Stiff-man syndrome: possible autoimmune etiology targeted against GABA-ergic cells.
We report the case of a female patient, who died at the age of 66 years. Besides an insulin-dependent diabetes mellitus (IDDM) she had developed the clinical symptoms of stiff-man-syndrome (SMS) and harbored autoantibodies against glutamate-decarboxylase (GAD) in blood and liquor. GAD catalyzes the biosynthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The autopsy revealed typical alterations observed in diabetes mellitus including an incomplete fibrosis of pancreatic Langerhans islets. A decrease of GABA-ergic cells in the cerebellar cortex was observed, and a size reduction of Renshaw cells in the spinal cord. Furthermore, a dilution series of a polyclonal GABA antibody delivered a reduced immunofluorescence in the cerebellum. In skeletal muscle a neurogenic atrophy was observed. As described in literature, the clinical symptoms decayed following clonazepam administration. We suggest that this case including GAD autoantibodies, dramatic loss of GAD-expressing pancreatic cells, and loss or atrophy of GABA secretory neurons, supports the hypothesis that SMS may be an autoimmune disease directed against GABA-ergic cells. Furthermore, we suggest a neuronal hypersensitivity at the spinal cord level caused by the atrophic Renshaw cells.
Warich-Kirches
M
M
Department of Neuropathology, Medical School, Otto-von-Guericke University, Magdeburg, Germany.
Von Bossanyi
P
P
Treuheit
T
T
Kirches
E
E
Dietzmann
K
K
Feistner
H
H
Wittig
H
H
D000368:Aged; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000032:analysis*; D006801:Humans; D010179:Pancreas / Q000737:chemistry*; D013116:Spinal Cord / Q000737:chemistry*; D016750:Stiff-Person Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase