{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:01:43Z","timestamp":1790517703044,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"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":[[2021,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaa745","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T04:11:00Z","timestamp":1606363860000},"page":"600-609","source":"Crossref","is-referenced-by-count":54,"title":["Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients"],"prefix":"10.1093","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6018-4057","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Lersy","sequence":"first","affiliation":[{"name":"Service d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilies","family":"Benotmane","sequence":"additional","affiliation":[{"name":"H\u00f4pital de Hautepierre, Strasbourg, France"},{"name":"Department of Virology, Strasbourg University Hospital, Strasbourg, France"},{"name":"INSERM U1109, LabEx TRANSPLANTEX, Strasbourg, France"},{"name":"Nephrology Transplantation Department, Strasbourg University Hospitals, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Helms","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, Service de M\u00e9decine Intensive R\u00e9animation, Nouvel H\u00f4pital Civil, Strasbourg, France"},{"name":"Immuno-Rhumatologie Mol\u00e9culaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, Facult\u00e9 de M\u00e9decine, F\u00e9d\u00e9ration Hospitalo-Universitaire OMICARE, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Collange","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, Service d\u2019Anesth\u00e9sie-R\u00e9animation, Nouvel H\u00f4pital Civil, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maleka","family":"Schenck","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, Service de M\u00e9decine-Intensive-R\u00e9animation, H\u00f4pital de Hautepierre, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Brisset","sequence":"additional","affiliation":[{"name":"Observatoire Fran\u00e7ais de la Scl\u00e9rose en Plaques, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Chammas","sequence":"additional","affiliation":[{"name":"Service d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Willaume","sequence":"additional","affiliation":[{"name":"Service d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses, Nouvel H\u00f4pital Civil, CHU de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Solis","sequence":"additional","affiliation":[{"name":"H\u00f4pital de Hautepierre, Strasbourg, France"},{"name":"Department of Virology, Strasbourg University Hospital, Strasbourg, France"},{"name":"INSERM U1109, LabEx TRANSPLANTEX, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Hansmann","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses, Nouvel H\u00f4pital Civil, CHU de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Fabacher","sequence":"additional","affiliation":[{"name":"Public Health, CHRU Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Caillard","sequence":"additional","affiliation":[{"name":"INSERM U1109, LabEx TRANSPLANTEX, Strasbourg, France"},{"name":"Nephrology Transplantation Department, Strasbourg University Hospitals, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Michel","family":"Mertes","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, Service d\u2019Anesth\u00e9sie-R\u00e9animation, Nouvel H\u00f4pital Civil, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Pottecher","sequence":"additional","affiliation":[{"name":"Service d\u2019Anesth\u00e9sie-R\u00e9animation & M\u00e9decine P\u00e9ri-Op\u00e9ratoire, H\u00f4pitaux Universitaires de Strasbourg\u2013F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Schneider","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, Service de M\u00e9decine-Intensive-R\u00e9animation, H\u00f4pital de Hautepierre, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhat","family":"Meziani","sequence":"additional","affiliation":[{"name":"H\u00f4pitaux Universitaires de Strasbourg, Service de M\u00e9decine Intensive R\u00e9animation, Nouvel H\u00f4pital Civil, Strasbourg, France"},{"name":"INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Fafi-Kremer","sequence":"additional","affiliation":[{"name":"H\u00f4pital de Hautepierre, Strasbourg, France"},{"name":"Department of Virology, Strasbourg University Hospital, Strasbourg, France"},{"name":"Immuno-Rhumatologie Mol\u00e9culaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d\u2019Immunologie et d\u2019H\u00e9matologie, Facult\u00e9 de M\u00e9decine, F\u00e9d\u00e9ration Hospitalo-Universitaire OMICARE, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Kremer","sequence":"additional","affiliation":[{"name":"Service d\u2019Imagerie, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"},{"name":"Engineering Science, Computer Science and Imaging Laboratory (ICube), Integrative Multimodal Imaging in Healthcare, UMR 7357, University of Strasbourg\u2013CNRS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,29]]},"reference":[{"key":"2021022419590790400_CIT0001","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":"2021022419590790400_CIT0002","doi-asserted-by":"crossref","first-page":"683","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":"2021022419590790400_CIT0003","article-title":"Understanding the immunologic characteristics of neurologic manifestations of SARS-CoV-2 and potential immunological mechanisms","author":"Mohammadi","journal-title":"Mol Neurobiol"},{"key":"2021022419590790400_CIT0004","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ijid.2020.03.062","article-title":"A first case of meningitis\/encephalitis associated with SARS-coronavirus-2","volume":"94","author":"Moriguchi","year":"2020","journal-title":"Int J Infect Dis"},{"key":"2021022419590790400_CIT0005","doi-asserted-by":"crossref","first-page":"E242","DOI":"10.1148\/radiol.2020202222","article-title":"Brain MRI findings in severe COVID-19: a retrospective observational study","volume":"297","author":"Kremer","year":"2020","journal-title":"Radiology"},{"key":"2021022419590790400_CIT0006","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s12311-020-01177-9","article-title":"A first case of acute cerebellitis associated with coronavirus disease (COVID-19): a case report and literature review","volume":"19","author":"Fadakar","year":"2020","journal-title":"Cerebellum"},{"key":"2021022419590790400_CIT0007","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1212\/WNL.0000000000010250","article-title":"Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid","volume":"95","author":"Virhammar","year":"2020","journal-title":"Neurology"},{"key":"2021022419590790400_CIT0008","article-title":"Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients","author":"Bellon","journal-title":"Clin Infect Dis"},{"key":"2021022419590790400_CIT0009","doi-asserted-by":"crossref","first-page":"117090","DOI":"10.1016\/j.jns.2020.117090","article-title":"Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms","volume":"418","author":"Neumann","year":"2020","journal-title":"J Neurol Sci"},{"key":"2021022419590790400_CIT0010","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1016\/S2666-5247(20)30066-5","article-title":"Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic","volume":"1","author":"Destras","year":"2020","journal-title":"Lancet Microbe"},{"key":"2021022419590790400_CIT0011","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1186\/s13054-020-03200-1","article-title":"Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients","volume":"24","author":"Helms","year":"2020","journal-title":"Crit Care"},{"key":"2021022419590790400_CIT0012","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00401-020-02213-y","article-title":"Correlates of critical illness-related encephalopathy predominate postmortem COVID-19 neuropathology","volume":"140","author":"Deigendesch","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2021022419590790400_CIT0013","doi-asserted-by":"crossref","first-page":"e245","DOI":"10.1016\/S2666-5247(20)30115-4","article-title":"Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study","volume":"1","author":"Hanley","year":"2020","journal-title":"Lancet Microbe"},{"key":"2021022419590790400_CIT0014","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1186\/s13054-020-03218-5","article-title":"Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients","volume":"24","author":"Remmelink","year":"2020","journal-title":"Crit Care"},{"key":"2021022419590790400_CIT0015","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMc2019373","article-title":"Neuropathological features of Covid-19","volume":"383","author":"Solomon","year":"2020","journal-title":"N Engl J Med"},{"key":"2021022419590790400_CIT0016","doi-asserted-by":"crossref","first-page":"e1868","DOI":"10.1212\/WNL.0000000000010112","article-title":"Neurologic and neuroimaging findings in patients with COVID-19: a retrospective multicenter study","volume":"95","author":"Kremer","year":"2020","journal-title":"Neurology"},{"key":"2021022419590790400_CIT0017","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/ene.13909","article-title":"Immunophenotyping of cerebrospinal fluid cells in ischaemic stroke","volume":"26","author":"Schulte-Mecklenbeck","year":"2019","journal-title":"Eur J Neurol"},{"key":"2021022419590790400_CIT0018","first-page":"18","article-title":"The blood brain barrier and the role of cytokines in neuropsychiatry","volume":"6","author":"Yarlagadda","year":"2009","journal-title":"Psychiatry (Edgmont)"},{"key":"2021022419590790400_CIT0019","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1111\/ene.14442","article-title":"Sandhu","volume":"27","author":"Alam","year":"","journal-title":"Eur J Neurol"},{"key":"2021022419590790400_CIT0020","article-title":"Cytokine release syndrome-associated encephalopathy in patients with COVID-19","author":"Perrin","journal-title":"Eur J Neurol"},{"key":"2021022419590790400_CIT0021","first-page":"86","article-title":"Detection of oligoclonal Ig bands: clinical significance and trends in methodological improvement","volume":"15","author":"Trbojevic-Cepe","year":"2004","journal-title":"EJIFCC"},{"key":"2021022419590790400_CIT0022","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1212\/WNL.0000000000003820","article-title":"Leptomeningeal gadolinium enhancement across the spectrum of chronic neuroinflammatory diseases","volume":"88","author":"Absinta","year":"2017","journal-title":"Neurology"},{"key":"2021022419590790400_CIT0023","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"2021022419590790400_CIT0024","article-title":"MRI brain findings in 126 patients with COVID-19: initial observations from a descriptive literature review","author":"Gulko","journal-title":"AJNR Am J Neuroradiol"},{"key":"2021022419590790400_CIT0025","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s12028-020-00978-4","article-title":"Neurological implications of COVID-19 infections","volume":"32","author":"Needham","year":"2020","journal-title":"Neurocrit Care"},{"key":"2021022419590790400_CIT0026","doi-asserted-by":"crossref","first-page":"e109","DOI":"10.1016\/S0140-6736(20)31282-4","article-title":"Early evidence of pronounced brain involvement in fatal COVID-19 outcomes","volume":"395","author":"von Weyhern","year":"2020","journal-title":"Lancet"},{"key":"2021022419590790400_CIT0027","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1161\/STROKEAHA.116.016289","article-title":"Critical illness-associated cerebral microbleeds","volume":"48","author":"Fanou","year":"2017","journal-title":"Stroke"},{"key":"2021022419590790400_CIT0028","doi-asserted-by":"crossref","first-page":"E223","DOI":"10.1148\/radiol.2020202040","article-title":"COVID-19-associated diffuse leukoencephalopathy and microhemorrhages","volume":"297","author":"Radmanesh","year":"2020","journal-title":"Radiology"},{"key":"2021022419590790400_CIT0029","article-title":"Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses","author":"Lersy","journal-title":"J Neurol"},{"key":"2021022419590790400_CIT0030","first-page":"e2481","article-title":"Improvement in sonographic vasospasm following intravenous milrinone in a subarachnoid hemorrhage patient with normal cardiac function","volume":"10","author":"Katyal","year":"2018","journal-title":"Cureus"},{"key":"2021022419590790400_CIT0031","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1007\/s00415-020-09951-9","article-title":"COVID-19-associated acute disseminated encephalomyelitis (ADEM)","volume":"267","author":"Parsons","year":"2020","journal-title":"J Neurol"},{"key":"2021022419590790400_CIT0032","article-title":"A case of acute disseminate encephalomyelitis after SARS-CoV-2 related acute respiratory distress syndrome","author":"Fitouchi","journal-title":"J Neuroradiol"},{"key":"2021022419590790400_CIT0033","article-title":"Concentric demyelination pattern in COVID-19-associated acute haemorrhagic leukoencephalitis: a lurking catastrophe","author":"Karapanayiotides","journal-title":"Brain"},{"key":"2021022419590790400_CIT0034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-020-02166-2","article-title":"Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology","volume":"140","author":"Reichard","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2021022419590790400_CIT0035","article-title":"Guillain-Barr\u00e9 syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases","author":"Abu-Rumeileh","journal-title":"J Neurol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaa745\/35522522\/jiaa745.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/223\/4\/600\/36355873\/jiaa745.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/223\/4\/600\/36355873\/jiaa745.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T20:00:35Z","timestamp":1614196835000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/223\/4\/600\/6010475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,29]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,11,29]]},"published-print":{"date-parts":[[2021,2,24]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaa745","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2,15]]},"published":{"date-parts":[[2020,11,29]]}}}