Vagus Nerve Stimulation Device Research Articles

Breast cancer at site of implanted vagus nerve stimulator

Vagus nerve stimulation (VNS) was approved for the management of intractable partial epilepsy in patients 12 years of age and older in 1997.1 The device was also approved in 2005 for treatment-resistant depression. The pulse generator is typically placed in the left pectoral region for stimulation of the left vagus nerve.1 We present two patients who had undergone chronic VNS and developed adenocarcinomas of the breast anatomically related to the pulse generators. The diagnostic yield of breast self-examination and mammography to identify early stages of breast cancer may be reduced by VNS. ### Patient 1. A 34-year-old woman had a VNS device implanted in 2003 for management of intractable partial epilepsy related to a large multilobar malformation of cortical development. The patient palpated a firm mass in 2006 under the pulse generator in the left pectoral region. An ultrasound of the left breast revealed an 8.8 cm by 11.5 cm mass. Biopsy indicated an invasive ductal carcinoma. The patient was treated …

Vagus nerve stimulation acutely alters food craving in adults with depression

Vagus nerve stimulation (VNS) is now available as a treatment for epilepsy and treatment-resistant depression. The vagus nerve plays a central role in satiety and short-term regulation of food intake and research suggests a relationship between VNS and weight loss. The underlying mechanisms of this relationship are unknown. The purpose of the current study was to determine whether acute cervical VNS might temporarily alter food cravings. Thirty-three participants were recruited for three groups; depression VNS, depression non-VNS, and healthy controls. Participants viewed 22 computerized images of foods twice in one session and completed ratings for food cravings after each image. The VNS participants' devices were turned on for one viewing of an image and off for the other (randomized order). Participants were blind to VNS condition (on versus off). Acute VNS device activation was associated with a significant change in cravings-ratings for sweet foods. A significant proportion of variability in VNS-related changes in cravings was accounted for by patients' clinical VNS device settings, acute level of depression, and body mass. Further studies are warranted addressing how acute or chronic VNS might modify eating behavior and weight.

Concomitant Use of Vagus Nerve Stimulation and Electroconvulsive Therapy for Treatment-resistant Depression

This study explored the use of electroconvulsive therapy (ECT) in the pivotal study of vagus nerve stimulation (VNS) for treatment-resistant depression. The clinical characteristics and outcomes of study participants who received ECT during the first 12 months of VNS were compared with those who did not receive ECT. Physicians were instructed to turn off VNS during administration of ECT. Of 205 (evaluable sample) patients who received VNS, 14 also received ECT. Participants who received ECT had a statistically significant greater number of hospital admissions (P = 0.037, Wilcoxon) and number of suicide attempts during their lifetimes (P= 0.022, Fisher exact test). Of 55 responders (> or =50% reduction in Hamilton Rating Scale for Depression-24 questions [HRSD-24] scores) after 12 months of VNS, 3 had received ECT. Of 32 remitters (HRSD-24 score, < or =9), 2 had received ECT. Administration of ECT did not affect the implanted VNS device, and the presence of the implanted VNS device did not affect the administration of ECT. Electroconvulsive therapy and VNS are not mutually exclusive. They can be used safely and effectively either sequentially or concurrently. Each can be prescribed as the depressive condition warrants-ECT for emergently worsening depressive symptoms and maintenance therapy and VNS for chronic, long-term therapy.

Acute and Long-term VNS Effects on Pain Perception in a Case of Treatment-Resistant Depression

Vagus Nerve Stimulation (VNS) is approved by the FDA for treatment of both epilepsy and depression. Recent work has shown that VNS acutely affects pain perception in humans, actually increasing pain sensitivity momentarily while the device is firing. It is unclear how this acutely increased sensitivity might change over time with treatment and how it might relate to longer-term therapeutic effects of VNS on pain. We describe a patient with treatment-resistant depression and a history of severe lumbar degenerative disease with resultant chronic low back pain. His depression and pain symptoms both seemed to respond to VNS. He eventually stopped all medications and remained depression and pain free for 35 months with no change in his device settings. Sixty-six months after VNS implantation and 64 months after his initial clinical antidepressant response, under single-blind conditions, we performed quantitative sensory testing with laboratory thermal pain procedures during acute VNS-on and -off conditions. Interestingly, despite a significant and profound anti-nociceptive clinical response for the previous 35 months, he had significant increases in painfulness ratings while the VNS device was actively firing compared with device-off conditions. This case suggests that VNS-induced acute increases in pain sensitivity can coexist with a clinical anti-nociceptive response. If the acutely increased sensitivity sets the stage for the slower chronic anti-pain effects, the increased acute sensitivity does not disappear. Acute and chronic effects of VNS on pain perception merit further research.

Vagus Nerve Stimulation Device Approved With Multiple Cautions

Vagus Nerve Stimulation Device Approved With Multiple Cautions

Vagus Nerve Stimulation Affects Pain Perception in Depressed Adults

Previous research suggests that vagus nerve stimulation (VNS) affects pain perception in epilepsy patients, with acute VNS decreasing pain thresholds and chronic VNS treatment increasing pain thresholds. However, no studies have investigated the effects of VNS on pain perception in chronically depressed adults, nor have controlled, systematic investigations been published on the differential effects of certain VNS device parameters on pain perception. The present study tried to replicate the results of previous research showing acute pronociceptive effects of VNS and determine the effects of various device parameter settings on pain tolerance. The present study also investigated the relationship among patients' levels of depression, duration of VNS treatment and VNS-induced changes in pain perception. A thermal pain challenge task was used to determine pain tolerance during VNS device activation using different combinations of VNS device parameter settings within subjects undergoing VNS therapy for chronic depression. Significant pronociceptive effects were found for acute VNS activation. Individual differences were found with respect to the VNS settings associated with the largest changes in pain perception. Severity of depression was inversely related to baseline pain tolerance, but depression severity was unrelated to VNS-induced acute changes in pain tolerance, as was the length of time participants had been undergoing VNS treatment. VNS appears to affect pain perception in depressed adults. Different VNS parameter settings may be associated with unique effects from patient to patient. More studies are needed to determine the long-term effects of VNS on pain perception.

Emerging Perspectives: Does VNS Work in Refractory Depression?

Vagus nerve stimulation (VNS), used to treat epilepsy since 1997, received FDA approval as an adjunctive therapy for treatment-resistant depression. Three multicenter studies, supported by the manufacturer of the implantable VNS device and conducted by the same research team, have now examined the device’s short- and longer-term efficacy in a group of 222 patients with clearly refractory depression (current episodes had failed to respond to 2–6 adequate trials of treatment, including ECT in one third of patients). All patients underwent surgery for device implantation. All patients had experienced at least four lifetime depression episodes, or the current episode had …

Vagus Nerve Stimulation Therapy after Failed Cranial Surgery for Intractable Epilepsy: Results from the Vagus Nerve Stimulation Therapy Patient Outcome Registry

To determine the effectiveness of vagus nerve stimulation (VNS) therapy among patients with persistent or recurrent seizures after lobar resection, callosotomy, and other cranial operations for intractable epilepsy. Data were obtained from the VNS therapy patient outcome registry, which was established after United States Food and Drug Administration approval of the VNS device in 1997 as a means of capturing open-label clinical data outside of protocol. The integrity of the systems for collecting and processing registry data was authenticated by an independent auditing agency. The effect of potential selection bias, however, remains uncertain. Two nonconsecutive cohorts were compared: patients tracked in the registry who had previously undergone cranial surgery for epilepsy (CS group, n = 921) and those who had not (non-CS group, n = 3822). For the CS group, the median reduction in seizure frequency was 42.5% after 3 months of VNS therapy, 42.9% at 6 months, 45.7% at 12 months, 52.0% at 18 months, and 50.5% at 24 months. For the non-CS group, analogous rates were 47.0%, 52.9%, 60.0%, 62.7%, and 66.7%, respectively. In the CS group, seizures were reduced by at least 50% in 55.1% of patients, at least 75% in 31.4% of patients, at least 90% in 17.3% of patients, and 100% in 5.1% of patients after 24 months of VNS therapy. Response rates were more pronounced in the non-CS group: at least 50% in 62.2% of patients, at least 75% in 43.7% of patients, at least 90% in 26.8% of patients, and 100% in 8.3% of patients. Patients in both groups experienced marked improvements in quality of life parameters. The effectiveness of VNS is maintained during prolonged stimulation, and overall seizure control continues to improve with time. Patients in whom prior cranial surgery had failed did not respond as favorably as all other patients receiving VNS therapy. Nonetheless, many of the former group improved substantially. Thus, on the basis of these open-label data, VNS therapy represents a potentially palliative treatment option for patients with refractory seizures after failed cranial surgery.

Vagal nerve stimulation technique: enhancing its efficacy and acceptability by augmentation with auto activation and deactivation mode of operation

The purpose of this article is to search for an additional modus operandi to improve the functioning of currently deployed vagal nerve stimulation (VNS) technique that is being used as an adjunctive therapy for intractable epilepsy, mainly complex partial seizures (partial onset with secondary generalization). The efficacy and success of current VNS technique is variable and limited, which can be attributed (to a considerable extent) to its present modi operandi. The mechanism of anti-epileptic action of VNS that has been hypothesized in the article is found to conform to observations and results in a large number of studies including those on VNS itself. Based on this mechanism in controlling seizures, the author proposes an additional mode of operation of the VNS device, (an auto activation and deactivation mode), designed to work on a feedback mechanism, which would deliver VNS as and when the brain requires it to abort/arrest the impending focal attack and/or its generalization, thus eliminating the limitations associated with the current VNS device. This mode should enhance its acceptability, efficacy and success.

The effect of vagus nerve stimulation on migraines

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

Evaluation of laryngeal function after implantation of the vagus nerve stimulation device

Objectives The vagus nerve stimulation device (VNS) is used for the management of seizures. This study evaluated what effect the diameter of the vagus nerve helical electrode might have on true vocal cord (TVC) mobility. The study was prompted after 2 cases of TVC immobility. Electrode nerve compression was suspect. Methods Eighteen patients underwent intraoperative vagus nerve measurement and electrode placement with subsequent voice and TVC evaluation. Electrode selection was based on vagus nerve measurements. Results Seven patients had vagus nerves measuring less than 2 mm diameter and received the 2-mm inner diameter electrode. Eleven patients had vagus nerves measuring more than 2 mm in diameter and received the 3-mm inner diameter electrode. No patients experienced transient or permanent hoarseness or paresis/paralysis. Conclusion Precise vagus nerve measurements and electrode selection appear to decrease the incidence of nerve compression injury and TVC immobility.

Correlation between GABA A receptor density and vagus nerve stimulation in individuals with drug-resistant partial epilepsy

Vagus nerve stimulation (VNS) is an important option for the treatment of drug-resistant epilepsy. Through delivery of a battery-supplied intermittent current, VNS protects against seizure development in a manner that correlates experimentally with electrophysiological modifications. However, the mechanism by which VNS inhibits seizures in humans remains unclear. The impairment of γ-aminobutyric acid (GABA)-mediated neuronal inhibition associated with epilepsy has suggested that GABA A receptors might contribute to the therapeutic efficacy of VNS. We have now applied single photon emission computed tomography (SPECT) with the benzodiazepine receptor inverse agonist [ 123 I ]iomazenil to examine cortical GABA A receptor density (GRD) before and 1 year after implantation of a VNS device in 10 subjects with drug-resistant partial epilepsy. VNS therapeutic responses resulted significantly correlated with the normalization of GRD. Moreover, a comparable control group, scheduled for a possible VNS implant, failed to show significant GRD variations after 1 year of a stable anti-epileptic treatment. These results suggest that VNS may modulate the cortical excitability of brain areas associated with epileptogenesis and that GABA A receptor plasticity contributes to this effect.

Vagus nerve stimulation therapy, epilepsy, and device parameters: scientific basis and recommendations for use.

Our understanding of a precise dose-response relationship for vagus nerve stimulation (VNS) therapy in the treatment of seizures is still evolving. Because several parameters are involved in VNS therapy, the individual contribution of each is not well understood. This review discusses the efficacy of stimulation parameters used in the VNS clinical trials. The background, influence on safety and efficacy, and role in helping to achieve seizure control are discussed for each VNS device parameter: output current, pulse duration, frequency, and duty cycle. Finally, we provide an algorithm for the adjustment of VNS device settings (see Appendices).

Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects

Stimulation of the vagus nerve in the neck can reduce seizures in epilepsy patients, and may be helpful in treating depression. PET studies have shown that vagus nerve stimulation (VNS) in epilepsy patients causes acute dose (intensity) dependent changes in regional cerebral blood flow. We sought to use the newly developed VNS synchronized fMRI technique to examine whether VNS BOLD signal changes depend on the frequency of stimulation. Six adults with recurrent depression were scanned inside a 1.5 T MR scanner. Data were acquired at rest, with the VNS device on for 7 s, and also, for comparison, while the patient listened to a tone for 7 s. In two separate back-to-back sessions, the VNS stimulation frequency was set to either 5 or 20 Hz. Data were transformed into Talairach space and then compared by condition. Compared to 5 Hz, 20 Hz VNS produced more acute activity changes from rest in regions similar to our initial VNS synchronized fMRI feasibility study in depression. Brain regions activated by hearing a tone were also greater when VNS was intermittently being applied at 20 Hz than at 5 Hz. In depressed adults, left cervical VNS causes regional brain activity changes that depend on the frequency of stimulation or total dose, or both. In addition to the acute immediate effects of VNS on regional brain activity, this study suggests further that VNS at different frequencies likely has frequency or dose dependent modulatory effects on other brain activities (e.g. hearing a tone).

Effect of vagal nerve stimulation on auditory and visual event‐related potentials

Chronic unilateral vagal nerve stimulation (VNS) has been recently introduced into the therapy for intractable epileptic seizures. Its effect on cognitive functions in VNS-treated patients remains controversial. The aim of the present study was to evaluate the possible impact of therapeutic VNS on cognitive functions by means of event-related potentials analysis. Ten patients with medically intractable epilepsy, who had been implanted with VNS devices, participated in the study. Auditory and visual event-related potentials (ERPs) were repeatedly recorded, first just before the implantation of VNS devices, and then again 3-6 months after the device activation. The effect of lower intensity stimulation on the P3 component of ERPs was assessed. No significant differences were found in auditory ERPs; the latencies of P3 as well as N2/P3 peak-to-peak amplitudes were virtually identical. The same was true for mean P3 latencies of visual ERPs. However, higher visual N2/P3 peak-to-peak amplitudes were observed in the responses to targets that followed VNS, with a significant finding at the electrodes investigated. When comparing the effect of VNS on visual N2/P3 amplitude in each electrode separately, the most expressive differences were found in the frontal region. This observation supports the theory of a possible positive effect of low-intensity VNS on the cognitive functions.

Vagus Nerve Stimulation: A New Form of Therapeutic Brain Stimulation

Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNSTM NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.

Aspiration: a potential complication to vagus nerve stimulation.

Vagus nerve stimulation (VNS) is reported to reduce the frequency of seizures in children and adults without causing serious side effects. However, clinical observation of swallowing difficulties in 2 children treated with VNS made further investigation necessary. Seven patients aged 4-18 years and treated with VNS for 6-14 months were investigated with videoradiography during barium swallow. The children performed 5-30 barium swallow investigations with the VNS device turned off, running as programmed, or set at continuous stimulations. The degree of aspiration was scored from 0 to 3. In 5 of 7 children, of whom reported transient swallowing difficulties, no change in the degree of aspiration was noted. The 2 children with swallowing difficulties, however. showed increased aspiration score when the stimulator was set at continuous stimulations. In 1 the score also appeared to increase with the VNS running as programmed (p > 0.05). Both children had severe mental and motor disabilities. Before and during VNS treatment patients should be evaluated with regard to swallowing problems. There needs to be an easy way to turn the device on and off to avoid aspirations, a hazardous and potentially life-threatening complication of VNS.