Efficacy Of Vagus Nerve Stimulation Research Articles

Use of vagal nerve stimulation as a treatment for refractory epilepsy in dogs

To evaluate safety and efficacy of vagal nerve stimulation in dogs with refractory epilepsy. Placebo-controlled, double-masked, crossover study. 10 dogs with poorly controlled seizures. A programmable pacemaker-like device designed to deliver intermittent stimulation to the left cervical trunk of the vagus was surgically implanted in each dog. Dogs were assigned randomly to two 13-week test periods, 1 with nerve stimulation and 1 without nerve stimulation. Owners recorded data on seizure frequency, duration, and intensity, as well as adverse effects. No significant difference in seizure frequency, duration, or severity was detected between overall 13-week treatment and control periods. During the final 4 weeks of the treatment period, a significant decrease in mean seizure frequency (34.4%) was detected, compared with the control period. Complications included transient bradycardia, asystole, and apnea during intraoperative device testing, and seroma formation, subcutaneous migration of the generator, and transient Horner's syndrome during the 14-day period between surgery and suture removal. No adverse effects of stimulation were detected, and most owners were satisfied with the treatment. Vagal nerve stimulation is a potentially safe approach to seizure control that appears to be efficacious in certain dogs and should be considered a possible treatment option when antiepileptic medications are ineffective.

Long-term effects of 24-month treatment with vagus nerve stimulation on behaviour in children with Lennox–Gastaut syndrome

The long-term effects of vagus nerve stimulation (VNS) on behaviour were studied in 19 children with Lennox–Gastaut syndrome. We used the following stimulation parameters: output current: 1 1 2 to 2 mA; signal frequency: 30 Hz frequency; signal pulse width: 500 μs; signal ‘on and off’ time: 30 s ‘on,’ 3 min ‘off.’ The test battery consisted of cognitive tests assessing mental age and quality of life measurements assessing independency, behavioural problems, and mood. The results show relatively small changes in the behavioural outcomes, concurrent with the modest effects of VNS on seizure frequency (an average of 20.6% seizure reduction). When baseline measurements are compared with the follow-up measures, neither the cognitive measure nor the quality of life measures show any deterioration and the cognitive measure (mental age) showed mild positive changes (gain of 4.2 months mental age during the follow-up period). None of the changes were statistically significant. Treatment effect was most prominent in the group with the highest mental age at baseline, which suggests that mental retardation is a negative prognostic factor for VNS treatment. Moreover, in this specific patient group, treatment effect did not increase with treatment duration. Some evidence during follow-up suggests a direct positive effect of VNS on behavioural function, independent of changes in seizure frequency. Long-term treatment with VNS is not associated with adverse behavioural effects. Mental retardation is a negative prognostic factor for the efficacy of VNS.

Vagus nerve stimulation for treatment of medically intractable seizures. Evaluation of long-term outcome

Vagus nerve stimulation (VNS) constitutes an adjunctive, modern management of medically intractable seizures, especially when surgery is inadvisable. Objective: To evaluate the long-term results as regards efficacy, safety and tolerability of VNS in epileptic subjects, with focal and/or generalised seizures, refractory to old and new AEDs, without indication for resective surgery. Patients: 51 epileptic subjects (30 males, 21 females), aged 7–49 years, have been implanted so far. Results: The results refer to the 47 subjects with a follow-up longer than 6 months. 22 (46.8%) of them had a greater than 50% reduction in seizure frequency, with a more than 75% reduction in 6. No significant difference was found in relation to type of seizures. The efficacy maintained steadily over time during the follow-up (mean 26.4 months). Twelve out of the 47 subjects had an improvement in alertness, attention and psychomotor activity. Complications were observed in 5 cases, leading to removal of the stimulator in 2. A moderate vocal hoarseness (40.4%), paresthesia (6.3%), pharingodinia and cough (4.3%) were the registered adverse events. Conclusions: Our results confirm that VNS is effective, safe and well tolerated and constitutes an alternative treatment for pharmacoresistant epileptic seizures.

Programmed and magnet-induced vagus nerve stimulation for refractory epilepsy.

Vagus nerve stimulation (VNS) is an effective alternative treatment for patients with refractory epilepsy. The generator produces intermittent stimulation trains and does not require patient intervention. Using currently available technology, continuous stimulation is incompatible with a reasonable battery life. Because earlier studies have demonstrated the persistence of a stimulation effect after discontinuation of the stimulation train, we intended to evaluate the clinical efficacy of VNS in both the programmed intermittent stimulation mode and the magnet stimulation mode. Patients, companions, and caregivers were instructed on how to administer additional stimulation trains when an aura or a seizure onset occurred. We assumed that patients or caregivers could recognize habitual seizures and were able to evaluate sudden interruption of these seizures. During a mean follow-up of 35 months, 46% of patients became responders, with a reduction in seizure frequency of more than 50%. Twenty-nine percent of patients stopped having convulsive seizures. In two thirds of patients who were able to self-administer or receive additional magnet stimulation, seizures could be interrupted consistently or occasionally. More than half of the patients who reported a positive effect of magnet stimulation became responders. Only three patients were able to use the magnet themselves. In most cases, support from caregivers was necessary. This study is the first to document the efficacy of magnet-induced VNS in a larger patient population during long-term follow-up. The magnet is a useful tool that provides patients who are treated with VNS and mainly caregivers of such patients with an additional means of controlling seizures. To further confirm the self-reported results from our patients, additional studies comparing programmed stimulation and magnet-induced stimulation during monitoring conditions are needed.

Vagus nerve stimulation and Lennox-Gastaut syndrome: a review of the literature and data from the VNS patient registry.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is usually refractory to medical management. When medication fails, alternative therapies are considered. Among these are two surgical options: corpus callosotomy and vagus nerve stimulation (VNS). Safety and efficacy are two important factor to consider when selecting an appropriate treatment. VNS is safer than callosotomy, but its efficacy is more difficult to assess. Available studies evaluate its effectiveness using a mixed population of patients (some with prior epilepsy surgery), a multitude of VNS settings, and variable endpoints. To estimate the efficacy of VNS in patients with LGS, a review of the medical literature and the VNS Patient Registry was performed. Within the limits of this type of study, the results showed that VNS appears to be equally as effective as callosotomy. Because VNS has a lower potential for adverse effects, these results suggest that VNS should be considered first in appropriately selected patients.

Vagus Nerve Stimulation in the Developmentally Disabled

Vagus nerve stimulation (VNS) with the neuro cybernetic prosthesis (NCP) is an approved treatment of partial seizures for patients 12 years and older. Developmentally disabled or mentally retarded patients with epilepsy may also benefit from VNS; however, their evaluation and management pose greater problems. A retrospective chart review was conducted on all patients diagnosed with mild to severe mental retardation who had an NCP implanted. Records of these 21 patients, ranging in age from 3 to 56 years, were reviewed regarding VNS efficacy, side effects, behavioral changes, and alterations in antiepileptic drugs (AEDs). Seizure types included partial onset and generalized. Sixteen patients had clearly evaluable seizures both pre- and postimplant, with a greater than 50% reduction in seizures noted in 68% (11/16) after 6 months of implant. There were no adverse events that prevented chronic stimulation. Institutional staff and family members were provided with both pre- and postoperative education on VNS and magnet use. VNS appeared to be an effective and well-tolerated therapy in this group of developmentally disabled patients with refractory epilepsy.

Efficacy of Vagal Nerve Stimulation in Children with Medically Refractory Epilepsy

The effects of vagal nerve stimulation (VNS) on seizure frequency and quality of life were analyzed retrospectively in children with medically refractory epilepsy. Thirty-eight children aged 11 months to 16 years underwent implantation of vagal nerve stimulators. Age of seizure onset, duration of epilepsy, and seizure type and frequency were recorded preoperatively. Age at implantation, length of follow-up, seizure type and frequency, and change in quality of life (QOL) were recorded postoperatively. Changes in QOL were assigned a QOL score by the caretakers on a visual analog scale of -1 (much worse) to +1 (much improved). The median follow-up period was 12 months (range, 10-18 mo). Eleven (29%), 15 (39%), 5 (13%), and 7 (18%) children had greater than 90% reduction, 50 to 90% reduction, less than 50% reduction, and no reduction in seizure frequency, respectively. For all children, seizure reduction by seizure type was as follows: atonic (80%), absence (65%), complex partial (48%), and generalized tonicoclonic (45%). The mean change in QOL score was 0.61. Eighty-six percent of the children had QOL scores of 0.5 (improved) or higher. Follow-up of at least 6 months was associated with greater seizure reduction (P = 0.05) and higher QOL score (P < 0.01). Seizure reduction was greater in children with onset of epilepsy after 1 year of age (P < 0.05). The age of the child and duration of epilepsy were not associated with greater or lesser degrees of seizure reduction. VNS provided improvements in seizure control for the majority of children regardless of age. QOL was improved in the majority of children with VNS. VNS should be considered for children with medically refractory epilepsy who have no surgically resectable focus.

Efficacy of Vagal Nerve Stimulation in Children with Medically Refractory Epilepsy

ABSTRACT OBJECTIVE The effects of vagal nerve stimulation (VNS) on seizure frequency and quality of life were analyzed retrospectively in children with medically refractory epilepsy. METHODS Thirty-eight children aged 11 months to 16 years underwent implantation of vagal nerve stimulators. Age of seizure onset, duration of epilepsy, and seizure type and frequency were recorded preoperatively. Age at implantation, length of follow-up, seizure type and frequency, and change in quality of life (QOL) were recorded postoperatively. Changes in QOL were assigned a QOL score by the caretakers on a visual analog scale of −1 (much worse) to +1 (much improved). RESULTS The median follow-up period was 12 months (range, 10–18 mo). Eleven (29%), 15 (39%), 5 (13%), and 7 (18%) children had greater than 90% reduction, 50 to 90% reduction, less than 50% reduction, and no reduction in seizure frequency, respectively. For all children, seizure reduction by seizure type was as follows: atonic (80%), absence (65%), complex partial (48%), and generalized tonicoclonic (45%). The mean change in QOL score was 0.61. Eighty-six percent of the children had QOL scores of 0.5 (improved) or higher. Follow-up of at least 6 months was associated with greater seizure reduction (P = 0.05) and higher QOL score (P &amp;lt; 0.01). Seizure reduction was greater in children with onset of epilepsy after 1 year of age (P &amp;lt; 0.05). The age of the child and duration of epilepsy were not associated with greater or lesser degrees of seizure reduction. CONCLUSION VNS provided improvements in seizure control for the majority of children regardless of age. QOL was improved in the majority of children with VNS. VNS should be considered for children with medically refractory epilepsy who have no surgically resectable focus.

Acute single photon emission computed tomographic study of vagus nerve stimulation in refractory epilepsy.

Left-sided vagus nerve stimulation (VNS) is an efficacious treatment for patients with refractory epilepsy. The precise mechanism of action remains to be elucidated. Only limited data on VNS-induced changes in regional cerebral blood flow (rCBF) are available. The aim of this study was to investigate rCBF changes during initial VNS with single-photon emission computed tomography (SPECT). In 12 patients (8 women, 4 men) with mean age of 32 years and mean duration of epilepsy of 19 years, VNS-induced rCBF changes were studied by means of a 99mTc-ethyl cysteinate dimer activation study with a single-day split-dose protocol before and immediately after initial stimulation. Images were acquired on a triple-head camera with fan-beam collimators and were reconstructed with scatter and attenuation correction. After coregistration to a standardized template, both a semiquantitative analysis using predefined volumes-of-interest (VOIs) as well as voxel-by-voxel analysis of the intrasubject activation were performed. During follow-up, efficacy of VNS in terms of seizure-frequency reduction was studied. The semiquantitative analysis, with reference to the total counts in all VOIs, revealed a significant decrease of activity in the left thalamus immediately after the initial stimulation train. These results agreed with voxel-by-voxel analysis. In our study ipsilateral thalamic hypoperfusion was the most significant finding. Mean frequency of complex partial seizures was reduced from 30 per month before implantation to six per month after implantation. VNS induces rCBF changes immediately after initial stimulation that can be studied with SPECT. VNS-induced changes in the thalamus may play an important role in suppression of seizures. However, no significant relation between the level of hypoperfusion and subsequent clinical efficacy was found.

Evaluation of Refractory Epilepsy Treated with Vagus Nerve Stimulation for up to 5 Years; Ventricular Asystole During Vagal Nerve Stimulation for Epilepsy in Humans; Acute Blood Flow Changes and Efficacy of Vagus Nerve Stimulation in Partial Epilepsy; Unexpected Places: How Did Vagal Nerve Stimulation Become a Treatment for Epilepsy?

Evaluation of Refractory Epilepsy Treated with Vagus Nerve Stimulation for up to 5 Years; Ventricular Asystole During Vagal Nerve Stimulation for Epilepsy in Humans; Acute Blood Flow Changes and Efficacy of Vagus Nerve Stimulation in Partial Epilepsy; Unexpected Places: How Did Vagal Nerve Stimulation Become a Treatment for Epilepsy?

Efficacy of Vagal Nerve Stimulation in Patients with Prior Epilepsy Surgery

Efficacy of Vagal Nerve Stimulation in Patients with Prior Epilepsy Surgery

Reassessment: Vagus nerve stimulation for epilepsy [RETIRED

A July 1997 assessment of the American Academy of Neurology (AAN) Therapeutics and Technology Subcommittee reviewed vagus nerve stimulation (VNS) for epilepsy, and concluded that it was promising, but not yet established.1 Subsequent to that review, a second multicenter, randomized, controlled clinical trial has shown safety and efficacy of VNS for treatment of intractable partial seizures. Given the importance of this novel therapy for epilepsy, and the new information provided by a second major study, the Therapeutics and Technology Subcommittee requested an update on VNS. Use of VNS in epilepsy has recently been reviewed.2-4 VNS uses intermittent stimulation of the left vagus nerve in the neck to reduce the frequency and intensity of seizures. Mechanism of action of VNS remains uncertain, but stimulation does not induce grossly visible alterations in the human EEG.5 Recent studies suggest that metabolic activation of certain thalamic, brainstem, and limbic structures may be important in mediating the effect of VNS.6,7 Depletion of norepinephrine in the locus coeruleus attenuates the antiseizure affect of VNS.8 After open-label studies,9,10 sponsors of VNS engaged in a multicenter randomized study, named E03,11 details of which were reviewed in the previous assessment.1 Results of this trial were positive, and the technology was considered promising, but the number of patients receiving VNS was insufficient to achieve Food and Drug Administration approval. Therefore, a second randomized, controlled, multicenter clinical trial, called E05, was undertaken.12 The E05 study12 of VNS evaluated 254 patients, ages 13 to 60 years, with intractable partial seizures. To be eligible, subjects had to have at least six complex partial, visible partial motor, or secondarily generalized seizures in the month before entry, and to be free from other complicating neurologic, psychiatric, or medical conditions. …

Vagus Nerve Stimulation for Refractory Epilepsy

The efficacy of vagus nerve stimulation (VNS) was evaluated in 24 patients, aged 4 to 40 years (median 18 years), at the New York Presbyterian Hospital-Cornell Medical Center, NY; Mercy Children’s Hospital, Kansas City; and University of California at San Diego.

Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy.

To determine possible sites of therapeutic action of vagus nerve stimulation (VNS), by correlating acute VNS-induced regional cerebral blood flow (rCBF) alterations and chronic therapeutic responses. We previously found that VNS acutely induces rCBF alterations at sites that receive vagal afferents and higher-order projections, including dorsal medulla, somatosensory cortex (contralateral to stimulation), thalamus and cerebellum bilaterally, and several limbic structures (including hippocampus and amygdala bilaterally). VNS-induced rCBF changes were measured by subtracting resting rCBF from rCBF during VNS, using [O-15]water and PET, immediately before ongoing VNS began, in 11 partial epilepsy patients. T-statistical mapping established relative rCBF increases and decreases for each patient. Percent changes in frequency of complex partial seizures (with or without secondary generalization) during three months of VNS compared with pre-VNS baseline, and T-thresholded rCBF changes (for each of the 25 regions of previously observed significant CBF change), were rank ordered across patients. Spearman rank correlation coefficients assessed associations of seizure-frequency change and t-thresholded rCBF change. Seizure-frequency changes ranged from 71% decrease to 12% increase during VNS. Only the right and left thalami showed significant associations of rCBF change with seizure-frequency change. Increased right and left thalamic CBF correlated with decreased seizures (p < 0.001). Increased thalamic synaptic activities probably mediate some antiseizure effects of VNS. Future studies should examine neurotransmitter-receptor alterations in reticular and specific thalamic nuclei during VNS.

Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years.

We assessed the long-term efficacy of vagus nerve stimulation (VNS) in 64 refractory epilepsy patients. After implantation, intermittent stimulation was delivered and seizure frequency and severity were counted. Average treatment time was 20 months. Nineteen of 47 patients with partial seizures, five of nine patients with idiopathic generalized seizures, and five of eight patients with Lennox-Gastaut syndrome had >50% seizure reduction. Side effects were mild. VNS is a safe and effective treatment for refractory epilepsy.

Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation.

Although vagus nerve stimulation (VNS) is now marketed throughout most of the world as a treatment for drug-resistant epilepsy, the therapeutic mechanism of action of VNS-induced seizure suppression has not yet been established. Elucidation of this mechanism is an important first step in the development of strategies to improve VNS efficacy. Because the locus coeruleus (LC) has been implicated in the antinociceptive effects of VNS, we chemically lesioned the LC in the present study to determine if it is a critical structure involved in the anticonvulsant mechanisms of VNS. Rats were chronically depleted of norepinephrine (NE) by a bilateral infusion of 6-hydroxydopamine (6-OHDA) into the LC. Two weeks later, they were tested with maximal electroshock (MES) to assess VNS-induced seizure suppression. In another experiment, the LC was acutely inactivated with lidocaine, and seizure suppression was tested in a similar fashion. VNS significantly reduced seizure severities of control rats. However, in animals with chronic or acute LC lesions, VNS-induced seizure suppression was attenuated. Our data indicate that the LC is involved in the circuitry necessary for the anticonvulsant effects of VNS. Seizure suppression by VNS may therefore depend on the release of NE, a neuromodulator that has anticonvulsant effects. These data suggest that noradrenergic agonists might enhance VNS-induced seizure suppression.

Effect of Vagus Nerve Stimulation on Intractable Epilepsy

Purpose: Since 1993, we have studied the efficacy and safety of vagus nerve stimulation (VNS) with a Neurocyberhetic Prosthesis (NCP) (Cyberonics, U.S.A.) against medically intractable epilepsy first in Japan. We summarize the intermediate results so far acquired in this report. Methods: Patients with intractable partial seizures were selected as candidates for implantation of the NCP. This type of therapy has been tested in individuals whose seizure activity has not been effectively controlled by pharmacotherapy. The result was a reduction in the rate of seizures in each period compared with the average number of seizures before implantation of the NCP. To avoid nerve fatigue, the upper limits of the parameters were set as follows: frequency, 30 Hz; pulse width, 1,000 μ; on time, 60 s; output current, 3.0 mA. After informed consent, the leads of the NCP were connected under general anesthesia to the cervical portion of the left vagus nerve. Those leads were connected through a subcutaneous tunnel with the NCP implanted subcutaneously on the breast. Thirty‐four patients have been implanted with the NCP, and 31 patients have started stimulation as of September, 1997. We have analyzed the data from 16 male and 15 female patients who were followed up for &gt;6 months with a mean follow‐up period of 20.0 months; their ages ranged from 19 to 52 years with a mean age of 31.2 years. Their types of seizures included 28 complex partial seizures (CPSs), 12 simple partial seizures (SPSs) and 11 secondarily generalized seizures (SGSs). The number of seizures during a month was counted for 3 consecutive months before implantation of NCP. These values were compared with average number of seizures that occurred during the 4–6 months after VNS. We also calculated the patients with a 50% reduction in seizure frequency compared with the baseline. Results: the mean seizure‐changing rates during the 4–6 months after stimulation were −26.4 2 13.2% (mean ± SEM) in total seizure numbers, −41.9 ± 13.0% in seizure with disturbance of consciousness, −37.0 ± 19.9% in SGSs, −70.4 ± 17.6% in CPSs, and −15.5 ± 16.2% in SPSs. The 50% reduction rates were 48.4% for all seizure types, 63.3% in seizures with disturbance of consciousness, 58.6% in CPSs, 63.6% in SGSs, and 47.1% in SPSs during the 4 4 months after stimulation. Conclusions: Our early results demonstrated the efficacy and safety of VNS with the NCP in medically intractable epilepsy. We adpated the VNS for intractable epilepsy, and our results demonstrated its efficacy. The reduction of seizures was observed more strongly in the latest 3 months than during the 4–6 months after starting the VNS. This result may be due to the characteristics of VNS or the period when we needed to adjust the parameters of the NCP. The efficacy of VNS during the latest 3 months is better than that of recent antiepileptic agents. However, we have not yet achieved any seizure‐free patients, although their seizure rates have been reduced. We need more experiences with VNS to determine the appropriate parameters and find out how to select the most suitable cases.

Vagus nerve stimulation for intractable epilepsy: a review.

Electrical stimulation of the vagus nerve in the neck by using a programmable stimulator similar to a cardiac pacemaker is being explored as a treatment for epilepsy. There is sound rationale based on studies of animal seizure models for pursuing this treatment modality, and early clinical trials provide support for efficacy in patients with intractable epilepsy at least equivalent to that of some of the new antiepileptic drugs. Safety and tolerability have been demonstrated in >800 patients worldwide since the first implant in 1988. Most of these had partial seizures for which resective epilepsy surgery was not feasible or had failed, but efficacy of vagal stimulation appears to be the same for both partial and generalized epilepsy. Specific selection criteria for this procedure have yet to be established, and further studies are warranted to determine whether vagal stimulation becomes an accepted procedure for epilepsy management.

Long-term follow-up of 37 patients with refractory partial seizures treated with vagus nerve stimulation

Stimulation of the vagus nerve for the treatment of refractory seizures of partial onset has been studied in two pilot studies and one randomized, blinded, parallel study. Results from the controlled study have been promising, but more information is required regarding the long-term safety and efficacy of vagus nerve stimulation. A cohort of the first 37 patients to finish the controlled study was examined on a long-term basis. The response of patients at 1 year and 18 months of stimulation revealed that efficacy does not decrease over time. The system is well-tolerated, and no major adverse events occurred with long-term exposure to the stimulation. Normal device end of service occurred in a majority of the patients, with most choosing to have their generators replaced. This analysis demonstrates that stimulation of the vagus nerve for the treatment of refractory epilepsy manifested by seizures of partial onset continues to be safe and effective over extended periods of time.

Vagus nerve stimulation for complex partial seizures: surgical technique, safety, and efficacy

Electrical stimulation of the vagus nerve has shown efficacy in controlling seizures in experimental models, and early clinical trials have suggested possible benefit in humans. Eleven patients with complex partial seizures were subjected to implantation of vagus nerve stimulators. Electrode contacts embedded in silicone rubber spirals were placed on the left vagus nerve in the low cervical area. A transcutaneously programmable stimulator module was placed in an infraclavicular subcutaneous pocket and connected to the electrode. One patient required replacement of the system due to electrode fracture. Another patient developed delayed ipsilateral vocal-cord paralysis; the technique was then modified to allow more tolerance for postoperative nerve edema. A third patient showed asymptomatic vocal-cord paresis on immediate postoperative laryngoscopy. Vagus nerve stimulation produces transient vocal-cord dysfunction while the current is on. Nine patients were randomly assigned to receive either high- or low-current stimulation, and seizure frequency was recorded. The high-current stimulation group showed a median reduction in seizure frequency of 27.7% compared to the preimplantation baseline, while the low-current stimulation group showed a median increase of 6.3%. This difference approached statistical significance. The entire population then received maximally tolerable stimulation. The high-current stimulation group showed a further 14.3% reduction, while the low-current stimulation group showed a 25.4% reduction compared to the blinded period. The efficacy of vagus nerve stimulation seemed to depend on stimulus parameters, and a cumulative effect was evident. These results are encouraging, and further study of this modality as an adjunct treatment for epilepsy is warranted.