GAD65 Autoimmune-Associated Epilepsy: Pathophysiology, Diagnosis, and Treatment

GAD65 autoimmune-associated epilepsy (AAE) is an underrecognized cause of epilepsy with common delays to immunotherapy. We review advances in its pathophysiology, diagnosis and management.

GAD65 AAE predominantly affects young women, presenting as drug resistant temporal lobe epilepsy (TLE), often without mesial temporal sclerosis. Patients lie within a continuum where T cell mediated inflammation predominates in early disease, temporally overlapping with progressive structural injury, which leads to chronic epilepsy. Diagnosis is supported by high-level antibody detection in serum (RIA > 20 nmol/L or > 2000 U/mL, ELISA > 10,000 IU/mL), and in select cases CSF testing may be helpful. Treatment requires both immunotherapy and antiseizure medications. Immunotherapy response is greatest in early disease but can occur at later stages. Epilepsy surgery workup and neuromodulation may benefit some patients, although seizure freedom is rare. GAD65 AAE can resemble non-autoimmune TLE. Phenotype-based antibody testing and early recognition are important to guide timely, individualized treatment.