Left-sided Vagus Nerve Stimulation Research Articles

Left-sided vagus nerve stimulation improves cardiopulmonary resuscitation outcomes in rats as effectively as right-sided vagus nerve stimulation.

Our group previously reported that right-sided vagus nerve stimulation (RVNS) significantly improved outcomes after cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA). However, whether left-sided vagus nerve stimulation (LVNS) could achieve the same effect as RVNS in CPR outcomes remains unknown. A rat model of CA was established using modified percutaneous epicardial electrical stimulation to induce ventricular fibrillation (VF). Rats were treated with LVNS or RVNS for 30 minutes before the induction of VF. All animals were observed closely within 72 hours after return of spontaneous circulation (ROSC), and their health and behavior were evaluated every 24 hours. Compared with those in the RVNS group, the hemodynamic measurements in the LVNS group decreased more notably. Vagus nerve stimulation (VNS) decreased the serum levels of tumor necrosis factor-alpha (TNF-α) and the arrhythmia score, and attenuated inflammatory infiltration in myocardial tissue after ROSC, regardless of the side of stimulation, compared with findings in the CPR group. Both LVNS and RVNS ameliorated myocardial function and increased the expression of α-7 nicotinic acetylcholine receptor in the myocardium after ROSC. Moreover, a clear improvement in 72-hour survival was shown with VNS pre-treatment, with no significant difference in efficacy when comparing the laterality of stimulation. LVNS may have similar effects as RVNS on improving outcomes after CPR.

Evaluation of heart rate variability in dogs during standard and microburst vagus nerve stimulation: A pilot study

Vagus nerve stimulation (VNS) is an established treatment for epilepsy and depression in human patients, but in both humans and dogs, optimal stimulation parameters remain unknown. Delivering afferent bursts of stimulation may be promising as a means of increasing efficacy, but evaluation of potential effects on the heart due to unavoidable efferent stimulation is required. The present study investigated heart rate variability (HRV) in healthy Beagle dogs treated with 1 h of sham, standard or microburst left-sided VNS in a crossover design. No significant differences were found between the stimulation paradigms for any of the cardiac parameters. Short-term left-sided VNS, including a novel bursting pattern (microburst VNS), had no statistically significant effect on HRV in ambulatory healthy dogs. Studies in a larger number of animals with long-term VNS are recommended.

Operative and Technical Complications of Vagus Nerve Stimulator Implantation

The treatment of refractory epilepsy by vagus nerve stimulation (VNS) is a well-established therapy option for patients not suitable for epilepsy surgery and therapy refractory depressions. To analyze surgical and technical complications after implantation of left-sided VNS in patients with therapy-refractory epilepsy and depression. One hundred five patients receiving a VNS or VNS-related operations (n = 118) from 1999 to 2008 were investigated retrospectively. At the time of operation, 84 patients were younger than 18 years, with a mean age of 10.5 years. Twenty (19%) patients had technical problems or complications. In 6 (5.7%) patients these problems were caused by the operation. The device was removed in 8 cases. The range of surgically and technically induced complications included electrode fractures, early and late onset of deep wound infections, transient vocal cord palsy, cardiac arrhythmia under test stimulation, electrode malfunction, and posttraumatic dysfunction of the stimulator. VNS therapy is combined with a wide spread of possible complications. Technical problems are to be expected, including electrode fracture, dislocation, and generator malfunction. The major complication in younger patients is the electrode fracture, which might be induced by growth during adolescence. Surgically induced complications of VNS implantation are comparably low. Cardiac symptoms and recurrent nerve palsy need to be taken into consideration.

Right-sided vagus nerve stimulation in humans: An effective therapy?

Vagus nerve stimulation (VNS) is an additive treatment option for refractory epilepsy. The electrode is placed on the cervical trunk of the left vagus nerve. In patients who are not suitable for left-sided vagus nerve stimulation (L-VNS) right-sided vagus nerve stimulation (R-VNS) may be as effective. In animal models epilepsy is sufficiently suppressed by R-VNS. In a 16 years old boy suffering from medically refractory psychomotoric seizures with secondary generalisation, L-VNS reduced the frequency of generalized seizures. A deep wound infection required the removal of the system eight weeks later. Cicatrisation did not allow preparation of the left vagus nerve, therefore we implanted R-VNS with sufficient seizure suppression. However, compared to L-VNS, the effect occurred months later and cardiac symptoms were induced by stimulation of the right vagus nerve. R-VNS seems to be an effective and alternative therapy in selected patients responding to L-VNS where a left-sided reimplantation is not possible. Placement and adjustment of the device should be performed under ECG control. Further studies are necessary to compare the efficacy of L-VNS and R-VNS.

Right‐sided vagus nerve stimulation inhibits induced spinal cord seizures

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Right‐sided Vagus Nerve Stimulation as a Treatment for Refractory Epilepsy in Humans

We present three children who underwent right-sided vagus nerve stimulation (R-VNS). This treatment option for people with refractory epilepsy has not been described in children. We reviewed our database of >350 patients implanted with vagus nerve stimulators and now describe our experience in three patients with R-VNS for the treatment of intractable seizures. All three patients improved dramatically with left-sided vagus nerve stimulation (L-VNS), but the devices had to be removed because of infection. The patients were thought to be at high risk for nerve injury if they were reapproached for L-VNSs; therefore R-VNSs were implanted. All three patients with an R-VNS had a reduction in seizures. Our first patient has had an R-VNS for 5 years; he has been seizure free for >2 years on R-VNS monotherapy. The second patient had an R-VNS for 8 months. His seizure control improved slightly, but not as dramatically as with L-VNS. The third child has had an R-VNS for >7 months and has cessation of his most disabling seizure type (generalized tonic-clonic seizures). None of the patients had cardiac side effects from therapeutic R-VNS. However, two of the three patients had respiratory events with R-VNS. VNS is known to be an effective treatment in pharmacoresistant epilepsy. R-VNS should be considered if a patient has significant benefit from L-VNS but is unable to continue with L-VNS. R-VNS appears also to have antiepilepsy effects. Additionally, our case report suggests that in some patients, a differential response is found regarding seizure control with R-VNS or L-VNS, raising the question whether L-VNS failures should pursue a trial of R-VNS. Patients should be cautioned and monitored for reactive airway disease if they undergo R-VNS. More research is needed to compare the effects of right- and left-sided VNS on cardiac and pulmonary function in humans and to determine which has the best antiseizure effect.

Left-sided vagus nerve stimulation decreases intracranial pressure without resultant bradycardia in the pig: a potential therapeutic modality for humans.

The medical literature is lacking in data regarding intracranial pressure in an animal model with concomitant vagus nerve and spinal cord stimulation. Ten pigs were anesthetized and placed in the supine position and an intracranial pressure monitor was inserted. Each study animal had a small laminectomy performed in the lumbar region and the left vagus nerve exposed within the carotid sheath. Intracranial pressure was monitored for 3 h in all animals. Eight animals at the end of 3 h of monitoring underwent vagus nerve stimulation and or spinal cord stimulation. Study and control animals had their intracranial pressure monitored for an additional 1 and 2 h respectively. Following vagus nerve stimulation, all animals had significant (p<0.05) decreases in their intracranial pressure with a lasting effect of 15-35 min (mean 18.5 min). No significant change in blood pressure was noted during stimulation of the vagus nerve. After spinal cord stimulation all animals responded with acute increases in their intracranial pressure (p<0.05). Left vagus nerve stimulation reliably decreases intracranial pressure in the pig. The mechanism of this action remains unclear and does not appear to be due to resultant bradycardia. Conversely, stimulation of the upper lumbar spinal cord increases intracranial pressure with simultaneous increases in heart rate. Following additional studies and with close observation of cerebral perfusion pressure, we believe that left vagus nerve stimulation may represent a novel adjunctive therapy for decreasing elevated intracranial pressure in posttraumatic human patients with head injuries. Additionally, according to this animal data, minimizing spinal cord stimulation should be considered in the acute setting following head injury so as to minimize iatrogenic elevation of intracranial pressure.

Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided

As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30 s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve.

Vagus Nerve Stimulation for Refractory Epilepsy

Left-sided vagus nerve stimulation (VNS) is a relatively new and efficacious neurophysiological treatment for patients with refractory epilepsy who were rejected for resective epilepsy surgery or who have had insufficient benefit from such a treatment. Animal experiments have shown that electrical stimulation of the vagus nerve can reduce the occurrence and duration of electrically and chemically induced seizures. The precise mechanism of action remains unclear. In 1988 the first vagus nerve stimulator was implanted in humans. Currently more than 7500 patients have been implanted world-wide. Randomized controlled clinical studies have shown a more than 50% reduction in seizure frequency in one third of the patients. Results on long-term treatment indicate that VNS remains effective over time and a trend towards improved seizure control with longer use of VNS was observed. VNS seems equally efficient in children. Hoarseness or voice change during stimulation are the most common side effects. VNS requires a substantial financial investment. Cost-efficacy studies have shown that these costs can easily be payed back by savings in epilepsy related direct medical costs in patients treated with VNS.

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.