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Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage (SAH). However, its efficacy, optimal dosing, and the adverse events associated with levetiracetam prophylaxis remain unclear. A systematic search of PubMed, Embase, and Cochrane central register of controlled trials (CENTRAL) database was conducted from January 1, 2000, to October 30, 2020, including articles addressing treatment with levetiracetam for seizure prophylaxis after SAH, ICH, TBI, and supratentorial neurosurgery. Non-English, pediatric (aged

Introduction: While the thrombotic complications of COVID-19 have been described, there are limited data on its implications in hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this group of patients are especially salient as empiric 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 3/1/20-5/15/20 at a NYC hospital system, during the coronavirus pandemic. We compared the demographic and clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital between 3/1/20-5/15/20 (contemporary controls) and 3/1/19-5/15/19 (historical controls), using Fischer’s exact test and non-parametric testing. We adjusted for multiple comparisons using the Bonferroni method. Results: During the study period, 19 out of 4071 (0.5%) patients who were hospitalized with COVID-19 had hemorrhagic stroke on imaging. Of all COVID-19 with hemorrhagic stroke, only 3 had non-aneurysmal SAH without intraparenchymal hemorrhage. Among hemorrhagic stroke and COVID-19 patients, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% vs 4.2% of contemporary and 10.0% of historical controls (both with p = Conclusion: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in COVID-19 patients 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 COVID-19 patients.

Objective: We aim to investigate infarct patterns and 90-day recurrence in patients with symptomatic intracranial atherosclerotic disease. Background: Large artery atherosclerosis subtype carries a high risk of early recurrent stroke despite medical management. Predictors of recurrence remain poorly understood. We hypothesized that border-zone infarcts are associated with a higher risk of recurrence. Design/Methods: We included consecutive patients admitted to NYU Langone Health (Manhattan and Brooklyn campuses) over 32-months with a diagnosis of acute ischemic stroke secondary to symptomatic intracranial or tandem atherosclerosis. Patients with purely extracranial stenosis were excluded. The primary predictor was infarct pattern (border-zone vs. non-border-zone infarction), defined in accordance to previous studies. We used univariate and multivariable cox-regression models to determine associations between infarct pattern and recurrent cerebrovascular events (RCVE) at 90-days. Results: Ninety-nine patients met the inclusion criteria; 95 were intracranial and 4 were tandem lesions. The mean age was 70 years, 58.6% were men, 15.1% Black and 16.1% Asian. The median symptom onset to arrival time was 1 day, nearly 74.7% of patients were treated with dual antiplatelet therapy and 99% were treated with high intensity statin. Within 90 days of follow up, 19.2% (19/99) had RCVE. In univariate analyses, the only factor associated with RCVE was border-zone infarct pattern when compared to non-border-zone infarct pattern (30.2% vs. 10.7%, p=0.02). In cox regression models, after adjusting for age and sex, border-zone infarct pattern was associated with increased risk of RCVE (adjusted HR 3.21 95% CI 1.21-8.51, p=0.019). Sensitivity analyses excluding patients with tandem lesions (n = 4) did not meaningfully change our findings (adjusted HR 3.04 95% CI 1.11-8.31, p=0.031). Conclusions: In real world post-SAMMPRIS medically treated patients with ICAD, infarct pattern was predictive of 90-day RCVE. Border-zone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for this high-risk cohort.

Introduction: While coronavirus disease 2019 (COVID-19) has been associated with acute ischemic stroke (AIS), the causal relationship has yet to be elucidated. Factors that likely confer increased stroke risk are COVID-19-associated coagulopathy and hyperinflammatory response. Studying clinical features of patients with otherwise undetermined cause of AIS could help better define COVID-19-associated stroke. Methods: We performed a multicenter cross-sectional study of consecutive patients presenting with AIS and COVID-19 to one of two large healthcare systems in New York City during the local COVID-19 surge from March 1, 2020 to May 31, 2020. In-hospital stroke cases were excluded. We compared demographic and clinical features of patients with COVID-19 and a cryptogenic AIS subtype to patients with COVID-19 and a determined subtype. Baseline characteristics and clinical variables were compared using chi-squared and Fisher exact tests. Results: A total of 62 patients with AIS and COVID-19 at the time of hospital arrival were identified. Of these, 30 were classified as having a cryptogenic subtype (80% after complete diagnotics evaluation), and 32 had an identifiable stroke mechanism. Patients with cryptogenic AIS were significantly younger (p=0.011) and less likely to have co-morbid hypertension (p=0.019), coronary artery disease (p=0.024), heart failure (p=0.039), atrial fibrillation ( Conclusion: Patients with AIS in the setting of COVID-19 and no other determined stroke mechanism were younger, less likely to have classic risk factors, and had higher d-dimer levels when compared to those with a determined mechanism. Further study of COVID-19-associated hypercoagulability as a mechanism of stroke is warranted.

The classical definition of coma denotes unarousable unresponsiveness with absent sleep–wake cycles and closed eyes, but comatose patients may defy that definition by showing eye-opening early after brain injury.

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

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.

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.

Encephalopathy is a common complication of COVID-19 that can both be a challenge to manage and also negatively impacts prognosis. Whilst encephalopathy may be due to common systemic causes, such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma, cerebrovascular involvement and seizures, which may be disproportionate to COVID-19 severity and which require specific management. The aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through a consensus agreement of the Global COVID-19 Neuro-Research Coalition. A systematic literature search of Medline, MedRxiv, and BioRx was conducted between 1st January 2020 and 11th June 2021 with additional review of references cited within the identified bibliographies. A modified Delphi-approach was then undertaken to develop recommendations along with a parallel approach to score the strength of both the recommendation and the supporting evidence. This manuscript presents analysis of contemporaneous evidence for definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and acute and long-term management.

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.

Background: 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. Methods: 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. Results: 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. Conclusions: 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., Summery In this study of 3,473 hospitalized COVID-19 patients, treatment with zinc and an ionophore was associated with a 24% reduced risk of in-hospital mortality in multivariable Cox regression analysis. A sensitivity analysis in a propensity score-matched cohort supported this finding.

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., Highlights • Patients with COVID-19 can have catastrophic brain injuries. • Family education about catastrophic brain injury is challenging during a pandemic. • The determination of brain death may be difficult in patients with COVID-19. • Medications and renal failure may confound brain death determination in COVID-19. • A modified apnea test may prevent high-risk aerosolization of COVID-19.

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. Electronic supplementary material The online version of this article (10.1007/s11239-020-02288-0) contains supplementary material, which is available to authorized users.

BackgroundWe aimed to compare the outcome of acute ischemic stroke (AIS) patients who received endovascular thrombectomy (EVT) with confirmed COVID-19 to those without.MethodsWe 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.ResultsWe 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 (PConclusionIn 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.

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.

Supplemental Digital Content is available in the text., 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.

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.

Highlights • Neurology teams can care for patients with COVID-19 in lieu of being redeployed. • Maintaining team structures has advantages to redeployment during pandemic surges. • Streamlining neurological services increases capacity to care for COVID-19 patients., 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.

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.

Background As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. Methods The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review with waiver-of-consent. Tier 2 consists of prospective functional and cognitive outcomes assessments with more detailed clinical, laboratory and radiographic data collection that would require informed consent. Tier 3 overlays Tiers 1 and 2 with experimental molecular, electrophysiology, pathology and imaging studies with longitudinal outcomes assessment and would require centers with specific resources. A multicenter pediatrics core has developed and launched a parallel study focusing on patients ages

Background and Purpose: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. Methods: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). Results: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P =0.003) and historical controls (25.0%, P Conclusions: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

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

Background: There is limited data on predictors of sICH in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. Methods: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke center over a 30-month period. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH to identify independent predictors of sICH with p Results: We identified 578 patients with acute ischemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: Thrombolysis in cerebral ischemia score, Alberta stroke program early computed tomography score (ASPECTS), and Glucose level, and using these predictors, we derived the weighted TAG score which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48-2.66, AUC=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22-1.79, AUC=0.69) cohorts. Conclusion: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

Introduction: The insular cortex controls several aspects of vital function including autonomic regulation, and strokes affecting the insula have been associated with dysautonomia, cardiac dysfunction, and arrhythmias. Previous studies have shown an association between insular strokes, elevated troponin levels, and atrial fibrillation (AF). In this study, we aim to determine the association between cardiac biomarkers and insular involvement of the infarct and hypothesize that insular involvement implicates a cardioembolic source. Methods: We abstracted data from a prospective comprehensive stroke center registry of consecutive patients with a discharge diagnosis of acute ischemic stroke who underwent brain imaging (CT or MRI) and work up to determine stroke mechanism. Data included demographics, clinical baseline variables, laboratory tests (including admission troponin level), and transthoracic echocardiographic variables (regional wall motion abnormalities, ejection fraction, and left atrial volume index), and stroke subtype. Multivariable logistic regression models were built to determine associations between AF, and cardiac biomarkers and insular infarcts. Results: We identified 1224 patients who met the inclusion criteria; 397 (32.4%) had insular involvement of the infarct. In multivariable models, insular infarcts were associated with AF (adjusted OR 1.73, 95% CI 1.23-2.43, p = 0.001) and left atrial volume index (adjusted OR per standard deviation increase 1.30, 95% CI 1.13-1.49, p = 0.001). There was a trend for association between insular involvement and positive troponin level (adjusted OR 1.45 95% CI 0.91-2.33, p = 0.122) but not with regional wall motion abnormalities (adjusted OR 1.13, 95% CI 0.69-1.84, p = 0.627). Insular involvement was associated with cardioembolic stroke subtype (45.8% vs. 26.7%, p Conclusion: The insular cortex is commonly involved in patients with atrial fibrillation and/or atrial dilation and maybe a neuroimaging biomarker of cardioembolic stroke. Larger studies are needed to confirm this association and test anticoagulation therapy in patients with insular infarcts.

Background and Purpose: The first of the 2 NINDS Stroke Study trials did not show a significant increase in early neurological improvement (ENI), defined as NIHSS improvement by ≥ 4, with alteplase treatment. We hypothesized that ENI defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods: We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as [(admission NIHSS score–24-hour NIHSS score)x100/admission NIHSS score] and delta NIHSS as (admission NIHSS score–24-hour NIHSS score). We compared ENI using these definitions between alteplase vs. placebo patients. We also used receiver operating characteristic (ROC) curve to determine the predictive association of ENI with excellent 3-month functional outcomes [Barthel Index (BI) score 95 – 100 and modified Rankin scale (mRS) 0-1], good 3-month functional outcome (mRS 0-2) and 3-month infarct volume. Results: There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared to the placebo group (28% vs. 15%, p = 0.045) but not median delta NIHSS (3 vs. 2, p = 0.471). ROC curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month BI (ROC percent 0.83, ROC delta 0.76, ROS admission 0.75), excellent 3-month mRS (ROC percent 0.83, ROC delta 0.74, ROS admission 0.78), and good 3-month mRS (ROC percent 0.83, ROC delta 0.76, ROS admission 0.78). Percentage change had a stronger association with 90-day infarct volume than delta NIHSS score and both delta NIHSS and percent change in NIHSS were more pronounced with faster treatment times. Conclusion: In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

Background: Symptomatic vertebrobasilar (VB) atherosclerotic disease is associated with a high risk of recurrent stroke despite optimal medical therapy. Objective: In this study, we aim to examine the prognosis and associations between risk factors and recurrent major cardiovascular events (MACE) in patients with symptomatic VB stenosis randomized in the medical arm of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study. Methods: Data from subjects in the medical arm of the SAMMPRIS trial with an infarct in the territory of vertebral or basilar arteries (n= 73) were analyzed. The primary outcome was MACE: defined as stroke, myocardial infarction, or other cardiovascular death during follow up. Mean risk factor values were compared between subjects who met the primary outcome at 2 years versus those who did not, using T-tests and χ2 tests. Results: Among 73 patients with VB stenosis randomized to medical treatment, 18 patients (24.6%) had recurrent MACE over a mean follow up of 2.8 years. This was significantly less than the rate of MACE in those with VB enrolled in the WASID trial (9.7 per 100-patient years vs. 20.9 per 100-patient years, p Conclusions: In patients with symptomatic VB disease, improvement of medical treatment over time led to a reduction in cardiovascular event rates but this risk remains elevated as nearly 1 in 5 patients had MACE within 2 years. Further risk factor optimization and lifestyle changes are needed to reduce the rates of MACE in this patient population.

OBJECTIVE: To determine the association between ruptured saccular aneurysms and aspirin use/aspirin dose. METHODS: Four thousand seven hundred one patients who were diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 with 6,411 unruptured and ruptured saccular intracranial aneurysms were evaluated. Univariable and multivariable logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and aspirin use, including aspirin dose. Inverse probability weighting using propensity scores was used to adjust for potential differences in baseline characteristics between cases and controls. Additional analyses were performed to examine the association of aspirin use and rerupture before treatment. RESULTS: In multivariate analysis with propensity score weighting, aspirin use (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.45–0.80) was significantly associated with decreased risk of ruptured intracranial aneurysms. There was a significant inverse dose-response relationship between aspirin dose and aneurysmal subarachnoid hemorrhage (OR 0.65, 95% CI 0.53–0.81). In contrast, there was a significant association between aspirin use and increased risk of rerupture before treatment (OR 8.15, 95% CI 2.22–30.0). CONCLUSIONS: In this large case-control study, aspirin therapy at diagnosis was associated with a significantly decreased risk of subarachnoid hemorrhage, with an inverse dose-response relationship among aspirin users. However, once rupture has occurred, aspirin is associated with an increased risk of rerupture before treatment.

Virhammar et al.1 present a case of acute necrotizing encephalopathy (ANE) in a patient with COVID-19 diagnosed by nasopharyngeal swab PCR1. SARS-CoV-2 PCR testing on 2 CSF specimens performed on days 9 and 12 after symptom onset was negative, whereas a third CSF specimen tested positive at a cycle threshold (Ct) of 34.29 at 21 days. Although interesting, these results do not indicate that SARS-CoV-2 is neurotropic. First, most experts consider Ct counts >40 to represent a negative test, and counts >34 may not represent meaningful disease.2 Because PCR testing can amplify contaminants, this result may be a false positive, particularly with negative initial CSF testing. Second, because ANE is typically a postinfectious disease, a biologically plausible causal link with a weakly positive CSF PCR at 21 days is not established. Third, a large series of patients with COVID-19 who had neurologic symptoms found SARS-CoV-2 PCR was negative in the CSF in 100% of patients.3 Although one study reportedly detected SARS-CoV-2 in a brain autopsy,4 no immunohistochemistry studies were performed, and rough endoplasmic reticulum may be mistaken for virions. Larger brain autopsy series using immunohistochemistry have not detected primary viral CNS invasion.5 Direct neurotropism of SARS-CoV-2 has yet to be definitively established.

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.

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.

Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement.Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed.Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not.Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates.

Ischemic stroke and intracranial hemorrhage (ICH) following left ventricular assist device (LVAD) placement are major causes of morbidity. The incidence and mortality associated with these events stratified by device type have not been systematically explored. A systematic review of PubMed was conducted from January 2007 through June 2016 for all English-language articles involving HeartMate II (HMII) and HeartWare LVAD patients. Ischemic stroke and/or ICH incidence (events per patient-year) and associated mortality rates were abstracted for each device type. Of 735 articles reviewed, 48 (11,310 patients) met inclusion criteria (33 HMII, six HeartWare, eight both devices, and one unspecified). The median duration of device support was 112 days (total 13,723 patient-years). Overall, ischemic stroke or ICH occurred in 9.8% (1110 persons and 0.08 events per patient year [EPPY]). Ischemic stroke occurred in a median of 6.0% or 0.06 EPPY (range 0–16% or 0–0.21 EPPY) of HMII patients versus 7.5% or 0.09 EPPY (range 4–17.1% or 0.01–0.94 EPPY) of HeartWare patients. ICH occurred in a median of 3.0% or 0.04 EPPY (range 0–13.5% or 0–0.13 EPPY) of HMII and 8.0% or 0.08 EPPY (range 3–23% or 0.01–0.56 EPPY) of HeartWare patients. The median mortality rate for LVAD-associated ischemic stroke was 31% (HMII: 33%, [range 2.4–75%] and HeartWare: 11.5% [range 3.9–40%]), and the median mortality rate following ICH was 71% (HMII: 75%, [range 3.9–100%] and HeartWare: 44%, [range 3.1–88%]). Ischemic stroke and ICH are common after LVAD placement, but heterogeneous event rates are reported in the literature. Given the high associated mortality, further prospective study is warranted.

PRELIMINARY REMARKSGuideline LimitationsPractice guidelines should be used in the context of individual patient characteristics and may be superseded by clinical judgment or patient preference. The use of practice guidelines does not guarantee specific outcome benefit but rather should serve as an e

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P

Background and Purpose: Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. Methods: Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). Results: Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). Conclusions: Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.

Infection has been associated with stroke in patients with left ventricular assist devices (LVAD); however, little data exist on the timing, type and mortality impact of infection-related stroke.Prospectively collected data of HeartMate II (N = 332) and HeartWare (N = 70) LVAD patients from a single center were reviewed. Only strokes (ischemic or hemorrhagic) that occurred within 6 weeks following a LVAD infection were considered in analyses. The association between LVAD infections (wound, pump pocket, driveline and/or bloodstream infection [BSI]), specific pathogens and ischemic and hemorrhagic strokes was evaluated using multivariable logistic regression analysis. The impact of infection-related stroke on cumulative survival was assessed using Kaplan-Meier analysis.Of 402 patients, LVAD infection occurred in 158 (39%) including BSI in 107 (27%), driveline infection in 67 (17%), wound infection in 31 (8%) and pump pocket infection in 24 (6%). LVAD infection-related stroke occurred in 20/158 (13%) patients in a median of 4 days (0-36 days) from documented infection. In multivariable analysis, ischemic stroke was associated with wound infection (aOR 9.0, 95% CI 2.4-34.0, P = 0.001) and BSI (aOR 7.7, 95% CI 0.9-66.0, P = 0.064), and hemorrhagic stroke was associated with BSI in 100% of cases (P = 0.01). There was no association with driveline or pump pocket infection. The cumulative survival rate among patients with infection-related stroke was significantly lower compared to those with LVAD infection but no stroke (log-rank P 0.001). There was a trend toward shorter stroke-free survival among patients with LVAD infection.LVAD infections, particularly BSI, are significantly associated with stroke, and infection-related stroke conferred significantly lower cumulative survival.

BackgroundLittle is known regarding long-term outcomes of patients hospitalized with COVID-19.MethodsWe 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.ResultsOf 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 2.03, 95%CI 1.22-3.40, P=0.01), 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.ConclusionsAbnormalities 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.

Withdrawal of life-sustaining therapy may lead to premature limitations of life-saving treatments among patients with intracranial hemorrhage, representing a self-fulfilling prophecy. We aimed to determine whether our algorithm for the withdrawal of life-sustaining therapy decision would accurately identify patients with a high probability of poor outcome, despite aggressive treatment.Retrospective analysis of prospectively collected data.Tertiary-care Neuro-ICU.Intraparenchymal, subdural, and subarachnoid hemorrhage patients.Baseline demographics, clinical status, and hospital course were assessed to determine the predictors of in-hospital mortality and 12-month death/severe disability among patients receiving maximal therapy. Multivariable logistic regression models developed on maximal therapy patients were applied to patients who underwent withdrawal of life-sustaining therapy to predict their probable outcome had they continued maximal treatment. A validation cohort of propensity score-matched patients was identified from the maximal therapy cohort, and their predicted and actual outcomes compared.Of 383 patients enrolled, there were 128 subarachnoid hemorrhage (33.4%), 134 subdural hematoma (35.0%), and 121 intraparenchymal hemorrhage (31.6%). Twenty-six patients (6.8%) underwent withdrawal of life-sustaining therapy and died, 41 (10.7%) continued maximal therapy and died in hospital, and 316 (82.5%) continued maximal therapy and survived to discharge. The median predicted probability of in-hospital death among withdrawal of life-sustaining therapy patients was 35% had they continued maximal therapy, whereas the median predicted probability of 12-month death/severe disability was 98%. In the propensity-matched validation cohort, 16 of 20 patients had greater than or equal to 80% predicted probability of death/severe disability at 12 months, matching the observed outcomes and supporting the strength and validity of our prediction models.The withdrawal of life-sustaining therapy decision may contribute to premature in-hospital death in some patients who may otherwise have been expected to survive to discharge. However, based on probability models, nearly all of the patients who underwent withdrawal of life-sustaining therapy would have died or remained severely disabled at 12 months had maximal therapy been continued. Withdrawal of life-sustaining therapy may not represent a self-fulfilling prophecy.

Although the incidence of subdural hematoma (SDH) has increased in the US in the last decade, limited prospective data exist examining risk factors for poor outcome. A prospective, observational study of consecutive SDH patients was conducted from 7/2008 to 11/2011. Baseline clinical data, hospital and surgical course, complications, and imaging data were compared between those with good versus poor 3-month outcomes (modified Rankin Scores [mRS] 0–3 vs. 4–6). A multivariable logistic regression model was constructed to identify independent predictors of poor outcome. 116 SDH patients (18 acute, 56 mixed acute/subacute/chronic, 42 subacute/chronic) were included. At 3 months, 61 (53 %) patients had good outcomes (mRS 0–3) while 55 (47 %) were severely disabled or dead (mRS 4–6). Of those who underwent surgical evacuation, 54/94 (57 %) had good outcomes compared to 7/22 (32 %) who did not (p = 0.030). Patients with mixed acuity or subacute/chronic SDH had significantly better 3-month mRS with surgery (median mRS 1 versus 5 without surgery, p = 0.002) compared to those with only acute SDH (p = 0.494). In multivariable analysis, premorbid mRS, age, admission Glasgow Coma Score, history of smoking, and fever were independent predictors of poor 3-month outcome (all p

Purpose: The shortage of organs for transplantation is an important medical and societal problem because transplantation is often the best therapeutic option for end-stage organ failure. Methods: We review the potential deceased organ donation pathways in adult ICU practice, i.e. donation after brain death (DBD) and controlled donation after circulatory death (cDCD), which follows the planned withdrawal of life-sustaining treatments (WLST) and subsequent confirmation of death using cardiorespiratory criteria. Results: Strategies in the ICU to increase the number of organs available for transplantation are discussed. These include timely identification of the potential organ donor, optimization of the brain-dead donor by aggressive management of the physiological consequence of brain death, implementation of cDCD protocols, and the potential for ex vivo perfusion techniques. Conclusions: Organ donation should be offered as a routine component of the end-of-life care plan of every patient dying in the ICU where appropriate, and intensivists are the key professional in this process.

The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes. The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated. Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage. This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.

Zika virus (ZIKV) has been associated with various neurologic complications in adults, including Guillain-Barre syndrome (GBS), transverse myelitis, meningoencephalitis, and ophthalmologic manifestations. Though some of these syndromes may be due to a postinfectious (molecular mimicry) mechanism, a direct viral pathogenic mechanism may be responsible in others. We present 3 cases of a newly described syndrome of ZIKV-associated acute transient polyneuritis. Acknowledgment: The authors thank Dr. Richard Hughes for his comments on this manuscript and acknowledge coauthor Dr. Daniel A. Amitrano who died prior to publication of this article.