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(searched for: Ischemic Stroke in COVID-19 Patients: A Narrative Review)
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, Shlee S. Song
Clinical and Applied Thrombosis/Hemostasis, Volume 27; doi:10.1177/10760296211002274

Abstract:
The purpose of this article is to address several challenging questions in the management of young patients (those age 60 and under) who present with ischemic stroke. Do genetic thrombophilic states, strongly associated with venous thrombosis, independently cause arterial events in adults? Should cases of patent foramen ovale be closed with mechanical devices in patients with cryptogenic stroke? What are the optimal treatments for cerebral vein thrombosis, carotid artery dissection, and antiphospholipid syndrome and are DOACs acceptable treatment for these indications? What is the mechanism underlying large vessel stroke in patients with COVID-19? This is a narrative review. We searched PubMed and Embase and American College of physicians Journal club database for English language articles since 2000 looking mainly at randomized clinical trials, Meta analyses, Cochran reviews as well as some research articles viewed to be cutting edge regarding anticoagulation and cerebrovascular disease. Searches were done entering cerebral vein thrombosis, carotid dissection, anticoagulation therapy and stroke, antiphospholipid antibody and stroke, stroke in young adults, cryptogenic stroke and anticoagulation, patent foramen ovale and cryptogenic stroke, COVID-19 and stroke.
A. Maury, A. Lyoubi, N. Peiffer-Smadja, T. de Broucker,
Published: 1 January 2021
Revue Neurologique, Volume 177, pp 51-64; doi:10.1016/j.neurol.2020.10.001

Abstract:
The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses. Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles. We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n = 13), acute necrotizing encephalopathy (ANE, n = 4), Bickerstaff's encephalitis (n = 5), generalized myoclonus (n = 3) and acute transverse myelitis (n = 7); other encephalitis including limbic encephalitis (n = 9) and miscellaneous encephalitis with variable radiologic findings (n = 26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n = 17), cerebral venous thrombosis (n = 8) and posterior reversible encephalopathy (n = 5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain–Barré syndrome (n = 31) and variants including Miller Fisher syndrome (n = 3), polyneuritis cranialis (n = 2) and facial diplegia (n = 2); isolated oculomotor neuropathy (n = 6); critical illness myopathy (n = 6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain–Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients. The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2.
Roberta Marina Ferreira De Oliveira, Pedro Henrique Chaves De Souza Aguiar, Raphael Wellerson Rodrigues Mayrink De Paula, Carlos Eduardo Nardouto Simões, Lucas Garrido Almeida, Alberto Barceló,
Journal of the American College of Emergency Physicians Open, Volume 2; doi:10.1002/emp2.12332

Abstract:
Objective The current study aimed to evaluate the mechanisms of stroke development during the coronavirus disease 2019 (COVID‐19) pandemic and analyze the related characteristics, such as etiology, age group, associated comorbidities, and prognosis. Methods A narrative was performed using the descriptors [“novel coronavirus”] AND [“stroke”] in the PubMed, Science Direct, Google Scholar, Lilacs, and Biblioteca Virtual em Saúde (BVS) databases, including studies published between December 1, 2019, and April 28, 2020. Results A total of 142 articles were identified, with 89 of them in the PubMed database, 46 in Science Direct, and 7 in Google Scholar. No articles were found using the defined keywords in the Lilacs and BVS databases. A total of 22 articles were included for final evaluation. We observed that infection by the novel coronavirus caused a greater risk of the occurrence of stroke, with several studies suggesting etiological mechanisms, such as the involvement of angiotensin‐converting enzyme 2, viral invasion, and hypoxia as well as the increase in D‐dimer and the reduction in platelets, which had been commonly observed in COVID‐19 cases. The most common complication of stroke was found among the elderly with preexisting comorbidities, mainly cardiovascular disease. We detected reports of strokes among young people with no preexisting risk factors for thromboembolic events, in which the mechanism related to the viral infection was the most probable cause. In this review, we confirmed that stroke is part of the spectrum of clinical manifestations resulting from COVID‐19 and is associated with a worse prognosis. Cerebrovascular lesions resulting from complications of the infection by the novel coronavirus occurred as a result of ischemic, hemorrhagic, and/or thromboembolic etiologies. Conclusion The occurrence of stroke during the pandemic as a result of the novel coronavirus has a multifactorial character, and emergency physicians should focus on systematic measures for its screening and accurate diagnosis as well as on appropriate interventions based on early decisionmaking that may have a favorable impact on reducing damage and saving lives.
Published: 28 September 2020
by MDPI
Journal of Clinical Medicine, Volume 9; doi:10.3390/jcm9103137

Abstract:
Coronavirus disease 2019 (COVID-19) is the most overwhelming medical threat of the past few decades. The infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause serious illness leading to respiratory insufficiency, and, in severely ill patients, it can progress to multiple organ failure leading to death. It has been noted from the earliest reports that the disease influences the hemostasis system and a hallmark of severe infection is elevated D-dimer levels. The profound coagulation changes in COVID-19 seem to be linked to inflammation-related events and severe endothelial cell injury. Besides the high incidence of venous thromboembolic events in SARS-CoV-2 infections, arterial events, including cerebrovascular events, were found to be associated with the disease. In this review, we aimed to summarize the available literature on COVID-19-associated coagulopathy and thrombosis. Furthermore, we performed a systematic search of the literature to identify the characteristics of stroke in COVID-19. Our findings showed that acute ischemic stroke (AIS) is the most frequent type of stroke occurring in infected patients. In most cases, stroke was severe (median NIHSS:16) and most of the patients had one or more vascular risk factors. Laboratory findings in AIS patients were consistent with COVID-19-associated coagulopathy, and elevated D-dimer levels were the most common finding. The outcome was unfavorable in most cases, as a large proportion of the reported patients died or remained bedridden. Limited data are available as yet on outcomes after acute vascular interventions in COVID-19 patients. In the future, well-designed studies are needed to better understand the risk of stroke in COVID-19, to optimize treatment, and to improve stroke care.
, , , Vasileios Arsenios Lioutas, Christos Krogias, Aristeidis H. Katsanos, Ashkan Shoamanesh, , Shima Shahjouei, Claudio Baracchini, et al.
Therapeutic Advances in Neurological Disorders, Volume 13; doi:10.1177/1756286420978004

Abstract:
Neurological manifestations are not uncommon during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A clear association has been reported between cerebrovascular disease and coronavirus disease 2019 (COVID-19). However, whether this association is causal or incidental is still unknown. In this narrative review, we sought to present the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describe the stroke syndromes and their prognosis and discuss several clinical, radiological, and laboratory characteristics that may aid in the prompt recognition of cerebrovascular disease during COVID-19. A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune reaction and inflammation, coagulopathy, COVID-19-associated cardiac injury with subsequent cardio-embolism, complications due to critical illness and prolonged hospitalization can all contribute as potential etiopathogenic mechanisms leading to diverse cerebrovascular clinical manifestations. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients with a prevalence ranging between 0.5% and 5%. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients in different cohort studies. Specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ to alarm clinicians in recognizing COVID-19-related stroke.
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