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Clinical Decision-Making in the Management of Multiple Sclerosis

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Clinical Neuroimmunology

Part of the book series: Current Clinical Neurology ((CCNEU))

Abstract

Multiple sclerosis is a complex heterogeneous disease. The introduction of several new disease modifying agents and the implications of treatment have increased the burden of decision making in MS therapeutics. There is now increasing data regarding unconventional use of approved therapies such as alternate dosing methods, use of DMD in untested populations such as patients > 60 years, escalation VS induction approaches, as well as other treatment related concerns including risk of rebound disease, treatment of PML and use of DMD post PML, management of pregnant MS patients and use of marijuana in MS patients. In this chapter we discuss the current data related to these topics with an intention to create a better understanding of some of these issues.

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References

  1. Comi G, Martinelli V, Rodegher M, Moiola L, Leocani L, Bajenaru O, et al. Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome. Mult Scler. 2013;19(8):1074–83.

    Article  CAS  PubMed  Google Scholar 

  2. Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol. 2009;8(11):987–97.

    Article  CAS  PubMed  Google Scholar 

  3. Kappos L, Edan G, Freedman MS, Montalban X, Hartung HP, Hemmer B, et al. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology. 2016;87(10):978–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kavaliunas A, Manouchehrinia A, Stawiarz L, Ramanujam R, Agholme J, Hedstrom AK, et al. Importance of early treatment initiation in the clinical course of multiple sclerosis. Mult Scler. 2017;23(9):1233–40.

    Article  PubMed  Google Scholar 

  5. Kinkel RP, Dontchev M, Kollman C, Skaramagas TT, O'Connor PW, Simon JH, et al. Association between immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome and long-term outcomes: a 10-year follow-up of the controlled high-risk avonex multiple sclerosis prevention study in ongoing neurological surveillance. Arch Neurol. 2012;69(2):183–90.

    Article  PubMed  Google Scholar 

  6. Miller AE, Wolinsky JS, Kappos L, Comi G, Freedman MS, Olsson TP, et al. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(10):977–86.

    Article  CAS  PubMed  Google Scholar 

  7. Romeo MAL, Martinelli V, Dalla Costa G, Colombo B, De Feo D, Esposito F, et al. Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response. Acta Neurol Scand. 2018;138(5):447–53.

    Article  PubMed  Google Scholar 

  8. Freedman MS. Induction vs. escalation of therapy for relapsing multiple sclerosis: the evidence. Neurol Sci. 2008;29(Suppl 2):S250–2.

    Article  PubMed  Google Scholar 

  9. Le Page E, Edan G. Induction or escalation therapy for patients with multiple sclerosis? Rev Neurol. 2018;174(6):449–57.

    Article  PubMed  Google Scholar 

  10. Merkel B, Butzkueven H, Traboulsee AL, Havrdova E, Kalincik T. Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: a systematic review. Autoimmun Rev. 2017;16(6):658–65.

    Article  PubMed  Google Scholar 

  11. Giovannoni G, Turner B, Gnanapavan S, Offiah C, Schmierer K, Marta M. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015;4(4):329–33.

    Article  PubMed  Google Scholar 

  12. Ingwersen J, Aktas O, Hartung HP. Advances in and algorithms for the treatment of relapsing-remitting multiple sclerosis. Neurotherapeutics. 2016;13(1):47–57.

    Article  CAS  PubMed  Google Scholar 

  13. Edan G, Le Page E. Induction therapy for patients with multiple sclerosis: why? When? How? CNS Drugs. 2013;27(6):403–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: when to start, when to change, when to stop? World J Clin Cases. 2015;3(7):545–55.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bevan CJ, Cree BA. Disease activity free status: a new end point for a new era in multiple sclerosis clinical research? JAMA Neurol. 2014;71(3):269–70.

    Article  PubMed  Google Scholar 

  16. Kappos L, De Stefano N, Freedman MS, Cree BA, Radue EW, Sprenger T, et al. Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297–305.

    Article  PubMed  Google Scholar 

  17. Matta AP, Nascimento OJ, Ferreira AC, Magalhaes TN, Benevides TP, Kirmse A, et al. No evidence of disease activity in multiple sclerosis patients. Expert Rev Neurother. 2016;16(11):1279–84.

    Article  CAS  PubMed  Google Scholar 

  18. Freedman MS. Are we in need of NEDA? Mult Scler. 2016;22(1):5–6.

    Article  PubMed  Google Scholar 

  19. Le Page E, Leray E, Taurin G, Coustans M, Chaperon J, Morrissey SP, et al. Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients. J Neurol Neurosurg Psychiatry. 2008;79(1):52–6.

    Article  PubMed  Google Scholar 

  20. Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group. Long-term safety profile of mitoxantrone in a french cohort of 802 multiple sclerosis patients: a 5-year prospective study. Mult Scler. 2011;17(7):867–75.

    Article  PubMed  CAS  Google Scholar 

  21. Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28. https://doi.org/10.1016/S0140-6736(12)61769-3.

    Article  CAS  PubMed  Google Scholar 

  22. Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39. https://doi.org/10.1016/S0140-6736(12)61768-1.

    Article  CAS  PubMed  Google Scholar 

  23. Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G, et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: results from the randomized extension trial of the CLARITY study. Mult Scler. 2018;24(12):1594–604.

    Article  CAS  PubMed  Google Scholar 

  24. Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008;7(7):626–36.

    Article  PubMed  Google Scholar 

  25. Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, Fassas A, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74(4):459–69.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Burt RK, Loh Y, Cohen B, Stefoski D, Balabanov R, Katsamakis G, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8(3):244–53.

    Article  CAS  PubMed  Google Scholar 

  27. Burt RK, Balabanov R, Han X, Sharrack B, Morgan A, Quigley K, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015;313(3):275–84.

    Article  PubMed  Google Scholar 

  28. Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Steinmiller KC, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88(9):842–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016;388(10044):576–85.

    Article  PubMed  Google Scholar 

  30. Sormani MP, Muraro PA, Saccardi R, Mancardi G. NEDA status in highly active MS can be more easily obtained with autologous hematopoietic stem cell transplantation than other drugs. Mult Scler. 2017;23(2):201–4.

    Article  PubMed  Google Scholar 

  31. Freedman MS. Is there a safe time to discontinue therapy in MS? Nat Rev Neurol. 2017;13:10–1.

    Article  CAS  Google Scholar 

  32. Kister I. Disease-modifying therapies can be safely discontinued in an individual with stable relapsing-remitting MS – YES. Mult Scler J. 2017;23(9):1188–090.

    Article  Google Scholar 

  33. Tobin WO, Weinshenker BG. Disease-modifying therapies can be safely discontinued in an individual with stable relapsing-remitting MS – NO. Mult Scler J. 2017;23(9):1190–2.

    Article  Google Scholar 

  34. European Study Group on interferon beta-1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet. 1998;352(9139):1491–7.

    Article  Google Scholar 

  35. Ontaneda D, Thompson AJ, Fox RJ, et al. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet. 2017;389(10076):1357–66.

    Article  PubMed  Google Scholar 

  36. Tremlett H, Zhao Y, Joseph J, et al. Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry. 2008;79(12):1368–74.

    Article  CAS  PubMed  Google Scholar 

  37. Khademi M, Dring AM, Gilthorpe JD, et al. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers. PLoS One. 2013;8(5):e63172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tortorella C, Bellacosa A, Paolicelli D, et al. Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis. J Neurol Sci. 2005;239(1):95–9.

    Article  CAS  PubMed  Google Scholar 

  39. Bar-Or A. The immunology of multiple sclerosis. Semin Neurol. 2008;28:29–45.

    Article  PubMed  Google Scholar 

  40. Tobin W, Weinshenker BG. Stopping immunomodulatory medications in MS: frequency, reasons, and consequences. Mult Scler Relat Disord. 2015;4:437–43.

    Article  CAS  PubMed  Google Scholar 

  41. Birnbaum G. Stopping disease modifying-therapy in nonrelapsing multiple sclerosis: experience from a clinical practice. Int J MS Care. 2017;9(1):11–4.

    Article  Google Scholar 

  42. Bonenfant J, Bajeux E, Deburghgraeve V, et al. Can we stop immunomodulatory treatments in secondary progressive multiple sclerosis? Eur J Neurol. 2017;24(2):237–44.

    Article  CAS  PubMed  Google Scholar 

  43. Kister I, Spelman T, Alroughani R, et al. Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study. J Neurol Neurosurg Psychiatry. 2016;87(10):1133–7.

    Article  PubMed  Google Scholar 

  44. Bsteh G, Feige J, Ehling R, et al. Discontinuation of disease-modifying therapies in multiple sclerosis – clinical outcome and prognostic factors. Mult Scler. 2017;23(9):1241–8.

    Article  PubMed  Google Scholar 

  45. Vellinga MM, Castelijns JA, Barkhof F, et al. Postwithdrawal rebound increase in T2 lesional activity in natalizumab-treated MS patients. Neurology. 2008;70(132):1150–1.

    Article  CAS  PubMed  Google Scholar 

  46. Hatcher SE, Waubant E, Nourbakhsh B, et al. Rebound syndrome in patients with multiple sclerosis after cessation of fingolimod treatment. JAMA Neurol. 2016;73(7):790–4.

    Article  PubMed  Google Scholar 

  47. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209–20.

    Article  CAS  PubMed  Google Scholar 

  48. Kappos L. Efficacy and safety of siponimod in secondary progressive multiple sclerosis: results of the placebo-controlled, double-blind, phase III EXPAND study. Neurology. 2017;88:CT.002.

    Article  Google Scholar 

  49. Giovannoni G, Hawkes C, Waubant E, Lublin F. The ‘field hypothesis’: rebound activity after stopping disease-modifying therapies. Mult Scler Relat Disord. 2017;15:A1.

    Article  PubMed  Google Scholar 

  50. Beran RG, Hegazi Y, Schwartz RS, Cordato DJ. Rebound exacerbation multiple sclerosis following cessation of oral treatment. Mult Scler Relat Disord. 2013;2(3):252–5.

    Article  PubMed  Google Scholar 

  51. Harmel P, Schlunk F, Harms L. Fulminant rebound of relapsing-remitting multiple sclerosis after discontinuation of dimethyl fumarate: a case report. Mult Scler. 2018;24(8):1131–3.

    Article  PubMed  Google Scholar 

  52. Yamout BI, Said M, Hannoun S, Zeineddine M, Massouh J, Khoury SJ. Rebound syndrome after teriflunomide cessation in a patient with multiple sclerosis. J Neurol Sci. 2017;380:79–81.

    Article  PubMed  Google Scholar 

  53. Frau J, Sormani MP, Signori A, et al. Clinical activity after fingolimod cessation: disease reactivation or rebound? Eur J Neurol. 2018;25(10):1270–5.

    Article  CAS  PubMed  Google Scholar 

  54. Vermersch P, Radue EW, Putzki N, Ritter S, Merschhemke M, Freedman MS. A comparison of multiple sclerosis disease activity after discontinuation of fingolimod and placebo. Mult Scler J Exp Transl Clin. 2017;3:2055217317730096–3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624444. Accessed 16 Sep 2018.

    PubMed  PubMed Central  Google Scholar 

  55. Sangalli F, Moiola L, Ferrè L, et al. Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients. Mult Scler Relat Disord. 2014;3(4):520–6.

    Article  PubMed  Google Scholar 

  56. Gueguen A, Roux P, Deschamps R, et al. Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014;85(9):1038–40.

    Article  PubMed  Google Scholar 

  57. Gündüz T, Kürtüncü M, Eraksoy M. Severe rebound after withdrawal of fingolimod treatment in patients with multiple sclerosis. Mult Scler Relat Disord. 2017;11:1–3.

    Article  PubMed  Google Scholar 

  58. Serafini B, Zandee S, Rosicarelli B, et al. Epstein-Barr virus-associated immune reconstitution inflammatory syndrome as possible cause of fulminant multiple sclerosis relapse after natalizumab interruption. J Neuroimmunol. 2018;319:9–12.

    Article  CAS  PubMed  Google Scholar 

  59. Serafini B, Scorsi E, Rosicarelli B, Rigau V, Thouvenot E, Aloisi F. Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal. J Neuroimmunol. 2017;307:14–7.

    Article  CAS  PubMed  Google Scholar 

  60. Larochelle C, Metz I, Lécuyer MA, et al. Immunological and pathological characterization of fatal rebound MS activity following natalizumab withdrawal. Mult Scler. 2017;23(1):72–81.

    Article  CAS  PubMed  Google Scholar 

  61. Cobo-Calvo Á, Figueras A, Bau L, et al. Leukocyte adhesion molecule dynamics after natalizumab withdrawal in multiple sclerosis. Clin Immunol. 2016;171:18–24.

    Article  CAS  PubMed  Google Scholar 

  62. Giacomini PS. Rebound disease in multiple sclerosis. Mult Scler. 2018;24(8):1137–8.

    Article  PubMed  Google Scholar 

  63. Mulero P, Neri MJ, Rodriguez M, Arenillas JF, Téllez N. Immune reconstitution inflammatory syndrome and natalizumab–is it possible before removing the drug? Mult Scler Relat Disord. 2014;3(5):659–61.

    Article  CAS  PubMed  Google Scholar 

  64. Haas J, Schneider K, Schwarz A, et al. Th17 cells: a prognostic marker for MS rebound after natalizumab cessation? Mult Scler. 2017;23(1):114–8.

    Article  CAS  PubMed  Google Scholar 

  65. Sánchez P, Meca-Lallana V, Vivancos J. Tumefactive multiple sclerosis lesions associated with fingolimod treatment: report of 5 cases. Mult Scler Relat Disord. 2018;25:95–8.

    Article  PubMed  Google Scholar 

  66. Voskuhl R. Rebound relapses after ceasing another disease-modifying treatment in patients with multiple sclerosis: are there lessons to be learned? JAMA Neurol. 2016;73(7):775–6.

    Article  PubMed  Google Scholar 

  67. Sato K, Niino M, Kawashima A, Yamada M, Miyazaki Y, Fukazawa T. Disease exacerbation after the cessation of fingolimod treatment in Japanese patients with multiple sclerosis. Intern Med. 2018;57(18):2647–55.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Giordana MT, Cavalla P, Uccelli A, et al. Overexpression of sphingosine-1-phosphate receptors on reactive astrocytes drives neuropathology of multiple sclerosis rebound after fingolimod discontinuation. Mult Scler. 2018;24(8):1133–7.

    Article  CAS  PubMed  Google Scholar 

  69. Bernard-Valnet R, Pignolet B, Biotti D, et al. Unexpected high multiple sclerosis activity after switching from fingolimod to alemtuzumab. Mult Scler Relat Disord. 2018;25:216–8.

    Article  PubMed  Google Scholar 

  70. Uphaus T, Oberwittler C, Groppa S, Zipp F, Bittner S. Disease reactivation after switching from natalizumab to daclizumab. J Neurol. 2017;264(12):2491–4.

    Article  PubMed  Google Scholar 

  71. Giovannoni G, Marta M, Davis A, Turner B, Gnanapavan S, Schmierer K. Switching patients at high risk of PML from natalizumab to another disease-modifying therapy. Pract Neurol. 2016;16(5):389–93.

    Article  PubMed  Google Scholar 

  72. Lo Re M, Capobianco M, Ragonese P, et al. Natalizumab discontinuation and treatment strategies in patients with multiple sclerosis (MS): a retrospective study from two Italian MS Centers. Neurol Ther. 2015;4(2):147–57.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Calabrese M, Pitteri M, Farina G, et al. Dimethyl fumarate: a possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events. J Neurol Neurosurg Psychiatry. 2017;88(12):1073–8.

    Article  PubMed  Google Scholar 

  74. Patti F, Leone C, Zappia M. Clinical and radiologic rebound after discontinuation of natalizumab therapy in a highly active multiple sclerosis patient was not halted by dimethyl-fumarate: a case report. BMC Neurol. 2015;15:252.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Alvarez-Gonzalez C, Adams A, Mathews J, et al. Cladribine to treat disease exacerbation after fingolimod discontinuation in progressive multiple sclerosis. Ann Clin Transl Neurol. 2017;4(7):506–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Longbrake EE, Kantor D, Pawate S, et al. Effectiveness of alternative dose fingolimod for multiple sclerosis. Neurol Clin Pract. 2018;8(2):102–7.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Tanak M, Park K, Tanaka K. Reduced fingolimod dosage treatment for patients with multiple sclerosis and lymphopenia or neutropenia. Mult Scler. 2013;19:1244–5.

    Article  Google Scholar 

  78. Yamout BI. Safety and efficacy of reduced fingolimod dosage treatment. J Neuroimmunol. 2015;285:13–5.

    Article  CAS  PubMed  Google Scholar 

  79. Zhovtis RL, Frohman TC, Foley J, et al. Extended interval dosing of natalizumab in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2016;87:885–9.

    Article  Google Scholar 

  80. Bomprezzi R, Pawate S. Extended interval dosing of natalizumab: a two-center, 7-year experience. Ther Adv Neurol Disord. 2014;7(5):227–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chan C, Siu R, Mellsop N, et al. Extended interval dosing of natalizumab in MS; a New Zealand experience. Neurology. 2018;90(15):6.351.

    Google Scholar 

  82. Herbert J, Zhovtis L, Tornatore C, et al. Multicenter retrospective study of extended dosing of natalizumab in multiple sclerosis: a strategy for mitigating risk of progressive multifocal leukoencephalopathy while maintaining efficacy. Neurology. 2014;82(10):2.251.

    Google Scholar 

  83. Ryerson LZ, Foley J, Chang I, et al. Natalizumab extended interval dosing (EID) is associated with a significant reduction in progressive multifocal leukoencephalopathy (PML) risk compared with standard interval dosing (SID) in the Touch® prescribing program. J Neurol Neurosurg Psychiatry. 2018;89:A29.

    Article  Google Scholar 

  84. Weinstock-Guttman B, Hagemeier J, Kavak KS, et al. Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation. J Neurol Neurosurg Psychiatry. 2016;87(9):937–43.

    Article  PubMed  Google Scholar 

  85. Schoergenhofer C, Schwameis M, Firbas C, et al. Single, very low rituximab doses in healthy volunteers – a pilot and a randomized trial: implications for dosing and biosimilarity testing. Sci Rep. 2018;8:124.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Salzer J, Svenningsson R, Alping P, et al. Rituximab in multiple sclerosis: a retrospective observational study on safety and efficacy. Neurology. 2016;87(20):2074–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Memon AB, Javed A, Caon C, et al. Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases. PLoS ONE. 2018;13(1):e0190425. https://doi.org/10.1371/journal.pone.0190425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Avasarala J. Anti-CD20 cell therapies in multiple sclerosis – a fixed dosing schedule for ocrelizumab is overkill. Drug Target Insights. 2017;11:1177392817737515.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Anton R, Haas M, Arlett P, et al. Drug-induced progressive multifocal leukoencephalopathy: European regulators’ perspective. Clin Pharmacol Ther. 2017;102(2):283–9.

    Article  CAS  PubMed  Google Scholar 

  90. Pavlovic D, Patera AC, Nyberg F, et al. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives. Ther Adv Neurol Disord. 2015;8(6):255–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. fda.gov/Drugs/DrugSafety/ucm424625.htm. First online: 25 Nov 2014, update 16 Jan 2016.

  92. fda.gov/Drugs/DrugSafety/ucm456919.ht. First online: 4 Aug 2015, update 6 Mar 2018.

  93. Biogen Idec. Tysabri (natalizumab) postmarketing safety update. TY-US-0113(11). 2016. https://medinfo.biogen.com/secure/pmlresource.

  94. Biogen Inc. Tysabri prescribing information (revised 08/2017). Cambridge, MA: Biogen Inc; 2017.

    Google Scholar 

  95. Tyler KL, Vollmer TL. To PLEX or not to PLEX in natalizumab-associated PML. Neurology. 2017;88:1108–9.

    Article  PubMed  Google Scholar 

  96. Vermersch P, Kappos L, Gold R, et al. Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology. 2011;76(20):1697–704.

    Article  CAS  PubMed  Google Scholar 

  97. Williamson EML, Berger JR. Diagnosis and treatment of progressive multifocal leukoencephalopathy associated with multiple sclerosis therapies. Neurotherapeutics. 2017;14:961–73.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Ho P, Koendgen H, Campbell N, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol. 2017;16:925–33.

    Article  CAS  PubMed  Google Scholar 

  99. Berger JR. Classifying PML risk with disease modifying therapies. Mult Scler Relat Disord. 2017;12:59–63.

    Article  PubMed  Google Scholar 

  100. Khatri BO, Man S, Giovannoni G, et al. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function. Neurology. 2009;72(5):402–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Landi D, Rossi ND, Zagaglia S, et al. No evidence of beneficial effects of plasmapheresis in natalizumab-associated PML. Neurology. 2017;88(12):1144–52.

    Article  CAS  PubMed  Google Scholar 

  102. Scarpazza C, Prosperini L, Rossi ND, et al. To do or not to do? Plasma exchange and timing of steroid administration in progressive multifocal leukoencephalopathy. Ann Neurol. 2017;82:697–705.

    Article  CAS  PubMed  Google Scholar 

  103. Stuve O, Marta CM, Bat-Or A, et al. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch Neurol. 2006;63(10):1383–7.

    Article  PubMed  Google Scholar 

  104. Wattjes MP, Wijburg MT, Vennegoor A, et al. MRI characteristics of early PML-IRIS after natalizumab treatment in patients with MS. J Neurol Neurosurg Psychiatry. 2016;87(8):879–84.

    Article  PubMed  Google Scholar 

  105. Maillart E, Vidal J, Brassat D, et al. Natalizumab-PML survivors with subsequent MS treatment. Neurol Neuroimmunol Neuroinflamm. 2017;4(3):e346.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Houtchens M. Multiple sclerosis and pregnancy. Clin Obstet Gynecol. 2013;56(2):342–9.

    Article  PubMed  Google Scholar 

  107. Voskuhl R, Momtazee C. Pregnancy: effect on multiple sclerosis, treatment considerations, and breastfeeding. Neurotherapeutics. 2017;14(4):974–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Brookings William LM. Management of multiple sclerosis during pregnancy. Prog Neurol Psychiatry. 2009;13(6):9–11.

    Article  Google Scholar 

  109. Alroughani R, Alowayesh MS, Ahmed SF, Behbehani R, Al-Hashel J. Relapse occurrence in women with multiple sclerosis during pregnancy in the new treatment era. Neurology. 2018;90(10):e840–e6.

    Article  PubMed  Google Scholar 

  110. Siroos B, Harirchian MH. Multiple sclerosis and pregnancy; what a neurologist may be asked for? Iran J Neurol. 2014;13(2):57–63.

    PubMed  PubMed Central  Google Scholar 

  111. Daroff RB, Fenichel GM, Jankovic J, Mazziotta J. Bradley’s neurology in clinical practice. 6th ed. Bridgewater: Elsevier Health Sciences; 2012. p. 1284–310.

    Google Scholar 

  112. Confavreux C, Hutchinson M, Hours MM, et al. Rate of pregnancy-related relapse in multiple sclerosis. N Eng J Med. 1998;339:285–91.

    Article  CAS  Google Scholar 

  113. Houtchens MK, Kaplan TB. Reproductive issues in MS. Semin Neurol. 2017;37(6):632–42.

    Article  PubMed  Google Scholar 

  114. Dahl J, Myhr KM, Daltveit AK, et al. Pregnancy, delivery and birth outcome in women with multiple sclerosis. Neurology. 2005;65:1961–3.

    Article  CAS  PubMed  Google Scholar 

  115. Bateman AM, Goldish GD. Autonomic dysreflexia in multiple sclerosis. J Spinal Cord Med. 2002;25:40–2.

    Article  PubMed  Google Scholar 

  116. Lu E, Wang BW, Guimond C, Synnes A, Sadovnick D, Tremlett H. Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review. Neurology. 2012;79(11):1130–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Karlsson G, Francis G, Koren G, et al. Pregnancy outcomes in the clinical development program of fingolimod in multiple sclerosis. Neurology. 2014;82(08):674–80.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Gold R, Phillips JT, Havrdova E, et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy out- comes from clinical trials and postmarketing experience. Neurol Ther. 2015;4(02):93–104.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Houtchens MK, Sadovnick AD. Health issues in women with multiple sclerosis. Vienna: Springer; 2017.

    Book  Google Scholar 

  120. Coyle PK. Management of women with multiple sclerosis through pregnancy and after childbirth. Ther Adv Neurol Disorder. 2016;9(03):198–210.

    Article  CAS  Google Scholar 

  121. Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy out- comes after maternal exposure to rituximab. Blood. 2011;117(05):1499–506.

    Article  CAS  PubMed  Google Scholar 

  122. Greenberger PA. Pharmacokinetics of prednisolone transfer to breast milk. Clin Pharmacol Ther. 1993;53:324.

    Article  CAS  PubMed  Google Scholar 

  123. Achiron A, KishnerT DM, et al. Effect of intravenous immunoglobulin treatment on pregnancy and postpartum related relapses in multiple sclerosis. J Neurol. 2004;251(9):1133–7.

    Article  CAS  PubMed  Google Scholar 

  124. Nelson LM, Franklin GM, Jones MC. Risk of multiple sclerosis exacerbation during pregnancy and breastfeeding. JAMA. 1988;259(23):3441–3.

    Article  CAS  PubMed  Google Scholar 

  125. Langer-Gould A, Huang SM, Gupta R, et al. Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch Neurol. 2009;66(8):958–63.

    Article  PubMed  Google Scholar 

  126. Potter D. The propagation, characterisation and optimisation of cannabis sativa L as a phytopharmaceutical. JP MlBiol CBiol FLS CMIOSH.

    Google Scholar 

  127. Da Rovare VP, Magalhaes GPA, Jardini GDA, et al. Cannabinoids for spasticity due to multiple sclerosis or paraplegia: a systemic review and meta-analysis of randomized clinical trials. Complement Ther Med. 2017;34:170–85.

    Article  PubMed  Google Scholar 

  128. Clark AJ, Ware MA, Yaser E, et al. Patterns of cannabis use among patients with multiple sclerosis. Neurology. 2004;62(11):2098–100.

    Article  CAS  PubMed  Google Scholar 

  129. Feinstein A, Banwell E, Pavisian B. What to make of cannabis and cognition in MS: in search of clarity amidst the haze. Mult Scler. 2015;21(14):1755–60.

    Article  CAS  PubMed  Google Scholar 

  130. Koppel BS, Brust JCM, Fife T, et al. Systemic review: efficacy and safety of medical marijuana in selected neurologic disorders. Neurology. 2014;82:1556–63.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Zajicek JP, Apostu VI. Role of cannabinoids in multiple sclerosis. CNS Drugs. 2011;25(3):187–201.

    Article  CAS  PubMed  Google Scholar 

  132. Rocha FC, Dos Santos Junior JG, Stefano SC, et al. Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas. J Neuro-Oncol. 2014;116(1):11–24.

    Article  CAS  Google Scholar 

  133. Glass M, Faull RL, Dragunow M. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 1997;77(2):299–318.

    Article  CAS  PubMed  Google Scholar 

  134. Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology, XXVII: classification of cannabinoid receptors. Pharmacol Rev. 2002;54:161–202.

    Article  CAS  PubMed  Google Scholar 

  135. Arévalo-Martin A, Vela JM, Molina-Holgado E, et al. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J Neurosci. 2003;23(7):2511–6.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Nielsen S, Germanos R, Weier M, et al. The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systemic review of reviews. Curr Neurol Neurosci Rep. 2018;18(2):8.

    Article  PubMed  CAS  Google Scholar 

  137. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systemic review and meta-analysis. JAMA. 2015;313:2456–73.

    Article  CAS  PubMed  Google Scholar 

  138. Giacoppo S, Bramanti P, Mazzon E. Sativex in the management of multiple sclerosis-related spasticity: an overview of the last decade of clinical evaluation. Mult Scler Relat Disord. 2017;17:22–31.

    Article  PubMed  Google Scholar 

  139. Markovà J, Essner U, Akmaz B, et al. Sativex® as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: a double-blind, placebo-controlled randomised clinical trial. Int J Neurosci. 2018;24:1–26.

    Google Scholar 

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Authors and Affiliations

  1. Rhode Island Hospital and Alpert Medical School of Brown University, Brown Neurology, Providence, RI, USA

    Syed A. Rizvi

  2. MS Fellow, Brown Neurology, Providence, RI, USA

    Joshua A. Stone & Saima T. Chaudhry

  3. Alpert Warren Medical School of Brown University, Providence, RI, USA

    Nichola Haddad & Jennifer O. Grimes

  4. Department of Neurology, Hartford Healthcare, University of Connecticut School of Medicine, Southington, CT, USA

    Brian Wong

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  1. Syed A. Rizvi
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  2. Joshua A. Stone
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  3. Saima T. Chaudhry
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  4. Nichola Haddad
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  5. Brian Wong
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  6. Jennifer O. Grimes
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Correspondence to Syed A. Rizvi .

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Editors and Affiliations

  1. Rhode Island Hospital and Alpert Medical School of Brown University, Brown Neurology, Providence, RI, USA

    Syed A. Rizvi

  2. Rhode Island Hospital and Alpert Medical School of Brown University, Brown Neurology, Providence, RI, USA

    Jonathan F. Cahill

  3. Department of Neurology, MS Comprehensive Care Center, Stony Brook University Medical Center, Stony Brook, NY, USA

    Patricia K. Coyle

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Rizvi, S.A., Stone, J.A., Chaudhry, S.T., Haddad, N., Wong, B., Grimes, J.O. (2020). Clinical Decision-Making in the Management of Multiple Sclerosis. In: Rizvi, S., Cahill, J., Coyle, P. (eds) Clinical Neuroimmunology. Current Clinical Neurology. Humana, Cham. https://doi.org/10.1007/978-3-030-24436-1_8

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