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Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, Thompson AJ. Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology. 2014; 83:1022-1024.","DOI":"10.1212\/WNL.0000000000000768"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Thompson AJ. Multiple sclerosis--a global disorder and still poorly managed. Lancet Neurol. 2008; 7:1078-1079.","DOI":"10.1016\/S1474-4422(08)70246-1"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Yan K, Balijepalli C, Desai K, Gullapalli L, Druyts E. Epidemiology of pediatric multiple sclerosis: A systematic literature review and meta-analysis. Mult Scler Relat Disord. 2020; 44:102260.","DOI":"10.1016\/j.msard.2020.102260"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Marrosu MG, Cocco E, Costa G, Murru MR, Mancosu C, Murru R, Lai M, Sardu C, Contu P. Interaction of loci within the HLA region influences multiple sclerosis course in the Sardinian population. J Neurol. 2006; 253:208-213.","DOI":"10.1007\/s00415-005-0957-y"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Patsopoulos NA, Barcellos LF, Hintzen RQ, <i>et al. <\/i>Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genet. 2013; 9:e1003926.","DOI":"10.1371\/journal.pgen.1003926"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Armon-Omer A, Waldman C, Simaan N, Neuman H, Tamir S, Shahien R. New insights on the nutrition status and antioxidant capacity in multiple sclerosis patients. Nutrients. 2019; 11:427.","DOI":"10.3390\/nu11020427"},{"key":"7","unstructured":"7. Nebbioso M, Scarsella G, Tafani M, Pescosolido N. Mechanisms of ocular neuroprotection by antioxidant molecules in animal models. J Biol Regul Homeost Agents. 2013; 27:197-209."},{"key":"8","unstructured":"8. Silva JP, Coutinho OP. Free radicals in the regulation of damage and cell death - basic mechanisms and prevention. Drug Discov Ther. 2010; 4:144-167."},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Pescosolido N, Barbato A, Pascarella A, Giannotti R, Genzano M, Nebbioso M. Role of protease-inhibitors in ocular diseases. Molecules. 2014; 19:20557-20569.","DOI":"10.3390\/molecules191220557"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Nijst TQ, Wevers RA, Schoonderwaldt HC, Hommes OR, de Haan AF. Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia. J Neurol Neurosurg Psychiatry. 1990; 53:951-954.","DOI":"10.1136\/jnnp.53.11.951"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Ji Z, Fan Z, Zhang Y, Yu R, Yang H, Zhou C, Luo J, Ke ZJ. Thiamine deficiency promotes T cell infiltration in experimental autoimmune encephalomyelitis: the involvement of CCL2. J Immunol. 2014; 193:2157-2167.","DOI":"10.4049\/jimmunol.1302702"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Lanska DJ. Chapter 30: historical aspects of the major neurological vitamin deficiency disorders: the water-soluble B vitamins. Handb Clin Neurol. 2010; 95:445-476.","DOI":"10.1016\/S0072-9752(08)02130-1"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Rawji KS, Young AMH, Ghosh T, <i>et al.<\/i> Correction to: Niacin-mediated rejuvenation of macrophage\/microglia enhances remyelination of the aging central nervous system. Acta Neuropathol. 2020; 139:911.","DOI":"10.1007\/s00401-020-02146-6"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Bubshait DK, Rashid A, Al-Owain MA, Sulaiman RA. Depression in adult patients with biotin responsive basal ganglia disease. Drug Discov Ther. 2016; 10:223-225.","DOI":"10.5582\/ddt.2016.01046"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Mastronardi FG, Min W, Wang H, Winer S, Dosch M, Boggs JM, Moscarello MA. Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-beta plus vitamin B12: treatment to modify notch-1\/sonic hedgehog balance. J Immunol. 2004; 172:6418-6426.","DOI":"10.4049\/jimmunol.172.10.6418"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Mastronardi FG, Tsui H, Winer S, Wood DD, Selvanantham T, Galligan C, Fish EN, Dosch HM, Moscarello MA. Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating diseases. Mult Scler. 2007; 13:596-609.","DOI":"10.1177\/1352458506072167"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Costantini A, Nappo A, Pala MI, Zappone A. High dose thiamine improves fatigue in multiple sclerosis. BMJ Case Rep. 2013; 2013:bcr2013009144.","DOI":"10.1136\/bcr-2013-009144"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Birnbaum G, Stulc J. 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Intern Med. 1994; 33:82-86.","DOI":"10.2169\/internalmedicine.33.82"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, Gout O, Lyon-Caen O, Tourbah A. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015; 4:159-169.","DOI":"10.1016\/j.msard.2015.01.005"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Tourbah A, Gout O, Vighetto A, <i>et al.<\/i> MD1003 (High-dose pharmaceutical-grade biotin) for the treatment of chronic visual loss related to optic neuritis in multiple sclerosis: A randomized, double-blind, placebo-controlled study. CNS Drugs. 2018; 32:661-672.","DOI":"10.1007\/s40263-018-0528-2"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Wang ZB, Gan Q, Rupert RL, Zeng YM, Song XJ. 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Asian J Med Sci. 2018; 9:32.","DOI":"10.3126\/ajms.v9i1.18510"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Thompson AJ, Banwell BL, Barkhof F, <i>et al.<\/i> Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17:162-173.","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects. BMC Clin Pharmacol. 2012; 12:4.","DOI":"10.1186\/1472-6904-12-4"},{"key":"30","doi-asserted-by":"crossref","unstructured":"31. Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy \u2212 A review. Nutrients. 2016; 8:68.","DOI":"10.3390\/nu8020068"},{"key":"31","doi-asserted-by":"crossref","unstructured":"32. Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, Thompson AJ, Miller DH. 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Multifocal and pattern-reversal visual evoked potentials <i>vs.<\/i> automated perimetry frequency-doubling technology matrix in optic neuritis. Indian J Ophthalmol. 2013; 61:59-64.","DOI":"10.4103\/0301-4738.99638"},{"key":"36","doi-asserted-by":"crossref","unstructured":"37. Coret F, P\u00e9rez-Miralles FC, Gasc\u00f3n F, Alcal\u00e1 C, Navarr\u00e9 A, Bernad A, Bosc\u00e1 I, Escutia M, Gil-Perotin S, Casanova B. Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies. Mult Scler J Exp Transl Clin. 2018; 4:2055217318783347.","DOI":"10.1177\/2055217318783347"},{"key":"37","unstructured":"38. Najafi MR, Shaygannajad V, Mirpourian M, Gholamrezaei A. Vitamin B(12) deficiency and multiple sclerosis; is there any association? Int J Prev Med. 2012; 3:286-289."},{"key":"38","doi-asserted-by":"crossref","unstructured":"39. McLaughlin L, Clarke L, Khalilidehkordi E, Butzkueven H, Taylor B, Broadley SA. 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Russo C, Morabito F, Luise F, Piromalli A, Battaglia L, Vinci A, Trapani Lombardo V, de Marco V, Morabito P, Condino F, Quattrone A, Aguglia U. Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis. J Neurol. 2008; 255:64-69.","DOI":"10.1007\/s00415-007-0668-7"},{"key":"43","doi-asserted-by":"crossref","unstructured":"45. Zhang DM, Ye JX, Mu JS, Cui XP. Efficacy of vitamin B supplementation on cognition in elderly patients with cognitive-related diseases. J Geriatr Psychiatry Neurol. 2017; 30:50-59.","DOI":"10.1177\/0891988716673466"},{"key":"44","doi-asserted-by":"crossref","unstructured":"46. Bourquin F, Capitani G, Gr\u00fctter MG. PLP-dependent enzymes as entry and exit gates of sphingolipid metabolism. Protein Sci. 2011; 20:1492-1508.","DOI":"10.1002\/pro.679"},{"key":"45","doi-asserted-by":"crossref","unstructured":"47. Johnson S. The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis. Med Hypotheses. 2000; 55:239-241.","DOI":"10.1054\/mehy.2000.1051"},{"key":"46","doi-asserted-by":"crossref","unstructured":"48. Jasse L, Vukusic S, Durand-Dubief F, Vartin C, Piras C, Bernard M, P\u00e9lisson D, Confavreux C, Vighetto A, Tilikete C. Persistent visual impairment in multiple sclerosis: prevalence, mechanisms and resulting disability. Mult Scler. 2013; 19:1618-1626.","DOI":"10.1177\/1352458513479840"},{"key":"47","doi-asserted-by":"crossref","unstructured":"49. Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers GC, Muraro PA. The relationship of age with the clinical phenotype in multiple sclerosis. 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