ABSTRACT Epilepsy is a common neurological disorder with a substantial global burden. Despite major advances in diagnosis and therapy, nearly one‐third of patients remain resistant to antiseizure medications, highlighting persistent gaps in understanding epileptogenesis and disease progression. Here, we review epidemiological evidence, time‐dependent seizure patterns, and pathogenic mechanisms that contribute to epilepsy. We discuss how genetic variants, ion‐channel dysfunction, altered synaptic transmission, neuroinflammation, metabolic and mitochondrial stress, structural remodeling, network reorganization, and epigenetic regulation converge to destabilize neural circuits. These processes interact across disease stages and promote persistent hyperexcitability. We further summarize how mechanistic advances are reshaping clinical management, including precision diagnostics, pharmacotherapy, surgery, neuromodulation, dietary and lifestyle intervention, chronotherapy, biomarker‐guided stratification, and emerging disease‐modifying approaches such as immunotherapy, pathway‐targeted treatment, RNA‐based therapeutics, and gene‐directed strategies. Data‐driven tools for seizure detection and forecasting are also discussed as complementary approaches for individualized care. Overall, current evidence supports a shift from empirical seizure suppression toward mechanism‐guided and individualized care. Future progress will require closer integration of molecular discovery, validated biomarkers, and real‐world implementation to achieve earlier, more equitable, and potentially disease‐modifying treatment.
Liu et al. (Tue,) studied this question.