Vagus Nerve Stimulation Implantation Research Articles

Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration

BackgroundCervical vagus nerve stimulation (VNS) has been widely accepted as adjunctive therapy for drug-resistant epilepsy and major depression. Its effects on glycemic control in humans were however poorly understood. The aim of our study was to investigate the potential effects of VNS on fasting blood glucose (FBG) in patients with drug-resistant epilepsy.MethodsPatients with drug-resistant epilepsy who had received VNS implants at the same hospital were retrospectively studied. Effects on FBG, weight, body mass index and blood pressure were evaluated at 4, 8 and 12 months of follow-up.Results32 subjects (11 females/21 males, 19 ± 9 years, body mass index 22.2 ± 4.0 kg/m2) completed 12-month follow-up. At the 4 months, there were no significant changes in FBG concentrations from baseline to follow-up in both Sham-VNS (4.89 ± 0.54 vs. 4.56 ± 0.54 mmol/L, N = 13, p = 0.101) and VNS (4.80 ± 0.54 vs. 4.50 ± 0.56 mmol/L, N = 19, p = 0.117) groups. However, after 8 (4.90 ± 0.42 mmol/L, N = 32, p = 0.001) and 12 (4.86 ± 0.40 mmol/L, N = 32, p = 0.002) months of VNS, FBG levels significantly increased compared to baseline values (4.52 ± 0.54 mmol/L, N = 32). Changes in FBG concentrations at both 8 (R2 = 0.502, N = 32, p < 0.001) and 12 (R2 = 0.572, N = 32, p < 0.001) months were negatively correlated with baseline FBG levels.ConclusionsOur study suggests that chronic cervical VNS elevates FBG levels with commonly used stimulation parameters in patients with epilepsy.Trial registration VNSRE, NCT02378792. Registered 4 March 2015—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02378792

Subgroup analysis of seizure and cognitive outcome after vagal nerve stimulator implantation in children.

Vagal nerve stimulator (VNS) implantation at an early age seems to lead to improved quality of life and cognitive outcome. The aim of this analysis is to evaluate whether specific patient or seizure characteristics might lead to better seizure control, cognitive outcome, and higher quality of life in children undergoing VNS implantation. Primary outcome measure was reduction in seizure frequency. Secondary outcome measures were epilepsy outcome assessed by McHugh and Engel classifications, reduction in antiepileptic drugs (AED), developmental and cognitive outcome, as well as quality of life assessed through the pediatric quality of life (PEDSQL™) questionnaire and care giver impression (CGI) scale. Forty-five consecutive children undergoing VNS implantation were analyzed for the following subgroups: age (categorized to 1-2years old, 3-5years old, 6-12years old, and 13-18years old), sex, underlying cause (categorized to idiopathic, encephalitis, stroke, syndromic), duration of preoperative seizures (dichotomized to under or above 89months, corresponding to the median of the whole cohort), and preoperative seizure frequency (dichotomized to under and above 360 seizures per month). Encephalitis as the underlying cause for seizures was the only variable significantly associated with higher reduction rate of seizure frequency. Patients with VNS implantation at the age of ≤ 2years showed a strong association with better developmental and cognitive outcome, as well as quality of life. Shorter duration of preoperative seizures and higher preoperative seizure frequency showed a strong association with better developmental outcome, as well as quality of life. Engel outcome scores were significantly better in patients with epilepsy due to encephalitis (100% Engel I-III). However, patients with epilepsy due to encephalitis showed significantly higher complication rates (71.4%, p = 0.045). Children suffering from epilepsy due to encephalitis show higher seizure reduction rates after VNS implantation when compared with children suffering from epilepsy due to other causes. Developmental and cognitive outcomes as well as quality of life of children undergoing VNS implantation is strongly associated with shorter duration of preoperative seizures and implantation at a young age.

(Invited) Self-Powered Wearable and Implantable Electrical Stimulation Devices for Biomedical Applications

Electrical stimulation (ES) is a widely used therapeutic treatment strategy. It showed significantly positive results in treating a variety of diseases, biological disorders, and neurological problems. Today, the emergence of wearable devices is rapidly reshaping the development of medical devices, pushing them from conventional bulky and rigid silicon electronics to flexible and primarily polymer-based systems. Among many types of functions, nanogenerators are developed as a unique device for converting biomechanical energy into electrical pulses. This talk will fist introduce the application of flexible nanogenerators as an implantable power source and its biosafety and compatibility. In addition, the pulsed electricity from nanogenerators can be applied directly as a ES signal for therapeutic treatment. In our recent research, we successfully implemented such an electromechanical system for skin wound healing, hair growth, and vagus nerve stimulation for obesity control. An electrical stimulation bandage was developed by integrating a flexible nanogenerator and a pair of dressing electrodes on a flexible substrate. Rat studies demonstrated rapid closure of a full-thickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to the electric field-facilitated fibroblast migration, proliferation and transdifferentiation. Via a similar design, the electrical pulses were applied to stimulate hair growth. Significantly facilitated hair regeneration results were obtained from Sprague-Dawley rats and nude mice, which was attributed to the improved secretion of vascular endothelial growth factor and keratinocyte growth factor. In another work, an implanted vagus nerve stimulation system was developed. The device comprises a flexible and biocompatible nanogenerator that is attached on the surface of stomach. It generates biphasic electric pulses in responsive to the peristalsis of stomach. The electric signals generated by this device stimulates the vagal afferent fibers to reduce food intake and achieve weight control. This strategy is successfully demonstrated on rat models. Within 100 days, the average body weight is controlled at 350 g, 38% less than the control groups. All the results bring a new concept in electrical therapeutic technology that is battery-free, self-activated and directly responsive to body activities. Keywords: Nanogenerator; Implantable medical devices; Wearable devices; Self-powered systems; Electrical stimulation;

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.

Vagus Nerve Stimulator implantation in a pregnant woman with drug resistant epilepsy

The aim is to present a case of successful implantation of Vagus Nerve Stimulator (VNS) in a woman with drug resistant epilepsy (DRE) during pregnancy. It is the first case of VNS implantation in the Russian Federation. The implantation, follow-up, and programming were carried out in the Bekhterev National Research Medical Centre of Psychiatry and Neurology, Saint-Petersburg. Material and method . Female patient, 28 y.o., was diagnosed with DRE more than 11 years ago. The course of her epilepsy deteriorated during pregnancy despite of the appropriate antiepileptic treatment. The EEG, MRI, and laboratory tests did not reveal any focal brain lesion that could necessitate surgical resection. After multidisciplinary consultations, no contraindications to VNS procedure were found. Results . The VNS system was implanted in this patient when she was 18-week-pregnant. The procedure resulted in a seizure reduction and allowed the patient to preserve her pregnancy and deliver a healthy child. Conclusion s. VNS Therapy® is safe and effective for the treatment of DRE. This successful case of VNS implantation in pregnancy opens new venues for the treatment of DRE in this group of patients. The authors declare the absence of conflict of interest with respect to this publication. All authors contributed equally to this article.

Surgical Outcomes in Post-Traumatic Epilepsy: A Single Institutional Experience.

Post-traumatic epilepsy (PTE) is a debilitating sequela of traumatic brain injury (TBI), occurring in up to 20% of severe cases. This entity is generally thought to be more difficult to treat with surgical intervention. To detail our experience with the surgical treatment of PTE. Patients with a history of head injury undergoing surgical treatment for epilepsy were retrospectively enrolled. Engel classification at the last follow-up was used to assess outcome of patients that underwent surgical resection of an epileptic focus. Reduction in seizure frequency was assessed for patients who underwent vagal nerve stimulator (VNS) or responsive neurostimulator (RNS) implantation. A total of 23 patients met inclusion criteria. Nineteen (82.6%) had mesial temporal sclerosis, 3 had lesional neocortical epilepsy (13.0%), and 1 had nonlesional neocortical epilepsy (4.3%). Fourteen patients (60.9%) underwent temporal lobectomy (TL), 2 underwent resection of a cortical focus (8.7%), and 7 underwent VNS implantation (30.4%). Three patients underwent RNS implantation after VNS failed to reduce seizure frequency more than 50%. In the patients treated with resection, 11 (68.8%) were Engel I, 3 (18.8%) were Engel II, and 2 (12.5%) were Engel III at follow-up. Average seizure frequency reduction in the VNS group was 30.6%±25.6%. RNS patients had reduction of seizure severity but seizure frequency was only reduced 9.6%±13.6%. Surgical outcomes of PTE patients treated with TL were similar to reported surgical outcomes of patients with nontraumatic epilepsy treated with TL. Patients who were not candidates for resection demonstrated variable response rates to VNS or RNS implantation.

Alteraciones respiratorias durante el sueño a consecuencia de la estimulación del nervio vago

Vagus nerve stimulation (VNS) is indicated in cases of refractory epilepsy. Its side effects are frequently minor, however, breathing disturbances during sleep have been previously reported. Our three cases are representative of sleep-disordered breathing that occurred as a consequence of VNS activity in patients with refractory epilepsy. Sleep apnoea was observed in two patients and stridor in one patient. Given the high prevalence of sleep apnoea-hypopnoea syndrome in patients with refractory epilepsy, implantation of VNS should be ideally preceded by an assessment of the breathing during sleep. Furthermore, sleep-disordered breathing should be considered as a rare complication of VNS, and sleep apnoea should be investigated alongside data regarding VNS firing.

The Immediate Effects of Vagus Nerve Stimulation in Intractable Epilepsy: An Intra-operative Electrocorticographic Analysis.

The purpose of this study was to investigate whether and how vagus nerve stimulation (VNS) reduces the epileptogenic activity in the bilateral cerebral cortex in patients with intractable epilepsy. We analyzed the electrocorticograms (ECoGs) of five patients who underwent callosotomy due to intractable epilepsy even after VNS implantation. We recorded ECoGs and analyzed power spectrum in both VNS OFF and ON phases. We counted the number of spikes and electrodes with epileptic spikes, distinguishing unilaterally and bilaterally hemispherically spread spikes as synchronousness of the epileptic spikes in both VNS OFF and ON phases. There were 24.80 ± 35.55 and 7.20 ± 9.93 unilaterally spread spikes in the VNS OFF and ON phases, respectively (P = 0.157), and 35.8 ± 29.21 and 10.6 ± 13.50 bilaterally spread spikes in the VNS OFF and ON phases, respectively (P = 0.027). The number of electrodes with unilaterally and bilaterally spread spikes in the VNS OFF and ON phases was 3.84 ± 2.13 and 3.59 ± 1.82 (P = 0.415), and 8.20 ± 3.56 and 6.89 ± 2.89 (P = 0.026), respectively. The ECoG background power spectra recordings in the VNS OFF and ON phases were also analyzed. The spectral power tended to be greater in the high-frequency band at VNS ON phase than OFF phase. This study showed the reduction of epileptogenic spikes and spread areas of the spikes by VNS as immediate effects, electrophysiologically.

Remote programming: A convenient and cost-effective measure of vagus nerve stimulation for children with epilepsy

This study aimed to evaluate the efficacy, adverse events and expense burden of outpatient versus remote programming for vagus nerve stimulation (VNS) in children with epilepsy. A total of 46 children with drug-resistant epilepsy, who underwent VNS at the Pediatric Epilepsy Center, Peking University First Hospital between March 2017 and June 2018, were enrolled into the study. Participants were assigned (non-randomized) into an outpatient programming group or remote programming group (where VNS parameters were adjusted through the internet) by parental choice. The responder rate, expenditure for VNS programming and adverse events were compared between the two groups.The median age at VNS implantation was 5.17 years (3.83–6.71), with the median epileptic course being 3.79 years (2.65–4.90). Twenty-four patients were assigned to the outpatient programming group and 22 were assigned to the remote programming group. Baseline data were comparable between the two groups, with the exception of the remote group having a longer distance between their place of residence and the hospital. The median time from VNS implantation to last follow-up was 1.33 years (1.25–1.75) and 1.46 years (1.17–1.58) in the outpatient and remote groups, respectively. In the outpatient programming group, 15 patients (62.5 %,) were VNS responders and four patients (16.6 %) became seizure-free. In the remote programming group, 16 patients (72.7 %) were VNS responders and four (17.4 %) became seizure-free. Cough and hoarseness were common adverse events in both the outpatient and remote groups (33.3 % vs. 18.2 %). There were no significant differences between the two groups in terms of adverse events. The median cost of each follow-up visit per patient in the outpatient group was 192.4 US dollars ($120.0–$376.5), of which travelling expenses were the major component, followed by accommodation fees, outpatient service fees and indirect costs. Whereas, patients in the remote programming group only needed to pay for the remote programming expense, which totaled 75.8 US dollars per person each time. The efficacy and adverse events were both comparable between the outpatient and remote programming patients. Remote programming was found to be a more cost-effective treatment, especially for patients living further away from centers specializing in epilepsy.

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.

Efficacy of Vagal Nerve Stimulation for Pharmacoresistant Poststroke Epilepsy

Vagal nerve stimulation (VNS) is an alternative palliative therapy for pharmacoresistant epilepsy. It has been reported to be effective for both focal and generalized epilepsy; however, most of the relevant studies have involved children or young patients. Some patients develop intractable epilepsy after stroke, despite taking antiepileptic drugs (AEDs). In this study, we investigated the efficacy of VNS for pharmacoresistant poststroke epilepsy (PPSE). We retrospectively studied 10 patients who underwent vagal nerve stimulator implantation for poststroke epilepsy after the seizures had proved refractory to appropriate AEDs. The seizure outcome was evaluated using the McHugh classification 2 years after the implantation. In total, 4 patients (40%) remained seizure-free throughout the 2-year duration. In addition, seizures were reduced by >50% after 2 years in 6 patients (60%). McHugh classification was class I for 5 patients and class II for 5 patients. Neither intraoperative complications nor postoperative adverse effects were reported. The average intensity of VNS was 1.75 mA. In this small study, VNS proved to be a safe and effective therapy for PPSE. Patients with poststroke epilepsy experience physical or mental decline; therefore, it is important to control seizures in them to avoid deterioration in their quality of daily life.

The Effectiveness of Medical and Surgical Treatment for Children With Refractory Epilepsy

Abstract INTRODUCTION Pediatric refractory epilepsy affects quality of life, clinical disability, and healthcare costs for patients and families. We aimed to show the impact of surgical treatment for pediatric epilepsy on healthcare utilization compared to medically treated pediatric epilepsy over 5 yr. METHODS The Pediatric Health Information System database was used to study hospitalized children with epilepsy using five published algorithms. Refractory epilepsy (RE) patients treated with either antiepileptic medications (AEDs) only or AEDs plus epilepsy surgery (ES) between 1/1/2008 and 12/31/2014 were included. Patients with a history of ES before 1/1/2008 or a vagus nerve stimulation implantation surgery were excluded. ICD-9-CM codes were used to identify ES. Healthcare utilization following the index date at 2- and 5-yr including inpatient, emergency department (ED), and all epilepsy-related visits were evaluated. The propensity scores (PS) method was used to match surgically and medically treated patients. Covariates associated with the probability of receiving surgical treatment were chosen in the logistic regression model for calculating PS. SAS 9.4 and Stata 14.0 were used for data management and statistical analysis. RESULTS A total of 2106 (17.1%) and 10186 (82.9%) were surgically and medically treated, respectively. A total of 4050 matched cases, 2025 per each treated group, were included. Overall survival rates of matched cases were 98.07% and 99.58% at 2-yr and 96.66% and 98.99% at 5-yr for medically and surgically treated patients, respectively. Within 5-yr follow-up, seizure-associated healthcare utilization was lower for the surgically treated group: number of inpatient visits were 3.9 vs 2.5 and ED visits were 3.2 vs 1.7 for medically and surgically treated patients, respectively. The number of AEDs at 1-yr follow-up was significantly lower for the surgically treated group (3.22 decreased to 2.59: surgical group, 3.24 decreased to 3.06: medical group). CONCLUSION We found a significant decrease in inpatient and ED visits and number of antiepileptic drug prescriptions, as well as higher survival rates, at 2- and 5-yr follow-up in the surgically treated group compared to the medically treated group for pediatric patients with refractory epilepsy. Pediatric epilepsy surgery can provide beneficial outcomes, favorable long-term effectiveness, and reduced healthcare utilization compared to medical management.

Clinical outcomes of closed-loop vagal nerve stimulation in patients with refractory epilepsy

PurposeThe AspireSR® is a vagal nerve stimulation (VNS) device that operates as a closed-loop system, delivering an automatic stimulation in response to an ictal heart rate increase that serves as a predictor for an imminent seizure.Our purpose is to assess the outcome of the AspireSR® in a patient population managed in a pediatric neurology unit. MethodsThe records of patients who underwent transplantation during 2015–2017 and are continuously followed in one pediatric-epilepsy clinic, were retrospectively analyzed. Collected information included demographics, use of antiepileptic drugs and seizure type, frequency and duration before and after VNS implantation. Results46 patients ages 5–31 years (mean 15.7 ± 5.8), mean age at implantation 14 ± 5.8 years, were included. 29 patients (63%) were new insertions and 17 of the patients (37%) underwent a VNS replacement to the AspireSR® model. Mean follow-up was 13 ± 7.5 months (range 2–29 months). The total cohort responder rate (patients with ≥50% reduction in seizure frequency compared to the pre-implantation period) was 60.9%. (62% in the new insertion group; while 59% in the replacement group had additional benefit over their former VNS model, p = 0.981). Epilepsy etiology, age, age at implantation and type of seizures pre-implantation showed no correlation to response-rate. Five patients (10.9%) experienced complete seizure-freedom following implantation (4/5 in the "new insertion" group). Responses were reported at median follow up of 5 ± 1.3 months post-implantation. 67.4% experienced shorter seizure duration post-implantation. ConclusionOur results suggest that the AspireSR® device provides an early and meaningful benefit to drug-resistant epilepsy patients, which is relevant for both patients with new insertions and those with replacements of former VNS devices.

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.

PSU8 THE EFFECTIVENESS OF TREATMENT CHOICES FOR REFRACTORY EPILEPSY AMONG PEDIATRIC POPULATION

To compare healthcare utilization following surgical or medical treatment for children with refractory epilepsy We extracted hospitalized children with epilepsy from the Pediatric Health Information System database using five published algorithms. Refractory epilepsy (RE) patients treated with either antiepileptic medications (AEDs) only or AEDs plus epilepsy surgery (ES) between 1/1/2008 and 12/31/2014 were included. Patients with a history of ES before 1/1/2008 or a vagus nerve stimulation implantation surgery were excluded. ICD-9-CM codes were used to identify ES. Healthcare utilization following the index date at 2- and 5- years including inpatient, emergency department (ED), and all epilepsy-related visits were evaluated. The propensity scores (PS) method was used to match surgically and medically treated patients. Covariates associated with the probability of receiving surgical treatment were chosen in the logistic regression model for calculating PS. SAS® 9.4 and Stata 14.0 were used for data management and statistical analysis. 10089 (82.8%) and 2083 (17.2%) were surgically and medically treated, respectively. Significant variations of subgroup distribution in age, race, insurance, sources of admission, primary diagnosis, and pediatric complex chronic conditions (p<0.001 for all binary tests) were identified between two groups. 4050 matched cases, 2025 per each treated group, were included. Compared to medically treated patients, utilization was reduced in the surgical group: at 2- and 5- years post-index date, there was a reduction of 40% and 42% of inpatient visits and 46% and 49% of ED visits. The total number (inpatient, ED, ambulatory visits) of epilepsy-associated visits were also reduced by 42%-45% in the surgical group compared to medically-treated group. In those who had surgery, the average reduction in AEDs was 16% at 2- and 5- years after treatment. Patients with refractory epilepsy treated with surgery had significant reductions in healthcare utilization compared with matched patients treated with antiepileptic medications only.

(Invited) Self-Powered Wearable and Implantable Electrical> Stimulation Devices for Medical Treatments

Electrical stimulation (ES) is a widely used therapeutic treatment strategy. It showed significantly positive results in treating a variety of diseases, biological disorders, and neurological problems. Today, the emergence of wearable devices is rapidly reshaping the development of medical devices, pushing them from conventional bulky and rigid silicon electronics to flexible and primarily polymer-based systems. Among many types of functions, nanogenerators are developed as a unique device for converting biomechanical energy into electrical pulses. Besides using it directly as a power source, this pulsed electricity can be applied directly as a ES signal for therapeutic treatment. In our recent research, we successfully implemented such an electromechanical system for skin wound healing and vagus nerve stimulation for obesity control. An electrical stimulation bandage was developed by integrating a flexible nanogenerator and a pair of dressing electrodes on a flexible substrate. Rat studies demonstrated rapid closure of a full-thickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to the electric field-facilitated fibroblast migration, proliferation and transdifferentiation. In another work, an implanted vagus nerve stimulation system was developed. The device comprises a flexible and biocompatible nanogenerator that is attached on the surface of stomach. It generates biphasic electric pulses in responsive to the peristalsis of stomach. The electric signals generated by this device stimulates the vagal afferent fibers to reduce food intake and achieve weight control. This strategy is successfully demonstrated on rat models. Within 100 days, the average body weight is controlled at 350 g, 38% less than the control groups. Both results bring a new concept in electrical therapeutic technology that is battery-free, self-activated and directly responsive to body activities.

Vagus Nerve Stimulation in Patients With Refractory Epilepsy: a case series

Approximately 33% of patients with epilepsy do not respond to treatment with a single antiepileptic drug. Many of these patients can benefit from neurosurgical treatment. However, not all patients are candidates for surgery, and in these cases vagus nerve stimulation (VNS) presents as a good therapeutic option. Objectives: Evaluation of efficiency, tolerability and safety in the control of seizures after VNS implantation in patients from a reference hospital. Methods: cross-sectional study examined 20 patients who underwent implantation of the VNS in our facilities between 2007 and 2014. Proportions and chi-square test were applied (statistical significance level set to p ≤ 0.05). Results: Mean follow-up was 31.3 months. Seizure frequency decreased in 55% of the patients. Among them, 11 patients believed that VNS had improved their quality of life. The mean reduction reported by other patients was 78.3%. More than 30% reported no adverse effects. About 70% of patients no longer required hospitalizations and 95% reported reduction in the number of hospitalizations. Conclusion: In this population, VNS proved to be a good option in the treatment of refractory epilepsy and also in providing a significant improvement in quality of life, (reduction of seizures and hospitalizations), mood, attention and memory, which directly reflects on their social and cognitive.

Investigating the Effect of Short Term Responsive VNS Therapy on Sleep Quality Using Automatic Sleep Staging.

The goal of this work is to objectively evaluate the effectiveness of responsive (or closed-loop) Vagus nerve stimulation (VNS) therapy in sleep quality in patients with medically refractory epilepsy. Using quantitative features obtained from electroencephalography, we first developed a new automatic sleep-staging framework that consists of a multi-class support vector machine (SVM) classification, based on a decision tree approach. To train and evaluate the performance of the framework, we used polysomnographic data of 23 healthy subjects from the PhysioBank database where the sleep stages have been visually annotated. We then used the trained classifier to label the sleep stages using data from 22 patients with epilepsy, treated with short term responsive VNS therapy during an epilepsy-monitoring unit visit, one month after VNS implantation, and ten VNS-naïve patients with epilepsy. Application of multi-class SVM classifier to classify the three sleep stages of awake, light sleep + rapid eye movement, and deep sleep achieved a classification accuracy of 90%. Results of the application of this methodology to VNS-treated and VNS-naïve patients revealed that the patients treated with short term responsive VNS therapy showed significant increase in sleep efficiency, and significant decrease in seizures plus interictal epileptiform discharges and awakenings. These results indicate that VNS treatment can reduce the epileptiform activities and thus help in achieving better sleep quality for patients with epilepsy. The proposed approach can be used to investigate the effect of long-term VNS therapy on sleep quality.

Vagus nerve stimulation for primary headache disorders: An anatomical review to explain a clinical phenomenon.

BackgroundNon-invasive stimulation of the vagus nerve has been proposed as a new neuromodulation therapy to treat primary headache disorders, as the vagus nerve is hypothesized to modulate the headache pain pathways in the brain. Vagus nerve stimulation can be performed by placing an electrode on the ear to stimulate the tragus nerve, which contains about 1% of the vagus fibers. Non-invasive vagus nerve stimulation (nVNS) conventionally refers to stimulation of the cervical branch of the vagus nerve, which is made up entirely of vagal nerve fibers. While used interchangeably, most of the research to date has been performed with nVNS or an implanted vagus nerve stimulation device. However, the exact mechanism of action of nVNS remains hypothetical and no clear overview of the effectiveness of nVNS in primary headache disorders is available.MethodsIn the present study, the clinical trials that investigated the effectiveness, tolerability and safety of nVNS in primary headache disorders were systematically reviewed. The second part of this study reviewed the central connections of the vagus nerve. Papers on the clinical use of nVNS and the anatomical investigations were included based on predefined criteria, evaluated, and results were reported in a narrative way.ResultsThe first part of this review shows that nVNS in primary headache disorders is moderately effective, safe and well-tolerated. Regarding the anatomical review, it was reported that fibers from the vagus nerve intertwine with fibers from the trigeminal, facial, glossopharyngeal and hypoglossal nerves, mostly in the trigeminal spinal tract. Second, the four nuclei of the vagus nerve (nuclei of the solitary tract, nucleus ambiguus, spinal nucleus of the trigeminal nerve and dorsal motor nucleus (DMX)) show extensive interconnections. Third, the efferents from the vagal nuclei that receive sensory and visceral input (i.e. nuclei of the solitary tract and spinal nucleus of the trigeminal nerve) mainly course towards the main parts of the neural pain matrix directly or indirectly via other vagal nuclei.ConclusionThe moderate effectiveness of nVNS in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems as described in animals.

Predictors of seizure reduction outcome after vagus nerve stimulation in drug-resistant epilepsy

PurposeTo evaluate the predictors of seizure reduction outcome after vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE). MethodsA meta-analysis was performed using relevant research from databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to predefined inclusion and exclusion criteria. The quality of studies was evaluated by using the Newcastle-Ottawa Scale (NOS) scale. All data was pooled by STATA 12.0 software for meta-analysis. ResultsThe review considered 1281 articles, and 16 articles with NOS score ≥6 were included in the analysis. The meta-analysis showed that at 6 m, 1, 2, 3, 4, 6 and 12 years after implantation, 33.99, 43.42, 46.50, 63.31, 52.71, 54.64, 70.37 and 82.90% of patients exhibited >50% reduction of seizure frequency after VNS. The duration of epilepsy showed a significant difference between the good responders and poor responders (p = 0.038), whereas age at VNS implantation (p = 0.305), age at seizure onset (p = 0.530), seizure type (p = 0.11), etiology (p = 0.187), and history of previous epilepsy surgery (p = 0.075) were not predictors of seizure reduction outcome after VNS. Several features about the electroencephalogram (EEG) feature and heart rhythm complexity (HRV) have not been analyzed by a sufficient number of studies. ConclusionsDRE patients with shorter duration of epilepsy may be better candidates for VNS rather than those who are younger at onset and implantation. Several EEG or HRV features may have predictive value but more research is needed.