Feasibility of Non-Invasive Vagus Nerve Stimulation (gammaCore VET™) for the Treatment of Refractory Seizure Activity in Dogs

Abstract

Idiopathic epilepsy is the most common chronic neurologic condition in dogs. Approximately 20-30% of those dogs are refractory to standard medical therapy and commonly experience side effects from antiepileptic drugs. Non-invasive vagus nerve stimulation (nVNS) has been frequently used in human medicine as an adjunct seizure therapy with low incidence of adverse events. Canine studies are limited to invasive surgical implants with no non-invasive evaluations currently published. We investigated the feasibility and efficacy of nVNS (gammaCore VET) as an adjunct treatment for refractory epilepsy in dogs. In total, 14 client-owned dogs completed the trial of either 8-or 16-week treatment periods during which they received 90-120 s stimulation three times per day in the region of the left cervical vagus nerve. Owners recorded seizure type (focal or generalized) and frequency as well as any adverse effects. Out of 14 dogs, nine achieved a reduction in seizure frequency and four were considered responders with a 50% or greater reduction in seizures from baseline to the final treatment period. However, there was no statistically significant difference in overall seizure frequency (p = 0.53) or percent change in seizure frequency between groups (p = 0.75). Adverse effects occurred in 25% of dogs originally enrolled, with reports of a hoarse bark and limb trembling, lethargy, behavioral changes, and an increase in seizure frequency. Non-invasive VNS was found to be safe and easy to administer with mild adverse events. It is considered a feasible treatment option as an adjunct therapy in refractory seizures and should be further investigated.

Case Report: 1-Year Follow-Up of Vagus Nerve Stimulation in a Dog With Drug-Resistant Epilepsy

“…Previous VNS clinical trials in veterinary medicine did not use the VNS external magnet ( 5 , 6 ). The termination of seizure activity and shortening of seizure durations and severity using a magnet-induced stimulation have been reported in humans ( 24 ).…”

“…A long-term follow-up study on epilepsy patients for whom VNS parameters were gradually adjusted reported gradual reductions in median seizure frequency of 25, 40, and 53% after 3, 6, and 12 months of VNS, respectively ( 4 ). In veterinary medicine, two clinical studies on surgically implantable VNS and transcutaneous non-invasive VNS indicated the potential of VNS as adjunctive therapy for dogs with DRE ( 5 , 6 ); mean reductions in seizure frequency of 34.4% and 25.9% were reported after 13 and 16 weeks of VNS, respectively. However, the long-term efficacy and safety of VNS in dogs and adjustments of VNS stimulus dosing remain unclear.…”

Strategies for precision vagus neuromodulation

“…Cervical, non-invasive VNS (nVNS) devices, such as GammaCore (NJ, USA), are designed primarily to stimulate myelinated sensory afferent vagus nerve fibers as they ascend through the neck in the carotid sheath, using a battery-powered external electrical stimulator. This device has been approved and is being prescribed in several countries mainly for the treatment of primary headache and is CE marked in the EU for the treatment of primary headache, epilepsy, bronchoconstriction, anxiety, depression, and gastric motility disorders (Mwamburi et al 2017 ; Robinson et al 2020 ). More recently, this device was also tested in a short-term proof-of-concept study for patients with treatment-refractory gastroparesis, as an alternative for implantable gastric electric stimulation devices (Paulon et al 2017 ).…”

Transcutaneous Cervical Vagus Nerve Stimulation Induces Changes in the Electroencephalogram and Heart Rate Variability of Healthy Dogs, a Pilot Study

“…Despite the favorable response observed in some dogs, the cost, unreliable functionality and short- and long-term complications make a surgically implanted device inaccessible for many drug-resistant patients ( 10 , 11 ). The tcVNS apparatus in dogs with drug resistant idiopathic epilepsy is reported to be well-tolerated; although no significant effect on the overall reported seizure frequency was found ( 12 ). Objective measures of tcVNS effects on vagus nerve activity remain to be described.…”