Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies

Abstract

Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy characterized by slowly progressive, asymmetric distal limb weakness without sensory loss. The clinical presentation of MMN may mimic amyotrophic lateral sclerosis, other variants of motor neuron disease, or chronic inflammatory demyelinating polyneuropathy with asymmetric onset. Differentiation is important, as these diseases differ in prognosis and treatment. The electrophysiological finding of conduction block in the absence of abnormalities in sensory nerves is the hallmark of MMN, but can be difficult to detect. Intravenous immunoglobulin is efficacious in most patients, but long-term maintenance therapy does not prevent slowly progressive axonal degeneration. Moreover, cyclophosphamide, although effective, has substantial adverse effects, and the efficacy of other immunosuppressive drugs, including rituximab, is not established. The underlying pathological mechanisms of MMN are unclear, but IgM autoantibodies against the ganglioside GM1 may cause changes in nodal and perinodal structures that compromise nerve conduction. Further elucidation of the disease mechanisms may ultimately lead to improved treatment strategies. In this Review, we discuss the diagnostic criteria for MMN, and provide an update on the current understanding of MMN pathogenesis. We also describe available treatments and promising new therapeutic strategies.

Key Points

  • Multifocal motor neuropathy (MMN) is a rare disorder characterized by asymmetric, predominantly distal limb weakness without evident sensory loss

  • MMN should be differentiated from amyotrophic lateral sclerosis, lower motor neuron disease, chronic inflammatory demyelinating polyneuropathy and Lewis–Sumner syndrome

  • The diagnosis of MMN is based on clinical and electrophysiological characteristics, and may be supported by results from ancillary investigations, especially in the absence of conduction block

  • MMN is thought to be an immune-mediated disorder in which B cells, autoantibodies and complement play an important role

  • Treatment with intravenous immunoglobulin is efficacious in most patients with MMN, but a slowly progressive decline in muscle strength usually occurs, owing to ongoing axonal degeneration

  • Several immunosuppressive therapies have been investigated in small, open-label studies, but conclusive evidence of efficacy is lacking

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Figure 1: Possible pathological mechanisms in MMN.
Figure 2: Management of MMN.

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Acknowledgements

W.-L. van der Pol, H. Franssen and L. H. van den Berg are supported by the Prinses Beatrix Fund.

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L. Vlam and W.-L. van der Pol researched the data for the article. All authors made substantial contributions to discussion of the article content. L. Vlam, W.-L. van der Pol and L. H. van den Berg contributed to writing the article. All authors contributed to review and/or editing of the manuscript before submission.

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Correspondence to Leonard H. van den Berg.

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L. H. van den Berg is a consultant to, on the Speakers bureau of, and receives grant/research support from Baxter International. W.-L. van der Pol and E. A. Cats receive grant/research support from Baxter International. H. Franssen is on the Speakers bureau of Baxter International. The other authors declare no competing interests.

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Supplementary Box 1

Diagnostic criteria for MMN1,2 (DOC 36 kb)

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Vlam, L., van der Pol, WL., Cats, E. et al. Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies. Nat Rev Neurol 8, 48–58 (2012). https://doi.org/10.1038/nrneurol.2011.175

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