Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. The temporal lobe plays a central role in the regulation of the "Central Autonomic Network," a complex system that encompasses cortical, midbrain, and brainstem regions that regulate autonomic cardiovascular functions (Figure 1). Clinical and experimental data show that the temporal lobe's pathological involvement can generate a broad spectrum of cardiac abnormalities, including heart rate changes, abnormal atrioventricular conduction, and ventricular repolarization. Glutamate receptors are widely expressed throughout the CAN. The blockade of glutamatergic pathways in the temporal lobe affects cardio-autonomic control. Perampanel (PER) is a non-competitive agonist of the AMPA receptor, an ionotropic glutamatergic subtype. This study aims to evaluate PER effects on cardiac autonomic control in patients affected by drug-resistant TLE.

Methods: We enrolled forty adults with a diagnosis of drug-resistant TLE treated with PER as add-on therapy (PER group) and 32 drug-resistant TLE age, sex, and seizure-frequency matched controls treated with an additional ASM as add-on therapy (No-PER group). Each patient underwent a 20-minute EEG + EKG recording in resting state before and after 6 months the introduction of add-on anti-seizure therapy. Heart rate variability (HRV) analysis was performed on EKG records. Time-domain and frequency domain analysis parameters were compared before and after PER introduction.

Results: Treatment regimens, as well as patients' clinical and demographic features, are summarized in Table 1. After the administration of PER, HRV analysis of treated patients showed significantly increased high frequency (HF) (p=0.02), a parameter indicative of increased vagal tone. A reduction in low frequency (LF) (p=0.001) and low-frequency/high-frequency ratio (LF/HF) (p=0.001) was also observed. In addition, according Linear Mixed Models, a multiplicative effect for the interaction between group-treatment for time was observed for Mean RR (p=0.03), LF (p=0.001) and HF (p=0.001). For low frequency/high frequency ratio (LF/HF) only a group effect was observed (p=0.001).

Conclusions: Our data provide experimental evidence to support the notion that PER increases the vagal tone in drug-resistant TLE patients. 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.

Funding: Please list any funding that was received in support of this abstract.: No funding was received for this study.