Vagus nerve stimulation

Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment-resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality 1).

Electrodes wrapped around the vagus nerve in the neck are connected to an implanted programmable generator to stimulate the nerve to reduce seizure frequency. As is also true with many AEDs, the mechanism of action is not well understood.

It was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS).

Ogbonnaya and Kaliaperumal described the evolution of the VNS and its use in different fields of medicine. They also reviewed the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for 'VNS' and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed.

Studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future 2).

Vagus nerve stimulation (VNS) is an established surgical treatment for medically intractable epilepsy with more than 75 000 devices implanted worldwide till 2015.

VNS likely has a positive effect on response inhibition, at least in patients with epilepsy that benefit clinically from the treatment, presumably relating to enhancements of response-inhibition mechanisms and, therefore, identify enhanced response inhibition as a possible cognitive benefit of VNS 3).

Vagus nerve stimulation (VNS) with vagus nerve stimulator delivered during rehabilitative training enhances neuroplasticity and improves recovery in models of cortical ischemic stroke.

Rats were trained to perform an automated, quantitative measure of forelimb function. Once proficient, rats received an intrastriatal injection of bacterial collagenase to induce ICH. Rats then underwent VNS paired with rehabilitative training (VNS+Rehab; n=14) or rehabilitative training without VNS (Rehab; n=12). Rehabilitative training began ≥9 days after ICH and continued for 6 weeks.

VNS paired with rehabilitative training significantly improved recovery of forelimb function when compared with rehabilitative training without VNS. The VNS+Rehab group displayed a 77% recovery of function, whereas the Rehab group only exhibited 29% recovery. Recovery was sustained after cessation of stimulation. Both groups performed similar amounts of trials during rehabilitative, and lesion size was not different between groups.

VNS paired with rehabilitative training confers significantly improved forelimb recovery after intracerebral hemorrhage (ICH) compared to rehabilitative training without VNS 4).

Vagus Nerve Stimulation Indications.

see Vagus nerve stimulation complications.

The new AspireSR generator offers a unique technical improvement over the previous Demipulse. Whether the highly interesting CBSD feature will provide an additional benefit for the patients, and will rectify the additional costs, respectively, cannot be answered in the short-term. The preoperative handling is straightforward, provided that certain recommendations are taken into consideration. The intraoperative handling is equivalent to former models-except for the placement of the generator, which might cause cosmetic issues and has to be discussed with the patient carefully. We recommend the consideration of the AspireSR in patients with documented ictal tachycardia to provide a substantial number of patients for later seizure outcome analysis 5).

see Vagus Nerve Stimulation outcome.

An Observational study of all 43 adult patients receiving VNS for >2 years at one single center. The mean duration of treatment was 9 years. At inclusion, a semi-structured interview on VNS effectiveness was performed. In patients without benefit, the VNS was turned off. The outcome was evaluated after an observation period of one year.

21 patients (49%) reported no clear benefit and stopped VNS. Only one of them resumed treatment within one year. Patients without benefit had received more new antiepileptic drugs (AEDs) during VNS treatment than those reporting benefit (p = 0.05). Other differences between the two groups were not found. Ten patients (23%) had been seizure free >1 year at inclusion (5 in the benefit and 5 in the non-benefit group). Seizure control was attributed to the response of another new treatment in the majority of these patients.

Half of the patients had not perceived clear benefit from VNS, and all but one terminated VNS without worsening of seizures within one year. The true outcome of long-term VNS is difficult to assess in real-world practice. The effect may be overestimated due to confounding factors, particularly the common introduction of novel AEDs and the natural course of the disorder. Patients without perceived benefit from long-term VNS should not routinely remain on treatment and be subject to undue generator re-implantations 6).

Howland RH. Vagus Nerve Stimulation. Curr Behav Neurosci Rep. 2014 Jun;1(2):64-73. PubMed PMID: 24834378; PubMed Central PMCID: PMC4017164.
Ogbonnaya S, Kaliaperumal C. Vagal nerve stimulator: Evolving trends. J Nat Sci Biol Med. 2013 Jan;4(1):8-13. doi: 10.4103/0976-9668.107254. PubMed PMID: 23633829; PubMed Central PMCID: PMC3633308.
Schevernels H, van Bochove ME, De Taeye L, Bombeke K, Vonck K, Van Roost D, De Herdt V, Santens P, Raedt R, Boehler CN. The effect of vagus nerve stimulation on response inhibition. Epilepsy Behav. 2016 Oct 12;64(Pt A):171-179. doi: 10.1016/j.yebeh.2016.09.014. PubMed PMID: 27743550.
Hays SA, Khodaparast N, Hulsey DR, Ruiz A, Sloan AM, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke. 2014 Oct;45(10):3097-100. doi: 10.1161/STROKEAHA.114.006654. Epub 2014 Aug 21. PubMed PMID: 25147331; PubMed Central PMCID: PMC4175144.
Schneider UC, Bohlmann K, Vajkoczy P, Straub HB. Implantation of a new Vagus Nerve Stimulation (VNS) Therapy® generator, AspireSR®: considerations and recommendations during implantation and replacement surgery-comparison to a traditional system. Acta Neurochir (Wien). 2015 Feb 13. [Epub ahead of print] PubMed PMID: 25673257.
Brodtkorb E, Samsonsen C, Jørgensen JV, Helde G. Epilepsy patients with and without perceived benefit from vagus nerve stimulation: A long-term observational single center study. Seizure. 2019 Sep 19;72:28-32. doi: 10.1016/j.seizure.2019.09.004. [Epub ahead of print] PubMed PMID: 31563121.
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