Publications by authors named "Jennifer Frontera"

119 Publications

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Crit Care Med 2021 Apr 21. Epub 2021 Apr 21.

Department of Neurology, NYU Gross man School of Medicine, New York, NY.

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http://dx.doi.org/10.1097/CCM.0000000000005084DOI Listing
April 2021

Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States.

PLoS One 2021 14;16(4):e0248728. Epub 2021 Apr 14.

Department of Neurology, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, United States of America.

Objective: To examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort.

Methods: We performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020-patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes.

Results: There were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44-0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge.

Conclusions: Patients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248728PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046225PMC
May 2021

Neurologic aspects of coronavirus disease of 2019 infection.

Curr Opin Infect Dis 2021 06;34(3):217-227

Department of Neurology, NYU School of Medicine, New York, New York, USA.

Purpose Of Review: Central and peripheral nervous system manifestations of coronavirus disease 2019 (COVID-19) have been frequently reported and may cause significant morbidity and mortality. This review details the latest evidence on the neuropathogenesis and neurologic complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Recent Findings: Commonly reported neurologic complications include toxic-metabolic encephalopathy, acute cerebrovascular disorders, seizures, and anoxic-brain injury. These complications represent secondary injury due to COVID-19 related hypoxia, sepsis, hypercoagulability, or hyperinflammation. Postinfectious complications, such as encephalitis, postinfectious demyelination, and Guillain-Barré syndrome have been reported, but are rare. Recent reports of persistent neurocognitive symptoms highlight the possibility of lasting impairment.

Summary: Although some neurologic complications should be treated with standard practices, further investigations are still needed to determine the optimal treatment of COVID-related neurologic complications, such as ischemic stroke. Entering into the next phase of the pandemic, investigations into the long-term neurologic and cognitive impacts of SARS-CoV-2 infection will be needed. Clinicians must have a high clinical suspicion for both acute and chronic neurologic complications among COVID-19 patients.
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http://dx.doi.org/10.1097/QCO.0000000000000731DOI Listing
June 2021

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19.

Neurocrit Care 2021 Mar 16. Epub 2021 Mar 16.

Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA.

Background: Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients.

Methods: We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission.

Results: Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001).

Conclusions: TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
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http://dx.doi.org/10.1007/s12028-021-01220-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962078PMC
March 2021

Decompressive Hemicraniectomy for Large Hemispheric Strokes.

Stroke 2021 Apr 15;52(4):1500-1510. Epub 2021 Mar 15.

Division of Neurocritical Care, Department of Neurology, New York University Langone Health (J.L., J.A.F.), New York, NY.

Large hemispheric infarcts occur in up to 10% of all ischemic strokes and can cause devastating disability. Significant research and clinical efforts have been made in hopes of mitigating the morbidity and mortality of this disease. Areas of interest include identifying predictors of malignant edema, optimizing medical and surgical techniques, selecting the patient population that would benefit most from decompressive hemicraniectomy, and studying the impact on quality of life of those who survive. Decompressive surgery can be a life-saving measure, and here we discuss the most up-to-date literature and provide a review on the surgical management of large hemispheric ischemic strokes.
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http://dx.doi.org/10.1161/STROKEAHA.120.032359DOI Listing
April 2021

Pearls and Oy-sters: Eyes Open Coma.

Neurology 2021 Feb 16. Epub 2021 Feb 16.

Department of Neurology, NYU Grossman School of Medicine, New York, NY, USA.

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http://dx.doi.org/10.1212/WNL.0000000000011715DOI Listing
February 2021

Cerebrospinal fluid in COVID-19: A systematic review of the literature.

J Neurol Sci 2021 02 10;421:117316. Epub 2021 Jan 10.

Department of Neurology, NYU Langone Medical Center, New York, NY 10016, USA; Department of Neurosurgery, NYU Langone Medical Center, New York, NY 10016, USA.

Objective: We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2.

Methods: We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom.

Results: We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 304 patients whose CSF was tested for SARS-CoV-2 PCR, there were 17 (6%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (13/17, 76%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 77 patients tested for autoimmune antibodies in the CSF, 4 (5%) had positive findings.

Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS- CoV-2 are unlikely to be related to direct viral neuroinvasion.
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http://dx.doi.org/10.1016/j.jns.2021.117316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833669PMC
February 2021

The National Institutes of Health COVID-19 NeuroDatabank and NeuroBiobank: A National Resource for Learning, Discovery, and Progress.

Front Neurol 2020 15;11:615061. Epub 2021 Jan 15.

Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United States.

Patients suffering from COVID-19 experience a wide range of symptoms and sequelae, including increasingly recognized neurological problems. A concerted effort is necessary to identify and characterize these issues, whether newly appearing as a result of COVID-19 disease or exacerbations of underlying conditions. A national resource to collect information and/or biospecimens regarding neurological complications of COVID-19 offers an opportunity for broad representation, harmonization, and rapid learning, all while ensuring robust protection of confidential information through the use of global unique identifiers to protect patient privacy.
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http://dx.doi.org/10.3389/fneur.2020.615061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843568PMC
January 2021

SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients.

Front Neurol 2020 11;11:587384. Epub 2020 Dec 11.

NYU Grossman School of Medicine and NYU Langone Health, New York, NY, United States.

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.
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http://dx.doi.org/10.3389/fneur.2020.587384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759491PMC
December 2020

Impact of COVID-19 on Outcomes in Ischemic Stroke Patients in the United States.

J Stroke Cerebrovasc Dis 2021 Feb 9;30(2):105535. Epub 2020 Dec 9.

Department of Neurology, University of Utah, 175 N. Medical Dr, Salt Lake City, UT 84132, United States. Electronic address:

Background: Studies have shown worse outcomes in patients with comorbid ischemic stroke (IS) and coronavirus disease 2019 (COVID-19), but have had small sample sizes.

Methods: We retrospectively identified patients in the Vizient Clinical Data Base® with IS as a discharge diagnosis. The study outcomes were in-hospital death and favorable discharge (home or acute rehabilitation). In the primary analysis, we compared IS patients with laboratory-confirmed COVID-19 (IS-COVID) discharged April 1-July 31, 2020 to pre-COVID IS patients discharged in 2019 (IS controls). In a secondary analysis, we compared a matched cohort of IS-COVID patients to patients within the IS controls who had pneumonia (IS-PNA), created with inverse-probability-weighting (IPW).

Results: In the primary analysis, we included 166,586 IS controls and 2086 IS-COVID from 312 hospitals in 46 states. Compared to IS controls, IS-COVID were less likely to have hypertension, dyslipidemia, or be smokers, but more likely to be male, younger, have diabetes, obesity, acute renal failure, acute coronary syndrome, venous thromboembolism, intubation, and comorbid intracerebral or subarachnoid hemorrhage (all p<0.05). Black and Hispanic patients accounted for 21.7% and 7.4% of IS controls, respectively, but 33.7% and 18.5% of IS-COVID (p<0.001). IS-COVID, versus IS controls, were less likely to receive alteplase (1.8% vs 5.6%, p<0.001), mechanical thrombectomy (4.4% vs. 6.7%, p<0.001), to have favorable discharge (33.9% vs. 66.4%, p<0.001), but more likely to die (30.4% vs. 6.5%, p<0.001). In the matched cohort of patients with IS-COVID and IS-PNA, IS-COVID had a higher risk of death (IPW-weighted OR 1.56, 95% CI 1.33-1.82) and lower odds of favorable discharge (IPW-weighted OR 0.63, 95% CI 0.54-0.73).

Conclusions: Ischemic stroke patients with COVID-19 are more likely to be male, younger, and Black or Hispanic, with significant increases in morbidity and mortality compared to both ischemic stroke controls from 2019 and to patients with ischemic stroke and pneumonia.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832426PMC
February 2021

Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study.

Res Sq 2020 Oct 26. Epub 2020 Oct 26.

Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.
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http://dx.doi.org/10.21203/rs.3.rs-94509/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605567PMC
October 2020

A Prospective Study of Neurologic Disorders in Hospitalized Patients With COVID-19 in New York City.

Neurology 2021 01 5;96(4):e575-e586. Epub 2020 Oct 5.

From the New York University Grossman School of Medicine (J.A.F., S.S., R.L., T.F., B.F., P.M.-V., T.S., S.B., D.Y., A.G., N.M., P.P., J.G., K.M., S.A., M.B., A.A., E.V., M.O., A.K., K.L., Daniel Friedman, David Friedman, M.H., J.H., S.T., J.H., N.A.-F., P.K., A.L., A.S.L., T.Z., D.E.K., B.M.C., J.T., S.Y., K.I., E.S., D.P., M.L., T.W., A.B.T., L.B., S.G.), New YorkUniversity of Pittsburgh School of Medicine (S.H.-Y.C., E.L.F.), PAThe Ohio State University (M.M., S.M.), ColumbusMedical University of Innsbruck (R.H.), AustriaThe Johns Hopkins University School of Medicine (C.R., J.I.S., W.Z.), Baltimore, MDUniversity of Utah School of Medicine (M.S., A.d.H.), Salt Lake CityUniversity of Cambridge (D.M.), UK.

Objective: To determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients and recorded new neurologic disorders and hospital outcomes.

Methods: We conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.

Results: Of 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17-1.62, < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, < 0.001).

Conclusions: Neurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.
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http://dx.doi.org/10.1212/WNL.0000000000010979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905791PMC
January 2021

Endovascular thrombectomy in acute ischemic stroke patients with COVID-19: prevalence, demographics, and outcomes.

J Neurointerv Surg 2020 Nov 28;12(11):1045-1048. Epub 2020 Sep 28.

Washington University School of Medicine in St Louis, St Louis, Missouri, USA.

Background: We aimed to compare the outcome of acute ischemic stroke (AIS) patients who received endovascular thrombectomy (EVT) with confirmed COVID-19 to those without.

Methods: We performed a retrospective analysis using the Vizient Clinical Data Base and included hospital discharges from April 1 to July 31 2020 with ICD-10 codes for AIS and EVT. The primary outcome was in-hospital death and the secondary outcome was favorable discharge, defined as discharge home or to acute rehabilitation. We compared patients with laboratory-confirmed COVID-19 to those without. As a sensitivity analysis, we compared COVID-19 AIS patients who did not undergo EVT to those who did, to balance potential adverse events inherent to COVID-19 infection.

Results: We identified 3165 AIS patients who received EVT during April to July 2020, in which COVID-19 was confirmed in 104 (3.3%). Comorbid COVID-19 infection was associated with younger age, male sex, diabetes, black race, Hispanic ethnicity, intubation, acute coronary syndrome, acute renal failure, and longer hospital and intensive care unit length of stay. The rate of in-hospital death was 12.4% without COVID-19 vs 29.8% with COVID-19 (P<0.001). In mixed-effects logistic regression that accounted for patient clustering by hospital, comorbid COVID-19 increased the odds of in-hospital death over four-fold (OR 4.48, 95% CI 3.02 to 6.165). Comorbid COVID-19 was also associated with lower odds of a favorable discharge (OR 0.43, 95% CI 0.30 to 0.61). In the sensitivity analysis, comparing AIS patients with COVID-19 who did not undergo EVT (n=2139) to the AIS EVT patients with COVID-19, there was no difference in the rate of in-hospital death (30.6% vs 29.8%, P=0.868), and AIS EVT patients had a higher rate of favorable discharge (32.4% vs 47.1%, P=0.002).

Conclusion: In AIS patients treated with EVT, comorbid COVID-19 infection was associated with in-hospital death and a lower odds of favorable discharge compared with patients without COVID-19, but not compared with AIS patients with COVID-19 who did not undergo EVT. AIS EVT patients with COVID-19 were younger, more likely to be male, have systemic complications, and almost twice as likely to be black and over three times as likely to be Hispanic.
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http://dx.doi.org/10.1136/neurintsurg-2020-016777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523171PMC
November 2020

Risk factors for intracerebral hemorrhage in patients with COVID-19.

J Thromb Thrombolysis 2021 May 24;51(4):953-960. Epub 2020 Sep 24.

Department of Neurology, New York University Langone Health, New York, NY, USA.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.
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http://dx.doi.org/10.1007/s11239-020-02288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511245PMC
May 2021

The Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Development of Case Report Forms for Global Use.

Neurocrit Care 2020 12 18;33(3):793-828. Epub 2020 Sep 18.

Departments of Critical Care Medicine, Neurology, and Neurosurgery, University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, Pittsburgh, PA, USA.

Since its original report in January 2020, the coronavirus disease 2019 (COVID-19) due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly become one of the deadliest global pandemics. Early reports indicate possible neurological manifestations associated with COVID-19, with symptoms ranging from mild to severe, highly variable prevalence rates, and uncertainty regarding causal or coincidental occurrence of symptoms. As neurological involvement of any systemic disease is frequently associated with adverse effects on morbidity and mortality, obtaining accurate and consistent global data on the extent to which COVID-19 may impact the nervous system is urgently needed. To address this need, investigators from the Neurocritical Care Society launched the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID). The GCS-NeuroCOVID consortium rapidly implemented a Tier 1, pragmatic study to establish phenotypes and prevalence of neurological manifestations of COVID-19. A key component of this global collaboration is development and application of common data elements (CDEs) and definitions to facilitate rigorous and systematic data collection across resource settings. Integration of these elements is critical to reduce heterogeneity of data and allow for future high-quality meta-analyses. The GCS-NeuroCOVID consortium specifically designed these elements to be feasible for clinician investigators during a global pandemic when healthcare systems are likely overwhelmed and resources for research may be limited. Elements include pediatric components and translated versions to facilitate collaboration and data capture in Latin America, one of the epicenters of this global outbreak. In this manuscript, we share the specific data elements, definitions, and rationale for the adult and pediatric CDEs for Tier 1 of the GCS-NeuroCOVID consortium, as well as the translated versions adapted for use in Latin America. Global efforts are underway to further harmonize CDEs with other large consortia studying neurological and general aspects of COVID-19 infections. Ultimately, the GCS-NeuroCOVID consortium network provides a critical infrastructure to systematically capture data in current and future unanticipated disasters and disease outbreaks.
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http://dx.doi.org/10.1007/s12028-020-01100-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500499PMC
December 2020

Association of race and ethnicity to incident epilepsy, or epileptogenesis, after subdural hematoma.

Neurology 2020 11 9;95(21):e2890-e2899. Epub 2020 Sep 9.

From the Division of Neurocritical Care and Emergency Neurology (S.C.B., L.K., E.J.G., J.A.K., G.J.F., K.N.S.), Department of Neurology, and Department of Neurosurgery (S.B.O.), Yale School of Medicine, New Haven, CT; David Geffen School of Medicine at UCLA (Z.A.K.), Los Angeles, CA; Department of Neurology (H.K., S.M.), Weill Cornell Medicine; and Department of Neurology (J.A.F.), New York University School of Medicine, New York.

Objective: To determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy.

Methods: We performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy.

Results: We identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28-1.64, < 0.001). Status epilepticus during the index SDH admission, although infrequent (n = 94 [0.3%]), was associated with a nearly 4-fold risk of epilepsy (HR 3.75, 95% CI 2.80-5.03, < 0.001). Alcohol use, drug use, smoking, renal disease, and markers of injury severity (i.e., intubation, surgical intervention, length of stay, disposition other than home) were also associated with epilepsy (all < 0.05).

Conclusions: We found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.
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http://dx.doi.org/10.1212/WNL.0000000000010742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734738PMC
November 2020

Keeping the team together: Transformation of an inpatient neurology service at an urban, multi-ethnic, safety net hospital in New York City during COVID-19.

Clin Neurol Neurosurg 2020 10 17;197:106156. Epub 2020 Aug 17.

Division of Neurology, NYU Langone Hospital-Brooklyn, Brooklyn, NY, United States; NYU Grossman School of Medicine, NY, NY United States.

The COVID-19 pandemic dramatically affected the operations of New York City hospitals during March and April of 2020. This article describes the transformation of a neurology division at a 450-bed tertiary care hospital in a multi-ethnic community in Brooklyn during this initial wave of COVID-19. In lieu of a mass redeployment of staff to internal medicine teams, we report a novel method for a neurology division to participate in a hospital's expansion of care for patients with COVID-19 while maintaining existing team structures and their inherent supervisory and interpersonal support mechanisms.
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http://dx.doi.org/10.1016/j.clineuro.2020.106156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430288PMC
October 2020

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System.

Neurocrit Care 2020 Aug 24. Epub 2020 Aug 24.

Department of Neurology, NYU Langone Medical Center, New York, NY, 10016, USA.

Background And Purpose: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19.

Methods: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method.

Results: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results.

Conclusion: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.
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http://dx.doi.org/10.1007/s12028-020-01077-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444897PMC
August 2020

Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City.

Crit Care Med 2020 12;48(12):e1211-e1217

Department of Medicine, NYU Grossman School of Medicine, New York, NY.

Objectives: Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients.

Design: Retrospective, multicenter, observational cohort study.

Setting: Four New York City hospitals that are part of the same health network.

Patients: Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020.

Interventions: None.

Measurements And Main Results: Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017).

Conclusions: Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.
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http://dx.doi.org/10.1097/CCM.0000000000004605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467047PMC
December 2020

Acute stroke care in a New York City comprehensive stroke center during the COVID-19 pandemic.

J Stroke Cerebrovasc Dis 2020 Sep 20;29(9):105068. Epub 2020 Jun 20.

Department of Neurology, New York Langone Health, New York, NY, United States. Electronic address:

Background And Purpose: The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS).

Methods: We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020).

Results: A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p = 0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 - 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305900PMC
September 2020

Special considerations in the assessment of catastrophic brain injury and determination of brain death in patients with SARS-CoV-2.

J Neurol Sci 2020 10 8;417:117087. Epub 2020 Aug 8.

NYU Langone Medical Center, Department of Neurology, New York, NY 10016, United States of America; NYU Langone Medical Center, Department of Neurosurgery, New York, NY 10016, United States of America.

Introduction: The coronavirus disease 2019 (Covid-19) pandemic has led to challenges in provision of care, clinical assessment and communication with families. The unique considerations associated with evaluation of catastrophic brain injury and death by neurologic criteria in patients with Covid-19 infection have not been examined.

Methods: We describe the evaluation of six patients hospitalized at a health network in New York City in April 2020 who had Covid-19, were comatose and had absent brainstem reflexes.

Results: Four males and two females with a median age of 58.5 (IQR 47-68) were evaluated for catastrophic brain injury due to stroke and/or global anoxic injury at a median of 14 days (IQR 13-18) after admission for acute respiratory failure due to Covid-19. All patients had hypotension requiring vasopressors and had been treated with sedative/narcotic drips for ventilator dyssynchrony. Among these patients, 5 had received paralytics. Apnea testing was performed for 1 patient due to the decision to withdraw treatment (n = 2), concern for inability to tolerate testing (n = 2) and observation of spontaneous respirations (n = 1). The apnea test was aborted due to hypoxia and hypotension. After ancillary testing, death was declared in three patients based on neurologic criteria and in three patients based on cardiopulmonary criteria (after withdrawal of support (n = 2) or cardiopulmonary arrest (n = 1)). A family member was able to visit 5/6 patients prior to cardiopulmonary arrest/discontinuation of organ support.

Conclusion: It is feasible to evaluate patients with catastrophic brain injury and declare brain death despite the Covid-19 pandemic, but this requires unique considerations.
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http://dx.doi.org/10.1016/j.jns.2020.117087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414304PMC
October 2020

Pearls & Oy-sters: Leukoencephalopathy in critically ill patients with COVID-19.

Neurology 2020 10 11;95(16):753-757. Epub 2020 Aug 11.

From the Departments of Neurology (H.H., H.E., M.C., E.V., I.K., L.K., H.W., S.G., J.F., T.Z., D.E.K., A. Lord, A. Lewis) and Neurosurgery (J.F., T.Z., D.E.K., A. Lord, A. Lewis), NYU Langone Medical Center, New York, NY.

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http://dx.doi.org/10.1212/WNL.0000000000010636DOI Listing
October 2020

Protocolized Urine Sampling is Associated with Reduced Catheter-Associated Urinary Tract Infections: A Pre- and Post-intervention Study.

Clin Infect Dis 2020 Aug 10. Epub 2020 Aug 10.

Department of Medicine, NYU School of Medicine, New York, NY.

Background: Standard urine sampling and testing techniques do not mitigate against detection of colonization, resulting in false positive catheter-associated urinary tract infections (CAUTI). We aim to evaluate if a novel protocol for urine sampling and testing reduces rates of CAUTI.

Methods: A pre-intervention and post-intervention study with a contemporaneous control group was conducted at two campuses (test and control) of the same academic medical center. The test campus implemented a protocol requiring urinary catheter removal prior to urine sampling from a new catheter or sterile straight catheterization, along with urine bacteria and pyuria screening prior to culture. Primary outcomes were test campus CAUTI rates compared between each 9-month pre- and post-intervention epoch. Secondary outcomes included the percent reductions in CAUTI rates compared between the test campus and a propensity-score matched cohort at the control campus.

Results:   A total of 7,991 patients from the test campus were included in the primary analysis, and 4,264 were included in the propensity-score matched secondary analysis. In primary analysis, CAUTI/1000-patients was reduced by 77% (6.6 to 1.5), CAUTI/1000-catheter days by 63% (5.9 to 2.2) and urinary catheter days/patient by 37% (1.1 to 0.69, all P≤0.001). In propensity score-matched analysis, CAUTI/1000-patients was reduced by 82% at the test campus versus 57% at the control campus, CAUTI/1000 catheter-days declined by 68% versus 57% and catheter-days/patient decreased by 44% versus 1% (all P<0.001).

Conclusions:  Protocolized urine sampling and testing aimed at minimizing contamination by colonization was associated with significantly reduced CAUTI infection rates and urinary catheter days.
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http://dx.doi.org/10.1093/cid/ciaa1152DOI Listing
August 2020

Stroke Treatment Delay Limits Outcome After Mechanical Thrombectomy: Stratification by Arrival Time and ASPECTS.

J Neuroimaging 2020 09 27;30(5):625-630. Epub 2020 Jun 27.

Department of Neurology, New York Langone Medical Center, New York, NY.

Background And Purpose: Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time-to-treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)-to-puncture time and good functional outcome.

Methods: We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN-to-puncture time and favorable outcome defined as Modified Rankin Score 0-2 on discharge.

Results: Among 421 patients, 328 were included in analysis. Increased LKN-to-puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15-minute delay = .98; 95% confidence interval [CI], .97-.99; P = .001). This was especially true when LKN-puncture time was 0-6 hours (aOR per 15-minute delay = .94; 95% CI, .89-.99; P = .05) or ASPECTS 8-10 (aOR = .98; 95% CI, .97-.99; P = .002) as opposed to when LKN-puncture time was 6-24 hours (aOR per 15-minute delay = .99; 95% CI, .97-1.00; P = .16) and ASPECTS <8 (aOR = .98; 95% CI, .93-1.03; P = .37).

Conclusion: Decreased LKN-groin puncture time improves outcome particularly in those with good ASPECTS presenting within 6 hours. Strategies to decrease reperfusion times should be investigated, particularly in those in the early time window and with good ASPECTS.
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http://dx.doi.org/10.1111/jon.12729DOI Listing
September 2020