title: Multifocal motor neuropathy human sera block distal motor nerve conduction in mice.
abstract: Multifocal motor neuropathy (MMN) is associated with serum autoantibodies to gangliosides, but their pathogenic role is uncertain. We have used a novel approach to study the effects of serum and plasma from 8 patients with this syndrome, 6 of whom were anti-GM1 positive. The nerve stimulus required to evoke muscle contraction and endplate potentials (EPPs) was measured in the mouse phrenic nerve-diaphragm preparation during 4 to 6 hours of direct application (plasma at 1:1 or serum 1:2 dilution) and following intraperitoneal injection of plasma (1 ml/day) for 1 to 5 days ("passive transfer"). Direct application of MMN serum or plasma produced a progressive increase in stimulus threshold, followed by complete block of nerve-evoked muscle contraction in 3 cases, and an associated decline to about 50% of the EPP amplitude followed by sudden loss of EPPs. These effects were complement independent. Even with complete block of nerve-evoked EPPs, miniature EPP (MEPP) frequency could be increased by raising external K+ to depolarize the nerve terminal directly. Passive transfer of 1 ml of MMN plasma (n = 5) for 3 days caused similar but less marked changes. These results demonstrate that serum factors in MMN can block nerve conduction at distal motor nerves.
authors.affiliation: Department of Clinical Neurology, University of Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Roberts
authors.forename: H J
authors.initials: HJ
authors.lastname: Willison
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.forename: J
authors.initials: J
authors.lastname: Newsom-Davis
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D005071:Evoked Potentials / Q000502:physiology; D005677:G(M1) Ganglioside / Q000097:blood* / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged; D009045:Motor Endplate / Q000502:physiology; D016472:Motor Neuron Disease / Q000097:blood* / Q000503:physiopathology*; D009046:Motor Neurons / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009407:Nerve Block; D009431:Neural Conduction / Q000502:physiology*
chemical_list: D007075:Immunoglobulin M; D005677:G(M1) Ganglioside