Publications by authors named "Kara Melmed"

32 Publications

Cerebrospinal fluid from COVID-19 patients with olfactory/gustatory dysfunction: A review.

Clin Neurol Neurosurg 2021 Jun 12;207:106760. Epub 2021 Jun 12.

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 reviewed the literature on cerebrospinal fluid (CSF) testing in patients with altered olfactory/gustatory function due to COVID-19 for evidence of viral neuroinvasion.

Methods: We performed a systematic review of Medline and Embase to identify publications that described at least one patient with COVID-19 who had altered olfactory/gustatory function and had CSF testing performed. The search ranged from December 1, 2019 to November 18, 2020.

Results: We identified 51 publications that described 70 patients who met inclusion criteria. Of 51 patients who had CSF SARS-CoV-2 PCR testing, 3 (6%) patients had positive results and 1 (2%) patient had indeterminate results. Cycle threshold (Ct; the number of amplification cycles required for the target gene to exceed the threshold, which is inversely related to viral load) was not provided for the patients with a positive PCR. The patient with indeterminate results had a Ct of 37 initially, then no evidence of SARS-CoV-2 RNA on repeat testing. Of 6 patients who had CSF SARS-CoV-2 antibody testing, 3 (50%) were positive. Testing to distinguish intrathecal antibody synthesis from transudation of antibodies to the CSF via breakdown of the blood-brain barrier was performed in 1/3 (33%) patients; this demonstrated antibody transmission to the CSF via transudation.

Conclusion: Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare in patients with altered olfactory/gustatory function. While pathology studies are needed, our review suggests it is unlikely that these symptoms are related to viral neuroinvasion.
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http://dx.doi.org/10.1016/j.clineuro.2021.106760DOI Listing
June 2021

COVID-19 associated brain/spinal cord lesions and leptomeningeal enhancement: A meta-analysis of the relationship to CSF SARS-CoV-2.

J Neuroimaging 2021 Jun 8. Epub 2021 Jun 8.

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

Background And Purpose: We reviewed the literature to evaluate cerebrospinal fluid (CSF) results from patients with coronavirus disease 2019 (COVID-19) who had neurological symptoms and had an MRI that showed (1) central nervous system (CNS) hyperintense lesions not attributed to ischemia and/or (2) leptomeningeal enhancement. We sought to determine if these findings were associated with a positive CSF severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR).

Methods: We performed a systematic review of Medline and Embase from December 1, 2019 to November 18, 2020. CSF results were evaluated based on the presence/absence of (1) ≥ 1 CNS hyperintense lesion and (2) leptomeningeal enhancement.

Results: In 117 publications, we identified 193 patients with COVID-19 who had an MRI of the CNS and CSF testing. There were 125 (65%) patients with CNS hyperintense lesions. Patients with CNS hyperintense lesions were significantly more likely to have a positive CSF SARS-CoV-2 PCR (10% [9/87] vs. 0% [0/43], p = 0.029). Of 75 patients who had a contrast MRI, there were 20 (27%) patients who had leptomeningeal enhancement. Patients with leptomeningeal enhancement were significantly more likely to have a positive CSF SARS-CoV-2 PCR (25% [4/16] vs. 5% [2/42], p = 0.024).

Conclusion: The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID-19 is associated with increased likelihood of a positive CSF SARS-CoV-2 PCR. However, a positive CSF SARS-CoV-2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.
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http://dx.doi.org/10.1111/jon.12880DOI Listing
June 2021

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage.

J Stroke Cerebrovasc Dis 2021 May 30;30(8):105870. Epub 2021 May 30.

Department of Neurology, NYU Langone University School of Medicine, New York, New York, USA; Department of Neurosurgery, NYU Langone Medical Center, New York, New York, USA.

Objectives: Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear.

Materials And Methods: We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis.

Results: Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02).

Conclusion: SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105870DOI Listing
May 2021

Cerebrospinal fluid findings in patients with seizure in the setting of COVID-19: A review of the literature.

Seizure 2021 May 17;89:99-106. Epub 2021 May 17.

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

We reviewed the literature on cerebrospinal fluid (CSF) studies in patients who had a seizure in the setting of COVID-19 infection to evaluate for evidence of viral neuroinvasion. We performed a systematic review of Medline and Embase to identify publications that reported one or more patients with COVID-19 who had a seizure and had CSF testing preformed. The search ranged from December 1st 2019 to November 18th 2020. We identified 56 publications which described 69 unique patients who met our inclusion criteria. Of the 54 patients whose past medical history was provided, 2 (4%) had epilepsy and 1 (2%) had a prior seizure in the setting of hyperglycemia, but the remaining 51 (94%) had no history of seizures. Seizure was the initial symptom of COVID-19 for 15 (22%) patients. There were 26 (40%) patients who developed status epilepticus. SARS-CoV-2 PCR testing was performed in the CSF for 45 patients; 6 (13%) had a positive CSF SARS-CoV-2 PCR, only 1 (17%) of whom had status epilepticus. The cycle thresholds were not reported. Evaluation for CSF SARS-CoV-2 antibodies (directly or indirectly, via testing for CSF oligoclonal bands or immunoglobulins) was performed in 26 patients, only 2 (8%) of whom had evidence of intrathecal antibody synthesis. Of the 11 patients who had CSF autoimmune antibody panels tested, 1 had NMDA antibodies and 1 had Caspr-2 antibodies. Detection of SARS-CoV-2 in the CSF of patients with seizures who have COVID-19 is uncommon. Our review suggests that seizures in this patient population are not likely due to direct viral invasion of the brain.
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http://dx.doi.org/10.1016/j.seizure.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127527PMC
May 2021

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications.

J Neurol Sci 2021 Jul 12;426:117486. Epub 2021 May 12.

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

Background: Little is known regarding long-term outcomes of patients hospitalized with COVID-19.

Methods: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep.

Results: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups.

Conclusions: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.
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http://dx.doi.org/10.1016/j.jns.2021.117486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113108PMC
July 2021

Meningitis in the Setting of Frontoethmoidal and Temporal Meningoencephaloceles.

Neurohospitalist 2021 Apr 10;11(2):183-184. Epub 2020 Sep 10.

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

This is a patient with multiple meningoencephaloceles which resulted in bacterial meningitis and subsequent status epilepticus. We identify impressive imaging findings demonstrating herniation of the meninges from nasal and bitemporal skull base defects possibly as a result of intracranial hypertension.
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http://dx.doi.org/10.1177/1941874420958839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958690PMC
April 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

Increase in Ventricle Size and the Evolution of White Matter Changes on Serial Imaging in Critically Ill Patients with COVID-19.

Neurocrit Care 2021 Mar 5. Epub 2021 Mar 5.

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

Background: Evolution of brain magnetic resonance imaging (MRI) findings in critically ill patients with coronavirus disease 2019 (COVID-19) is unknown.

Methods: We retrospectively reviewed 4530 critically ill patients with COVID-19 admitted to three tertiary care hospitals in New York City from March 1 to June 30, 2020 to identify patients who had more than one brain MRI. We reviewed the initial and final MRI for each patient to (1) measure the percent change in the bicaudate index and third ventricular diameter and (2) evaluate changes in the presence and severity of white matter changes.

Results: Twenty-one patients had two MRIs separated by a median of 22 [Interquartile range (IQR) 14-30] days. Ventricle size increased for 15 patients (71%) between scans [median bicaudate index 0.16 (IQR 0.126-0.181) initially and 0.167 (IQR 0.138-0.203) on final imaging (p < 0.001); median third ventricular diameter 6.9 mm (IQR 5.4-10.3) initially and 7.2 mm (IQR 6.4-10.8) on final imaging (p < 0.001)]. Every patient had white matter changes on the initial and final MRI; between images, they worsened for seven patients (33%) and improved for three (14%).

Conclusions: On serial imaging of critically ill patients with COVID-19, ventricle size frequently increased over several weeks. White matter changes were often unchanged, but in some cases they worsened or improved, demonstrating there is likely a spectrum of pathophysiological processes responsible for these changes.
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http://dx.doi.org/10.1007/s12028-021-01207-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935478PMC
March 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

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

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

Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus.

Epilepsia 2020 10 18;61(10):e135-e139. Epub 2020 Sep 18.

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

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.
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http://dx.doi.org/10.1111/epi.16683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537028PMC
October 2020

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

Neurocrit Care 2021 06 24;34(3):748-759. 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
June 2021

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

Cerebral Microbleeds and Leukoencephalopathy in Critically Ill Patients With COVID-19.

Stroke 2020 09 5;51(9):2649-2655. Epub 2020 Aug 5.

Department of Neurology (S.A., A.L., K.M., S.G.), NYU Langone Health, New York, NY.

Background And Purpose: We conducted this study to investigate the prevalence and distribution of cerebral microbleeds and leukoencephalopathy in hospitalized patients with coronavirus disease 2019 (COVID-19) and correlate with clinical, laboratory, and functional outcomes.

Methods: We performed a retrospective chart review of 4131 COVID-19 positive adult patients who were admitted to 3 tertiary care hospitals of an academic medical center at the epicenter of the COVID-19 pandemic in New York City from March 1, 2020, to May 10, 2020, to identify patients who had magnetic resonance imaging (MRI) of the brain. We evaluated the MRIs in detail, and identified a subset of patients with leukoencephalopathy and/or cerebral microbleeds. We compared clinical, laboratory, and functional outcomes for these patients to patients who had a brain MRI that did not show these findings.

Results: Of 115 patients who had an MRI of the brain performed, 35 (30.4%) patients had leukoencephalopathy and/or cerebral microbleeds. Patients with leukoencephalopathy and/or cerebral microbleeds had neuroimaging performed later during the hospitalization course (27 versus 10.6 days; <0.001), were clinically sicker at the time of brain MRI (median GCS 6 versus 14; <0.001), and had higher peak D-dimer levels (8018±6677 versus 3183±3482; <0.001), lower nadir platelet count (116.9±62.2 versus 158.3±76.2; =0.03), higher peak international normalized ratio (2.2 versus 1.57; <0.001) values when compared with patients who had a brain MRI that did not show these findings. They required longer ventilator support (34.6 versus 9.1 days; <0.001) and were more likely to have moderate and severe acute respiratory distress syndrome score (88.6% versus 23.8%, <0.001). These patients had longer hospitalizations (42.1 versus 20.9 days; <0.001), overall worse functional status on discharge (mRS 5 versus 4; =0.001), and higher mortality (20% versus 9%; =0.144).

Conclusions: The presence of leukoencephalopathy and/or cerebral microbleeds is associated with a critical illness, increased mortality, and worse functional outcome in patients with COVID-19.
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http://dx.doi.org/10.1161/STROKEAHA.120.030940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434006PMC
September 2020

Clinical Impact of Hematoma Expansion in Left Ventricular Assist Device Patients.

World Neurosurg 2020 11 1;143:e384-e390. Epub 2020 Aug 1.

Division of Stroke and Cerebrovascular Diseases, Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.

Background: Hematoma expansion (HE) is associated with poor outcome in patients with intracerebral hemorrhage (ICH), but the impact on patients with an left ventricular assist device (LVAD) is unknown. We aimed to define the occurrence of HE in the LVAD population and to determine the association between HE and mortality.

Methods: We performed a retrospective cohort study of LVAD patients and intentionally matched anticoagulated controls without LVAD admitted to Columbia University Irving Medical Center with ICH between 2008 and 2019. We compared HE occurrence between patients with an LVAD and those without an LVAD using regression modeling, adjusting for factors known to influence HE. We evaluated pump thrombosis following anticoagulation reversal. We examined the association between HE and hospital mortality using Poisson regression modeling adjusting for factors associated with poor outcome.

Results: Among 605 patients with an LVAD, we identified 28 patients with ICH meeting the study's inclusion criteria. Our LVAD ICH cohort was predominantly male (71%), with a mean age of 56 ± 10 years. The median baseline hematoma size was 20.1 mL (interquartile range [IQR], 8.6-46.9 mL), and the median ICH score was 1 (IQR, 1-2). There was no significant difference in occurrence of HE in LVAD patients and matched non-LVAD patients (adjusted odds ratio [OR], 1.3; 95% confidence interval [CI], 0.4-4.2). There was an association between HE and in-hospital mortality in LVAD patients (adjusted OR, 4.8; 95% CI, 1.4-6.2).

Conclusions: HE occurrence appears to be similar in LVAD and non-LVAD patients. HE has a significant impact on LVAD ICH mortality, underscoring the importance of adequate coagulopathy reversal and blood pressure management in these patients.
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http://dx.doi.org/10.1016/j.wneu.2020.07.169DOI Listing
November 2020

Hemorrhagic stroke and anticoagulation in COVID-19.

J Stroke Cerebrovasc Dis 2020 Aug 23;29(8):104984. Epub 2020 May 23.

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

Background And Purpose: Patients with the Coronavirus Disease of 2019 (COVID-19) are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population.

Methods: Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications.

Results: We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37-83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small- moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery.

Conclusions: Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245254PMC
August 2020

Use and Removal of Inferior Vena Cava Filters in Patients With Acute Brain Injury.

Neurohospitalist 2020 Jul 28;10(3):188-192. Epub 2020 Feb 28.

Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute, New York, NY, USA.

Background: Few data exist regarding the rate of inferior vena cava (IVC) filter retrieval among brain-injured patients.

Methods: We conducted a retrospective cohort study using inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients aged ≥65 years who were hospitalized with acute brain injury. The primary outcome was the retrieval of IVC filter at 12 months and the secondary outcomes were the association with 30-day mortality and 12-month freedom from pulmonary embolism (PE). We used codes to ascertain filter placement and retrieval and codes to ascertain venous thromboembolism (VTE) diagnoses. We used standard descriptive statistics to calculate the crude rate of filter placement. We used Cox proportional hazards analysis to examine the association between IVC filter placement and mortality and the occurrence of PE after adjustment for demographics, comorbidities, and mechanical ventilation. We used Kaplan-Meier survival statistics to calculate cumulative rates of retrieval 12 months after filter placement.

Results: Among 44 641 Medicare beneficiaries, 1068 (2.4%; 95% confidence interval [CI], 2.3%-2.5) received an IVC filter, of whom 452 (42.3%; 95% CI, 39.3%-45.3) had a diagnosis of VTE. After adjusting for demographics, comorbidities, and mechanical ventilation, filter placement was not associated with a reduced risk of mortality (hazard ratio [HR], 1.0; 95% CI, 0.8-1.3) regardless of documented VTE. The occurrence of pulmonary embolism at 12 months was associated with IVC filter placement (HR, 3.19; 95% CI, 1.3-3.3) in the most adjusted model. The cumulative rate of filter retrieval at 12 months was 4.4% (95% CI, 3.1%-6.1%); there was no significant difference in retrieval rates between those with and without VTE.

Conclusions: In a large cohort of Medicare beneficiaries hospitalized with acute brain injury, IVC filter placement was uncommon, but once placed, very few filters were removed. IVC filter placement was not associated with a reduced risk of mortality and did not prevent future PE.
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http://dx.doi.org/10.1177/1941874420907531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271624PMC
July 2020

Respiratory and Blood Stream Infections are Associated with Subsequent Venous Thromboembolism After Primary Intracerebral Hemorrhage.

Neurocrit Care 2021 02;34(1):85-91

Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Background: Infection and venous thromboembolism (VTE) are associated with worse outcomes after intracerebral hemorrhage (ICH). The relationship between infection and VTE in ICH patients is unclear. We hypothesized that infection would be associated with subsequent VTE after ICH.

Methods: We retrospectively studied consecutively admitted spontaneous primary ICH patients from 2009 to 2018 surviving beyond 24 h. The primary predictor variable was infection, diagnosed prior to VTE. The primary outcome was VTE. We used multivariable logistic regression models to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for VTE risk after infection of any type, after adjusting for ICH score, length of stay and days to deep venous thrombosis (DVT) prophylaxis. Similar analysis was done to estimate the association of infection subtypes, including respiratory and urinary and blood stream infections (BSI) with VTE.

Results: There were 414 patients (mean age 65 years, 47% female) that met were analyzed. Infection was diagnosed in 181 (44%) patients. Incident VTE was diagnosed in 36 (9%) patients, largely comprised of DVT (n = 32; 89%). Infection overall was associated with increased risk of subsequent VTE (adjusted OR 4.5, 95% CI 1.6-12.6). Respiratory (adjusted OR 5.7, 95% CI 2.8-11.7) and BSI (adjusted OR 4.0, 95% CI 1.3-11.0) were associated with future VTE. Urinary and other infections were not associated with subsequent VTE.

Conclusions: Infections are associated with subsequent risk of VTE among patients with ICH. Further investigation is required to elucidate mechanisms behind this association and to improve VTE prevention after ICH.
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http://dx.doi.org/10.1007/s12028-020-00974-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223996PMC
February 2021

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices.

J Neuroimaging 2020 05 10;30(3):297-302. Epub 2020 Feb 10.

Department of Neurology and Comprehensive Stroke Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Background And Purpose: Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH).

Methods: From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices.

Results: We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (±SD) PI of .43 (±.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (±.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (±.24). In intra-arterial balloon pump patients, mean PI was 1.01 (±.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (±32.33) cm/seconds and PI of .74 (±.14) approached normal values.

Conclusion: TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.
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http://dx.doi.org/10.1111/jon.12694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321834PMC
May 2020

Hematoma Expansion Differences in Lobar and Deep Primary Intracerebral Hemorrhage.

Neurocrit Care 2019 08;31(1):40-45

Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Background: Hematoma expansion (HE) after intracerebral hemorrhage (ICH) is associated with worse outcome. Lobar ICHs are known to have better outcomes compared to deep ICH; however, it is unclear whether there are HE differences between these locations. We sought to investigate the hypothesis that lobar ICH has less HE compared to deep ICH.

Methods: Primary ICH patients admitted between 2009 and 2016 were included in a prospective single-center ICH cohort study. Patients with preceding anticoagulant use, coagulopathy on admission labs, or presenting after 24 h from symptom onset were excluded. Lobar and deep ICH patients with baseline and follow-up computed tomography (CT) (within 24 h of admission CT) were evaluated. HE was defined primarily as relative growth > 33% given expected baseline hematoma volume differences between locations. Other commonly utilized definitions of HE: > 6 mL, and > 33% or > 6 mL, were additionally assessed. Multivariable logistic regression was used to assess the association of ICH location with HE while adjusting for previously identified covariates of HE.

Results: There were 59 lobar and 143 deep ICH patients analyzed. Lobar ICH patients had significantly larger baseline hematoma volumes, lower admission systolic blood pressure, and longer times to admission CT compared to deep ICH. Multivariable logistic regression revealed an association of lobar ICH with lower odds of HE (> 33%) [odds ratio (OR) 0.32; 95% confidence interval (CI) 0.11-0.93; p = 0.04] compared to deep ICH after adjusting for baseline ICH volume, blood pressure, and time to CT. Secondary analysis did not identify an association of lobar ICH with HE defined as > 6 mL (adjusted OR 1.44; 95% CI 0.59-3.50; p = 0.41) or > 33% or > 6 mL (adjusted OR 0.71; 95% CI 0.29-1.70; p = 0.44).

Conclusion: We identified less HE in lobar compared to deep ICH. The use of absolute growth thresholds in defining HE may be limited when assessing groups with largely different baseline hematoma sizes. Further study is required to replicate our findings and investigate mechanisms for HE differences between lobar and deep ICH locations.
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http://dx.doi.org/10.1007/s12028-018-00668-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609462PMC
August 2019

Statins and perihemorrhagic edema in patients with spontaneous intracerebral hemorrhage.

Neurology 2019 04 6;92(18):e2145-e2149. Epub 2019 Feb 6.

From the Departments of Neurology (J.W., S.A., K.M., D.J.R., J.C., S.P.) and Neurosurgery (E.S.C.), Columbia University Medical Center, New York, NY; Department of Neurology (J.W.), Yale School of Medicine, New Haven, CT; and Departments of Neurology, Neurosurgery, and Radiology (F.A.-M.), Westchester Medical Center, New York Medical College, Valhalla.

Objective: To test the hypothesis that in patients with spontaneous intracerebral hemorrhage (ICH), perihemorrhagic edema to hematoma ratio (rPHE) on admission CT scan (aCT) is unaffected by home statin use when time from symptom onset to aCT is controlled for.

Methods: In a single-center prospective cohort of 176 consecutive ICH patients, 2 investigators independently determined hematoma and perihemorrhagic edema (PHE) volumes by using semiautomated validated software. rPHE were dichotomized at the median ratio (>0.75 vs ≤0.75). We used binary logistic regression to test for associations with rPHE.

Results: In patients using statins as home medication before hospital admission (n = 38) compared to patients without prior statin use (n = 138), median PHE volumes were 15.8 mL (interquartile range [IQR] 6.5-39.4) vs 10.8 mL (IQR 5.1-26.8), = 0.2. rPHE was 0.71 (IQR 0.56-1.0) vs 0.74 (IQR 0.52-1.0), = 0.79. In a binary logistic regression model, time of aCT relative to symptom onset (odds ratio [OR] 1.02, confidence interval [CI] 1.01-1.12, = 0.016) and presence of intraventricular hemorrhage on aCT (OR 0.40, CI 0.20-0.78, = 0.007) were but prior statin use was not (OR 1.17, CI 0.55-2.52, = 0.68) associated with rPHE.

Conclusion: Use of statins before hospital admission for ICH is not associated with reduced rPHE on admission CT. In future studies, imaging timing relative to ICH onset needs to be controlled for in order to avoid confounding.
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http://dx.doi.org/10.1212/WNL.0000000000006931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512886PMC
April 2019

Endovascular Treatment of Cerebral Venous Sinus Thrombosis and Insights into Intracranial Coagulopathy.

J Stroke Cerebrovasc Dis 2019 Apr 8;28(4):e7-e9. Epub 2019 Jan 8.

Columbia University, Vagelos College of Physicians & Surgeons, New York, New York.

Cerebral venous sinus thrombosis (CVST) requires anticoagulation to promote vessel recanalization. Current anticoagulation paradigms utilize plasma tests from peripheral venous/arterial samples for therapeutic monitoring. We describe a medically-refractory case of CVST in a 35-year-old woman later found to have JAK2 mutation and essential thrombocytosis. Despite therapeutic anticoagulation levels, worsening cerebral edema and progression to coma prompted endovascular treatment. Failed endovascular thrombectomy attempts led to placement of 2 separate indwelling microcatheters for continuous infusion of tissue plasminogen activator (tPA). Forty-hours of continuous-tPA in addition to systemic intravenous-heparin led to complete radiographic and clinical resolution of CVST. Whole blood coagulation testing using Rotational Thromboelastometry (ROTEM) from simultaneous samples taken intracranially (via cerebral microcatheters) and peripherally (via antecubital vein) all revealed prolonged intrinsic pathway activation clotting times consistent with heparin anticoagulation use. However, both intracranial ROTEM samples identified faster clotting times compared to the peripheral sample suggesting lower anticoagulation levels intracranially. Our findings were speculative and hypothesis generating as to whether this explained medical treatment failure. If there are coagulopathy differences at local sites of injury not adequately captured by peripheral blood draws, further investigation is required to identify better approaches to avoid under-treatment of similar cases.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441363PMC
April 2019

Dispersion in Scores on the Richmond Agitation and Sedation Scale as a Measure of Delirium in Patients with Subdural Hematomas.

Neurocrit Care 2019 06;30(3):626-634

Division of Critical Care Neurology, Department of Neurology, Columbia University Medical Center, Milstein Hospital Building, 177 Fort Washington Avenue, 8-300 Center, New York, NY, 10032, USA.

Background: Delirium is a frequent complication of critical illness, but its diagnosis is more difficult in brain-injured patients due to language impairment and disorders of consciousness. We conducted a prospective cohort study to determine whether Richmond Agitation and Sedation Scale (RASS) scores could be used to reliably diagnose delirium in the setting of brain injury. We also examined clinical factors associated with delirium in patients with subdural hematomas (SDH) and assessed its impact on functional outcome at discharge.

Methods: We prospectively enrolled 55 patients with the primary diagnosis of SDH admitted to the neurological intensive care unit (ICU) and screened them for delirium with the Confusion Assessment Method-ICU (CAM-ICU). As our primary outcome, we examined whether the standard deviation of RASS scores (RASS dispersion) could be used to diagnose delirium. We also looked at trends in RASS scores as a way to distinguish different causes of delirium. Then, using logistic regression, we identified factors associated with delirium in patients with SDH and quantified the impact of delirium on the modified Rankin Scale at discharge.

Results: Delirium as defined by the CAM-ICU was present in 35% (N = 19) of patients. RASS dispersion correlated well with the CAM-ICU (AUC of the ROC was 0.84). Analyzing the temporal trend of changes in the RASS was helpful in identifying new brain injuries as the underlying etiology of CAM-ICU positivity. Age, APACHE II scores on admission, baseline functional impairment, midline shift on initial imaging, and infections were associated with an increased risk of delirium. Delirium was associated with a worse functional outcome.

Conclusions: RASS dispersion correlates highly with CAM-ICU positivity, and monitoring trends in RASS scores can identify delirium caused by new brain injuries. Delirium as defined by the CAM-ICU is common in patients with SDH and portends worse outcomes.
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http://dx.doi.org/10.1007/s12028-018-0649-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520162PMC
June 2019

Intracerebral Hemorrhagic Expansion Occurs in Patients Using Non-Vitamin K Antagonist Oral Anticoagulants Comparable with Patients Using Warfarin.

J Stroke Cerebrovasc Dis 2017 Aug 21;26(8):1874-1882. Epub 2017 Jun 21.

Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Non-vitamin K antagonist oral anticoagulant (NOAC) use has significantly reduced intracerebral hemorrhagic (ICH) risk compared with standard anticoagulant treatment. Hematoma expansion (HE) is a known predictor of mortality in warfarin-associated ICH. Little is known about HE in patients using NOACs.

Methods: We conducted a retrospective chart review of patients with ICH admitted to Cedars-Sinai Medical Center from October 2010 to June 2016. We identified patients with concomitant administration of an oral anticoagulant and collected data including evidence of HE on imaging and modified Rankin Scale (mRS) at discharge. We defined HE as relative (≥33% increase) or absolute expansion (≥12 mL). We compared outcomes of patients with and without HE.

Results: Out of 814 patients with ICH who were admitted, we identified 9 patients with recent NOAC use and 18 intentionally matched controls on warfarin. We found no significant differences in National Institutes of Health Stroke Scale or ICH score on presentation (median [interquartile range] 15 [5,21] versus 7 [1.25,19.5] [P = .41] and 2 [1,4] versus 1 [1,3] [P = .33]) between patients on NOACs and those on warfarin. Four out of the 9 patients on NOAC and 5 of the 18 patients on warfarin demonstrated HE, with no significant difference (P = .42). There were no significant differences in mRS on discharge between groups (P = .52).

Conclusions: In our coagulopathic NOAC patient population, HE occurs within 6 hours in 44% of patients. This case series did not have sufficient statistical power to detect significant differences between the groups. To our knowledge, this is one of the largest case series reporting on HE with concomitant NOAC use.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.04.025DOI Listing
August 2017

Meta-Analysis of Pre-Clinical Trials of Therapeutic Hypothermia for Intracerebral Hemorrhage.

Ther Hypothermia Temp Manag 2017 Sep 1;7(3):141-146. Epub 2016 Dec 1.

Department of Neurology, Cedars-Sinai Medical Center , Los Angeles, California.

Therapeutic hypothermia (TH) is a potent neuroprotectant for experimental ischemic stroke, but studies of TH for intracerebral hemorrhage (ICH) are emerging. We systematically reviewed the experimental literature to assess TH efficacy for ICH. We found 18 suitable papers; quality scores were moderately good. Compared with normothermia, TH reduced measures of edema (mean effect size (95% CI) -1.6873 (-2.3640, -1.0106), p < 0.0001) or blood-brain barrier leakage (p < 0.0001) and improved behavioral outcomes (p < 0.0001). There was no evidence of publication bias. In this meta-analysis of available preclinical studies of ICH, TH is potently effective for reducing perihematomal edema and for improving behavioral outcomes.
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http://dx.doi.org/10.1089/ther.2016.0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612495PMC
September 2017

Teaching NeuroImages: Diffuse cerebral vasospasm and multiple intracranial abscesses from Bacillus cereus.

Neurology 2016 08;87(9):e97-8

From Cedars-Sinai Medical Center, Los Angeles, CA.

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http://dx.doi.org/10.1212/WNL.0000000000003046DOI Listing
August 2016

Central neuropathic pain in MS is due to distinct thoracic spinal cord lesions.

Ann Clin Transl Neurol 2014 Aug 28;1(8):554-61. Epub 2014 Jul 28.

Atkinson Research Laboratory, Barrow Neurological Institute 350 W. Thomas Road, Phoenix, Arizona, 85013.

Objective: To determine a neuro-anatomic cause for central neuropathic pain (CNP) observed in multiple sclerosis (MS) patients.

Methods: Parallel clinical and neuro-anatomical studies were performed. A clinical investigation of consecutively acquired MS patients with and without CNP (i.e. cold allodynia or deep hyperesthesia) within a single MS center was pursued. A multivariate logistic regression model was used to assess the relationship between an upper central thoracic spinal cord focus to central pain complaints. To identify the hypothesized autonomic interneurons with bilateral descending projections to lumbosacral sensory neurons, retrograde single- and double-labeling experiments with CTb and fluorescent tracers were performed in three animal species (i.e. rat, cat, and monkey).

Results: Clinical data were available in MS patients with (n = 32; F:23; median age: 34.6 years (interquartile range [IQR]: 27.4-45.5)) and without (n = 30; F:22; median age: 36.6 years [IQR: 31.6-47.1]) CNP. The value of a central focus between T1-T6 in relation to CNP demonstrated a sensitivity of 96.9% (95% confidence interval [CI]: 83.8-99.9) and specificity of 83.3% (95% CI: 65.3-94.4). A significant relationship between CNP and a centrally located focus within the thoracic spine was also observed (odds ratio [OR]: 155.0 [95% CI lower limit: 16.0]; P < 0.0001, two-tailed Fisher exact test). In all animal models, neurons with bilateral descending projections to the lumbosacral superficial dorsal horn were concentrated in the autonomic intermediomedial nucleus surrounding the mid-thoracic central canal.

Interpretation: Our observations provide the first evidence for the etiology of CNP. These data may assist with the development of refined symptomatic therapies and allow for insights into unique pain syndromes observed in other demyelinating subtypes.
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http://dx.doi.org/10.1002/acn3.85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184558PMC
August 2014

Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.

Nat Neurosci 2011 Oct 23;14(12):1569-73. Epub 2011 Oct 23.

Department of Psychology and Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.

Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. The analgesic efficacy of the vasopressin analog desmopressin revealed a similar interaction between the drug and acute stress, as desmopressin inhibition of capsaicin pain was only observed in nonstressed subjects. Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent, to the best of our knowledge, the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.
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http://dx.doi.org/10.1038/nn.2941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225498PMC
October 2011

The beta3 subunit of the Na+,K+-ATPase mediates variable nociceptive sensitivity in the formalin test.

Pain 2009 Aug 22;144(3):294-302. Epub 2009 May 22.

Department of Psychology and Centre for Research on Pain, McGill University, 1205 Dr. Penfield Ave., Montreal, Que., Canada H3A 1B1 Department of Neurology and Neurosurgery, Montreal Neurological Institute, and Centre for Research on Pain, McGill University, Montreal, Que., Canada H3A 2B4 Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA Department of Genetics and Genomics, Roche Palo Alto, Palo Alto, CA 94304, USA Integrated DNA Technologies Inc., Coralville, IA 52241, USA Department of Anesthesiology, Stanford University, Palo Alto, CA 94304, USA Department of Anesthesia, Stanford University, Stanford, CA 94305, USA.

It is widely appreciated that there is significant inter-individual variability in pain sensitivity, yet only a handful of contributing genetic variants have been identified. Computational genetic mapping and quantitative trait locus analysis suggested that variation within the gene coding for the beta3 subunit of the Na+,K+-ATPase pump (Atp1b3) contributes to inter-strain differences in the early phase formalin pain behavior. Significant strain differences in Atp1b3 gene expression, beta3 protein expression, and biophysical properties of the Na+,K+ pump in dorsal root ganglia neurons from resistant (A/J) and sensitive (C57BL/6J) mouse strains supported the genetic prediction. Furthermore, in vivo siRNA knockdown of the beta3 subunit produced strain-specific changes in the early phase pain response, completely rescuing the strain difference. These findings indicate that the beta3 subunit of the Na+,K+-ATPase is a novel determinant of nociceptive sensitivity and further supports the notion that pain variability genes can have very selective effects on individual pain modalities.
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http://dx.doi.org/10.1016/j.pain.2009.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744953PMC
August 2009