Data-Driven Clinical Phenotyping of Adult Epilepsy Using Latent Class Analysis: A Regional Cohort Study from Southern...

Background/Objectives: Adult epilepsy is clinically heterogeneous, and individual clinical predictors may not fully capture the multidimensional burden associated with drug-resistant epilepsy (DRE). This study aimed to identify latent clinical phenotypes in adults with epilepsy and examine their cross-sectional associations with DRE and broader disease burden. Methods: This regional observational cohort study used a source database of 1100 patients with epilepsy. After excluding two patients aged <18 years, the adult analytic cohort included 1098 patients. Complete-case latent class analysis (LCA) was performed in 1054 patients using age at onset, disease duration, seizure type, seizure frequency, serial seizures/status, postictal confusion, neurological status, neuroimaging category, and number of antiseizure medications. Model selection was based on statistical fit, class size, and clinical interpretability. Internal clinical validation outcomes included DRE, quality of life, cognitive screening, and stigma scores. Post hoc characterization described the classes by epilepsy etiology, derived epilepsy type, and seizure categories aligned with current terminology. Results: A three-class solution was selected, with class sizes of 314, 465, and 275. DRE prevalence increased stepwise across classes: 5.7%, 14.2%, and 33.1%, respectively (p < 0.001). In adjusted analysis, Class 2 had higher odds of DRE than Class 1 (odds ratio 2.70, 95% confidence interval 1.56-4.67), while Class 3 showed the strongest association (odds ratio 8.19, 95% confidence interval 4.15-16.16; both p < 0.001). Higher-burden classes showed lower quality-of-life and cognitive scores and higher stigma scores. Conclusions: LCA identified three clinically interpretable, burden-enriched phenotypic profiles associated with a stepwise gradient in DRE and broader multidimensional disease burden. These cross-sectional profiles may provide a useful framework for describing clinical heterogeneity in adult epilepsy and generating hypotheses for future validation studies.