Role Of Vagus Nerve Stimulation Research Articles

Role of Vagus Nerve Stimulation in Refractory and Super Refractory Status Epilepticus: A Pediatric Case Series.

Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE. We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up. We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE. Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS's potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights.

Anti-inflammatory effects of vagus nerve stimulation in pediatric patients with epilepsy.

The neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease. Here we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy. Thus, we studied the impact that VNS treatment has on PBMCs isolated from a cohort of existing patients with medically refractory epilepsy. A comparison of genome-wide changes in gene expression was made between the epilepsy patients treated and non-treated with vagus nerve stimulation. The analysis showed downregulation of genes related to stress, inflammatory response, and immunity, suggesting an anti-inflammatory effect of VNS in epilepsy patients. VNS also resulted in the downregulation of the insulin catabolic process, which may reduce circulating blood glucose. These results provide a potential molecular explanation for the beneficial role of the ketogenic diet, which also controls blood glucose, in treating refractory epilepsy. The findings indicate that direct VNS might be a useful therapeutic alternative to treat chronic inflammatory conditions.

Bibliometric analysis of publication trends and research hotspots in vagus nerve stimulation: A 20-year panorama.

As a promising neuromodulation technique, vagus nerve stimulation (VNS) has been utilized to treat diverse diseases and the number of VNS studies has grown prosperously. Nonetheless, publication trends and research hotspots in this field remain unknown. This study aimed to perform a bibliometric analysis to systematically identify publication trends and research hotspots in VNS research within a 20-year panorama. The Web of Science Core Collection (WoSCC) database was retrieved to screen eligible VNS-related publications from 2002 to 2021. The online analytic tool of the WoSCC database was used to analyze various bibliometric parameters, such as the number of annual publications, the output of countries/regions, journals, total citations, citations per publication, and the Hirsch index. Bibliometrics (http://bibliometric.com/) and CiteSpace (version 5.6.R3) were used to identify research trends and hotspots. A total of 7,283 publications were included for analysis. The annual number of publications increased stably but it increased significantly in recent years. The top five prolific countries were the United States, China, Germany, England, and France. The top five productive institutions were the University of California (Los Angeles), Harvard Medical School, Harvard University, University College London, and the University of Texas at Dallas. Notably, there was a geographical imbalance in countries and institutions. In addition, Epilepsy & Behavior, Epilepsia, and Plos One were the top three journals with the largest number of VNS publications. Michael P Kilgard was the most prolific author. Moreover, evolving research hotspots mainly included the effectiveness and mechanism of VNS on epilepsy, the role of VNS as an anti-inflammatory regulator, the application of VNS for psychiatric disorders, and the neuromodulation effect of VNS in headache management. This study has revealed the overall publication trends and evolving research trends at a global level over a 20-year panorama. The potential collaborators, institutions, hotspots, and future research trends are also identified in this field, which will help guide new research directions of VNS.

Efficacy and Safety of Vagus Nerve Stimulation in Stroke Rehabilitation: A Systematic Review and Meta-Analysis

Introduction: Recent randomized controlled trials (RCTs) have assessed the role of vagus nerve stimulation (VNS) when paired with standard rehabilitation in stroke patients. This review aimed to evaluate the efficacy and safety of VNS as a novel treatment option for post-stroke recovery. Methods: We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL Plus for articles published from their date of inception to June 2021. RCTs investigating the efficacy or safety of VNS on post-stroke recovery were included. The outcomes were upper limb sensorimotor function, health-related quality of life, level of independence, cardiovascular effects, and adverse events. The risk of bias was assessed using the Cochrane risk-of-bias tool, while the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. Review Manager 5.4 was used to conduct the meta-analysis. Results: Seven RCTs (n = 236 subjects) met the eligibility criteria. Upper limb sensorimotor function, assessed by the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), improved at day 1 (n = 4 RCTs; standardized mean difference [SMD] 1.01; 95% confidence interval [CI]: 0.35–1.66) and day 90 post-intervention (n = 3 RCTs; SMD 0.64; 95% CI: 0.31–0.98; moderate certainty of evidence) but not at day 30 follow-up (n = 2 RCTs; SMD 1.54; 95% CI: −0.39 to 3.46). Clinically significant upper limb sensorimotor function recovery, as defined by ≥6 points increase in FMA-UE, was significantly higher at day 1 (n = 2 RCTs; risk ratio [RR] 2.01; 95% CI: 1.02–3.94) and day 90 post-intervention (n = 2 RCTs; RR 2.14; 95% CI: 1.32–3.45; moderate certainty of the evidence). The between-group effect sizes for upper limb sensorimotor function recovery was medium to large (Hedges’ g 0.535–2.659). While the level of independence improved with VNS, its impact on health-related quality of life remains unclear as this was only studied in two trials with mixed results. Generally, adverse events reported were mild and self-limiting. Conclusion: VNS may be an effective and safe adjunct to standard rehabilitation for post-stroke recovery; however, its clinical significance and long-term efficacy and safety remain unclear.

Difficult-to-Treat Depression and the Role of Vagus Nerve Stimulation

It has been argued that reconceptualizing treatment-resistant depression as difficult-to-treat depression (DTD) is of both semantic and clinical benefit. Whereas treatment-resistant depression, by definition, most commonly focuses entirely on repeated pharmacological treatment trials, DTD takes a more holistic perspective, considering all treatment modalities — psychotherapeutic, neurostimulatory, psychosocial, self-help, and pharmacological, from a perspective of a chronic disease management model. A key element of the DTD model is frequent reviews of treatment direction, and whether additional options should be considered, including less commonly used treatments, such as implanted vagus nerve stimulation. This selective review considers the potential role of vagus nerve stimulation, both as an acute treatment and for prophylaxis, the implications of previous electroconvulsive therapy response, and the impact of the treatment on quality of life, in the context of the DTD model of care. [ Psychiatr Ann . 2022;52(7):266–271.]

The Role of Vagus Nerve Stimulation in Depression: What We Know?

IntroductionDepression is a leading cause of disability affecting over 300 million indivuals worldwide. About 1/3 of patients with depression fail to achive remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD). In view of such facts, vagus nerve stimulation (VNS) therapy was approved as an adjunctive long-term treatment for TRD.ObjectivesThe authors elaborate a narrative literature review about de effectiveness of VNS in treatment for TRD.MethodsPubMed database searched using the terms “treatment-resistant depression”, “vagus nerve stimulation”ResultsThe pathophysiology of depression is complex and includes social environmental stress factors, genetic and biological processes, inflammation, and disturbances in monoamine neurotransmission. The overdrive of the HPA axis is most consistently seen in subjects with more severe depression, when the cortisol feedback inhibitory mechanisms are impaired, contributing to cytokine oversecretion. It has been shown that chronic exposure to elevated inflammatory cytokines can lead to depression. The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood and imune response. VNS therapy has a demonstrated anti-inflammatory effect which might be a significant reason for its efficacy in patients who did not respond to antidepressants. Treatments thar target the vagus nerve increase the vagal tone and inhibit cytokine production and the stimulation of vagal aferente fibers in the gut influences monaminergic brain systems.ConclusionsThe mecanismos by which VNS may benefit patients nonresponsive to conventional antidepressants is unclear, with further research need to clarify this.DisclosureNo significant relationships.

Adjunctive vagus nerve stimulation for treatment-resistant depression: a preliminary study

Background This study is the first to assess the safety and therapeutic efficacy of vagus nerve stimulation (VNS) as an adjunctive treatment for Chinese patients suffering from treatment-resistant depression (TRD). Methods A total of seven patients with TRD underwent surgical implantation of a VNS device were followed over a 9-month period. The 24-item Hamilton Rating Scale for Depression (HAMD-24) and the 14-item Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms, respectively. Neurocognitive function was measured with the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (WMS). Results After 3 months of treatment with VNS, the antidepressant response and remission rates were 42.9% and 28.6%, respectively. After 9 months of treatment with VNS, the response and remission rates increased to 85.7% and 57.1%, respectively. Significant time main effects were identified for HAMD-24 scores, HAMA scores, the WMS memory quotient, and the full intelligence quotients measured with the WAIS (all ps < 0.05). The most frequent adverse effects of VNS treatment were voice alteration (100%) and cough frequency increase (71.4%). Conclusion This preliminary study indicated that adjunctive VNS was effective and safe in treating Chinese patients who were suffering from TRD, and its efficacy increased with time. Key points There is positive evidence to support the role of VNS as an adjunctive treatment in Chinese patients with TRD. The antidepressant efficacy of adjunctive VNS for Chinese patients with TRD increased with time. The most frequent adverse effects of VNS treatment were voice alteration and cough frequency increase.

Percutaneous vagus nerve stimulation modulates glia activity and rescues acute Aβ deposition in a mouse model of delirium superimposed on dementia.

Millions of Americans live with Alzheimer's disease (AD) and routinely require common surgical interventions, such as orthopedic surgery. However, these potentially life-saving procedures often increase the risk for further cognitive complications, such as delirium, which in many cases associate with worse prognosis and even death. Currently, we do not have effective strategies to prevent postoperative neuroinflammation and treat delirium. Using an AD-like mouse model (CVN-AD) we established a translational paradigm to study delirium superimposed on dementia [1]. Here we describe the effects of a minimally-invasive ultrasound guided percutaneous approach to stimulate the vagus nerve (termed pVNS) [2] in CVN-AD mice after orthopedic surgery. A 30-minute stimulation at 10 Hz was performed in 12-months-old CVN-AD mice before subjecting them to tibial fracture and repair. Surgery induced a robust neuroinflammatory response in these mice, with evident morphological changes in microglia and astrocytes, as well as an acute deposition of Aβ plaques in the hippocampus compared to age-matched controls. pVNS after surgery rescued morphological changes in microglia and astrocytes, as well as effectively reduced Aβ plaques deposition in the hippocampus at 24 hours. Notably, pVNS altered the autophagy-lysosomal pathway by increasing TFEB and LAMP1 expression, which are key regulators of autophagy and lysosomal biogenesis. These changes were observed using Nanostring assay on hippocampal tissue combined with immunofluorescence staining. Overall, these data highlight a novel role for vagus nerve stimulation in regulating neuroimmune interactions and resolving inflammation in delirium superimposed on dementia.

The role of vagus nerve stimulation in the treatment of refractory epilepsy: clinical outcomes and impact on quality of life

BackgroundVagus nerve stimulation (VNS) is used as a complementary therapy to pharmacological treatment in patients with refractory epilepsy. This study aims to evaluate the efficacy of VNS in reducing seizure frequency, severity, and duration; reducing the number of antiepileptic drugs administered; and improving patients’ quality of life. Material and methodsWe analysed the clinical progression of 70 patients with refractory epilepsy treated with VNS at Hospital Universitario de Alicante and Hospital Clínico de Valencia. Data were collected before and after the procedure. The difference in seizure frequency pre- and post-VNS was classified using the McHugh scale. Data were also collected on seizure duration and severity, the number of drugs administered, and quality of life. ResultsAccording to the McHugh classification, 12.86% of the patients were Class I, 44.29% were Class II, 40% were Class III, and the remaining 2.86% of patients were Class IV-V. A ≥ 50% reduction in seizure frequency was observed in 57.15% of patients. Improvements were observed in seizure duration in 88% of patients and in seizure severity in 68%; the number of drugs administered was reduced in 66% of patients, and 93% reported better quality of life. ConclusionsVNS is effective for reducing seizure frequency, duration, and severity and the number of antiepileptic drugs administered. It also enables an improvement in patients’ quality of life.

The Role of Vagus Nerve Stimulation in Sepsis

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. The infection triggers a host response with an early hyperinflammatory and subsequent anti-inflammatory phase, both regulated by homeostatic mechanisms. A breakdown of these regulatory mechanisms can result in an exaggerated immune response which leads to complications. The vagus nerve plays a central role in regulating inflammation and the balance between the sympathetic and parasympathetic arms of the autonomic nervous system through the “cholinergic anti-inflammatory pathway”. Several experimental models support the notion that external stimulation of the vagus nerve can modulate inflammation and restore the sympatho-vagal balance which may translate to improved outcomes in sepsis. Here, we review the pathophysiologic basis and evidence behind vagus nerve stimulation in sepsis.

Response to Letter to the Editor Regarding: “The Use of Non-Invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated With COVID-19: A Theoretical Hypothesis and Early Clinical Experience”

Response to Letter to the Editor Regarding: “The Use of Non-Invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated With COVID-19: A Theoretical Hypothesis and Early Clinical Experience”

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.

Effect of vagus nerve stimulation on tissue damage and function loss in a mouse myocardial ischemia-reperfusion model.

In cardiac ischemia, acute inflammatory responses further increase the detrimental effect on myocardial tissue. Since vagus nerve stimulation (VS) attenuates inflammatory responsiveness this study examines the effect of VS on myocardial damage development in a cardiac ischemia-reperfusion (IR) mouse model. 54 male C57Bl/6j mice were subjected to an IR procedure with or without prior VS. The effects on inflammatory responsiveness, infarct size, cardiac function, neutrophils, lymphocytes and vascular endothelial growth factor (VEGF) in the infarcted myocardium were measured at 48 h after intervention. Group results were compared with unpaired Mann-Whitney or Kruskall-Wallis test. A significant decrease in inflammatory responsiveness was not verified by decreased TNFα levels in blood from VS and IR treated mice. The percentage infarct size over area at risk was smaller in the group with VS + IR compared with IR (22.4 ± 10.2% vs 37.6 ± 9.0%, p = 0.003). The degree of the reduction in cardiac function was not different between the IR groups with or without VS and no group differences were found in amounts of neutrophils, CD3+ lymphocytes and VEGF in the reperfused mouse heart. The present study does not provide clear evidence of a reducing role for VS on cardiac function loss. This could mean that VS has a less inhibiting effect on myocardial inflammation than may be expected from the literature.

Is There a Role for Vagus Nerve Stimulation in the Treatment of Posttraumatic Stress Disorder?

Is There a Role for Vagus Nerve Stimulation in the Treatment of Posttraumatic Stress Disorder?

The role of vagus nerve stimulation in refractory epilepsy.

Vagus nerve stimulation is an adjunctive therapy used to treat patients with refractory epilepsy who are not candidates for resective surgery or had poor results after surgical procedures. Its mechanism of action is not yet fully comprehended but it possibly involves modulation of the locus coeruleus, thalamus and limbic circuit through noradrenergic and serotonergic projections. There is sufficient evidence to support its use in patients with focal epilepsy and other seizure types. However, it should be recognized that improvement is not immediate and increases over time. The majority of adverse events is stimulation-related, temporary and decreases after adjustment of settings. Future perspectives to improve efficacy and reduce side effects, such as different approaches to increase battery life, transcutaneous stimulation and identification of prognostic factors, should be further investigated.

Vagus nerve stimulation and late-onset bradycardia and asystole: Case report

Vagus nerve stimulation (VNS) therapy is approved in the United States by the FDA in 1997 for medically refractory partial epilepsy in patients of ages 12 years and above. The most common stimulation-associated side effects are voice alteration, hoarseness, throat and neck pain, headache, cough, and dyspnea. Four patients with VNS had late-onset bradycardia and asystole, attributed to VNS stimulation. Their ages were 13, 17, 47, and 55. Cardiac symptoms were noted after 2.33–9 years postimplantation [1–4]. Three cases had symptoms correlated with stimulation, monitored by electrocardiogram [1,2,4]. This new case report highlights cardiac syncope with very similar clinical presentation as previous four cases, and raises the concern for cardiac symptoms, even many years after VNS implantation.

Effect of vagus nerve stimulation on focal transient cerebral ischemia and reperfusion in adult male white new zealand rabbits

Background: Oxidative stress has been implicated in the pathophysiology of cerebral ischemia. Pentraxin-3 plays an important role in innate immune responses and in inflammatory diseases. Our aim was to evaluate pentraxin-3 serum level on focal transient cerebral ischemia and reperfusion model in rabbits and to assess the anti-inflammatory and anti-oxidant effects of vagus nerve stimulation. Materials and methods: Focal transient cerebral ischemia and reperfusion was induced by occlusion of the right common carotid artery for 2 hours followed by reperfusion for one hour. Stimulating electrodes were implanted on the cervical part of the right vagus nerve. Vagus nerve stimulation was started 30 min following right common carotid artery ligation for a period of one hour. The stimulation signals were delivered every five minutes for 30 seconds. All the procedures were duplicated but no stimulus was delivered in the control group. Serum level of pentraxin-3, lipid peroxide and total thiols were determined at baseline, at end of ischemia and at end of reperfusion and the animal decapitated and neuronal damage was evaluated. Results: We found that vagus nerve stimulation caused reduction of the ischemic features with revival of the cell shape and size. It also resulted in decreased serum levels of pentraxin-3 and lipid peroxide whereas the level of total thiols was increased. Conclusion: We concluded that the observed diversity in pentraxin-3, lipid peroxide and total thiols serum levels in cerebral ischemia and reperfusion may reflect relative roles in the biology. Anti-inflammatory and anti-oxidant role of vagus nerve stimulation in cerebral ischemia and reperfusion may represent a marker of altered cerebral function, and may provide potential therapeutic applications.

The inhibitory effects of vagus nerve stimulation in drug refractory epilepsy rat brains on the overexpression of the multidrug resistance protein

Objective To study the role of vagus nerve stimulation in the regulating of multidrug resistance genes related to protein (P-glycoprotein) overexpression in rat brains with drug refractory epilepsy (mainly refers to the hippocampus and the piriform cortex).Methods Lithium-Pilocarpine was used to kindle the rats to establish the temporal lobe epilepsy model and then rat models were induced with drug-refractory epilepsy by Sodium phenobarbital (PB).The rats were randomly divided into 4 groups,and then implanted with VNS electrodes.Modified parameters were used in the procedure of VNS (frequency -30Hz,pluse width-0.5ms,current-0.5 mA,stimulation time-30 s,interval-5 min,12h/d).Fluctuations in epileptic seizure frequencies were observed,and the amount of P-gp overexpression was detected before and after four weeks in each treatment group.Results (1) The VNS and VNS + PBgroups had a 79.6％ and 85.9％ decrease in the average number of seizures.The sham VNS + PB and saline groups had no significant improvements ; (2) The expression of P-gp levels in the VNS + PB group had significant statistical differences compared with the sham VNS + PB group (P ＜ 0.05).Conclusion VNS can effectively reduce the frequency of seizures of the RE,and it has a strong inhibitory effect on the overexpression of the multidrug resistance protein (P-gp) o Furthermore,better therapeutic effect can be achieved with this drug combination. Key words: Refractory epilepsy; Vagus nerve stimulation; Multidrug resistant gene; P-glycoprotein; Status epilepticus

Case report: Vagal nerve stimulation and late onset asystole

Rohit Shankar , Victor Oluwaseyi Olotu *, Nicholas Cole , Heather Sullivan , Caryn Jory c Neuropsychiatry, Epilepsy and Memory Service, Cornwall Partnership NHS Foundation Trust, Chy Govenek, Threemilestone Industrial Estate, Threemilestone, Truro, Cornwall TR4 9LD, United Kingdom Care of the Elderly Department, Royal Cornwall Hospital NHS Trust, Treliske, Truro, Cornwall TR1 3LJ, United Kingdom c East Cornwall Resource Centre, Cornwall Partnership NHS Foundation Trust, Unit 10, Bodmin Business Centre, Harleigh Road, Bodmin, Cornwall PL31 1AH, United Kingdom

Efficacy of vagus nerve stimulation in posttraumatic versus nontraumatic epilepsy

In the US, approximately 500,000 individuals are hospitalized yearly for traumatic brain injury (TBI), and posttraumatic epilepsy (PTE) is a common sequela of TBI. Improved treatment strategies for PTE are critically needed, as patients with the disorder are often resistant to antiepileptic medications and are poor candidates for definitive resection. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy that results in a ≥ 50% reduction in seizure frequency in approximately 50% of patients after 1 year of therapy. The role of VNS in PTE has been poorly studied. The aim of this study was to determine whether patients with PTE attain more favorable seizure outcomes than individuals with nontraumatic epilepsy etiologies. Using a case-control study design, the authors retrospectively compared seizure outcomes after VNS therapy in patients with PTE versus those with nontraumatic epilepsy (non-PTE) who were part of a large prospectively collected patient registry. After VNS therapy, patients with PTE demonstrated a greater reduction in seizure frequency (50% fewer seizures at the 3-month follow-up; 73% fewer seizures at 24 months) than patients with non-PTE (46% fewer seizures at 3 months; 57% fewer seizures at 24 months). Overall, patients with PTE had a 78% rate of clinical response to VNS therapy at 24 months (that is, ≥ 50% reduction in seizure frequency) as compared with a 61% response rate among patients with non-PTE (OR 1.32, 95% CI 1.07-1.61), leading to improved outcomes according to the Engel classification (p < 0.0001, Cochran-Mantel-Haenszel statistic). Vagus nerve stimulation should be considered in patients with medically refractory PTE who are not good candidates for resection. A controlled prospective trial is necessary to further examine seizure outcomes as well as neuropsychological outcomes after VNS therapy in patients with intractable PTE.