Vagus Nerve Stimulation Implantation Research Articles

241 Disparities in Access to Epilepsy Surgery Care in Children With Drug Resistant Epilepsy: Implications For Long-Term Survival Outcomes

INTRODUCTION: Our recent publication in Lancet Child and Adolescent Health examined long-term survival rates for pediatric patients with drug-resistant epilepsy (DRE) treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery in a large United States (US) administrative database. The difference in survival probabilities was statistically significant (p < .001). Adjusted probabilities of survival beyond 10 years were 89.27% for the ASMs only cohort (95%CI, 87.71%-90.85%), 92.65% for VNS cohort (95%CI, 90.62%-94.72%), and 98.45% for cranial surgery cohort (95%CI, 97.53%-99.38%). METHODS: Patients aged 0-17 years with DRE between 01/01/2004-31/12/2020 were identified from the Pediatric Health Information System data set across 49 US pediatric hospitals. Patients treated with ASMs only or ASMs plus VNS or ASMs plus cranial epilepsy surgery were included. Chi-square tests determined associations between treatment time and preoperative factors such as treatment type, age, sex, race/ethnicity, insurance type, geographic region, epilepsy type, and medical complexity (presence of pediatric complex chronic conditions [PCCCs]). RESULTS: 18,292 total patients were included: 10,240 patients treated with ASMs only, 5,019 patients with ASMs plus VNS, 3,033 patients with ASMs plus cranial epilepsy surgery. There were significant differences in age, geographic region, race/ethnicity, presence of PCCCs, diagnosis, and insurance type (p < 0.001). Those treated surgically, either with VNS implantation or cranial epilepsy surgery, were 2 years older than ASMs only. ASMs only patients were less ikely to be reported as non-Hispanic white (51.78%), less likely have a focal/partial epilepsy diagnosis (8.74%), and less likely carry private medical insurance (35.82%). CONCLUSIONS: We show a link of disparities in pediatric epilepsy surgery care and survival outcomes. Focused strategies are needed to expand access to comprehensive epilepsy care with neurosurgical evaluation and offerings when appropriate.

Vagus Nerve Stimulation as an Alternative to Maintenance Electroconvulsive Therapy for Difficult-to-Treat Depression.

Vagus nerve stimulation (VNS), an implantable neurostimulator, provides a valuable long-term treatment option for patients with difficult-to-treat depression. It has been reported that previous response to electroconvulsive therapy (ECT) might predict a better response to VNS and that VNS could reduce or eliminate the need for maintenance ECT in some patients. We present the case of a patient who received a total of more than 120 sessions of ECT over the course of 13 years because of a major depressive disorder, with favorable response but without achieving full remission. After implantation of VNS, ECT was discontinued, and her depressive symptoms improved, achieving remission within 12 months. This case supports VNS as an alternative to maintenance ECT in patients with difficult-to-treat depression who have shown previous response to ECT treatment.

Impact of Adjunctive VNS on Drug Load, Depression Severity, and Number of Neuromodulatory Maintenance Treatments.

Vagus nerve stimulation (VNS) is a long-term adjunctive treatment option in patients with difficult-to-treat depression (DTD). A total of n = 20 patients (mean age 52.6 years) were included in the multicenter, prospective, observational, naturalistic RESTORE-LIFE study and were treated with adjunctive VNS as an add-on to treatment as usual. Exploratory and secondary outcome parameters from a single center were investigated for this present analysis. The overall mean drug load slightly decreased from 4.5 at baseline to 4.4 at 12 months (Z = -0.534, p = 0.594). The drug load was lower in previous electroconvulsive therapy (ECT) responders than in non-responders. There was a reduction in the mean number of hospitalizations per month after VNS implantation (Z = 1.975, p = 0.048) and a significant decrease in the mean Montgomery Åsberg Depression Rating Scale (MADRS) score from 27.3 at baseline to 15.3 at 12 months (T = 4.230, degree of freedom (df) = 19, p = 0.001). A history of ECT response at baseline was associated with greater improvement in the MADRS score after 12 months of VNS (F = 8.171, p = 0.013). The number of neuromodulatory maintenance treatments decreased during the follow-up period. In summary, there was an alleviation in the burden of illness among DTD patients treated with VNS.

Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series.

The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization. We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression. Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians. VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy.

Efficacy of vagus nerve stimulation for children with drug-resistant epilepsy: Retrospective study

IntroductionAccording to current investigations, there are controversy in our knowledge regarding the safety and efficacy of Vagus Nerve Stimulation (VNS) in children younger than 12 years old. Therefore, we performed this study and aimed to better evaluate the safety and efficacy of VNS in children younger than 12 years. MethodThe retrospective study comprised two groups. In the first group, patients (N = 19) underwent VNS implantation procedure and second group, (N = 21) received no VNS implantation. The main study parameters are as follows: (1) Primary outcome evaluated the proportion of cases with >50 % reduction of seizures at the last follow-up. (2) Changes in patients’ status in VNS group after procedure compared to before procedure. (3) Patient's complaints in VNS group compared to control group. ResultsOur results demonstrated that there was a significant reduction in the frequency of seizures (per month) in patients 6 months after VNS surgery compared to before VNS surgery (1044.3 ± 1526.7 VS 220.7 ± 421.6; P value = 0.028). 57.9 % of patients underwent VNS showed the response rate of 50 % reduction in seizure frequency. There was significant improvement in memory problem, work/ school limitation, social limitation, and tachycardia 6 months after VNS procedure compared to before VNS procedure in patients. The most common reported side effects were difficulty swallowing (31.5 %) and coughing (31.5 %) followed by stomach discomfort (15.8 %). ConclusionConsidering the significant reduction in the frequency of seizures and improvement of life aspects including in memory problem, work/ school limitation, social limitation, we recommend VNS as an effective treatment modality for drug-resistant epilepsy in children. However, the combination of VNS with other treatment modalities that could improve other aspects of quality such as energy levels, sleep pattern, and feeling management of life is recommended.

Vagus nerve stimulation for the treatment of narcolepsy

Background and objectiveNo study on neurostimulation in narcolepsy is available until now. Arousal- and wake-promoting effects of vagus nerve stimulation (VNS) have been demonstrated in animal experiments and are well-known as side effects of VNS therapy in epilepsy and depression. The objective was to evaluate the therapeutic effect of VNS on daily sleepiness and cataplexies in narcolepsy. MethodsIn our open-label prospective comparative study, we included narcolepsy patients who were treated with VNS because of depression or epilepsy and compared them to controls without narcolepsy treated with VNS for depression or epilepsy (18 patients in each group, aged 31.5 ± 8.2 years). We evaluated daily sleepiness (Epworth Sleepiness Scale, ESS) and the number of cataplexies per week before the implantation of VNS and at three and six month follow-ups. ResultsCompared to baseline (ESS: 15.9 ± 2.5) patients with narcolepsy showed a significant improvement on ESS after three months (11.2 ± 3.3, p < 0.05) and six months (9.6 ± 2.8, p < 0.001) and a trend to reduction of cataplexies. No significant ESS-improvement was observed in patients without narcolepsy (14.9 ± 3.9, 13.6 ± 3.7, 13.2 ± 3.5, p = 0.2 at baseline, three and six months, correspondingly). Side effects did not differ between the study groups. ConclusionIn this first evaluation of VNS in narcolepsy, we found a significant improvement of daily sleepiness due to this type of neurostimulation. VNS could be a promising non-medical treatment in narcolepsy.

Unveiling of vagus nerve anatomical assessment with ultrasonography before vagus nerve stimulation implantation

Unveiling of vagus nerve anatomical assessment with ultrasonography before vagus nerve stimulation implantation

Making Sense of Vagus Nerve Stimulation for Stroke.

Implantable vagus nerve stimulation, paired with high-dose occupational therapy, has been shown to be effective in improving upper limb function among patients with stroke and received regulatory approval from the US Food and Drug Administration and the Centers for Medicare & Medicaid Services. Combining nonsurgical and surgical approaches of vagus nerve stimulation in recent meta-analyses has resulted in misleading reports on the efficacy of each type of stimulation among patients with stroke. This article aims to clarify the confusion surrounding implantable vagus nerve stimulation as a poststroke treatment option, highlighting the importance of distinguishing between transcutaneous auricular vagus nerve stimulation and implantable vagus nerve stimulation. Recent meta-analyses on vagus nerve stimulation have inappropriately combined studies of fundamentally different interventions, outcome measures, and participant selection, which do not conform to methodological best practices and, hence, cannot be used to deduce the relative efficacy of the different types of vagus nerve stimulation for stroke rehabilitation. Health care providers, patients, and insurers should rely on appropriately designed research to guide well-informed decisions.

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy.

To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs. Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.

Long-term effects of vagus nerve stimulation therapy on cognitive functioning in patients with drug-resistant epilepsy.

Despite the increasing use of vagus nerve stimulation (VNS) for drug-resistant epilepsy, its impact on cognitive functioning remains insufficiently investigated. We aimed to comprehensively assess changes in cognition after long-term VNS therapy in a prospective sample of adults with epilepsy. Between December 2019 and March 2023, patients scheduled for VNS implantation were invited for neuropsychological assessment, including tests of executive functions, working and short-term memory (recall of a verbal logical story and the Rey-Osterrieth complex figure (ROCF)), and social cognition. Participants were re-evaluated after a year of VNS therapy and the pre- and postoperative scores were compared by means of the Student's t or Wilcoxon's signed rank tests for paired samples. Patients available only after a longer follow-up (more than 24 months) were also re-examined and included in a secondary analysis. The study included 28 PWE (16, 57.1% female, average age 33.7 ± 10.0 years). Twenty-two PWE followed-up at 14.5 ± 4.8 months had worse categorical verbal fluency than preoperatively (t = 2.613, p = 0.016). After including patients with long follow-up (n = 28, 21.6 ± 11.4 months), the group scored better on the delayed recall of the ROCF (17.09 ± 8.84 to 20.65 ± 8.32 points, t(22) = - 2.618, p = 0.016) and the Happé strange stories test (5.0 ± 2.6 to 6.1 ± 2.1 points, t(14) = - 3.281, p = 0.005). No significant changes were observed in other cognitive domains (p > 0.05). We suggest improvements in a task of social cognition and short-term visual memory after longer use of VNS therapy. Such findings should be confirmed in larger trials after controlling for changes in ictal or interictal activity.

Effects of vagus nerve stimulation on the quality of sleep and sleep apnea in patients with drug-resistant epilepsy: A systematic review.

The objective was to systematically evaluate the current evidence surrounding the effect of vagus nerve stimulation (VNS) on quality of sleep and obstructive sleep apnea (OSA) among patients with epilepsy. A literature search was conducted using the Embase and MEDLINE databases. Studies were included if they involved patients with drug-resistant epilepsy treated with VNS and used validated tools to report on quality of sleep or sleep apnea. The literature search yielded 112 citations related to VNS and sleep quality, and 82 citations related to sleep apnea. Twelve articles were included in the review, of which five measured quality of sleep among patients who underwent VNS, six studies measured sleep apnea, and one study measured both outcomes. Studies measuring quality of sleep used different methods, including sleep quality questionnaires and the percentage of sleep in each cycle. Studies also varied in patient populations, the use of control groups, and whether multiple measurements were taken for each patient. Some studies found improved sleep quality after VNS, whereas others found reductions in deep sleep stages. Additionally, mixed results in sleep quality were found when comparing patients with epilepsy who received VNS treatment versus patients with epilepsy who did not receive VNS treatment. Variables such as VNS intensity and age could potentially confound quality of sleep. Studies measuring sleep apnea consistently found increased proportions of patients diagnosed with OSA or increased sleep index scores after VNS implantation. Overall, the effect of VNS on quality of sleep remains unclear, as studies were very heterogeneous, although the effect on sleep apnea has consistently shown an increase in sleep apnea severity indices after VNS implantation. Future studies with consistent measures and discussions of confounding are required to determine the effect of VNS on quality of sleep, and the effect of VNS parameters should be further explored among patients who develop sleep apnea.

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

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

Vagus nerve stimulation for treating developmental and epileptic encephalopathy in young children.

To investigate the clinical variables that might predict the outcome of developmental and epileptic encephalopathy (DEE) after vagus nerve stimulation (VNS) therapy and identify the risk factors for poor long-term outcome. We retrospectively studied 32 consecutive children with drug-resistant DEE who had undergone VNS surgery from April 2019 to July 2021, which were not suitable for corpus callosotomy. In spite of combining valproic acid, levetiracetam, lamotrigine, topiramate, etc. (standard anti-seizure medicine available in China) it has not been possible to effectively reduce seizures in the population we investigate (Cannabidiol and brivaracetam were not available in China). A responder was defined as a frequency reduction decrease > 50%. Seizure freedom was defined as freedom from seizures for at least 6 months. Sex, electroencephalograph (EEG) group, neurodevelopment, time lag, gene mutation, magnetic resonance imaging (MRI), and epilepsy syndrome were analyzed with Fisher's exact test, The age at onset and age at VNS therapy were analyzed with Kruskal-Wallis test, statistical significance was defined as p < 0.05. And used the effect size to correction. Among the 32 patients, the median age at VNS implantation was 4.7 years (range: 1-12 years). At the most recent follow-up, five children (15.6%) were seizure-free and 22 (68.8%) were responders. Univariate analysis demonstrated that the responders were significantly associated with mild development delay/intellectual disability (p = 0.044; phi coefficient = 0.357) and a multifocal EEG pattern (p = 0.022; phi coefficient = -0.405). Kaplan-Meier survival analyses demonstrated that a multifocal EEG pattern (p = 0.049) and DEE without epileptic spasm (ES) (p = 0.012) were statistically significant (p = 0.030). Multivariate analysis demonstrated that DEE with ES had significant predictive value for poor long-term outcome (p = 0.014, hazard ratio = 5.433, confidence interval = 1.402-21.058). Our study suggested that VNS was a generally effective adjunct treatment for DEE. Although the predictive factors for VNS efficacy remain unclear, it should be emphasized that patients with ES are not suitable candidates for epilepsy surgery. Further investigations are needed to validate the present results.

Vagal nerve stimulator-associated sleep disordered breathing secondary to vagal-induced laryngospasm in pediatric populations: Case presentation and systematic review.

Sleep disordered breathing (SDB) is a well-documented complication of vagus nerve stimulation (VNS) in the literature. Yet, a formal consensus on its management has not been established, particularly in the pediatric population. This study aims to evaluate the current literature on VNS-associated SDB in order to further characterize its presentation, pathogenesis, diagnosis, and treatment. A literature review from 2001 to November 8, 2021 was conducted to search for studies on SDB during vagal nerve stimulation in pediatric populations. Of 277 studies screened, seven studies reported on pediatric patients with VNS-associated SDB. Several investigators found on polysomnogram that periods of apnea/hypopnea correlated with VNS activity. When VNS settings were lowered or turned off, symptoms would either improve or completely resolve. VNS-associated SDB is a well described complication of VNS implantation, occurring due to an obstructive process from vagal stimulation and laryngeal contraction. Diagnosis can be made via polysomnogram. Recommended treatment is through adjustment of VNS settings. However, those who are unable to tolerate this, or who have had pre-existing obstructive issues prior to VNS, should pursue other treatment options such as non-invasive positive pressure or surgery directed by DISE findings.

Effect of vagus nerve stimulation against generalized seizure and status epilepticus recurrence.

Vagus nerve stimulation (VNS) is a palliative surgery for drug-resistant epilepsy. The two objectives of this study were to (1) determine the seizure type most responsive to VNS and (2) investigate the preventive effect on status epilepticus (SE) recurrence. We retrospectively reviewed 136 patients with drug-resistant epilepsy who underwent VNS implantation. We examined seizure outcomes at 6, 12, and 24 months following implantation of VNS as well as at the last visit to the Juntendo Epilepsy Center. Univariate analysis and multivariate logistic regression models were used to estimate the prognostic factors. 125 patients were followed up for at least 1 year after VNS implantation. The percentage of patients with at least a 50% reduction in seizure frequency compared with prior to VNS implantation increased over time at 6, 12, and 24 months after VNS implantation: 28, 41, and 52%, respectively. Regarding overall seizure outcomes, 70 (56%) patients responded to VNS. Of the 40 patients with a history of SE prior to VNS implantation, 27 (67%) showed no recurrence of SE. The duration of epilepsy, history of SE prior to VNS implantation and seizure type were correlated with seizure outcomes after VNS implantation in univariate analysis (p = 0.05, p < 0.01, and p = 0.03, respectively). In multivariate logistic regression analysis, generalized seizure was associated with VNS response [odds ratio (OR): 4.18, 95% CI: 1.13-15.5, p = 0.03]. A history of SE prior to VNS implantation was associated with VNS non-responders [(OR): 0.221, 95% CI: 0.097-0.503, p < 0.01]. The duration of epilepsy, focal to bilateral tonic-clonic seizure and epileptic spasms were not significantly associated with VNS responders (p = 0.07, p = 0.71, and p = 0.11, respectively). Following 125 patients with drug-resistant epilepsy for an average of 69 months, 56% showed at least 50% reduction in seizure frequency after VNS implantation. This study suggests that generalized seizure is the most responsive to VNS, and that VNS may reduce the risk of recurrence of SE. VNS was shown to be effective against generalized seizure and also may potentially influence the risk of further events of SE, two marker of disease treatment that can lead to improved quality of life.

Intractable hiccups after VNS implantation: a case report

BackgroundHiccups (medically termed, “singultus”), when intractable, can cause significant medical consequences such as aspiration, malnutrition, and depression, leading to poor quality of life. Several case reports have shown that vagus nerve stimulator (VNS) implantation can help treat central idiopathic intractable hiccups. However, we present a contrary case of a patient who developed intractable singultus following VNS placement for medically refractory epilepsy.Case presentationWe report a 71-year-old male patient with drug-resistant epilepsy who underwent VNS implantation and developed intractable hiccups shortly thereafter. The hiccups were severe and persistent, such that the patient developed a Mallory-Weiss tear, which required intensive care, invasive intubation and mechanical ventilation, and a prolonged rehabilitation course. Despite multiple therapies including phrenic nerve block and Nissen fundoplication, the patient’s hiccups persisted and only stopped once the VNS was permanently deactivated.ConclusionsLittle is known about the incidence of hiccups after VNS implantation. We present one case of hiccups as a direct consequence of VNS implantation. The clinical impact of this report is significant given the relative unfamiliarity of hiccups as an adverse effect of VNS implantation. Neurologists and epileptologists, who present VNS implantation as a surgical option for seizure control to their patients, should be aware of the possibility of singultus development and its significant physical and emotional ramifications.

Efficacy and Tolerability of Ultra Rapid Duty Cycling Vagus Nerve Stimulation for Medically Refractory Absence Seizures

BackgroundSignificant knowledge gap exists on vagus nerve stimulation (VNS) efficacy and tolerability in medically refractory absence seizures (MRAS). This retrospective review of patients with MRAS aims to narrow this knowledge gap by comparing ultra rapid duty cycling ([URDC] ON time seven seconds, OFF time 0.2 minutes) with less frequent stimulations of rapid duty cycling (RDC, OFF time <1.1 minutes) and normal duty cycling (NDC, OFF time ≥1.1 minutes). MethodsPatients with MRAS aged less than 21 years who underwent VNS implantation were identified. Patient demographics, antiepileptic medications, seizure types, frequency, VNS parameters, outcomes of seizure reduction rate (SRR), and seizure freedom were extracted and compared among NDC, RDC, and URDC patient cohorts. ResultsThirty-six patients with MRAS were identified. After a mean follow-up of 32.6 months, responder rate ([RR], SRR ≥50%) for URDC was 80% for absence seizures and 80% for all seizure types versus 66.67% and 66.77% for NDC and 78.57% and 57.14% for RDC, respectively. Six of 10 patients (60%) on URDC achieved complete seizure freedom. A higher rate of subjective improvement in academic performance, attention, and developmental gain was noted in the URDC group. Patients on URDC tolerated higher output current (mean 3.025 mA) with minimal side effects but required a battery change sooner. ConclusionsVNS is a safe and effective nonpharmacologic management choice in patients with MRAS. The data presented demonstrate that the combination of URDC and high output current provides better RR and seizure freedom. Apart from a reduced battery life, this parameter modality seems to be well-tolerated.

Predictive factors for successful vagus nerve stimulation in patients with refractory epilepsy: real-life insights from a multicenter study.

Vagus nerve stimulation (VNS) therapy is an established treatment for patients with drug-resistant epilepsy that reduces seizure frequency by at least 50% in approximately half of patients; however, the characteristics of the patients with the best response have not yet been identified. Thus, it is important to identify the profile of patients who would have the best response to guide early indications and better patient selection. This retrospective study evaluated vagus nerve stimulation (VNS) as an adjuvant therapy for patients with drug-resistant epilepsy from six epilepsy centers in Brazil. Data from 192 patients aged 2-66 years were analyzed, and all patients received at least 6 months of therapy to be included. Included patients were aged 2-66 years (25.6 ± 14.3), 105 (54.7%) males and 87 (45.8%) females. Median follow-up interval was 5 years (range, 2005-2018). Overall, the response rate (≥50% seizure reduction) after VNS implantation was 65.6% (126/192 patients). Most patients had 50-90% seizure reduction (60.9%) and nine patients became seizure-free. There were no serious complications associated with VNS implantation. The rate of a ≥ 50% seizure reduction response was significantly higher in patients with no history of neurosurgery. The presence of focal without generalized seizures and focal discharges on interictal EEG was associated with better response. Overall, etiological predictors of a better VNS response profile were tumors while a worse response to VNS was related to the presence of vascular malformations and Lennox-Gastaut Syndrome. We observed an association between a better response to VNS therapy no history of neurosurgery, focal interictal epileptiform activity, and focal seizure pattern. Additionally, it is important to highlight that age was not a determinant factor of the response, as children and adults had similar response rates. Thus, VNS therapy should be considered in both adults and children with DRE.

Additional Effect of High-output Current and/or High-duty Cycle in Vagus Nerve Stimulation for Adolescent/Adult Intractable Epilepsy.

A vagus nerve stimulation (VNS) device delivers electrical pulses to the vagus nerve at a rhythm defined by the duty cycle. The standard therapeutic range is advocated for an output current of 1.5-2.25 mA and a duty cycle of 10%. As the optimal settings vary from patient to patient, some patients may benefit from additional seizure reduction when stimulated beyond the standard range. A total of 74 patients (15 children aged <12 years and 59 adolescents/adults) who underwent VNS implantation between 2011 and 2020 and who were followed up for at least 2 years were included in this retrospective study. Stimulation parameters exceeding 2.25 mA of output current, 25% of duty cycle, and 0.5625 (2.25 mA × 25%) of current × duty cycle were defined as high stimulation. The proportion achieved an additional seizure reduction of 20%, and the 50% seizure reduction rate at the last follow-up was compared between adolescents/adults and children. Approximately 40% of patients in adolescents/adults treated with high stimulation experienced an additional acute effect, resulting in a 50% or greater reduction in seizures in almost all patients. Moreover, in adolescents/adults, 22.2%-41.9% of the patients were treated with high stimulation, and the responder rate was 69.5%. Conversely, the responder rate in children was 26.7%, significantly worse than that in adolescents/adults, despite higher stimulation. VNS with high-stimulation settings is effective for adolescent and adult patients with intractable epilepsy. Even high stimulation may not be effective in extremely refractory pediatric epilepsy with a high seizure frequency.

Pediatric vagal nerve stimulator explantation: A comprehensive literature review and tertiary care experience.

Patients with medically-refractory epilepsy who undergo vagal nerve stimulator (VNS) implantation to reduce seizure burden sometimes require device removal. Complete explantation refers to the removal of both the generator and vagal nerve leads, and is uncommonly performed by otolaryngologists due to the perceived risk associated with lead removal. This comprehensive literature review and case series studies safety outcomes among pediatric patients undergoing complete VNS explantation. Literature review and tertiary care case series. PubMed, Embase, Web of Science, and Google Scholar were searched to identify all articles involving VNS explantation prior to January 2023. A retrospective review of pediatric patients undergoing complete VNS explantation from 2009 to 2023at our tertiary center was also conducted. After screening, 36 articles were retained involving 399 patients (139 confirmed children) who underwent complete VNS explantation. 26 patients (6.5%) experienced 1+ peri/post-operative complications. These included temporary VF paresis or dysphonia (n=14; 3.6%), permanent vocal fold (VF) paralysis/paresis (n=6; 1.5%), internal jugular vein injury (n=4; 1.0%), temporary dysphagia (n=2; 0.50%), and cable-bowstring phenomenon (n=1; 0.25%). Data from our tertiary care center revealed eight patients (6M: 2F) with a mean age of 11.4±6.2 years. Devices were removed for clinical ineffectiveness (n=2), infection (n=2), lead failures (n=2), and increased lead impedance (n=2). Mean total length of implantation was 44.4±40.3 months. Mean follow-up was 44.8±35.2 months. No complications were identified. Complete VNS device removal in pediatric patients is technically feasible with low reported complications. Working alongside neurosurgery, otolaryngologists offer unique expertise in dissection along the vagus nerve and may thus add value to the practice of VNS surgery.