Rinsho Shinkeigaku (Clinical Neurology)

Symposium 2

Isaacs's syndrome and associated diseases

Osamu Watanabe, M.D., Ph.D.1)

1)Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences

Isaacs' syndrome is an antibody-mediated potassium channel disorder. Clinical symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation following muscle contraction, and hyperhidrosis. Hyperexcitability of the peripheral nerve cause these symptoms, which are relieved by administration of Na channel blockers and immunotherapy. The target channel proteins are voltage-gated potassium channels (VGKCs). The suppression of voltage-gated outward K+ current by antibodies induces hyperexcitability of the peripheral nerve. Electrophysiological findings show that antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiological, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve. "VGKC antibodies" are also detected in Morvan syndrome (severe insomnia with neuromyotonia and various autonomic disorders) and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC antibodies" are mainly directed toward associated proteins (for example LGI-1, CASPR-2) that complex with VGKCs themselves. The "VGKC antibodies" are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. CASPR-2 antibodies are present in the majority of patients with Morvan syndrome.
Full Text of this Article in Japanese PDF (880K)

(CLINICA NEUROL, 53: 1067|1070, 2013)
key words: VGKC complex antibody, hyperexcitability, LGI-1, CASPR-2

(Received: 30-May-13)