Perampanel enhances the cardiovagal tone and heart rate variability (HRV) in patients with drug-resistant temporal lobe epilepsy

•Anti-seizure medication (ASM) can alter Heart Rate Variability (HRV) and vagal output.•The blockade of glutamatergic pathways in the temporal lobe affects cardio-autonomic control.•A reduction of HRV and vagal output can increase the risk of arrhythmia and cardiovascular dysfunction.•Perampanel increases the cardio vagal tone in patients with drug-resistant temporal lobe epilepsy (DRTLE).•Add-on therapy with Perampanel may be cardioprotective in patients suffering from DRTLE. The temporal lobe plays a central role in the regulation of the "Central Autonomic Network" and cardiovascular functions. The blockade of glutamatergic pathways in the temporal lobe affects cardio-autonomic control. Perampanel (PER) is a non-competitive agonist of the AMPA receptor. This study evaluated PER effects on cardiac autonomic control in patients affected by drug-resistant TLE (DRTLE). We enrolled 40 adults with DRTLE treated with PER as add-on therapy (PER group) and 32 DRTLE age, sex, and seizure-frequency matched controls treated with different additional anti-seizure medication (ASM) as add-on therapy (No-PER group). HRV analysis was performed on 5-minute EKG recording in resting state before and 6-months after the introduction of add-on ASM. Linear Mixed Models (LMM) were used to analyzed HRV variables according to time (baseline and 6-months follow-up) and groups. At baseline no differences were detected between PER group and No-PER group according to time-domain and frequency-domain HRV parameters. At the follow-up, in PER group a multiplicative effect for the interaction between treatment and time was observed for MeanRR (ms) (p=0.03), LnRMSSD (ms) (p=0.04), LnHF (ms2) (p