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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Epilepsy
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1502668
This article is part of the Research Topic Pharmaco-Resistance in Epileptic Conditions View all articles

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

Provisionally accepted
Giovanni Assenza Giovanni Assenza 1,2*Biagio Sancetta Biagio Sancetta 1Lorenzo Ricci Lorenzo Ricci 1Carlo Vico Carlo Vico 1Flavia Narducci Flavia Narducci 1Marilisa Boscarino Marilisa Boscarino 1Jacopo Lanzone Jacopo Lanzone 3Pierantonio Menna Pierantonio Menna 4Claudio Liguori Claudio Liguori 5Francesca Izzi Francesca Izzi 6Nicola Biagio Mercuri Nicola Biagio Mercuri 6Vincenzo Di Lazzaro Vincenzo Di Lazzaro 1Mario Tombini Mario Tombini 1
  • 1 Research Unit of neurology, Department of Medicine and Surgery, Campus Bio-Medico University, Rome, Italy
  • 2 Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Lazio, Italy
  • 3 Neurology Unit, San Raffaele Scientific Institute (IRCCS), Milan, Lombardy, Italy
  • 4 Operative Research Unit of Clinical Pharmacology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
  • 5 Sleep Medicine Centre, Neurology Unit, University Hospital of Rome Tor Vergata, Rome, Italy
  • 6 Sleep Medicine Centre, University Hospital of Rome Tor Vergata, Rome, Sicily, Italy

The final, formatted version of the article will be published soon.

    Objective: Quantitative electroencephalography (qEEG) metrics are demonstrated to correlate with and predict clinical response in people with epilepsy. Cenobamate is an effective antiseizure medication recently approved as add-on therapy for people with epilepsy (people 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.We performed a prospective study with a cohort of 18 people with epilepsy (8 females, 47±16 years old) and 25 healthy subjects (HS). They underwent 19-channel EEG before and 6 months after cenobamate. 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 tested 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: 11/16 people with epilepsy (69%, 2 dropped 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). PLV decrease correlated with seizure reduction (p<0.03). Regression analysis showed a strong association between PLV modulation and cenobamte responsiveness (sensitivity 0.75, specificity 0.84, accuracy 0.81) Conclusions: Cenobamate induces an EEG connectivity modulation which is highly associated with cenobamate clinical response. Significance: Connectivity analysis of pharmaco-EEG can provide new hints toward the development of innovative bio-markers and precision medicine in people with epilepsy.

    Keywords: Cenobamate, pharmaco-EEG, EEG connectivity, Drug-resistant epilepsy, response biomarker

    Received: 27 Sep 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Assenza, Sancetta, Ricci, Vico, Narducci, Boscarino, Lanzone, Menna, Liguori, Izzi, Mercuri, Di Lazzaro and Tombini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Giovanni Assenza, Research Unit of neurology, Department of Medicine and Surgery, Campus Bio-Medico University, Rome, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.