Qualitative EEG morphology predicts early Antiseizure medication response in newly diagnosed epilepsy: A prospective...

Epilepsy is a complex neurological disorder with diverse electroclinical characteristics. While diagnosis is guided by the ILAE 2025 classification, the prognostic value of specific interictal epileptiform discharge (IED) morphologies for initial antiseizure medication (ASM) selection remains incompletely characterized.

To determine whether qualitative EEG characteristics at diagnosis predict early ASM responsiveness across six major epilepsy syndromes.

In this prospective cohort study, 150 newly diagnosed, drug-naïve patients (25 per syndrome) including Focal Epilepsy, FBTCS, BECTS, CAE, GGE, and JME underwent standardized baseline EEG with activation procedures. ASMs were prescribed according to routine clinical practice. Follow-up clinical evaluation and EEG were performed at 3 months. The primary outcome was EEG normalization; secondary outcomes included ≥50% seizure reduction and seizure freedom.

EEG normalization rates varied significantly across syndromes, ranging from 76% in CAE to 20% in FBTCS. Qualitative IED morphology was associated with normalization (p < 0.01). Patients achieving EEG normalization at 3 months were significantly more likely to be seizure free (p < 0.001).

In well-defined electroclinical syndromes, qualitative IED morphology appears to provide additional prognostic information regarding early ASM response. These findings suggest that EEG morphology may complement syndrome-based assessment and that variability in spike and sharp-wave morphology may reflect underlying electrophysiological heterogeneity extending beyond fixed syndrome labels, supporting further investigation using standardized morphology analysis in larger, controlled studies.