HETEROGENEITY OF AUTOANTIBODIES IN STIFF-MAN SYNDROME

Stiff-man syndrome is a rare neurological disorder characterized by skeletal muscle rigidity and spasms in which detection of circulating anti-glutamic acid decarboxylase antibodies has suggested an autoimmune pathogenesis. To further define the role of autoimmunity in the pathogenesis, we studied anti-glutamic acid decarboxylase antibodies, as well as organ- and non-organ-specific autoantibodies in 13 patients with stiff-man syndrome and 127 patients with other neurological disorders. Thyrogastric antibodies were more frequent in patients with stiff-man syndrome (46%) than in those with other neurological disorders (12%) (p < 0.05). Non-organ-specific antibodies were found at a similar frequency in the patients with stiff-man syndrome (61%) and those with other neurological disorders (65%). Islet-cell autoantibodies and anti-glutamic acid decarboxylase antibodies were more common in stiff-man syndrome patients (38% and 31%) compared to the patients with other neurological disorders (6% and 3%, respectively; p < 0.001). With the exception of 1 patient in the other neurological disorders group, anti-glutamic acid decarboxylase antibodies were always associated with islet-cell autoantibodies. Four patients with stiff-man syndrome had an associated solid tumor: 3 of them had antibodies recognizing a 125/130-kd protein and not glutamic acid decarboxylase. Our study indicates that with immunological markers, patients with stiff-man syndrome can be subdivided into three groups: (1) patients with circulating islet-cell autoantibodies, anti-glutamic acid decarboxylase as well as other organ-specific autoantibodies, and the frequent association with an autoimmune disease (autoimmune variant); (2) patients with associated neoplasms and circulating non-organ-specific autoantibodies but neither islet-cell nor anti-glutamic acid decarboxylase autoantibodies (paraneoplastic variant); and (3) patients with no evidence of any known autoantibody or association with other clinically evident diseases (idiopathic variant). We conclude that the presence of anti-glutamic acid decarboxylase antibodies is restricted to a subgroup of stiff-man syndrome patients with associated autoimmune diseases. The absence of these antibodies does not exclude a diagnosis of stiff-man syndrome, which is still based on clinical and neurophysiological evidence.