Pragmatic screening for autoimmune‐associated epilepsy in drug‐resistant epilepsy of unknown etiology in resource‐limited settings: A hypothesis‐generating study

Abstract Objective To evaluate the feasibility of investigating autoimmune etiology in adults with drug‐resistant epilepsy (DRE) of unknown origin in resource‐limited settings and to develop a pragmatic, hypothesis‐generating screening approach to guide autoantibody testing. Methods A prospective observational study including adults with DRE of unknown etiology was conducted at a tertiary epilepsy center in Brazil. All patients underwent standardized assessment including inflammatory and autoimmunity markers, brain magnetic resonance imaging (MRI), electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, and application of the APE2 and ACES scores. Clinical, laboratory, and imaging findings were analyzed in the context of published autoimmune‐associated epilepsy (AAE) profiles to inform a pragmatic screening strategy. Results Twenty‐six patients (46.2% female; median epilepsy duration: 18.5 years) were included. EEG findings were nonspecific. Six patients developed mesial temporal abnormalities on follow‐up MRI. CSF protein elevation was observed in 37.5%, oligoclonal bands in 13.6%, and elevated IgG index in 18.2%. Antinuclear antibodies were detected in 26.9%. APE2 score ≥ 4 was present in 57.7%, while ACES score ≥ 2 occurred in 11.5%. Due to limited access to antibody testing, only one patient underwent CSF autoantibody analysis, confirming high‐titer anti‐GAD65. Based on integrated clinical, laboratory, and imaging findings, a pragmatic screening algorithm was proposed to prioritize candidates for autoantibody testing. Significance In resource‐limited settings, systematic use of accessible clinical and laboratory markers may help identify patients with higher pre‐test probability of AAE. A pragmatic screening approach may improve diagnostic efficiency and support individualized decision‐making when comprehensive antibody testing is not readily available.