Proof-of-Concept of Respiration-Triggered Vagus Nerve Stimulation to Treat Epilepsy

Vagus nerve stimulation (VNS) is an adjunctive treatment against epilepsy. It is proposed for patients who do not respond to antiepileptic drugs and for whom it is impossible to surgically remove an epileptogenic focus. VNS consists of an implanted pulse generator that delivers trains of electrical pulses to the left vagus nerve, which induces antiepileptic effects for both focal and generalized seizures. In current VNS practice, stimulation is performed at a regular pace with fixed stimulation parameters, without considering the patient's physiological state. As the mechanisms of action of VNS remain to be fully elucidated, this stimulation scheme may not be optimal. This work presents an acute setup allowing to apply VNS with respiration feedback. More specifically, it can apply VNS in phase with respiration (either inspiration or expiration) measured by a thermistor. A microcontroller was implemented to control the stimulation peace at every exhalation, by processing the respiration signal. The stimulation parameters used were: 500μA current intensity, 500μs pulse-width, at 40Hz, and 30sec ON/30sec OFF dutty cycle. It was validated in vivo in four healthy anesthetized rats. The detection of exhalations had an average sensitivity of 96.5±3.07%, an average positive predictive value of 93.6±4.51%, and the overall mean average dose was 19.78±0.68 pulses/second. This system allows future in vivo VNS experiments to compare performance with the standard VNS in treating epilepsy.