Glutamic acid decarboxylase (GAD) antibodies in epilepsy: Diagnostic yield and therapeutic implications

PURPOSE The aetiology of adult onset epilepsy remains unascertained in a significant proportion of patients. Antibodies directed against neuronal antigens have been suggested to have a potential pathogenic role in some cases of epilepsy. We describe a series of patients with adult onset epilepsy in whom antibodies to glutamic acid decarboxylase (GAD Abs) have been identified. METHODS All patients attending a regional epilepsy service with unexplained adult onset epilepsy' were tested for the presence of GAD Abs. Those with high serum titres underwent CSF analysis, and were offered additional treatment with immunotherapy. Those who underwent immunotherapy were monitored by monthly review. Clinical details and response to treatment was collated by review of notes. RESULTS Of 112 patients tested, high serum titres were found in 6 (5.4%) patients. These patients had clinical and electroencephalographic evidence of focal epilepsy. CSF analysis revealed oligoclonal bands and intrathecal GAD Abs in all patients. Five patients received immunotherapy. No improvement in seizures was observed in any. One patient with equivocal MRI evidence of hippocampal sclerosis and concordant video EEG and PET scan, achieved 12 months seizure freedom following temporal lobectomy. CONCLUSIONS The relevance of GAD Abs to epilepsy remains uncertain. Our experience does not support the routine use of immunotherapy in patients with epilepsy and GAD Abs. Larger studies enrolling greater numbers of patients are required to identify sufficient numbers of patients for controlled treatment trials.