Cenobamate modulates EEG cortical activity and connectivity in individuals with drug-resistant epilepsy: a pharmaco-EEG study.

Abstract

Objective: Quantitative electroencephalography (qEEG) metrics are demonstrated to correlate with and predict clinical response in individuals with epilepsy. Cenobamate is an effective anti-seizure medication recently approved as an add-on therapy for individuals with epilepsy, but its effects on qEEG are unknown. We aimed to evaluate the modulation of qEEG metrics induced by cenobamate and its relationship with clinical response.

Methods: We performed a prospective study with a cohort of 18 individuals with epilepsy (8 women, 47 ± 16 years old) and 25 healthy subjects (HS). They underwent a 19-channel EEG before and 6 months after cenobamate administration. Power spectral density (PSD) and phase locking value (PLV) for delta, theta, alpha, beta, and gamma frequency bands were calculated. Correlation analysis and analysis of covariance exhibited significant cenobamate-induced changes in qEEG and their relationship with seizure frequency changes. A regression analysis was performed to evaluate the association with clinical responders.

Results: A total of 11 out of 16 individuals with epilepsy (69%, with 2 dropping out) were cenobamate responders (≥50% seizure frequency reduction). Cenobamate did not modify any PSD parameter but induced significant changes in PLV levels (p < 0.01). A decrease in PLV correlated with seizure reduction (p < 0.03). Regression analysis showed a strong association between PLV modulation and cenobamate responsiveness (a sensitivity of 0.75, a specificity of 0.84, and an accuracy of 0.81).

Conclusion: Cenobamate induces an EEG connectivity modulation that is highly associated with cenobamate clinical response.

Significance: Connectivity analysis of pharmaco-EEG can provide new hints toward the development of innovative biomarkers and precision medicine in individuals with epilepsy.