Autoimmune mechanisms in drug-resistant focal epilepsy: Pathophysiology, biomarkers, and therapeutic implications

This review explores the role of autoimmune mechanisms in drug-resistant epilepsy (DRE), with emphasis on etiology, mechanisms of drug resistance, and potential immunomodulatory interventions. A structured review of clinical and experimental studies was conducted to assess current knowledge on the interplay between molecular mechanisms and immune responses in DRE. Particular attention was given to the involvement of the mTOR pathway, blood-brain barrier (BBB) dysfunction, astrocyte activation, and overexpression of efflux transporters, as well as the presence of neuronal autoantibodies such as N-methyl-D-aspartate receptor (NMDAR) and GluR3. The available evidence suggests that, although conventional pharmacologic approaches fail in a subset of patients, immunologic diagnostics and targeted therapies - including intravenous immunoglobulin, corticosteroids, rituximab, and plasmapheresis - may provide clinical benefit. Seizure reduction has been reported in selected patients; however, therapeutic response remains heterogeneous and is limited by small study populations. In conclusion, early identification of autoimmune mechanisms in DRE may help optimize treatment strategies, improve patient outcomes, and reduce the long-term clinical and societal burden of the disease.