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      Stroke in a Feverish Patient with COVID-19 Infection and Unknown Endocarditis

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          Abstract

          Dear Editor, Stroke is the most-common neurological complication of infective endocarditis (IE), occurring in about 35% of cases.1 Ischemic stroke occurs due to the embolization of infected valve material to the brain. Recognizing the possibility of IE within the very short time window available for intravenous thrombolysis in acute ischemic stroke is often difficult. The possible clinical indications of IE are being young with no risk factors, multiple ischemic or hemorrhagic brain lesions, valve abnormalities, preceding weight loss, and fever.1 The difficulty that clinicians experience identifying IE may increase in the presence of another cause of fever. We present the case of a 59-year-old male with a biological prosthetic aortic valve that had been placed 5 years previously. He was admitted to the emergency department due to sudden-onset aphasia and right facial deficit. Low-grade fever over the previous 20 days and moderate dry cough were reported, and the patient had been treated with azithromycin and hydroxychloroquine. A neurological evaluation confirmed global aphasia and slight right lower facial deficit, while the findings of brain CT were normal and CT angiography was negative for large-vessel occlusions. A chest CT scan disclosed features that were highly consistent with COVID-19 interstitial pneumopathy. The diagnosis was also supported by low oxygen saturation levels at baseline, promptly reaching normal values under noninvasive oxygen administration. Laboratory examinations detected neutrophilic leucocytosis with a normal lymphocyte count, slightly elevated international normalized ratio, and normal creatine phosphokinase levels. Systemic recombinant tissue plasminogen activator administration was applied 130 minutes after the clinical onset of aphasia. At the end of the infusion, the patient developed nasal bleeding that was successfully managed with mechanical compression. Therapy with lopinavir/ritonavir (100/25 mg) was started. Brain CT performed at 24 hours after the intravenous thrombolysis showed foci of hemorrhagic transformation in the left frontal lobe, left occipital lobe, and right cerebellar hemisphere (Fig. 1), but the neurological condition of the patient had significantly improved. Transthoracic echocardiography performed on day 3 after the stroke showed IE at the level of the biological prosthetic valve and a suspected periprosthetic abscess. Blood-specimen cultures showed growth of Enterococcus faecalis, which responded to ampicillin at 3 g four times daily and ceftriaxone at 2 g twice daily. A brain CT scan performed 10 days later showed reabsorption of the hemorrhagic foci. Intravenous thrombolysis is the standard acute treatment for patients with ischemic stroke, but it is contraindicated in cerebral septic embolism arising from endocarditic lesions due to the high risk of hemorrhage. Although successful cases of thrombolysis have been reported, the overall outcomes are likely to be poor.2 The rate of postthrombolytic hemorrhagic transformation is significantly higher in patients with IE, and the rate of favorable outcomes is a significantly lower in these patients.3 However, excluding this diagnostic hypothesis requires both a high index of clinical suspicion and the emergency availability of echocardiography, which is not considered in current guidelines as mandatory before thrombolysis. Thus, interpreting the clinical and chest-CT picture of the present patient as an expression of ischemic stroke in the context of COVID-19 infection led to underestimation of the alternative hypothesis of embolic stroke in IE. In this patient, COVID-19 infection was a confounding element and we think that it was not connected to IE. COVID-19 infection may lead both to superimposed bacterial disease and to increased activation of procoagulant cascade. Actually, due to the increasing awareness of the thromboembolic risk in these patients, the current practice in our institution includes prophylactic low-molecular-weight heparin for at least 14 days even in ambulatory COVID-19 patients who are dismissed from the hospital and waiting isolated at home to receive the negative result for a nasal swab. To conclude, clinical scenarios in acute-ischemic-stroke patients with fever are often complex, due to both the rapid decisions required and the difficulty in performing echocardiography on an urgent basis. The present case emphasizes the need for echocardiography in urgent practice to ensure the correct differential diagnosis on etiologies when deciding whether a patient with ischemic stroke should be subjected to thrombolytic therapy. In the present era of the COVID-19 pandemic, we think that the risk-and-benefit equation in feverish patients questions any rigid guidelines, also considering that there is evidence that fibrinolytic therapy in acute lung injury and ARDS improves survival.4

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          Most cited references4

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          Tissue plasminogen activator (tPA) treatment for COVID‐19 associated acute respiratory distress syndrome (ARDS): A case series

          Abstract A prothrombotic coagulopathy is commonly found in critically ill COVID‐19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID‐19 respiratory failure is a relatively preserved lung compliance and high Alveolar‐arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low‐compliance in ARDS. The COVID‐19 pandemic is overwhelming the world’s medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID‐19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.
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            Thrombolysis for Ischemic Stroke Associated With Infective Endocarditis: Results From the Nationwide Inpatient Sample

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              When the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis

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                Author and article information

                Journal
                J Clin Neurol
                J Clin Neurol
                JCN
                Journal of Clinical Neurology (Seoul, Korea)
                Korean Neurological Association
                1738-6586
                2005-5013
                October 2020
                09 September 2020
                : 16
                : 4
                : 707-708
                Affiliations
                Neurology Unit, “A. Manzoni” Hospital-ASST Lecco, Lecco, Italy.
                Author notes
                Correspondence: Vittorio Mantero, MD. Neurology Unit, “A. Manzoni” Hospital-ASST Lecco, Via dell'Eremo 9/11, 23900 Lecco, Italy. Tel +390341489332, vittorio.mantero@ 123456hotmail.com
                Author information
                https://orcid.org/0000-0002-1216-9853
                Article
                10.3988/jcn.2020.16.4.707
                7541976
                33029982
                c88aebd9-eb3c-4da7-9b8e-87f14ea0d753
                Copyright © 2020 Korean Neurological Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 May 2020
                : 15 June 2020
                : 16 June 2020
                Categories
                Letter to the Editor

                Neurology
                Neurology

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