eMedicine Specialties > Neurology > Neuromuscular Diseases

Multifocal Motor Neuropathy With Conduction Blocks

Author: Sasa Zivkovic, MD, MSc, Assistant Professor, Department of Neurology, Division of Neuromuscular Diseases, University of Pittsburgh and VA Pittsburgh Healthcare System
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Updated: Jan 25, 2008

Introduction

Background

Multifocal motor neuropathy (MMN) with conduction block is an acquired immune-mediated demyelinating neuropathy with slowly progressive weakness, fasciculations, and cramping, without significant sensory involvement.

Clinically, it may resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but muscle atrophy and more rapid progression are lacking. Duration of disease prior to diagnosis ranges from several months to more than 15 years.

Unlike ALS, MMN usually responds to treatment with intravenous immunoglobulin (IVIG) or cyclophosphamide, even after many years of duration.

Pathophysiology

The complete cascade of events leading to motor nerve dysfunction and weakness in MMN is not fully understood, but it appears to be related to disimmune events. Histopathologic and electrodiagnostic studies demonstrate the presence of both demyelinating and axonal injury. Motor nerves are primarily affected, although mild demyelination has been demonstrated in sensory nerves as well. Efficacy of immunomodulatory and immunosuppressive treatment further supports the immune nature of MMN.

Titers of anti-GM1 antibodies are frequently elevated (>50%), but their role has not been established even though they remain a useful marker for the diagnosis of MMN. While fluctuations in anti-GM1 titers do not correlate with clinical symptoms in most patients treated with IVIG, titers may decrease after treatment with cyclophosphamide and rituximab, correlating with improved strength. Selective involvement of motor nerves with high titers of anti-GM1 antibodies is somewhat surprising because antibodies bind both to ventral and dorsal spinal roots. Binding has also been shown to occur at the nodes of Ranvier, at compact or outer myelin of Schwann cells, and at the motor end plate of the neuromuscular junction.

Frequency

United States

MMN is a rare disorder, and its lifetime prevalence is estimated to be 1 case in 100,000 population.

International

Reported prevalence of MMN in other countries is similar to that in the United States.

Mortality/Morbidity

Most patients maintain productive lives despite ongoing symptoms, and up to 94% remain employed.

Fatal outcomes have been reported only rarely, and at least some case reports describe patients with other entities, including motor neuron disease.

• Rarely, multifocal motor neuropathy may be associated with a B-cell lymphoma producing monoclonal antibodies against GM1 and GD1b myelin glycolipids.
• Gradual progression of symptoms may lead to significant disability.

Race

No racial predilection exists.

Sex

MMN is more common in males (the male-to-female ratio is about 3:1).

Age

The mean age of onset is 40 years. Eighty percent of patients are aged 20-50 years at presentation.

Clinical

History

Typically, multifocal motor neuropathy (MMN) manifests with a slowly progressive, asymmetric, predominantly distal weakness developing over years. Weakness usually starts in a distribution of a single peripheral nerve with unilateral wrist drop, foot drop, or grip weakness. Initial involvement of the distal upper extremities is most common. Rarely, MMN may manifest with initial phrenic or cranial nerve involvement. Cramps and twitching are common, but muscle atrophy is minimal if present at all. Sensory symptoms are minimal or absent. Transient exacerbation may occur during pregnancy.

Electrodiagnostic evaluation may document the presence of asymptomatic conduction blocks in other clinically unaffected nerves, and it may document more extensive involvement in patients with relatively few symptoms. Positive serology for anti-GM1 antibodies is supportive of the diagnosis of MMN, particularly higher titers.

Clinical and electrodiagnostic criteria for the diagnosis of MMN include the following:

• Definite MMN
  • Weakness without objective sensory loss in the distribution of 2 or more nerves is present.
  • Definite conduction block is present in 2 or more motor nerves outside of common entrapment sites.
  • Sensory nerve conduction velocity is normal across the segments with demonstrated motor conduction block.
  • Results are normal for sensory nerve conduction studies on all tested nerves, with a minimum of 3 nerves tested.
  • Upper motor neuron signs, including spasticity, clonus, extensor plantar response, and pseudobulbar palsy are absent.
• Probable MMN
  • Weakness without objective sensory loss in the distribution of 2 or more nerves.
  • The presence of either (1) probable conduction block in 2 or more motor nerve segments that are not common entrapment sites or (2) definite conduction block in one motor nerve and probable conduction block in a different motor nerve segment (uncommon entrapment sites).
  • Sensory nerve conduction velocity is normal across the segments with demonstrated motor conduction block.
  • Results are normal for sensory nerve conduction studies on all tested nerves, with a minimum of 3 nerves tested.
  • Upper motor neuron signs, such as spasticity, clonus, extensor plantar response, and pseudobulbar palsy are absent.

Physical

On physical examination, the most remarkable finding is asymmetric weakness in the distribution of individual peripheral nerves that is out of proportion to muscle atrophy. Fasciculations may be present.

• Cranial nerves
  • Cranial nerves are rarely affected, but this may be an uncommon initial manifestation of MMN. Cranial nerve involvement may be limited to the twelfth cranial nerve.
  • Speech is normal.
• Deep tendon reflexes: Deep tendon reflexes may be absent (particularly in affected limbs) or normal. Early in the course, tendon reflexes may be brisk.
• Motor strength
  • Asymmetric weakness may occur in a nonmyotomal pattern, usually in the distribution of individual nerves. The upper limbs, particularly the hands, are more commonly involved than the lower limbs.
  • Muscles innervated by motor nerves with persistent conduction block are usually weak.
• Muscle atrophy: Atrophy may be present in weak muscles, but it is fairly mild. Late in the disease course atrophy may be more prevalent.
• Upper motor neuron signs: These signs are absent.
• Muscle tone: Tone is decreased or normal. No clonus, extensor plantar response, or pseudobulbar palsy is present. Pathologic reflexes (eg, Babinski, Hoffman) are not present.
• Sensory examination: Findings are normal, and the sensory loss is suggestive of Lewis-Sumner syndrome (multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]).
• Coordination: Coordination is normal.
• Gait: Gait is usually normal, unless more prominent involvement of lower extremity muscles occurs.
• Fasciculations and cramping: These are common and may occur outside of the distribution of clinically affected nerves.
• Other: No rash or gynecomastia is present.

Causes

MMN is an autoimmune peripheral neuropathy without a known cause.

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