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

Background: Autoantibodies to glutamic acid decarboxylase (GAD-A) are prese nt in type 1 diabetes and stiff man syndrome (SMS), and have also been repo rted in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SM S and GAD-A, implying that epilepsy sometimes is associated with anti-GAD a utoimmunity. Methods: The authors investigated the prevalence of GAD-A in p atients with therapy-resistant localization-related epilepsy (n = 51) and g eneralized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant hu man GAD65. Results: GAD-A were found in eight patients with localization-re lated epilepsy, whereas none of the patients with generalized epilepsy, oth er 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 patie nts 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 i mmunohistochemistry and immunoblotting. Both of them had longstanding thera py-resistant temporal lobe epilepsy but did not have diabetes. One had a hi story of autoimmune disease, whereas the other had serologic evidence of mu ltiple autoantibodies without any clinical signs of autoimmune disease. Con clusions: GAD autoimmunity may be associated with refractory localization-r elated epilepsy.