Abstracts

Rationale: Autoantibodies to neuronal proteins contribute to the pathological process in an increasing number of childhood and adult epileptic syndromes and in encephalitic seizure-related disorders. Recently, antibodies to leucine-rich glioma inactivated 1 (LGI1), a protein within the voltage-gated potassium channel complex (VGKC), were identified in patients with faciobrachial dystonic seizures (FBDS). This represents the first clinically-distinctive immunotherapy-responsive adult-onset epilepsy syndrome. In this study we examined the prevalence of these and other antibodies to neuronal proteins in cohorts of patients with recent and with long standing epilepsies. Methods: Serum samples were collected from newly-diagnosed epilepsy patients, taken before the start of a clinical treatment trial (n=181) and from a cohort of consecutive epilepsy patients attending specialist clinics (n=235). All were tested for antibodies to the NMDA receptor, VGKC-complex, GAD and the glycine receptor using cell-based or radioimmunoprecipitation assays Results: Antibodies were detected in 46/416 (11%) of patients, compared to less than 0.5% in controls. The most common antibody was to the VGKC-complex in 21 patients (5% of all patients). Antibodies to the NMDA-receptor (1.7%), glutamic acid decarboxylase (1.7%) and the glycine receptor (2.8%) were also detected. Antibodies were slightly more frequent in patients with duration of diagnosis of less than one year (13.4%) compared to patients of duration over 1 year (10.1%). There was a significantly higher incidence of positive antibodies in patients with cryptogenic rather than symptomatic LRE (15 vs 7%) Of the recent-onset patients, 10 antibody positive patients (50%) were nonresponsive to their first ever AED compared with 51/161 (31.6%) of patients without detected antibodies. Conclusions: The results suggest an immune-mediated component in some forms of epilepsy, although further studies will be required to establish whether the antibodies are directly pathogenic or merely markers of a secondary immune response.