Dose-dependent laryngeal muscle evoked potentials as an indicator of effective vagus nerve stimulation

• ¹ Ghent University, Internal Disease/Neurology, Belgium

Rationale| Vagus nerve stimulation (VNS) is a neuromodulatory treatment for refractory epilepsy and depression. The major drawbacks of VNS are 1/ the lack of response in a third of patients and 2/ the fact that the optimal stimulation parameters are unknown. Vagal nerve recordings in both an experimental and clinical setting may be useful to overcome these drawbacks. In this study, VNS-induced laryngeal muscle evoked potentials (LMEPs) were recorded in rats as a biomarker for effective activation of the vagus nerve. Methods| Rats (n=18) were implanted with a bipolar stimulation cuff-electrode around the left vagus nerve. After at least two weeks of recovery, VNS-induced LMEPs were recorded under anesthesia using a monopolar EMG needle electrode placed subcutaneously near the laryngeal muscles and a distant reference electrode on the skull of the rat. Biphasic VNS pulses of 250 µs per phase were used. The output current of the pulses was gradually ramped-up from 0.1 mA to 1.0 mA in steps op 0.1 mA. For each intensity, 20 sweeps were averaged to improve the signal to noise ratio. Results| VNS-induced LMEPs were reproducibly recorded in 16/18 rats. The LMEPs were characterized by a negative peak with a latency of 2.6 ms ± 0.9 ms after the onset of the stimulation pulse. The threshold for evoking LMEPs was variable, ranging from 0.1 mA to 0.7 mA (0.4 mA ± 0.2 mA). Conclusion| This minimally invasive technique could be used both in animal studies and in clinical practice 1/ to identify non-responders due to inactivity of the vagus nerve and 2/ to determine individual stimulation parameter requirements for efficient activation of the vagus nerve. Short comment: Nervus vagus stimulatie is een behandeling voor epilepsiepatiënten die geen baat hebben bij medicatie. Twee nadelen van de therapie zijn dat 1/ een derde van de patiënten geen effect ervaart, mogelijks doordat de zenuw niet geactiveerd wordt en 2/ dat de optimale stimulatieparameters niet gekend zijn. In deze studie werd een techniek geoptimaliseerd om na te gaan of de nervus vagus effectief geactiveerd wordt bij verschillende nervus vagus stimulatie intensiteiten in ratten. Deze techniek zou getest kunnen worden bij patiënten om 1/ na te gaan of de zenuw effectief geactiveerd wordt en 2/om de stimulatie parameters per patiënt te optimaliseren.