Abstracts

Rationale: Different autoantibodies have been found to be associated with epilepsy. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the conversion of L-glutamic acid to inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In addition to insulin-dependent diabetes mellitus (IDDM) and stiff person syndrome (SPS), antibodies to GAD have also been found in single patients with epilepsy, but the clinical determinants of epilepsy associated with GAD-antibodies (GAD-A) are still lacking. Methods: We measured GAD-A with a radioimmunoassay (RIA) in sera of 275 well-evaluated patients with refractory focal or primarily generalized epilepsy. The positive samples were confirmed by immunohistochemistry (IHC) and Western blotting (WB). Epilepsy was classified based on patient history, seizure semiology and high resolution brain MRI. The possibility of brain atrophy in MRI was evaluated in the patients with increased level of GAD-A. Results: 15 patients had increased levels of GAD-A. 7 patients had high level of GAD-A similar to SPS, 6 of them having temporal lobe epilepsy (TLE) (Table). In the patient with IGE (GAD-A 24124 U/ml) the syndrome type classification was difficult with features of both primarily generalized and focal seizures. 8 patients had low level of GAD-A similar to IDDM. The patients with high levels of GAD-A had antibodies both in serum and cerebrospinal fluid (CSF) by immunohistochemistry (Figure) and immunoblotting. the prevalence of increased level of GAD-A was 2.3 times higher in the patients with TLE that in the patients with extra-TLE, although the association was not statistically significant (OR: 2.35, 95% CI: 0.49-11.20; P =0.282). Conclusions: The prevalence of high levels of GAD-A was increased in the subgroup of patients with TLE, characterized with refractory epilepsy. The abundance of projections from medial temporal lobe to other areas in the brain may explain the increased levels of GAD-A specifically in TLE. The finding supports the possibility of immunological alteration in some patients with epilepsy. In patients with high level GAD-A the finding could be confirmed by IHC and WB. It is concluded that patients with epilepsy and GAD-A in RIA should be tested for both IHC and WB.