Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus

N Engl J Med. 1988 Apr 21;318(16):1012-20. doi: 10.1056/NEJM198804213181602.


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 insulin-dependent 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 nervous-tissue 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 stiff-man syndrome, and they raise the possibility of an autoimmune pathogenesis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / analysis*
  • Autoimmune Diseases / immunology
  • Brain / immunology
  • Diabetes Mellitus, Type 1 / complications*
  • Epilepsy / complications*
  • Female
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulin G / analysis
  • Immunohistochemistry
  • Middle Aged
  • Muscle Rigidity / complications
  • Muscle Rigidity / immunology*
  • Spasm / complications
  • Spasm / immunology*
  • Syndrome
  • gamma-Aminobutyric Acid / physiology


  • Autoantibodies
  • Immunoglobulin G
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase