{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:28:39Z","timestamp":1788049719050,"version":"build-2784847793"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological\/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6\/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P\u2009=\u20090.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6\/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17\/23 modified Rankin scale 4\u20136), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012\u20132.225; P\u2009=\u20090.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.<\/jats:p>","DOI":"10.1093\/brain\/awaa239","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T19:10:48Z","timestamp":1593630648000},"page":"3089-3103","source":"Crossref","is-referenced-by-count":243,"title":["Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description"],"prefix":"10.1093","volume":"143","author":[{"given":"Francisco","family":"Hern\u00e1ndez-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hern\u00e1n","family":"Sandoval Valencia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Ang\u00e9lica","family":"Barbella-Aponte","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Collado-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d3scar","family":"Ayo-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1208-8033","authenticated-orcid":false,"given":"Cristina","family":"Barrena","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-1490","authenticated-orcid":false,"given":"Juan David","family":"Molina-Nuevo","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Garc\u00eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Lozano-Seti\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Alcahut-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Mart\u00ednez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"S\u00e1nchez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Anaesthesia Intensive Care Unit, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Segura","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Albacete, Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"2020102603504711100_awaa239-B1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1161\/01.STR.24.1.35","article-title":"Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment","volume":"24","author":"Adams","year":"1993","journal-title":"Stroke"},{"key":"2020102603504711100_awaa239-B2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1177\/1747493020921664","article-title":"Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019 (COVID-19): a pooled analysis of published literature","volume":"15","author":"Aggarwal","year":"2020","journal-title":"Int J Stroke"},{"key":"2020102603504711100_awaa239-B3","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1021\/acschemneuro.0c00122","article-title":"Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms","volume":"11","author":"Baig","year":"2020","journal-title":"ACS Chem Neurosci"},{"key":"2020102603504711100_awaa239-B4","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.3174\/ajnr.A0929","article-title":"Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema","volume":"29","author":"Bartynski","year":"2008","journal-title":"AJNR Am J Neuroradiol"},{"key":"2020102603504711100_awaa239-B5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/STROKEAHA.113.001654","article-title":"Characteristics and outcomes of patients with multiple cervical artery dissection","volume":"45","author":"B\u00e9jot","year":"2014","journal-title":"Stroke"},{"key":"2020102603504711100_awaa239-B6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1182\/blood-2004-01-0107","article-title":"Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow","volume":"104","author":"Bernardo","year":"2004","journal-title":"Blood"},{"key":"2020102603504711100_awaa239-B7","doi-asserted-by":"crossref","DOI":"10.1136\/jnnp-2020-323586","article-title":"Characteristics of ischaemic stroke associated with COVID-19","author":"Beyrouti","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2020102603504711100_awaa239-B8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12883-020-01664-w","article-title":"Incidence and predictive factors of diaphragmatic dysfunction in acute stroke","volume":"20","author":"Catal\u00e1-Ripoll","year":"2020","journal-title":"BMC Neurol"},{"key":"2020102603504711100_awaa239-B9","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1148\/rg.265055090","article-title":"Cerebral amyloid angiopathy: CT and MR imaging findings","volume":"26","author":"Chao","year":"2006","journal-title":"Radiographics"},{"key":"2020102603504711100_awaa239-B10","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jns.2016.11.021","article-title":"The Cerebral Haemorrhage Anatomical RaTing inStrument (CHARTS): development and assessment of reliability","volume":"372","author":"Charidimou","year":"2017","journal-title":"J Neurol Sci"},{"key":"2020102603504711100_awaa239-B11","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/ene.12352","article-title":"Higher baseline international normalized ratio value correlates with higher mortality in intracerebral hemorrhage during warfarin use","volume":"21","author":"Curtze","year":"2014","journal-title":"Eur J Neurol"},{"key":"2020102603504711100_awaa239-B12","article-title":"Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis","author":"Ciceri","year":"2020","journal-title":"Crit Care Resusc"},{"key":"2020102603504711100_awaa239-B13","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1182\/blood-2011-02-306597","article-title":"Unraveling the scissile bond: how ADAMS13 recognizes and cleaves von Willebrand factor","volume":"118","author":"Crawley","year":"2011","journal-title":"Blood"},{"key":"2020102603504711100_awaa239-B14","doi-asserted-by":"crossref","first-page":"734","DOI":"10.3174\/ajnr.A2351","article-title":"Suspicious neuroimaging pattern of thrombotic microangiopathy","volume":"32","author":"Ellchuk","year":"2011","journal-title":"AJNR Am J Neuroradiol"},{"key":"2020102603504711100_awaa239-B15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.thromres.2020.04.014","article-title":"Severe COVID-19 infection associated with endothelial activation","volume":"190","author":"Escher","year":"2020","journal-title":"Thromb Res"},{"key":"2020102603504711100_awaa239-B16","doi-asserted-by":"crossref","DOI":"10.1148\/radiol.2020200432","article-title":"Sensitivity of chest CT for COVID-19: comparison to RT-PCR","author":"Fang","year":"2020","journal-title":"Radiology"},{"key":"2020102603504711100_awaa239-B17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1161\/CIRCRESAHA.109.208645","article-title":"Brain-selective over-expression of human Angiotensin Converting Enzyme 2 attenuates neurogenic hypertension","volume":"106","author":"Fen","year":"2010","journal-title":"Circ Res"},{"key":"2020102603504711100_awaa239-B18","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J Pathol"},{"key":"2020102603504711100_awaa239-B19","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3174\/ajnr.A1588","article-title":"Hemorrhage in posterior reversible encephalopathy syndrome: imaging and clinical features","volume":"30","author":"Hefzy","year":"2009","journal-title":"AJNR Am J Neuroradiol"},{"key":"2020102603504711100_awaa239-B20","article-title":"M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med","year":"2020"},{"key":"2020102603504711100_awaa239-B21","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1056\/NEJMc2008597","article-title":"Neurologic features in severe SARS-CoV-2 infection","volume":"382","author":"Helms","year":"2020","journal-title":"N Engl J Med"},{"key":"2020102603504711100_awaa239-B22","doi-asserted-by":"crossref","first-page":"104578","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104578","article-title":"Simultaneous angioplasty and mechanical thrombectomy in tandem carotid occlusions. Incidence of reocclusions and prognostic predictors","volume":"29","author":"Hern\u00e1ndez-Fern\u00e1ndez","year":"2020","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"2020102603504711100_awaa239-B23","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1007\/s00270-017-1718-x","article-title":"Histopathological and bacteriological analysis of thrombus material extracted during mechanical thrombectomy in acute stroke patients","volume":"40","author":"Hern\u00e1ndez-Fern\u00e1ndez","year":"2017","journal-title":"Cardiovasc Intervent Radiol"},{"key":"2020102603504711100_awaa239-B24","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s12975-020-00818-9","article-title":"COVID-19-related stroke","volume":"11","author":"Hess","year":"2020","journal-title":"Transl Stroke Res"},{"key":"2020102603504711100_awaa239-B25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"2020102603504711100_awaa239-B26","doi-asserted-by":"crossref","DOI":"10.1148\/radiol.2020202222","article-title":"Brain MRI findings in severe COVID-19: a retrospective observational study","author":"Kremer","year":"2020","journal-title":"Radiology"},{"key":"2020102603504711100_awaa239-B27","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1007\/s00330-020-06817-6","article-title":"CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19)","volume":"30","author":"Li","year":"2020","journal-title":"Eur Radiol"},{"key":"2020102603504711100_awaa239-B28","article-title":"Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis","author":"Li","year":"2020","journal-title":"J Med Virol"},{"key":"2020102603504711100_awaa239-B29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1001\/jamaneurol.2020.1127","article-title":"Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China","volume":"77","author":"Mao","year":"2020","journal-title":"JAMA Neurol"},{"key":"2020102603504711100_awaa239-B30","doi-asserted-by":"crossref","DOI":"10.1161\/STROKEAHA.120.030106","article-title":"Break in the stroke chain of survival due to COVID-19","author":"Montaner","year":"2020","journal-title":"Stroke"},{"key":"2020102603504711100_awaa239-B31","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.2215\/CJN.08921209","article-title":"Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome","volume":"5","author":"Nathanson","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"2020102603504711100_awaa239-B32","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s12028-018-0581-1","article-title":"Neuroimaging findings in sepsis-induced brain dysfunction: association with clinical and laboratory findings","volume":"30","author":"Orhun","year":"2019","journal-title":"Neurocrit Care"},{"key":"2020102603504711100_awaa239-B33","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMc2009787","article-title":"Large-vessel stroke as a presenting feature of COVID-19 in the young","author":"Oxley","year":"2020","journal-title":"N Engl J Med"},{"key":"2020102603504711100_awaa239-B34","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/jmv.25915","article-title":"Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)","volume":"92","author":"Paniz-Mondolfi","year":"2020","journal-title":"J Med Virol"},{"key":"2020102603504711100_awaa239-B35","doi-asserted-by":"crossref","DOI":"10.1148\/radiol.2020202040","article-title":"COVID-19 -associated diffuse leukoencephalopathy and microhemorrhages","author":"Radmanesh","year":"2020","journal-title":"Radiology"},{"key":"2020102603504711100_awaa239-B36","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jocn.2020.04.054","article-title":"Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis","volume":"76","author":"Radmanesh","year":"2020","journal-title":"J Clin Neurosci"},{"key":"2020102603504711100_awaa239-B37","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.chest.2020.04.003","article-title":"The role of chest imaging in patient management during the COVID-19 pandemic: a multinational consensus statement from the Fleischner Society","volume":"158","author":"Rubin","year":"2020","journal-title":"Chest"},{"key":"2020102603504711100_awaa239-B38","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1161\/STROKEAHA.120.030329","article-title":"Acute stroke care is at risk in the era of COVID-19: experience at a comprehensive stroke center in Barcelona","volume":"51","author":"Rudilosso","year":"2020","journal-title":"Stroke"},{"key":"2020102603504711100_awaa239-B39","article-title":"Has the aetiology of ischaemic stroke changed in the past decades? Analysis and comparison of data from current and historical stroke databases","author":"S\u00e1nchez-Larsen","year":"2016","journal-title":"Neurologia"},{"key":"2020102603504711100_awaa239-B40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/RTI.0000000000000524","article-title":"Radiological Society of North America expert consensus statement on reporting chest CT findings related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA","volume":"35","author":"Simpson","year":"2020","journal-title":"J Thorac Imaging"},{"key":"2020102603504711100_awaa239-B41","article-title":"Impact of COVID-19 outbreak in ischemic stroke admissions and in-hospital mortality in North-West Spain","author":"Tejada Meza","year":"2020","journal-title":"Int J Stroke"},{"key":"2020102603504711100_awaa239-B42","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"2020102603504711100_awaa239-B43","year":"2020"},{"key":"2020102603504711100_awaa239-B44","doi-asserted-by":"crossref","DOI":"10.1111\/jth.14859","article-title":"D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19","author":"Zhang","year":"2020","journal-title":"J Thromb Haemost"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awaa239\/33893971\/awaa239.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/10\/3089\/34032391\/awaa239.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/10\/3089\/34032391\/awaa239.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T07:51:15Z","timestamp":1603698675000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/143\/10\/3089\/5869424"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,7,9]]},"published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awaa239","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,7,9]]}}}