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      Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis

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          Abstract

          During the SARS-CoV2 pandemic, several cases of Posterior Reversible Encephalopathy Syndrome (PRES) and of Reversible Cerebral Vasoconstriction Syndrome (RCVS) in COVID-19 patients have been reported, but the link between these syndromes and COVID-19 is unclear. We performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to evaluate whether SARS-CoV2 infection or the drugs used to treat it could be deemed potential risk factors for PRES or RCVS. We performed a literature search. We found 70 articles (60 on PRES and 10 on RCVS) concerning n = 105 patients (n = 85 with PRES, n = 20 with RCVS). We analyzed the clinical characteristics of the two populations separately, then performed an inferential analysis to search for other independent risk factors. We found fewer than usual PRES-related (43.9%) and RCVS-related (45%) risk factors in patients with COVID-19. Such a low incidence of risk factors for PRES and RCVS might suggest the involvement of COVID-19 as an additional risk factor for both diseases due to its capability to cause endothelial dysfunction. We discuss the putative mechanisms of endothelial damage by SARS-CoV2 and antiviral drugs which may underlie the development of PRES and RCVS.

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

          David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
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            Methodological quality and synthesis of case series and case reports

            Case reports and case series are uncontrolled study designs known for increased risk of bias but have profoundly influenced the medical literature and continue to advance our knowledge. In this guide, we present a framework for appraisal, synthesis and application of evidence derived from case reports and case series. We propose a tool to evaluate the methodological quality of case reports and case series based on the domains of selection, ascertainment, causality and reporting and provide signalling questions to aid evidence-based practitioners and systematic reviewers in their assessment. We suggest using evidence derived from case reports and case series to inform decision-making when no other higher level of evidence is available.
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              Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys

              Summary The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae 1 . No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.
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                Author and article information

                Contributors
                f.pilato@policlinicocampus.it
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                4 April 2023
                : 1-27
                Affiliations
                [1 ]GRID grid.9657.d, ISNI 0000 0004 1757 5329, Department of Medicine and Surgery, Unit of Neurology, , Neurophysiology, Neurobiology and Psychiatry, Università Campus Bio-Medico di Roma, ; Via Alvaro del Portillo, 21, 00128 Rome, Italy
                [2 ]GRID grid.488514.4, ISNI 0000000417684285, Institute of Neurology, , Fondazione Policlinico Universitario Campus Bio-Medico, ; Via Alvaro del Portillo, 200, 00128 Rome, Italy
                [3 ]GRID grid.411075.6, ISNI 0000 0004 1760 4193, Institute of Radiology, , Fondazione Policlinico Universitario Agostino Gemelli IRCCS, ; Largo A. Gemelli, 1, 00168 Rome, Italy
                Author information
                http://orcid.org/0000-0002-7248-3916
                Article
                11684
                10.1007/s00415-023-11684-4
                10071475
                37014421
                06f553e4-d051-4ab7-86ae-6d83ac145372
                © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 15 January 2023
                : 26 February 2023
                : 21 March 2023
                Categories
                Review

                Neurology
                rcvs,pres,sars-cov2,covid-19,antiviral drugs,endothelial dysfunction
                Neurology
                rcvs, pres, sars-cov2, covid-19, antiviral drugs, endothelial dysfunction

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