The authors declare that they have no competing interests in relation to this work. Potential conflicts of interest outside the submitted work are as follows: TZ has nothing to disclose. LM received compensations for speaking activities and/or for participating to advisory board from Merck, Celgene, Biogen, Sanofi, Novartis, Roche, Alexion, and Amgen. SG received compensation for speaking activities from Bristol Squibb Meyer, Novartis, Merck. AN has nothing to disclose. CZ received compensation for speaking activities, and/or consulting services, from Alexion, AstraZeneca, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Roche, Sanofi. IG has nothing to disclose. AG received compensation for speaking activities from Novartis. FE received consulting and speaking fees from Novartis and Sanofi Genzyme. MGS has nothing to disclose. PMVR 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 Multiple Sclerosis and Related Disorders; and Associate Co-Editor for Europe and Africa for Multiple Sclerosis Journal. M. 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 Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, 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.

Approval was received from the institutional ethical standards committee on human experimentation of IRCCS Ospedale San Raffaele for any experiments using human subjects. Written informed consent was obtained from all subjects prior to study participation according to the Declaration of Helsinki.