{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:24:58Z","timestamp":1790504698633,"version":"4.1.0"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["PA 0185"],"award-info":[{"award-number":["PA 0185"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Fund for Clinical Neuroscience at Ume\u00e5 University Hospital"},{"name":"Regional Agreement Between Ume\u00e5 University and V\u00e4sterbotten County Council on Cooperation in the Field of Medicine, Odontology and Health"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2\u00a0years. During the extension phase, treatment with 25\u00a0mg rituximab was administered every 6\u00a0months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>IT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Classification of evidence<\/jats:title>\n                <jats:p>This study provides class IV evidence that intraventricularly administered rituximab in progressive MS is associated with a risk for bacterial meningitis and does not halt disease progression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>EU Clinical Trial Register<\/jats:title>\n                <jats:p>EudraCT; 2008-002626-11 and 2012-000721-53<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-020-10210-0","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T08:20:47Z","timestamp":1599726047000},"page":"651-657","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Intrathecal treatment trial of rituximab in progressive MS: results after a 2-year extension"],"prefix":"10.1007","volume":"268","author":[{"given":"Joakim","family":"Bergman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Burman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommy","family":"Bergenheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-2220","authenticated-orcid":false,"given":"Anders","family":"Svenningsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"10210_CR1","doi-asserted-by":"publisher","first-page":"e1893","DOI":"10.1212\/WNL.0000000000006500","volume":"91","author":"J Bergman","year":"2018","unstructured":"Bergman J, Burman J, Gilthorpe JD, Zetterberg H, Jiltsova E, Bergenheim T, Svenningsson A (2018) Intrathecal treatment trial of rituximab in progressive MS: an open-label phase 1b study. Neurology 91:e1893\u2013e1901","journal-title":"Neurology"},{"key":"10210_CR2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1212\/WNL.59.5.679","volume":"59","author":"JA Cohen","year":"2002","unstructured":"Cohen JA, Cutter GR, Fischer JS, Goodman AD, Heidenreich FR, Kooijmans MF, Sandrock AW, Rudick RA, Simon JH, Simonian NA, Tsao EC, Whitaker JN (2002) Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 59:679\u2013687","journal-title":"Neurology"},{"key":"10210_CR3","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1001\/jamaneurol.2014.1895","volume":"71","author":"JA Cohen","year":"2014","unstructured":"Cohen JA, Krishnan AV, Goodman AD, Potts J, Wang P, Havrdova E, Polman C, Rudick RA (2014) The clinical meaning of walking speed as measured by the timed 25-foot walk in patients with multiple sclerosis. JAMA Neurol 71:1386\u20131393","journal-title":"JAMA Neurol"},{"key":"10210_CR4","doi-asserted-by":"publisher","first-page":"1862","DOI":"10.1177\/1352458518808189","volume":"24","author":"EJ Fox","year":"2018","unstructured":"Fox EJ, Markowitz C, Applebee A, Montalban X, Wolinsky JS, Belachew S, Fiore D, Pei J, Musch B, Giovannoni G (2018) Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: findings from the phase III randomized ORATORIO trial. Mult Scler 24:1862\u20131870","journal-title":"Mult Scler"},{"key":"10210_CR5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1601277","author":"SL Hauser","year":"2016","unstructured":"Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L, Opera I, Investigators OIC (2016) Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMoa1601277","journal-title":"N Engl J Med"},{"key":"10210_CR6","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/ana.21867","volume":"66","author":"K Hawker","year":"2009","unstructured":"Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH (2009) Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 66:460\u2013471","journal-title":"Ann Neurol"},{"key":"10210_CR7","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S1474-4422(14)70256-X","volume":"14","author":"DH Mahad","year":"2015","unstructured":"Mahad DH, Trapp BD, Lassmann H (2015) Pathological mechanisms in progressive multiple sclerosis. 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N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMoa1606468","journal-title":"N Engl J Med"},{"key":"10210_CR9","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1200\/JCO.2006.09.7311","volume":"25","author":"JL Rubenstein","year":"2007","unstructured":"Rubenstein JL, Fridlyand J, Abrey L, Shen A, Karch J, Wang E, Issa S, Damon L, Prados M, McDermott M, O'Brien J, Haqq C, Shuman M (2007) Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol 25:1350\u20131356","journal-title":"J Clin Oncol"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-020-10210-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-020-10210-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-020-10210-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T23:30:38Z","timestamp":1631057438000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-020-10210-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,8]]},"references-count":9,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10210"],"URL":"https:\/\/doi.org\/10.1007\/s00415-020-10210-0","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,8]]},"assertion":[{"value":"1 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Joakim Bergman reports no disclosures. Joachim Burman reports no disclosures. Tommy Bergenheim reports no disclosures. Anders Svenningsson reports no disclosures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The original ITT-PMS study and the extension study were both approved by the Regional Ethical Review Board in Ume\u00e5 and registered with the EU Clinical Trial Register (EudraCT; 2008-002626-11 and 2012-000721-53, respectively). The trials were performed in accordance with standards of GCP and the principles of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}