Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis

Abstract Objective Antibodies to glutamic acid decarboxylase (GAD) have been described in a few patients with temporal lobe epilepsies consistent with limbic encephalitis (LE). We studied a cohort of patients with recent‐onset temporal lobe epilepsy caused by LE to test for GAD antibody positivity and response to immunotherapies. Methods Over a period of 3.75 years, 138 patients aged ≥18 years investigated at the Department of Epileptology, University of Bonn, for recent‐onset epilepsy were prospectively collected and studied for cliniconeuroradiological features of LE, autoantibodies, and treatment responses. Results Fifty‐three adult patients fulfilled the criteria for LE: (1) limbic signs and symptoms for ≤5 years and (2) brain MRI revealing mediotemporal encephalitis (T2/fluid attenuated inversion recovery hyperintensity without atrophy). Nine had high‐titer GAD antibodies; 10 had voltage‐gated potassium channel (VGKC) antibodies. Patients with GAD antibodies were younger (median age, 23 years; range, 17‐66 years) ( p = 0.003) and presented with seizures only, whereas polymorphic limbic features were more common in the VGKC antibody‐positive group ( p < 0.001). None had tumors. Patients with GAD antibodies more frequently had cerebrospinal fluid oligoclonal bands ( p = 0.009) and intrathecal secretion of the specific antibody ( p = 0.01). Following monthly intravenous methylprednisolone pulses, GAD antibodies remained highly elevated in 6/6 patients, whereas VGKC antibodies normalized in 6/9 patients ( p = 0.03). Despite more intense anticonvulsive treatment in the GAD antibody‐positive group ( p = 0.01), none of these patients became seizure free, unlike all of the patients with VGKC antibodies ( p < 0.001). Interpretation High‐titer GAD antibodies define a form of nonparaneoplastic LE. This is a chronic, nonremitting disorder and should be included in the differential diagnosis of patients with TLE and mediotemporal encephalitis. Therapeutic trials of other immunotherapies should be undertaken. ANN NEUROL 2010;67:470–478