Acquired slow-channel syndrome: a form of myasthenia gravis with prolonged open time of the acetylcholine receptor channel.
A 32-year-old female presented with a 2-year history of fluctuating generalized weakness including extraocular, bulbar, and limb muscles, suggesting myasthenia gravis, but with poor response to pyridostigmine and unusual electromyographic findings. After rest, power increased on repeated maximal contractions, followed by progressive weakness. There were decremental responses at low-frequency stimulation, but incremental responses at high frequencies, and single stimuli evoked repetitive compound muscle action potentials. Plasmapheresis was ineffective. In a conventional assay, antibodies against acetylcholine receptors (AChRs) were borderline. However, in an assay using cells expressing mainly adult-type human AChRs, the patient's serum was positive. Thymectomy revealed a hyperplastic thymus. An intercostal muscle specimen revealed small miniature end-plate potentials, 0.22+/-0.02 mV instead of 0.56+/-0.05 mV in controls. The number of 125I-alpha-bungarotoxin binding sites was normal. The decay time constant of end-plate potentials was increased from 5.3+/-0.6 msec in controls to 23+/-3.6 msec in the patient. Ultrastructurally, there was no destruction of the end plate. Transfer of the patient's plasma to mice in vivo produced similar physiological changes in their diaphragms. We conclude that the patient has an immune-mediated disorder, in which an antibody specific to the adult form of the AChRs alters the channel properties, reducing total current and slowing the closure. We propose the name "acquired slow-channel syndrome" for this variant of myasthenia gravis.
Department of Neurology and Clinical Neurophysiology, Leiden University Medical Centre, The Netherlands.
A R
AR
Wintzen
J J
JJ
Plomp
P C
PC
Molenaar
J G
JG
van Dijk
G T
GT
van Kempen
R M
RM
Vos
J H
JH
Wokke
A
A
Vincent
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001769:Blood; D015220:Calcium Channels / Q000276:immunology; D004576:Electromyography; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007366:Intercostal Muscles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D009157:Myasthenia Gravis / Q000097:blood / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D001323:Autoantibodies; D015220:Calcium Channels; D007473:Ion Channels; D011950:Receptors, Cholinergic