{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:38:15Z","timestamp":1789609095745,"version":"build-2803163510"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Fingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML); however, its discontinuation may cause severe immune reconstitution inflammatory syndrome (IRIS). As both of these conditions (especially fingolimod induced PML) are rarely described in medical case reports distinguishing between PML-IRIS and MS-IRIS may be diagnostically challenging.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We report a patient with severe clinical decline (Expanded Disability Status Scale (EDSS) increasing from 3.5 to 7.5) and multiple, large, contrast-enhancing lesions on brain magnetic resonance imaging (MRI) a few months after fingolimod withdrawal. The diagnostic possibilities included IRIS due to fingolimod withdrawal versus PML-IRIS. The JC virus (JCV) antibody index was positive (2.56); however, cerebrospinal fluid (CSF) JCV real-time polymerase chain reaction (JCV-PCR) was negative and brain biopsy was not performed. After a long course of aggressive treatment (several pulsed methylprednisolone infusions, plasmapheresis, intravenous dexamethasone, oral mirtazapine) the patient gradually recovered (EDSS 2.5) and MRI lesions decreased.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This case report demonstrates the importance of monitoring patients carefully after the discontinuation of fingolimod for PML-IRIS and rebound MS with IRIS as these conditions may manifest similarly.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-022-02839-3","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T12:03:22Z","timestamp":1660910602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Progressive multifocal leukoencephalopathy or immune reconstitution inflammatory syndrome after fingolimod cessation? A case report"],"prefix":"10.1186","volume":"22","author":[{"given":"D.","family":"Mickeviciene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3953-597X","authenticated-orcid":false,"given":"A.","family":"Baltusiene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Afanasjeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Afanasjevas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Gleizniene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Rastenyte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JR.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"2839_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fimmu.2018.00138","volume":"9","author":"EA Mills","year":"2018","unstructured":"Mills EA, Mao-Draayer Y. Understanding progressive multifocal leukoencephalopathy risk in multiple sclerosis patients treated with immunomodulatory therapies: A bird\u2019s eye view. Front Immunol. 2018;9:13. https:\/\/doi.org\/10.3389\/fimmu.2018.00138 Frontiers Media S.A.","journal-title":"Front Immunol."},{"key":"2839_CR2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005529","author":"JR Berger","year":"2018","unstructured":"Berger JR, Cree BA, Greenberg B, Hemmer B, Ward BJ, Dong VM, et al. Progressive multifocal leukoencephalopathy after fingolimod treatment. Neurology. 2018. https:\/\/doi.org\/10.1212\/WNL.0000000000005529.","journal-title":"Neurology"},{"issue":"10","key":"2839_CR3","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1111\/cns.12992","volume":"24","author":"ME Evangelopoulos","year":"2018","unstructured":"Evangelopoulos ME, Miclea A, Schrewe L, Briner M, Salmen A, Engelhardt B, et al. Frequency and clinical characteristics of Multiple Sclerosis rebounds after withdrawal of Fingolimod. CNS Neurosci Ther. 2018;24(10):984\u20136. https:\/\/doi.org\/10.1111\/cns.12992 Blackwell Publishing Ltd.","journal-title":"CNS Neurosci Ther"},{"issue":"19","key":"2839_CR4","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1212\/WNL.0000000000002654","volume":"86","author":"TV Gyang","year":"2016","unstructured":"Gyang TV, Hamel J, Goodman AD, Gross RA, Samkoff L. Fingolimod-associated PML in a patient with prior immunosuppression. Neurology. 2016;86(19):1843\u20135. https:\/\/doi.org\/10.1212\/WNL.0000000000002654 Lippincott Williams and Wilkin.","journal-title":"Neurology"},{"key":"2839_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70040-5","volume-title":"Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis","author":"TS Tan","year":"2010","unstructured":"Tan TS, Koralnik IJ. 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J Investig Med High Impact Case Rep. 2020. https:\/\/doi.org\/10.1177\/2324709620939802.","journal-title":"J Investig Med High Impact Case Rep"},{"issue":"2","key":"2839_CR8","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s40120-019-00160-9","volume":"8","author":"B Barry","year":"2019","unstructured":"Barry B, Erwin AA, Stevens J, Tornatore C. Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations. Neurol Ther. 2019;8(2):241\u201350. https:\/\/doi.org\/10.1007\/s40120-019-00160-9 Springer Healthcare.","journal-title":"Neurol Ther"},{"key":"2839_CR9","unstructured":"R. Fox, B. Cree, B. Greenberg, B. Hemmer, B.J. Ward, D. Ontaneda, A. Moore, Y. Zhang, R. Sullivan, P. Girase, T. Hach, J.R. Berger. Update on the risk estimates of progressive multifocal leukoencephalopathy related to fingolimod. Oral presentation at the 8thJoint ACTRIMS-ECTRIMS Meeting, MSVirtual2020, September 11\u201213, 2020. https:\/\/www.medcommshydhosting.com\/MSKnowledgecenter\/ectrims\/presentations\/CPO\/FC02.02.pdf."},{"key":"2839_CR10","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41582-020-00427-y","volume":"17","author":"I Cortese","year":"2021","unstructured":"Cortese I, Reich DS, Nath A. Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease. Nat Rev Neurol. 2021;17:37\u201351. https:\/\/doi.org\/10.1038\/s41582-020-00427-y.","journal-title":"Nat Rev Neurol"},{"key":"2839_CR11","doi-asserted-by":"publisher","DOI":"10.1111\/cen3.12397","author":"F Yoshii","year":"2017","unstructured":"Yoshii F, Moriya Y, Ohnuki T, Ryo M, Takahashi W. Neurological safety of fingolimod: An updated review\u2019\u2019. 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Berger has received grant support from Biogen and Genentech\/Roche. He has received honoraria as a consultant for Amgen, Biogen, Bristol Myers Squibb\/Celgene, Dr. Reddy, EMD Serono, Encycle, Excision-Bio, Genentech\/Roche, Genzyme, MAPI, Merck, Millennium\/Takeda, Morphic, and Shire.D. Mickeviciene reports grants and consulting fees from Merck\/EMD Serono, Novartis, Roche, and Sanofi Genzyme, outside the submitted work.A. Baltusiene has no conflict of interest.B. Afanasjeva has no conflict of interest.D. Afanasjevas has no conflict of interest.Prof. R. Gleizniene has no conflict of interest.Prof. D. Rastenyte has no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"306"}}