Journal of Clinical Immunology

, Volume 33, Supplement 1, pp 33–37 | Cite as

Neuromyelitis Optica: Potential Roles for Intravenous Immunoglobulin

  • Dean M. WingerchukEmail author


Neuromyelitis optica (NMO) is an idiopathic central nervous system inflammatory demyelinating disease that causes optic neuritis, transverse myelitis, and other CNS syndromes. It is distinct from multiple sclerosis and is associated with autoantibodies that target aquaporin-4 (AQP4), an astrocyte water channel. Evidence indicating antibody-mediated immune injury in NMO includes its association with other autoimmune diseases, lesional pathology that reveals prominent complement activation and immunoglobulin deposition, pathogenic potential of AQP4 autoantibodies based on in vitro studies, and reports of putative animal models of the disease. The rationale and potential role for intravenous immunoglobulin in NMO will be discussed in the context of both relapse treatment and relapse prevention.


Neuromyelitis optica aquaporin-4 intravenous immunoglobulin 


  1. 1.
    Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805–15.PubMedCrossRefGoogle Scholar
  2. 2.
    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(4):473–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12.PubMedCrossRefGoogle Scholar
  4. 4.
    O’Riordan JI, Gallagher HL, Thompson AJ, Howard RS, Kingsley DP, Thompson EJ, et al. Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica. J Neurol Neurosurg Psychiatry. 1996;60(4):382–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006;66(10):1485–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Wingerchuk DM, Pittock SJ, Lucchinetti CF, Lennon VA, Weinshenker BG. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain. 2002;125(Pt 7):1450–61.PubMedCrossRefGoogle Scholar
  9. 9.
    Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain. 2007;130(Pt 5):1235–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP, Kryzer TJ, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007;69(24):2221–31.PubMedCrossRefGoogle Scholar
  11. 11.
    Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med. 2008;205(11):2473–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Bradl M, Misu T, Takahashi T, Watanabe M, Mader S, Reindl M, et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol. 2009;66(5):630–43.PubMedCrossRefGoogle Scholar
  13. 13.
    Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC, et al. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain. 2010;133(Pt 2):349–61.PubMedCrossRefGoogle Scholar
  14. 14.
    Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2012;78(13):1009–15. doi: 10.1212/WNL.0b013e31824de293.PubMedCrossRefGoogle Scholar
  15. 15.
    Leite MI, Coutinho E, Lana-Peixoto M, Apostolos S, Waters P, Sato D, et al. Myasthenia gravis and neuromyelitis optica spectrum disorder: a multicenter study of 16 patients. Neurology. 2012;78(20):1601–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Jarius S, Paul F, Franciotta D, de Seze J, Munch C, Salvetti M, 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(8):1135–43. doi: 10.1177/1352458511431728.PubMedCrossRefGoogle Scholar
  17. 17.
    Dalakas MC. The use of intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: evidence-based indications and safety profile. Pharmacol Ther. 2004;102:177–93.PubMedCrossRefGoogle Scholar
  18. 18.
    Yu Z, Lennon VA. Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med. 1999;340:227–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Okada K, Matsushita T, Kira J, Tsuji S, Okada K, Matsushita T et al. B-cell activating factor of the TNF family is upregulated in neuromyelitis optica. Neurology. 74(2):177–8.Google Scholar
  20. 20.
    Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2008;10:55–66.PubMedCrossRefGoogle Scholar
  21. 21.
    Weinshenker BG, O’Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46:878–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Ii Y, Shindo A, Sasaki R, Naito Y, Tanaka K, Kuzuhara S, et al. Reversible stenosis of large cerebral arteries in a patient with combined Sjogren’s syndrome and neuromyelitis optica spectrum disorder. Rheumatol Int. 2008;28(12):1277–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Nakano Y, Miyamoto K, Inatsugi Y, Suzuki H, Kusunoki S, Nakano Y, et al. Senile-onset recurrent myelitis with anti-aquaporin-4 antibody. Brain Nerve. 2009;61(5):601–4.PubMedGoogle Scholar
  24. 24.
    Cree BAC, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology. 2005;64(7):1270–2.PubMedCrossRefGoogle Scholar
  25. 25.
    Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, et al. Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol. 2009;66(9):1128–33.PubMedCrossRefGoogle Scholar
  26. 26.
    Jacob A, Weinshenker BG, Violich I, McLinskey N, Krupp L, Fox RJ, et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol. 2008;65(11):1443–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Madrekar J, et al. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology. 2011;77:659–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Magraner MJ, Coret F, Casanova B. The effect of intravenous immunoglobulin on neuromyelitis optica. Neurologia. 2012. doi: 10.1016/j.nrl.2012.03.014.
  29. 29.
    Bakker J, Metz L. Devic’s neuromyelitis optica treated with intravenous gamma globulin (IVIG). Can J Neurol Sci. 2004;31(2):265–7.PubMedGoogle Scholar
  30. 30.
    Okada K, Tsuji S, Tanaka K. Intermittent intravenous immunoglobulin successfully prevents relapses of neuromyelitis optica. Intern Med. 2007;46(19):1671–2.PubMedCrossRefGoogle Scholar
  31. 31.
    Magana SM, Matiello M, Pittock SJ, McKeon A, Lennon VA, Rabinstein AA, et al. Posterior reversible encephalopathy syndrome in neuromyelitis optica spectrum disorders. Neurology. 2009;72(8):712–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of NeurologyMayo ClinicScottsdaleUSA

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