Central nervous system hyperexcitability disorders, known as stiff-man/person syndrome (SPS), are thought to be related to the regulatory disturbance of inhibitory synaptic transmission of motor neurons in the brainstem and spinal cord. SPS is characterized by stiffness and
spasms of the axis and limbs and is divided into two clinical subgroups: classic SPS, which affects the lumbar, trunk, and proximal limb muscles, and SPS-plus syndrome. The latter comprises (1) the stiff-limb subtype, in which symptom is limited to the lower limbs; (2) jerking
stiff-man syndrome, characterized by chronically progressive stiffness and
myoclonus; and (3) acute-onset and
progressive encephalomyelitis with rigidity and
myoclonus. Almost 80% of patients with classic SPS harbor
autoantibodies against
glutamic acid decarboxylase 65 (GAD65). In approximately 30-40% of patients, SPS accompanies type I diabetes, and anti-GAD65
antibodies are detected frequently in type I diabetes. However, the antibody-recognizing
epitopes might be different between SPS and diabetes. Other
autoantibodies against
glycine receptor α1 (12% of patients with SPS) and
GABA(A)-receptor associated
protein (70% of patients with SPS) have been reported. In paraneoplastic SPS,
anti-amphiphysin antibodies have been shown in patients with
breast cancer or
small cell lung cancer. One case of mediastinal
tumor with anti-
gephyrin antibodies has also been reported. However, the roles of these
autoantibodies in the pathomechanisms of SPS have not yet been elucidated.