Low rate of glutamic acid decarboxylase 65 (GAD-65) antibodies in chronic epilepsy

Autoantibodies against glutamic acid decarboxylase 65 (GAD-65) have been identified in patients with chronic epilepsy. In this study, we ask (1) what is the frequency of GAD-65 antibodies in chronic epilepsy? (2) what is the frequency and type of epilepsy in individuals with GAD-65 antibodies?

For cohort 1, serum samples of patients with epilepsy (without type I diabetes) were obtained from our biobank. Samples were tested for GAD-65 antibodies using a cell-based assay and confirmed by immunohistochemistry. For cohort 2, patients with positive GAD-65 antibodies were identified and their medical records were reviewed for the presence and characteristics of epilepsy.

Cohort 1 included 270 patients, of which 53% were women; median age was 47 years; median duration of epilepsy was 16 years. Epilepsy was focal in 87% (temporal lobe in 20%), and drug-resistant in 45%. GAD-65 antibodies were present in two out of 270 cases (0.7%) and zero controls. Cohort 2 consisted of 23 patients with known GAD-65 antibodies, of which ten had epilepsy (43%). Of these, 80% were women with a median age of 40 years and a median duration of epilepsy of 18 years. All ten patients had focal epilepsy, nine had temporal lobe epilepsy, and seven were drug resistant.

In patients with chronic epilepsy, the frequency of GAD-65 antibodies detected with our cell-based assay was substantially lower than previously reported with use of other methods. When present, GAD-65 antibodies are associated with drug-resistant temporal lobe epilepsy. GAD-65 positive epilepsy patients merit further investigation.