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Colegio de Medicina Interna de México.

2019, Number 5

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Med Int Mex 2019; 35 (5)

Consensus for the diagnosis and treatment of multiple sclerosis in ISSSTE patients

Aguilar-Juárez PA, Castillo-Lara RA, Ceballos-Godina M, Colorado-Ochoa HJ, Espinosa-Zacarías JP, Flores-Ramírez FG, García S, García-Huerta LG, González-Cruz M, Granados-Aguilar MI, León-Jiménez C, Llamas-López L, Martínez-Gurrola MA, Núñez-Orozco L, Quiñones-Aguilar S, Sauri-Suárez S, Solórzano-Gómez E, Vega-Gaxiola SB

Language: Spanish
References: 100
Page: 732-771
PDF size: 881.44 Kb.


ABSTRACT

Multiple sclerosis is one of the main demyelinating diseases of the central nervous system, which impacts not only economically but also socially. The Mexican Institute of Security and Social Services of State Workers (ISSSTE) has most of the disease modifying treatments for this disease and to optimize its use, a group of neurologists from the institution met to make a document on general aspects of diagnosis and treatment called: Consensus for the diagnosis and treatment of multiple sclerosis in ISSSTE patients. The objective of this consensus is to give recommendations on the different therapeutic alternatives against multiple sclerosis for adults and children.


REFERENCES

  1. Martínez-Altarriba MC, Ramos-Campoy O, Luna-Calcaño IM, Arrieta-Antón E. Revisión de la esclerosis múltiple (2). Diagnóstico y tratamiento. Semergen 2015;41(6):324-328. DOI: 10.1016/j.semerg.2014.07.011.

  2. Markowitz CE. Multiple sclerosis update. Am J Manag Care. 2013;19(16):S294-S300.

  3. Waubant E, Mowry EM, Krupp L, et al. Antibody response to common viruses and human leukocyte antigen-DRB1 in pediatric multiple sclerosis. Mult Scler 2013 June;19(7):891- 895. doi: 10.1177/1352458512469693.

  4. Banwell B, Bar-Or A, Arnold DL, et al. Clinical, environmental and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol. 2011;10(5):436-445. doi: 10.1016/S1474-4422(11)70045-X.

  5. Waldman A, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M, Banwell B. Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research. Lancet Neurol 2014 September;13(9):936-948. doi: 10.1016/ S1474-4422(14)70093-6.

  6. Catálogo único de Unidades Médicas del Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), diciembre de 2015. http://www.issste. gob.mx/images/downloads/todo-el-publico/umedicas/ Catalogo_unico_unidades_medicas_dic_2016final.pdf

  7. Corona T, Flores J. Esclerosis múltiple (EM) en América Latina. Rev Española Esclerosis Múltiple 2009 Septiembre; 12:5-8.

  8. Sistema Integral de Abasto de Medicamentos (SIAM), datos a diciembre 2018. Datos proporcionados por la Dra. Sandra Quiñones.

  9. Sand K. Classification, diagnosis, and differential diagnosis of multiple sclerosis. Curr Opin Neurol 2015;28:193-205. doi: 10.1097/WCO.0000000000000206.

  10. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the MacDonald criteria. Ann Neurol 2011;69:292-302. doi: 10.1002/ ana.22366.

  11. Miller DH, Weinshenker BG, Filippi M, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 2008;14:1157-1174. doi: 10.1177/1352458508096878. E

  12. Rovira À, Wattjes MP, Tintoré M, et al. MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis–clinical implementation in the diagnostic process. Nat Rev Neurol 2015;11:471-482. doi: 10.1038/nrneurol.2015.106.

  13. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018;17:162-173. doi: 10.1016/S1474- 4422(17)30470-2.

  14. Charil A, Yousry TA, Rovaris M, et al. MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”. Lancet Neurol 2006 October;5(10): 841-852. DOI: 10.1016/S1474-4422(06)70572-5.

  15. Filippi M, Rocca MA, Ciccarelli O, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol 2016 March; 15(3):292-303. doi: 10.1016/S1474-4422(15)00393-2.

  16. Información para prescribir del interferón beta 1-β 8 millones SC. https://www.ema.europa.eu/en/documents/productinformation/ betaferon-epar-product-information_es.pdf

  17. Información para prescribir del interferón beta 1-α 6 millones IM. http://www.medicamentosplm.com/home/ productos/avonex_solucion/51/101/6454/146

  18. Información para prescribir del interferón beta 1-α 6 millones SC. http://www.medicamentosplm.com/Home/ productos/rebif_nf_solucion/115/101/50804/146

  19. Información para prescribir del interferón beta 1-α 12 millones SC. http://www.medicamentosplm.com/Home/ productos/rebif_solucion_inyectable/115/101/9515/162

  20. Información para prescribir del acetato de glatiramer. http://www.medicamentosplm.com/Home/productos/ copaxone_solucion_inyectable/182/101/7036/162

  21. Información para prescribir del natalizumab. http://www. medicamentosplm.com/Home/productos/tysabri_solucion_ inyectable/51/101/33807/162

  22. Información para prescribir del fingolimod. http://www. medicamentosplm.com/Home/productos/gilenya_capsulas/ 122/101/44575/14

  23. Información para prescribir teriflunomida. https://www. ema.europa.eu/en/documents/product-information/ aubagio-epar-product-information_es.pdf

  24. Información para prescribir de dimetilfumarato. https:// www.ema.europa.eu/en/documents/product-information/ tecfidera-epar-product-information_es.pdf

  25. Información para prescribir mitoxantrona. http://www. medicamentosplm.com/Home/productos/bresnix_solucion_ inyectable/2337/101/60473/162

  26. Información para prescribir alemtuzumab. https://www. ema.europa.eu/en/documents/product-information/ lemtrada-epar-product-information_es.pdf

  27. Información para prescribir daclizumab. https://www.ema. europa.eu/en/documents/product-information/zinbrytaepar- product-information_es.pdf

  28. Daclizumab retiro del mercado. https://www.fundacionfemeba. org.ar/blog/farmacologia-7/post/alertas-deseguridad- retiro-del-mercado-de-daclizumab-45415

  29. Información para prescribir amplia ocrelizumab. Proporcionada por el laboratorio

  30. Información para prescribir rituximab. http://www. medicamentosplm.com/Home/productos/mabthera_solucion_ inyectable/154/101/8514/162

  31. Información para prescribir cladribina. https://www. ema.europa.eu/en/documents/product-information/ mavenclad-epar-product-information_es.pdf

  32. Información para prescribir ciclofosfamida. http://www. medicamentosplm.com/Home/productos/formitex_solucion_ inyectable/134/101/44805/162

  33. Rudick RA, Stuart WH, Calabresi PA, et al; SENTINEL investigators: Natalizumab vs. interferon beta 1-a for relapsisng multiple sclerosis. N Engl J Med 2003;348:911-923.

  34. Polman CH, O’Connor PW, Havrdova E, et al; AFFIRM investigators: A randomized, placebo controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354(9):899-910. DOI: 10.1056/NEJMoa044397.

  35. Goodman AD, Rossman H, Bar-Or A, et al. GLANCE: results of a phase 2, randomized, double-blind, placebo-controlled study. Neurology 2009; 72: 806-812. doi: 10.1212/01. wnl.0000343880.13764.69.

  36. Rudick R, Goodman A, Kappos I. Six-year natalizumab efficacy and safety data from STRATA study. 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. October 2-5 2013. Copenhagen, Denmark.

  37. Butzkueven H, Kappos L, Pellegrini F, et al. Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results. J Neurol Neurosurg Psychiatry 2014;85:1190-1197. doi: 10.1136/jnnp-2013-306936.

  38. Foley J, Carrillo-Infante C, Wenten M, et al. Long-term safety of natalizumab treatment in multiple sclerosis (MS) in clinical practice: results from the Tysabri global observational program in safety (TYGRIS). http://onlinelibrary. ectrims-congress.eu/ectrims/2016/32nd/145912/ john.foley.long-term.safety.of.natalizumab.treatment. in.multiple.sclerosis.html

  39. Avasarala J. The TOUCH program and natalizumab: Fundamental flaw in patient protection [version 3; referees: 2 approved, 1 approved with reservations]. F1000Research 2016;4:1450. doi: 10.12688/f1000research.7513.3.

  40. Bozic C, Richman S, Plavina T, et al. Anti-John Cunninham Virus prevalence in multiple sclerosis patients. Baseline results of STRATIFY-1. Ann Neurol 2011;70(5):742-750. doi: 10.1002/ana.22606.

  41. JC Virus Antibody Study of Participants with Relapsing Forms of MS receiving Treatment with Natalizumab (STRATIFY- 2). https://clinicaltrials.gov/ct2/show/NCT01070836.

  42. Lee P, Plavina T, Castro A, et al. A second-generation ELISA (STRATIFY JCVTM DxSelectTM) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol. 2013; 57:141-146. doi: 10.1016/j.jcv.2013.02.002.

  43. Coles AJ, Fox E, Vladic A, et al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial. Neurology 2012;78:1069-1078. doi: 10.1212/ WNL.0b013e31824e8ee7.

  44. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. CARE-MS I Lancet 2012;380:1819- 1828. doi: 10.1016/S0140-6736(12)61769-3.

  45. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after diseasemodifying therapy: a randomized controlled phase III trial. CARE-MS II investigators. Lancet 2012;380:1829-1839. doi: 10.1016/S0140-6736(12)61768-1.

  46. Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. FREE DOMS Study Group. N Engl J Med 2010;362(5):387-401. doi: 10.1056/NEJMoa0909494.

  47. Devonshire V, Havrdova E, Radue EW, et al. Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the doubleblind randomised, placebo-controlled FREEDOMS study. Lancet Neurol 2012;11:420-428. doi: 10.1016/S1474- 4422(12)70056-X.

  48. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. TRANSFORMS Study Group. N Engl J Med 2010;362(5):402- 415. DOI: 10.1056/NEJMoa0907839.

  49. Khatri B, Barkhof F, Comi G, et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol 2011;10:520-529. doi: 10.1016/ S1474-4422(11)70099-0.

  50. Derfuss T, Sastre-Garriga J, Montalban X, et al. The ACROSS Study: Long-term efficacy of fingolimod in patients with RRMS (follow-up at 10 years).

  51. O’Connor P, Wolinski JS, Confaveraux C, et al. Randomized trial for oral teriflunomide for relapsing multiple sclerosis. TEMSO Trial Group. N Engl J Med 2011;365: 1293-1303. DOI: 10.1056/NEJMoa1014656.

  52. Confavreux C, O’Connor P, Comi G, et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurology 2014;13(3):247-256. doi: 10.1016/ S1474-4422(13)70308-9.

  53. Kappos L, Comi G, Confaveraux C, et al. The efficacy and safety of teriflunomide in patients with relapsing MS: results from TOWER (extended) Study a phase III placebo controlled study. 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Mult Scler October 2012;18.

  54. Miller AE, Wolinsky JS, Kappos L, et al. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebocontrolled, phase 3 trial. Lancet Neurol 2014;13:977-986. doi: 10.1016/S1474-4422(14)70191-7.

  55. Vermersch P, Czlonkowska A, Grimaldi LM, et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. TENERE Trail Group. Mult Scler J 2014 May;20(6):705-716. doi: 10.1177/1352458513507821.

  56. Freedman MS, Wolinsky J, Comi G, et al. Safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis treated with interferon beta. TERACLES Study Group. 8th World Congress on Controversies in Neurology, 2014. http://www.comtecmed.com/cony/2014/Uploads/ Editor/Freedman.pdf

  57. Rog D, Stalla-Bourdillon A, Brette S, Coyle PK. Teriflunomide in clinical practice: TERI-PRO study design. J Neurol Neurosurg Psychiatry 2014;85(10):A1-A57. http://dx.doi. org/10.1136/jnnp-2014-309236.144.

  58. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. DEFINE Study Investigators. N Engl J Med 2012;367:1098-1107. DOI: 10.1056/NEJMoa1114287.

  59. Fox RJ, Miller DH, Phillips T, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. CONFIRM Study Investigators. N Engl J Med 2012;367:1087- 1097. DOI: 10.1056/NEJMoa1206328.

  60. Gold R, Arnold DL, Bar-Or A, et al. Long-term effects of delayed-release dimethylfumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study. Mult Scler J 2017;23(2):253-265. doi: 10.1177/1352458516649037.

  61. Hauser SL, Bar-Or G, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis OPERA I and OPERA II Clinical Investigators. N Engl J Med 2017;376:221- 234. doi: 10.1056/NEJMoa1601277.

  62. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis ORATORIO Clinical Investigators. N Engl J Med 2017;376:209- 220. doi: 10.1056/NEJMoa1606468.

  63. Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. CLARITY Study Group. N Engl J Med 2010;362:416-426. DOI: 10.1056/NEJMoa0902533.

  64. Giovannoni G, Sorensen PS, Cook S, et al. Safety and efficacy of cladribine tablets in patients with relapsingremitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler J 2017. DOI: 10.1177/1352458517727603.

  65. Leist TP, Comi G, Cree BAC, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol 2014;13:257-267. doi: 10.1016/S1474-4422(14)70005-5.

  66. Rommer PS, Eichstadt K, Ellenberger D, et al. Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry. Mult Scler J 2018; DOI:10:1177/1352458518799580. doi: 10.1177/1352458518799580.

  67. Brenner P, Piehl F. Fatigue and depression in multiple sclerosis: pharmacological and non-pharmacological interventions. Acta Neurol Scand 2016;134(Suppl 200):47-54. doi: 10.1111/ane.12648.

  68. Turri M, Teatini F, Donato F, et al. Pain modulation after oromucosal cannabinoid spray (SATIVEX®) in patients with multiple sclerosis: a study with quantitative sensory testing and laser – evoked potentials. Medicines 2018;5:59: doi:10.3390/medicines5030059.

  69. Johnen A, Landmeyer NC, Bürkner PC, Wiendl H, Meuth SG, Holling H. Distinct cognitive impairments in different disease courses of multiple sclerosis–A systematic review and meta-analysis. Neurosci Biobehav Rev 2017;83:568- 578. doi: 10.1016/j.neubiorev.2017.09.005.

  70. Höh AE, Beisse C. Okulomotorik und multiple sklerose. Ophthalmologe 2014;111:727-732.

  71. Preziosi G, Gordon-Dixon A, Emmanuel A. Neurogenic bowel dysfunction in patients with multiple sclerosis: prevalence, impact, and management strategies. Degener Neurol Neuromuscul Dis 2018;8:79-90. doi: 10.2147/ DNND.S138835.

  72. Dubey D, Sguigna P, Stüve O. Managing disability in progressive multiple sclerosis. Curr Treat Options Neurol 2016;18:27. doi: 10.1007/s11940-016-0412-7.

  73. Tur C. Fatigue management in multiple sclerosis. Curr Treat Options Neurol 2016;18:26. doi: 10.1007/s11940- 016-0411-8.

  74. Ayache SS, Chalah MA. Fatigue in multiple sclerosis – Insights into evaluation and management. Clin Neurophysiol 2017;47:139-171. doi: 10.1016/j.neucli.2017.02.004.

  75. Oreja-Guevara C, Montalban X, de Andrés C, et al. Documento de consenso sobre la espasticidad en pacientes con esclerosis múltiple. Rev Neurol 2013;57(8):359-373. DOI: https://doi.org/10.33588/rn.5708.2013374.

  76. Rivera-Díaz RC, Arcila-Lotero MA, Campuzano-Escobar D. Baclofeno intratecal para el tratamiento de la espasticidad. Reporte de caso con revisión sistemática. Rev Colomb Anestesiol 2013;41(3):229-235. https://doi.org/10.1016/j. rca.2013.03.004.

  77. Lorente-Fernández L, Monte-Boquet E, Pérez-Miralles F, et al. Experiencia clínica con los cannabinoides en la terapia de la espasticidad en la esclerosis múltiple. Neurología 2014;29(5):257-260. DOI: 10.1016/j.nrl.2013.06.014.

  78. Motl RW, Goldman MD, Benedict RHB. Walking impairment in patients with multiple sclerosis: exercise training as a treatment option. Neuropsychiatric Dis Treat 2010;6:767- 774. doi: 10.2147/NDT.S10480.

  79. Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, doubleblind, controlled trial. Lancet 2009;373:732-738. doi: 10.1016/S0140-6736(09)60442-6.

  80. Ojeda-López MC, Rodríguez-Weber F, Amaya-Sánchez LE. Diagnóstico diferencial del temblor. Acta Médica Grupo Ángeles 2009;7(3):143-149.

  81. Bermejo PE, Oreja-Guevara C, Díez-Tejedor E. El dolor en la esclerosis múltiple: prevalencia, mecanismos, tipos y tratamiento. Rev Neurol 2010;50(2):101-108. https://doi. org/10.33588/rn.5002.2008613.

  82. Nathoo N, Mackie A. Treating depression in multiple sclerosis with antidepressants: A brief review of clinical trials and exploration of clinical symptoms to guide treatment decisions. Mult Scler Rel Dis 2017;18:177-180. doi: 10.1016/j. msard.2017.10.004.

  83. Pöttgen J, Rose A, van de Vis W, et al. Sexual dysfunctions in MS in relation to neuropsychiatric aspects and its psychological treatment: A scoping review. PLoS ONE 2018;13(2):e0193381. https://doi.org/10.1371/journal. pone.0193381.

  84. Francomano D, Ilacqua A, Cortese A, et al. Effects of daily tadalafil on lower urinary tract symptoms in young men with multiple sclerosis and erectile dysfunction: a pilot study. J Endocrinol Invest 2017 Mar;40(3):275-279. doi: 10.1007/s40618-016-0557-y.

  85. Ghezzi A, Baroncini D, Zaffaroni M, Comi G. Pediatric versus adult MS: similar or different? Multiple Sclerosis Demyelinating Disorders 2017;2:5.

  86. Chou IJ, Whitehouse WP, Wang HS, Tanasescu R, Constantinescu CS. Diagnostic modalities in multiple sclerosis: Perspectives in children. Biomed J 2014; 37(2):50-59. doi: 10.4103/2319-4170.129269.

  87. Huppke B, Ellenberger D, Rosewich H, Friede T, Gärtner J, Huppke P. Clinical presentation of pediatric multiple sclerosis before puberty. Eur J Neurol 2014 Mar;21(3):441-446. doi: 10.1111/ene.12327.

  88. Waldman A, Ness J, Pohl D, et al. Pediatric multiple sclerosis. Clinical features and outcome. Neurology 2016;87(Suppl 2):S74-S81. doi: 10.1212/WNL.0000000000003028.

  89. Chou IJ, Wang HS, Whitehouse WP, Constantinescu CS. Paediatric multiple sclerosis: Update on diagnostic criteria, imaging, histopathology and treatment choices. Curr Neurol Neurosci Rep 2016;16:68. doi: 10.1007/s11910- 016-0663-4.

  90. Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adultonset multiple sclerosis. Arch Neurol 2009 Jan;66(1):54-59. doi: 10.1001/archneurol.2008.505.

  91. Till C, Ghassemi R, Aubert-Broche B, et al. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology 2011 May;25(3):319-332. doi: 10.1037/a0022051.

  92. De Meo E, Meani A, Moiola L, et al. Dynamic gray matter volume changes in pediatric multiple sclerosis: A 3.5 year MRI study. Neurology 2019;92(15). doi: 10.1212/ WNL.0000000000007267.

  93. O´Connor KC, López-Amaya C, Gagne D, et al. Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol 2010 Jun;223(1-2):92-99. doi: 10.1016/j.jneuroim.2010.02.019.

  94. Vargas-Lowy D, Kivisäkk P, Gandhi R, et al. Increased Th17 response to myelin peptides in pediatric MS. Clin Immunol 2013 Mar;146(3):176-184. doi: 10.1016/j. clim.2012.12.008.

  95. Fernández O, Tintoré M, Saiz A, et al. Revisión de las novedades del Congreso ECTRIMS 2017, presentadas en la X Reunión Post-ECTRIMS (I). Rev Neurol 2018;67(1):15-27. https://doi.org/10.33588/rn.6702.2018193.

  96. Jancic J, Nikolic B, Ivancevic N, et al. Multiple sclerosis in pediatrics: current concepts and treatment options. Neurol Ther 2016;5:131-143. DOI: 10.1007/s40120- 016-0052-6.

  97. Ghezzi A, Amato MP, Makhani N, Shreiner T, Gärtner J, Tenembaum S. Pediatric multiple sclerosis. Conven tional first-line treatment and general management. Neurology 2016;87(Suppl 2):S97-S102. doi: 10.1212/ WNL.0000000000002823.

  98. Tenembaum SN 2013. Treatment of multiple sclerosis and neuromielitis optica in children and adolescents. Clin Neurol Neurosurg 2013 Dec;115(Suppl 1):S21-S29. doi: 10.1016/j.clineuro.2013.09.016.

  99. Fragoso YD, Alves-León SV, Barreira AA, et al. Fingolimod prescribed for the treatment of multiple sclerosis in patients younger than age 18 years. Pediatr Neurol 2015 Aug;53(2):166-168. doi: 10.1016/j.pediatrneurol.2015.03.024.

  100. Van Haren K, Waubant E. Therapeutic advances in pediatric multiple sclerosis. J Peds 2013 September;163(3):631-637. doi: 10.1016/j.jpeds.2013.04.028.




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