Vagus nerve stimulation for drug-resistant epilepsy

Abstract

Vagus nerve stimulation (VNS) is a neuromodulatory therapeutic option for drug-resistant epilepsy. In randomised controlled trials, VNS implantation has resulted in over 50% reduction in seizure frequency in 26%–40% of patients within 1 year. Long-term uncontrolled studies suggest better responses to VNS over time; however, the assessment of other potential predictive factors has led to contradictory results. Although initially designed for managing focal seizures, its use has been extended to other forms of drug-resistant epilepsy. In this review, we discuss the evidence supporting the use of VNS, its impact on seizure frequency and quality of life, and common adverse effects of this therapy. We also include practical guidance for the approach to and the management of patients with VNS in situ.

The Pharmacoresistant Epilepsy: An Overview on Existent and New Emerging Therapies

“…VNS has been approved in the USA by Food and Drug Administration (FDA) as an adjunctive treatment for DRE in 1997, but its use has also been studied in other fields of medicine (e.g., depression, heart failure, stroke, and tinnitus) ( 119 ). Although initially approved for partial-onset seizures in people aged over 12 years, VNS is now used in adults and children with DRE not eligible for resective surgery, suffering from either focal or generalized seizures ( 120 ).…”

“…This approach consists of periodic electrical stimulation delivered to the vagus nerve supplied by a programmable pulse generator, generally implanted subcutaneously under the left clavicle and connected to a lead wire wrapped around the vagus nerve distal to the recurrent laryngeal nerve. Stimulation of the left vagus nerve is preferred because it is thought to have less likely cardiac effects (e.g., bradycardia) rather than the right nerve that innervates the sinoatrial node directly ( 119 ). The exact mechanism of action of VNS on seizure control is not yet fully understood.…”

“…Concording with the antiseizure effect, other amino acid changes in CNS reported after VNS are increased levels of the inhibitory neurotransmitter GABA and decreased levels of excitatory amino acid aspartate ( 121 ). An altered function of the limbic system, reticular activating system, and cortical structures (i.e., orbitofrontal cortex, temporal lobes) showed by functional neuroimaging, and the even stronger evidence of desynchronising effect on EEG scalp registration of VNS are thought to contribute to the antiseizure effect of this treatment ( 119 ). Traditional VNS includes baseline stimulation (open-loop) and magnet mode (on-demand).…”

“…Magnet mode stimulation allows the patient or caregiver to deliver adjunctive stimulation at the occurrence of a seizure, triggered by swiping a magnet over the pulse generator ( 122 ). Responsive VNS is a modern approach based on closed-loop auto-stimulation, which automatically delivers stimulation triggered by ictal tachycardia, a marker for seizure onset occurring in >80% of both generalized and focal seizures ( 119 , 122 ). Generally, it is recommended to start with baseline stimulation 2 weeks after device implantation.…”

“…The main AEs reported are hoarseness, cough, dyspnea, pain, paresthesia, nausea, and headache ( 124 ). High-quality evidence from RCTs focused on focal epilepsies in adult patients with DRE, and however observational studies suggest VNS may also be effective in generalized epilepsies ( 119 ).…”