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Published in:

01-01-2013

Immune Pathogenesis and Treatment of Multifocal Motor Neuropathy

Authors: Lotte Vlam, Leonard H. van den Berg, Elisabeth A. Cats, Sanne Piepers, W.-Ludo van der Pol

Published in: Journal of Clinical Immunology | Special Issue 1/2013

Abstract

Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated chronic disorder characterized by asymmetric distal limb weakness and conduction block. The exact pathogenesis of MMN is still unclear, but IgM anti-GM1 antibodies, which can be detected in sera from approximately half of all MMN patients, are thought to play an important role. Treatment with intravenous immunoglobulin (IVIG) is effective in the vast majority of patients, but, despite IVIG maintenance treatment, many patients experience a slowly progressive decline in muscle strength. In this review we will summarize the results from studies on pathogenesis. We will discuss current treatment strategies of MMN and how insight into MMN pathogenesis may translate into novel therapies in the future.

Vlam L, van der Pol WL, Cats EA, Straver DC, Piepers S, Franssen H, et al. Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies. Nat Rev Neurol. 2011;8(1):48–58.PubMedCrossRef

Cats EA, van der Pol WL, Piepers S, Franssen H, Jacobs BC, van den Berg-Vos RM, et al. Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy. Neurology. 2010;75(9):818–25.PubMedCrossRef

Van Asseldonk JT, Van den Berg LH, Kalmijn S, Van den Berg-Vos RM, Polman CH, Wokke JH, et al. Axon loss is an important determinant of weakness in multifocal motor neuropathy. J Neurol Neurosurg Psychiatry. 2006;77(6):743–7.PubMedCrossRef

Rojas-Garcia R, Tizzano E, Cusco I, Gallardo E, Barcelo MJ, de Andres I, et al. The absence of survival motor neuron 2 gene may play a role in multifocal motor neuropathy. Neurology. 2002;59(7):1112–3.PubMedCrossRef

Cats EA, Jacobs BC, Yuki N, Tio-Gillen AP, Piepers S, Franssen H, et al. Multifocal motor neuropathy: association of anti-GM1 IgM antibodies with clinical features. Neurology. 2010;75(22):1961–7.PubMedCrossRef

Willison HJ, Yuki N. Peripheral neuropathies and anti-glycolipid antibodies. Brain. 2002;125(Pt 12):2591–625.PubMedCrossRef

Susuki K, Baba H, Tohyama K, Kanai K, Kuwabara S, Hirata K, et al. Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Glia. 2007;55(7):746–57.PubMedCrossRef

Susuki K, Rasband MN, Tohyama K, Koibuchi K, Okamoto S, Funakoshi K, et al. Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers. J Neurosci. 2007;27(15):3956–67.PubMedCrossRef

Piepers S, Jansen MD, Cats EA, van Sorge NM, van den Berg LH, van der Pol WL. IVIg inhibits classical pathway activity and anti-GM1 IgM-mediated complement deposition in MMN. J Neuroimmunol. 2010;229(1–2):256–62.PubMedCrossRef

10.

Yuki N, Watanabe H, Nakajima T, Spath PJ. IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal motor neuropathy. J Neurol Neurosurg Psychiatry. 2011;82(1):87–91.PubMedCrossRef

11.

Kokubun N, Nishibayashi M, Uncini A, Odaka M, Hirata K, Yuki N. Conduction block in acute motor axonal neuropathy. Brain. 2010;133(10):2897–908.PubMedCrossRef

12.

Galban-Horcajoa F, Fitzpatricka AM, Huttona AJ, Dunna SM, Kalnab G, Brennana KM, et al. Antibodies to heteromeric glycolipid complexes in multifocal motor neuropathy. Eur J Neurol. Published online 22 jun 2012.

13.

Pestronk A, Choksi R, Blume G, Lopate G. Multifocal motor neuropathy: serum IgM binding to a GM1 ganglioside-containing lipid mixture but not to GM1 alone. Neurology. 1997;48:1104–6.PubMedCrossRef

14.

Pestronk A, Chuquilin M, Choksi R. Motor neuropathies and serum IgM binding to NS6S heparin disaccharide or GM1 ganglioside. J Neurol Neurosurg Psychiatry. 2010;81(7):726–30.PubMedCrossRef

15.

Terenghi F, Allaria S, Scarlato G, Nobile-Orazio E. Multifocal motor neuropathy and Campylobacter jejuni reactivity. Neurology. 2002;59(2):282–4.PubMedCrossRef

16.

Sutedja NA, Otten HG, Cats EA, Piepers S, Veldink JH, van der Pol WL, et al. Increased frequency of HLA-DRB1*15 in patients with multifocal motor neuropathy. Neurology. 2010;74(10):828–32.PubMedCrossRef

17.

Cats EA, Bertens AS, Veldink JH, van den Berg LH, van der Pol WL. Associated autoimmune diseases in patients with multifocal motor neuropathy and their family members. J Neurol. 2011 Nov 23. [Epub ahead of print]

18.

Vlam L, Cats EA, Seelen M, van Vught PW, van den Berg LH, van der Pol WL. Multifocal motor neuropathy is not associated with genetic variation in PTPN22, BANK1, Blk, FCGR2B, CD1A/E, and TAG-1 genes. J Peripher Nerv Syst. 2011;16(3):175–9.PubMedCrossRef

19.

Harbo T, Andersen H, Hess A, Hansen K, Sindrup SH, Jakobsen J. Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial. Eur J Neurol. 2009;16(5):631–8.PubMedCrossRef

20.

Eftimov F, Van Schaik IN. Immunotherapy of multifocal motor neuropathy. Expert Opin Biol Ther. 2011;11(3):329–42.PubMedCrossRef

21.

Piepers S, Van den Berg-Vos R, Van der Pol WL, Franssen H, Wokke J, Van den Berg L. Mycophenolate mofetil as adjunctive therapy for MMN patients: a randomized, controlled trial. Brain. 2007;130(Pt 8):2004–10.PubMedCrossRef

22.

Kuitwaard K, de Gelder J, Tio-Gillen AP, Hop WC, van Gelder T, van Toorenenbergen AW, et al. Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barre syndrome. Ann Neurol. 2009;66(5):597–603.PubMedCrossRef

23.

Fitzpatrick AM, Mann CA, Barry S, Brennan K, Overell JR, Willison HJ. An open label clinical trial of complement inhibition in multifocal motor neuropathy. J Peripher Nerv Syst. 2011;16(2):84–91.PubMedCrossRef

24.

Qu H, Ricklin D, Lambris JD. Recent developments in low molecular weight complement inhibitors. Mol Immunol. 2009;47(2–3):185–95.PubMedCrossRef

25.

Phongsisay V, Susuki K, Matsuno K, Yamahashi T, Okamoto S, Funakoshi K, et al. Complement inhibitor prevents disruption of sodium channel clusters in a rabbit model of Guillain-Barre syndrome. J Neuroimmunol. 2008;205(1–2):101–4.PubMedCrossRef

26.

Chaudhry V, Cornblath DR. An open-label trial of rituximab (Rituxan(R)) in multifocal motor neuropathy. J Peripher Nerv Syst. 2010;15(3):196–201.PubMedCrossRef

Title: Immune Pathogenesis and Treatment of Multifocal Motor Neuropathy
Authors: Lotte Vlam
Leonard H. van den Berg
Elisabeth A. Cats
Sanne Piepers
W.-Ludo van der Pol
Publication date: 01-01-2013
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue Special Issue 1/2013
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-012-9779-8

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