Klinische Neurophysiologie 2003; 34(3): 119-126
DOI: 10.1055/s-2003-42250
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Multifokale motorische Neuropathie: Klinische und elektrophysiologische Charakteristika

Multifocal Motor Neuropathy: Clinical and Electrophysiological FindingsA.  Jaspert1 , H.  Grehl2
  • 1Klinik für Neurologie und Klinische Neurophysiologie, Alfried Krupp Krankenhaus, Essen
  • 2Neurologische Klinik, Evangelisches und Johanniter-Klinikum Duisburg
Further Information

Publication History

Publication Date:
18 September 2003 (online)

Zusammenfassung

Die multifokale motorische Neuropathie (MMN) ist eine behandelbare, vermutlich immunvermittelte Neuropathie. Die klinische Symptomatik ist durch asymmetrische, rein motorische Defizite charakterisiert, die dem Verteilungsmuster peripherer Nerven entsprechen und vorwiegend distale Abschnitte an den oberen Extremitäten betreffen. Die typischen elektrophysiologischen Befunde der MMN sind multifokale, häufig persistierende Leitungsblöcke, die die Abgrenzung der MMN von den nichtbehandelbaren Motoneuronerkrankungen erlauben. Da die Demyelinisierung bei der MMN nicht so ausgedehnt ist wie bei der chronisch-entzündlichen demyelinisierenden Polyneuropathie (CIDP), sind die Nervenleitgeschwindigkeiten oft normal. Um die Nachweismöglichkeit eines Leitungsblockes zu verbessern, sollten mittels spezieller elektrophysiologischer Stimulationstechniken proximale Nervenabschnitte mituntersucht werden. Antikörpertiter gegen GM1-Ganglioside können bei der MMN erhöht sein, reichen aber zur Diagnosesicherung nicht aus. Hoch dosierte intravenöse Immunglobuline (ivIg) und Zyklophosphamid sind die beiden einzigen gesicherten effektiven Therapieverfahren der MMN. IvIg sind aufgrund ihres günstigen Nebenwirkungsprofils die Therapie der ersten Wahl. Kortikosteroide und Plasmapherese können die neurologischen Symptome verschlechtern. Die schnelle Besserung nach einer Immunglobulintherapie könnte durch die Neutralisierung funktionell blockierender Antikörper bedingt sein. Immunglobuline sind auch im Langzeitverlauf effektiv. Bei einigen Patienten kann jedoch die Erkrankung trotz regelmäßiger Immunglobulinbehandlungen fortschreiten. Da eine Immunglobulinlangzeittherapie teuer ist, kann sie auch in Kombination mit Zyklophosphamid durchgeführt werden, um Immunglobuline einzusparen.

Abstract

Multifocal motor neuropathy (MMN) is a treatable, probably immune-mediated neuropathy. Typical clinical symptoms are asymmetrical pure motor deficits in a peripheral nerve distribution, predominantly affecting distal parts of upper limbs. The characteristic electrophysiological findings of MMN are multifocal and often persistent conduction blocks that can be differentiated from untreatable motor neuron disease. Since demyelination in MMN is not as widespread as in chronic inflammatory demyelinating polyneuropathy (CIDP), nerve conduction velocities are often normal. To improve the diagnosis of conduction blocks, electrophysiological studies should include proximal nerve segments using special stimulation techniques. Antibody titres against GM1 gangliosides may be elevated in MMN, but are not sufficient for diagnostic values. High dose intravenous immunoglobulins (IVIG) and cyclophosphamide are the only effective therapies in MMN, IVIG being the treatment of choice because of its less serious side effects. Corticosteroids and plasma exchange therapy may aggravate neurological deficits. Rapid improvement after IVIG application may be caused by neutralisation of functional blocking antibodies. IVIG is also effective in the long-term course. In some patients, however, disease progression may be observed despite of regular IVIG treatment. As long-lasting IVIG treatment is expensive, combination with cyclophosphamide may be performed to reduce the IVIG dosage. Application of further immunomodulatory drugs in MMN should be investigated in the future.

Literatur

  • 1 Lewis R A, Sumner A J, Brown M J, Asbury A K. Multifocal demyelinating neuropathy with persistent conduction block.  Neurology. 1982;  32 958-964
  • 2 Berg-Vos R M Van den, Berg L H Van den, Franssen H, Vermeulen M, Witkamp T D, Jansen G H, Es H W van, Kerkhoff H, Wokke J HJ. Multifocal inflammatory demyelinating neuropathy: A distinct clinical entity?.  Neurology. 2000;  54 26-32
  • 3 Biessels G J, Franssen H, Berg L H Van den, Gibson A, Kappelle L J, Venables G S, Wokke J HJ. Multifocal motor neuropathy.  J Neurol. 1997;  244 143-152
  • 4 Chaudhry V, Corse A, Cornblath D, Kuncl R, Freimer M, Griffin J. Multifocal Motor Neuropathy: Electrodiagnostic Features.  Muscle Nerve. 1994;  17 198-205
  • 5 Jaspert A, Claus D, Grehl H, Neundörfer B. Multifocal motor neuropathy: clinical and electrophysiological findings.  J Neurol. 1996;  243 684-692
  • 6 Leger J M. Multifocal motor neuropathy and chronic inflammatory demyelinating polyradiculoneuropathy.  Curr Opin Neurol. 1995;  8 359-363
  • 7 Lange D J, Trojaborg W, Latov N, Hays A P, Younger D S, Uncini A, Blake D M, Hirano M, Burns S M, Lovelace R E, Rowland L P. Multifocal motor neuropathy with conduction block: Is it a distinct clinical entity?.  Neurology. 1992;  42 497-505
  • 8 Taylor B V, Wright R A, Harper C M, Dyck P J. Natural history of 46 patients with multifocal motor neuropathy with conduction block.  Muscle Nerve. 2000;  23 900-908
  • 9 Nobile-Orazio E. Multifocal motor neuropathy.  J Neurol Neurosurg Psychiatry. 1996;  60 599-603
  • 10 O'Leary C P, Mann A C, Lough J, Willison H J. Muscle hypertrophy in multifocal motor neuropathy is associated with continuous motor unit activity.  Muscle Nerve. 1997;  20 479-485
  • 11 Cornblath D R, Sumner A J, Daube J, Gilliat R W, Brown W F, Parry G J, Albers J W, Miller R G, Petajan J. Conduction block in clinical practice.  Muscle Nerve. 1991;  14 869-871
  • 12 Cappellari A, Nobile-Orazio E, Meucci N, Levi-Minzi G, Scarlato G, Barbieri S. Criteria for early detection of conduction block in multifocal motor neuropathy (MMN): a study based on control populations and follow-up of MMN patients.  J Neurol. 1997;  244 625-630
  • 13 Olney R K. Consensus criteria for the diagnosis of partial conduction block.  Muscle & Nerve. 1999;  22, Suppl 8 225-229
  • 14 Katz J S, Wolfe G I, Bryan W W, Jackson C E, Amato A A, Barohn R J. Electrophysiologic findings in multifocal motor neuropathy.  Neurology. 1997;  48 700-707
  • 15 Berg-Vos R M Van den, Franssen H, Wokke J HJ, Es H W van, Berg L H Van den. Multifocal Motor Neuropathy: Diagnostic Criteria that Predict the Response to Immunoglobulin Treatment.  Ann Neurol. 2000;  48 919-926
  • 16 Abu-Shakra S R, Cornblath D R, Avila O L, Chaudhry V, Freimer M, Glass J D, Reim J W, Ronnett G V. Conduction block in diabetic neuropathy.  Muscle Nerve. 1991;  14 858-862
  • 17 Rhee E K, England J D, Sumner A J. A computer simulation of conduction block: effects produced by actual block versus interphase cancellation.  Ann Neurol. 1990;  28 146-156
  • 18 Franssen H, Wieneke G H, Wokke J HJ. The influence of temperature on conduction block.  Muscle Nerve. 1999;  22 166-173
  • 19 Rasminsky M. The effects of temperature on conduction block in demyelinating nerve fibers.  Arch Neurol. 1973;  28 287-292
  • 20 Kaji R, Bostock H, Kohara N, Murase N, Kimura J, Shibasaki H. Activity-dependent conduction block in multifocal motor neuropathy.  Brain. 2000;  123 1602-1611
  • 21 Cappelen-Smith C, Kuwabara S, Lin C S-Y, Mogyoros I, Burke D. Activity-Dependent Hyperpolarization and Conduction Block in Chronic Inflammatory Demyelinating Polyneuropathy.  Ann Neurol. 2000;  48 826-832
  • 22 Jaspert A, Claus D, Grehl H, Kerling F, Neundörfer B. Wertigkeit der proximalen Leitungsblockuntersuchung in der Diagnostik entzündlicher Neuropathien.  Nervenarzt. 1995;  66 445-454
  • 23 Mills K R, Murray N MF. Electrical stimulation over the human vertebral column: Which neural elements are excited?.  Electroenceph clin Neurophysiol. 1986;  63 582-589
  • 24 Claus D. Conduction studies in proximal nerves.  Schweizer Archiv für Neurologie und Psychiatrie. 1991;  142 531
  • 25 Azulay J-P, Rihet R, Pouget J, Cador F, Blin O, Boucraut J, Serratrice G. Long-term follow-up of multifocal motor neuropathy with conduction block under treatment.  J Neurol Neurosurg Psychiatry. 1997;  62 391-394
  • 26 Bouche P, Moulonguet A, Ben Younes-Chennoufi A, Adams D, Baumann N, Meininger V, Léger J-M, Said G. Multifocal motor neuropathy with conduction block: a study of 24 patients.  J Neurol Neurosurg Psychiatry. 1995;  59 38-44
  • 27 Elliott J L, Pestronk A. Progression of multifocal motor neuropathy during apparently successful treatment with human immunoglobulin.  Neurology. 1994;  44 967-968
  • 28 Kolimas R J, Harati Y. Multifocal motor neuropathy: value of electrophysiologic studies and motor nerve biopsy.  Muscle Nerve. 1990;  13 868
  • 29 Krarup C, Stewart J D, Sumner A J, Pestronk A, Lipton S A. A syndrome of asymmetric limb weakness with motor conduction block.  Neurology. 1990;  40 118-127
  • 30 Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force . Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP).  Neurology. 1991;  41 617-618
  • 31 Pestronk A, Choksi R. Multifocal motor neuropathy. Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates.  Neurology. 1997;  49 1289-1292
  • 32 Santoro M, Uncini A, Corbo M. Experimental conduction block induced by serum from a patient with anti-GM1 antibodies.  Ann Neurol. 1992;  31 385-390
  • 33 Benatar M, Willison H J, Vincent A. Immune-mediated peripheral neuropathies and voltage-gated sodium channels.  Muscle Nerve. 1999;  22 108-110
  • 34 Wurz A, Brinkmeier H, Wollinsky K H, Mehrkens H H, Kornhuber H H, Rudel R. Cerebrospinal fluid and serum from patients with inflammatory polyradiculoneuropathy have opposite effects on sodium channels.  Muscle Nerve. 1995;  18 772-781
  • 35 Takigawa T, Yasuda H, Kikkawa R, Shigeta Y, Saida T, Kitasato H. Antibodies against GM1 ganglioside affect K+ and Na+ currents in isolated rat myelinated nerve fibers.  Ann Neurol. 1995;  37 436-442
  • 36 Hirota N, Kaji R, Bostock H, Shindo K, Kawasaki T, Kotaro M, Oka N, Kohara N, Saida T, Kimura J. The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons.  Brain. 1997;  120 2159-2169
  • 37 Weber F, Rüdel R, Aulkemeyer P, Brinkmeier H. Anti-GM1 antibodies can block neuronal voltage-gated sodium channels.  Muscle Nerve. 2000;  23 1414-1420
  • 38 Dalakas M C. Intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: present status and practical therapeutic guidelines.  Muscle Nerve. 1999;  22 1479-1497
  • 39 Donaghy M, Mills K R, Boniface S J, Simmons J, Wright I, Gregson N, Jacobs J. Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin.  J Neurol Neurosurg Psychiatry. 1994;  57 778-783
  • 40 Claus D, Specht S, Zieschang M. Plasmapheresis in multifocal motor neuropathy: a case report.  J Neurol Neurosurg Psychiatry. 2000;  68 533-535
  • 41 Carpo M, Cappellari A, Mora G, Pedotti R, Barbieri S, Scarlato G, Nobile-Orazio E. Deterioration of multifocal motor neuropathy after plasma exchange.  Neurology. 1998;  50 1480-1482
  • 42 Feldman E L, Bromberg M B, Albers J W, Pestronk A. Immunosuppressive Treatment in Multifocal Motor Neuropathy.  Ann Neurol. 1991;  30 397-401
  • 43 Azulay J-P, Blin O, Pouget J, Boucraut J, Billé-Turc F, Carles G, Serratrice G. Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: A double-blind, placebo-controlled study.  Neurology. 1994;  44 429-432
  • 44 Chaudhry V, Corse A, Cornblath D, Kuncl R, Drachman D, Freimer M, Miller R, Griffin J. Multifocal motor neuropathy: Response to human immune globulin.  Ann Neurol. 1993;  33 237-242
  • 45 Grehl H, Jaspert A, Claus D, Neundörfer B. Long-term therapy with high-dose intravenous immunoglobulins (IVIG) in inflammatory neuropathies.  European Journal of Neurology. 1997;  4 266-273
  • 46 Léger J M, Younes-Chennoufi A B, Chassande B, Davila G, Bouche P, Baumann N, Brunet P. Human immunoglobulin treatment of multifocal motor neuropathy and polyneuropathy associated with monoclonal gammopathy.  J Neurol Neurosurg Psychiatry. 1994;  57, Suppl 46-49
  • 47 Nobile-Orazio E, Meucci N, Barbieri S, Carpo M, Scarlato G. High dose intravenous immunoglobulin therapy in multifocal motor neuropathy.  Neurology. 1993;  43 537-544
  • 48 Berg L H Van den, Kerkhoff H, Oey P L, Franssen H, Mollee I, Vermeulen M, Jennekens F GI, Wokke J HJ. Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study.  J Neurol Neurosurg Psychiatry. 1995;  59 248-252
  • 49 Berg L H Van den, Franssen H, Oey P L, Wokke J HJ. The effect of intravenous immunoglobulin treatment in patients with multifocal motor neuropathy or lower motor neuron disease.  J Neurol. 1995;  242, Suppl 2 149
  • 50 Berg L H Van den, Franssen H, Wokke J H. Improvement of multifocal motor neuropathy during long-term weekly treatment with human immunoglobulin.  Neurology. 1995;  45 987-988
  • 51 Berg L H Van den, Franssen H, Wokke J HJ. The long-term effect of intravenous immunoglobulin treatment in multifocal motor neuropathy.  Brain. 1998;  121 421-428
  • 52 Doorn P A van, Brand A, Strengers P F, Meulstee J, Vermeulen M. High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-blind, placebo-controlled, crossover study (see comments).  Neurology. 1990;  40 209-212
  • 53 Federico P, Zochodne D W, Hahn A F, Brown W F, Feasby T E. Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study.  Neurology. 2000;  55 1256-1262
  • 54 Léger J-M, Chassande B, Musset L, Meininger V, Bouche P, Baumann N. Intravenous immunoglobulin therapy in multifocal motor neuropathy. A double-blind, placebo-controlled study.  Brain. 2001;  124 145-153
  • 55 Cabre P, Smadja D, Odry L, Donikian J C, Vernant J C. Acute kidney failure following intravenous administration of high doses of immunoglobulins (letter).  Presse Med. 1994;  23 142
  • 56 Silbert P L, Knezevic W V, Bridge D T. Cerebral infarction complicating intravenous immunoglobulin therapy for polyneuritis cranialis.  Neurology. 1992;  42 257-258
  • 57 Bertorini T E, Nance A M, Horner L H, Greene W, Gelfand M S, Jaster J H. Complications of intravenous gammaglobulin in neuromuscular and other diseases.  Muscle Nerve. 1996;  19 388-391
  • 58 Berg-Vos R M Van den, Franssen H, Visser J, Visser M de, Haan R J de, Wokke J HJ, Berg L H Van den. Disease severity in multifocal motor neuropathy and its association with the response to immunoglobulin treatment.  J Neurol. 2002;  249 330-336
  • 59 Meucci N, Cappellari A, Barbieri S, Scarlato G, Nobile-Orazio E. Long-term effect of intravenous immunoglobulins and oral cyclophosphamide in multifocal motor neuropathy.  J Neurol Neurosurg Psychiatry. 1997;  63 765-769
  • 60 Martina I S, Doorn P A van, Schmitz P I, Meulstee J, Meché F GA van der. Chronic motor neuropathies: response to interferon-beta 1a after failure of conventional therapies.  J Neurol Neurosurg Psychiatry. 1999;  66 197-201
  • 61 Levine T D, Pestronk A. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using Rituximab.  Neurology. 1999;  52 1701-1704
  • 62 Scheglmann K, Rentz E. Treatment of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy with high dose intravenous immunoglobulin with IgM, IgA in addition to IgG.  J Neurol. 2000;  247, Suppl 3 S III/64
  • 63 Ellis C M, Leary S, Payan J, Shaw C, Hu M, O'Brien M, Leigh P N. Use of human intravenous immunoglobulin in lower motor neuron syndromes.  J Neurol Neurosurg Psychiatry. 1999;  67 15-19
  • 64 Pestronk A, Chaudhry V, Feldman E L, Griffin J W, Cornblath D R, Denys E H, Glasberg M, Kuncl R W, Olney R K, Yee W C. Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies.  Ann Neurol. 1990;  27 316-326

PD Dr. Andrea Jaspert

Klinik für Neurologie und Klinische Neurophysiologie · Alfried Krupp Krankenhaus

Alfried-Krupp-Straße 21

45117 Essen-Rüttenscheid