Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
Total Results:
22914
EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults
The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.
PMCID:8972311
PMID: 34724065
ISSN: 1523-5866
CID: 5219272
Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer
Resistance to targeted therapies is an important clinical problem in HER2-positive (HER2+) breast cancer. "Drug-tolerant persisters" (DTPs), a sub-population of cancer cells that survive via reversible, non-genetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKIs) in other malignancies, but DTPs following HER2 TKI exposure have not been well characterized. We found that HER2 TKIs evoke DTPs with a luminal-like or a mesenchymal-like transcriptome. Lentiviral barcoding/single cell RNA-sequencing reveal that HER2+ breast cancer cells cycle stochastically through a "pre-DTP" state, characterized by a G0-like expression signature and enriched for diapause and/or senescence genes. Trajectory analysis/cell sorting show that pre-DTPs preferentially yield DTPs upon HER2 TKI exposure. Cells with similar transcriptomes are present in HER2+ breast tumors and are associated with poor TKI response. Finally, biochemical experiments indicate that luminal-like DTPs survive via estrogen receptor-dependent induction of SGK3, leading to rewiring of the PI3K/AKT/mTORC1 pathway to enable AKT-independent mTORC1 activation.
PMID: 34911733
ISSN: 2159-8290
CID: 5085072
Practical guidance for telemedicine use in neuro-oncology
While the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations.
PMCID:8965064
PMID: 35371525
ISSN: 2054-2577
CID: 5219512
Feigning or forgetfulness: The effect of memory impairment severity on word choice test performance
OBJECTIVE:This study cross-validated the word choice test (WCT) in a diverse neuropsychiatric sample and examined the effect of increasing verbal memory impairment severity on WCT performance. METHOD/METHODS:Data from 147 clinically referred patients (113 valid/34 invalid) who completed the WCT, Rey Auditory Verbal Learning Test (RAVLT), and four independent criterion PVTs were analyzed. RAVLT memory impairment bands used were: ≥37T (normal memory); 30T-36T (below average scores/mild impairment); and ≤29T (extremely low scores/severe impairment). RESULTS:WCT and RAVLT were moderately correlated. The invalid group had significantly worse performance on the WCT and RAVLT. For the overall sample, the WCT yielded an area under the curve (AUC) = .79, with 62% sensitivity/93% specificity at a cut-score of ≤41. When the sample was subdivided by memory impairment severity, the severe impairment group had significantly lower WCT scores than the normal group. Moreover, the WCT retained moderate classification accuracy among the normal memory (AUC = .85) and mild memory impairment (AUC = .76) groups, with sensitivities of 65% and 62% (≥91% specificity) at their respective optimal cut-scores of ≤44 and ≤42. In contrast, the WCT had low classification accuracy among those with severe memory impairment (AUC = .66), with only 15% sensitivity/95% specificity at the optimal cut-score of ≤30. CONCLUSION/CONCLUSIONS:The WCT is generally useful for detecting invalid neuropsychological test performance, although, its classification accuracy was diminished among patients with severe memory impairment. Therefore, while the WCT remains a viable option for performance validity assessment, neuropsychologists should carefully consider its use when this level of severe memory impairment is known or suspected.
PMID: 32723147
ISSN: 1744-4144
CID: 5592512
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
PMCID:9005347
PMID: 35379992
ISSN: 1546-1718
CID: 5213092
mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis
BACKGROUND:Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models. OBJECTIVE:To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants. METHODS:Randomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976). RESULTS:The trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression. CONCLUSIONS:Sirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.
PMID: 35040506
ISSN: 1531-8257
CID: 5131432
Anxiety, worry, and job satisfaction: effects of COVID-19 care on critical care anesthesiologists [Letter]
PMCID:8756752
PMID: 35025026
ISSN: 1496-8975
CID: 5118922
Comparing the Independent and Aggregated Accuracy of Trial 1 and the First 10 TOMM Items for Detecting Invalid Neuropsychological Test Performance Across Civilian and Veteran Clinical Samples
Previous studies support using two abbreviated tests of the Test of Memory Malingering (TOMM), including (a) Trial 1 (T1) and (b) the number of errors on the first 10 items of T1 (T1e10), as performance validity tests (PVTs). In this study, we examined the independent and aggregated predictive utility of TOMM T1 and T1e10 for identifying invalid neuropsychological test performance across two clinical samples. We employed cross-sectional research to examine two independent and demographically diverse mixed samples of military veterans and civilians (VA = 108; academic medical center = 234) of patients who underwent neuropsychological evaluations. We determined validity groups by patient performance on four independent criterion PVTs. We established concordances between passing/failing the TOMM T1e10 and T1, followed by logistic regression to determine individual and aggregated accuracy of T1e10 and T1 for predicting validity group membership. Concordance between passing T1e10 and T1 was high, as was overall validity (87-98%) across samples. By contrast, T1e10 failure was more highly concordant with T1 failure (69-77%) than with overall invalidity status (59-60%) per criterion PVTs, whereas T1 failure was more highly concordant with invalidity status (72-88%) per criterion PVTs. Logistic regression analyses demonstrated similar results, with T1 accounting for more variance than T1e10. However, combining T1e10 and T1 accounted for the most variance of any model, with T1e10 and T1 each emerging as significant predictors. TOMM T1 and, to a lesser extent, T1e10 were significant predictors of independent criterion-derived validity status across two distinct clinical samples, but they did not offer improved classification accuracy when aggregated.
PMID: 35139315
ISSN: 1558-688x
CID: 5592972
Recurrent intracerebral hemorrhages due to central nervous system vasculitis: A neuropsychological case report [Case Report]
OBJECTIVE:Primary angiitis of the central nervous system (PACNS) is a rare and devastating form of vasculitis that destroys the vessels of the brain and spinal cord, resulting in progressive and debilitating neurologic symptoms. The objective of the present study was to detail the diagnostic process of a case of a patient with PACNS who suffered from six intracerebral hemorrhages (ICHs). METHOD/METHODS:The patient was an African American woman with a history of recurrent ICHs of unclear etiology who received serial neuropsychological evaluations over the course of a 5-year period. Two comprehensive neuropsychological evaluations are included, as well as an overview of her clinical course, including differential diagnostic considerations and treatment planning. RESULTS:Neuropsychological assessment revealed marked deficits in visuospatial abilities and processing speed associated with her underlying neuropathology. Integrated review of her medical records indicated a probable diagnosis of PACNS as the likely etiology of her recurrent ICHs. CONCLUSIONS:This study demonstrates the importance of differential diagnosis of low base-rate conditions, functional neuroanatomy and neurobehavioral phenomenology, serial assessment, and cognitive reserve in clinical neuropsychological practice.
PMID: 32715901
ISSN: 1744-4144
CID: 5592712
Acute ischaemic stroke associated with SARS-CoV-2 infection in North America
BACKGROUND:To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS:Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS:A total of 230 COVID-19 patients with AIS were included. 67.0% (154/230) were older than 60 years, while 33.0% (76/230) were younger. Median (IQR) National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.0 (17.0) and 42.8% (89/208) presented with large vessel occlusion (LVO). Approximately 50.2% (102/203) of the patients had poor outcomes with an observed mortality rate of 38.8% (35/219). Age >60 years (aOR: 4.60, 95% CI 1.89 to 12.15, p=0.001), diabetes mellitus (aOR: 2.53, 95% CI 1.14 to 5.79, p=0.025), increased NIHSS at admission (aOR: 1.10, 95% CI 1.05 to 1.16, p<0.001), LVO (aOR: 3.02, 95% CI 1.27 to 7.44, p=0.014) and no IV tPA (aOR: 2.76, 95% CI 1.06 to 7.64, p=0.043) were significantly associated with poor functional outcome. CONCLUSION/CONCLUSIONS:There may be a relationship between COVID-19 associated AIS and severe disability or death. We identified several factors that predict worse outcomes, and these outcomes were more frequent compared with global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-dimer, predicted both morbidity and mortality.
PMCID:8804309
PMID: 35078916
ISSN: 1468-330x
CID: 5154472
