Underwent Vagus Nerve Stimulator Research Articles

Efficacy of vagus nerve stimulation for drug-resistant epilepsy in a survivor of poor-grade subarachnoid hemorrhage: A case report

A man in his 60s had undergone clipping for a subarachnoid hemorrhage (SAH) due to a ruptured anterior communicating artery aneurysm in his 40s. He survived cerebral vasospasms following surgery for poor-grade SAH and required anti-seizure medications (ASMs) for post-stroke epilepsy. More than 20 years after the clipping, he developed focal impaired awareness seizure, which decreased his quality of life (QOL). Computed tomography (CT) showed an infarct in the left frontal lobe. 123I-iomazenil single-photon emission CT showed decreased benzodiazepine accumulation in the left frontal and medial temporal lobes. An interictal electroencephalogram showed epileptic discharges in the left temporal region. We diagnosed focal epilepsy and adjusted ASMs based on seizure control. However, the seizures were not controlled, and the adverse effects worsened with dosage increase. The condition was diagnosed as drug-resistant epilepsy, and the patient underwent vagus nerve stimulation. Postoperatively, we confirmed control of seizures and improvement of QOL.

Dual-Device Neuromodulation in Epilepsy

Current methods of neuromodulation have been shown to reduce seizures in patients with drug-resistant epilepsy, and in a small percentage of patients it has rendered them seizure-free when surgical resection is not feasible. While polytherapy with antiseizure medication is not uncommon, dual neurostimulation has received limited attention. We set out to identify trends and changes in the use of dual neurostimulation to understand choosing device combinations. We reviewed the Mayo Clinic database in Florida of patients who underwent vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) from October 1998 through September 2021. The prevalence of active VNS with DBS or RNS was considered dual therapy. In total, 131 patients (71 female) underwent 164 VNS-associated procedures, 28 received RNS, and 8 received DBS (6 anterior thalamic DBS; 2 thalamic centromedian nucleus DBS). Active dual stimulation occurred in 3 of 28 patients who received RNS and 8 of 8 patients who received DBS (P= 0.006), mean duration of 28 and 16.3 months, respectively. Patients who received VNS-DBS were more likely to have a previous response to VNS (P= 0.025) and were unresponsive to more antiseizure medications (P= 0.020). The VNS-RNS group had focal seizures more likely to have electroclinical localization (P= 0.005) and more frequently underwent invasive electroencephalographic monitoring (P= 0.026). The ability to localize was the primary decision-maker in prompting RNS versus DBS. RNS surgery was more likely to be preceded by invasive electroencephalographic monitoring. Previous VNS responsiveness was more prominent in patients with DBS. Dual therapy was safe. Prospective multicenter studies of dual-device neuromodulation are needed.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders

IntroductionLittle is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. MethodsA total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. ResultsNineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). ConclusionEpilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

Vagus nerve stimulation in pediatric patients with failed epilepsy surgery.

Adequate control of pharmacoresistant epilepsy continues to be a challenge. Multiple studies have reported the benefits of epilepsy surgery and vagus nerve stimulation for children with pharmacoresistant epilepsy. Little is known about the role of vagus nerve stimulation for children with failed epilepsy surgeries. The aim of this study was to examine the effects of vagus nerve stimulation on seizure frequency reduction for children with failed epilepsy surgeries. We retrospectively reviewed 85 children with pharmacoresistant epilepsy who underwent vagus nerve stimulation. Six of these patients underwent epilepsy surgery before vagus nerve stimulation (group I) and 79 patients received only vagus nerve stimulation (group II). We recorded seizure frequency at 3, 12, 24 and 36months after vagus nerve stimulator implantation. Both groups had reduced seizure frequencies at the 3-, 12-, 24- and 36-month follow-up (p = 0.044 for group I trends and 0.008 for group II trends). Vagus nerve stimulator implantations significantly improve seizure frequency for children with or without previous epilepsy surgery at 3, 12, 24 and 36months. These findings suggest that vagus nerve stimulation should be considered an alternative therapy for pediatric patients with previous failed surgeries.

Analysis of pharmacotherapy regimen and costs in patients with drug-resistant epilepsy following vagus nerve stimulation therapy: a single-center study (Poland).

Approximately 30-40% of patients with drug-resistant epilepsy (DRE) who underwent vagus nerve stimulator (VNS) implantation achieve above 50% reduction in seizure frequency. VNS proves effective in reducing frequency of seizures in DRE patients, when combined with antiepileptic drugs (AEDs). This raises a question whether improvement of clinical parameters is achieved with VNS only or relies on combined therapy with AEDs. The aim of the study was the analysis of impact of VNS on clinical recovery of patients with DRE and the analysis of pharmacotherapy costs and drug regimen following VNS implantation in DRE patients. The study included all the patients who had VNS implanted at our department in the years 2014-2018. The patients would be followed up for 2years after the VNS implantation date. The most commonly used drugs included levetiracetam, lacosamide, valproate, oxcarbazepine, and topiramate. Average cost of AEDs in year 1 following VNS implantation was between EUR 15.53 (CLB) and EUR 545.52 (TGB) and in year 2 between EUR 13.51 (NTZ) and EUR 779.44 (LAC). The greatest number of seizures affected the group of patients treated with three drugs. A statistically significant improvement in seizure frequency was observed in the group of patients treated with two and three drugs. With the rising costs of healthcare, the importance of economic efficiency is becoming increasingly relevant. VNS is a reasonable option for saving money in the healthcare system while ensuring measurable clinical and therapeutic outcomes over the long term.

Economic and clinical evaluation of vagus nerve stimulation therapy.

The medical and social care of drug-resistant epilepsy (DRE) entails significant costs. Approximately 30 to 40 percent of patients with DRE who underwent vagus nerve stimulator (VNS) implantation achieve anabove 50percent reduction in seizure frequency. The study objective was to analyze the effect of VNS on clinical effects improvement and therapy cost reduction in patients with DRE over a 2-year follow-up period. The second purpose of the study was to compare average costs of VNS treatment of patients with DRE in selected countries, taking into account the purchasing power parity. The study included all the patients who had VNS implanted at our department between 2014 and 2018. Data on clinical events and medical costs were collected prospectively and obtained from medical documentation. We also reviewed relevant literature on costs of VNS therapy in patients with DRE from the last 18years. Resource utilization and epilepsy-related events were reduced during the follow-up period compared to the baseline. Average total cost was estimated at EUR7703.59 in year1 and at EUR7108.38 in year2 following VNS implantation. Average direct costs of VNS treatment of patients with DRE over the last 18years varied between the countries and ranged from EUR24790.43 in the United States to EUR64.84 in the United Kingdom. Vagus nerve stimulator is a cost-effective therapy yielding measurable clinical and therapeutic outcomes over the long term. Moreover, theanalysis contained in this review highlights the poor consensus of methodological approaches.

Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy.

To describe the response to vagus nerve stimulator (VNS) in otherwise neurotypical children with medically intractable primary generalized epilepsy. Retrospective chart review of patients who underwent vagus nerve stimulator surgery between January 2011 and December 2015. Eleven patients were identified. Median follow-up duration was 2.5 years (1.2-8.4 years). Prior to vagus nerve stimulator surgery, all patients had at least 1 seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11 (55%) reported fewer than 1 seizure per month. Three patients (27%) reported complications related to vagus nerve stimulator surgery, and no patients required device removal. In children with medically intractable primary generalized epilepsy, vagus nerve stimulator is well tolerated and appears to lead to improvement in seizure frequency. Improvement was not attributable to epilepsy classification, age at vagus nerve stimulator implantation, output current, duty cycle, or follow-up duration.

Vagus nerve stimulation in children less than 3 years with medically intractable epilepsy

ObjectiveTo describe the characteristics of children less than three years of age with medically intractable epilepsy, who underwent Vagus Nerve Stimulator (VNS) therapy at Children's Hospital of Pittsburgh between 2004 and 2011. Methods: Retrospective chart review. Results: Seventeen patients were identified; adequate follow-up was available for 15. Median follow up duration was 4.3 years (1.4–10.2 years). 12/15 (80%) had a known etiology for their epilepsy. All patients had more than 1 seizure per week prior to VNS and a history of status epilepticus was frequent (40%, 6/15). Five patients (33%) reported improved seizure frequency at one year after VNS. A normal MRI was associated with seizure improvement (p=0.007). No patient had status epilepticus after VNS at one-year follow-up. At three years after VNS, four patients had experienced status epilepticus with only one patient experiencing multiple episodes. Complications were seen in 2/15 (13%) patients and in 2/21 (9.5%) procedures. Significance: A normal MRI was associated with seizure improvement at one year in children less than three years of age at the time of VNS implant. The degree of overall seizure reduction was modest, but the frequency of status epilepticus was decreased after VNS implant. VNS was tolerated well in this age group.

The prognosis of refractory epilepsy patients rejected from epilepsy surgery.

Up to one-third of individuals diagnosed as having epilepsy continue to have seizures despite appropriate anti-epileptic drug treatment. These patients are often referred for presurgical evaluation, and many are rejected from focal resective surgery due to medical reasons or, alternatively, they choose not to undergo it. We compared the outcomes and characteristics of the non-operated patients who continued on medical therapy alone with those who underwent vagus nerve stimulator (VNS) implantation in addition to medical therapy. The medical records of consecutive adult patients referred for presurgical evaluation for suitability for epilepsy surgery in the Tel-Aviv Sourasky Medical Center between 2007 and 2011 and were rejected from or decided against surgery were reviewed. Updated information on seizure frequency was supplemented by telephone interviews between April and July, 2013. Fifty-two patients who continued solely on medical therapy and 35 patients who additionally underwent VNS implantation were included in the study. Forty-seven of the former and 33 of the latter agreed to be interviewed. There was a significant improvement in the seizure frequency between the time of the presurgical evaluation and the time of the interview in both groups. Eight medically treated patients (17%) and 2 patients who also underwent VNS implantation (6%) reported being seizure-free during the preceding 3 months. A considerable minority of patients with refractory epilepsy who were rejected or chose not to undergo epilepsy surgery may improve over time and even become seizure-free following adjustment of anti-epileptic drugs with or without concomitant VNS.

Long-term outcome of vagus nerve stimulation therapy after failed epilepsy surgery

Objective Adequate control of intractable epilepsy continues to be a challenge. Little is known about the role of VNS therapy in intractable epilepsy in patients who failed to respond to surgical management. The objective of the present study is to determine the efficacy of vagus nerve stimulation therapy in patients with intractable epilepsy who have failed surgical and medical therapy. Methods All the patients who had persistent seizures after cranial surgery who subsequently underwent vagus nerve stimulator (VNS) placement at our institution from 1998 to 2008 were included in the study. Thirty-seven consecutive patients were enrolled and followed for the outcome measures of seizure burden, anti-epileptic drug (AED) burden and quality of life (QoL). Minimum follow-up was 18 months. Results Overall, 24 (64.9%), 9 (24.3%), 4 (10.8%) patients reported less than 30%, between 30% and 60% and greater than 60% reduction in seizure frequency after VNS placement, respectively at a mean of 5 years follow-up period. Post-VNS anti-epileptic requirement exhibited a decreasing trend. 17 patients (45.9%) report an improvement in QoL (better or much better). Conclusion VNS therapy in patients who have failed medical and surgical therapies only provides marginal improvement in seizure control but has greater likelihood to improve subjective QoL issues. In addition, VNS has the potential to reduce AED burden without adversely impacting seizure management. Given the low surgical risk of VNS placement, vagus nerve stimulation as a therapeutic modality should be individualized to achieve best clinical response and fewest side effects.

Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: Long-term outcomes and predictors of response

ObjectiveThe goal of this study was to assess the efficacy and safety of vagus nerve stimulation in a consecutive series of adults and children with treatment-resistant epilepsy (TRE). MethodsIn this retrospective review of a prospectively created database of 436 consecutive patients who underwent vagus nerve stimulator implantation for TRE between November 1997 and April 2008, there were 220 (50.5%) females and 216 (49.5%) males ranging in age from 1 to 76years at the time of implantation (mean: 29.0±16.5). Thirty-three patients (7.6%) in the primary implantation group had inadequate follow-up (<3months from implantation) and three patients had early device removal because of infection and were excluded from seizure control outcome analyses. ResultsDuration of vagus nerve stimulation treatment varied from 10days to 11years (mean: 4.94years). Mean seizure frequency significantly improved following implantation (mean reduction: 55.8%, P<0.0001). Seizure control ≥90% was achieved in 90 patients (22.5%), ≥75% seizure control in 162 patients (40.5%), ≥50% improvement in 255 patients (63.75%), and <50% improvement in 145 patients (36.25%). Permanent injury to the vagus nerve occurred in 2.8% of patients. ConclusionVagus nerve stimulation is a safe and effective palliative treatment option for focal and generalized TRE in adults and children. When used in conjunction with a multidisciplinary and multimodality treatment regimen including aggressive antiepileptic drug regimens and epilepsy surgery when appropriate, more than 60% of patients with TRE experienced at least a 50% reduction in seizure burden. Good results were seen in patients with non-U.S. Food and Drug Administration-approved indications. Prospective, randomized trials are needed for patients with generalized epilepsies and for younger children to potentially expand the number of patients who may benefit from this palliative treatment.

Refractory epilepsy in tuberous sclerosis: Vagus nerve stimulation with or without subsequent resective surgery

Objective The goal of the work described here was to assess the efficacy and safety of vagus nerve stimulation in a cohort of patients with tuberous sclerosis complex with refractory epilepsy. Furthermore, we examined the impact of vagus nerve stimulation failure on the ultimate outcome following subsequent intracranial epilepsy surgery. Methods A retrospective review was performed on 19 patients with refractory epilepsy and TSC who underwent vagus nerve stimulator (VNS) implantation. There were 11 (58%) females and 8 (42%) males aged 2 to 44 years when the VNS was implanted (mean: 14.7 ± 12 years). Twelve patients underwent primary VNS implantation after having failed a mean of 7.1 antiepileptic drugs. Two patients (17%) had generalized epilepsy, one had a single seizure focus, three (25%) had multifocal epilepsy, and six (50%) had multifocal and generalized epilepsy. Seven patients were referred for device removal and evaluation for intracranial procedures. One patient in the primary implantation group was lost to follow-up and excluded from outcome analysis. Results All implantations and removals were performed without permanent complications. The duration of treatment for primary VNS implants varied from 8.5 months to 9.6 years (mean: 4.9 years). Mean seizure frequency significantly improved following VNS implantation (mean reduction: 72%, P < 0.002). Two patients had Engel Class I (18%), one had Class II (9%), seven had Class III (64%), and one had Class IV (9%) outcome. Three patients with poor response to vagus nerve stimulation therapy at our center underwent resection of one or more seizure foci (Engel Class I, two patients; Engel Class III, one patient). Seven patients referred to our center for VNS removal and craniotomy underwent seizure focus resection (6) or corpus callosotomy (1) (Engel Class II: 2, Engel III: 2; Engel IV: 3). In total, 8 of 10 (80%) patients experienced improved seizure control following intracranial surgery (mean reduction: 65%, range: 0–100%, P < 0.05). Conclusions VNS is a safe and effective treatment option for medically refractory epilepsy in patients with tuberous sclerosis complex. Nine of 11 patients (82%) experienced at least a 67% reduction in seizure burden. Lack of response to vagus nerve stimulation does not preclude subsequent improvement in seizure burden with intracranial epilepsy surgery.

Quality of Life and Seizure Outcome After Vagus Nerve Stimulation in Children With Intractable Epilepsy

This study examined the effect of vagus nerve stimulation on quality of life in children with epilepsy using a validated quality-of-life scale and an empirical technique that accounts for measurement error in assessing individual change (the reliable change index). Participants were 34 children with severe intractable epilepsy who underwent vagus nerve stimulation and 19 children with intractable epilepsy who received medical management. Parent-completed epilepsy-specific and global ratings at baseline and after 1 year indicated that most children had no changes in quality of life following vagus nerve stimulation (52%-77%), similar to the comparison group. There was a trend for decreases to be less common in the vagus nerve stimulation group (14% vs 37%, P < .07), but there was no relation between improved quality of life and seizure control. The results raise questions about the mechanisms that underlie changes in quality of life after vagus nerve stimulation in this group of children.

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.