Autoantibodies to glutamic acid decarboxylase (GAD) in focal and generalized epilepsy: A study on 233 patients.

Background: Autoantibodies to glutamic acid decarboxylase (GADA) have been associated to a wide range of neurologic conditions, including epilepsy. However, the spectrum of epileptic conditions associated with GADA is not completely established. We aimed to determine the occurrence of GADA in a large series of patients with different epilepsy types. Moreover, we assessed whether specific subgroups of patients are associated to GAD autoimmunity.

Methods: GADA were measured by radioimmunoassay in a series of consecutive unselected epileptic patients observed over a 2-years-period. Patients with neuromuscular features, acute or subacute encephalopathic course, cognitive deterioration or psychiatric symptoms were excluded.

Results: Two hundred thirty-three patients (121 women, mean age: 29.3 years; range: 6-78) were recruited. There were eighty-three (35.6%) patients with idiopathic (66 generalized, 17 focal) epilepsy; fifty-nine (25.3%) with cryptogenic (52 focal, 7 generalized) epilepsy, and ninety-one (39.0%) with symptomatic (75 focal, 16 generalized) epilepsy. GADA were detected in six (2.58%) patients. Two had idiopathic generalized epilepsy associated with diabetes mellitus type 1 (DM1); the other four patients suffered from cryptogenic temporal epilepsy and no history or signs of DM1. GADA positive patients could not be distinguished by seizure frequency or number of AEDs. However, in these cases, the mean epilepsy duration (8.5+/-5.0 years) was shorter compared to the other 48 GADA-negative patients with cryptogenic focal epilepsy (17.3+/-9.6) (p<0.0001).

Conclusions: We confirm that GAD autoimmunity may be associated with some forms of epilepsy. The preferential identification in patients with cryptogenic temporal epilepsy deserves particularly further investigation.