A case of stiff-man syndrome with an antineuronal autoantibody against an 80 kDa protein

A 23-year-old Japanese man had noted intermittent muscle stiffness in his lower limbs and trunk in addition to painful muscle cramps in his back over one year. The muscle stiffness continued and eventually spread to his upper limbs. Neurological examinations revealed saccadic ocular movement and stiffness in the masseter, neck and four limbs and truncal muscles, enhanced by both voluntary and passive movements. Although the mobility of his joints was severely limited, the muscle strength was preserved. Electromyograms showed the continuous firing of normal motor units at rest, which disappeared both during sleep and after the intravenous administration of 10 mg of diazepam. An oral glucose tolerance test showed a normal pattern. Both the adrenal and thyroid functions were normal. No antibody against glutamic acid decarboxylase was detected in either the patient's serum or cerebrospinal fluid (CSF). The serum antibody against the voltage-gated potassium channel was also negative. Western blot analysis revealed the presence of an antibody in his serum and CSF which reacted with an 80kDa protein in the rat cerebrum, cerebellum and human spinal cord, but not in the rat liver. This patient was thus diagnosed as having stiff-man syndrome. Treatment with oral diazepam (50mg/day), a GABA(A) agonist, proved to be effective, whereas baclofen (75mg/day), a GABA(B) agonist, was not. These results suggest the dysfunction of the GABA neurons in this case, similar to that as previously observed in other cases of stiff-man syndrome while, in addition, the function of the GABA(B) receptor was also markedly disturbed in this case.