Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy

Neurology. 2000 Jul 12;55(1):46-50. doi: 10.1212/wnl.55.1.46.


Background: Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity.

Methods: The authors investigated the prevalence of GAD-A in patients with therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant human GAD65.

Results: GAD-A were found in eight patients with localization-related epilepsy, whereas none of the patients with generalized epilepsy, other neurologic disorders (n = 38), or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD-A, similar to SMS, whereas six patients had significantly lower titers, characteristic of type 1 diabetes. The two patients with high levels of GAD-A had GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of them had longstanding therapy-resistant temporal lobe epilepsy but did not have diabetes. One had a history of autoimmune disease, whereas the other had serologic evidence of multiple autoantibodies without any clinical signs of autoimmune disease.

Conclusions: GAD autoimmunity may be associated with refractory localization-related epilepsy.

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Cerebellum / drug effects
  • Cerebellum / immunology
  • Cerebellum / pathology
  • Drug Resistance / immunology*
  • Epilepsy / blood
  • Epilepsy / drug therapy
  • Epilepsy / immunology*
  • Epilepsy / pathology*
  • Female
  • Glutamate Decarboxylase / blood
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Radioligand Assay


  • Autoantibodies
  • Glutamate Decarboxylase