Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal...

Glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibodies have been associated with multiple nonneurological and neurological syndromes including autoimmune epilepsy (AE). Although immunotherapy remains the cornerstone for the treatment of AE, those with GAD65 Ab-associated AE (GAD65-AE) remain refractory to immunotherapy and antiseizure medication (ASM). Outcomes of epilepsy surgery in this patient population have also been unsatisfactory. The role of neuromodulation therapy, particularly direct brain-responsive neurostimulation therapy, has not been previously examined in GAD65-AE. Here, we describe four consecutive patients with refractory GAD-65-associated temporal lobe epilepsy (GAD65-TLE) receiving bilateral hippocampal RNS System treatment. The RNS System treatment was well tolerated and effective in this study cohort. Three patients had a >50% clinical seizure reduction, and one patient became clinically seizure-free following resective surgery informed by the RNS System data with continued RNS System treatment. In all four of our patients, the long-term ambulatory data provided by the RNS System allowed us to gain objective insights on electrographic seizure lateralization, patterns, and burden as well as guided immunotherapy and ASM optimization. Our results suggest the potential utility of the RNS System in the management of ASM intractable GAD65-AE.