VNS Implantation Research Articles

Variation in access to specialist services for neurosurgical procedures in adults with epilepsy in England, a cohort study.

To understand if primary consultation at tertiary epilepsy centres (TEC) in England impacts access to neurosurgical procedures (resective surgery, vagus nerve stimulator [VNS], deep brain stimulator [DBS]). Adults with epilepsy, and with a first neurology outpatient visit (index) between 01/01/2013 and 31/12/2015, were followed using English Hospital Episode Statistics from index date to 31/12/2019. Analyses were stratified by geographic location, learning disability record, and whether the index or follow-up visits were at a TEC. 84,093 people were included, with mean 5.5 years of follow-up. 12.4% of the cohort had learning disability (range 10.1%-17.4% across regions). TEC consultations varied by National Health Service regions and Clinical Commissioning Groups. 37.5% of people (11.2%-75.0% across regions) had their index visit at a TEC; and, of those not initially seen at a TEC, 10.6% (6.5%-17.7%) subsequently attended a tertiary centre. During follow-up, 11.1% people (9.5%-13.2%) visited a neurosurgery department, and 2.3% of those (0.9%-5.0%) then underwent a neurosurgical procedure, mainly VNS implantation. Median time from index date to first visit at a neurosurgery centre was 7 months (range 6-8 months across regions) and 40 months to procedure (36.5-49 months, 37.0 months in people with index visit at a TEC and 49.0 months otherwise). People with learning disability were less likely to have resective surgery (<0.5% versus 1.0% in those without) and more likely to undergo VNS implantation (5.8% versus 0.8%). Although clinically recommended for suitable individuals, neurosurgical procedures in epilepsy remain uncommon even after consultation at a TEC. Geographical variation in access to TECs was present.

Favorable combinations of antiseizure medication with vagus nerve stimulation to improve health-related quality of life in patients with epilepsy

BackgroundVagus nerve stimulation (VNS) is a non-pharmacological treatment of refractory epilepsy, which also has an antidepressive effect. The favorable combinations of VNS with specific mechanisms of action of antiseizure medication (ASM) on mood and health-related quality of life (HrQol) have not yet been studied. The objective was to identify favourable combinations of specific ASMs with VNS for the HrQoL and depression in refractory epilepsy. MethodsWe performed an observational study including patients with refractory epilepsy and an implanted VNS (N = 151). In the first 24 months after VNS implantation, all patients were on stable ASM therapy. We used the standardized questionnaires QOLIE10, EQVAS and EQ5D to evaluate HrQoL as well as the Beck Depression Inventory (BDI). Multiple regression analysis was performed to evaluate the synergistic combinations of ASM with VNS for HrQoL. ResultsAt the year-two follow-up (N = 151, age 45.2 ± 17.0 years), significant improvement (p < 0.05) in BDI scores was found for combination of VNS with SV2A modulators (58.4 %) or AMPA antagonists (44.4 %). A significant increase of HrQoL by at least 30 % (p < 0.05) was measured for a combination of VNS with SV2A modulators (brivaracetam, levetiracetam) or slow sodium channel inhibitors (eslicarbazepine, lacosamide). ConclusionThe results of our study suggests a favorable effect of the combination of SV2A modulators or slow sodium channel inhibitors with VNS on the HrQoL in comparison to other ASMs. Besides the possible synergistic effects on the seizure frequency, the amelioration of behavioral side effects of SV2A modulators by VNS is an important factor of HrQoL-improvement in these combinations.

Baseline characteristics of a European patient population with difficult-to-treat depression (RESTORE-LIFE) treated with adjunctive vagus nerve stimulation

BackgroundMajor depressive disorder is a complex heterogeneous disorder. Treatment is especially challenging for patients with “difficult-to-treat depression” (DTD): a less stigmatizing and more clinically relevant framework defining depression that continues to cause significant burden despite usual treatment efforts. MethodsRESTORE-LIFE is a prospective, observational, multicenter, post-market study being conducted in Europe and is designed to reflect real-world clinical application of adjunctive Vagus Nerve Stimulation Therapy (VNS) for DTD. Baseline characteristics of RESTORE-LIFE patients were analyzed and compared to published treatment-resistant depression (TRD) trials. ResultsThis analysis includes the initial 98 RESTORE-LIFE patients who commenced treatment with VNS. Patients had a mean of 11.4 failed anti-depressant treatments, 1.1 suicide attempts, 87 % had prior electroconvulsive therapy, and 36 % had an endocrine/metabolic comorbidity. On average, disease severity was comparable to that in TRD trials (n = 15,463). However, RESTORE-LIFE patients appear to have been experiencing DTD for a longer duration and their DTD was characterized by a lack of positive mental health and meaningfulness of life, to a greater degree than by excess of negative mood. Despite high comorbidity rates in RESTORE-LIFE, VNS implantation was performed safely with no discontinuations due to surgical adverse events. LimitationsRESTORE-LIFE enrolls any patient receiving adjunctive VNS for DTD. Prescription of VNS may be biased by differences in practices amongst sites and countries. ConclusionsThe present analysis offers insight into contemporary real-world use of VNS Therapy for DTD in Europe representing a comprehensive characterization of DTD and how this population may differ from those in the TRD literature.

Synergistic effects of vagus nerve stimulation and antiseizure medication

IntroductionVagus nerve stimulation (VNS) is an effective, non-pharmacological therapy for epileptic seizures. Until now, favorable combinations of different groups of antiseizure medication (ASM) and VNS have not been sufficiently addressed. The aim of this study was to identify the synergistic effects between VNS and different ASMs.MethodsWe performed an observational study of patients with epilepsy who were implanted with VNS and had a stable ASM therapy during the first 2 years after the VNS implantation. Data were collected from the Mainz Epilepsy Registry. The efficacy of VNS depending on the concomitantly used ASM group/individual ASMs was assessed by quantifying the responder rate (≥ 50% seizure reduction compared to the time of VNS implantation) and seizure freedom (absence of seizures during the last 6 months of the observation period).ResultsOne hundred fifty one patients (mean age 45.2 ± 17.0 years, 78 females) were included in the study. Regardless of the used ASM, the responder rate in the whole cohort was 50.3% and the seizure freedom was 13.9%. Multiple regression analysis showed that combination of VNS with synaptic vesicle glycoprotein (SV2A) modulators (responder rate 64.0%, seizure freedom 19.8%) or slow sodium channel inhibitors (responder rate 61.8%, seizure freedom 19.7%) was associated with a statistically significant better responder rate and seizure freedom than combinations of VNS and ASM with other mechanism of action. Within these ASM groups, brivaracetam showed a more favorable effect than levetiracetam, whereas lacosamide and eslicarbazepine were comparable in their effects.ConclusionOur data suggest that the combination of VNS with ASMs belonging to either SV2A modulators or slow sodium channel inhibitors could be optimal to achieve a better seizure control following VNS. However, these preliminary data require further validation under controlled conditions.

0541 Obstructive Sleep Apnea Following Vagus Nerve Stimulator Implantation: A Meta-Analysis

Abstract Introduction Vagus nerve stimulation (VNS) treatment for patients with intractable epilepsy has been shown to effectively lower seizure frequency and improve quality of life. However, due to stimulation of the vagus nerve, alterations in both central regulation of breathing and laryngeal muscle stimulation can precipitate obstructive sleep apnea (OSA). While there have been case reports describing OSA following VNS implantation, there has yet to be a detailed evaluation of this complication in a large cohort of VNS patients. The objective of this meta-analysis was to determine OSA rates in patients following VNS implantation. Methods English full-text articles were searched for on Pubmed, Scopus, and Embase databases. Articles had to follow patients before and after VNS implantation; report apnea-hypopnea index (AHI), respiratory disturbance index (RDI), or OSA rates following VNS implantation; be from a clinical trial, cohort, or case-control study. Two reviewers reviewed articles and a third settled disagreements. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies were used. Following Freeman-Tukey transformation, the generic inverse variance method with random effects model was used for meta-analysis. Results Ten studies, seven retrospective and three prospective, representing a cohort of 306 patients were included in this study. Pooled OSA rates following VNS implantation were 27.3%, 95% CI: 15.1 - 41.5%. Subgroup analysis found no difference in rates between studies of pediatric populations (22.1%, 95% CI: 8.2 - 40.5%) and adult populations (31.9%, 95% CI: 18.9 - 47.5%) following VNS implantation (P = 0.39). There was significant heterogeneity in pooled analysis (P &amp;lt; 0.00001, I2 = 100%), but no inter-subgroup heterogeneity (I2 = 0%). Conclusion Obstructive sleep apnea is a common adverse effect following VNS treatment and patients should be monitored following implantation. There are no differences in OSA rates between pediatric and adult populations. Routine screening for OSA following VNS implantation may be a reasonable choice. Support (if any) No institutional or NIH funding was received for this project

Effect of vagus nerve stimulation in patient with prolonged postictal encephalopathy

AbstractVagus nerve stimulation (VNS) has rarely been used in adult patients with status epilepticus (SE). Although evidence for VNS's effect on consciousness is largely lacking, VNS implantation may be considered an option in a prolonged unconscious state after SE. Here, we present the case of a woman with prolonged SE whose consciousness incompletely recovered after seizure cessation with conventional therapy but fully recovered after activation of VNS.

Laryngology Outcomes Following Implantable Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) devices have gained widespread acceptance for treatment of resistant epilepsy and depression. The increasing number of procedures has resulted in an increasing number of iatrogenic injuries to the vagus nerve, which can have a significant effect on vocalization and quality of life. To determine the relative frequency of laryngeal adverse effects reported to the US Food and Drug Administration (FDA) after VNS implantation and to analyze associated VNS device problems. This retrospective cross-sectional analysis queried the FDA Manufacturer and User Facility Device Experience database of adverse events in the US between 1996 and 2020. The primary outcome was the percent of adverse events reported to the FDA that included patients who received VNS with laryngeal adverse effects and the associated proportion of device problems after VNS surgery. A total of 12 725 iatrogenic vagus nerve issues were documented after VNS implantation, with apnea (n = 395; 3.1%) being the most common patient problem. Overall, 187 reports of laryngeal adverse effects associated with VNS devices were identified and represented the eighth most common iatrogenic vagus nerve problem reported to the FDA. Laryngeal adverse effects included 78 reports of voice alteration and 57 reports of paresis/paralysis. The VNS device problems frequently associated with laryngeal adverse effects were high impedance (n = 15, 8.02%), incorrect frequency delivery (n = 10, 5.35%), and battery problems (n = 11, 5.88%). The number of laryngeal adverse effect reports per year peaked in 2012 with 43 cases. This cross-sectional study found that although the literature demonstrates that vocal changes occur with nearly all VNS devices, the FDA receives adverse event reports of voice changes. Our results emphasize a potential need to improve patient counseling prior to VNS surgery to better set patient expectations regarding vocal changes and to prevent unnecessary patient concern. In addition, reports of vocal fold paresis/paralysis potentially suggest that patients may benefit from preoperative laryngeal assessment to differentiate preexisting vocal fold paralysis from that caused by VNS surgery.

Early surgical approaches in pediatric epilepsy - a systematic review and meta-analysis.

Drug-resistant epilepsy occurs in up to 30% of children suffering from seizures and about 10% qualify for surgical treatment. The aim of this systematic review and meta-analysis is to analyze the potential benefit of early epilepsy surgery in children concerning primarily seizure and developmental outcome. PubMed and Embase databases were searched using a systematic search strategy to identify studies on pediatric epilepsy surgery under 3years from their inception up to 2022. Outcome measures were seizure outcome, postoperative complications, seizure onset, and reduction rate of antiepileptic drugs. A meta-analysis was thereafter performed for all included cohort studies. A p-value of < 0.05 was considered as statistically significant. A total of 532 patients were analyzed with 401 patients (75%) receiving resective or disconnective surgery under the age of 3years and 80 patients (15%) receiving surgery older than 3years. The remaining 51 patients (9%) underwent VNS implantation. Pooled outcome analysis for resective/disconnective surgery showed favorable outcome in 68% (95% CI [0.63; 0.73]), while comparative analysis between the age groups showed no significant difference (77% early group and 75% late group; RR 1.03, 95% CI [0.73; 1.46] p = 0.75). Favorable outcome for the VNS cohort was seen in 52%, 65% in the early and 45.1% in the late group (RR 1.4393, 95% CI [0.87; 2.4] z = 1.42, p = 0.16). Developmental outcome was improved in 26%. Morbidity rate was moderate and showed no significant difference comparing the age groups, and overall surgical mortality rate was very low (0.1%). Epilepsy surgery in pediatric age, especially under the age of 3years, is a feasible and safe way to treat intractable epilepsy. Further comparative studies of prospective nature, analyzing not only seizure but also developmental outcome, should be the focus of future studies.

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial

ObjectiveVagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. MethodsThe pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. ResultsThe rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. ConclusionsThis study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

Long-term outcomes and prognosis factors of vagus nerve stimulation in patients with refractory epilepsy

Abstract Background Vagus nerve stimulation (VNS) is an effective treatment for patients with refractory epilepsy, yet with varied predictive factors and heterogeneous long-term outcomes. Adjustment of VNS parameters is critical for obtaining favorable efficacy. In this study, we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy. Methods Eighty-six patients (59 males and 27 females) who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled. The clinical data, including sex, age at epilepsy onset, VNS implantation, epilepsy duration, seizure type, MRI findings, history of neurosurgical operations, and responder rate (responders were those with ≥50% seizure reduction), were analyzed. Results Four-year follow-up data were available for 76 patients (53 males and 23 females). The mean current intensity at the last follow-up was 1.8 ± 0.3 mA (range: 0.75–2.5 mA). The mean seizure reduction was 36.2% at 6 months, 38.5% at 1 year, 69.4% at 3 years, and 56.7% at 4 years. A favorable outcome of ≥50% reduction in seizure frequency occurred in 40.0% of the patients at 6 months, 55.9% at 1 year with 4 patients being seizure-free, 63.2% at 3 years with 5 patients being seizure-free, and 68.4% at 4 years with 5 patients being seizure-free. Earlier onset age (P &lt; 0.001) and shorter duration (P = 0.042) were associated with favorable prognosis. Compared with generalized tonic-clonic seizures, tonic seizures had a favorable outcome (P = 0.026). Twenty-three patients underwent neurosurgical operations before VNS implantation, and the responder rate was 60.9% at the last follow-up. Conclusions VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment. The stimulation efficacy increases over time after implantation, and earlier exposure to VNS improves the prognosis.

Quality of Life in Elderly Epilepsy Patients Implanted With Vagus Nerve Stimulators

Older epilepsy patients are a fragile group with higher risk of comorbidities and at times, less tolerant to antiseizure medications(ASM). Many of these patients are medically resistant(MR) to ASM and other treatments are required. There is a lack of understanding regarding how improvement of seizures could have an improvement on their quality of life. The goal of this study is to analyze the rates of quality of life(QOL) and how they relate to seizure frequency in MR elderly patients who undergo VNS implantation.

Effect of Vagus Nerve Stimulation on Blood Inflammatory Markers in Children with Drug-Resistant Epilepsy: A Pilot Study.

Background: Since one of the suggested mechanisms of action of VNS on epilepsy is the reduction of central inflammation, we carried out a comprehensive analysis of blood inflammatory markers in children considered for VNS surgery. Materials and methods: Five pediatric patients were studied. An extensive analysis of blood inflammatory markers was performed before surgery (T0) and six weeks after VNS implantation (T1). An epileptological outcome was obtained according to the McHugh score. Results: The variations of IgA, IgE, IgG, CD19, and PTX3 displayed a tendency toward a positive statistical correlation between T0 and T1. According to McHugh score, the patients were divided into Group 1 (i.e., Class I) and Group 2 (i.e., Classes II and III). IL-1β and PTX-3 tended to decrease more in Group 1, while TNF-α decreased in Group 2 (−56.65%) and slightly increased (+3.61%) in Group 1 at T1 without statistical correlation. Conclusions: The variation of IL-1β and PTX-3 seem to be related to a better outcome; thus, they do not reach statistical significance. A larger series of patients is needed to determine whether biochemical changes could relay with the clinical improvement of epilepsy.

Voice changes following vagus nerve stimulator implantation in the paediatric population

The voice changes following VNS implantation may be due to direct injury to the vagus nerve at the time of implantation, these patients present with a true vocal cord paresis, or may result from coactivation of the efferent fibers of the recurrent laryngeal nerve by the VNS. The object of the study was to objectively document the incidence of these two forms of voice disorder following VNS insertion.

Grey and white matter microstructure changes in epilepsy patients with vagus nerve stimulators

ObjectivesVagus nerve stimulation (VNS) has been widely used as an effective treatment for patients with drug-resistant epilepsy (DRE). However, little is known about grey matter (GM) and white matter (WM) microstructure changes caused by VNS. This study aimed to detect consistent GM and WM alterations in epilepsy patients with vagus nerve stimulators. MethodsThe diffusion tensor imaging data was acquired from 15 patients who underwent VNS implantation. The voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to detect group differences in GM and WM microstructure and explore their correlation with postoperative seizure reduction. ResultsAfter 3 months of stimulation, GM density reduced in right cerebellum, left superior temporal gyrus, right inferior temporal gyrus and left thalamus, and increased in left cerebellum, left inferior parietal lobule, left middle occipital gyrus and left gyrus rectus. No significant volume changes had been found in 14 subcortical nuclei. The fractional anisotropy (FA) values reduced in left superior longitudinal fasciculus and left corticospinal tract, and increased in bilateral cingulum and body of corpus callosum. The mean diffusivity (MD) values reduced in right retrolenticular part of internal capsule, right posterior corona radiata and right superior longitudinal fasciculus. The seizure reduction had positive correlation trends with the volume reduction in left nucleus accumbens and right amygdala, and MD reduction in right medial lemniscus and right posterior corona radiata. ConclusionsThe results showed that VNS could cause changes of GM density, WM FA and MD values in epilepsy patients. The volume and MD reduction in some subcortical structures might participate in the seizure frequency reduction of VNS.

Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy.

We describe a multicenter experience with VNS implantation in pediatric patients with epileptic encephalopathy. Our goal was to assess VNS efficacy and identify potential predictors of favorable outcome. This was a retrospective study. Inclusion criteria were: ≤18 years at the time of VNS implantation and at least one year of follow-up. All patients were non-candidates for excisional procedures. Favorable clinical outcome and effective VNS therapy were defined as seizure reduction >50%. Outcome data were reviewed at one, two, three and five years after VNS implantation. Fisher's exact test, Kaplan-Meier and multiple logistic regression analysis were employed. Twenty-seven patients met inclusion criteria. Responder rate (seizure frequency reduction ≥ 50%) at one-year follow-up was 25.9%, and 15.3% at last follow-up visit. The only variable significantly predicting favorable outcome was time to VNS implantation, with the best outcome achieved when VNS implantation was performed within five years of seizure onset (overall response rate of 83.3% at one year of follow-up and 100% at five years). In total, 63% of patients evidenced improved QOL at last follow-up visit. Only one patient exited the study due to an adverse event at two years from implantation. Early VNS implantation within five years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients with epileptic encephalopathy. Improved QOL and a very low incidence of adverse events were observed.

Management and outcome of vagus nerve stimulator implantation: experience of an otolaryngeal/neuropediatric cooperation

ObjectiveVagus nerve stimulator (VNS) implantation is an established therapy for pharmacoresistant epilepsy that is not amenable to curative epilepsy surgery. Historically, VNS implantation has been performed by neurosurgeons, but otolaryngologist involvement is increasingly common. In this retrospective study, we aimed to evaluate the efficacy and safety of VNS implantation in children and adolescents from the otolaryngologists’ perspective.MethodsThis study included children and adolescents who had undergone VNS implantation at the study center between 2014 and 2018. Patient files were analyzed with regards to the durations of device implantation and hospitalization, postoperative complications, and clinical outcome, including seizure frequency, clinical global impression of improvement (CGI-I) score, and quality of life (QoL).ResultsA total of 73 children underwent VNS surgery. The median age at implantation was 9.3 ± 4.6 years, and median epilepsy duration before VNS surgery was 6 ± 4 years. Lennox–Gastaut syndrome was the most common syndrome diagnosis (62.3%), and structural abnormalities (49.3%) the most frequent etiology. Operation times ranged from 30 to 200 min, and median postoperative hospitalization length was 2 ± 0.9 days. No complications occurred, except for four revisions and two explantations due to local infections (2.7%). Among our patients, 76.7% were responders (≥ 50% reduction in seizure frequency), 72.1% showed improved CGI-I scores, and 18.6–60.5% exhibited considerable improvements in the QoL categories energy, emotional health, and cognitive functions.ConclusionOur results indicate that VNS implantation is a highly effective and safe treatment option for children and adolescents with AED-refractory epilepsies who are not candidates for curative epilepsy surgery.

Outpatient vagus nerve stimulation surgery in patients with drug-resistant epilepsy with severe intellectual disability

PurposeVagus nerve stimulation (VNS) implantation is increasingly proposed in outpatient procedure. Some epilepsy syndromes are associated with severe neurodevelopmental disabilities (intellectual disability, autism) and often motor or sensory handicaps, making ambulatory surgery more complex. MethodsWe prospectively assessed the feasibility and safety of outpatient VNS implantation in 26 adult patients with drug-resistant epilepsy with severe intellectual disability between December 2017 and October 2020. ResultsThe male-to-female ratio was 0.9 and the mean age on surgery day was 23.1 years. Seventeen patients (65.4%) suffered from epileptic encephalopathy, 7 (26.9%) from cryptogenic or genetic generalized epilepsy, and 2 (7.7%) from severe multifocal epilepsy. Postoperatively, all patients were discharged the day of surgery. No patient was admitted to a hospital or have consulted within one month due to postoperative complications. There was no surgery-related complication during patients’ follow-up. ConclusionOur study highlights the safety and feasibility of VNS surgery in an outpatient setting for patients with severe intellectual disability. We report detailed protocol and preoperative checklist to optimize outpatient VNS surgery in these not able-bodied patients. Severe disabilities or epilepsy-associated handicaps should not be an exclusion criterion when considering ambulatory VNS implantation.

Pre-ictal heart rate variability alterations in focal onset seizures and response to vagus nerve stimulation

PurposeVagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. MethodsDRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min timeframes: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). Results104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of ≥ 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. ConclusionVNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/non-linear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS.

Epilepsy duration as an independent predictor of response to vagus nerve stimulation

BackgroundVagus nerve stimulation (VNS) is a form of neuromodulation that has been used to treat individuals with drug-resistant epilepsy (DRE). Although many retrospective studies have explored the predictors of VNS treatment efficacy, the data have been inconsistent, and no VNS studies to date have used the 2017 ILAE epilepsy classification system. MethodsIn this single-center retrospective study, we reviewed data from 77 patients who underwent VNS implantation between 2011 and 2019. Data regarding patient gender, epilepsy duration, age at implantation, numbers of antiepileptic drugs, MRI findings, history of craniotomy, epilepsy classification, stimulation current intensity, stimulation duration, and responder status (responders were those with ≥ 50 % seizure frequency reduction) were analyzed via univariate analysis or receiver operating characteristic (ROC) curves to select possible related factors and classification cutoffs. Then, binary logistic regression analysis was used to identify the variables that significantly predicted responder status. ResultsIn the inclusion group, the mean stimulation duration, mean seizure reduction, and responder rate was 47.2 months, 42.6 %, and 50.6 %, respectively. The univariate analysis indicated that seizure types and MRI findings might be related categorical variables (P < 0.05). After performing binary logistic regression and creating ROC curves for the continuous variables, epilepsy duration was chosen as a related variable, with 12.5 years as the classification cutoff (P = 0.002). A binary logistic regression of risk factors showed that epilepsy duration was significantly related to responder status (P < 0.05). ConclusionEpilepsy duration is an independent predictor for responders to VNS. VNS is more likely to be efficacious in those with an epilepsy duration < 12.5 years, especially those with a duration of 5–12.5 years.

Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience

IntroductionVagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for responsiveness to VNS. MethodsWe retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation between 1997 and 2018. Patients with ≥50% reduction of seizure frequency compared with the baseline were defined as “responders”. The clinical characteristics of responders and nonresponders were compared. ResultsA total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonresponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction. ConclusionOur series had a diverse etiological profile and patients with transition to adult care. Long-term follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges.