Vagus Nerve Stimulator Insertion Research Articles

Effect of vagus nerve stimulation on emergency department utilization in children with drug-resistant epilepsy: a retrospective cohort study.

Epilepsy affects approximately 470,000 children in the United States. The estimated median incidence is 50.4 cases per 100,000 persons per year. There are approximately 3.1 million seizure-related emergency department (ED) visits per year among children. Vagus nerve stimulation (VNS) is a treatment option for drug-resistant epilepsy (DRE). While its primary goal is to decrease seizure burden, VNS may decrease seizure intensity and improve quality of life. The authors assessed whether VNS decreased the number of seizure-related ED visits in a cohort of children with DRE. The authors performed a retrospective chart review of pediatric patients (aged 0-21 years) who underwent implantation of a vagus nerve stimulator between January 2009 and January 2020 at the University of Pittsburgh Medical Center Children's Hospital of Pittsburgh. They used paired t-tests to assess differences in the number of ED visits 2 years before versus 2 years after VNS device implantation. Univariable linear regression analyses were used to test associations of preoperative characteristics with change in the number of ED visits following vagus nerve stimulator insertion. This study included 240 patients. Compared with patients without seizure-related ED visits before VNS, patients with ≥ 1 ED visits were younger in age at first VNS surgery (9.5 vs 10.8 years), had a shorter epilepsy duration before VNS surgery (5.8 vs 7.4 years), had a later year of device implantation (2014 vs 2012), and on average took more antiseizure medications (ASMs; 2.4 vs 2.1). There was no significant difference between the total number of seizure-related ED visits pre- versus post-VNS surgery (1.72 vs 1.59, p = 0.50), and no difference in status epilepticus-related visits (0.59 vs 0.46, p = 0.17). Univariable linear regression analyses revealed a mean change in ED visits of +0.3 for each year prior to 2022 and -0.5 for each additional ASM that patients took before vagus nerve stimulator insertion. This single-institution analysis demonstrated no significant change in the number of seizure-related ED visits within 2 years following VNS device implantation. Earlier VNS surgery was associated with more seizure-related ED visits after device insertion, suggesting that medical management and center experience may play a role in decreasing seizure-related ED visits. A greater number of ASMs was associated with fewer seizure-related ED visits after VNS device insertion, suggesting the role of medical management, patient baseline seizure threshold, and caregiver comfort with at-home seizure management.

131 Multi-Institutional Study on MRI-guided Laser Interstitial Thermal Therapy for Corpus Callosotomy (MRIgLITT-CC): Technique Variation, Ablation Coverage, and Need for Additional Surgery

INTRODUCTION: MRI-guided laser interstitial thermal therapy for corpus callosotomy (MRIgLITT-CC) offers palliation of intractable drop events and atonic, tonic, and generalized tonic-clonic seizures. METHODS: This multi-institutional retrospective study included pediatric patients with medically intractable epilepsy undergoing MRIgLITT-CC. Surgical details, post-operative radiographic results, and need for additional epilepsy surgery were recorded. Percent coverages of the intended ablation zones (anterior, complete, or posterior corpus callosotomy) were estimated from MRI. Data were summarized using descriptive statistics and compared using Chi-square tests. RESULTS: A total of 27 subjects (18 male, 9 female) with mean age 13 years +/- 5 years (4 years, 21 years) underwent planned complete (13, 48%), anterior (11, 41%), or posterior (3, 11%) MRIgLITT-CC. Planned complete MRIgLITT-CC entailed 2 (1/13, 8%), 3 (6/13, 46%), or 4 (6/13, 46%) trajectories with 100% (8/13, 62%) or 95-99% (5/13, 38%) coverage of the planned callosal ablation zone. Anterior MRIgLITT-CC cases included 1 (1/11, 9%), 2 (8/11, 73%), or 3 (1/11, 9%) trajectories to achieve 100% (7/11, 64%), 95-99% (2/11, 18%), 90-94% (1/11, 9%), or <90% (1/11, 9%) coverage of the planned callosal ablation zone. There were no significant differences in percent coverage of intended ablation zone as a function of trajectory number (p = 0.6). Three subjects (11%) required repeat callosal surgery while four subjects (15%) underwent additional vagus nerve stimulator (VNS) insertion during clinic follow-up (mean 11.7 months +/-10.6 months; [0.4 months, 37.1 months]). The need for repeat callosal surgery differed significantly between subjects with 100% and less than 100% ablation coverage (0/16 vs. 3/11, p = 0.03). CONCLUSION: In this multi-institutional study, MRIgLITT-CC yielded 100% or 95-99% coverage of the intended callosal ablation zone in most subjects. Trajectory variation between centers did not impact percent coverage of the intended ablation zone. Few subjects required repeat callosal surgery, particularly those with less than 100% ablation zone coverage, or additional VNS insertion.

Vagus nerve stimulation: a 20-year Australian experience.

Vagus nerve stimulation (VNS) therapy was first approved in the mid-1990s in the USA, Europe and Australia, with demonstrable efficacy in paediatric populations. Benefit in seizure frequency reduction can be observed up to 2years post-intervention; however, few studies assess outcomes beyond this period. Furthermore, paediatric cohort sizes are small, limiting generalisability of outcome assessments. We evaluate VNS insertion outcomes and complications or side-effects in a large paediatric cohort, over a 20-year period from Queensland's first VNS insertion. A retrospective review was conducted of all paediatric VNS insertions at the Queensland Children's Hospital (QCH) and the Mater Children's Hospital/Mater Children's Private Hospital (MCH/MCPH) Brisbane. A minimum of 1-year follow-up from 1999 to 2020 was required for inclusion. Patients were assessed on demographics, epilepsy details, seizure outcomes and complications or side-effects. In this extended follow-up cohort (76 patients, 7.2 ± 5.3years), 51.3% of patients had ≥ 50% seizure frequency reduction, while 73.7% experienced an Engel III outcome (worthwhile benefit) or better. Eleven patients (14.9%) were seizure-free at follow-up, and 81.6% retained long-term therapy. Stimulation-related side-effects are common (17.1%) but rarely result in stimulation cessation (3.9%). Cessation occurred in 14 patients (18.4%) and most commonly related to minimal benefit (13.2%). Demographics, aetiology, seizure nature and surgical factors did not influence outcomes. Over extended treatment periods, a large proportion of patients will benefit significantly from VNS therapy. Approximately 4 of 5 patients will retain VNS therapy, and in cases of cessation, this is most commonly related to minimal benefit. Underlying demographics, aetiology or seizure nature do not influence outcomes. This 20-year Queensland assessment of VNS therapy outcomes informs long-term expectation of VNS therapy.

Sleep disordered breathing in children receiving vagus nerve stimulation therapy

ObjectiveThe effects of vagus nerve stimulation (VNS) on sleep disordered breathing (SDB) have been reported in limited case series. Detailed studies, particularly in the pediatric population, have not been performed. The primary purpose of this study is to describe clinical characteristics, polysomnographic findings, and management of children treated with VNS. MethodsA retrospective review of medical records and polysomnography data was performed in patients ages 0–20 years old receiving VNS therapy for refractory epilepsy at Cincinnati Children's Hospital Medical Center. Results22 subjects met the inclusion criteria. 50% were male. The mean age at the time of VNS insertion was 8.4 ± 4.0 years. The mean age at the first PSG was 10.6 ± 4.3 years. Common presentations to sleep clinics included snoring (77.3%), frequent nighttime awakening (68.1%), and parasomnias (63.6%). The median apnea-hypopnea index (AHI) was 4.5/hr (IQR 3.0–13.1) and the median obstructive index (OI) was 4.1/hr (1.5–12.8). Obstructive sleep apnea (OSA) was diagnosed after VNS insertion in 19 patients (86.4%), 8 of which (36.3%) had severe OSA. Six patients (27.3%) had significant hypoventilation. For management, 6 patients (27.2%) were treated with bilevel PAP, 3 patients (13.6%) with CPAP, 2 patients (9.1%) with ventilator, 4 patients (18.2%) with upper airway surgeries, and 9 patients (40.9%) received medications only. ConclusionsSDB is common in pediatric patients with medically refractory epilepsy managed with VNS who were referred to sleep medicine clinics. Both OSA and nocturnal alveolar hypoventilation are relatively common in this population. Management of SDB often involves the use of positive airway pressure therapy or upper airway surgeries. Further studies are needed to assess the prevalence, risk factors, and the effect of treatments on epilepsy control. This study highlights the need for screening of SDB prior to and following VNS implantation.

Seizure improvement following vagus nerve stimulator (VNS) battery change with cardiac-based seizure detection automatic stimulation (AutoStim): early experience in a regional paediatric unit.

The recent VNS models (AspireSR® Model 106, SenTiva™ Model 1000 (VNS Therapy®, LivaNova)) include a new function of cardiac-based seizure detection (CBSD) automatic stimulation, known as 'AutoStim'. This algorithm uses tachycardia as a proxy to a seizure, and the battery delivers a closed-loop electrical current in addition to its programmed stimulation. This function leads to further seizure reduction in adults, but this advantage has not been reported in the paediatric population. This study aims to investigate whether battery change with AutoStim leads to further seizure reduction in children. This observational study included the first 10 cases of VNS battery change from non-AutoStim to AutoStim function. During the battery change operation, the new VNS was switched on, with the same normal and magnet mode settings as the previous VNS. The AutoStim mode was activated at the same time. Data on seizure burden were collected at 3 time points: (1) before the first VNS insertion, (2) before battery replacement (post-1st VNS) and (3) 12months post-battery change (post-AutoStim). The net effect of AutoStim, the only changed parameter, was evaluated by comparing the seizure burden prior to and 12months following battery change in each child. The seizure reduction improved significantly from 60 to 83% following battery change with AutoStim. Categorising the outcome according the McHugh classification, children achieving class I and II outcome (≥ 50% seizure reduction) improved from 70 to 90%. This is the first study to demonstrate the additional efficacy of AutoStim in children treated with VNS.

Efficacy of VNS for Drug-Resistant Epilepsy in Structural Brain Lesions

Background: Vagus nerve stimulation (VNS) has been used for the treatment of drug-resistant epilepsy, especially in patients who are not candidates for surgical intervention. In fact, it was approved by the US FDA in 1997 as an adjunctive treatment for medically intractable epilepsy. Objective: In this study, we investigated the efficacy of VNS in drug-resistant epilepsy associated with structural brain lesions (SBLs). Methods: We retrospectively analyzed the effect of VNS on 25 patients diagnosed with intractable epilepsy-associated SBL, and compared the results to 19 patients with intractable epilepsy and normal neuroimaging. All patients underwent VNS insertion at the National Neurosciences Institute, King Fahad Medical City (Riyadh, Saudi Arabia) between 2008 and 2018. Results: The response rate (RR) for patients with drug-resistant epilepsy-associated SBL was 24% after 3 months, 36% after 6 months, and 48% after 1 year, reaching 76% over time. The mean follow-up period was 63.3 months. For non-SBL patients, the RR was 10.5% after 3 months, 36.8% after 6 months, and 47.4% after 1 year, reaching 73.7% over time. The mean follow-up period was 59.2 months. There was no statistically significant difference between the two groups regarding RR, VNS settings, and other parameters, including anti-epileptic drug use and demographics data. Conclusion: VNS is strongly considered for intractable epilepsy in SBL patients, especially if they are not candidates for surgical intervention. Over time, those patients will receive increased benefits from VNS therapy.

Preoperative evaluation and surgical management of infants and toddlers with drug-resistant epilepsy.

OBJECTIVE Despite perioperative risks, epilepsy surgery represents a legitimate curative or palliative treatment approach for children with drug-resistant epilepsy (DRE). Several factors characterizing infants and toddlers with DRE create unique challenges regarding optimal evaluation and management. Epilepsy surgery within children < 3 years of age has received moderate attention in the literature, including mainly case series and retrospective studies. This article presents a systematic literature review and explores multidisciplinary considerations for the preoperative evaluation and surgical management of infants and toddlers with DRE. METHODS The study team conducted a systematic literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, targeting studies that investigated children < 3 years of age undergoing surgical treatment of DRE. Using the PubMed database, investigators selected peer-reviewed articles that reported seizure outcomes with or without developmental outcomes and/or perioperative complications. Studies were eliminated based on the following exclusion criteria: sample size < 5 patients; and inclusion of patients > 3 years of age, when demographic and outcomes data could not be separated from the cohort of patients < 3 years of age. RESULTS The study team identified 20 studies published between January 1990 and May 2017 that satisfied eligibility criteria. All selected studies represented retrospective reviews, observational studies, and uncontrolled case series. The compiled group of studies incorporated 465 patients who underwent resective or disconnective surgery (18 studies, 444 patients) or vagus nerve stimulator insertion (2 studies, 21 patients). Patient age at surgery ranged between 28 days and 36 months, with a mean of 16.8 months (1.4 years). DISCUSSION The study team provided a detailed summary of the literature review, focusing on the etiologies, preoperative evaluation, surgical treatments, seizure and developmental outcomes, and potential for functional recovery of infants and toddlers with DRE. Additionally, the authors discussed special considerations in this vulnerable age group from the perspective of multiple disciplines. CONCLUSIONS While presenting notable challenges, pediatric epilepsy surgery within infants and toddlers (children < 3 years of age) offers significant opportunities for improved seizure frequency, neuro-cognitive development, and quality of life. Successful evaluation and treatment of young children with DRE requires special consideration of multiple aspects related to neurological and physiological immaturity and surgical morbidity.

BS17. The “Uncommonly Common” horner syndrome following a VNS insertion

The Vagus nerve stimulation (VNS) therapy is approved in the USA as an adjunctive treatment in reducing the frequency of seizures in patients aged 4 years and older with partial-onset seizures refractory to antiepileptic drugs (AEDs). Globally, it has been implanted in more than 100,000 patients. Some of the commonly reported surgical complications of the device include infection, postoperative hoarseness, and pain. Here, we report a case of Horner syndrome subsequent to a VNS placement. Case report and literature review. A 61 year-old woman with drug-resistant focal epilepsy who previously underwent a selective left amygdalohippocampectomy at an outside hospital and achieved class 4 ILAE Epilepsy surgery outcome scale, underwent a VNS placement. There were no reported intraoperative complications. When seen in a follow-up 2 weeks post-operatively, the patient reported new onset excessive lacrimation and blurry vision in the left eye. A detailed examination revealed a left miotic pupil and partial left ptosis. She denied hemifacial anhidrosis and no changes in skin temperature or appearance were detected on the exam. Based on the above findings a diagnosis of left Horner syndrome was established. These signs and symptoms remained without improvement upon a subsequent follow-up, about 4 weeks post-operatively. When her findings first became apparent to the treating neurologist, the surgeon who placed the device was immediately contacted. The surgeon, however, did not find the discovery alarming, stating that Horner syndrome is “commonly observed” post-VNS implantation. An extensive literature search of VNS-related Horner syndrome returned maximum 7 references (both human and animal data) on PubMed and several book references on the Google search engine. Additionally, a limited poll of the epileptology colleagues and LivaNova representatives yielded zero personal reports of the phenomenon. Only two human studies with sizable patient samples that referenced the syndrome were identified. The first study retrospectively reviewed the charts of all adult epilepsy patients treated by VNS with ⩾1 year follow-up. Out of 34 patients (14 males; mean age = 29.9 years) who received a VNS, 1 patient developed Horner syndrome (2.9% of the patient group). The second study analyzed 251 procedures that were performed on 143 patients (81 males, 98 adults (mean age 35.8 years) and 45 children (mean age 10.1 years)). They found 1 case (0.7% of the group) of the syndrome. Based on the reviewed studies, Horner syndrome complicating a VNS implant was seen in 0.7–2.9% procedures. The pathophysiology of Horner syndrome following VNS placement has been postulated to reflect traction on the sympathetic fibers along the internal carotid artery or injury to or manipulation of the sympathetic plexus immediately beneath the carotid sheath. Horner syndrome is a potentially avoidable neurological complication following VNS placement, and while rare, is in fact an “uncommon” complication.

0874 SLEEP DISORDERED BREATHING IN CHILDREN WITH REFRACTORY EPILEPSY TREATED WITH VAGUS NERVE STIMULATOR

Vagus nerve stimulation (VNS) is an effective treatment option for medically refractory epilepsy. The effects of VNS on sleep disordered breathing (SDB) were reported in some case series. However, studies in pediatric population are not well-described. The primary purpose of our study is to describe clinical characteristics, and polysomnographic findings in children with VNS. A retrospective review of medical records and polysomnographic results was performed in pediatric patients aged 0–20 years old with refractory epilepsy at CCHMC. Only children with VNS treatment at the time of sleep study were included. 22 subjects met the criteria for entry into this study. 77.3% of subjects had localization related epilepsy, 13.6% had generalized epilepsy, and 9.1% had features of both generalized and localization related epilepsy. 54.5% were male. The mean age at the time of VNS insertion was 8.4 ± 4.2 years. The mean age at the first PSG after VNS insertion was 10.9 ± 4.6 years. Three patients had obstructive sleep apnea (OSA) prior to VNS insertion. Common presentations at sleep clinics included snoring (81.8%) frequent night awakening (68.2%), parasomnia (68.2%), daytime sleepiness (45.5%) and gasping (45.5%). The mean apnea-hypopnea index (AHI) was 11.5 ± 18.8/hr (median 4.1; range 0 - 69.2) and the mean obstructive index (OI) was 10.9 ± 18.5/hr (median 3.9; range 0 - 67.1). Obstructive sleep apnea (OSA) was diagnosed after VNS insertion in 19 patients (86.4%), 6 of which (27.2%) had severe OSA. One patient (4.5%) had co-existing central sleep apnea on subsequent polysomnography. 8 patients (36.4%) had significant hypoventilation. For management, 31.8% of patients were treated with BiPAP, 9.1% with CPAP, 9.1% with ventilator, 18.2% with upper airway surgery (adenotonsillectomy and/or uvulopalatopharyngoplasty) and 36.4% were treated conservatively. Sleep disordered breathing, including obstructive sleep apnea and hypoventilation, is common among children with medically refractory epilepsy treated with VNS. The mechanism is currently unknown, but may involve the effect of VNS firing on upper airway muscle tone or central respiratory control. Further studies are needed to assess what factors associated with VNS play a crucial role in the upper airway collapsibility. None

Predictors of Response to Vagus Nerve Stimulation in Childhood-Onset Medically Refractory Epilepsy

This study explored predictors of response to vagus nerve stimulation in childhood-onset epilepsy. This retrospective chart review included all patients with new vagus nerve stimulator insertion between January 1, 2006, and December 31, 2011. Primary outcome was change in seizure frequency classified on the International League Against Epilepsy scale. Overall, 67.4% (95% confidence limits 53.3%-81.6%) of the patients had outcome of class 4 or better, and 4 patients (9.3%, 95% confidence interval 0.5%-18.1%) achieved complete seizure freedom (mean follow-up 3.5 y). Absence of magnetic resonance imaging (MRI) lesion (odds ratio 6.068, 95% confidence interval 1.214-30.329, P = .028) and duration of epilepsy before implantation (odds ratio 1.291, 95% confidence interval 1.015-1.642, P = .038) were found to be statistically significant predictors of good outcome and provided a sufficient fit to the data (area under the receiver operating characteristic curve .80, Hosmer-Lemeshow goodness of fit P = .92). This study provides preliminary evidence that nonlesional patients are significantly more likely to have better outcome with vagus nerve stimulation.

Vagus nerve stimulation for children with treatment-resistant epilepsy: a consecutive series of 141 cases

The authors undertook this study to analyze the efficacy of vagus nerve stimulation (VNS) in a large consecutive series of children 18 years of age and younger with treatment-resistant epilepsy and compare the safety and efficacy in children under 12 years of age with the outcomes in older children. The authors retrospectively reviewed 141 consecutive cases involving children (75 girls and 66 boys) with treatment-resistant epilepsy in whom primary VNS implantation was performed by the senior author between November 1997 and April 2008 and who had at least 1 year of follow-up since implantation. The patients' mean age at vagus nerve stimulator insertion was 11.1 years (range 1-18 years). Eighty-six children (61.0%) were younger than 12 years at time of VNS insertion (which constitutes off-label usage of this device). Follow-up was complete for 91.8% of patients and the mean duration of VNS therapy in these patients was 5.2 years (range 25 days-11.4 years). Seizure frequency significantly improved with VNS therapy (mean reduction 58.9%, p < 0.0001) without a significant reduction in antiepileptic medication burden (median number of antiepileptic drugs taken 3, unchanged). Reduction in seizure frequency of at least 50% occurred in 64.8% of patients and 41.4% of patients experienced at least a 75% reduction. Major (3) and minor (6) complications occurred in 9 patients (6.4%) and included 1 deep infection requiring device removal, 1 pneumothorax, 2 superficial infections treated with antibiotics, 1 seroma/hematoma treated with aspiration, persistent cough in 1 patient, severe but transient neck pain in 1 patient, and hoarseness in 2 patients. There was no difference in efficacy or complications between children 12 years of age and older (FDA-approved indication) and those younger than 12 years of age (off-label usage). Linear regression analyses did not identify any demographic and clinical variables that predicted response to VNS. Vagus nerve stimulation is a safe and effective treatment for treatment-resistant epilepsy in young adults and children. Over 50% of patients experienced at least 50% reduction in seizure burden. Children younger than 12 years had a response similar to that of older children with no increase in complications. Given the efficacy of this device and the devastating effects of persistent epilepsy during critical developmental epochs, randomized trials are needed to potentially expand the indications for VNS to include younger children.

Efficacy of vagus nerve stimulation over time: Review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS > 10 years

ObjectiveStudies have reported improved seizure control with increased duration of vagus nerve stimulation (VNS) but are prone to methodological biases. We analyzed the efficacy of VNS over time in patients with treatment-resistant epilepsy (TRE) who underwent VNS therapy 10 or more years. MethodsWe retrospectively reviewed 65 consecutive patients (29 females) who underwent VNS therapy ≥10years. The mean age at VNS insertion was 30.0years. Forty-four adults (≥18years; 67.7%) and 21 children (32.3%) were included. Seizure frequency and antiepileptic drug (AED) regimens were recorded prior to VNS and, following VNS insertion, at 6months, 1year, 2years, and every 2years thereafter. ResultsThe mean duration of VNS therapy for this group was 10.4years, and the mean decrease in seizure frequency at last follow-up was 76.3%. The mean reduction in seizures at 6months and years 1, 2, 4, 6, 8, and 10years was 35.7, 52.1, 58.3, 60.4, 65.7, 75.5, and 75.5%, respectively. Seizure frequency was significantly reduced from baseline at each of the recorded intervals (P<0.001). There was a trend toward increased AED burden in the latter years of the follow-up period. ConclusionFollowing a “ramp-up” and accommodation period throughout the initial 24months after VNS implantation, seizure control improved slightly over the subsequent years of therapy and eventually stabilized. Variation in seizure frequency, however, was common, and frequent changes in AED regimens or stimulation parameters were likely an important and possibly synergistic component of seizure control.

Cardiac Rhythm Disturbance in a Depressed Patient After Implantation With a Vagus Nerve Stimulator

A 52-year-old woman with a long-standing history of treatment-resistant depression failed multiple courses of electroconvulsive therapy and various trials of antidepressant medications. As a result, the patient was deemed a good candidate for vagus nerve stimulation (VNS) therapy and underwent VNS insertion in May 2006. However, in December 2007, she began to experience recurrent falls and was referred to a cardiologist for a syncope evaluation. During a portable 30-day cardiac event recording, she was noted to have intermittent second- and third-degree heart block with ventricular standstill, which was felt by her cardiologist to be associated with VNS stimulation. We believe this to be the first reported case of heart block related to VNS in a depressed patient.