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.

Yale University/VA Connecticut Healthcare System, New Haven, CT, USA.
Neurology (Impact Factor: 8.3). 03/2012; 78(13):1009-15. DOI: 10.1212/WNL.0b013e31824de293
Source: PubMed

ABSTRACT To assess the evidence for the efficacy of IV immunoglobulin (IVIg) to treat neuromuscular disorders.
The MEDLINE, Web of Science, and EMBASE databases were searched (1966-2009). Selected articles were rated according to the American Academy of Neurology's therapeutic classification of evidence scheme; recommendations were based on the evidence level.
IVIg is as efficacious as plasmapheresis and should be offered for treating Guillain-Barré syndrome (GBS) in adults (Level A). IVIg is effective and should be offered in the long-term treatment of chronic inflammatory demyelinating polyneuropathy (Level A). IVIg is probably effective and should be considered for treating moderate to severe myasthenia gravis and multifocal motor neuropathy (Level B). IVIg is possibly effective and may be considered for treating nonresponsive dermatomyositis in adults and Lambert-Eaton myasthenic syndrome (Level C). Evidence is insufficient to support or refute use of IVIg in the treatment of immunoglobulin M paraprotein-associated neuropathy, inclusion body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher syndrome, or in the routine treatment of postpolio syndrome or in children with GBS (Level U). IVIg combined with plasmapheresis should not be considered for treating GBS (Level B). More data are needed regarding IVIg efficacy as compared with other treatments/treatment combinations. Most studies concluded IVIg-related serious adverse effects were rare. Given the variable nature of these diseases, individualized treatments depending on patient need and physician judgment are important.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Prolonged intravenous immunoglobulin (IVIG) therapy is used for the chronic autoimmune neuropathies CIDP and MMN, but the doses and treatment intervals are usually chosen empirically due to a paucity of data from dose-response studies. Recent studies of the electrophysiology and immunology of these diseases suggest that antibody-induced reversible dysfunction of nodes of Ranvier may play a role in conduction block and disability which responds to immunotherapy more rapidly than would be expected for demyelination or axonal damage per se. Clinical reports suggest that in some cases, the effects of each dose of IVIG may be transient, wearing-off before the next dose is due. These observations lead us to hypothesize that that therapeutic IgG acts by competing with pathologic autoantibodies and that individual patients may require different IgG levels for optimal therapeutic effects. Frequent IVIG dosing and weekly subcutaneous IgG have been tried as ways of continuously maintaining high serum IgG levels, resulting in stabilization of neuromuscular function in small case series. Frequent grip strength and disability measurements, performed by the patient at home and reported electronically, can be used to assess the extent and duration of responses to IgG doses. Individualization of IgG treatment regimens may optimize efficacy, minimize disability, and identify non-responders. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc.
    Muscle & Nerve 11/2014; 51(3). DOI:10.1002/mus.24526 · 2.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement.
    Immunotherapy 10/2014; 6(10):1113-26. DOI:10.2217/imt.14.67 · 2.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mounting evidence suggests that autoantibodies contribute to the pathogenesis of demyelination in the PNS and CNS. Rapid reversal of electrophysiological blockade after plasmapheresis or intravenous immunoglobulin treatment for acute or chronic inflammatory demyelinating polyneuropathy is more likely to result from removal or neutralization of an antibody that impairs saltatory conduction than from remyelination. Although up to 30% of patients with acute or chronic inflammatory demyelinating polyneuropathy harbour autoantibodies, specific antigens have been identified in no more than 13% of cases. To date, autoantigens identified at the node of Ranvier include neurofascin 186, gliomedin and possibly moesin in the nodal domain, and contactin-1, Caspr1 and neurofascin 155 in the paranodal domain. In some patients with multiple sclerosis, paranodal CNPase and juxtaparanodal contactin-2 trigger a humoral response. This Review explores the molecular anatomy of the node of Ranvier, focusing on proteins with extracellular domains that could serve as antigens. The clinical implications of node-specific antibody responses are addressed, and the best approaches to identify antibodies that target nodal proteins are highlighted. Also discussed are the roles of these antibodies as either secondary, disease-exacerbating responses, or as a primary effector mechanism that defines demyelination or axonal degeneration at the node, identifies disease subtypes or determines response to treatments.
    Nature Reviews Neurology 01/2015; DOI:10.1038/nrneurol.2014.260 · 14.10 Impact Factor