eMedicine Specialties > Neurology > Neuromuscular Diseases
Multifocal Motor Neuropathy With Conduction Blocks: Treatment & Medication
Updated: Jan 25, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Multifocal motor neuropathy (MMN) is associated with slowly progressive weakness, but most patients are able to remain productive and employed. However, gradual progression may lead to significant disability. Physical and occupational therapy may be helpful in individual cases.
Diet
No specific diet is indicated for patients with MMN.
Activity
The level of activity depends on the extent of patient symptoms and disability.
Medication
Multifocal motor neuropathy (MMN) is an immune-mediated disorder, and while multiple immunomodulatory and immunosuppressive treatments have been used, only intravenous immunoglobulin (IVIG) and cyclophosphamide have been consistently effective. Anecdotal reports also indicate that rituximab, interferon-beta, azathioprine, and cyclosporine may be efficacious.
The presence of conduction blocks or elevated titers of anti-GM1 antibodies are not reliable predictors of response to treatment with IVIG.
Cyclophosphamide may be used in combination with plasmapheresis.
Corticosteroids or plasmapheresis (without cyclophosphamide) is not effective, and in some cases, MMN may even worsen. Mycophenolate is ineffective as adjunct treatment with IVIG.
Recent reports describe effective treatment with cyclosporine and rituximab in a small number of patients, but additional data are needed before these would be recommended for treatment of MMN.
Other treatments used with variable success include interferon-beta and azathioprine.
Immunoglobulins
IVIG infusions are the mainstay of MMN treatment. Patients are initially treated with IVIG (2 g/kg) over 2-5 days, followed by maintenance infusions. The frequency of maintenance treatments depends on patients' symptoms, and it is usually every 4-8 weeks. Maintenance dose is determined by patient's response and typically ranges from 1-2 g/kg per treatment.
Long-term IVIG treatment improves muscle strength and functional disability, but the responsiveness may decrease over time.
If IVIG is not (sufficiently) effective, then alternative treatments (eg, cyclophosphamide, rituximab, cyclosporin) should be considered.
Immunoglobulin, intravenous (Gamimune, Gammar-P, Sandoglobulin, Gammagard)
Neutralizes circulating myelin antibodies through anti-idiotypic antibodies. Down-regulates proinflammatory cytokines, including INF-gamma. Blocks Fc receptors on macrophages, suppresses inducer T and B cells and augments suppressor T cells, blocks complement cascade, and promotes remyelination. May increase CSF IgG (10%).
After 3-7 years of treatment, IVIG may become less effective, possibly because of development of axonal degeneration.
In other patients, few doses of IVIG may induce prolonged remission.
Adult
Starting dose: 2 g/kg IV over 2-5 d
Maintenance dose: 1-2 g/kg IV q4-8wk; dose is titrated to symptoms; some patients may require IV infusions q2-4mo or may even go into prolonged remissions
Pediatric
Not established
Globulin preparation may interfere with immune response to live-virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)
Documented hypersensitivity; IgA deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor serum urea and creatinine levels because IVIG increases risk of renal tubular necrosis in elderly patients and in patients with diabetes mellitus, volume depletion, and preexisting kidney disease; check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and risk of thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); laboratory result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
Immunosuppressive agents
Cyclophosphamide is primarily used in patients with severe symptoms that do not respond to IVIG infusions and may be combined with plasmapheresis. Use of cyclophosphamide induced remission in 50-80% patients, but it is not routinely administered because of potential adverse effects. Oral cyclophosphamide is not as effective as intravenous therapy, and has the potential for more frequent dose-limiting adverse effects, so intravenous infusions are preferred.
The use of cyclophosphamide should be limited to more severely affected patients given the potential adverse effects.
Cyclophosphamide (Cytoxan)
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
Pretreatment with 2 plasma exchanges on 2 consecutive days followed by 1 g/m2 IV monthly for 6 mo
Pediatric
Not established
Allopurinol may increase risk of bleeding or infection and may enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Unsafe in pregnancy
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; increased risk of bladder carcinoma
Immunomodulators
These agents are used to modify the activity of the immune system.
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.
Adult
375 mg/m2 IV qwk for 4 doses (days 1, 8, 15, and 22)
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Hypotension, bronchospasm, and angioedema may occur; discontinue treatment if life-threatening cardiac arrhythmias occur
More on Multifocal Motor Neuropathy With Conduction Blocks |
| Overview: Multifocal Motor Neuropathy With Conduction Blocks |
| Differential Diagnoses & Workup: Multifocal Motor Neuropathy With Conduction Blocks |
 Treatment & Medication: Multifocal Motor Neuropathy With Conduction Blocks |
| Follow-up: Multifocal Motor Neuropathy With Conduction Blocks |
| Multimedia: Multifocal Motor Neuropathy With Conduction Blocks |
| References |
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References
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Further Reading
Keywords
MMN, multifocal motor neuropathy with conduction block, acquired immune-mediated demyelinating neuropathy, amyotrophic lateral sclerosis, ALS, demyelinating injury, axonal injury, anti-GM1 antibodies, intravenous immunoglobulin, IVIG, cyclophosphamide, muscle atrophy, autoimmune peripheral neuropathy, autoimmune peripheral neuropathy, nerve conduction study, NCS, multifocal motor involvement, axonal degeneration
