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Potential conflicts of interest outside the submitted work are as follows: M Jiang has nothing to disclose. M Rubin has nothing to disclose. L. Storelli received speakers\u2019 honoraria from Biogen Idec. M Grosselle has nothing to disclose. F Esposito has nothing to disclose. E Pagani has nothing to disclose. M Margoni, A Meani has nothing to disclose. 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\n                      Multiple Sclerosis and Related Disorders\n                      ; and Associate Co-Editor for Europe and Africa for\n                      Multiple Sclerosis Journal\n                      . M. Filippi is Editor-in-Chief of the\n                      Journal of Neurology\n                      , Associate Editor of\n                      Human Brain Mapping\n                      ,\n                      Neurological Sciences,\n                      and\n                      Radiology\n                      ; 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. P Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck, Bristol Myers Squibb, Genzyme, Horizon and Sanofi.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the institutional ethics committee of IRCCS Ospedale San Raffaele, Milan, Italy (Protocol No. 2015\u201333). Written informed consent was obtained from all participants before study participation according to the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"538"}}