{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:38:20Z","timestamp":1789609100382,"version":"build-2803163510"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"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":["J Neurol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background\/objective<\/jats:title>\n                <jats:p>The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>As of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132\u00a0months (median 76\u00a0months) was available in 11\/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6\/11.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-023-11924-7","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T14:01:43Z","timestamp":1695218503000},"page":"374-385","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study"],"prefix":"10.1007","volume":"271","author":[{"given":"Tobias","family":"Moser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Baumgartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Bsteh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Di Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Enzinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Fertl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Koppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulus S.","family":"Rommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Safoschnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Seifert-Held","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Stepansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-5533","authenticated-orcid":false,"given":"Johann","family":"Sellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"11924_CR1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1527-3458.2007.00003.x","volume":"13","author":"O Stuve","year":"2007","unstructured":"Stuve O, Bennett JL (2007) Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri) in inflammatory diseases. 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A.B. received travel support from Biogen, Novartis and Sanofi\/Genzyme. T.B. has participated in meetings sponsored by and received honoraria (lectures, advisory boards, and consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Almirall, Bayer, Biogen, Biologix, Bionorica, Celgene\/Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK), Janssen-Cilag, Medday, Merck, Novartis, Octapharma, Roche, Sanofi Genzyme, Teva, and TG Pharmaceuticals. G.B. has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene\/BMS, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene\/BMS, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. He has received financial support in the past 12\u00a0months by unrestricted research grants (Celgene\/BMS, Novartis). F.DP. has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Horizon, Janssen-Cilag, Merck, Novartis, Sanofi-Genzyme, Teva, Celgene and Roche. Her institution has received research grants from Roche. C.E. has received funding for travel and speaker honoraria from Biogen, Bayer, Merck, Novartis, Roche, Shire, Genzyme, and Teva; has received research support from Biogen, Merck, and Teva; and is serving on scientific advisory boards for Bayer, Biogen, Celgene\/BMS, Merck, Novartis, Roche, and Teva. E.F. has participated in advisory boards and scientific meetings, she also received honoraria for lectures and travel funding on behalf of Biogen, Celgene\/BMS, Novartis, Janssen, Sanofi-Genzyme and Teva. P.SR. received honorary for lectures or consultancy from Alexion, Allmiral, Amicus, Biogen, Genzyme, Horizon, Merck, Novartis, Roche, Sandoz, Teva; and received research grants from Amicus, Merck and Roche. G.S. received honoraria for participation in advisory boards and travel support from Schering, Biogen Idec, Sanofi, Teva, Genzyme, Roche, Merck, Novartis, Pfizer. J.S. received honoraria for lectures, preparation of teaching material, and participation in scientific advisory boards from Astra Zeneca, Biogen, BMS\/Celgene, Horizon, Immunic, Janssen, Lundbeck, Merck, Novartis, Pfizer, Roche, Sandoz and Sanofi. The remaining authors report no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}