STIFF-MAN SYNDROME - POSSIBLE AUTOIMMUNE ETIOLOGY TARGETED AGAINST GABAERGIC CELLS

We report the case of a female patient, who died at the age of 66 year s. Besides an insulin-dependent diabetes mellitus (IDDM) she had devel oped the clinical symptoms of stiff-man-syndrome (SMS) and harbored au toantibodies against glutamate-decarboxylase (GAD) in blood and liquor . GAD catalyzes the biosynthesis of the inhibitory neurotransmitter ga mma-aminobutyric acid (GABA). The autopsy revealed typical alterations observed in diabetes mellitus including an incomplete fibrosis of pan creatic Langerhans islets. A decrease of GABA-ergic cells in the cereb ellar cortex was observed, and a size reduction of Renshaw cells in th e spinal cord. Furthermore, a dilution series of a polyclonal GABA ant ibody delivered a reduced immunofluorescence in the cerebellum. In ske letal muscle a neurogenic atrophy was observed. As described in litera ture, the clinical symptoms decayed following clonazepam administratio n. We suggest that this case including GAD autoantibodies, dramatic lo ss of GAD-expressing pancreatic cells, and loss or atrophy of GABA sec retory neurons, supports the hypothesis that SMS may be an autoimmune disease directed against GABA-ergic cells. Furthermore, we suggest a n euronal hypersensitivity at the spinal cord level caused by the atroph ic Renshaw cells.