Journal
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
Volume 99, Issue -, Pages 16-23Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.seizure.2022.04.013
Keywords
Key words for use by abstracting services; AMPA; glutamate; third-generation anti-seizure drugs; heart rate variability; autonomic control
Categories
Funding
- Italian Department of Health [RF-2013-02358785, NET-2011-023467841]
- AIRAlzh Onlus (ANCC-COOP)
- European Union [84166]
- Alzheimer's Association [18PTC-19-602325]
- Alzheimer's Association-GAAIN Exploration to Evaluate Novel Alzheimer's Queries [GEENA-Q-19-596282]
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The temporal lobe plays a central role in regulating the Central Autonomic Network and cardiovascular functions. This study suggests that Perampanel (PER) may increase vagal tone and have a cardioprotective effect by reducing the risk of cardiac arrhythmias.
Objective: 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). Methods: 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. Results: At baseline no differences were detected between PER group and No-PER group according to timedomain 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<0.001), HF n.u. (p=0.001), HF% (p=0.002) with increased values, and for LnLF (ms2) (p=0.001), LF n.u. (p=0.001), LF% (p=0.01), and LF/HF (p<0.001) with reduced values. The change in seizure frequency after add-on therapy was comparable between the two groups (p=0.81) Conclusions: Our data support the notion that PER increases the vagal tone in DRTLE. This activity may exert a cardioprotective effect by reducing the risk of developing cardiac arrhythmias. Furthermore, given the correlations between HRV modifications and the occurrence of SUDEP, future studies will need to test the protective effects of PER on SUDEP.
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