{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:18:28Z","timestamp":1761920308861,"version":"3.41.0"},"reference-count":96,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,6,18]],"date-time":"2017-06-18T00:00:00Z","timestamp":1497744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Exp Neuroim"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fingolimod (<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>) is the first oral medication approved for treatment of relapsing\u2013remitting multiple sclerosis (<jats:styled-content style=\"fixed-case\">RRMS<\/jats:styled-content>). Its effectiveness and safety were confirmed in several phase<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>clinical trials, but proper evaluation of safety in the real patient population requires long\u2010term post\u2010marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>patients, and there have been side\u2010effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>; (ii) safety profile; (iii) post\u2010marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>withdrawal; (vi) relationship between<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>and progressive multifocal leukoencephalopathy; (vii)<jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>and progressive multifocal leukoencephalopathy\u2010related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.<\/jats:p>","DOI":"10.1111\/cen3.12397","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T04:12:45Z","timestamp":1497845565000},"page":"233-243","source":"Crossref","is-referenced-by-count":39,"title":["Neurological safety of fingolimod: An updated review"],"prefix":"10.1111","volume":"8","author":[{"given":"Fumihito","family":"Yoshii","sequence":"first","affiliation":[{"name":"Department of Neurology Saiseikai Hiratsuka Hospital Hiratsuka Japan"},{"name":"Department of Neurology Tokai University Oiso Hospital Oiso Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Moriya","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokai University Oiso Hospital Oiso Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohide","family":"Ohnuki","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokai University Oiso Hospital Oiso Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafuchi","family":"Ryo","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokai University Oiso Hospital Oiso Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wakoh","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokai University Oiso Hospital Oiso Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMct1101691"},{"key":"e_1_2_12_3_1","first-page":"261","article-title":"Fingolimod for multiple sclerosis and emerging indications: appropriate patient selection, safety precautions, and special considerations","volume":"12","author":"Ayzenberg I","year":"2016","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909494"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70049-3"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907839"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-310597"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.1051"},{"key":"e_1_2_12_9_1","first-page":"CD009371","article-title":"Fingolimod for relapsing\u2010remitting multiple sclerosis","volume":"4","author":"La Mantia L","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511435984"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-14-21"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2014.03.002"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-14-65"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513500551"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516645868"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-017-0794-5"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1343794"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285616628766"},{"key":"e_1_2_12_19_1","unstructured":"https:\/\/drs-net.novartis.co.jp\/dr\/products\/product\/gilenya\/. Accessed December 1 2016."},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-009-0178-z"},{"key":"e_1_2_12_21_1","first-page":"3557","article-title":"Analysis of pathological characteristics of acute and chronic cerebral tumefactive demyelinating lesions","volume":"94","author":"Sun C","year":"2014","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000344567.51394.e3"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31824c46ad"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512458009"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512463768"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182735cb3"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182735c7a"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31829deeb4"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513481395"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000435293.34351.11"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.06.013"},{"key":"e_1_2_12_32_1","article-title":"Tumefactive demyelinating lesions in patients with relapsing remitting multiple sclerosis treated with fingolimod","volume":"12","author":"Totaro R","year":"2014","journal-title":"J Neurol Neurophysiol"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00039"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.5692\/clinicalneurol.cn-000515"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2015.05.007"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12563"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000435305.95271.84"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.06.022"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35314"},{"key":"e_1_2_12_40_1","first-page":"21","article-title":"Tumefactive demyelinating lesions: spectrum of disease, diagnosis and treatment","volume":"7","author":"Totaro R","year":"2016","journal-title":"Curr Neurobiol"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.7224\/1537-2073.2014-078"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2013-305456"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821e7c8a"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.1057"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512454773"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6744-7"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2012.11.001"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12195"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-014-1800-y"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen3.12118"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2014-206314"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2015.03.022"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-015-0377-2"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285615594575"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.0826"},{"key":"e_1_2_12_56_1","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2016-215596","article-title":"Severe tumefactive rebound of multiple sclerosis following fingolimod cessation","volume":"2016","author":"Salam S","year":"2016","journal-title":"BMJ Case Rep"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2016.11.003"},{"key":"e_1_2_12_58_1","unstructured":"https:\/\/www.ms-supportnavi.com\/ja-jp\/home\/med\/tys\/safety\/04.html. Accessed December 1 2016."},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107829"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20160721"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24286"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828c2fa1"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-015-0316-4"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821a446b"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8217-x"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285615602832"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003740"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000321"},{"key":"e_1_2_12_69_1","unstructured":"https:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm456919.htm. Accessed December 1 2016."},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002654"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2017.01.006"},{"key":"e_1_2_12_72_1","first-page":"891","article-title":"Neuropathology of natalizumab\u2010associated progressive multifocal leukoencephalopathy","volume":"67","author":"Kanda T","year":"2015","journal-title":"Brain Nerve"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12699"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174005"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318253d61e"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825caf2c"},{"key":"e_1_2_12_77_1","first-page":"809252","article-title":"Neuroimaging of natalizumab complications in multiple sclerosis: PML and other associated entities","volume":"2015","author":"Honce JM","year":"2015","journal-title":"Mult Scler Int"},{"key":"e_1_2_12_78_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.21315\/mjms2016.23.5.12","article-title":"Natalizumab\u2010related progressive multifocal leukoencephalopathy\u2010immune reconstitution inflammatory syndrome: a case report highlighting clinical and MRI features","volume":"23","author":"Purohit B","year":"2016","journal-title":"Malays J Med Sci"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-311411"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1471-7"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0900-5"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31822e55e7"},{"key":"e_1_2_12_83_1","first-page":"307872","article-title":"PML\u2010IRIS during fingolimod diagnosed after natalizumab discontinuation","volume":"2014","author":"Killestein J","year":"2014","journal-title":"Case Rep Neurol Med"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2014.08.016"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2016.01.010"},{"key":"e_1_2_12_86_1","first-page":"5876798","article-title":"Progressive multifocal leukoencephalopathy in a multiple sclerosis patient diagnosed after switching from natalizumab to fingolimod","volume":"2016","author":"Sinnecker T","year":"2016","journal-title":"Case Rep Neurol Med"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.6240"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000283"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000323"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000325"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7169-7"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2016.03.003"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-016-0599-3"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511431973"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2016.03.004"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.5692\/clinicalneurol.53.513"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen3.12032"}],"container-title":["Clinical and Experimental Neuroimmunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen3.12397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen3.12397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T19:00:21Z","timestamp":1750359621000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen3.12397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,18]]},"references-count":96,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1111\/cen3.12397"],"URL":"https:\/\/doi.org\/10.1111\/cen3.12397","archive":["Portico"],"relation":{},"ISSN":["1759-1961","1759-1961"],"issn-type":[{"type":"print","value":"1759-1961"},{"type":"electronic","value":"1759-1961"}],"subject":[],"published":{"date-parts":[[2017,6,18]]}}}