F. D. Lublin, S. C. Reingold, and J. A. Cohen, Defining the clinical course of multiple sclerosis: 312 the 2013 revisions, Neurology, vol.83, issue.3, pp.278-286, 2014.

B. D. Trapp and P. K. Stys, Virtual hypoxia and chronic necrosis of demyelinated axons in 314 multiple sclerosis, Lancet Neurol, vol.8, issue.3, pp.280-291, 2009.

H. Hartung, R. Gonsette, and N. König, Mitoxantrone in progressive multiple sclerosis: a 316 placebo-controlled, double-blind, randomised, multicentre trial, Lancet, vol.360, issue.9350, pp.317-2018, 2002.

K. Hawker, P. O'connor, and M. S. Freedman, Rituximab in patients with primary 319 progressive multiple sclerosis: results of a randomized double-blind placebo-controlled 320 multicenter trial, Ann Neurol, vol.66, issue.4, pp.460-471, 2009.

X. Montalban, S. L. Hauser, and L. Kappos, Ocrelizumab versus placebo in primary 322 progressive multiple sclerosis, N Engl J Med, vol.376, issue.3, pp.209-220, 2017.

L. Kappos, A. Bar-or, and B. Cree, Siponimod versus placebo in secondary progressive 324 multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study, Lancet, vol.325, pp.1263-1273, 2018.

M. Anagnostouli, E. Livaniou, and J. O. Nyalala, Cerebrospinal fluid levels of biotin in 327 various neurological disorders, Acta Neurol Scand, vol.99, issue.6, pp.387-392, 1999.

P. Paul, L. Debruyne, D. Bernard, and D. , Pharmacokinetics and 329 pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple 330 sclerosis, Expert Opin Drug Metab Toxicol, vol.12, issue.3, pp.327-344, 2016.

M. F. Mccarty and J. J. Dinicolantonio, Neuroprotective potential of high-dose biotin, Hypotheses, vol.332, pp.145-149, 2017.

C. Confavreux, D. A. Compston, and O. R. Hommes, EDMUS, a European database for 342 multiple sclerosis, J Neurol Neurosurg Psychiatry, vol.55, issue.8, pp.671-676, 1992.

H. Tremlett, F. Zhu, and J. Petkau, Natural, innate improvements in multiple sclerosis 344 disability, Mult Scler, vol.18, issue.10, pp.1412-1421, 2012.

G. P. Rice, M. Filippi, and G. Comi, Cladribine and progressive MS: clinical and MRI outcomes 346 of a multicenter controlled trial. Cladribine MRI Study Group, Neurology, vol.54, issue.5, pp.347-1145, 2000.

O. Andersen, I. Elovaara, and M. Färkkilä, Multicentre, randomised, double blind, placebo 349 controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary 350 progressive multiple sclerosis, J Neurol Neurosurg Psychiatry, vol.75, issue.5, pp.706-710, 2004.

G. Birnbaum and J. Stulc, High dose biotin as treatment for progressive multiple sclerosis

, Mult Scler Relat Disord, vol.18, pp.141-143, 2017.

C. Donze, M. A. Guyot, and B. Lenne, Effect of MD1003 (high dose pharmaceutical grade 354 biotin) on dexterity, cognitive, and quality of life measures in a cohort of patients with non, p.355