Autoantibodies to Glutamic Acid Decarboxylase in a Patient with Stiff-Man Syndrome, Epilepsy, and Type I Diabetes Mellitus

TLDR

Stiff‑man syndrome is a rare central nervous system disorder characterized by progressive, fluctuating muscle rigidity and painful spasms, and it can be associated with endocrine disorders such as insulin‑independent diabetes and epilepsy. The study aimed to determine whether autoimmunity against the nervous system exists in a patient with stiff‑man syndrome, epilepsy, and type I diabetes mellitus. IgG with an oligoclonal pattern was elevated in cerebrospinal fluid, and both serum and CSF produced identical intense gray‑matter staining that matched antibodies to glutamic acid decarboxylase, indicating that GABAergic pathways may be impaired and suggesting an autoimmune pathogenesis. Published in N Engl J Med 1988; 318:1012–20.

Abstract

Stiff-man syndrome is a rare disorder of the central nervous system consisting of progressive, fluctuating muscle rigidity with painful spasms. It is occasionally associated with endocrine disorders, including insulindependent diabetes, and with epilepsy. We investigated the possible existence of autoimmunity against the nervous system in a patient with stiff-man syndrome associated with epilepsy and Type I diabetes mellitus. Levels of IgG, which had an oligoclonal pattern, were elevated in the cerebrospinal fluid. The serum and the cerebrospinal fluid produced an identical, intense staining of all gray-matter regions when used to stain brain sections according to an indirect light-microscopical immunocytochemical procedure. The staining patterns were identical to those produced by antibodies to glutamic acid decarboxylase (the enzyme responsible for the synthesis of gamma-aminobutyric acid). A band comigrating with glutamic acid decarboxylase in sodium dodecyl sulfate–polyacrylamide gels appeared to be the only nervoustissue antigen recognized by cerebrospinal fluid antibodies, and the predominant antigen recognized by serum antibodies. These findings support the idea that an impairment of neuronal pathways that operate through gamma-aminobutyric acid is involved in the pathogenesis of stiffman syndrome, and they raise the possibility of an autoimmune pathogenesis. (N Engl J Med 1988; 318: 1012–20.)