Abstracts

Rationale: Previous reports have observed an association between focal drug resistant epilepsy and antibodies to glutamic acid decarboxylase (anti-GAD). GAD catalizes the synthesis of gammaaminobutyric acid (GABA) , the mayor inhibitory neurotransmitter in the central nervous system. Anti-GAD are markers for type I diabetes mellitus insulin dependent (DM1) and, in high levels, anti-GAD have been found in several neurological diseases including stiff-person syndrome, cerebelar ataxia, limbic encephalitis, and focal epilepsy. Purpose: To describe the clinical and immunological profile of a series of patients with temporal lobe epilepsy with anti-GAD Methods: A basic immunological battery including serum anti-GAD were determined in all patients with cryptogenic temporal lobe epilepsy with age at onset older than 20. Anti-GAD antibodies were analyzed by RIA; values >1UI/ml considered positive. Serum and CSF (when available) of anti-GAD-positive patients were also studied by immunohistochemistry on HEK293 cells transfected with the B1 and B2 subunits of the GABAB receptor (GABABR). Results: Eight (6 women) of 45 screened patients, were anti-GAD positive (17.7%). Mean age 57 (29-75) years, mean age at epilepsy onset 50 (27-70) years. None reported initial precipitating injury. Brain MRI was pathologic in only 1 patient: right hippocampal hyperintensity on FLAIR sequences. Brain positron emission tomography (PET) with fluodesoxiglucose was done in 2 patients showing unilateral medial temporal hypometabolism. Epilepsy was controlled in 4 patients (<1 seizure/6 month), and considered pharmacoresistant in 4 (50%). Three patients (37.5%) referred important memory impairment since the beginning of the epilepsy and three a mayor depressive episode. Seven patients (87.5%) reported one or more concomitant autoimmune diseases (DM1: 4, hypothyroidism 4, myasthenia 1, rheumatoid arthritis 1, celiac disease 1, lupus 1, polyglandular autoimmune disease 1). One patient with pharmacoresistant epilepsy was treated with corticoids and immunoglobulins with only transient improvement. Anti-GAD levels ranged between 42 and 100.000 UI/ml. CSF, done in 4 patients, did not show positive oligoclonal bands or pleocytosis, The ratio of serum/CSF anti-GAD levels did not support a specific intrathecal synthesis of anti-GAD in any patient. None of the patients had concurrent GABABR antibodies. Conclusions: Focal epilepsy with antiGAD antibodies is not rare. The epilepsy it is not always pharmacoresistant and is often associated with memory impairment, depression and other autoimmune diseases.