# Cortical Excitability Before and After Long‐Term Perampanel Treatment for Epilepsy

## TL;DR

This study examines how perampanel, a medication for epilepsy, affects brain excitability over time using transcranial magnetic stimulation.

## Contribution

The study identifies motor cortex excitability as a potential biomarker for tracking perampanel treatment outcomes in epilepsy.

## Key findings

- In responders, motor cortex excitability increased significantly with higher perampanel doses.
- Nonresponders showed no significant changes in motor cortex excitability.
- TEPs showed no significant differences between measurements or groups.

## Abstract

Antiseizure medications (ASMs), which may influence cortical excitability, are the mainstay of epilepsy treatment. Transcranial magnetic stimulation (TMS) helps evaluate cortical excitability. We assessed changes in TMS responses using serial TMS measurements in people treated with an adjunctive noncompetitive AMPA‐receptor antagonist.

We included adults with refractory, active epilepsy (≥ 1 seizure/month), advised to start adjunctive treatment with the noncompetitive AMPA‐receptor antagonist perampanel as outpatients. After informed consent, we performed TMS measurement at three points: baseline before starting perampanel, at around 2 months after starting (4 mg/day), and at a final/effective dose around 6 months. Dependent on seizure reduction (> 50%), participants were dichotomized into responders (Rs) and nonresponders (NRs). We compared changes in motor cortex excitability through the rMT using a linear mixed‐effects model. We evaluated TMS‐evoked potentials (TEPs) to single pulse and paired pulse using within‐subject Monte Carlo–based permutation analysis.

We included 18 adults, of whom 17 (6 R, 11 NR, 1 lost to follow‐up) had baseline and second‐month measurements, and nine (4 R, 5 NR) had all three. In responders, motor cortex excitability, quantified by rMT, significantly increased with increasing dose. Conversely, no significant changes were seen in the NR subgroup. TEPs for the single pulse and paired pulse showed no significant clusters for any peaks between measurement and group comparisons.

The TEPs showed no significant changes between measurements and/or groups. Motor cortex excitability quantified by rMT is a potential biomarker to track or predict treatment outcomes in people starting adjunctive perampanel for epilepsy.