Use of Intravenous Immunoglobulin in Neurology

  • Marinos C. Dalakas


Intravenous immunoglobulin (IVIg) has made a major impact in the treatment of certain autoimmune neurological disorders by providing therapy for previously untreatable, or poorly managed, conditions. Based on controlled trials, IVIg is approved as first-line therapy for patients with GBS, CIDP, and multifocal motor neuropathy. In CIDP, where the largest controlled study was performed, IVIg is also effective in the chronic management of the disease by preventing relapses and axonal loss and maintaining remissions over a 48-week period. Controlled studies have also shown that IVIg is effective as second-line therapy in dermatomyositis, myasthenia gravis, and stiff-person syndrome; it is however ineffective in paraproteinemic IgM-anti-MAG demyelinating polyneuropathies, inclusion body myositis, and Alzheimer disease. IVIg exerts multiple actions on the immunoregulatory network by variably affecting complement activation, autoantibodies, and inflammatory mediators relevant for each neurological disorder. Biomarkers are needed to identify patients who require continuous IVIg immunotherapy for chronic management and for patients more likely to respond to IVIg from the outset.


Intravenous immunoglobulin Autoimmune neuropathies Inflammatory myopathies Stiff-person syndrome Myasthenia gravis 


  1. Bain PG, Motomura M, Newsom-Davis J, et al. Effects of intravenous immunoglobulin on muscle weakness and calciumchannel autoantibodies in the Lambert–Eaton myasthenic syndrome. Neurology. 1996;47:678–68.CrossRefPubMedGoogle Scholar
  2. Basta M, Dalakas MC. High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest. 1994;94:1729–35. Scholar
  3. Dalakas MC, Elder G, Hallett M, et al. A long term follow-up study of patients with postpoliomyelitis neuromuscular symptoms. N Engl J Med. 1986;314:959–63.CrossRefPubMedGoogle Scholar
  4. Dalakas MC. Morphological changes in the muscles of patients with post-poliomyelitis neuromuscular symptoms. Neurology. 1988;38:99–104.CrossRefPubMedGoogle Scholar
  5. Dalakas MC. The use of intravenous immunoglobulin in the treatment of autoimmune neurological disorders: evidence-based indications and safety profile. Pharmacol Ther. 2004a;102:177–93.CrossRefPubMedGoogle Scholar
  6. Dalakas MC. Inflammatory disorders of muscle: progress in polymyositis, dermatomyositis and inclusion body myositis. Curr Opin Neurol. 2004b;17(5):561–7.CrossRefPubMedGoogle Scholar
  7. Dalakas MC. Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA. 2004;291:2367–75. Scholar
  8. Dalakas MC. Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol. 2011;7:507–17. Scholar
  9. Dalakas MC. Inflammatory myopathies. N Engl J Med. 2015;372:1734–47.CrossRefPubMedGoogle Scholar
  10. Dalakas MC, Gooch C. Close to the node but far enough: what nodal antibodies tell us about CIDP and its therapies. Neurology. 2016;86:1–2.CrossRefGoogle Scholar
  11. Dalakas MC, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med. 1993;329:1993–2000. Scholar
  12. Dalakas MC, et al. A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy. Ann Neurol. 1996;40:792–5. Scholar
  13. Dalakas MC, et al. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology. 1997;48:712–6.CrossRefPubMedGoogle Scholar
  14. Dalakas MC, et al. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med. 2001;345:1870–6. Scholar
  15. Dodel RC, et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2004;75:1472–4. Scholar
  16. Federico P, Zochodne DW, Hahn AF, Brown WF, Feasby TE. Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study. Neurology. 2000;55:1256–62.CrossRefPubMedGoogle Scholar
  17. Gajdos P, Chevret S, Clair B, Tranchant C, Chastang C. Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group. Ann Neurol. 1997;41:789–96. Scholar
  18. Gajdos P, et al. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial. Arch Neurol. 2005;62:1689–93. Scholar
  19. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. Cochrane Database Syst Rev. 2012;12:CD002277. Scholar
  20. Gold R, Stangel M, Dalakas MC. Drug insight: the use of intravenous immunoglobulin in neurology—therapeutic considerations and practical issues. Nat Clin Pract Neurol. 2007;3:36–44. Scholar
  21. Gonzalez H, et al. Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial. Lancet Neurol. 2006;5:493–500. Scholar
  22. Hahn AF, Beydoun SR, Lawson V, et al. A controlled trial of IVIG in multifocal motor neuropathy. J Peripher Nerv Syst. 2013;18:321–30.CrossRefPubMedGoogle Scholar
  23. Hughes RA, et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008;7:136–44. Scholar
  24. Hughes RA, Dalakas MC, Cornblath DR, et al. Clinical applications of intravenous immunoglobulin in neurology. Clin Exp Immunol. 2009;158(Suppl 1):34–2.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Kuitwaard K, et al. Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barre syndrome. Ann Neurol. 2009;66:597–603. Scholar
  26. Lunneman JD, Quast I, Dalakas MC. Efficacy of intravenous immunoglobulin in neurological diseases. Neurotherapeutics. 2015a;13:34–46.CrossRefGoogle Scholar
  27. Lunneman JD, Nimmerjahn F, Dalakas MC. Intravenous immunoglobulin in neurology: mode of action and clinical efficacy. Nat Rev Neurol. 2015b;11:80–9.CrossRefGoogle Scholar
  28. O’Hanlon TP, Dalakas MC, Plotz PH, Miller FW. Predominant α/β T cell receptor variable and joining gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies. J Immunol. 1994;152:2569–76.PubMedGoogle Scholar
  29. Raju R, Dalakas MC. Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biologic validation of clinical relevant genes. Brain. 2005;128:1887–96.CrossRefPubMedGoogle Scholar
  30. Relkin NR, Thomas RG, Rissman RA, et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology. 2017;88:1–8.CrossRefGoogle Scholar
  31. Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barre syndrome. Plasma Exchange/Sandoglobulin Guillain-Barre Syndrome Trial Group. Lancet. 1997;349:225–30.CrossRefGoogle Scholar
  32. Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nat Rev Immunol. 2002;2:797–804. Scholar
  33. Yuki N, Hartung HP. Guillain-Barre syndrome. N Engl J Med. 2012;366:2294–304. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Neuroimmunology Unit, Department of PathophysiologyNational and Kapodistrian University of Athens Medical SchoolAthensGreece

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