhibition does not relate to better function, as it does distally. SIGNIFICANCE/CONCLUSIONS:The results expand our knowledge about segment-specific neurophysiology and its relevance to impairment after stroke.
PMID: 37224604
ISSN: 1878-5883
CID: 5503772
Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design
IMPORTANCE/UNASSIGNED:The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS/UNASSIGNED:cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE/UNASSIGNED:RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALSGOV IDENTIFIER/UNASSIGNED:Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.
PMID: 37214806
CID: 5770522
Spatial distribution and determinants of childhood vaccination refusal in the United States
Parental refusal and delay of childhood vaccination has increased in recent years in the United States. This phenomenon challenges maintenance of herd immunity and increases the risk of outbreaks of vaccine-preventable diseases. We examine US county-level vaccine refusal for patients under five years of age collected during the period 2012-2015 from an administrative healthcare dataset. We model these data with a Bayesian zero-inflated negative binomial regression model to capture social and political processes that are associated with vaccine refusal, as well as factors that affect our measurement of vaccine refusal. Our work highlights fine-scale socio-demographic characteristics associated with vaccine refusal nationally, finds that spatial clustering in refusal can be explained by such factors, and has the potential to aid in the development of targeted public health strategies for optimizing vaccine uptake.
PMID: 37069031
ISSN: 1873-2518
CID: 5466032
Observational study of organisational responses of 17 US hospitals over the first year of the COVID-19 pandemic
OBJECTIVES:The COVID-19 pandemic has required significant modifications of hospital care. The objective of this study was to examine the operational approaches taken by US hospitals over time in response to the COVID-19 pandemic. DESIGN, SETTING AND PARTICIPANTS:This was a prospective observational study of 17 geographically diverse US hospitals from February 2020 to February 2021. OUTCOMES AND ANALYSIS:We identified 42 potential pandemic-related strategies and obtained week-to-week data about their use. We calculated descriptive statistics for use of each strategy and plotted percent uptake and weeks used. We assessed the relationship between strategy use and hospital type, geographic region and phase of the pandemic using generalised estimating equations (GEEs), adjusting for weekly county case counts. RESULTS:We found heterogeneity in strategy uptake over time, some of which was associated with geographic region and phase of pandemic. We identified a body of strategies that were both commonly used and sustained over time, for example, limiting staff in COVID-19 rooms and increasing telehealth capacity, as well as those that were rarely used and/or not sustained, for example, increasing hospital bed capacity. CONCLUSIONS:Hospital strategies during the COVID-19 pandemic varied in resource intensity, uptake and duration of use. Such information may be valuable to health systems during the ongoing pandemic and future ones.
PMID: 37156578
ISSN: 2044-6055
CID: 5503282
