Multifocal motor neuropathy (MMN) is a rare and potentially disabling disease of the motor nerves. It usually causes weakness in mainly one limb. The arms are more commonly affected than the legs. Men are more likely than women to develop MMN. In some instances, patients with MMN may be suspected to have other diseases such as Lou Gehrig's disease also known as Amyotrophic Lateral Sclerosis (ALS). However the pattern of involvement is that of multiple peripheral motor nerves in MMN while the motor neuron segment (myotome) is affected in ALS. Furthermore, MMN patients lack the abnormal increase in reflexes that is seen in ALS. Unlike ALS, the overwhelming majority of MMN patients have normal longevity.

MMN patients benefit from the evaluation by a neurologist with special expertise in the peripheral nerves. MMNis suspected in patients who have weakness without loss of sensation in primarily one arm or leg that worsens very slowly over several years. This presentation is easy to distinguish from that of the GBS which progresses over 2 to 4 weeks. Unlike MMN, CIDPsufferers have abnormal sensation and most have both sides of their body equally affected.

The Lewis-Sumner syndrome (LSS) has features that overlap with MMN. Both MMN and LSS results in asymmetric weakness (one side being weaker than the other) that progresses over months to years in association with conduction block (see below). LSS affects the motor and sensory nerves, and responds to treatment with either corticosteroids or MG. In contradistinction, MMN affects only the motor nerves. MMN patients do not respond to corticosteroid therapy or may even get worse. More details on the LSS can be found in the spring 2008 issue of The Communicator.

If untreated, MMN is a disabling disease. Treatment begins after the diagnosis is suspected then confirmed with one of two tests. These are a nerve conduction study and a blood test. The nerve conduction study involves the delivery of incremental levels of electric shocks to a peripheral nerve. In the arm this is typically done at the wrist and elbow. Most MMN patients have conduction block in at least one motor nerve. Conduction block means that the electrical stimulus fails to travel across a nerve segment. This failure results from loss of myelin function (nerve insulation) over several adjacent nodes of Ranvier. The later are areas of the nerve axon (cable) in between segments of myelin that allow for effIcient electrical impulse propagation down the nerve. It is extremely important that the nerve conduction test includes a survey of the nerves controlling weak muscles. A diligent search will demonstrate conduction block in the most MMN suspects.

Markedly elevated GMI antibody titers are detectable in the blood of about 50% of MMN patients. The G in GMI stands for ganglioside which is a sugar and fat molecule. The letter M (mono) indicates the number of sialic acid residues, in this case one. The number 1 refers to the order of migration of GMI on thin-layer chromatography. These IgM antibodies to GM1 have been localized to the area of nerve, in between segments of myelin, called nodes of Ranvier. GMI antibodies have also been identifIed in the axonal motor variant of GBS. In the later, GMI antibodies are of the IgG subtype. In MMN, the GMI antibody class is IgM.

Most patients with MMN respond to treatment. The fIrSt line treatment involves modulation of the immune system with intravenous gammaglobulin (MG). Immunoglobulins are a portion of the blood made up of antibodies that the immune response produces in response to infections. Thousands of blood donors contribute to a batch of MG. Upward of 70% of MMN cases respond to MG. The mechanism of action of MG in MMN is complex and not fully understood. MG acts by neutralizing the GMI antibodies (idiotypeantidiotype interaction), blocking the recruitment of macrophages (scavenger immune cells) and interfering with the activation of complement (a component of the immune system). However the response to MG is transient and requires on average monthly retreatment for several years. Remissions are rare.

For the MMN patients who do not respond to MG, suppression of the immune system is the next treatment. This is usually done with intravenous infusion of a chemotherapy agent known as cyclophosphamide. The role of more targeted treatment with rituximab, a monoclonal antibody against a specific group of antibody-producing immune cells (CD20+ cells), warrants further investigation.

More research is certainly needed in MMN. A multi-center study of the effectiveness of 10%MG for the treatment of MMN is currently under way. For a full listing of available research studies in this rare disease, the reader may visit http://clinicaltrials.gov/. Once there, the user can search for clinical trials under the term "multifocal motor neuropathy". The direct link is to that is http:// clinicaltrials.gov/ ct2/results ?term =multifocal+motor+neuropathy.