Multifokale motorische Neuropathie: Klinische Merkmale, Pathophysiologie und Therapie

Zusammenfassung

Die multifokale motorische Neuropathie (MMN) gehört zur Gruppe der immunologisch vermittelten entzündlichen Neuropathien. Sie ist klinisch gekennzeichnet durch langsam progrediente, distal betonte, asymmetrische Paresen besonders an den oberen Extremitäten ohne begleitendes sensibles Defizit. Charakteristische Zusatzbefunde sind multifokale persistierende Leitungsblöcke (LB) und eine regelmäßige Assoziation mit hochtitrigen Anti-GM1-IgM-Antikörpern. Wichtige Differenzialdiagnosen umfassen die Motoneuronerkrankungen (spinale Muskelatrophie, amyotrophe Lateralsklerose) sowie andere entzündliche Neuropathien, insbesondere die chronisch-inflammatorische demyelinisierende Neuropathie (CIDP) und das Lewis-Sumner-Syndrom (MADSAM-Neuropathie). Therapie der Wahl sind hoch dosierte intravenöse Immunglobuline (IVIG); Kortikosteroide und Plasmapherese sind gänzlich unwirksam. Die exakte nosologische Einordnung innerhalb der Immunneuropathien ist weiterhin offen, hinsichtlich der optimalen Langzeittherapie fehlen bislang kontrollierte klinische Studien.

Abstract

Multifocal motor neuropathy (MMN) is an immune-mediated disorder which is clinically characterised by slowly progressive, predominantly distal, asymmetrical limb weakness without sensory deficit. The upper limbs are more often affected than the lower limbs. Diagnostic features are persistent multifocal partial conduction blocks (CB) and high-titre anti-GM1 IgM-antibodies. The most important differential diagnoses include motor-neuron diseases (spinal muscle atrophies, amyotrophic lateral sclerosis) and other chronic dysimmune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and the Lewis-Sumner syndrome (MADSAM neuropathy). High-dose intravenous immunoglobulins (IVIG) are the first-line treatment while corticosteroids and plasma exchange are generally not effective. In spite of significant successes in elucidating the underlying disease mechanisms, important aetiopathological issues and the optimum long-term therapy remain to be clarified.

Key words

multifocal motor neuropathy - motor conduction block - anti-GM1-antibodies - therapy

Literatur

• 1 Chad D A, Hammer K, Sargent J. Slow resolution of multifocal weakness and fasciculation: a reversible motor neuron syndrome.  Neurology. 1986;  36 1260-1263
• 2 Roth G, Rohr J, Magistris M R, Ochsner F. Motor neuropathy with proximal multifocal persistent conduction block, fasciculations and myokymia. Evolution to tetraplegia.  Eur Neurol. 1986;  25 416-423
• 3 Parry G J, Clarke S. Multifocal acquired demyelinating neuropathy masquerading as motor neuron disease.  Muscle Nerve. 1988;  11 103-107
• 4 Pestronk A, Cornblath D R, Ilyas A A, Baba H, Quarles R H, Griffin J W, Alderson K, Adams R N. A treatable multifocal motor neuropathy with antibodies to GM1 ganglioside.  Ann Neurol. 1988;  24 73-78
• 5 Kornberg A J, Pestronk A. The clinical and diagnostic role of anti-GM1 antibody testing.  Muscle Nerve. 1994;  17 100-104
• 6 Biessels G J, Franssen H, Berg L H van den, Gibson A, Kappelle L J, Venables G S, Wokke J H. Multifocal motor neuropathy.  J Neurol. 1997;  244 143-152
• 7 Nobile-Orazio E. Multifocal motor neuropathy.  J Neuroimmunol. 2001;  115 4-18
• 8 Leger J M, Behin A. Multifocal motor neuropathy.  Curr Opin Neurol. 2005;  18 567-573
• 9 Nobile-Orazio E, Cappellari A, Priori A. Multifocal motor neuropathy: current concepts and controversies.  Muscle Nerve. 2005;  31 663-680
• 10 Asseldonk J T Van, Franssen H, Berg-Vos R Van den, Wokke J H, Berg L H Van den. Multifocal motor neuropathy.  Lancet Neurol. 2005;  4 309-319
• 11 Charles N, Benoit P, Vial C, Bierme T, Moreau T, Bady B. Intravenous immunoglobulin treatment in multifocal motor neuropathy.  Lancet. 1992;  340 182
• 12 Chaudhry V, Corse A M, Cornblath D R, Kuncl R W, Drachman D B, Freimer M L, Miller R G, Griffin J W. Multifocal motor neuropathy: response to human immune globulin.  Ann Neurol. 1993;  33 237-242
• 13 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
• 14 Umapathi T, Hughes R A, Nobile-Orazio E, Leger J M. Immunosuppressive treatment for multifocal motor neuropathy.  Cochrane Database Syst Rev. 2002;  2 ,  CD003217
• 15 Umapathi T, Hughes R A, Nobile-Orazio E, Leger J M. Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy.  Cochrane Database Syst Rev. 2005;  3 , 
• 16 Olney R K, Lewis R A, Putnam T D, Campellone Jr J V. American Association of Electrodiagnostic Medicine. Consensus criteria for the diagnosis of multifocal motor neuropathy.  Muscle Nerve. 2003;  27 117-121
• 17 Joint Task Force of the EFNS and the PNS . European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.  J Peripher Nerv Syst. 2006;  11 9-19
• 18 Leger J M. Multifocal motor neuropathy and chronic inflammatory demyelinating polyradiculoneuropathy.  Curr Opin Neurol. 1995;  8 359-363
• 19 Saperstein D S, Katz J S, Amato A A, Barohn R J. Clinical spectrum of chronic acquired demyelinating polyneuropathies.  Muscle Nerve. 2001;  24 311-324
• 20 Doorn P A Van, Garssen M P. Treatment of immune neuropathies.  Curr Opin Neurol. 2002;  15 623-631
• 21 Kieseier B C, Kiefer R, Gold R, Hemmer B, Willison H J, Hartung H P. Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system.  Muscle Nerve. 2004;  30 131-156
• 22 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
• 23 Asseldonk J T Van, Berg L H Van den, Berg-Vos R M Van den, Wieneke G H, Wokke J H, Franssen H. Demyelination and axonal loss in multifocal motor neuropathy: distribution and relation to weakness.  Brain. 2003;  126 186-198
• 24 Mäurer M, Stoll G, Toyka K V. Multifocal motor neuropathy presenting as chronic progressive proximal leg weakness.  Neuromuscul Disord. 2004;  14 380-382
• 25 Bouche P, Moulonguet A, Younes-Chennoufi A B, Adams D, Baumann N, Meininger V, Leger J M, Said G. Multifocal motor neuropathy with conduction block: a study of 24 patients.  J Neurol Neurosurg Psychiatry. 1995;  59 38-44
• 26 Kaji R, Shibasaki H, Kimura J. Multifocal demyelinating motor neuropathy: cranial nerve involvement and immunoglobulin therapy.  Neurology. 1992;  42 506-509
• 27 Magistris M, Roth G. Motor neuropathy with multifocal persistent conduction blocks.  Muscle Nerve. 1992;  15 1056-1057
• 28 Berg-Vos R M Van den, Franssen H, Visser J, Visser M de, Haan R J de, Wokke J H, 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
• 29 Terenghi F, Meucci N, Nobile-Orazio E. Long-term disability in multifocal motor neuropathy and its relation to IVIg therapy.  J Periph Nerv Syst. 2003;  8 67
• 30 Bradley W G, Bennett R K, Good P, Little B. Proximal chronic inflammatory polyneuropathy with multifocal conduction block.  Arch Neurol. 1988;  45 451-455
• 31 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
• 32 White J R, Sachs G M, Gilchrist J M. Multifocal motor neuropathy with conduction block and Campylobacter jejuni.  Neurology. 1996;  46 562-563
• 33 Abruzzese M, Reni L, Schenone A, Mancardi G L, Primavera A. Multifocal motor neuropathy with conduction block after Camphylobacter jejuni enteritis.  Neurology. 1997;  48 544
• 34 Sugie K, Murata K, Ikoma K, Suzumura A, Takayanagi T. A case of acute multifocal motor neuropathy with conduction block after Campylobacter jejuni enteritis.  Rinsho Shinkeigaku. 1998;  38 42-45
• 35 Capasso M, Caporale C M, Pomilio F, Gandolfi P, Lugaresi A, Uncini A. Acute motor conduction block neuropathy Another Guillain-Barré syndrome variant.  Neurology. 2003;  61 617-622
• 36 Parry G J. Motor neuropathy with multifocal presistent conduction blocks.  Muscle Nerve. 1992;  15 1057
• 37 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
• 38 Chaudhry V, Corse A M, Cornblath D R, Kuncl R W, Freimer M L, Griffin J W. Multifocal motor neuropathy: electrodiagnostic features.  Muscle Nerve. 1994;  17 198-205
• 39 Jaspert A, Claus D, Grehl H, Neundörfer B. Multifocal motor neuropathy: clinical and electrophysiological findings.  J Neurol. 1996;  243 684-692
• 40 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
• 41 Jamieson P W, Giuliani M J, Martinez A J. Necrotizing angiopathy presenting with multifocal conduction blocks.  Neurology. 1991;  41 442-444
• 42 Hömberg V, Reiners K, Toyka K V. Reversible conduction block in human ischemic neuropathy after ergotamine abuse.  Muscle Nerve. 1992;  15 467-470
• 43 Brown W F, Feasby T E. Conduction block and denervation in Guillain-Barré polyneuropathy.  Brain. 1984;  107 219-239
• 44 Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force . Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force.  Neurology. 1991;  41 617-618
• 45 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
• 46 Kimura J. Principles and pitfalls of nerve conduction studies.  Ann Neurol. 1984;  16 415-429
• 47 Taylor P K. CMAP dispersion, amplitude decay, and area decay in a normal population.  Muscle Nerve. 1993;  16 1181-1187
• 48 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
• 49 Oh S J, Kim D E, Kuruoglu H R. What is the best diagnostic index of conduction block and temporal dispersion?.  Muscle Nerve. 1994;  17 489-493
• 50 Sumner A J. Separating motor neuron diseases from pure motor neuropathies. Multifocal motor neuropathy with persistent conduction block.  Adv Neurol. 1991;  56 399-403
• 51 Lange D J, Trojaborg W, McDonald T D, Blake D M. Persistent and transient „conduction block” in motor neuron diseases.  Muscle Nerve. 1993;  16 896-903
• 52 Schulte-Mattler W J, Müller T, Georgiadis D, Kornhuber M E, Zierz S. Length dependence of variables associated with temporal dispersion in human motor nerves.  Muscle Nerve. 2001;  24 527-533
• 53 American Association of Electrodiagnostic Medicine . Consensus criteria for the diagnosis of partial conduction block.  Muscle Nerve. 1999;  8 225-229
• 54 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
• 55 Katz J S, Barohn R J, Kojan S, Wolfe G I, Nations S P, Saperstein D S, Amato A A. Axonal multifocal motor neuropathy without conduction block or other features of demyelination.  Neurology. 2002;  58 615-620
• 56 Berg-Vos R M Van den, Franssen H, Wokke J H, 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
• 57 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
• 58 Corse A M, Chaudhry V, Crawford T O, Cornblath D R, Kuncl R W, Griffin J W. Sensory nerve pathology in multifocal motor neuropathy.  Ann Neurol. 1996;  39 319-325
• 59 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
• 60 Arunachalam R, Osei-Lah A, Mills K R. Transcutaneous cervical root stimulation in the diagnosis of multifocal motor neuropathy with conduction block.  J Neurol Neurosurg Psychiatry. 2003;  74 1329-1331
• 61 Schulte-Mattler W J, Georgiadis D, Tietze K, Zierz S. Relation between maximum discharge rates on electromyography and motor unit number estimates.  Muscle Nerve. 2000;  23 231-238
• 62 Nodera H, Bostock H, Izumi Y, Nakamura K, Urushihara R, Sakamoto T, Murase N, Shimazu H, Kusunoki S, Kaji R. Activity-dependent conduction block in multifocal motor neuropathy: magnetic fatigue test.  Neurology. 2006;  67 280-287
• 63 Pakiam A S, Parry G J. Multifocal motor neuropathy without overt conduction block.  Muscle Nerve. 1998;  21 243-245
• 64 Berg-Vos R M Van den, Franssen H, Wokke J H, Berg L H Van den. Multifocal motor neuropathy: long-term clinical and electrophysiological assessment of intravenous immunoglobulin maintenance treatment.  Brain. 2002;  125 1875-1886
• 65 Terenghi F, Cappellari A, Bersano A, Carpo M, Barbieri S, Nobile-Orazio E. How long is IVIg effective in multifocal motor neuropathy?.  Neurology. 2004;  62 666-668
• 66 Bech E, Jakobsen J, Orntoft T F. ELISA-type titertray assay of IgM anti-GM1 autoantibodies.  Clin Chem. 1994;  40 1331-1334
• 67 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
• 68 Holloway R G, Feasby T E. To test or not to test? That is the question.  Neurology. 1999;  53 1905-1907
• 69 McCombe P A, Wilson R, Prentice R L. Results of testing for anti-GM1 antibodies.  J Clin Neurosci. 2000;  7 209-212
• 70 Cavanna B, Carpo M, Pedotti R, Scarpini E, Meucci N, Allaria S, Scarlato G, Nobile-Orazio E. Anti-GM2 IgM antibodies: clinical correlates and reactivity with a human neuroblastoma cell line.  J Neuroimmunol. 1999;  94 157-164
• 71 Latov N, Hays A P, Donofrio P D, Liao J, Ito H, McGinnis S, Konstadoulakis M, Freddo L, Shy M E. Monoclonal IgM with unique specificity to gangliosides GM1 and GD1b and to lacto-N-tetraose associated with human motor neuron disease.  Neurology. 1988;  38 763-768
• 72 Sadiq S A, Thomas F P, Kilidireas K, Protopsaltis S, Hays A P, Lee K W, Romas S N, Kumar N, Berg L Van den, Santoro M. The spectrum of neurologic disease associated with anti-GM1 antibodies.  Neurology. 1990;  40 1067-1072
• 73 Lamb N L, Patten B M. Clinical correlations of anti-GM1 antibodies in amyotrophic lateral sclerosis and neuropathies.  Muscle Nerve. 1991;  14 1021-1027
• 74 Hughes R A, Hadden R D, Gregson N A, Smith K J. Pathogenesis of Guillain-Barre syndrome.  J Neuroimmunol. 1999;  100 74-97
• 75 Schaik I N van, Bossuyt P M, Brand A, Vermeulen M. Diagnostic value of GM1 antibodies in motor neuron disorders and neuropathies: a meta-analysis.  Neurology. 1995;  45 1570-1577
• 76 Alaedini A, Sander H W, Hays A P, Latov N. Antiganglioside antibodies in multifocal acquired sensory and motor neuropathy.  Arch Neurol. 2003;  60 42-46
• 77 Berg-Vos R M Van den, Berg L H, Franssen H Van den, Vermeulen M, Witkamp T D, Jansen G H, Es H W Van, Kerkhoff H, Wokke J H. Multifocal inflammatory demyelinating neuropathy: a distinct clinical entity?.  Neurology. 2000;  54 26-32
• 78 Taylor B V, Gross L, Windebank A J. The sensitivity and specificity of anti-GM1 antibody testing.  Neurology. 1996;  47 951-955
• 79 Freddo L, Yu R K, Latov N, Donofrio P D, Hays A P, Greenberg H S, Albers J W, Allessi A G, Keren D. Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease.  Neurology. 1986;  36 454-458
• 80 Corse A M, Chaudhry V, Crawford T O, Cornblath D R, Kuncl R W, Griffin J W. Sensory nerve pathology in multifocal motor neuropathy.  Ann Neurol. 1996;  39 319-325
• 81 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
• 82 Auer R N, Bell R B, Lee M A. Neuropathy with onion bulb formations and pure motor manifestations.  Can J Neurol Sci. 1989;  16 194-197
• 83 Taylor B V, Dyck P J, Engelstad J, Gruener G, Grant I, Dyck P J. Multifocal motor neuropathy: pathologic alterations at the site of conduction block.  J Neuropathol Exp Neurol. 2004;  63 129-137
• 84 Kaji R, Oka N, Tsuji T, Mezaki T, Nishio T, Akiguchi I, Kimura J. Pathological findings at the site of conduction block in multifocal motor neuropathy.  Ann Neurol. 1993;  33 152-158
• 85 Es H W Van, Berg L H Van den, Franssen H, Witkamp T D, Ramos L M, Notermans N C, Feldberg M A, Wokke J H. Magnetic resonance imaging of the brachial plexus in patients with multifocal motor neuropathy.  Neurology. 1997;  48 1218-1224
• 86 Duggins A J, McLeod J G, Pollard J D, Davies L, Yang F, Thompson E O, Soper J R. Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy.  Brain. 1999;  122 1383-1390
• 87 European Neuromuscular Center . 79^th International Workshop: multifocal motor neuropathy.  Neuromusc Disord. 2001;  11 309-314
• 88 Traynor B J, Codd M B, Corr B, Forde C, Frost E, Hardiman O. Amyotrophic lateral sclerosis mimic syndromes: a population-based study.  Arch Neurol. 2000;  57 109-113
• 89 Berg-Vos R M Van den, Berg L H Van den, Visser J, Visser M de, Franssen H, Wokke J H. The spectrum of lower motor neuron syndromes.  J Neurol. 2003;  250 1279-1292
• 90 Hughes R A. The spectrum of acquired demyelinating polyradiculoneuropathy.  Acta Neurol Belg. 1994;  94 128-132
• 91 Oh S J, Claussen G C, Kim D S. Motor and sensory demyelinating mononeuropathy multiplex (multifocal motor and sensory demyelinating neuropathy): a separate entity or a variant of chronic inflammatory demyelinating polyneuropathy?.  J Peripher Nerv Syst. 1997;  2 362-369
• 92 Lewis R A. Multifocal motor neuropathy and Lewis Sumner syndrome: two distinct entities.  Muscle Nerve. 1999;  22 1738-1739
• 93 Saperstein D S, Amato A A, Wolfe G I, Katz J S, Nations S P, Jackson C E, Bryan W W, Burns D K, Barohn R J. Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.  Muscle Nerve. 1999;  22 560-566
• 94 Viala K, Renie L, Maisonobe T, Behin A, Neil J, Leger J M, Bouche P. Follow-up study and response to treatment in 23 patients with Lewis-Sumner syndrome.  Brain. 2004;  127 2010-2017
• 95 Beydoun S R. Multifocal motor neuropathy with conduction block misdiagnosed as multiple entrapment neuropathies.  Muscle Nerve. 1998;  21 813-815
• 96 Reiners K. Neurophysiologische und morphologische Aspekte der Nervenleitung. I. Grundlagen und Problematik des Leitungsblocks.  Z EEG-EMG. 1997;  28 96-102
• 97 Kaji R. Physiology of conduction block in multifocal motor neuropathy and other demyelinating neuropathies.  Muscle Nerve. 2003;  27 285-296
• 98 Feasby T H, Brown W F, Gilbert J J, Hahn A F. The pathological basis of conduction block in human neuropathies.  J Neurol Neurosurg Psychiatry. 1986;  48 239-244
• 99 Bostock H, Sharief M K, Reid G, Murray N M. Axonal ion channel dysfunction in amyotrophic lateral sclerosis.  Brain. 1995;  118 217-225
• 100 Veugelers B, Theys P, Lammens M, Hees J Van, Robberecht W. Pathological findings in a patient with amyotrophic lateral sclerosis and multifocal motor neuropathy with conduction block.  J Neurol Sci. 1996;  136 64-70
• 101 Burke D, Kiernan M C, Bostock H. Excitability of human axons.  Clin Neurophysiol. 2001;  112 1575-1585
• 102 Kiernan M C, Guglielmi J M, Kaji R, Murray N M, Bostock H. Evidence for axonal membrane hyperpolarization in multifocal motor neuropathy with conduction block.  Brain. 2002;  125 664-675
• 103 Priori A, Cinnante C, Pesenti A, Carpo M, Cappellari A, Nobile-Orazio E, Scarlato G, Barbieri S. Distinctive abnormalities of motor axonal strength-duration properties in multifocal motor neuropathy and in motor neurone disease.  Brain. 2002;  125 2481-2490
• 104 Schluep M, Steck A J. Immunostaining of motor nerve terminals by IgM M protein with activity against gangliosides GM1 and GD1b from a patient with motor neuron disease.  Neurology. 1988;  38 1890-1892
• 105 Thomas F P, Adapon P H, Goldberg G P, Latov N, Hays A P. Localization of neural epitopes that bind to IgM monoclonal autoantibodies (M-proteins) from two patients with motor neuron disease.  J Neuroimmunol. 1989;  21 31-39
• 106 O'Hanlon G M, Paterson G J, Wilson G, Doyle D, McHardie P, Willison H J. Anti-GM1 ganglioside antibodies cloned from autoimmune neuropathy patients show diverse binding patterns in the rodent nervous system.  J Neuropathol Exp Neurol. 1996;  55 184-195
• 107 Thomas F P, Thomas J E, Sadiq S A, Berg L H Van den, Roelofs R I, Latov N, Hays A P. Human monoclonal IgM anti-Gal(beta 1 - 3)GalNAc autoantibodies bind to the surface of bovine spinal motoneurons.  J Neuropathol Exp Neurol. 1990;  49 89-95
• 108 Corbo M, Quattrini A, Lugaresi A, Santoro M, Latov N, Hays A P. Patterns of reactivity of human anti-GM1 antibodies with spinal cord and motor neurons.  Ann Neurol. 1992;  32 487-492
• 109 Ogawa-Goto K, Funamoto N, Ohta Y, Abe T, Nagashima K. Myelin gangliosides of human peripheral nervous system: an enrichment of GM1 in the motor nerve myelin isolated from cauda equina.  J Neurochem. 1992;  59 1844-1849
• 110 Santoro M, Uncini A, Corbo M, Staugaitis S M, Thomas F P, Hays A P, Latov N. Experimental conduction block induced by serum from a patient with anti-GM1 antibodies.  Ann Neurol. 1992;  31 385-390
• 111 Uncini A, Santoro M, Corbo M, Lugaresi A, Latov N. Conduction abnormalities induced by sera of patients with multifocal motor neuropathy and anti-GM1 antibodies.  Muscle Nerve. 1993;  16 610-615
• 112 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
• 113 Harvey G K, Toyka K V, Zielasek J, Kiefer R, Simonis C, Hartung H P. Failure of anti-GM1 IgG or IgM to induce conduction block following intraneural transfer.  Muscle Nerve. 1995;  18 388-394
• 114 Hirota N, Kaji R, Bostock H, Shindo K, Kawasaki T, Mizutani K, 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
• 115 Benatar M, Willison H J, Vincent A. Immune-mediated peripheral neuropathies and voltage-gated sodiums channels.  Muscle Nerve. 1999;  22 108-110
• 116 Azulay J P, Rihet P, 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
• 117 Leger 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
• 118 Pestronk A, Adams R N, Kuncl R W, Drachman D B, Clawson L L, Cornblath D R. Differential effects of prednisone and cyclophosphamide on autoantibodies in human neuromuscular disorders.  Neurology. 1989;  39 628-633
• 119 Roberts M, Willison H J, Vincent A, Newsom-Davis J. Multifocal motor neuropathy human sera block distal motor nerve conduction in mice.  Ann Neurol. 1995;  38 111-118
• 120 Berg L H Van den, Lokhorst H, Wokke J H. Pulsed high-dose dexamethasone is not effective in patients with multifocal motor neuropathy.  Neurology. 1997;  48 1135
• 121 Azulay J P, Blin O, Pouget J, Boucraut J, Bille-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
• 122 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
• 123 Stangel M, Hartung H P, Marx P, Gold R. Intravenous immunoglobulin treatment of neurological autoimmune diseases.  J Neurol Sci. 1998;  153 203-214
• 124 Comi G, Amadio S, Galardi G, Fazio R, Nemni R. Clinical and neurophysiological assessment of immunoglobulin therapy in five patients with multifocal motor neuropathy.  J Neurol Neurosurg Psychiatry. 1994;  57 35-37
• 125 Cappellari A, Nobile-Orazio E, Meucci N, Scarlato G, Barbieri S. Multifocal motor neuropathy: a source of error in the serial evaluation of conduction block.  Muscle Nerve. 1996;  19 666-669
• 126 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
• 127 Berg L H Van den, Franssen H, Wokke J H. The long-term effect of intravenous immunoglobulin treatment in multifocal motor neuropathy.  Brain. 1998;  121 421-428
• 128 Vucic S, Black K R, Chong P S, Cros D. Multifocal motor neuropathy: decrease in conduction blocks and reinnervation with long-term IVIg.  Neurology. 2004;  63 1264-1269
• 129 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
• 130 Pringle C E, Belden J, Veitch J E, Brown W F. Multifocal motor neuropathy presenting as ophthalmoplegia.  Muscle Nerve. 1997;  20 347-351
• 131 Brannagan 3rd  T H, Alaedini A, Gladstone D E. High-dose cyclophosphamide without stem cell rescue for refractory multifocal motor neuropathy.  Muscle Nerve. 2006;  34 246-250
• 132 Martina I S, Doorn P A van, Schmitz P I, Meulstee J, Meche F G van der. Chronic motor neuropathies: response to interferon-beta1a after failure of conventional therapies.  J Neurol Neurosurg Psychiatry. 1999;  66 197-201
• 133 Nemni R, Santuccio G, Calabrese E, Galardi G, Canal N. Efficacy of cyclosporine treatment in multifocal motor neuropathy.  J Neurol. 2003;  250 1118-1120
• 134 Pestronk A, Florence J, Miller T, Choksi R, Al-Lozi M T, Levine T D. Treatment of IgM antibody associated polyneuropathies using rituximab.  J Neurol Neurosurg Psychiatry. 2003;  74 485-489
• 135 Rojas-Garcia R, Gallardo E, Andres I de, Luna N de, Juarez C, Sanchez P, Illa I. Chronic neuropathy with IgM anti-ganglioside antibodies: lack of long-term response to rituximab.  Neurology. 2003;  61 1814-1816