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      Repeated cardioembolic stroke after COVID-19 mRNA vaccination: A case report : Repeated cardioembolic stroke after COVID-19 RNA vaccination

      case-report
      Author(s): , MD * , , MD, PhD, , MD, PhD, , MD, PhD
      Publication date (Electronic):
      Journal: Journal of Stroke and Cerebrovascular Diseases
      Publisher: Elsevier Inc.
      Keywords: COVID-19, mRNA vaccine, ischemic stroke, recurrent stroke

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          Abstract

          Objective

          : There have been no reports suggesting a relationship between the COVID-19 mRNA vaccines that encodes the spike glycoprotein of SARS-CoV-2 and cerebrovascular disease. A case of repeated cardioembolic stroke after vaccination with the BNT162b2 (Pfizer) COVID-19 mRNA vaccine is presented.

          Methods

          : Imaging and laboratory findings, treatment decisions, and the outcome of this case are presented.

          Results

          : An 83-year-old Japanese woman developed right hemiplegia and motor aphasia three days after receiving her first dose of the BNT162b2 (Pfizer) COVID-19 mRNA vaccine. She had been taking rivaroxaban for persistent atrial fibrillation for 10 years, but had no symptomatic ischemic strokes. On magnetic resonance imaging (MRI) the left middle cerebral artery (MCA) was occluded. Intravenous recombinant tissue-plasminogen activator (rt-PA) therapy and mechanical thrombectomy were performed, and she recovered almost fully. However, three days after the second dose, she developed left hemiplegia and left hemispatial neglect. MRI showed occlusion of the right MCA. Only mechanical thrombectomy was performed again, but it could not be resumed due to the hard thrombus.

          Discussion

          : In this case, it is difficult to exclude a causal relationship between the COVID-19 mRNA vaccine and ischemic stroke. This association needs to be carefully monitored.

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          Neurological associations of COVID-19

          Mark Ellul, Laura Benjamin, Bhagteshwar Singh … (2020)
          Summary Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.
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            Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination

            Marie Scully, Deepak Singh, Robert Lown … (2021)
            Background The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity. Methods We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications. Results In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d -dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms. Conclusions Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.
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              Is Open Access

              Stroke in COVID-19: A systematic review and meta-analysis

              Stefania Nannoni, Rosa de Groot, Steven Bell … (2020)
              Background Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear. Aims We aimed to characterize the incidence, risk factors, clinical–radiological manifestations, and outcome of COVID-19-associated stroke. Methods Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019–September 2020). The review protocol was previously registered (PROSPERO ID = CRD42020185476). Data were extracted from articles reporting ≥5 stroke cases in COVID-19. We complied with the PRISMA guidelines and used the Newcastle–Ottawa Scale to assess data quality. Data were pooled using a random-effect model. Summary of review Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis. Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0–1.9). The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%). Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7–22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94–27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34–9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61–6.02), and severe infection (OR = 5.10; 95%CI: 2.72–9.54). Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3–9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63–4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43–7.90). Conclusions Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors. The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Stroke Cerebrovasc Dis
                Journal ID (iso-abbrev): J Stroke Cerebrovasc Dis
                Title: Journal of Stroke and Cerebrovascular Diseases
                Publisher: Elsevier Inc.
                ISSN (Print): 1052-3057
                ISSN (Electronic): 1532-8511
                Publication date PMC-release: 22 November 2021
                Publication date (Electronic): 22 November 2021
                Electronic Location Identifier: 106233
                Affiliations
                [0001]Department of Neurology, Matsue Red Cross Hospital
                Author notes
                [* ]Corresponding Author: Kentaro Yoshida, M.D., Department of Neurology, Matsue Red Cross Hospital, 200 Horomachi, Matsue, Shimane 690-8506, Japan, Tell: +81-852-24-2111
                Article
                Publisher Item ID: S1052-3057(21)00638-8 Publisher ID: 106233
                DOI: 10.1016/j.jstrokecerebrovasdis.2021.106233
                PMC ID: 8606267
                PubMed ID: 34883321
                SO-VID: 3ac20055-3ba5-4898-a262-5a1b8a501eb7
                Copyright © © 2021 Elsevier Inc. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 13 October 2021
                Date revision received : 4 November 2021
                Date accepted : 16 November 2021
                Categories
                Subject: Case Report

                Keywords: covid-19,mrna vaccine,ischemic stroke,recurrent stroke
                Data availability:
                Keywords: covid-19, mrna vaccine, ischemic stroke, recurrent stroke

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