Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. Initially developed by James Leonard Corning to compress or stimulate the carotid sheath, VNS typically refers to an implantable electrode. However, non-invasive VNS delivered transcutaneously via the auricular branch of the vagus nerve, or through the skin to the cervical nerve, is being investigated in clinical research. Invasive VNS is used as an adjunct treatment for certain types of intractable epilepsy, cluster headaches, migraine, treatment-resistant depression and stroke rehabilitation.
Medical use
Epilepsy VNS is used to treat drug-resistant epilepsy. For refractive epilepsy, cervical VNS on the left side is FDA-approved. In the United States, VNS is approved as adjunctive therapy for those 4 years of age or older with refractory focal onset seizures. In the European Union, VNS is approved as an adjunctive therapy for patients with either generalized or focal onset seizures without any age restrictions. It is recommended that VNS is only pursued following an adequate trial of at least 2 appropriately chosen anti-seizure medications and that the patient is ineligible for epilepsy surgery. This is because epilepsy surgery is associated with a higher probability of resulting in seizure freedom. Patients who have poor adherence or tolerance of anti-seizure medications may be good candidates for VNS. VNS may provide benefit for particular epilepsy syndromes and seizure types such as Lennox-Gastaut syndrome, tuberous sclerosis complex related epilepsy, refractory absence seizures, and atonic seizures. There are also reports of VNS being successfully utilized in patients with refractory and super-refractory status epilepticus. Several clinical studies, including a long-term retrospective review published in 2020, have reported that VNS can reduce seizure frequency in patients with drug-resistant epilepsy associated with structural brain lesions.
Cluster headaches and migraine The UK National Institute for Health and Care Excellence (NICE) in the UK recommends VNS for cluster headaches. In 2017 the FDA approved the non-invasive gammaCore VNS system for treatment of episodic cluster headache and expanded its approved usage to acute treatment of pain associated with migraine. Two randomized, double-blind, and sham-controlled studies have administered nVNS to patients with episodic cluster headaches; both demonstrated a significant effect in reducing acute cluster attacks.
Treatment-resistant depression VNS is used to treat treatment-resistant major depressive disorder (TR-MDD). For treatment resistant depression, cervical VNS on the left side is FDA-approved. The UK NICE guidance (from 2020) stated that "Evidence on its efficacy is limited in quality" and encouraged further research studies "in the form of randomised controlled trials with a placebo or sham stimulation arm."
Chronic pain VNS has been used to treat chronic pain due to various causes, although the mechanisms for this relief have yet to be determined.
Heart failure VNS has shown to be of value in the treatment of heart failure. One study did not show a reduction in death rates, but did show improvement in six-minute hall walk duration and quality of life.
Atrial fibrillation Animal studies have shown the capacity of low-level VNS to reduce inducibility of atrial fibrillation. This effect has been proposed to be due to inhibition of the ganglionated plexi.
Stroke treatment and rehabilitation VNS can be used either invasively or non-invasively to treat ischemic stroke. Invasive VNS can only be applied invasively (by surgery), but non-invasive VNS can be used in acute settings. In 2021, the U.S. Food and Drug Administration approved the MicroTransponder Vivistim Paired VNS System (Vivistim System) to treat moderate to severe upper extremity motor deficits associated with chronic ischemic stroke.
Efficacy
Epilepsy A meta-analysis of 74 clinical studies with 3321 patients found that VNS produced an average 51% reduction in seizures after 1 year of therapy. Approximately 50% of patients had an equal to or greater than 50% reduction in seizures at the time of last follow-up. Long-term studies have shown that response to VNS increases over time. For instance, a study that followed 74 patients for 10–17 years found a seizure frequency reduction of 50-90% in 38.4%, 51.4%, 63.6% and 77.8% of patients at 1-, 2-, 10- and 17-years following implantation, respectively. Approximately, 8% have total resolution of seizures. VNS has also been shown to reduce rates of sudden unexpected death in epilepsy (SUDEP) and to improve quality of life metrics. A number of predictors of a favorable clinical response have been identified including epilepsy onset > 12 years of age, generalized epilepsy type, non-lesional epilepsy, posttraumatic epilepsy and those who have less than a 10-year history of seizures. Long-term cognitive outcomes are at least stable following VNS. One study of children with epilepsy found that a post hoc analysis revealed a dose–response correlation for VNS.
Depression A 2022 narrative review concluded that VNS is an effective and well-tolerated therapy for chronic and treatment-resistant depression. Importantly, the review also noted that the therapeutic effect of VNS in this context may take 3–12 months to materialize but may be persistent long-term. One study of only 10 weeks found no effect. A 2020 review concluded "Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. In one study higher electrical dose parameters were associated with response durability.
… excerpt ends here. Continue reading the full article.
