Antibody Prevalence in Epilepsy before Surgery (APES) in drug‐resistant focal epilepsy

Objective There is a growing recognition of immune‐mediated causes in patients with focal drug‐resistant epilepsy (DRE); however, they are not systematically assessed in the pre‐surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune‐mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies. Methods We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. Results` A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub‐cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)–specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80. Significance Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune‐mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre‐surgical evaluation for focal refractory epilepsy with unknown cause.