Multifocal Motor Neuropathy With Conduction Blocks 

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

Background

Multifocal motor neuropathy (MMN) with conduction block is an acquired immune-mediated demyelinating neuropathy with slowly progressive weakness, fasciculations, and cramping, without significant sensory involvement.

Clinically, it may resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but muscle atrophy and more rapid progression are lacking. Duration of disease prior to diagnosis ranges from several months to more than 15 years.

Unlike ALS, MMN usually responds to treatment with intravenous immunoglobulin (IVIG) or cyclophosphamide, even after many years of duration.[1, 2, 3]

Next

Pathophysiology

The complete cascade of events leading to motor nerve dysfunction and weakness in MMN is not fully understood, but it appears to be related to dysimmune events. Histopathologic and electrodiagnostic studies demonstrate the presence of both demyelinating and axonal injury. Motor nerves are primarily affected, although mild demyelination has been demonstrated in sensory nerves as well. Efficacy of immunomodulatory and immunosuppressive treatment further supports the immune nature of MMN. Rare cases of MMN have been reported following treatment with tumor necrosis factor (TNF)-α antagonists.[4]

Titers of anti-GM1 antibodies are frequently elevated (>50%), but their role has not been established even though they remain a useful marker for the diagnosis of MMN. Experimental study results suggest that autoantibodies bound to gangliosides may activate the complement cascade pathway leading to the dysfunction of sodium channel function in peripheral motor nerve fibers.[5] The benefit of treatment with IVIG may be at least partly attributed to the blockade of complement pathway activation.[6]

While fluctuations in anti-GM1 titers do not correlate with clinical symptoms in most patients treated with IVIG, titers may decrease after treatment with cyclophosphamide and rituximab, correlating with improved strength. Selective involvement of motor nerves with high titers of anti-GM1 antibodies is somewhat surprising because antibodies bind both to ventral and dorsal spinal roots. Binding has also been shown to occur at the nodes of Ranvier, at compact or outer myelin of Schwann cells, and at the motor end plate of the neuromuscular junction.

Histopathologic studies of fascicular nerve biopsies showed multifocal fiber degeneration and loss with frequent regenerating nerve clusters and without significant segmental demyelination or onion bulb formation. The presence of multifocal fiber loss would explain persisting functional abnormalities and would support a need for early treatment.[7]

Previous
Next

Epidemiology

Frequency

United States

MMN is a rare disorder, and its lifetime prevalence is estimated to be 1 case in 100,000 population.

International

Reported prevalence of MMN in other countries is similar to that in the United States.

Mortality/Morbidity

Dexterity and walking ability are commonly affected to some extent, but most patients are able to maintain autonomy with indoor and outdoor activities.[8] Most patients maintain productive lives despite ongoing symptoms, and up to 94% remain employed.[1] However, gradual progression of symptoms may also lead to significant disability.[9]

Fatal outcomes have been reported only rarely, and at least some case reports describe patients with other entities, including motor neuron disease.

Rarely, multifocal motor neuropathy may be associated with a B-cell lymphoma producing monoclonal antibodies against GM1 and GD1b myelin glycolipids.

Race

No racial predilection exists.

Sex

MMN is more common in males (the male-to-female ratio is about 3:1).

Age

The mean age of onset is 40 years. Eighty percent of patients are aged 20-50 years at presentation.

Previous
Proceed to Clinical Presentation
 
 
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.