Multifocal Motor Neuropathy With Conduction Blocks Medication

  • Author: Sasa Zivkovic, MD, PhD; Chief Editor: Nicholas Lorenzo, MD   more...
 
Updated: Oct 5, 2011
 

Medication Summary

Multifocal motor neuropathy (MMN) is an immune-mediated disorder, and while multiple immunomodulatory and immunosuppressive treatments have been used, only intravenous immunoglobulin (IVIG)[12, 13, 14] and cyclophosphamide have been consistently effective. Anecdotal reports also indicate that rituximab,[15, 16, 17] interferon-beta, azathioprine and cyclosporine may be efficacious.[18, 19]

The presence of conduction blocks or elevated titers of anti-GM1 antibodies are not reliable predictors of response to treatment with IVIG.

Most patients (~80-90%) improve with IVIG, but frequently long-term maintenance IVIG infusions are required to prevent worsening of symptoms.[14]

Cyclophosphamide may be used in combination with plasmapheresis. Lack of benefit was reported for 1 patient who received high-dose cyclophosphamide treatment followed by autologous stem cell transplantation.[20]

Corticosteroids or plasmapheresis (without cyclophosphamide) is not effective, and in some cases, MMN may even worsen. Mycophenolate is ineffective as adjunct treatment with IVIG.[21]

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.

Next

Immune Globulin

Class Summary

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. Infusions are performed in an inpatient setting (hospital), in outpatient settings (infusion center or physician's office), or at home. Most patients improve with IVIG treatments (~80-90%), and dosing must be individualized based on patient's response.

Subcutaneous immunoglobulin (SCIG) therapy is used as an alternative to IVIG and can provide more treatment flexibility and autonomy for the patients.

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.

View full drug information

Immunoglobulin, intravenous (Gamimune, Gammar-P, Sandoglobulin, Gammagard Liquid and S/D, Gammunex, Carimune, Flebogamma, Gamaplex, Octigam, Privigen)

 

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.

View full drug information

Immune globulin, subcutaneous (Hizentra, Gammagard Liquid, and Gamunex-C )

 

Immune globulin subcutaneous is used to treat patients with primary immune deficiency. It supplies a wide spectrum of IgG antibodies against bacteria, viral, mycoplasma, and parasitic agents, as well as their antigenic toxins. It is also used in patients with poor venous access and those that want to be able to self-administer to increase independence in administration.

Previous
Next

Immunomodulators

Class Summary

These agents are used to modify the activity of the immune system.

View full drug information

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.

Previous
Next

Immunosuppressive Agents

Class Summary

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.

View full drug information

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.

Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

Sasa Zivkovic, MD, PhD  Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, University of Pittsburgh and VA Pittsburgh Healthcare System

Sasa Zivkovic, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Peripheral Nerve Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Paul E Barkhaus, MD  Professor, Department of Neurology, Medical College of Wisconsin; Director of Neuromuscular Diseases, Milwaukee Veterans Affairs Medical Center

Paul E Barkhaus, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Glenn Lopate, MD  Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

Nicholas Lorenzo, MD  Consulting Staff, Neurology Specialists and Consultants

Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and American College of Physician Executives

Disclosure: Nothing to disclose.

References

  1. Taylor BV, Wright RA, Harper CM, Dyck PJ. Natural history of 46 patients with multifocal motor neuropathy with conduction block. Muscle Nerve. Jun 2000;23(6):900-8. [Medline].

  2. Slee M, Selvan A, Donaghy M. Multifocal motor neuropathy: the diagnostic spectrum and response to treatment. Neurology. Oct 23 2007;69(17):1680-7. [Medline].

  3. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision. J Peripher Nerv Syst. Dec 2010;15(4):295-301. [Medline].

  4. Cocito D, Bergamasco B, Tavella A, Poglio F, Paolasso I, Costa P, et al. Multifocal motor neuropathy during treatment with infliximab. J Peripher Nerv Syst. Dec 2005;10(4):386-7. [Medline].

  5. Susuki K, Rasband MN, Tohyama K, Koibuchi K, Okamoto S, Funakoshi K, et al. Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers. J Neurosci. Apr 11 2007;27(15):3956-67. [Medline].

  6. Yuki N, Watanabe H, Nakajima T, Späth PJ. IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal motor neuropathy. J Neurol Neurosurg Psychiatry. Jul 28 2010;[Medline].

  7. Taylor BV, Dyck PJ, Engelstad J, Gruener G, Grant I, Dyck PJ. Multifocal motor neuropathy: pathologic alterations at the site of conduction block. J Neuropathol Exp Neurol. Feb 2004;63(2):129-37. [Medline].

  8. Erdmann PG, Lindeman E, Cats EA, van den Berg LH. Functioning of patients with multifocal motor neuropathy. J Peripher Nerv Syst. Jun 2010;15(2):113-9. [Medline].

  9. Lange DJ, Weimer LH, Trojaborg W, et al. Multifocal motor neuropathy with conduction block: slow but not benign. Arch Neurol. Dec 2006;63(12):1778-81. [Medline].

  10. Straver DC, van Asseldonk JT, Notermans NC, Wokke JH, van den Berg LH, Franssen H. Cold paresis in multifocal motor neuropathy. J Neurol. Feb 2011;258(2):212-7. [Medline]. [Full Text].

  11. Vucic S, Dawson K, Sun D, Cros D. Pure motor mononeuropathy with distal conduction block: an unusual presentation of multifocal motor neuropathy with conduction blocks. Clin Neurophysiol. Oct 2004;115(10):2323-8. [Medline].

  12. Vucic S, Black KR, Chong PS, Cros D. Multifocal motor neuropathy: decrease in conduction blocks and reinnervation with long-term IVIg. Neurology. Oct 12 2004;63(7):1264-9. [Medline].

  13. Van den Berg-Vos RM, Franssen H, Wokke JH, Van den Berg LH. Multifocal motor neuropathy: long-term clinical and electrophysiological assessment of intravenous immunoglobulin maintenance treatment. Brain. Aug 2002;125(Pt 8):1875-86. [Medline].

  14. Cats EA, van der Pol WL, Piepers S, Franssen H, Jacobs BC, van den Berg-Vos RM, et al. Correlates of outcome and response to IVIg in 88 patients with multifocal motor neuropathy. Neurology. Aug 31 2010;75(9):818-25. [Medline].

  15. Ruegg SJ, Fuhr P, Steck AJ. Rituximab stabilizes multifocal motor neuropathy increasingly less responsive to IVIg. Neurology. Dec 14 2004;63(11):2178-9. [Medline].

  16. Pestronk A, Florence J, Miller T, et al. Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry. Apr 2003;74(4):485-9. [Medline].

  17. Stieglbauer K, Topakian R, Hinterberger G, Aichner FT. Beneficial effect of rituximab monotherapy in multifocal motor neuropathy. Neuromuscul Disord. Jul 2009;19(7):473-5. [Medline].

  18. [Guideline] Hughes RA. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. Mar 2006;11(1):1-8. [Medline].

  19. Nemni R, Santuccio G, Calabrese E, Galardi G, Canal N. Efficacy of cyclosporine treatment in multifocal motor neuropathy. J Neurol. Sep 2003;250(9):1118-20. [Medline].

  20. Axelson HW, Oberg G, Askmark H. No benefit of treatment with cyclophosphamide and autologous blood stem cell transplantation in multifocal motor neuropathy. Acta Neurol Scand. Jun 2008;117(6):432-4. [Medline].

  21. [Best Evidence] Umapathi T, Hughes RA, Nobile-Orazio E, Léger JM. Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy. Cochrane Database Syst Rev. Jan 21 2009;CD003217. [Medline].

  22. Boonyapisit K, Katirji B. Multifocal motor neuropathy presenting with respiratory failure. Muscle Nerve. Dec 2000;23(12):1887-90. [Medline].

  23. Chaudhry V, Corse AM, Cornblath DR, et al. Multifocal motor neuropathy: electrodiagnostic features. Muscle Nerve. Feb 1994;17(2):198-205. [Medline].

  24. Donofrio PD. Immunotherapy of idiopathic inflammatory neuropathies. Muscle Nerve. Sep 2003;28(3):273-92. [Medline].

  25. Feldman EL, Bromberg MB, Albers JW, Pestronk A. Immunosuppressive treatment in multifocal motor neuropathy. Ann Neurol. Sep 1991;30(3):397-401. [Medline].

  26. Felice KJ, Goldstein JM. Monofocal motor neuropathy: Improvement with intravenous immunoglobulin. Muscle Nerve. May 2002;25(5):674-8. [Medline].

  27. Harbo T, Andersen H, Jakobsen J. Long-term therapy with high doses of subcutaneous immunoglobulin in multifocal motor neuropathy. Neurology. Oct 12 2010;75(15):1377-80. [Medline].

  28. Katz JS, Saperstein DS. Asymmetric Acquired Demyelinating Polyneuropathies: MMN and MADSAM. Curr Treat Options Neurol. Mar 2001;3(2):119-125. [Medline].

  29. Katz JS, Wolfe GI, Bryan WW, et al. Electrophysiologic findings in multifocal motor neuropathy. Neurology. Mar 1997;48(3):700-7. [Medline].

  30. Lambrecq V, Krim E, Rouanet-Larrivière M, Lagueny A. Sensory loss in multifocal motor neuropathy: A clinical and electrophysiological study. Muscle Nerve. Feb 2009;39(2):131-6. [Medline].

  31. Nobile-Orazio E, Cappellari A, Priori A. Multifocal motor neuropathy: current concepts and controversies. Muscle Nerve. Jun 2005;31(6):663-80. [Medline].

  32. Olney RK, Lewis RA, Putnam TD, et al. Consensus criteria for the diagnosis of multifocal motor neuropathy. Muscle Nerve. Jan 2003;27(1):117-21. [Medline].

  33. Pestronk A. Multifocal motor neuropathy: diagnosis and treatment. Neurology. Dec 1998;51(6 Suppl 5):S22-4. [Medline].

  34. Pestronk A, Lopate G, Kornberg AJ, et al. Distal lower motor neuron syndrome with high-titer serum IgM anti-GM1 antibodies: improvement following immunotherapy with monthly plasma exchange and intravenous cyclophosphamide. Neurology. Nov 1994;44(11):2027-31. [Medline].

 
Previous
Next
 
Nerve conduction studies demonstrating conduction block with temporal dispersion after proximal stimulation.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.