{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T20:01:45Z","timestamp":1774641705883,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Natalizumab (<jats:styled-content style=\"fixed-case\">NTZ<\/jats:styled-content>) is an effective drug for the treatment of relapsing\u2010remitting multiple sclerosis. In some patients discontinuation is mandatory due to the risk of progressive multifocal leukoencephalopathy. However, severe clinical and radiological worsening has been described after drug cessation. Our aim was to describe the clinical and radiological features of the rebound phenomenon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Patients switched from<jats:styled-content style=\"fixed-case\">NTZ<\/jats:styled-content>to Fingolimod (<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>) who had presented a rebound after discontinuation were selected. Clinical and magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) data were collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four<jats:styled-content style=\"fixed-case\">JC<\/jats:styled-content>virus positive patients were included. The mean disease duration was 9.5\u00a0years (<jats:italic><jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content><\/jats:italic>: 4.12) with a mean time of 3.1\u00a0years on<jats:styled-content style=\"fixed-case\">NTZ<\/jats:styled-content>. All patients started<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>within 3\u20134\u00a0months. Neurological deterioration started in a mean time of 3.5\u00a0months (<jats:italic><jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content><\/jats:italic>: 2.08) with multifocal involvement: 75% motor disturbances, 50% cognitive impairment, 25% seizures. The average worsening in Expanded Disability Status Scale [<jats:styled-content style=\"fixed-case\">EDSS<\/jats:styled-content>] was of 3.25 points (<jats:italic><jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content><\/jats:italic>: 2.33). The<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>showed a very large increase in T2 and gadolinium\u2010enhanced lesions (mean: 23.67,<jats:italic><jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content><\/jats:italic>: 18.58). All patients received 5\u00a0days of IV methylprednisolone, one patient required plasma exchange. All the patients presented neurological deterioration with an<jats:styled-content style=\"fixed-case\">EDSS<\/jats:styled-content>worsening of 1.13 points (<jats:italic><jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content><\/jats:italic>: 0.48). After the rebound three patients continued treatment with<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>, only one patient restarted<jats:styled-content style=\"fixed-case\">NTZ<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Discontinuation of<jats:styled-content style=\"fixed-case\">NTZ<\/jats:styled-content>treatment may trigger a severe rebound with marked clinical and radiological worsening. A very careful evaluation of benefit\u2010risk should be considered before<jats:styled-content style=\"fixed-case\">NTZ<\/jats:styled-content>withdrawal, and a close monitoring and a short washout period is recommended after drug withdrawal.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.671","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T01:42:38Z","timestamp":1489542158000},"source":"Crossref","is-referenced-by-count":38,"title":["Catastrophic outcome of patients with a rebound after Natalizumab treatment discontinuation"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-0771","authenticated-orcid":false,"given":"In\u00e9s","family":"Gonz\u00e1lez\u2010Suarez","sequence":"first","affiliation":[{"name":"Neurology Department Multiple Sclerosis Center IdiSSC Hospital Clinico San Carlos Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Rodr\u00edguez de Antonio","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital Universitario de Fuenlabrada Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Orviz","sequence":"additional","affiliation":[{"name":"Neurology Department Multiple Sclerosis Center IdiSSC Hospital Clinico San Carlos Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Moreno\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Demyelinating Disease Unit Neurology Department Hospital Universitario 12 de Octubre Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda D.","family":"Valle\u2010Arcos","sequence":"additional","affiliation":[{"name":"Demyelinating Disease Unit Neurology Department Hospital Universitario 12 de Octubre Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi A.","family":"Matias\u2010Guiu","sequence":"additional","affiliation":[{"name":"Neurology Department Multiple Sclerosis Center IdiSSC Hospital Clinico San Carlos Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Valencia","sequence":"additional","affiliation":[{"name":"Neurology Department Multiple Sclerosis Center IdiSSC Hospital Clinico San Carlos Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Jorquera Moya","sequence":"additional","affiliation":[{"name":"Radiology Department IdiSSC Hospital Clinico San Carlos Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Oreja\u2010Guevara","sequence":"additional","affiliation":[{"name":"Neurology Department Multiple Sclerosis Center IdiSSC Hospital Clinico San Carlos Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2014.05.028"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.6240"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.80.7_supplement.S41.003","article-title":"Natalizumab effects during a 6\u2010month dose interruption: Relationship of pharmacokinetic (PK), pharmacodynamic (PD), and MRI measurements","volume":"80","author":"Cree B.","year":"2013","journal-title":"Neurology"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512458009"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000109933"},{"key":"e_1_2_7_8_1","unstructured":"European Medicines Agency(2016).European Medicines Agency recommends additional measures to better manage risk of progressive multifocal leukoencephalopathy (PML) with Tysabri. 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