Treatment of multifocal motor neuropathy.

OPINION STATEMENT: Multifocal motor neuropathy (MMN) is a treatable immune disorder of the peripheral nerves that is characterized clinically by slowly progressive or stepwise asymmetric distal > proximal, upper > lower limb weakness in multiple motor nerve distributions; electrophysiologically by multifocal motor demyelination, specifically partial motor conduction block; laboratory evidence of high serum anti-GM1 IgM antibodies; and remarkable treatment response to intravenous immunoglobulin (IVIG). IVIG has become the treatment of choice, and the U.S. Food and Drug Administration (FDA) has approved Gammagard Liquid 10 % [immune globulin infusion (human)] as a treatment for multifocal motor neuropathy (MMN). Response to IVIG in MMN is dose- and frequency-dependent, most patients needing high (2 g/kg) and frequent (every 4-8 weeks) doses for several years. Over time, response to IVIG may decrease despite higher and more frequent dosing of IVIG treatment. Subcutaneous immunoglobulin (dose equivalent to IVIG) given in weekly fashion has recently been used with equal efficacy and fewer side effects. There are some case reports and non-randomized trials suggesting variable results from therapeutic or adjunctive use of other immunosuppressive or immunomodulatory agents such as cyclophosphamide, cyclosporine, methotrexate, azathioprine, interferon beta-1a, and rituximab. Of these, cyclophosphamide and rituximab are the only immune treatments that have shown some benefits in case reports. One randomized controlled trial of mycophenolate mofetil used as adjunctive agent did not prove efficacious in altering the disease course. Although MMN, like chronic inflammatory demyelinating polyneuropathy (CIDP), is a chronic immune-mediated demyelinating neuropathy, the use of corticosteroids and plasma exchange - two other therapies used in CIDP - is not beneficial for MMN. Further investigations are warranted to evaluate the immunopathogenesis of MMN and to explore options for dose, frequency, and duration of IVIG treatment as well as the use of alternative immunomodulatory agents either as primary therapeutic or adjunctive agents.