Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN) with conduction block is an acquired immune-mediated demyelinating neuropathy, which causes slowly progressive weakness, fasciculations, and cramping. It can resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but distinction is important since MMN usually improves with immunosuppressive treatment.

MMN is more common in men than women with a mean age at onset of 40 years (range of 20–70). The most common initial symptoms are wrist drop, grip weakness, and foot drop. Weakness progresses asymmetrically, but usually remains more prominent in the arms than in the legs. Weakness is typically more pronounced than would be suggested by the degree of muscle atrophy present. Affected patients also complain of muscle cramps and fasciculations. Tendon reflexes are reduced in affected regions. Sensory complaints are unusual.

These symptoms and signs from MMN are very similar to those seen in early ALS, and many patients are initially misdiagnosed with this disorder. MMN can usually be distinguished from ALS by its more slowly progressive disease course, the absence of upper-motor-neuron signs such as spasticity and hyperreflexia and the lack of difficulty with speech and swallowing.

However a carefully planned and executed electrodiagnostic study (EMG) is critical for distinguishing these disorders. MMN is a demyelinating neuropathy, while ALS is an anterior horn cell (motor neuronopathy) which causes secondary axonal degeneration of the motor nerve. When one suspects MMN clinically, identifying partial motor conduction block is critical in confirming the diagnosis.

The presence of high titers of antibodies to GM1 ganglioside can also be useful for confirming the diagnosis of MMN, but are only present in 20-60% of patients, and are rarely present in ALS patients, underscoring the importance of clinical suspicion and the EMG for making the diagnosis.

MMN is an immune mediated disorder and strength can recover after  repeated treatments with intravenous immunoglobulin (IVIG), whereas ALS does not respond to this or any other treatment, hence the importance of distinguishing these 2 disorders:

Disease                                                           MMN                                           ALS
Distribution of weakness                        Asymmetric,Arms                Ultimately generalized
Upper motor neuron findings                 Absent                                   Usually present
EMG                                                        Conduction block                   Motor axonal loss
Anti GM1 Ab                                               20-60%                                  10%
Response to IVIG                                       Yes                                           No

The clinical pictures below are from a patient with longstanding generalized weakness that I encountered several years ago.  The first picture shows his severe upper  limb atrophy (and weakness):

His EMG showed conduction block, suggesting MMN:

And the second picture showed the clinical improvement that had already occurred after 6 monthly treatments with IVIG:

Obviously it is important to at least consider this treatable disorder in all patients with suspected ALS or motor neuron disease, and it is very important to see a neurology specialist with additional training and certification in neuromuscular medicine and/or electrodiagnostic medicine. Click here or call 732 923-5576 to find out more about the Central Jersey MDA and Neuromuscular Center at the Monmouth Neuroscience Institute.