Since multifocal motor neuropathy is recognized to be an immune-mediated disorder, several immunomodulatory therapies have been tried, including intravenous immune globulin(IVIG), cyclophosphamide, rituximab, steroids, azathioprine, and plasma exchange.
Intravenous immune globulin (Gamimune, Gammar-P, Sandoglobulin, Gammagard) has been found to be effective in patients reported in the literature with 80% of 170 MMN patients treated with IVIG having shown improvement. This includes 4 placebo-controlled trials in 46 patients. Beneficial effects from IVIG begin within days, and some times hours after the infusion, peak at an average of 2 weeks and the effect lasts from several weeks to months. Most patients require periodic maintenance doses of IVIG. The dose and frequency of IVIG administration needs to be individualized depending on the length of benefit received which appears to vary between patients but is relatively constant in individual patients.
Based on experience, IVIg is the first-line treatment for MMN. Most physicians prescribe the first treatment with IVIG at a dose of 2g/kg divided over 5 days. After giving the first dose of IVIG, the duration of effectiveness should be determined. Most patients who experience a dramatic benefit have a relapse, which again responds to intravenous immune globulin treatment. For most, this “yo-yo effect” is unacceptable, and it is prudent to give these patients another dose before the anticipated time of relapse. Maintenance doses of IVIG, if needed, are generally 2g/kg and can be given over 2 days. Patients who experience minimal benefit or patients whose disease is stable may not need a second treatment for years. Occasional patients have a long lasting remission after a single course of IVIG. In cases where more frequent administrations are needed (< 2 months), it is worthwhile to try reducing the dose of intravenous immune globulin at each administration, and thus to arrive at the minimal dose with maximal effectiveness. For example, doses of 0.4 g/kg weekly, 0.8g/kg every two weeks, or 1 g/kg every month are some of the alternative dosing strategies that may work in individual patients.
Transient headache, chills, myalgia, and nausea are common and can be managed by nonsteroidal anti-inflammatory medication and slowing the infusion rate. Severe headaches or other intolerable allergic side effects may be prevented by pre-administration methylprednisolone (60-100 mg IV) and diphenhydramine (25-50 mg IV) 30 minutes prior to IVIG infusion. Sometimes a different brand of IVIG may be necessary to avoid side effects (for a listing of brands see attached table). The lot number and name of the commercial preparations of intravenous immune globulin used in each case should be recorded. Caution should be used in giving intravenous immune globulin to elderly people, or to patients with IgA deficiency, borderline renal dysfunction, or cardiac dysfunction. A complete listing of possible side-effects can be found in the package insert for each product.
The mechanism of intravenous immune globulin’s immunomodulatory effects are not fully understood. The rapidity of clinical and electrophysiological improvement after intravenous immune globulin suggests that improvement is unlikely to be due to structural remyelination of demyelinated axons. One hypothesis is that intravenous immune globulin, by supplying an anti-idiotypic antibody, may act by interfering with antibody binding or accessibility to the antigen, perhaps at the level of the nodes of Ranvier Improvement in strength correlates with a variable, but not consistent, reduction in partial motor conduction block and no consistent change in anti-GM1 antibody titers.
Cyclophosphamide (Cytoxan) is perhaps the only immunosuppressive agent (besides IVIG) that has shown to have consistent efficacy (50%) in the treatment of multifocal motor neuropathy with 20 of 40 cases so treated showing improvement. Improvement has been reported to coincide with decrease in the anti-GM1 antibody titers which may occur between 2-5 months after initiation of the treatment. However, cyclophosphamide is not routinely given because of its toxic side effects, including bone marrow suppression, increased risk of infections, hemorragic cystitis, infertility, teratogenecity, alopecia, nausea, vomiting and an increased risk of hematological malignancies. Daily oral (100-150 mg/day) or periodic intravenous (1 -3 gm/M2 ) regimens have been used for periods of 6 months.
Rituximab (Rituxan): Second-line agent that may be used for patients with MMN who do not respond to IVIG. Efficacy is based on anecdotal reports. While most patients exhibiting response to rituximab had positive anti-GM1 IgM antibodies, improvement was observed in seronegative patients as well. Antibody genetically engineered chimeric murine/human monoclonal antibody directed against CD20 antigen found on surface of normal and malignant B lymphocytes. Antibody is an IgG1 kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences.
Corticosteroids: Unlike chronic inflammatory demyelinating polyneuropathy, steroids have rarely been effective in the treatment of multifocal motor neuropathy, with a response rate of 11%; 7 of 64 cases reported in the literature have been reported to improve either alone or in combination with other modalities. It is important to note that over 20% of patients with MMN have been reported to worsen in strength, sometimes dramatically, after initiation of corticosteroids treatment.
Plasmapheresis: Similar to corticosteroids the experience of most investigators with plasma exchange (PE) has been negative with improvement reported in only 4 of 20 cases in the literature. Also like steroids, some patients may even worsen after PE.
Azathioprine: Three of 4 MMN patients treated with azathioprine have been reported to improve, but the numbers are too small to make any conclusions about this immunosuppressive agent.