Neuropathological findings in 2068 individuals with drug‐resistant epilepsy based on updated classification systems: A multicenter retrospective cohort study from China

Abstract Objective This study was undertaken to investigate the histopathological spectrum of drug‐resistant epilepsy (DRE) in a large Chinese surgical cohort using updated World Health Organization (WHO) and International League Against Epilepsy (ILAE) classifications, and to examine its associations with seizure onset age, lesion location, and postoperative seizure outcomes. Methods This retrospective, multicenter cohort study consecutively enrolled individuals who underwent resective epilepsy surgery between January 2011 and December 2020 at three Chinese hospitals. Histopathological diagnoses were updated by two independent neuropathologists based on the 2021 WHO and 2022 ILAE classifications, supplemented by immunohistochemistry and whole exome sequencing when indicated. Postoperative seizure outcome data were collected from medical records and telephone follow‐up, with the primary outcome defined as Engel class I at 1, 2, and 5 years after surgery, and Engel class Ia assessed as a secondary outcome. Results Of 2099 surgically treated individuals, 2068 with complete data were included. The predominant pathologies were hippocampal sclerosis (HS; 28.4%), epilepsy‐related tumors (20.7%), and malformations of cortical development (MCD; 15.4%). Childhood onset epilepsy was associated with MCD and HS, whereas adult onset cases favored non‐low‐grade epilepsy‐related tumors and vascular malformations, with developmental lesions presenting earliest. Whole exome sequencing confirmed mTOR pathway variants in 65.2% of focal cortical dysplasia II cases and SLC35A2 mutations in 62.5% of mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy cases. Among 293 individuals with complete 1‐, 2‐, and 5‐year outcome data (284 included in the adjusted prognostic model), no‐lesion cases had significantly lower odds of Engel class I at 5 years than HS (odds ratio [OR] = .21, 95% confidence interval [CI] = .08–.56, p = .002). Temporal lobe location predicted favorable Engel class I outcome (OR = 2.78, 95% CI = 1.31–5.90, p = .008). Engel class Ia results were not statistically significant. Significance Applying the updated WHO and ILAE classifications in this Chinese surgical cohort helps to characterize the pathological spectrum of DRE and may assist in postoperative outcome evaluation.