Nerve excitability changes after intravenous immunoglobulin infusions in multifocal motor neuropathy and chronic inflammatory demyelinating neuropathy

Boërio, Delphine; Créange, Alain; Hogrel, Jean‐Yves; Guéguen, Antoine; Bertrand, Dominique; Lefaucheur, Jean‐Pascal

doi:10.1016/j.jns.2010.02.002

Cited by 29 publications

(44 citation statements)

References 44 publications

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“…IVIG has been shown to block binding of anti‐ganglioside antibodies from MMN patients in an ELISA (Yuki et al ., ) , but IVIG can also have anti‐id effects on specific T‐cell receptors (Lacroix‐Desmazes et al ., ) . As occurs in CIDP, a decrease in strength‐duration time‐constant for CMAP follows IVIG infusions in MMN, suggesting that decreased axonal excitability contributes to the pathology (Boerio et al ., ) . Axonal excitability improves shortly after IVIG infusions, but these effects wane in subsequent weeks, before the next infusion is due (Priori et al ., ; Van den Berg‐Vos et al ., ; Terenghi et al ., ) .…”

Section: Multifocal Motor Neuropathymentioning

confidence: 96%

Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies

Berger

McCallus²,

Lin

2013

J Peripheral Nervous Sys

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Intravenous immunoglobulin (IVIG) is widely used in autoimmune neuromuscular diseases whose pathogenesis is undefined. Many different effects of IVIG have been demonstrated in vitro, but few studies actually identify the mechanism(s) most important in vivo. Doses and treatment intervals are generally chosen empirically. Recent studies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy show that some effects of IVIG are readily reversible and highly dependent on the serum IgG level. This suggests that in some autoantibody-mediated neuromuscular diseases, IVIG directly competes with autoantibodies that reversibly interfere with nerve conduction. Mechanisms of action of IVIG which most likely involve direct competition with autoantibodies include: neutralization of autoantibodies by anti-idiotypes, inhibition of complement deposition, and increasing catabolism of pathologic antibodies by saturating FcRn. Indirect immunomodulatory effects are not as likely to involve competition and may not have the same reversibility and dose-dependency. Pharmacodynamic analyses should be informative regarding most relevant mechanism(s) of action of IVIG as well as the role of autoantibodies in the immunopathogenesis of each disease. Better understanding of the role of autoantibodies and of the target(s) of IVIG could lead to more efficient use of this therapy and better patient outcomes.

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Section: Multifocal Motor Neuropathymentioning

confidence: 96%

Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies

Berger

McCallus²,

Lin

2013

J Peripheral Nervous Sys

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“…In recent years, studies in patients and in animal models have highlighted the importance of autoantibodies against gangliosides and/or membrane proteins in the acute motor axonal neuropathy (AMAN) form of GBS, MMN, and possibly acute inflammatory demyelinatiang polyradiculopathy and CIDP . These results have led to the hypothesis that antibody‐induced alterations in the distribution of ion channels and/or structural proteins in the nodes of Ranvier may interfere with conduction or cause outright block by reversibly interfering with axon function . These functional alterations may be more rapidly responsive to therapy than classically described pathologic changes such as demyelination or destruction of axons .…”

mentioning

confidence: 99%

Optimizing IgG therapy in chronic autoimmune neuropathies: A hypothesis driven approach

Berger

Allen

2015

Muscle and Nerve

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Prolonged intravenous immunoglobulin (IVIG) therapy is used for the chronic autoimmune neuropathies chronic idiopathic demyelinating polyneuropathy and multifocal motor neuropathy, 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 nonresponders. Muscle Nerve 51: 315–326, 2015

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“…One hypothesis is that at sensory nerves the density of Na + /K + ATPase is higher and their cumulative function can correct for the ion fluxes so no conduction block is seen [51, 54–57]. The relatively rapid response to IVIg treatment in all probability does not reflect remyelination, and is more likely due to a decrease in persistent Na + current [58]. …”

Section: Immune Pathophysiology Of Mmnmentioning

confidence: 99%

MMN: From Immunological Cross-Talk to Conduction Block

et al. 2014

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Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy characterized by progressive, asymmetric distal limb weakness and conduction block (CB). Clinically MMN is a pure motor neuropathy, which as such can mimic motor neuron disease. GM1-specific IgM antibodies are present in the serum of approximately half of all MMN patients, and are thought to play a key role in the immune pathophysiology. Intravenous immunoglobulin (IVIg) treatment has been shown to be effective in MMN in five randomized placebo-controlled trials. Despite long-term treatment with intravenous immunoglobulin (IVIg), which is efficient in the majority of patients, slowly progressive axonal degeneration and subsequent muscle weakness cannot be fully prevented. In this review, we will discuss the current understanding of the immune pathogenesis underlying MMN and how this may cause CB, available treatment strategies and future therapeutic targets.

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Nerve excitability changes after intravenous immunoglobulin infusions in multifocal motor neuropathy and chronic inflammatory demyelinating neuropathy

Cited by 29 publications

References 44 publications

Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies

Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies

Optimizing IgG therapy in chronic autoimmune neuropathies: A hypothesis driven approach

MMN: From Immunological Cross-Talk to Conduction Block

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