[Immune-mediated neuromyotonia (Isaacs' syndrome)--clinical aspects and pathomechanism].
Neuromyotonia occurs due to several causes such as hereditary, immune-mediated and degenerative neurological disorders. Isaacs' syndrome (immune-mediated neuromyotonia) is an antibody-mediated potassium channel disorder (channelopathy). Clinical symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation following muscle contraction (pseudomyotonia), and hyperhidrosis; these symptoms are due to hyperexcitability of the peripheral nerve, including autonomic nerve. These symptoms are relieved by the administration of Na channel blocker and immunotherapy. Recent studies show that this disease is not infrequently associated with neoplasm, especially thymoma. The target channel proteins of the antigens are voltage-gated potassium channels (VGKCs), specifically dendrotoxin-sensitive fast potassium channels. The suppression of voltage-gated outward K+ current by antibodies induces the hyper- excitability of the peripheral nerve. The findings of patch clamp studies show that antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiologic, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve and/or within the terminal arborization. Anti-VGKC antibodies were also found to be positive in patients with Morvan's syndrome, limbic encephalitis and temporal epilepsy. Thus, an increasing number of immune-mediated neurological disorders with anti-VGKC antibodies are being identified. However, except in Morvan's syndrome, it is rare to find symptoms pertaining to involvement of both the peripheral and central nervous system in the same patient with anti-VGKC antibodies. The differences in the pathomechanism of Isaacs' syndrome and limbic encephalitis are still unclear.
Arimura
Kimiyoshi
K
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Watanabe
Osamu
O
D001323:Autoantibodies; D006801:Humans; D007167:Immunotherapy; D020386:Isaacs Syndrome / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D020361:Paraneoplastic Syndromes, Nervous System; D015221:Potassium Channels / Q000276:immunology; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*
D001323:Autoantibodies; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated