Advertisement

Neuromyelitis Optica Spectrum Disorder

  • Samira SaadounEmail author
  • Vincent T. W. Chang
  • Marios C. Papadopoulos
Chapter
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system, also known as Devic’s syndrome, that typically manifests with optic neuritis and transverse myelitis and, like other antibody-mediated autoimmune diseases, primarily affects women. Most NMO cases are caused by a circulating autoantibody termed NMO-IgG or AQP4-IgG that targets the astrocytic water channel protein aquaporin-4 (AQP4). Some NMO cases are caused by a circulating autoantibody against the myelin oligodendrocyte glycoprotein termed MOG-IgG. A small proportion of NMO cases, termed seronegative NMO, are not associated with an autoantibody. AQP4-IgG binds extracellular conformational epitopes on AQP4, activates complement, which in turn causes inflammatory cell infiltration, demyelination and pan-necrosis. Acute NMO exacerbations are treated with methylprednisolone or plasmapheresis. Some drugs used to treat multiple sclerosis, such as interferon beta and natalizumab, exacerbate NMO. Maintenance treatment options include prednisolone, mycophenylate, mitoxantrone, cyclophosphamide, azathioprine, rituximab, tocilizumab and eculizumab. The discoveries of AQP4-IgG and MOG-IgG have shown that NMO is a distinct entity from multiple sclerosis with fundamentally different pathophysiology and treatment.

Keywords

AQP4-IgG Aquaporin-4 MOG-IgG Myelin oligodendrocyte glycoprotein Neuromyelitis optica spectrum disorders NMO-IgG Optic neuritis Transverse myelitis 

References

  1. 1.
    Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation. 2013;10:8.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Papadopoulos MC, Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol. 2012;11:535–44.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202:473–7.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Hinson SR, Pittock SJ, Lucchinetti CF, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007;69:2221–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Guo Y, Weigand SD, Popescu BF, et al. Pathogenic implications of cerebrospinal fluid barrier pathology in neuromyelitis optica. Acta Neuropathol. 2017;133:597–612.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain. 2002;125:1450–61.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006;66:1485–9.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Bradl M, Misu T, Takahashi T, et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol. 2009;66:630–43.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain. 2007;130:1235–43.PubMedCrossRefGoogle Scholar
  11. 11.
    Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133:349–61.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. Hagerstown, MD. 2015;85:177–89.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Jurynczyk M, Messina S, Woodhall MR, et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017;140:3128–38.PubMedCrossRefGoogle Scholar
  14. 14.
    Chang T, Waters P, Woodhall M, Vincent A. Recurrent Optic Neuritis Associated With MOG Antibody Seropositivity. Neurologist. 2017;22:101–2.PubMedCrossRefGoogle Scholar
  15. 15.
    Kim SM, Woodhall MR, Kim JS, et al. Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS. Neurol Neuroimmunol Neuroinflamm. 2015;2:e163.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Waters P, Woodhall M, O’Connor KC, et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm. 2015;2:e89.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Dos Passos GR, Oliveira LM, da Costa BK, et al. MOG-IgG-Associated Optic Neuritis, Encephalitis, and Myelitis: Lessons Learned From Neuromyelitis Optica Spectrum Disorder. Front Neurol. 2018;9:217.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Etemadifar M, Nasr Z, Khalili B, Taherioun M, Vosoughi R. Epidemiology of neuromyelitis optica in the world: a systematic review and meta-analysis. Mult Scler Int. 2015;2015:174720.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6:805–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Eskandarieh S, Nedjat S, Abdollahpour I, et al. Environmental risk factors in neuromyelitis optica spectrum disorder: a case-control study. Acta Neurol Belg. 2018;118:277–87.PubMedCrossRefGoogle Scholar
  21. 21.
    Jarius S, Wildemann B, Paul F. Neuromyelitis optica: clinical features, immunopathogenesis and treatment. Clin Exp Immunol. 2014;176:149–64.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Jarius S, Paul F, Franciotta D, et al. Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature. Mult Scler. 2012;18:1135–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Matiello M, Kim HJ, Kim W, et al. Familial neuromyelitis optica. Neurology. 2010;75:310–5.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Brum DG, Barreira AA, dos Santos AC, et al. HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis. Mult Scler. 2010;16:21–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Wang H, Dai Y, Qiu W, et al. HLA-DPB1 0501 is associated with susceptibility to anti-aquaporin-4 antibodies positive neuromyelitis optica in southern Han Chinese. J Neuroimmunol. 2011;233:181–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Misaka T, Abe K, Iwabuchi K, et al. A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach. FEBS Lett. 1996;381:208–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Mobasheri A, Marples D, Young IS, Floyd RV, Moskaluk CA, Frigeri A. Distribution of the AQP4 water channel in normal human tissues: protein and tissue microarrays reveal expression in several new anatomical locations, including the prostate gland and seminal vesicles. Channels (Austin). 2007;1:29–38.CrossRefGoogle Scholar
  28. 28.
    Wakayama Y, Jimi T, Inoue M, et al. Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy. Arch Neurol. 2002;59:431–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS. Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues. J Biol Chem. 1994;269:5497–500.PubMedGoogle Scholar
  30. 30.
    Saadoun S, Waters P, Leite MI, Bennett JL, Vincent A, Papadopoulos MC. Neuromyelitis optica IgG causes placental inflammation and fetal death. J Immunol. 2013;191:2999–3005.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Malik R, Lewis A, Cree BA, et al. Transient hyperCKemia in the setting of neuromyelitis optica (NMO). Muscle Nerve. 2014;50:859–62.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Guo Y, Lennon VA, Popescu BF, et al. Autoimmune aquaporin-4 myopathy in neuromyelitis optica spectrum. JAMA Neurol. 2014;71:1025–9.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Suzuki N, Takahashi T, Aoki M, et al. Neuromyelitis optica preceded by hyperCKemia episode. Neurology. 2010;74:1543–5.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Saadoun S, Papadopoulos MC. Role of membrane complement regulators in neuromyelitis optica. Mult Scler. 2015;21:1644–54.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Rosito S, Nicchia GP, Palazzo C, et al. Supramolecular aggregation of aquaporin-4 is different in muscle and brain: correlation with tissue susceptibility in neuromyelitis optica. J Cell Mol Med. 2018;22:1236–46.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Nour MM, Nakashima I, Coutinho E, et al. Pregnancy outcomes in aquaporin-4-positive neuromyelitis optica spectrum disorder. Neurology. 2016;86:79–87.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Borisow N, Hellwig K, Paul F. Neuromyelitis optica spectrum disorders and pregnancy: relapse-preventive measures and personalized treatment strategies. EPMA J. 2018;9:249–56.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Banwell B, Marrie RA. Increased relapse rate during pregnancy and postpartum in neuromyelitis optica. Neurology. 2017;89:2220–1.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Huang Y, Wang Y, Zhou Y, et al. Pregnancy in neuromyelitis optica spectrum disorder: A multicenter study from South China. J Neurol Sci. 2017;372:152–6.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Shimizu Y, Fujihara K, Ohashi T, et al. Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder. Mult Scler. 2016;22:1413–20.PubMedCrossRefGoogle Scholar
  41. 41.
    Jurewicz A, Selmaj K. Relapse of neuromyelitis optica during pregnancy--treatment options and literature review. Clin Neurol Neurosurg. 2015;130:159–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Kim W, Kim SH, Nakashima I, et al. Influence of pregnancy on neuromyelitis optica spectrum disorder. Neurology. 2012;78:1264–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Bourre B, Marignier R, Zephir H, et al. Neuromyelitis optica and pregnancy. Neurology. 2012;78:875–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol. 2014;10:493–506.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Papadopoulos MC, Verkman AS. Aquaporin water channels in the nervous system. Nat Rev Neurosci. 2013;14:265–77.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Saadoun S, Papadopoulos MC. Aquaporin-4 in brain and spinal cord oedema. Neuroscience. 2010;168:1036–46.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Saadoun S, Papadopoulos MC, Watanabe H, Yan D, Manley GT, Verkman AS. Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci. 2005;118:5691–8.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Zador Z, Magzoub M, Jin S, Manley GT, Papadopoulos MC, Verkman AS. Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain. FASEB J. 2008;22:870–9.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Papadopoulos MC, Kim JK, Verkman AS. Extracellular space diffusion in central nervous system: anisotropic diffusion measured by elliptical surface photobleaching. Biophys J. 2005;89:3660–8.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Papadopoulos MC, Binder DK, Verkman AS. Enhanced macromolecular diffusion in brain extracellular space in mouse models of vasogenic edema measured by cortical surface photobleaching. FASEB J. 2005;19:425–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Binder DK, Papadopoulos MC, Haggie PM, Verkman AS. In vivo measurement of brain extracellular space diffusion by cortical surface photobleaching. J Neurosci. 2004;24:8049–56.PubMedCrossRefGoogle Scholar
  52. 52.
    Verkman AS, Phuan PW, Asavapanumas N, Tradtrantip L. Biology of AQP4 and anti-AQP4 antibody: therapeutic implications for NMO. Brain Pathol. 2013;23:684–95.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Jin BJ, Rossi A, Verkman A. Model of Aquaporin-4 Supramolecular Assembly in Orthogonal Arrays Based on Heterotetrameric Association of M1-M23 Isoforms. Biophys J. 2011;100:2936–45.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Pisani F, Mola MG, Simone L, et al. Identification of a point mutation impairing the binding between aquaporin-4 and neuromyelitis optica autoantibodies. J Biol Chem. 2014;289:30578–89.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Nishiyama S, Misu T, Nuriya M, et al. Complement-dependent and -independent aquaporin 4-antibody-mediated cytotoxicity in human astrocytes: Pathogenetic implications in neuromyelitis optica. Biochem Biophys Rep. 2016;7:45–51.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Kitley J, Woodhall M, Leite MI, Palace J, Vincent A, Waters P. Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO. Neurol Neuroimmunol Neuroinflamm. 2015;2:e121.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Phuan PW, Ratelade J, Rossi A, Tradtrantip L, Verkman AS. Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays. J Biol Chem. 2012;287:13829–39.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Saadoun S, Waters P, MacDonald C, et al. Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain. Ann Neurol. 2012;71:323–33.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Zhang H, Verkman AS. Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica. J Clin Invest. 2013;123:2306–16.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Burda JE, Sofroniew MV. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 2014;81:229–48.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Bush TG, Puvanachandra N, Horner CH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 1999;23:297–308.PubMedCrossRefGoogle Scholar
  62. 62.
    Ren Z, Wang Y, Duan T, et al. Cross-immunoreactivity between bacterial aquaporin-Z and human aquaporin-4: potential relevance to neuromyelitis optica. J Immunol. 2012;189:4602–11.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Cree BA, Spencer CM, Varrin-Doyer M, Baranzini SE, Zamvil SS. Gut microbiome analysis in neuromyelitis optica reveals overabundance of Clostridium perfringens. Ann Neurol. 2016;80:443–7.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Adawi M, Bisharat B, Bowirrat A. Systemic Lupus Erythematosus (SLE) Complicated by Neuromyelitis Optica (NMO – Devic’s Disease): Clinic-Pathological Report and Review of the Literature. Clin Med Insights Case Rep. 2014;7:41–7.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Kovacs KT, Kalluri SR, Boza-Serrano A, et al. Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study. Mult Scler. 2016;22:1192–201.PubMedCrossRefGoogle Scholar
  66. 66.
    Iorio R, Rindi G, Erra C, Damato V, Ferilli M, Sabatelli M. Neuromyelitis optica spectrum disorder as a paraneoplastic manifestation of lung adenocarcinoma expressing aquaporin-4. Mult Scler. 2015;21:791–4.PubMedCrossRefGoogle Scholar
  67. 67.
    Jarius S, Franciotta D, Paul F, et al. Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance. J Neuroinflammation. 2010;7:52.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Shimizu F, Ransohoff RM. GRP78 autoantibodies initiate the breakdown of the blood-brain barrier in neuromyelitis optica. Oncotarget. 2017;8:106175–6.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Uchida T, Mori M, Uzawa A, et al. Increased cerebrospinal fluid metalloproteinase-2 and interleukin-6 are associated with albumin quotient in neuromyelitis optica: Their possible role on blood-brain barrier disruption. Mult Scler. 2017;23:1072–84.PubMedCrossRefGoogle Scholar
  70. 70.
    Takeshita Y, Obermeier B, Cotleur AC, et al. Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm. 2017;4:e311.PubMedCrossRefGoogle Scholar
  71. 71.
    Nishiyama S, Ito T, Misu T, et al. A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset. Neurology. 2009;72:1960–1.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Kaneko K, Sato DK, Nakashima I, et al. Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J Neurol Neurosurg Psychiatry. England. 2016;87:1257–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Levy M. Does aquaporin-4-seronegative neuromyelitis optica exist? JAMA Neurol. United States. 2014;71:271–2.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Pache F, Zimmermann H, Mikolajczak J, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflammation. 2016;13:282.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Pandit L, Asgari N, Apiwattanakul M, et al. Demographic and clinical features of neuromyelitis optica: A review. Mult Scler. 2015;21:845–53.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Kim HJ, Paul F, Lana-Peixoto MA, et al. MRI characteristics of neuromyelitis optica spectrum disorder: An international update. Neurology. Hagerstown, MD. 2015;84:1165–73.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Sinnecker T, Schumacher S, Mueller K, et al. MRI phase changes in multiple sclerosis vs neuromyelitis optica lesions at 7T. Neurol Neuroimmunol Neuroinflamm. 2016;3:e259.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Duan Y, Liu Z, Liu Y, et al. Metabolic changes in normal-appearing white matter in patients with neuromyelitis optica and multiple sclerosis: a comparative magnetic resonance spectroscopy study. Acta Radiol. 2017;58:1132–7.PubMedCrossRefGoogle Scholar
  80. 80.
    de Seze J, Blanc F, Kremer S, et al. Magnetic resonance spectroscopy evaluation in patients with neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2010;81:409–11.PubMedCrossRefGoogle Scholar
  81. 81.
    Waters P, McKeon A, Leite M, et al. Serologic diagnosis of NMO: A multicenter comparison of aquaporin-4-IgG assays. Neurology. Hagerstown, MD. 2012;78:665–71.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Jiao Y, Fryer JP, Lennon VA, et al. Updated estimate of AQP4-IgG serostatus and disability outcome in neuromyelitis optica. Neurology. Hagerstown, MD. 2013;84:1197–204.CrossRefGoogle Scholar
  83. 83.
    Crane JM, Lam C, Rossi A, Gupta T, Bennett JL, Verkman AS. Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays. J Biol Chem. 2011;286:16516–24.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Jarius S, Ruprecht K, Stellmann JP, et al. MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature. J Neuroinflammation. 2018;15:88.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Kim SH, Kim W, Huh SY, Lee KY, Jung IJ, Kim HJ. Clinical Efficacy of Plasmapheresis in Patients with Neuromyelitis Optica Spectrum Disorder and Effects on Circulating Anti-Aquaporin-4 Antibody Levels. J Clin Neurol. 2013;9:36–42.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Chihara N, Aranami T, Sato W, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108:3701–6.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Cabre P, Mejdoubi M, Jeannin S, et al. Treatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study. J Neurol. 2018;265:917–25.PubMedCrossRefGoogle Scholar
  88. 88.
    Ringelstein M, Ayzenberg I, Harmel J, et al. Long-term Therapy With Interleukin 6 Receptor Blockade in Highly Active Neuromyelitis Optica Spectrum Disorder. JAMA Neurol. 2015;72:756–63.PubMedCrossRefGoogle Scholar
  89. 89.
    Pittock SJ, Lennon VA, McKeon A, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12:554–62.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Kitley J, Evangelou N, Kuker W, Jacob A, Leite MI, Palace J. Catastrophic brain relapse in seronegative NMO after a single dose of natalizumab. J Neurol Sci. 2014;339:223–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Bar-Or A, Steinman L, Behne JM, et al. Restoring immune tolerance in neuromyelitis optica: Part II. Neurol Neuroimmunol Neuroinflamm. 2016;3:e277.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Steinman L, Bar-Or A, Behne JM, et al. Restoring immune tolerance in neuromyelitis optica: Part I. Neurol Neuroimmunol Neuroinflamm. 2016;3:e276.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Weinshenker BG, Barron G, Behne JM, et al. Challenges and opportunities in designing clinical trials for neuromyelitis optica. Neurology. Hagerstown, MD. 2015;84:1805–15.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Samira Saadoun
    • 1
    Email author
  • Vincent T. W. Chang
    • 1
  • Marios C. Papadopoulos
    • 1
  1. 1.Academic Neurosurgery Unit, St. George’s, University of LondonLondonUK

Personalised recommendations