[Isaacs' syndrome, stiff person syndrome and Satoyoshi disease: pathomechanisms and treatment].
Neurological disorders with characteristic clinical manifestations of painful muscle cramp and stiffness are not infrequent. The immune-mediated mechanism with specific antibodies among these diseases is particularly important for treatment. Isaacs' syndrome (acquired neuromyotonia) is an antibody-mediated potassium channelopathy. The suppression of voltage-gated potassium channel (VGKC) by antibodies induces peripheral nerve hyperexcitability. Antibodies may decrease VGKC density by cross-linking F (ab)2 fractions and increasing the degradation rate of VGKCs. Stiff person syndrome (SPS) and its variants show characteristic symptoms and signs of central nervous system hyperexcitability due to antibodies to the GABA-ergic system such as glutamic acid decarboxylase (GAD), amphiphysin 1 and gephyrin. The role of GAD is the subject of debate, however, recent studies reveal the intrathecal synthesis of GAD which is specific for SPS and appears to impair GABA synthesis. Satoyoshi disease is characterized by painful muscle cramp, baldness, intractable diarrhea, bone and joint deformity, and endocrine disturbances. Muscle cramp may be due to inhibition of the spinal interneuron and hyperexciatability of the anterior horn cell. In patients with Satoyoshi disease, sera reacted with an 85 kDa protein of human brain lysate. In all these disorders, suppression or removal of specific antibodies is critical, however, the effects are short-lived, and supplemental treatment to reduce the hyperexcitability of the peripheral or central nervous system will be needed.
Arimura
Kimiyoshi
K
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences.
D006801:Humans; D020386:Isaacs Syndrome / Q000503:physiopathology*; D016750:Stiff-Person Syndrome / Q000503:physiopathology*