Background:

Vagus Nerve Stimulation (VNS), delivered via surgically implanted cuff electrodes on the left cervical vagus, is used to treat drug-resistant epilepsy (DRE). VNS is believed to act on the brain to reduce seizures by chronic neuromodulation, but it is not known what effects it has on other systems, including the sympathetic nervous system. Here we tested the hypothesis that chronic VNS reduces muscle sympathetic nerve activity (MSNA).

Methods:

Nineteen patients between the ages of 18-66 years with a diagnosis of DRE were recruited from the Alfred Health epilepsy clinics. Spontaneous bursts of MSNA were recorded via a tungsten microelectrode inserted percutaneously into a muscle fascicle of the common peroneal nerve. MSNA recordings were obtained from 11 DRE patients with implanted VNS devices who had been stimulated chronically (>6 months stimulation) and 8 DRE patients yet to receive a VNS implant. Baseline recordings were obtained in existing VNS patients, lying supine with their VNS device stimulating at their clinically set parameters (1.125-3.5 mA, 20 Hz, 250μs, duty cycle 10%-35%).

Results:

Patients without VNS (n=8) had a mean of 26.6 ± 9.5 (SD) bursts/min at rest, while those treated with VNS (n=11) had a mean of 13.1 ± 7.9 SD bursts/min, measured between trains of VNS. Although VNS did not appear to affect MSNA acutely, MSNA was significantly lower in patients following chronic VNS (p=0.0017).

Conclusions:

While VNS appeared to have no acute effects on MSNA at rest, nor during manouevres that increase MSNA, such as passive head-up tilt, MSNA was reduced in patients with chronic VNS treatment compared to those without. Chronic VNS treatment may have a protective effect on cardiovascular risk by reducing sympathetic activity. This may contribute to the mechanism behind risk-reduction for sudden unexplained death in epilepsy (SUDEP) in VNS-treated patients (Ryvlin et al., 2018).