EEG Markers of Treatment Resistance in Idiopathic Generalized Epilepsy: From Standard EEG Findings to Advanced Signal Analysis

Idiopathic generalized epilepsy (IGE) represents a common form of epilepsy in both adult and pediatric epilepsy units. Although IGE has been long considered a relatively benign epilepsy syndrome, a remarkable proportion of patients could be refractory to treatment. While some clinical prognostic factors have been largely validated among IGE patients, the impact of routine electroencephalography (EEG) findings in predicting drug resistance is still controversial and a growing number of authors highlighted the potential importance of capturing the sleep state in this setting. In addition, the development of advanced computational techniques to analyze EEG data has opened new opportunities in the identification of reliable and reproducible biomarkers of drug resistance in IGE patients. In this manuscript, we summarize the EEG findings associated with treatment resistance in IGE by reviewing the results of studies considering standard EEGs, 24-h EEG recordings, and resting-state protocols. We discuss the role of 24-h EEG recordings in assessing seizure recurrence in light of the potential prognostic relevance of generalized fast discharges occurring during sleep. In addition, we highlight new and promising biomarkers as identified by advanced EEG analysis, including hypothesis-driven functional connectivity measures of background activity and data-driven quantitative findings revealed by machine learning approaches. Finally, we thoroughly discuss the methodological limitations observed in existing studies and briefly outline future directions to identify reliable and replicable EEG biomarkers in IGE patients.