Vagus Nerve Stimulation Implantation Research Articles

Neurostimulation in generalized epilepsy: A systematic review and meta-analysis.

There are three neurostimulation devices available to treat generalized epilepsy: vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). However, the choice between them is unclear due to lack of head-to-head comparisons. A systematic comparison of neurostimulation outcomes in generalized epilepsy has not been performed previously. The goal of this meta-analysis was to determine whether one of these devices is better than the others to treat generalized epilepsy. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review of PubMed, Embase, and Web of Science was performed for studies reporting seizure outcomes following VNS, RNS, and DBS implantation in generalized drug-resistant epilepsy between the first pivotal trial study for each modality through August 2022. Specific search criteria were used for VNS ("vagus", "vagal", or "VNS" in the title and "epilepsy" or "seizure"), DBS ("deep brain stimulation", "DBS", "anterior thalamic nucleus", "centromedian nucleus", or "thalamic stimulation" in the title and "epilepsy" or "seizure"), and RNS ("responsive neurostimulation" or "RNS" in the title and "epilepsy" or "seizure"). From 4409 articles identified, 319 underwent full-text reviews, and 20 studies were included. Data were pooled using a random-effects model using the meta package in R. Sufficient data for meta-analysis were available from seven studies for VNS (n= 510) and nine studies for DBS (n= 87). Data from RNS (five studies, n= 18) were insufficient for meta-analysis. The mean (SD) follow-up durations were as follows: VNS, 39.1 (23.4) months; DBS, 23.1 (19.6) months; and RNS, 22.3 (10.6) months. Meta-analysis showed seizure reductions of 48.3% (95% confidence interval [CI] = 38.7%-57.9%) for VNS and 64.8% (95% CI=54.4%-75.2%) for DBS (p= .02). Our meta-analysis indicates that the use of DBS may lead to greater seizure reduction than VNS in generalized epilepsy. Results from RNS use are promising, but further research is required.

Efficacy of vagus nerve stimulation in 95 children of drug-resistant epilepsy with structural etiology

Vagus nerve stimulation (VNS) is one of the treatment options for drug-resistant epilepsy (DRE). To analyze the efficacy of VNS in children of DRE with structural etiology, we conducted a cohort study including 95 patients of DRE with structural etiology who underwent VNS treatment. Patients were followed up every 3 months at the outpatient department or via a remote programming platform. The median follow-up period was 2.6 years (range 1.0–4.6 years). The respective responder rates at 6, 12, 18, and 24 months of follow-up were 40.0% (38/95), 52.6% (50/95), 56.0% (47/84), and 59.7% (37/62). The respective seizure-free rates at 12, 18, and 24 months of follow-up were 8.4% (8/95), 9.5% (8/84), and 9.7% (6/62). The patients were divided into four groups based on etiologies: malformations of cortical development (n = 26), post-encephalitic lesions (n = 36), perinatal brain injury lesions (n = 31), and hippocampal sclerosis (n = 2). The respective responder rates at 12 months of follow-up in these groups were 53.8% (14/26), 52.8% (19/36), 51.6% (16/31), and 50.0% (1/2). There were no significant differences in gender, age at onset, age at stimulator implantation, epilepsy duration prior to VNS implantation, number of anti-seizure medications ever tried before VNS treatment, pulse amplitude of VNS, specific structural etiologies, lobe distribution or hemispheric side of structural lesions between responders and non-responders. Of the 95 patients, 8 (8.4%) underwent lesion surgery or hemispherectomy before VNS implantation, and 6/8 (75%) of these patients had a >50% reduction in seizure frequency. One patient who had a corpus callosotomy before VNS implantation had no response to VNS treatment. In conclusion, VNS is an effective treatment in children of DRE with structural etiology. There was no significant difference in VNS efficacy in patients with different structural etiologies. Vagus nerve stimulation treatment may also control seizures well in some patients with poor outcomes after lesion resection or hemispherectomy before VNS implantation.

Impact of Vagus Nerve Stimulation for the Treatment of Drug-resistant Epilepsy on Patterns of Use and Cost of Health Care Services and Pharmacotherapy: Comparisons of the 24-Month Periods Before and After Implantation

PurposeThis study examines the impact of vagus nerve stimulation (VNS) as treatment for drug-resistant epilepsy (DRE) on the use and cost of health care services and pharmacotherapy. MethodsUsing a large US health care claims database, we identified all patients with DRE who underwent VNS between January 1, 2012 and December 31, 2019. VNS implantation date was designated as the index date, and patients had to be continuously enrolled for the 24-month period before this date (preindex period). Outcomes included all-cause and epilepsy-related hospitalization, emergency department (ED) visits, and health care costs; health care claims resulting in an epilepsy diagnosis and all claims for antiseizure medications were deemed epilepsy related. Preindex data, except care related to preoperative medical clearance for VNS, were used to estimate multivariate regression models predicting outcomes during the 24-month postindex period (follow-up period). Predicted outcomes during follow-up were then compared with observed values. As a sensitivity analysis, we also replicated all analyses among subgroups defined by comorbid depression. FindingsA total of 659 patients underwent VNS for DRE and met the selection criteria. For the composite outcome of all-cause hospitalizations and ED visits, observed values were 42% lower than expected during the 24-month follow-up period; for the composite outcome of epilepsy-related hospitalizations and ED visits, observed values were 49% lower (P < 0.001 for both). Observed mean total all-cause costs, inclusive of costs of the procedure, were not significantly different than expected costs by month 19 of follow-up; mean total epilepsy-related costs were comparable by month 18. Findings were similar in subgroups with and without depression, although nominally greater differences (observed – expected) were seen in those with comorbid depression. ImplicationsOur findings suggest that VNS is associated with decreased risk of hospitalization or ED visits (all cause and epilepsy related) during the 2-year period subsequent to implantation and may become cost-neutral within 2 years of implantation (vs continued medical management of DRE without VNS). Although expected outcomes were estimated based on the 24-month period before implantation, the degree to which they approximated what would have happened in the absence of VNS is unknowable. Further research is needed to better understand the extend and duration of the impact of VNS on seizure frequency and severity and health-related quality of life, including its performance among those with and without comorbid depression.

The Clinical Impact of Vagal Nerve Stimulator Implantation on Laryngopharyngeal Function in Children: A Single-Center Experience.

A vagal nerve stimulator (VNS) has been established as the treatment of choice for children with refractory epilepsy. The outcomes of the procedure have been well documented in adults but are less clear in children. The goal of our study was to review laryngopharyngeal (LP) function following VNS implantation in children. Case series with chart review. Tertiary-care children's hospital. Voice, swallowing, and sleep apnea symptoms were extracted from the charts of children who underwent VNS implantation between 2013 and 2021. A questionnaire was sent to parents of implanted children to ascertain the degree of the social and functional impact of the implant. There were 69 patients, aged 2.3 to 21.4 years old, who met the inclusion criteria. LP symptoms were most common during the first year following implantation; 26 patients (37.6%) demonstrated at least 1 symptom (voice alteration, chronic cough, sleep-disordered breathing, or dysphagia), and 15 patients required adjustments to their implant settings. The incidence of symptoms and the need to adjust VNS settings significantly dropped during years 2 to 5 and 6 to 8 (22% vs 7% and 5%, respectively, p = .0002). The mean score of the Pediatric Voice Handicap Index differed greatly from a normal control group on each subscale and the total score. LPdysfunction in children following VNS implantation is comparable to adults, with the most burden noticed during the first year after implantation. The presence of voice alterations did not correlate with the presence of dysphagia and sleep-disordered breathing. Thorough evaluation, preferably by a multidisciplinary team, is required to assess LP dysfunction postoperatively.

Vagus Nerve Stimulation for Drug Resistant Epilepsy: Clinical Outcome, Adverse Events, and Potential Prognostic Factors in a Single Center Experience.

Vagus nerve stimulation (VNS) has been used for adjunctive treatment in drug resistant epilepsy (DRE) for decades. Nevertheless, information is lacking on possible potential prognostic factors. Our study presents the efficacy and safety of VNS with a focus on prognostic factors in 45 patients with DRE. We retrospectively evaluated the clinical outcome of 45 consecutive patients with DRE undergoing VNS implantation in The First Affiliated Hospital of Anhui Medical University between November 2016 and August 2021. Medical records were aggregated across all patient visits. Cox proportional hazards regression was used to estimate the prognostic factors. Significant decrease in seizure frequency was observed after intermittent stimulation of the vagus nerve. According to the modified McHugh classification, 11 patients (24.4%) were Class I, 11 patients (24.4%) were Class II, four patients (8.9%) were Class III, 10 patients (22.2%) were Class IV, and nine patients (20.0%) were Class V. Notably, 22 patients (48.9%) were responders and four patients (8.9%) were seizure-free at the final follow-up. No significant prognostic factors were found in this cohort. Furthermore, 37 patients reported improved quality of life. Of the patients, 22 (48.9%) experienced adverse events after surgery; hoarseness, discomfort at the surgical site, and coughing were the most common. The results confirmed the efficacy and safety of VNS. No prognostic factors were identified.

Vagus nerve stimulation in people with epilepsy and intellectual disability—English version

BackgroundIn view of the still high rate of pharmaco-resistance in epilepsy, it is crucial to shed light on the non-pharmacological forms of therapy. Consideration of the patient group with epilepsy and intellectual disability is important for several reasons: it is a relevant patient group with an even higher proportion of drug-resistant courses than in people with epilepsy and normal intelligence. Resective epilepsy surgery is often not possible due to multifocal or diffuse brain damage. There are specific syndromes to consider as well as cognitive and behavioral peculiarities. Vagus nerve stimulation is discussed as a possible palliative therapy option.Aim of the workBased on a literature search, the present work sheds light on the importance of vagus nerve stimulation in the treatment of people with epilepsy and mental disabilities with special consideration of specific syndromes.ResultsDepending on the syndrome, the nature of the studies and the observational period, different outcomes of vagus nerve stimulation are observed. Compared to people with epilepsy and normal intelligence, there is a similar spectrum of side effects.DiscussionVagus nerve stimulation may be discussed in people with epilepsy and intellectual disability, bearing in mind the palliative nature of the intervention and the need for implantation of a device. It should be remembered that magnetic resonance imaging can only be used to a limited extent in the presence of an implanted vagus nerve stimulator.

Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database

Aim Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. Materials and methods We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. Results Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. Limitations Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. Conclusions After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

Long-term outcomes after NORSE: Treatment with vagus nerve stimulation.

New-onset refractory status epilepticus (NORSE) is associated with high mortality, therapy-resistant epilepsy (TRE), and poor cognitive and functional outcomes. Some patients develop multifocal TRE, for whom surgery with a curative intention, is not an option. In these patients, vagus nerve stimulation (VNS) is performed as a palliative treatment. We report the long-term outcomes regarding seizure frequency, functional and cognitive outcome, and effectiveness of VNS in two patients with TRE as a consequence of NORSE. In the first patient with cryptogenic NORSE, VNS implantation occurred during the acute stage, probably contributing to the cessation of her status epilepticus. However, in the long-term follow-up, the patient persisted with daily multifocal seizures. In the second patient, VNS implantation was delayed to manage his epilepsy when the NORSE, ultimately due to autoimmune encephalitis, had resolved. During long-term follow-up, no reduction in seizure frequency was achieved. This evidence supporting the use of VNS in patients with TRE after NORSE warrants further investigation.

PO097 / #1036 VAGAL NERVE DUPLICATION DURING VNS INTERVENTION: A CASE SERIES: E-POSTER VIEWING

The cervical vagus nerve (CVN) should be viewed not only as anatomical entity, but also as a morphological entity of the peripheral autonomic nervous system; a composite of different fibers and anastomosing and hitchhiking branches of different origin with different neurotransmitters, which can act parasympathetic, sympathetic, somato-efferent or viscero-afferent in function.1 Anatomical variations exist and we report on three cases where an anomaly of the anatomy of the CVN was found during VNS (vagal nerve stimulation) implantation.

A prediction model integrating synchronization biomarkers and clinical features to identify responders to vagus nerve stimulation among pediatric patients with drug-resistant epilepsy.

AimsVagus nerve stimulation (VNS) is a neuromodulation therapy for children with drug‐resistant epilepsy (DRE). The efficacy of VNS is heterogeneous. A prediction model is needed to predict the efficacy before implantation.MethodsWe collected data from children with DRE who underwent VNS implantation and received regular programming for at least 1 year. Preoperative clinical information and scalp video electroencephalography (EEG) were available in 88 children. Synchronization features, including phase lag index (PLI), weighted phase lag index (wPLI), and phase‐locking value (PLV), were compared between responders and non‐responders. We further adapted a support vector machine (SVM) classifier selected from 25 clinical and 18 synchronization features to build a prediction model for efficacy in a discovery cohort (n = 70) and was tested in an independent validation cohort (n = 18).ResultsIn the discovery cohort, the average interictal awake PLI in the high beta band was significantly higher in responders than non‐responders (p < 0.05). The SVM classifier generated from integrating both clinical and synchronization features had the best prediction efficacy, demonstrating an accuracy of 75.7%, precision of 80.8% and area under the receiver operating characteristic (AUC) of 0.766 on 10‐fold cross‐validation. In the validation cohort, the prediction model demonstrated an accuracy of 61.1%.ConclusionThis study established the first prediction model integrating clinical and baseline synchronization features for preoperative VNS responder screening among children with DRE. With further optimization of the model, we hope to provide an effective and convenient method for identifying responders before VNS implantation.

The Feasibility of Outpatient Type I Thyroplasty with Laryngeal Reinnervation.

Type I thyroplasty has increasingly been performed on an outpatient basis. Laryngeal reinnervation is recognized for its long-term and functional benefits but is typically performed inpatient under general anesthesia. Herein we report the first published outpatient type I thyroplasty with laryngeal reinnervation performed under monitored anesthesia care (MAC). Three adults underwent type I thyroplasty with ansa cervicalis to recurrent laryngeal nerve (RLN) reinnervation. A 23-year-old female with a history of generalized idiopathic epilepsy s/p vagal nerve stimulator implantation presented with persistent dysphonia. She developed longstanding left vocal fold paralysis. She underwent left type I thyroplasty with silastic implant and ansa cervicalis to RLN neurorrhaphy under MAC-local anesthesia. The patient was discharged home on the day of surgery. Two additional patients underwent the same procedure, including a 58-year-old male with postsurgical dysphonia who was admitted for overnight observation due to a small amount of incisional crepitus and a 23-year-old female with postsurgical vocal cord paralysis who was admitted overnight due to multiple comorbidities. Both were discharged on post-operative day one without issue and demonstrated improvement in voice at follow up. Outpatient type I thyroplasty with laryngeal reinnervation under MAC is feasible with proper patient selection.

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.]

Up to What Extent Does Dravet Syndrome Benefit From Neurostimulation Techniques?

BackgroundDravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown.MethodsWe searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively.ResultsThe Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs.ConclusionMore than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.

Results of vagus nerve stimulator implantation in children and adolescents with treatment-refractory epilepsy

Vagus nerve stimulation (VNS) is atherapeutic procedure that can be applied in apalliative setting in patients with treatment-refractory epilepsy who are not suitable for epilepsy surgery. The mechanism of action of VNS is currently not completely understood but appears to depend on amodification of neurotransmitter metabolism. Data of 25patients with treatment-refractory epilepsy who underwent implantation of avagus nerve stimulator were retrospectively analyzed in amonocentric study. Areduction in epileptic seizure rate of 28% was observed 3months after initial activation and of 32.9% after 6-12months. The responder rate (reduction in seizure rate of more than 50% compared to before implantation) was 40% 6-12months after initial activation. In one third of patients, areduction in epileptic seizure rate of at least 75% occurred. Adverse effects of surgery or the stimulation were rare.

Effects of Long-Term Vagus Nerve Electrical Stimulation Therapy on Acute Cerebral Infarction and Neurological Function Recovery in Post MCAO Mice.

Background Vagus nerve stimulation therapy is proven to produce neuroprotective effects against central nervous system diseases and reduce neurological injury, having a positive effect on the recovery of neurological functions in mouse model of stroke. Objective This study was aimed at exploring a wider time window for VNS treatment, investigating the long-term behavioral improvement of long-term VNS in mice after pMCAO, and exploring the antiapoptotic properties of VNS and its role in autophagy, all of which may be a permanent deficiency potential mechanism of neuroprotection in hemorrhagic stroke. Methods Permanent focal cerebral ischemia and implantation of vagus nerve stimulator were performed through intracavitary occlusion of the right middle cerebral artery (MCA). The vagus nerve stimulation group received five times vagus nerve stimulation from 6 h after surgery for 5 days. Adhesive removal test and NSS neurological score were used to evaluate the neurological deficit of mice. TTC staining of mouse brain tissue was performed one week after surgery in order to assess the area of cerebral infarction. Additionally, frozen sections were stained with Fluoro-Jade B to observe the apoptotic cells in the ischemic penumbra of brain tissue. Finally, Western blot was used to detect the changes in the levels of apoptosis-related proteins such as cleaved-caspase3 and Bcl-2 and autophagy-related proteins such as mTOR, Beclin-1, and LC3-II in brain tissue. Results VNS can effectively reduce the behavioral score of pMCAO mice; TTC results showed that VNS could effectively reduce the infarct area after pMCAO (P < 0.05). After VNS intervention of the pMCAO group compared with the pMCAO+VNI group, the FJB-positive cells in the VNS group were significantly decreased (P < 0.05); Western Blot analysis showed that the expression of cleaved-caspase3 in the brain tissue of mice increased after pMCAO (P < 0.05), and the expression of Bcl-2 decreased (P < 0.05). This change could be effectively reversed after VNS intervention (P < 0.05). Conclusion VNS could effectively improve the behavioral performance of mice after permanent stroke in addition to significantly reducing the infarct size of the brain tissue. The mechanism may be related to the effective reduction of cell apoptosis and excessive autophagy after pMCAO by VNS.

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study.

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 (p = 0.01, p = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).

Abstract WMP44: Complications Of Implanted Vagal Nerve Stimulation: A Systematic Review And Meta-analysis

Introduction: Vagus nerve stimulation (VNS) is a surgical technique that has been used to modulate disease processes by activating the parasympathetic system and has been used to treat conditions such as epilepsy and depression. More recently, VNS has been a promising tool in ischemic stroke rehabilitation. However, there has been no literature summarizing the adverse effects of this procedure, information that is critical for both patients and providers when obtaining informed consent for this novel treatment. This systematic review and meta-analysis aims to report the adverse effects of VNS. Methods: A systematic review was performed in accordance with PRISMA guidelines in order to identify common complications after VNS therapy. The search was executed in three databases: Cochrane Central Register of Controlled Trials, Embase, and Ovid MEDLINE. All prospective, randomized controlled trials using implanted VNS therapy in adult patients were eligible for inclusion. Case studies and studies lacking complete complication reports were excluded. Extracted data included technology name, location of implantation, follow-up duration, purpose of VNS, and adverse event rates. Results: After title-and-abstract screening of 4933 studies identified by the created search strategy, 21 studies were selected for final inclusion. Included papers studied VNS as a potential therapy for epilepsy (9), depression (8), anxiety (1), ischemic stroke (1), chronic heart failure (1), and fibromyalgia (1). In total, 1474 patients received VNS implantation in the 21 studies. The 5 most common post-implant adverse events were voice alteration/hoarseness (n=671, 45.5%), paresthesia (n = 233, 15.8%), cough (n = 221, 15.0%), dyspnea (n = 211, 14.3%), and pain (n = 170, 11.5%). Conclusions: Complications from VNS are relatively mild and transient, with reduction in severity and number of adverse events with increasing follow-up time. The most common complications included voice changes or hoarseness, increased cough, and pain with swallowing after surgery. In summary, VNS presents a powerful tool for the treatment of many difficult-to-treat conditions. In the future, the use of VNS in recovery after intracerebral hemorrhage should be explored.

Reducing VNS stimulation parameters: Is it safe?

Abstract Introduction Vagal nerve stimulation (VNS) is an adjuvant therapy used in the treatment of patients with refractory epilepsy who are not candidates for resective surgery or who have limited results after surgical procedures. Currently, there is enough evidence to support its use in patients with various types of epilepsy. Therefore, the present study was conducted to explore the possibility of optimizing therapy by reducing the consumption of the system's battery. Methods The prospective and double-blind analysis consisted in the evaluation of 6 patients submitted to VNS implantation for 3 months, followed by adjustment of the stimulation settings and continuity of follow-up for another month. The standard protocol was replaced by another with a frequency value of 20 Hz instead of 30 Hz to increase battery life. The safety of this procedure was evaluated through the assessment of two main variables: seizures and side effects. Results The stimulation at 20 Hz showed 68% reduction in the incidence of seizures (p = 0.054) as well as low incidence of side effects. Conclusion The present study suggests that the reduction of the stimulation frequency from 30 to 20 Hz is a safe procedure, and it does not compromise the effectiveness of therapy.

Vagus nerve stimulation outcome prediction: from simple parameters to advanced models.

Since its approval as an adjunct treatment for refractory partial epilepsy, the positive effects of vagus nerve stimulation (VNS) on seizure frequency and severity have been supported by many studies. Seizure reduction of more than 50 % can be expected in at least 50 % of patients. However, a complete post-VNS seizure freedom is rarely achieved and 25 % of patients do not benefit from VNS. Our study provides an overview of the potential predictors of VNS response, from the most simple and basic data to sophisticated EEG processing studies and functional imaging studying brain connectivity. The data support better outcomes in younger patients with early VNS implantation, in patients with posttraumatic epilepsy or tuberous sclerosis, and in patients without bilateral interictal epileptiform discharges. The variability of heart activity has also been studied with some promising results. Because the generally accepted hypothesis of the VNS mechanism is the modulation of synaptic activity in multiple cortical and subcortical regions of the brain, the studies of brain response to external stimulation and/or of brain connectivity were used for models predicting the effect of VNS in individual patients. Although the predictive value of these models is high, the required special equipment and sophisticated mathematical tools limit their routine use (Ref. 58). Keywords: epilepsy, vagus nerve stimulation, response predictor, EEG.

TVNS in the management of headache and pain.

First clinical observations of the therapeutic effect of vagus nerve stimulation were of patients who were treated for refractory epilepsy with a fully implanted vagus nerve stimulator, who also reported an improvement of their migraine and cluster headache. With the development of non-invasive vagus nerve stimulation, first clinical studies concerning a possible therapeutic effect in migraine and cluster headache were performed. In a controlled study, transcutaneous cervical vagus nerve stimulation (tcVNS) showed a significant but limited effect in acute treatment of a migraine attack. There was no significant prophylactic effect in episodic migraine. Concerning cluster headache, there was a clear beneficial effect in the prophylaxis of chronic cluster headache and in the attack treatment in episodic cluster headache. There are fewer studies in the literature on the effect of transcutaneous auricular vagus nerve stimulation (taVNS), with a partial overlap with studies on electrical ear acupuncture. In a small controlled clinical trial, there was a significant effect of taVNS in the prevention of chronic migraine. In less defined clinical studies, there were some positive signs that the method may be beneficial in chronic back pain and in unspecific gastro-intestinal pain in adolescents. Based on the available evidence, it is probable that vagus nerve stimulation can have a clinically meaningful influence on pain syndromes, but there are still several questions (e.g. frequency of the stimulation; duration of the stimulation; differential effects of auricular vagus stimulation and cervical vagus stimulation) to answer before vagus stimulation can be used widely in the clinic.