Ion channel and striational antibodies define a continuum of autoimmune neuromuscular hyperexcitability.
Neuromuscular hyperexcitability is a characteristic of Isaacs' syndrome. Autoantibodies specific for voltage-gated potassium channels (VGKC) or ganglionic nicotinic acetylcholine receptors (AChR) are markers of this disorder. To determine the frequency of these ion channel antibodies and of related neuron- and muscle-specific antibodies in patients with acquired neuromuscular hyperexcitability, we tested serum specimens from 77 affected patients (35 neuromyotonia, 32 cramp-fasciculation syndrome, 5 rippling muscle syndrome, and 5 focal neuromuscular hyperexcitability) and 85 control subjects. Among study patients, 14% had coexisting myasthenia gravis, and 16% had an associated neoplasm. We found that 35% had VGKC antibodies, 12% ganglionic AChR antibodies, 16% muscle AChR antibodies, and 10% striational antibodies. Overall, 55% had serological evidence of neurological autoimmunity compared to 2% of control subjects. Patients with neuromyotonia were more frequently seropositive (71%) than patients with cramp-fasciculation syndrome (31%). We conclude that acquired neuromuscular hyperexcitability consists of a continuum of clinical disorders with a common autoimmune pathogenesis.
Vernino
Steven
S
Department of Neurology, Mayo Clinic and Mayo Foundation, 200 First Street S.W., Rochester, Minnesota 55905, USA. vernino.steven@mayo.edu
Lennon
Vanda A
VA
D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D006801:Humans; D007473:Ion Channels / Q000276:immunology*; D020386:Isaacs Syndrome / Q000097:blood / Q000276:immunology*; D009046:Motor Neurons / Q000276:immunology* / Q000378:metabolism; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000276:immunology* / Q000378:metabolism; D009157:Myasthenia Gravis / Q000097:blood / Q000276:immunology; D009469:Neuromuscular Junction / Q000276:immunology* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D007473:Ion Channels; D009124:Muscle Proteins; D024642:Potassium Channels, Voltage-Gated; D011978:Receptors, Nicotinic