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      Cerebrovascular Disease in Patients with COVID-19: A Review of the Literature and Case Series

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          COVID-19 has been associated with a hypercoagulable state causing cardiovascular and neurovascular complications. To further characterize cerebrovascular disease (CVD) in COVID-19, we review the current literature of published cases and additionally report the clinical presentation, laboratory and diagnostic testing results of 12 cases with COVID-19 infection and concurrent CVD from two academic medical centers in Houston, TX, USA, between March 1 and May 10, 2020. To date, there are 12 case studies reporting 47 cases of CVD in COVID-19. However, only 4 small case series have described the clinical and laboratory findings in patients with COVID-19 and concurrent stroke. Viral neurotropism, endothelial dysfunction, coagulopathy and inflammation are plausible proposed mechanisms of CVD in COVID-19 patients. In our case series of 12 patients, 10 patients had an ischemic stroke, of which 1 suffered hemorrhagic transformation and two had intracerebral hemorrhage. Etiology was determined to be embolic without a clear cause identified in 6 ischemic stroke patients, while the remaining had an identifiable source of stroke. The majority of the patients had elevated inflammatory markers such as D-dimer and interleukin-6. In patients with embolic stroke of unclear etiology, COVID-19 may have played a direct or indirect role in the processes that eventually led to the strokes while in the remaining cases, it is unclear if infection contributed partially or was an incidental finding.

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          Most cited references 13

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          Viral infections and antiphospholipid antibodies.

           I W Uthman,  A Gharavi (2002)
          To study the relationship between viral infections and the induction of antiphospholipid (aPL) antibodies. We reviewed the medical literature from 1968 until 2000 using MEDLINE and the key words virus, infection, antiphospholipid, and anticardiolipin. Anticardiolipin antibodies and/or lupus anticoagulant were associated with a number of viral infections, including hepatitis C virus, human immunodeficiency virus, cytomegalovirus, varicella zoster, Epstein-Barr virus, adenovirus, and parvovirus B. In many instances, the presence of these antibodies was associated with thrombosis. The clinical significance of finding aPL antibodies in patients with viral infections remains unknown. In some patients, these antibodies may be transient and disappear within 2 or 3 months. In other susceptible individuals, they may persist and raise the question of whether infections may trigger the development of aPL antibodies in autoimmune diseases. Copyright 2002, Elsevier Science (USA). All rights reserved.
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            D-dimer is a significant prognostic factor in patients with suspected infection and sepsis.

            The aim of the study was to determine whether C-reactive protein (CRP), procalcitonin (PCT), and d-dimer (DD) are markers of mortality in patients admitted to the emergency department (ED) with suspected infection and sepsis. We conducted a prospective cohort in a university hospital in Medellín, Colombia. Patients were admitted between August 1, 2007, and January 30, 2009. Clinical and demographic data and Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores as well as blood samples for CRP, PCT, and DD were collected within the first 24 hours of admission. Survival was determined on day 28 to establish its association with the proposed biomarkers using logistic regression and receiver operating characteristic curves. We analyzed 684 patients. The median Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores were 10 (interquartile range [IQR], 6-15) and 2 (IQR, 1-4), respectively. The median CRP was 9.6 mg/dL (IQR, 3.5-20.4 mg/dL); PCT, 0.36 ng/mL (IQR, 0.1-3.7 ng/mL); and DD, 1612 ng/mL (IQR, 986-2801 ng/mL). The median DD in survivors was 1475 ng/mL (IQR, 955-2627 ng/mL) vs 2489 ng/mL (IQR, 1698-4573 ng/mL) in nonsurvivors (P=.0001). The discriminatory ability showed area under the curve-receiver operating characteristic for DD, 0.68; CRP, 0.55; and PCT, 0.59. After multivariate analysis, the only biomarker with a linear relation with mortality was DD, with an odds ratio of 2.07 (95% confidence interval, 0.93-4.62) for values more than 1180 and less than 2409 ng/mL and an odds ratio of 3.03 (95% confidence interval, 1.38-6.62) for values more than 2409 ng/mL. Our results suggest that high levels of DD are associated with 28-day mortality in patients with infection or sepsis identified in the emergency department. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Stroke in the young in the northern Manhattan stroke study.

              Stroke and stroke subtype incidence in young black and Hispanic populations have not been well studied. The purpose of this study was to determine stroke incidence rates in these populations and to compare rates among various race-ethnic, sex, and age groups. A population-based incidence study identified all cases of first stroke in Northern Manhattan from 1993 to 1997. Stroke and stroke subtype incidence rates were calculated for younger (20 to 44 years of age) and older (>/=45 years of age) adults. The relative risk (RR) of stroke in blacks and Hispanics compared with whites was calculated. Stroke subtypes, infarct subtypes, and case fatality rates were compared in the young and old and in different race-ethnic groups and sexes. Over 4 years, 74 cases of first stroke in young patients were discovered (47% women, 12% black, 80% Hispanic, 8% white). The stroke incidence rates (cases per 100 000 persons per year) in the young were 23 overall, 10 for infarct, 7 for intracerebral hemorrhage (ICH), and 6 for subarachnoid hemorrhage. The RR of stroke in the young was greatest for blacks (2.4; 95% CI, 0.8 to 6.7) and Hispanics (2.5; 95% CI, 1.1 to 5.8) compared with whites. ICH was more frequent in men with a RR of 3.7 (95% CI, 1.4 to 10.1). Case fatality rates at 30 days were higher in blacks (38%) and Hispanics (16%) compared with whites (0%). Young blacks and Hispanics have greater stroke incidences than young whites.

                Author and article information

                Case Reports in Neurology
                S. Karger AG
                May – August 2020
                11 June 2020
                : 12
                : 2
                : 199-209
                aDepartment of Neurology, University of Texas Health Science Center at Houston, Houston, Texas, USA
                bInstitute for Stroke and Cerebrovascular Disease, University of Texas Health Science Center at Houston, Houston, Texas, USA
                cDepartment of Neurosurgery, University of Texas Health Science Center at Houston, Houston, Texas, USA
                dDepartment of Neurology, Houston Methodist Neurological Institute, Houston, Texas, USA
                eDepartment of Neurology, Baylor College of Medicine, Houston, Texas, USA
                fDepartment of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
                Author notes
                *Sujan Reddy, Department of Neurology, University of Texas Health Science Center at Houston, MSB 7.044, 6431 Fannin Street, Houston, TX 77030 (USA),
                508958 PMC7325208 Case Rep Neurol 2020;12:199–209
                © 2020 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 1, Pages: 11
                Single Case – General Neurology


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