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Serum factor in Miller-Fisher variant of Guillain-Barré syndrome and neurotransmitter release
M Roberts1, H Willison, A Vincent
1Department of Clinical Neurology, John Radcliffe Hospital, University of Oxford, UK.
Abstract:
Serum IgG autoantibodies to GQ1b ganglioside are associated with the acute phase of the Miller-Fisher syndrome (MFS). We investigated the effects of three anti-GQ1b-positive MFS sera in the mouse phrenic-nerve/diaphragm preparation. Miniature endplate potential frequencies increased eight-fold within 25 min, declined rapidly, and ceased altogether after 3 h, when nerve stimulation no longer evoked a response. One MFS convalescent serum (anti-GQ1b negative) and sera from healthy controls and from patients with other neurological diseases were without effect. Thus muscle weakness in MFS may be caused by a serum factor, likely to be GQ1b antibody, that leads to failure of acetylcholine release from motor nerve terminals.
Insights
Serum IgG autoantibodies targeting GQ1b ganglioside are linked to Miller-Fisher syndrome (MFS). These antibodies impair acetylcholine release, causing muscle weakness by disrupting nerve terminal function.
Area of Science:
- Neurology
- Immunology
- Neurophysiology
Background:
- Miller-Fisher syndrome (MFS) is an autoimmune neurological disorder.
- Serum IgG autoantibodies against GQ1b ganglioside are characteristic of the acute phase of MFS.
Purpose of the Study:
- To investigate the functional effects of anti-GQ1b antibodies from MFS patients on neuromuscular transmission.
- To determine the role of GQ1b antibodies in the pathogenesis of MFS-associated muscle weakness.
Main Methods:
- Utilized the mouse phrenic-nerve/diaphragm preparation.
- Applied sera from MFS patients (anti-GQ1b positive and negative), healthy controls, and patients with other neurological diseases.
- Measured miniature endplate potential frequencies and response to nerve stimulation.
Main Results:
- Anti-GQ1b-positive MFS sera significantly increased miniature endplate potential frequencies initially.
- This effect rapidly declined, leading to a complete cessation of evoked responses after 3 hours.
- Convalescent MFS serum (anti-GQ1b negative) and control sera had no significant effect.
Conclusions:
- Serum factors, likely GQ1b antibodies, cause muscle weakness in MFS.
- These antibodies impair acetylcholine release from motor nerve terminals.
- This mechanism explains the neuromuscular dysfunction observed in Miller-Fisher syndrome.