Isaacs' syndrome as a potassium channelopathy of the nerve

Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated potassium channel disorder (channelopathy). The target channel proteins of the antigens are voltage-gated potassium channels (VGKCs), especially dendrotoxin-sensitive fast potassium channels. The suppression of voltage-gated outward K+ current by antibodies induces hyperexcitability of the peripheral nerve. Patch clamp studies show that antibodies may not directly block the kinetics of VGKCs but may decrease channel density. Electrophysiological, pharmacological, and immunological findings indicate that the site of origin of spontaneous discharges is principally in the distal portion of the motor nerve and/or within the terminal arborization. The spectrum of potassium channelopathies is expanding. The existence of antibodies against VGKCs should be considered in patients who present with generalized nerve hyperexcitability of undetermined etiology. © 2002 Wiley Periodicals, Inc. Muscle Nerve Supplement 11: S55–S58, 2002