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. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 702–707, 2002

[1]  G Plazzi,et al.  Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. , 2001, Brain : a journal of neurology.

[2]  S. Vernino,et al.  Persistent facial myokymia associated with K+ channel antibodies , 2001, Neurology.

[3]  K. Chan,et al.  ANNA‐3 anti‐neuronal nuclear antibody: Marker of lung cancer‐related autoimmunity , 2001, Annals of neurology.

[4]  E. Benarroch,et al.  CRMP‐5 neuronal autoantibody: Marker of lung cancer and thymoma‐related autoimmunity , 2001, Annals of neurology.

[5]  G. Farrugia,et al.  Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. , 2000, The New England journal of medicine.

[6]  C. Ansevin.  Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular hyperexcitability. , 2000, Neurology.

[7]  A. Vincent,et al.  Morvan’s syndrome associated with voltage-gated K channel antibodies , 2000, Neurology.

[8]  G. Walker,et al.  Identification of autoantibodies associated with rippling muscles and myasthenia gravis that recognize skeletal muscle proteins: possible relationship of antigens and stretch-activated ion channels. , 1999, Biochemical and biophysical research communications.

[9]  R. Maselli,et al.  Morvan’s fibrillary chorea: a paraneoplastic manifestation of thymoma , 1998, Journal of neurology, neurosurgery, and psychiatry.

[10]  V. Lennon,et al.  Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer‐related syndromes , 1998, Neurology.

[11]  J. Newsom-Davis,et al.  Autoimmune Neuromyotonia (Isaacs' Syndrome): An Antibody‐mediated Potassium Channelopathy , 1997, Annals of the New York Academy of Sciences.

[12]  V. Lennon.  Serologic profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome , 1997, Neurology.

[13]  I. Kitajima,et al.  Antibodies to potassium channels pc12 in serum of Isaacs' syndrome: Western blot and immunohistochemical studies , 1997, Muscle & nerve.

[14]  O. Pongs,et al.  Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia , 1997, Annals of neurology.

[15]  E. Dropcho.  Antiamphiphysin antibodies with small‐cell lung carcinoma and paraneoplastic encephalomyelitis , 1996, Annals of neurology.

[16]  C. Ansevin,et al.  Rippling muscles and myasthenia gravis with rippling muscles. , 1996, Archives of neurology.

[17]  P. Trouillas,et al.  Improvement of Isaacs' syndrome after treatment with azathioprine. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[18]  D. Stephan,et al.  A rippling muscle disease gene is localized to 1q41 , 1994, Neurology.

[19]  K. Mills,et al.  Immunological associations of acquired neuromyotonia (Isaacs' syndrome). Report of five cases and literature review. , 1993, Brain : a journal of neurology.