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  • Updated 10.24.2020
  • Released 09.22.1998
  • Expires For CME 10.24.2023

Motor and multifocal motor neuropathies

Introduction

Overview

Motor neuropathies and multifocal motor neuropathy with conduction block are treatable causes of neuropathy that present with the clinical syndrome of asymmetric motor weakness with atrophy, which may mimic amyotrophic lateral sclerosis. The diagnosis of the disorder relies on the typical clinical presentation as well as electrodiagnostic findings of conduction block at noncompression sites and often on anti-GM1 IgM antibodies on serum testing. The mainstay of therapy includes intravenous immunoglobulin, but often other immunomodulating therapy is required for long-term management. In this article, the author summarizes the most recent literature covering pathophysiology, diagnostic criteria, and treatment for motor neuropathy.

Key points

• Multifocal motor neuropathy is a treatable cause of neuropathy that may mimic amyotrophic lateral sclerosis.

• The diagnosis of multifocal motor neuropathy relies on the typical clinical presentation, electrophysiology demonstrating conduction block outside of compression sites, and the presence of anti-GM1 IgM antibodies.

• The primary diseases to consider in the differential diagnosis of multifocal motor neuropathy include amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy, and Lewis Sumner syndrome (multifocal acquired demyelinating sensory and motor neuropathy).

• Motor neuropathies and multifocal motor neuropathy often respond to treatment with intravenous immunoglobulin, but in some patients, long-term management requires the use of other immunosuppressant medications.

Historical note and terminology

Motor neuropathy is manifested by weakness, often with muscle atrophy and fasciculations and normal sensory functions. It can be generalized, or involve 1 or several nerves, and can be slowly progressive or acute in onset. The motor axons or nerve fibers are primarily affected, distinguishing it from motor neuron disease wherein the perikaryon or nerve cell body is primarily involved. Motor neuropathy is often immunologically mediated, and can respond to immunosuppressive therapies, whereas motor neuron disease does not.

The majority of clinical research, epidemiology, and treatment trials assessing motor neuropathy have focused on multifocal motor neuropathy, also known as multifocal motor neuropathy with conduction block. This describes the clinical entity of asymmetric motor neuropathy, often with conduction block or other demyelinating findings on electrodiagnostic studies and sometimes with anti-GM1 ganglioside antibodies. Less typical clinical pictures are also included in the framework of multifocal motor neuropathy, including a more symmetric neuropathy, those without conduction block, and those without GM1 antibodies; these neuropathies are at times referred to as “motor neuropathy” without using the term multifocal motor neuropathy but in many series and clinical care are considered a shared entity in terms of pathophysiology and management. A separate category is motor neuropathies associated with other causes, including those with amyloidosis. These motor neuropathies should be clinically managed according to their associated etiology and generally considered separately from the spectrum of multifocal motor neuropathy. Except where specifically noted, the majority of this article addresses the entity of what is commonly referred to as multifocal motor neuropathy when describing motor neuropathies.

Motor neuropathy is described in papers dating back to the 1920s (139; 68; 180). Interest in the syndrome, however, has flourished since the 1980s with the discovery of autoantibodies to glycolipid neural antigens and nerve conduction abnormalities, such as conduction block, which have aided in identifying patients with motor neuropathy.

Peters and Clatanoff described a patient with spinal muscular atrophy and an IgM monoclonal gammopathy who improved following treatment with chlorambucil (133). In retrospect, that patient probably suffered from motor neuropathy, rather than from motor neuron disease. The first documented case of a patient with motor neuropathy and an IgM monoclonal gammopathy was reported by Rowland and colleagues (141). That patient presented with progressive weakness, muscle atrophy and fasciculations, and had an IgM kappa monoclonal gammopathy. Motor conduction velocities were slow, with normal sensory conductions. Postmortem examination revealed a normal number of anterior horn cells with central chromatolysis (implicating a peripheral neuropathy) and severe loss of nerve fibers in the anterior roots.

Multifocal demyelinating neuropathy with persistent conduction block was first described by Lewis and colleagues. They reported several patients with a chronic demyelinating sensorimotor neuropathy, characterized clinically by mononeuritis multiplex and electrophysiologically by persistent multifocal conduction block (100). In 1985, Parry and Clarke described several patients with a syndrome resembling motor neuron disease, but with multifocal motor conduction block and normal sensory conductions (128).

IgM anti-GM1 antibodies were first described by Freddo and associates in a patient with lower motor neuron syndromes and IgM monoclonal gammopathy (56). A second patient with the same syndrome improved with immunosuppressive therapy (95). Pestronk and colleagues reported that patients with multifocal motor neuropathy and conduction block also had high titers of IgM anti-GM1 antibodies and coined the term “multifocal motor neuropathy” (131).

Katz and colleagues have proposed a separate entity known as “multifocal acquired motor axonopathy” (or MAMA neuropathy) to describe those patients with pure motor neuropathy without electrophysiologic conduction block or demyelination. Some of these patients have GM1 antibodies, and clinically they appear to respond similarly to therapy (78; 55). Although the authors of these reports argue that there are differences in the clinical and serologic qualities of the patients described, many feel that this subset of patients likely represents the same pathophysiologic spectrum as multifocal motor neuropathy, but in which the typical electrophysiologic findings of conduction bock cannot be captured anatomically or temporally.

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