{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:26Z","timestamp":1753891586427,"version":"3.41.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>To describe a new case of neuromyelitis optica spectrum disorder (NMOSD) induced by the administration of interferon-alpha (IFN\u03b1) and to raise awareness of this rare drug-induced disease of IFN\u03b1 treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single case study and comprehensive literature review of eight cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 24-year-old man was diagnosed with cerebral venous thrombosis and essential thrombocythemia. He had been undergoing IFN\u03b1 treatment (IFN\u03b1-2b, 3 million IU per day) without any side effects for 18 months, at which point the patient developed persistent hiccups, nausea, urinary retention, and numbness. Spinal magnetic resonance imaging revealed a longitudinal abnormality extending from the medulla to the entire spinal cord. The patient was positive for anti-aquaporin-4 antibody (AQP4-IgG) in both the serum and cerebrospinal fluid (CSF), which confirmed the diagnosis of NMOSD. Thus, recombinant IFN\u03b1-2b was suspended immediately. Because his condition did not improve after 6-day treatment of methylprednisolone pulse therapy (1,000 mg for 3 days, then 500 mg for 3 days), intravenous immunoglobulin (0.4 g\/kg\/day for 5 days) was administered. The patient gradually improved. Low-dose prednisolone and mycophenolate mofetil were subsequently administered as a long-term treatment. The patient was discharged with subtle limb numbness and their expanded disability status score (EDSS) was 1. At the 1-year follow-up, the patient had not relapsed and tested negative for AQP4-IgG. We further identified the eight patients with IFN\u03b1-induced NMOSD. The median onset age was 59 years, and the median time of IFN\u03b1 exposure was 18 months. Optic neuritis was the most common initial symptom (five, 55.6%), followed by myelitis in three patients and area postrema syndrome in one patient. More than half (five, 55.6%) of the patients were monophasic. After IFN\u03b1 discontinuation and immunotherapy, most (seven, 77.8%) patients remained relapse-free. However, only one patient was free of sequelae.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights the potential pathogenic risk of NMOSD of IFN\u03b1 treatment. Given the high disability rates of this rare drug-induced disease, it is crucial to monitor the early manifestations of NMOSD during IFN\u03b1 treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.872684","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T09:18:37Z","timestamp":1650878317000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Interferon-Alpha-Induced Neuromyelitis Optica Spectrum Disorder"],"prefix":"10.3389","volume":"13","author":[{"given":"Jie","family":"Rao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangwang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S1474-4422(12)70133-3","article-title":"Aquaporin 4 and neuromyelitis optica","volume":"11","author":"Papadopoulos","year":"2012","journal-title":"Lancet Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3578","DOI":"10.1093\/brain\/awr262","article-title":"Micro-Rna dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity","volume":"134","author":"Guerau-de-Arellano","year":"2011","journal-title":"Brain."},{"key":"B4","doi-asserted-by":"publisher","first-page":"pe70","DOI":"10.1126\/stke.4162007pe70","article-title":"Type I interferons as anti-inflammatory mediators","volume":"2007","author":"Benveniste","year":"2007","journal-title":"Sci STKE."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3489","DOI":"10.1007\/s00415-019-09395-w","article-title":"Comparative efficacy and acceptability of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis","volume":"267","author":"Li","year":"2020","journal-title":"J Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"17562864211039648","DOI":"10.1177\/17562864211039648","article-title":"Multiple sclerosis therapy consensus group (Mstcg): position statement on disease-modifying therapies for multiple sclerosis (white paper)","volume":"14","author":"Wiendl","year":"2021","journal-title":"Ther Adv Neurol Disord."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1177\/1352458512439439","article-title":"Does interferon beta treatment exacerbate neuromyelitis optica spectrum disorder?","volume":"18","author":"Kim","year":"2012","journal-title":"Mult Scler."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1001\/archneurol.2010.188","article-title":"Interferon beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers","volume":"67","author":"Palace","year":"2010","journal-title":"Arch Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S1474-4422(19)30445-4","article-title":"Neuromyelitis optica in patients with increased interferon alpha concentrations","volume":"19","author":"Williams","year":"2020","journal-title":"Lancet Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.2169\/internalmedicine.51.7771","article-title":"New-onset type 1 diabetes mellitus and anti-aquaporin-4 antibody positive optic neuritis associated with type 1 interferon therapy for chronic hepatitis C","volume":"51","author":"Kawazoe","year":"2012","journal-title":"Intern Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.5692\/clinicalneurol.52.19","volume":"52","author":"Yamasaki","year":"2012","journal-title":"Rinsho Shinkeigaku."},{"key":"B12","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1007\/s00415-013-7202-x","article-title":"Fulminant myelitis with Nmo igg antibody following treatment with interferon alpha","volume":"261","author":"Usmani","year":"2014","journal-title":"J Neurol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/2050-6511-15-56","article-title":"A case of classic neuromyelitis optica (devic's syndrome) triggered by pegylated-interferon alpha","volume":"15","author":"Mangioni","year":"2014","journal-title":"BMC Pharmacol Toxicol."},{"key":"B14","first-page":"180","article-title":"Multiple sclerosis with positive anti-aquaporin-4 antibody, manifested after interferon-alpha-2b\/ribavirin therapy for chronic hepatitis C. A case report","volume":"66","author":"Kajiyama","year":"2007","journal-title":"Neurol Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.msard.2019.04.023","article-title":"Neuromyelitis optica spectrum disorder occurred after interferon alpha therapy in malignant melanoma","volume":"32","author":"Gao","year":"2019","journal-title":"Mult Scler Relat Disord."},{"key":"B16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.55563\/clinexprheumatol\/ddxmp9","article-title":"Myeloid neoplasms and autoimmune diseases: markers of association","volume":"40","author":"Galimberti","year":"2022","journal-title":"Clin Exp Rheumatol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.lrr.2013.06.004","article-title":"Myeloproliferative neoplasms in five multiple sclerosis patients","volume":"2","author":"Thorsteinsdottir","year":"2013","journal-title":"Leuk Res Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3341\/kjo.2011.25.1.33","article-title":"Analysis of the causes of optic disc swelling","volume":"25","author":"Jung","year":"2011","journal-title":"Korean J Ophthalmol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1097\/WNO.0b013e31821a8b0b","article-title":"Papilledema: the vexing issues","volume":"31","author":"Trobe","year":"2011","journal-title":"J Neuroophthalmol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.jfo.2017.02.002","volume":"40","author":"Rougier","year":"2017","journal-title":"J Fr Ophtalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2147\/JPR.S60633","article-title":"Idiopathic intracranial hypertension: ongoing clinical challenges and future prospects","volume":"9","author":"Julayanont","year":"2016","journal-title":"J Pain Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.cgh.2012.11.021","article-title":"Intractable nausea and vomiting from autoantibodies against a brain water channel","volume":"11","author":"Iorio","year":"2013","journal-title":"Clin Gastroenterol Hepatol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev.immunol.23.021704.115843","article-title":"Type I interferons (alpha\/beta) in immunity and autoimmunity","volume":"23","author":"Theofilopoulos","year":"2005","journal-title":"Annu Rev Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"491","DOI":"10.2165\/11591110-000000000-00000","article-title":"The mechanism of action of interferon-beta in relapsing multiple sclerosis","volume":"25","author":"Kieseier","year":"2011","journal-title":"CNS Drugs."},{"key":"B25","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/s41571-021-00588-9","article-title":"Harnessing cytokines and chemokines for cancer therapy","volume":"19","author":"Propper","year":"2022","journal-title":"Nat Rev Clin Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/S0140-6736(13)60954-X","article-title":"Immunopathogenic mechanisms of systemic autoimmune disease","volume":"382","author":"Wahren-Herlenius","year":"2013","journal-title":"Lancet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jaut.2018.08.003","article-title":"Interferon alpha: the key trigger of Type 1 diabetes","volume":"94","author":"Lombardi","year":"2018","journal-title":"J Autoimmun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"11286","DOI":"10.3390\/ijms222011286","article-title":"The pathogenesis, molecular mechanisms, and therapeutic potential of the interferon pathway in systemic lupus erythematosus and other autoimmune diseases","volume":"22","author":"Ramaswamy","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/glia.22608","article-title":"Interferons in the central nervous system: a few instruments play many tunes","volume":"62","author":"Owens","year":"2014","journal-title":"Glia."},{"key":"B30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1097\/CND.0000000000000214","article-title":"Autoimmune neuromuscular diseases induced by immunomodulating drugs","volume":"20","author":"Supakornnumporn","year":"2018","journal-title":"J Clin Neuromuscul Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.msard.2016.05.016","article-title":"Longstanding spastic paraparesis in a patient infected with hepatitis C virus and seropositive for aquaporin-4 antibody - case report and review of the literature","volume":"8","author":"Ferreira","year":"2016","journal-title":"Mult Scler Relat Disord."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1053\/j.gastro.2016.02.039","article-title":"Extrahepatic manifestations of hepatitis C: a meta-analysis of prevalence, quality of life, and economic burden","volume":"150","author":"Younossi","year":"2016","journal-title":"Gastroenterology."},{"key":"B33","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/s12974-020-02003-z","article-title":"Microglial responses to peripheral Type 1 interferon","volume":"17","author":"Aw","year":"2020","journal-title":"J Neuroinflammation."},{"key":"B34","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.immuni.2016.04.005","article-title":"Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment","volume":"44","author":"Blank","year":"2016","journal-title":"Immunity."},{"key":"B35","doi-asserted-by":"publisher","first-page":"577742","DOI":"10.1016\/j.jneuroim.2021.577742","article-title":"Clinicoradiological comparative study of aquaporin-4-Igg seropositive neuromyelitis optica spectrum disorder (Nmosd) and Mog antibody associated disease (Mogad): a prospective observational study and review of literature","volume":"361","author":"Nagireddy","year":"2021","journal-title":"J Neuroimmunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1093\/brain\/aws321","article-title":"Chronic exposure of astrocytes to interferon-alpha reveals molecular changes related to aicardi-goutieres syndrome","volume":"136","author":"Cuadrado","year":"2013","journal-title":"Brain."},{"key":"B37","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1586\/eci.12.106","article-title":"Fueling autoimmunity: Type I interferon in autoimmune diseases","volume":"9","author":"Di Domizio","year":"2013","journal-title":"Expert Rev Clin Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s00109-016-1421-4","article-title":"Cause and consequences of the activated Type I interferon system in Sle","volume":"94","author":"Eloranta","year":"2016","journal-title":"J Mol Med (Berl)."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1038\/s41467-020-16625-7","article-title":"Transcriptomics and proteomics reveal a cooperation between interferon and T-helper 17 cells in neuromyelitis optica","volume":"11","author":"Agasing","year":"2020","journal-title":"Nat Commun."},{"key":"B40","first-page":"332","article-title":"Myelin-specific Th17 cells induce severe relapsing optic neuritis with irreversible loss of retinal ganglion cells in C57bl\/6 mice","volume":"22","author":"Larabee","year":"2016","journal-title":"Mol Vis."},{"key":"B41","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.expneurol.2013.02.005","article-title":"Neuromyelitis optica-like pathology is dependent on Type I interferon response","volume":"247","author":"Khorooshi","year":"2013","journal-title":"Exp Neurol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"703249","DOI":"10.3389\/fneur.2021.703249","article-title":"An experimental model of neuromyelitis optica spectrum disorder-optic neuritis: insights into disease mechanisms","volume":"12","author":"Soerensen","year":"2021","journal-title":"Front Neurol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1172\/JCI134816","article-title":"Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion","volume":"130","author":"Chen","year":"2020","journal-title":"J Clin Invest."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3961","DOI":"10.1172\/JCI138804","article-title":"Microglia complement astrocytes in neuromyelitis optica","volume":"130","author":"Moinfar","year":"2020","journal-title":"J Clin Invest."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1002\/glia.23154","article-title":"Type I interferon pathway in cns homeostasis and neurological disorders","volume":"65","author":"Blank","year":"2017","journal-title":"Glia."},{"key":"B46","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1002\/glia.23938","article-title":"Type I interferon-activated microglia are critical for neuromyelitis optica pathology","volume":"69","author":"Wlodarczyk","year":"2021","journal-title":"Glia."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1002\/glia.23460","article-title":"Microglia have a more extensive and divergent response to interferon-alpha compared with astrocytes","volume":"66","author":"Li","year":"2018","journal-title":"Glia."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1523\/JNEUROSCI.2830-13.2014","article-title":"Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain","volume":"34","author":"Campbell","year":"2014","journal-title":"J Neurosci."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.872684\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T09:18:41Z","timestamp":1650878321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.872684\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,25]]},"references-count":48,"alternative-id":["10.3389\/fneur.2022.872684"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.872684","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2022,4,25]]},"article-number":"872684"}}