Faculty Bibliography
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school:SOM
Department/Unit:Neurology
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23384
Sudden unexpected death in epilepsy
PURPOSE OF REVIEW/OBJECTIVE:Sudden unexpected death in epilepsy (SUDEP) is a major contributor to premature mortality in people with epilepsy. This review provides an update on recent findings on the epidemiology of SUDEP, clinical risk factors and potential mechanisms. RECENT FINDINGS/RESULTS:The overall risk rate of SUDEP is approximately 1 per 1000 patients per year in the general epilepsy population and that children and older adults have a similar incidence. Generalized convulsive seizures (GCS), perhaps through their effects on brainstem cardiopulmonary networks, can cause significant postictal respiratory and autonomic dysfunction though other mechanisms likely exist as well. Work in animal models of SUDEP has identified multiple neurotransmitter systems, which may be future targets for pharmacological intervention. There are also chronic functional and structural changes in autonomic function in patients who subsequently die from SUDEP suggesting that some SUDEP risk is dynamic. Modifiable risks for SUDEP include GCS seizure frequency, medication adherence and nighttime supervision. SUMMARY/CONCLUSIONS:Current knowledge of SUDEP risk factors has identified multiple targets for SUDEP prevention today as we await more specific therapeutic targets that are emerging from translational research studies.
PMID: 35102124
ISSN: 1473-6551
CID: 5182232
Perceptions Regarding the SARS-CoV-2 Pandemic's Impact on Neurocritical Care Delivery: Results From a Global Survey
BACKGROUND:The SARS-CoV-2 (COVID-19) pandemic has impacted many facets of critical care delivery. METHODS:An electronic survey was distributed to explore the pandemic's perceived impact on neurocritical care delivery between June 2020 and March 2021. Variables were stratified by World Bank country income level, presence of a dedicated neurocritical care unit (NCCU) and experiencing a COVID-19 patient surge. RESULTS:Respondents from 253 hospitals (78.3% response rate) from 47 countries (45.5% low/middle income countries; 54.5% with a dedicated NCCU; 78.6% experienced a first surge) participated in the study. Independent of country income level, NCCU and surge status, participants reported reductions in NCCU admissions (67%), critical care drug shortages (69%), reduction in ancillary services (43%) and routine diagnostic testing (61%), and temporary cancellation of didactic teaching (44%) and clinical/basic science research (70%). Respondents from low/middle income countries were more likely to report lack of surge preparedness (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8) and struggling to return to prepandemic standards of care (OR, 12.2; 95% CI, 4.4-34) compared with respondents from high-income countries. Respondents experiencing a surge were more likely to report conversion of NCCUs and general-mixed intensive care units (ICUs) to a COVID-ICU (OR 3.7; 95% CI, 1.9-7.3), conversion of non-ICU beds to ICU\ beds (OR, 3.4; 95% CI, 1.8-6.5), and deviations in critical care and pharmaceutical practices (OR, 4.2; 95% CI 2.1-8.2). Respondents from hospitals with a dedicated NCCU were less likely to report conversion to a COVID-ICU (OR, 0.5; 95% CI, 0.3-0.9) or conversion of non-ICU to ICU beds (OR, 0.5; 95% CI, 0.3-0.9). CONCLUSION/CONCLUSIONS:This study reports the perceived impact of the COVID-19 pandemic on global neurocritical care delivery, and highlights shortcomings of health care infrastructures and the importance of pandemic preparedness.
PMID: 34882104
ISSN: 1537-1921
CID: 5326642
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
Interaction Between Cerebellum and Cerebral Cortex, Evidence from Dynamic Causal Modeling
The interaction of the cerebellum with cerebral cortical dynamics is still poorly understood. In this paper, dynamical causal modeling is used to examine the interaction between cerebellum and cerebral cortex as indexed by MRI resting-state functional connectivity in three large-scale networks on healthy young adults (N = 200; Human Connectome Project dataset). These networks correspond roughly to default mode, task positive, and motor as determined by prior cerebellar functional gradient analyses. We find uniform interactions within all considered networks from cerebellum to cerebral cortex, providing support for the notion of a universal cerebellar transform. Our results provide a foundation for future analyses to quantify and further investigate whether this is a property that is unique to the interactions from cerebellum to cerebral cortex.
PMID: 34146220
ISSN: 1473-4230
CID: 5454372
The Uniform Determination of Death Act is Being Revised
The Uniform Determination of Death Act (UDDA), the recommended legal statute for determination of death in the United States, was initially formulated in 1981. Forty years later, because of the concerns of experts in medicine, law, ethics, and philosophy, the Uniform Law Commission (ULC) created a drafting committee to update the UDDA. The drafting committee, which has until 2023 to propose revisions to the ULC Executive Committee, will need to determine how to address the following key questions about the UDDA: (1) Should the term "irreversible" be replaced by the term "permanent"? (2) Is absence of hypothalamic-pituitary-axis-induced antidiuretic hormone secretion included in "all functions of the entire brain," and if so, how can we reconcile the fact that this is not tested in the medical standards for determination of death by neurologic criteria published by the American Academy of Neurology and the Society of Critical Care Medicine, American Academy of Pediatrics, and Child Neurology Society? (3) What are the accepted medical standards for determination of death? (4) Is consent needed to determine death? and (5) How should objections to the use of neurologic criteria to declare death be handled? Once the ULC finalizes revisions to the UDDA, individual states will have the opportunity to decide whether to adopt the revisions in whole or in part. Hopefully, the revised UDDA will provide clarity and consistency about the legal distinction between life and death for physicians, lawyers, and the public at large. The events that led to the formation of the drafting committee and the potential consequences of revising the UDDA are discussed herein.
PMID: 35102538
ISSN: 1556-0961
CID: 5153472
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
The ConTraSt database for analysing and comparing empirical studies of consciousness theories
Understanding how consciousness arises from neural activity remains one of the biggest challenges for neuroscience. Numerous theories have been proposed in recent years, each gaining independent empirical support. Currently, there is no comprehensive, quantitative and theory-neutral overview of the field that enables an evaluation of how theoretical frameworks interact with empirical research. We provide a bird's eye view of studies that interpreted their findings in light of at least one of four leading neuroscientific theories of consciousness (N = 412 experiments), asking how methodological choices of the researchers might affect the final conclusions. We found that supporting a specific theory can be predicted solely from methodological choices, irrespective of findings. Furthermore, most studies interpret their findings post hoc, rather than a priori testing critical predictions of the theories. Our results highlight challenges for the field and provide researchers with an open-access website ( https://ContrastDB.tau.ac.il ) to further analyse trends in the neuroscience of consciousness.
PMID: 35190711
ISSN: 2397-3374
CID: 5175042
A Known-Groups Validation of the Medical Symptom Validity Test and Analysis of the Genuine Memory Impairment Profile
This study cross-validated the Medical Symptom Validity Test (MSVT) in a mixed neuropsychiatric sample and examined its accuracy for identifying invalid neuropsychological performance using a known-groups design. Cross-sectional data from 129 clinical patients who completed the MSVT were examined. Validity groups were established using six, independent criterion performance validity tests, which yielded 98 patients in the valid group and 31 in the invalid group. All MSVT subtest scores were significantly lower in the invalid group (η
PMID: 33371720
ISSN: 1552-3489
CID: 5592772
Visually sensitive seizures: An updated review by the Epilepsy Foundation
Light flashes, patterns, or color changes can provoke seizures in up to 1 in 4000 persons. Prevalence may be higher because of selection bias. The Epilepsy Foundation reviewed light-induced seizures in 2005. Since then, images on social media, virtual reality, three-dimensional (3D) movies, and the Internet have proliferated. Hundreds of studies have explored the mechanisms and presentations of photosensitive seizures, justifying an updated review. This literature summary derives from a nonsystematic literature review via PubMed using the terms "photosensitive" and "epilepsy." The photoparoxysmal response (PPR) is an electroencephalography (EEG) phenomenon, and photosensitive seizures (PS) are seizures provoked by visual stimulation. Photosensitivity is more common in the young and in specific forms of generalized epilepsy. PS can coexist with spontaneous seizures. PS are hereditable and linked to recently identified genes. Brain imaging usually is normal, but special studies imaging white matter tracts demonstrate abnormal connectivity. Occipital cortex and connected regions are hyperexcitable in subjects with light-provoked seizures. Mechanisms remain unclear. Video games, social media clips, occasional movies, and natural stimuli can provoke PS. Virtual reality and 3D images so far appear benign unless they contain specific provocative content, for example, flashes. Images with flashes brighter than 20 candelas/m2 at 3-60 (particularly 15-20) Hz occupying at least 10 to 25% of the visual field are a risk, as are red color flashes or oscillating stripes. Equipment to assay for these characteristics is probably underutilized. Prevention of seizures includes avoiding provocative stimuli, covering one eye, wearing dark glasses, sitting at least two meters from screens, reducing contrast, and taking certain antiseizure drugs. Measurement of PPR suppression in a photosensitivity model can screen putative antiseizure drugs. Some countries regulate media to reduce risk. Visually-induced seizures remain significant public health hazards so they warrant ongoing scientific and regulatory efforts and public education.
PMID: 35132632
ISSN: 1528-1167
CID: 5167142
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
