Lacosamide modulates alpha-band network hubness: a quantitative EEG study in drug-Naïve focal epilepsy

Objective: This study investigates pharmaco-EEG changes induced by Lacosamide (LCM) in drug-naive people with focal epilepsy (PwE) and explores the association between quantitative EEG (qEEG) and long-term clinical outcome. Methods: We retrospectively identified 28 PwE and 25 healthy controls (HC). PwE were classified as seizure-free (SF) or non-seizure-free (NSF) after two years of LCM. EEGs were acquired before and ∼ 6 months after LCM. Power spectral density (PSD), amplitude-envelope correlation (AEC), and graph-theoretical metrics were compared between PwE and HC. Logistic regression was employed to examine the association between long-term outcomes (two-year seizure freedom) and qEEG metrics, in combination with clinical variables (sex, aetiology, seizure type, baseline EEG). Results: LCM did not significantly modify global-averaged qEEG metrics (p > 0.05). Theta-band PSD was higher in PwE than HC. PwE exhibited higher alpha-band betweenness centrality (BtwC) than HC only before LCM (p = 0.007). Alpha-band BtwC provided the greatest discriminative value for seizure freedom (accuracy = 0.86; area under the curve [AUC] = 0.88). Conclusions: Although no significant differences were observed between pre- and post-LCM conditions, alpha-band BtwC showed a return toward a more physiological state after treatment, suggesting partial network normalization. Combining qEEG with clinical data improved long-term outcome discrimination, with alpha-band BtwC as the most relevant feature. Significance: Graph-theoretical qEEG metrics offer additional insight into LCM's neurophysiological effects in focal epilepsy.