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FC has nothing to disclose. AG has nothing to disclose. LF has nothing to disclose. LM received compensation for speaking activities, travel grant, and participation in advisory board from Biogen, Bristol-Myers Squibb, Novartis, Roche, Sanofi-Genzyme, Merck-Serono, Biogen, and Alexion. M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Roche; and speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Celgene, Horizon Therapeutics Italy, Merck Serono SpA, Mitsubishi-Tanabe Pharma, Neuraxpharm, Novartis, Roche, Sandoz, and Sanofi. She receives research support from the MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders; and Associate Co-Editor for Europe and Africa for Multiple Sclerosis Journal. Prof. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Almirall, Biogen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Roche, Sanofi; speaking activities from Amgen, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Chiesi Italia SpA, Eisai, Eli Lilly, Fujirebio, Genzyme, Janssen, Merck, Neopharmed Gentili, Neuraxpharm, Novartis, Novo Nordisk, Roche, Sanofi, Takeda; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Eli Lilly, GE Healthcare Ltd, Merck, Neuraxpharm, Novartis, Roche, Sandoz, Sanofi, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the ethical committee of IRCCS Ospedale San Raffaele and conducted according to the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients signed an informed consent for the recording of their clinical data in the Italian MS and Related Disorders Register (IMS&RD), and their use for research purposes.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. 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