{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:28:03Z","timestamp":1793726883433,"version":"4.6.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold><jats:italic>Neuromyelitis optica<\/jats:italic> spectrum disorder (NMOSD) is a relapsing autoimmune-related neurological disorder of the central nervous system. Most patients with NMOSD have serum anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). In addition to optic neuritis and myelitis, other insidious symptoms such as depressive state and chronic fatigue in NMOSD are gradually being recognized.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> To elucidate the impact of low- to medium-dose oral prednisolone (PSL) as a relapse prevention therapy for psychiatric disturbances and chronic fatigue in NMOSD, we evaluated clinical data from 39 patients with AQP4-IgG-positive NMOSD, along with the details of present and cumulative oral PSL dosage.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Thirty-six of the 39 patients were treated with low- to medium-dose oral PSL, and the mean and standard deviation of the present daily dose of oral PSL were 7.9 \u00b1 4.0 mg\/day. None of the patients were treated with a daily PSL dose of &amp;gt;15 mg. As a result, the disease duration and the untreated period before starting oral PSL showed weak to moderate correlations with the subsequent severities of psychiatric disturbance and fatigue level. Meanwhile, none of the other treatment-related variables evaluated, such as the present oral PSL daily dose, cumulative PSL dose, months of oral PSL administration, previous courses of steroid pulse therapy, and coadministered immunosuppressants, were correlated with these insidious symptoms.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our results suggest that the use of long-term low- to medium-dose oral PSL  \u226415 mg daily for relapse prevention in AQP4-IgG-positive NMOSD would not aggravate the psychiatric and fatigue conditions. On the contrary, early initiation of oral PSL for relapse prevention, together with significantly decreased relapse rate, alleviated the subsequent depressive state and fatigue from the disease.<\/jats:p>","DOI":"10.3389\/fneur.2021.608149","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T04:29:55Z","timestamp":1613968195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Early Treatment Initiation With Oral Prednisolone for Relapse Prevention Alleviates Depression and Fatigue in Aquaporin-4\u2013Positive Neuromyelitis optica Spectrum Disorder"],"prefix":"10.3389","volume":"12","author":[{"given":"Tetsuya","family":"Akaishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juichi","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","article-title":"A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis","volume":"364","author":"Lennon","year":"2004","journal-title":"Lancet."},{"key":"B2","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":"B3","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1084\/jem.20050304","article-title":"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel","volume":"202","author":"Lennon","year":"2005","journal-title":"J Exp Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e0177230","DOI":"10.1371\/journal.pone.0177230","article-title":"Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life","volume":"12","author":"Seok","year":"2017","journal-title":"PLoS ONE"},{"key":"B5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jneuroim.2015.05.007","article-title":"Depressive state and chronic fatigue in multiple sclerosis and neuromyelitis optica","volume":"283","author":"Akaishi","year":"2015","journal-title":"J Neuroimmunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0224419","DOI":"10.1371\/journal.pone.0224419","article-title":"Difference in fatigue and pain between neuromyelitis optica spectrum disorder and multiple sclerosis","volume":"15","author":"Masuda","year":"2020","journal-title":"PLoS ONE."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e17184","DOI":"10.1097\/MD.0000000000017184","article-title":"Comparison of psychiatric disturbances in patients with multiple sclerosis and neuromyelitis optica","volume":"98","author":"Shin","year":"2019","journal-title":"Medicine"},{"key":"B8","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/nrneurol.2017.117","article-title":"Fatigue as a symptom or comorbidity of neurological diseases. Nature reviews","volume":"13","author":"Penner","year":"2017","journal-title":"Neurology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.4103\/1735-1995.200275","article-title":"Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence","volume":"22","author":"Etemadifar","year":"2017","journal-title":"J Res Med Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s11940-015-0387-9","article-title":"Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic","volume":"18","author":"Kessler","year":"2016","journal-title":"Curr Treat Options Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1001\/jamaneurol.2014.2057","article-title":"Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder","volume":"71","author":"Huh","year":"2014","journal-title":"JAMA Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s11940-015-0378-x","article-title":"Acute and chronic management of neuromyelitis optica spectrum disorder","volume":"17","author":"Sherman","year":"2015","journal-title":"Curr Treatment Options Neurol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1177\/1352458507077189","article-title":"Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis","volume":"13","author":"Watanabe","year":"2007","journal-title":"Multiple Sclerosis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1212\/WNL.51.4.1219","article-title":"Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine","volume":"51","author":"Mandler","year":"1998","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/S1474-4422(20)30078-8","article-title":"Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial","volume":"19","author":"Traboulsee","year":"2020","journal-title":"Lancet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1056\/NEJMoa1900866","article-title":"Eculizumab in Aquaporin-4-positive neuromyelitis optica spectrum disorder","volume":"381","author":"Pittock","year":"2019","journal-title":"N Engl J Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1056\/NEJMoa1901747","article-title":"Trial of satralizumab in neuromyelitis optica spectrum disorder","volume":"38","author":"Yamamura","year":"2019","journal-title":"N Engl J Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"13890","DOI":"10.1038\/s41598-020-70919-w","article-title":"Progressive patterns of neurological disability in multiple sclerosis and neuromyelitis optica spectrum disorders","volume":"10","author":"Akaishi","year":"2020","journal-title":"Sci Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1212\/01.wnl.0000254502.87233.9a","article-title":"A secondary progressive clinical course is uncommon in neuromyelitis optica","volume":"68","author":"Wingerchuk","year":"2007","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e79649","DOI":"10.1371\/journal.pone.0079649","article-title":"Neuromyelitis optica in Austria in 2011: to bridge the gap between neuroepidemiological research and practice in a study population of 8.4 million people","volume":"8","author":"Aboul-Enein","year":"2013","journal-title":"PLoS ONE."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e640","DOI":"10.1212\/NXI.0000000000000640","article-title":"Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence","volume":"7","author":"Akaishi","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflammat."},{"key":"B22","doi-asserted-by":"publisher","first-page":"S94","DOI":"10.4103\/0976-500X.120975","article-title":"Corticosteroid-related central nervous system side effects","volume":"4","author":"Ciriaco","year":"2013","journal-title":"J Pharmacol Pharmacotherapeut"},{"key":"B23","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1710-1492-9-30","article-title":"A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Allergy Asthma Clin Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0033-3182(89)72293-3","article-title":"Psychiatric side effects of steroid therapy","volume":"30","author":"Kershner","year":"1989","journal-title":"Psychosomatics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"116671","DOI":"10.1016\/j.jns.2020.116671","article-title":"Repeated follow-up of AQP4-IgG titer by cell-based assay in neuromyelitis optica spectrum disorders (NMOSD)","volume":"410","author":"Akaishi","year":"2020","journal-title":"J Neurol Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1093\/brain\/awm062","article-title":"Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre","volume":"130","author":"Takahashi","year":"2007","journal-title":"Brain"},{"key":"B27","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0022-3999(93)90081-P","article-title":"Development of a fatigue scale","volume":"37","author":"Chalder","year":"1993","journal-title":"J Psychosomat Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1001\/archneurol.2011.249","article-title":"Brain involvement in neuromyelitis optica spectrum disorders","volume":"68","author":"Chan","year":"2011","journal-title":"Arch Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"414","DOI":"10.3389\/fneur.2020.00414","article-title":"Mirror-image lesions in sequential relapses of AQP4-positive neuromyelitis optica spectrum disorder","volume":"11","author":"Muir","year":"2020","journal-title":"Front Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.nic.2016.12.010","article-title":"Neuromyelitis optica spectrum disorders","volume":"27","author":"Akaishi","year":"2017","journal-title":"Neuroimaging Clin North Am"},{"key":"B31","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.jneuroim.2016.02.011","article-title":"Factors that impact health-related quality of life in neuromyelitis optica spectrum disorder: anxiety, disability, fatigue and depression","volume":"293","author":"Shi","year":"2016","journal-title":"J Neuroimmunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e286","DOI":"10.1212\/NXI.0000000000000286","article-title":"Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder","volume":"3","author":"Chavarro","year":"2016","journal-title":"Neurol Neuroimmunol Neuroinflammat."},{"key":"B33","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.msard.2017.11.002","article-title":"Psychiatric comorbidities and suicidality among patients with neuromyelitis optica spectrum disorders in Argentina","volume":"19","author":"Fernandez","year":"2018","journal-title":"Mult Scler Relat Disord"},{"key":"B34","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1001\/archpsyc.56.6.527","article-title":"Decreased memory performance in healthy humans induced by stress-level cortisol treatment","volume":"56","author":"Newcomer","year":"1999","journal-title":"Arch General Psychiatr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4088\/PCC.v03n0104","article-title":"Mood and cognitive changes during systemic corticosteroid therapy","volume":"3","author":"Brown","year":"2001","journal-title":"Primary Care Companion J Clin Psychiatr."},{"key":"B36","doi-asserted-by":"publisher","first-page":"169","DOI":"10.7861\/clinmedicine.19-2-169","article-title":"Neuromyelitis optica spectrum disorders","volume":"19","author":"Huda","year":"2019","journal-title":"Clin Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00401-013-1116-7","article-title":"Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica","volume":"125","author":"Misu","year":"2013","journal-title":"Acta Neuropathol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1152\/japplphysiol.00460.2010","article-title":"Thermoregulation in multiple sclerosis","volume":"109","author":"Davis","year":"2010","journal-title":"J Appl Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1159\/000361045","article-title":"Uhthoff's phenomenon in multiple sclerosis and neuromyelitis optica","volume":"72","author":"Park","year":"2014","journal-title":"Eur Neurol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1136\/jnnp-2018-320050","article-title":"Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis","volume":"90","author":"Manjaly","year":"2019","journal-title":"J Neurol Neurosurg Psychiatr."},{"key":"B41","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.clinph.2009.12.013","article-title":"Fatigue in multiple sclerosis: mechanisms and management","volume":"121","author":"Vucic","year":"2010","journal-title":"Clin Neurophysiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/cns.12411","article-title":"Sleep disturbances, and depression correlated with fatigue in neuromyelitis optica spectrum disorder","volume":"21","author":"Pan","year":"2015","journal-title":"CNS Neurosci Ther"},{"key":"B43","doi-asserted-by":"publisher","first-page":"8914","DOI":"10.1073\/pnas.1712475114","article-title":"Inflammation correlates with symptoms in chronic fatigue syndrome","volume":"114","author":"Komaroff","year":"2017","journal-title":"Proc Natl Acad Sci USA."},{"key":"B44","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1186\/s13075-015-0784-1","article-title":"Fatigue in chronic inflammation - a link to pain pathways","volume":"17","author":"Louati","year":"2015","journal-title":"Arthrit Res Therapy"},{"key":"B45","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.jns.2003.11.005","article-title":"Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial","volume":"218","author":"Tomassini","year":"2004","journal-title":"J Neurol Sci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s13311-015-0400-8","article-title":"Present and future therapies in neuromyelitis optica spectrum disorders","volume":"13","author":"Kleiter","year":"2016","journal-title":"Neurotherapeutics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1177\/1941874412458678","volume":"3","year":"2013","journal-title":"Neurohospitalist"},{"key":"B48","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.ophtha.2008.12.001","article-title":"Use of inhaled and oral corticosteroids and the long-term risk of cataract","volume":"116","author":"Wang","year":"2009","journal-title":"Ophthalmology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1002\/art.38210","article-title":"Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis","volume":"66","author":"del","year":"2014","journal-title":"Arthrit Rheumatol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.608149\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T04:29:59Z","timestamp":1613968199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.608149\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,22]]},"references-count":49,"alternative-id":["10.3389\/fneur.2021.608149"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.608149","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,22]]},"article-number":"608149"}}