Multifocal motor neuropathy

Synonyms

3

Overview

Multifocal motor neuropathy (MMN) is a rare neuropathy characterized by progressive, asymmetric muscle weakness and atrophy (wasting). Signs and symptoms include weakness in the hands and lower arms; cramping; involuntary contractions or twitching; and atrophy of affected muscles. MMN is thought to be due to an abnormal immune response, but the underlying cause is not clear. Most people treated with intravenous immune globulin (IVIG) have rapid improvement in weakness, but maintenance IVIG is usually required for sustained improvement.
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. 

Symptoms

Signs and symptoms may include:

  • weakness
  • cramping
  • involuntary contractions or twitching
  • wasting (atrophy) of affected muscles.

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.

Causes

The exact underlying cause of multifocal motor neuropathy (MMN) is poorly understood. It is considered an immune-mediated disorder (due to an abnormal immune system response), both because IVIG therapy improves symptoms, and many patients have anti-GM1 antibodies. Research to further understand the cause of MMN is underway.

Prevention

We are not aware of any evidence that multifocal motor neuropathy (MMN) is inherited or of any reports of familial cases (occurring in more than one person in a family). Furthermore, to our knowledge, no specific genes known to be associated with MMN have been identified.

Diagnosis

Clinical and electrodiagnostic criteria for the diagnosis of MMN:

  • Weakness without objective sensory loss in the distribution of 2 or more nerves is present for more than 1 month
  • Definite motor conduction block is present in at least one motor nerve with normal sensory nerve conductions
  • Exclusion criteria not present

Probable MMN:

  • Weakness without objective sensory loss in the distribution of 2 or more nerves
  • The presence of probable motor conduction block in 2 or more motor nerve segments with normal sensory nerve conduction studies
  • Exclusion criteria not present

OR:

  • Weakness without objective sensory loss in the distribution of one nerve
  • The presence of probable motor conduction block in one motor nerve segments with normal sensory nerve conduction studies
  • Exclusion criteria are not present.
  • At least 2 supportive criteria met

Supportive criteria:

  • Elevated titers of serum IgM anti-GM1 antibodies
  • Increased cerebrospinal fluid (CSF) protein (< 1 g/L)
  • MRI shows increased signal on T2-weighted imaging of brachial plexus with diffuse nerve swelling
  • Objective clinical improvement following intravenous immunoglobulin (IVIG) treatment

Exclusion criteria:

  • Upper motor neuron signs, such as spasticity, clonus, extensor plantar response
  • Marked bulbar involvement
  • Sensory involvement more marked than minor vibration loss in the lower limbs
  • Diffuse symmetric weakness during initial weeks

Prognosis

Prognosis of Multifocal motor neuropathy with conduction block: variable, walking and ability to perform daily activities can be affected to a large degree in some cases

Treatment

Multifocal motor neuropathy (MMN) is considered treatable with intravenous immune globulin (IVIG).
Early treatment shortly after symptoms begin is recommended. Most people have a fairly rapid improvement in weakness with IVIG, but the improvement generally does not last beyond a few months. Maintenance IVIG infusions are usually needed every two to six weeks. For those with severe disease whose symptoms don't respond to IVIG (or for those who become resistant), treatment options are limited. Several reports have suggested that cyclophosphamide may be partially effective.