{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:06:00Z","timestamp":1789499160929,"version":"build-2803163510"},"reference-count":39,"publisher":"BMJ","funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23ek0109680"],"award-info":[{"award-number":["JP23ek0109680"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health, Labor, and Welfare of Japan","award":["23FC1009"],"award-info":[{"award-number":["23FC1009"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2025,9,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathogenic mechanisms underlying autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A), a central nervous system disorder associated with GFAP autoimmunity, remain controversial. The present study aimed to investigate the potential role of the intrathecal reactivation of Epstein\u2013Barr virus (EBV) in patients with GFAP-A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EBV-DNA levels were measured in the cerebrospinal fluid (CSF) and blood samples of 14 patients with GFAP-A and 28 patients with other disorders. IgM and IgG antibodies against EBV viral capsid antigen (VCA) and IgG antibodies against early antigen (EA) were also measured in serum samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      EBV-DNA was detected in the CSF samples in 10 of the 14 patients with GFAP-A and in 1 of the 28 patients in the disease control group, with a significant difference between the two groups (71.4% vs 3.6%; p&lt;0.0001). Conversely, EBV-DNA was not detected in the blood of the 13 patients with GFAP-A. In patients with GFAP-A, the CSF-EBV-DNA level was significantly associated with the worst modified Rankin scale score during the acute phase (r\n                      <jats:sub>s<\/jats:sub>\n                      =0.6143, p=0.0194). Serum antibody profiling revealed evidence of past EBV infection, with VCA-IgG positivity and VCA-IgM and\/or EA-IgG negativity observed in 92.9% of the patients with GFAP-A.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study findings suggest that GFAP autoimmunity is associated with intrathecal EBV reactivation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2025-336773","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:05:20Z","timestamp":1764248720000},"page":"jnnp-2025-336773","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Intrathecal Epstein\u2013Barr virus reactivation in patients with autoimmune glial fibrillary acidic protein astrocytopathy"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0787-4486","authenticated-orcid":false,"given":"Hideo","family":"Handa","sequence":"first","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-1863","authenticated-orcid":false,"given":"Akiyuki","family":"Uzawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-255X","authenticated-orcid":false,"given":"Masahiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-0720","authenticated-orcid":false,"given":"Takahiro","family":"Iizuka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kitasato University School of Medicine, Sagamihara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manato","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0705-9892","authenticated-orcid":false,"given":"Atsuhiko","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8788-9089","authenticated-orcid":false,"given":"Takayoshi","family":"Shimohata","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-8578","authenticated-orcid":false,"given":"Satoshi","family":"Kuwabara","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine School of Medicine, Chiba University, Chiba, Japan"},{"name":"Research Institute of Disaster Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"2025112705051751000_jnnp-2025-336773v1.1","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1001\/jamaneurol.2016.2549","article-title":"Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis","volume":"73","author":"Fang","year":"2016","journal-title":"JAMA Neurol"},{"key":"2025112705051751000_jnnp-2025-336773v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24881"},{"key":"2025112705051751000_jnnp-2025-336773v1.3","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316583"},{"key":"2025112705051751000_jnnp-2025-336773v1.4","doi-asserted-by":"crossref","DOI":"10.1007\/s00401-023-02678-7","article-title":"New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis","volume":"147","author":"Guo","year":"2024","journal-title":"Acta Neuropathol"},{"key":"2025112705051751000_jnnp-2025-336773v1.5","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302911"},{"key":"2025112705051751000_jnnp-2025-336773v1.6","doi-asserted-by":"crossref","DOI":"10.1186\/s40001-024-01926-0","article-title":"The EBV connection: a severe case of GFAP-A with central hypoventilation unresponsive to IVIG and literature review","volume":"29","author":"Wang","year":"2024","journal-title":"Eur J Med Res"},{"key":"2025112705051751000_jnnp-2025-336773v1.7","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1111\/cns.14336","article-title":"Epstein-Barr virus: To be a trigger of autoimmune glial fibrillary acidic protein astrocytopathy?","volume":"29","author":"Li","year":"2023","journal-title":"CNS Neurosci Ther"},{"key":"2025112705051751000_jnnp-2025-336773v1.8","article-title":"A case of EBV encephalomyelitis with positive anti-GFAP-IgG antibody with recurrent fever and dysuresia as the main symptoms: Case report and retrospective analysis","volume":"101","author":"Wang","year":"2022","journal-title":"Medicine (Abingdon)"},{"key":"2025112705051751000_jnnp-2025-336773v1.9","doi-asserted-by":"crossref","first-page":"578174","DOI":"10.1016\/j.jneuroim.2023.578174","article-title":"Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy","volume":"382","author":"Zhang","year":"2023","journal-title":"J Neuroimmunol"},{"key":"2025112705051751000_jnnp-2025-336773v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.04.016"},{"key":"2025112705051751000_jnnp-2025-336773v1.11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2169\/internalmedicine.2751-23","article-title":"Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Following SARS-CoV-2 Infection","volume":"63","author":"Tajiri","year":"2024","journal-title":"Intern Med"},{"key":"2025112705051751000_jnnp-2025-336773v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2018.02.020"},{"key":"2025112705051751000_jnnp-2025-336773v1.13","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.2169\/internalmedicine.4741-24","article-title":"Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Caused by Influenza A Infection","volume":"64","author":"Okano","year":"2025","journal-title":"Intern Med"},{"key":"2025112705051751000_jnnp-2025-336773v1.14","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0000000000000790"},{"key":"2025112705051751000_jnnp-2025-336773v1.15","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1007\/s12035-024-04660-0","article-title":"Novel Perspectives Focused on the Relationship Between Herpesvirus Encephalitis and Anti-GFAP-Antibody-Positive Astrocytopathy","volume":"62","author":"Liao","year":"2025","journal-title":"Mol Neurobiol"},{"key":"2025112705051751000_jnnp-2025-336773v1.16","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-330626"},{"key":"2025112705051751000_jnnp-2025-336773v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2019.04.004"},{"key":"2025112705051751000_jnnp-2025-336773v1.18","doi-asserted-by":"crossref","DOI":"10.1186\/s12985-020-1285-7","article-title":"Automated quantification of Epstein-Barr virus in whole blood for post-transplant lymphoproliferative disorders monitoring","volume":"17","author":"Salmona","year":"2020","journal-title":"Virol J"},{"key":"2025112705051751000_jnnp-2025-336773v1.19","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.diagmicrobio.2018.12.015","article-title":"Evaluation of the new Abbott Real-Time EBV assay: fully automated quantification of EBV in whole blood by targeting BLLF1","volume":"94","author":"Lee","year":"2019","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2025112705051751000_jnnp-2025-336773v1.20","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.816098","article-title":"Epstein-Barr Virus and Neurological Diseases","volume":"8","author":"Zhang","year":"2021","journal-title":"Front Mol Biosci"},{"key":"2025112705051751000_jnnp-2025-336773v1.21","doi-asserted-by":"crossref","DOI":"10.3390\/v15030656","article-title":"Virological Markers in Epstein-Barr Virus-Associated Diseases","volume":"15","author":"Lupo","year":"2023","journal-title":"Viruses"},{"key":"2025112705051751000_jnnp-2025-336773v1.22","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7722-7733.1999"},{"key":"2025112705051751000_jnnp-2025-336773v1.23","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.virol.2021.04.005","article-title":"Glial cell response to Epstein-Barr Virus infection: A plausible contribution to virus-associated inflammatory reactions in the brain","volume":"559","author":"Jakhmola","year":"2021","journal-title":"Virology (Auckl)"},{"key":"2025112705051751000_jnnp-2025-336773v1.24","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2425670122","article-title":"Epstein-Barr virus and the immune microenvironment in multiple sclerosis: Insights from high-dimensional brain tissue imaging","volume":"122","author":"Orr","year":"2025","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025112705051751000_jnnp-2025-336773v1.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902623116"},{"key":"2025112705051751000_jnnp-2025-336773v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04432-7"},{"key":"2025112705051751000_jnnp-2025-336773v1.27","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms11122825","article-title":"Epstein-Barr Virus Encephalitis: A Review of Case Reports from the Last 25 Years","volume":"11","author":"Peuchmaur","year":"2023","journal-title":"Microorganisms"},{"key":"2025112705051751000_jnnp-2025-336773v1.28","article-title":"An Adult Case of Acute EBV Cerebellitis","volume":"4","author":"Muscat","year":"2017","journal-title":"Eur J Case Rep Intern Med"},{"key":"2025112705051751000_jnnp-2025-336773v1.29","doi-asserted-by":"crossref","DOI":"10.1177\/13596535231161488","article-title":"Case report and literature review: A hiccup patient developed encephalitis and duodenal perforation","volume":"28","author":"Kong","year":"2023","journal-title":"Antivir Ther"},{"key":"2025112705051751000_jnnp-2025-336773v1.30","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815613563"},{"key":"2025112705051751000_jnnp-2025-336773v1.31","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1111\/ene.13332","article-title":"Anti-N-methyl-D-aspartate receptor encephalitis and Epstein-Barr virus: another tale on autoimmunity?","volume":"24","author":"Danieli","year":"2017","journal-title":"Eur J Neurol"},{"key":"2025112705051751000_jnnp-2025-336773v1.32","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000015726","article-title":"Anti-N-methyl-D-aspartate receptor encephalitis associated with reactivated Epstein-Barr virus infection in pediatric patients: Three case reports","volume":"98","author":"Hou","year":"2019","journal-title":"Medicine (Baltimore)"},{"key":"2025112705051751000_jnnp-2025-336773v1.33","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1001\/jamaneurol.2024.0272","article-title":"Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis","volume":"81","author":"Cortese","year":"2024","journal-title":"JAMA Neurol"},{"key":"2025112705051751000_jnnp-2025-336773v1.34","doi-asserted-by":"publisher","DOI":"10.1080\/13550280260422730"},{"key":"2025112705051751000_jnnp-2025-336773v1.35","doi-asserted-by":"publisher","DOI":"10.2174\/187152712801661220"},{"key":"2025112705051751000_jnnp-2025-336773v1.36","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071030"},{"key":"2025112705051751000_jnnp-2025-336773v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2019.576999"},{"key":"2025112705051751000_jnnp-2025-336773v1.38","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.msard.2019.01.036","article-title":"Astrocytic damage in glial fibrillary acidic protein astrocytopathy during initial attack","volume":"29","author":"Yang","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"2025112705051751000_jnnp-2025-336773v1.39","doi-asserted-by":"crossref","DOI":"10.1111\/ene.70102","article-title":"A Comparative Study of 141 Glial Fibrillary Acidic Protein Immunoglobulin G Positive Cases","volume":"32","author":"Zhang","year":"2025","journal-title":"Eur J Neurol"}],"container-title":["Journal of Neurology, Neurosurgery &amp; Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jnnp-2025-336773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:05:23Z","timestamp":1764248723000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnnp.bmj.com\/lookup\/doi\/10.1136\/jnnp-2025-336773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":39,"alternative-id":["10.1136\/jnnp-2025-336773"],"URL":"https:\/\/doi.org\/10.1136\/jnnp-2025-336773","relation":{},"ISSN":["0022-3050","1468-330X"],"issn-type":[{"value":"0022-3050","type":"print"},{"value":"1468-330X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]}}}