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• The first meta-analysis comparing seizure reduction after replacing tVNS with cbVNS. • Switching devices could be associated with ≥50 % and ≥80 % reduction in seizures. • There was no difference in the rate of complete seizure freedom between groups. • In DRE patients undergoing battery replacement, cbVNS devices could be considered. For patients with drug-resistant epilepsy (DRE) who are not suitable for surgical resection, neuromodulation with vagus nerve stimulation (VNS) is an established approach. However, there is limited evidence of seizure reduction when replacing traditional VNS (tVNS) device with a cardiac-based one (cbVNS). This meta-analysis compares the seizure reduction achieved by replacing tVNS with cbVNS in a population with DRE. We systematically searched PubMed, Embase, and Cochrane Central following PRISMA guidelines. The main outcomes were number of patients experiencing a ≥ 50 % and ≥80 % reduction in seizures, as defined by the McHugh scale. Additionally, we assessed the number of patients achieving freedom from seizures. We included 178 patients with DRE from 7 studies who were initially treated with tVNS and subsequently had it replaced by cbVNS. The follow-up for cbVNS ranged from 6 to 37.5 months. There was a statistically significant reduction in seizure frequency with the replacement of tVNS by cbVNS, using a ≥ 50 % (OR 1.79; 95 % CI 1.07 to 2.97; I²=0 %; p = 0.03) and a ≥ 80 % (OR 2.06; 95 % CI 1.17 to 3.62; I²=0 %; p = 0.01) reduction threshold. Nineteen (13 %) participants achieved freedom from seizures after switching to cbVNS. There was no difference in the rate of freedom from seizures between groups (OR 1.85; 95 % CI 0.81 to 4.21; I²=0 %; p = 0.14). In patients with DRE undergoing battery replacement, cbVNS might be associated with seizure reduction (≥50 % and ≥80 % threshold) after switching from tVNS. Randomised controlled trials are necessary to validate these findings. [ABSTRACT FROM AUTHOR]

• Despite NICE guidance, visits to neurosurgery clinics remain uncommon and are seldom followed by surgical interventions. • Access to tertiary centres and neurosurgical procedures in adults with epilepsy in England, varies by region and CCGs. • Access to neurosurgical procedures is delayed, particularly if a person's initial visit is not at a tertiary epilepsy centre. • VNS use remains low, although it is higher in people with learning disability, who are less likely to have resective surgery. 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. [ABSTRACT FROM AUTHOR]

• VNS is a safe and effective treatment option for refractory IGE. • VNS-related side-effects are common but rarely result in treatment discontinuation. • VNS is a viable option for females of childbearing age with refractory IGE who have failed multiple treatments, including valproate. Refractory idiopathic generalised epilepsy (IGE; also known as genetic generalised epilepsy) is a clinical challenge due to limited available therapeutic options. While vagus nerve stimulation (VNS) is approved as an adjunctive treatment for drug-resistant focal epilepsy, there is limited evidence supporting its efficacy for refractory IGE. We conducted a single-centre retrospective analysis of adult IGE patients treated with VNS between January 2003 and January 2022. We analysed the efficacy, safety, tolerability, stimulation parameters and potential clinical features of VNS response in this IGE cohort. Twenty-three IGE patients were implanted with VNS between January 2003 and January 2022. Twenty-two patients (95.65%) were female. The median baseline seizure frequency was 30 per month (interquartile range [IQR]= 140), including generalised tonic-clonic seizures (GTCS), absences, myoclonus, and eyelid myoclonia with/without absences. The median number of baseline anti-seizure medications (ASM) was three (IQR= 2). Patients had previously failed a median of six ASM (IQR= 5). At the end of the study period, VNS therapy remained active in 17 patients (73.9%). amongst patients who continued VNS, thirteen (56.5% of the overall cohort) were considered responders (≥50% seizure frequency reduction). Amongst the clinical variables analysed, only psychiatric comorbidity correlated with poorer seizure outcomes, but was non-significant after applying the Bonferroni correction. Although 16 patients reported side-effects, none resulted in the discontinuation of VNS therapy. Over half of the patients with refractory IGE experienced a positive response to VNS therapy. VNS represents a viable treatment option for patients with refractory IGE, particularly for females, when other therapeutic options have been exhausted. [ABSTRACT FROM AUTHOR]

Objective: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes., Methods: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines., Results: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline., Conclusion: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To explore abnormalities of topological properties in drug-resistant epilepsy (DRE) patients after vagus nerve stimulation (VNS) by analyzing brain functional networks using graph theory.Methods: Fifteen patients and eight healthy controls (HC) were scanned separately with resting-state functional magnetic resonance imaging (rs-fMRI). Graph theoretical analyses were chosen to compare the global (small-world parameters [γ, λ, σ, Cp, and Lp], and network efficiency [Eg and Eloc]), and nodal (BC, DC, and NE) properties in preoperative patients (EPpre), postoperative patients (EPpost) and HC.Results: HC, EPpre and EPpost all satisfied the criteria for small-world properties (σ > 1) within the sparsity range of 0.05-0.5. Compared with EPpre, EPpost performed higher in λ and Eloc but lower in γ, σ, and Cp. Compared with HC, EPpre exhibited decreased BC, DC or NE in the right inferior frontal gyrus, right superior temporal gyrus, bilateral cingulate gyri, right supplementary motor area, right superior occipital gyrus, right Heschl gyrus, and left calcarine fissure; increased BC in the left postcentral/precentral gyrus, right paracentral lobule, left rolandic operculum, and left supramarginal gyrus, and increased NE in the right caudate nucleus. Compared with EPpre, EPpost showed increased BC, DC or NE in the bilateral inferior frontal gyrus, right middle frontal gyrus, bilateral cingulate gyri, right superior temporal gyrus, and right Heschl gyrus and decreased BC in the left fusiform gyrus.Conclusion: VNS downregulated small-world properties in DRE, and caused changes in some key nodes to reorganize the transmission ability of the large-scale network. [ABSTRACT FROM AUTHOR]

Introduction: Transcutaneous auricular vagus nerve stimulation (t-VNS) has been proposed as an alternative method for the treatment of various neurological and psychiatric disorders. Contrary to the classic invasive vagus nerve stimulation (i-VNS), t-VNS does not require surgical intervention. The application of t-VNS for the treatment of epilepsy has been poorly studied. Hence, we performed a systematic review of the literature to elucidate efficacy, adverse effects and technical features of t-VNS in patients with epilepsy.Material and Methods: We systematically searched MEDLINE and SCOPUS databases using the following keywords: [TRANSCUTANEOUS VAGUS NERVE STIMULATION OR TRANSCUTANEOUS VAGAL NERVE STIMULATION] AND [EPILEPSY OR SEIZURES]. We searched for observational studies in English concerning the application of t-VNS for the treatment of epilepsy in humans. The full-text version of relevant studies was obtained and reviewed. Technical parameters of the stimulation, percentage of seizure frequency reduction, QOLIE-31(Quality of Life In Epilepsy-31) and LSSS (Liverpool Seizure Severity Scale) questionnaires and adverse effects were recorded and analyzed.Results: A total of 10 studies with 350 patients were included. Both bilateral and unilateral placement of the electrode were applied. Stimulation frequency varied from 10-30Hz, while treatment intensity was usually adjusted according to patients' preferences and tolerance (around 1mA) and below the pain threshold. In the clinical trials included in our review, the mean seizure frequency reduction varied from 30 to 65%. Eight and four studies provided information about QOLIE-31 and LSSS questionnaires respectively. Three studies reported a statistically significant (p<0,05) improvement in patients' quality of life and two studies reported statistically significant (p<0,05) seizure severity reduction. The most common side effect was headache (8,9%), followed by skin irritation at the placement site (7,1%) and nasopharyngitis (5,1%). No serious or life-threatening side effects were reported.Conclusion: Due to the heterogeneity of the included studies, no safe conclusions could be extracted concerning the efficacy of t-VNS. However, the results of this review suggest that patients with epilepsy could possibly benefit from the use of t-VNS. The present study also emphasizes the limitations of previous clinical trials concerning the applications of t-VNS in people with epilepsy and thus could be a guidance for the conduction of future trials. [ABSTRACT FROM AUTHOR]

Purpose: Vagus nerve stimulaton (VNS) has been used for adjunctive treatment of drug-resistant epilepsy for more than 25 years. The true efficacy has been debated, as blinded randomized controlled trials are unavailable. The aim of this study was to evaluate the patient-reported perceived benefit of VNS and to compare clinical characteristics of patients with and without benefit.Methods: Observational study of all 43 adult patients receiving VNS for >2 years at one single center. Mean duration of treatment was 9 years. At inclusion, a semi-structured interview on VNS effectiveness was performed. In patients without benefit, the VNS was turned off. The outcome was evaluated after an observation period of one year.Results: 21 patients (49%) reported no clear benefit and stopped VNS. Only one of them resumed treatment within one year. Patients without benefit had received more new antiepileptic drugs (AEDs) during VNS treatment than those reporting benefit (p = 0.05). Other differences between the two groups were not found. Ten patients (23%) had been seizure free >1 year at inclusion (5 in the benefit and 5 in the non-benefit group). Seizure control was attributed to the response of another new treatment in the majority of these patients.Conclusion: Half of the patients had not perceived clear benefit from VNS, and all but one terminated VNS without worsening of seizures within one year. The true outcome of long-term VNS is difficult to assess in real-world practice. The effect may be overestimated due to confounding factors, particularly the common introduction of novel AEDs and the natural course of the disorder. Patients without perceived benefit from long-term VNS should not routinely remain on treatment and be subject to undue generator re-implantations. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the evidence regarding dietary, immunological, surgical, and other emerging treatments for refractory status epilepticus (RSE)/super-RSE (SRSE).Methods: Narrative literature review including relevant human studies.Results: Hypothermia and brenaxolone were tested in randomized controlled trials for RSE/SRSE management, while other interventions have only limited evidence for their efficacy and safety. Clinical trials including the HYBERNATUS study found the efficacy of therapeutic hypothermia to be no better than placebo for RSE/SRSE, and raised concerns about its safety. Ketogenic diet has shown possible efficacy in RSE/SRSE in several case series, with electrographic seizure resolution within 7 days in 20%-90% patients in larger (n = 8-17) reports. A review of 37 pediatric patients reported seizure control with immunotherapy in only 7 patients. A phase 3 double-blind trial showed that brexanolone was no better than placebo for successful wean of 3rd line anesthetic agent(s) and freedom from RSE for ≥24 hours. Epilepsy surgery has been reported to successfully control seizures in small series; however, pre-surgical evaluation is confounded by ongoing ictal activity and anesthetic infusions. Vagus nerve stimulation was reported to be associated with cessation of RSE/SRSE in 21/28 patients in a review of anecdotal reports. There is no evidence for use of pyridoxine and magnesium outside of specific indications.Conclusions: There is only anecdotal evidence for dietary, immunological, surgical, and other treatments for RSE/SRSE, often confounded by multiple concurrent treatments, and heterogeneity in their use and assessment of outcomes. Clinical trials for therapeutic hypothermia and brexanolone have not shown a significant advantage over comparators. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the predictors of seizure reduction outcome after vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE).Methods: A 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.Results: The 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.Conclusions: DRE 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. [ABSTRACT FROM AUTHOR]

Purpose: The paper presents a long-term follow-up study of VNS patients, analyzing seizure outcome, medication changes, and surgical problems.Method: 74 adults with VNS for 10 to 17 years were evaluated yearly as: non-responder - NR (seizure frequency reduction <50%), responder - R (reduction ≥ 50% and <90%), and 90% responder - 90R (reduction ≥ 90%). Delayed R or 90R (≥ 4 years after surgery), patients with antiepileptic medication changes and battery or complete system replacement were identified. Statistical analysis of potential outcome predictors (age, seizure duration, MRI, seizure type) was performed.Results: The rates of R and 90R related to the patients with outcome data available for the study years 1, 2, 10, and 17 were for R 38.4%, 51.4%, 63.6%, and 77.8%, and for 90R 1.4%, 5.6%, 15.1%, and 11.1%. The absolute numbers of R and 90R increased until years 2 and 6. Antiepileptic therapy was changed in 62 patients (87.9%). There were 11 delayed R and four delayed 90R, with medication changes in the majority. At least one battery replacement was performed in 51 patients (68.9%), 49 of whom R or 90R. VNS system was completely replaced in 7 patients (9.5%) and explanted in 7 NR (9.5%). No significant predictor of VNS outcome was found.Conclusions: After an initial increase, the rate of R and 90R remains stable in long-term follow-up. The changes of antiepileptic treatment in most patients potentially influence the outcome. Battery replacements or malfunctioning system exchange reflect the patient's satisfaction and correlate with good outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Perform a systematic review of the literature on the effects of vagus nerve stimulation (VNS), deep brain stimulation (DBS) and epilepsy surgery in subjective and objective sleep parameters.Methods: We performed a literature search in the main medical databases: Medline, Embase, Cochrane, DARE and LILACS, looking for studies that evaluated the effects of VNS, DBS or epilepsy surgery on sleep parameters. In all, 36 studies, coming from 11 countries, including reviews, cohort studies, case series and case reports were included.Results: VNS induces sleep apnoea dependent of the stimulation variables. This condition can be reverted modifying these settings. Surgical procedures for epilepsy cause an improvement in objective and subjective sleep parameters that depend on the success of the procedure evaluated through ictal frequency control. There is evidence that non-pharmacologic treatment of epilepsy has different effects on sleep patterns.Conclusion: It is advisable to include objective and subjective sleep parameters in the initial evaluation and follow-up of patients considered for invasive procedures for epilepsy control, especially with VNS due to the risk of sleep apnoea. More high quality studies are needed. [ABSTRACT FROM AUTHOR]

Rationale: Dravet Syndrome (DS) is a severe epileptic encephalopathy of childhood involving intractable seizures, recurrent status epilepticus and cognitive decline. Because DS is a rare disease, available data is limited and evidence-based treatment guidelines are lacking. Vagus nerve stimulation (VNS) is an established neurostimulation treatment for intractable epilepsy, however little evidence is published on its efficacy in patients with DS.Methods: We performed a meta-analysis of all peer-reviewed English language studies reporting seizure outcomes of patients with DS treated with adjunctive vagus nerve stimulation. The primary and secondary outcome measures were ≥50% reduction of seizures or of the most-debilitating seizure type and seizure reduction per patient.Results: 13 studies comprising 68 patients met the inclusion criteria of which 11 were single-center retrospective case series, one was a multi-center retrospective analysis and one was a case report. 52.9% of patients experienced a ≥50% reduction of seizures and the average seizure reduction, which could only be assessed in n=28 patients was 50.8%. 7 out of 13 studies reported additional benefits of VNS, however this could not be assessed systematically.Conclusion: Vagus nerve stimulation appears to reduce seizure frequency in patients with DS. Based on this preliminary analysis, controlled trials of VNS in this rare condition using patient-centric outcome measures are indicated. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the quality of information available on the internet for carers of children with epilepsy considering treatment with Vagus Nerve Stimulation (VNS).Methods: Selected key phrases were entered into two popular search engines (Google™, Yahoo™). These phrases were: "Vagus nerve stimulator", alone and in combination with "childhood epilepsy", "paediatric epilepsy" and "epilepsy in childhood"; "VNS", and "VNS epilepsy". The first 50 hits per search were then screened. Of 600 identified sites, duplicated (262), irrelevant (230) and inaccessible (15) results were excluded. 93 websites were identified for evaluation using the DISCERN instrument, an online validation tool for patient information websites.Results: The mean DISCERN score of all analysed websites was 39/80 (49%; SD 13.5). This equates to Fair to borderline Poor global quality, (Excellent=80-63; Good=62-51; Fair=50-39; Poor=38-27; Very poor=26-15). None of the analysed sites obtained an Excellent quality rating. 13% (12) obtained a Good score, 40% (37) obtained an Average score, 35% (33) obtained a Poor score, and 12% (11) obtained a Very poor score. The cohort of websites scored particularly poorly on assessment of whether reliable, holistic information was presented, for instance provision of reliable sources, (28%, SD 18) and discussion of alternative treatments, (30%, SD 14).Conclusion: To facilitate patient-centred shared decision-making, high quality information needs to be available for patients and families considering VNS. This study identifies that such information is difficult to locate on the internet. There is a need to develop focussed and reliable online patient resources for VNS. [ABSTRACT FROM AUTHOR]

Purpose: Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treating patients with drug-resistant epilepsy. The impact of VNS on cardiovascular autonomic function remains to be fully understood. We determined changes in cardiovascular sympathetic and parasympathetic, and hemodynamic function in association with VNS in patients with drug-resistant focal epilepsy.Method: Longitudinal (n=15) evaluation of beat-to-beat blood pressure (BP) and heart rate variability (HRV), baroreflex sensibility, and hemodynamic function performed before VNS implantation, 6-months after implantation, and a mean of 12-months after implantation; and cross-sectional study (n=14) of BP and HR variability and baroreflex sensitivity during VNS on and VNS off.Results: In the longitudinal study, no differences were observed between the baseline, the 6-month visit, and the final visit in markers of parasympathetic cardiovagal tone or baroreflex sensitivity. Systolic and diastolic BP upon 5-min of head-up tilt increased significantly after VNS implantation (Systolic BP: -16.69±5.65mmHg at baseline, 2.86±16.54mmHg at 6-month, 12.25±12.95mmHg at final visit, p=0.01; diastolic BP: -14.84±24.72mmHg at baseline, 0.86±16.97mmHg at 6-month, and 17±12.76mmHg at final visit, p=0.001).Conclusion: VNS does not seem to produce alterations in parasympathetic cardiovagal tone, regardless of the laterality of the stimulus. We observed a slight increase in sympathetic cardiovascular modulations. These changes had no significant hemodynamic implications. These findings contribute to the understanding of potential mechanisms of action of VNS. [ABSTRACT FROM AUTHOR]

Brain stimulation is increasingly used in epilepsy patients with insufficient therapeutic response to pharmacological treatment. Whereas vagus nerve stimulation with implanted devices has been used in large and heterogeneous patient groups, new devices also enable targeted brain stimulation at the site of seizure generation (responsive neurostimulation) or at network hubs (thalamic stimulation). Both responsive neurostimulation systems targeting the epileptic focus and the latest vagus nerve stimulators are intended to stimulate during the ictal phase to disrupt clinical seizure manifestation of reduce seizure severity. Furthermore, transcutaneous stimulation approaches are now available, although their efficacy remains uncertain. This review explains the concepts underlying brain stimulation, provides an overview of efficacy and tolerability data and discusses the rational use of the growing spectrum of neuromodulatory strategies available. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623).Methods: Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS.Results: Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials.Conclusions: The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. [ABSTRACT FROM AUTHOR]

Purpose A novel vagus nerve stimulation (VNS) device was recently approved in Europe which rapidly detects increases in heart rates (HR) and applies an additional stimulus if HR-increases exceed a given threshold. The effects of HR-triggered VNS-pulses on seizures were not reported yet under controlled conditions. Here, we quantified the effects of HR-triggered VNS-pulses on the seizure duration in one patient. Methods The novel VNS device was implanted in a 29-year old man with refractory epilepsy. After implantation, the patient underwent video-EEG telemetry for 68 h with no changes in anticonvulsant drugs. On the first day the patient only received sham-stimulation. During the following 46 h HR-related VNS-stimulation was set to 2 mA. Seizure duration was determined based on clinical signs. Results Twelve stereotypical seizures were recorded (six during sham- and six during the active stimulation). The VNS device recognised a total of 139 events as a seizure and correctly identified 11 seizures. The HR-triggered VNS-stimulation significantly reduced the total seizure duration from 33.2 ± 4.8 s to 26.5 ± 5 s and the remaining seizure duration after the onset of the extra-stimulation from 27.8 ± 4.3 s to 16.2 ± 3.2 s. With the given configuration in this patient, sensitivity and specificity of HR-based seizure-detection amounted to 92% and 13.5%, respectively. Conclusions This case illustrates that VNS-stimulation in response to seizure-related HR-increases is able to significantly reduce seizure duration. Despite the limitations of our case, its promising results should prompt larger studies to confirm the clinical benefit of this novel device. [ABSTRACT FROM AUTHOR]

Purpose To evaluate clinical outcomes, quality-adjusted life years (QALY), cost effectiveness and cost utility associated with VNS therapy in children with refractory epilepsy in a developing country. Methods Retrospective review of all children who underwent VNS implantation at King Abdullah University Hospital and Jordan University Hospital in Jordan. Results Twenty eight patients (16 males) had implantation of the VNS therapy system between the years 2007 and 2011. Mean age at implantation was 9.4 years. Mean duration of epilepsy prior to implantation was 6.5 years. The most common seizure type was generalized tonic clonic seizures. Fifteen patients showed a 50% or more reduction in seizure frequency. There was a significant reduction in total number of seizures ( p = 0.002) and emergency room (ER) visits ( p = 0.042) after VNS therapy. Atonic seizures were more likely to respond than generalized tonic clonic seizures, p = 0.034. Direct hospital costs prior to VNS implantation were analyzed in relation to ER visits and intensive care unit (ICU) admissions. Cost savings per patient did reduce the financial burden of the device by about 30%. There was a QALY gain per lifetime of 3.78 years for children and 1 year for adolescents. Conclusion Response to VNS implantation in Jordan was favorable and similar to what has been previously reported. QALY gain and cost per QALY analysis were encouraging. Cost savings were related to reduction in seizure severity. In circumstances of limited resources as in developing countries, targeting patients with frequent utilization of health services would improve cost effectiveness. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the efficacy of vagus nerve stimulation (VNS) in pediatric patients with medically refractory epilepsy. Method: We reviewed the medical records of 252 consecutive patients who underwent VNS implantation at a single center over a 5-year period. Patients with complete 6- and 12-month follow-up data were included. Analysis was also done across various subgroups including gender, age at implantation, seizure type, abnormal MRI findings pre-implantation, number of medications at baseline, history of SE, and duration of epilepsy. Results: Complete follow-up data were available for 69 patients. Median seizure reduction for these patients was 50% (Q1: 0%; Q3: 73%) at 6 months and 40% (Q1: −25%; Q3: 75%) at 12 months. When stratified by baseline seizure frequency, there was a significant reduction from baseline of 61% at 6 months and 69% at 12 months for patients in the high-baseline frequency group. There were no significant reductions at month 6 or 12 months for the lower-baseline frequency group. Adverse events were reported in 40.6% (28 out of 69 patients). Six patients had the VNS removed for reasons including lack of efficacy and side effects and were excluded from the study group. Conclusion: VNS provides significant seizure reduction, in particular in pediatric patients with a higher baseline seizure frequency. [Copyright &y& Elsevier]

Abstract: Purpose: Vagus nerve stimulation (VNS) therapy is a procedure to control seizure frequency in patients with medically intractable epilepsy. However, there is no data on efficacy in the subset of these patients with brain tumors. The purpose of this study is to evaluate the efficacy of VNS therapy in patients with brain tumor-associated medically intractable epilepsy. Methods: Data from the VNS therapy Patient Outcome Registry, maintained by the manufacturer of the device, Cyberonics Inc. (Houston, TX, USA), was queried to characterize the response of patients in whom a brain tumor was listed as the etiology of epilepsy. A case–control analysis was implemented and patient outcome was measured by Engel classification, median seizure response and responder rate (≥50% seizure reduction) using t-tests and chi-squared tests. Results: In 107 patients with an epilepsy etiology related to a brain tumor, seizure reduction was 45% at 3 months and 79% at 24 months with a responder rate of 48% at 3 months and 79% at 24 months. There was no statistical difference in seizure reduction compared with 326 case–control patients from the registry without brain tumors. There was no significant difference in anti-epileptic drug (AED) usage from baseline to 24 months post implant in either group. Conclusions: VNS therapy is equally effective in patients who suffer seizures secondary to brain tumors as in patients without history of a brain tumor. VNS therapy is a viable treatment option for patients with brain tumor associated medically intractable epilepsy, assuming cytoreductive and other adjuvant therapies have been fully explored. [Copyright &y& Elsevier]

Abstract: Purpose: A proportion of patients with childhood and juvenile absence epilepsies (CAE, JAE) are likely to be classified as medically refractory. In view of evidence gap for the treatment of such patients, this series is reported to generate estimate for efficacy of vagus nerve stimulation (VNS) in this patient population. Methods: Patients were identified by a chart review of all VNS recipients between January 1, 2006 and December 31, 2011. The diagnosis of CAE and JAE was based on conventional criteria. Details of demography, epilepsy phenomenology, management and outcomes were extracted. The outcome measures included reduction in daily seizure frequency measured as a percentage of pre-VNS seizure frequency and classified on International League Against Epilepsy (ILAE) outcome scale. Results: Nine patients (7 CAE, 2 JAE) with a mean age of seizure onset of 5.4 years (±3.9) were identified. Mean duration of epilepsy prior to VNS implant was found to be 3.9 years (±1.4). These patients had failed a median of 5 anti-epileptic drugs before being referred for consideration of surgical treatment. After a mean follow-up of 33.9 months (±25.5, minimum 4 months), 1 patient attained complete seizure freedom (ILAE class 1), 6 had ILAE class 4 and 2 had ILAE class 5 outcomes, respectively. Mean reduction in daily seizure frequency was found to be 53.5±60.3% (1-sided p-value for paired t-test=0.04), with a 50% responder rate of 55.6%. Conclusion: VNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy. [Copyright &y& Elsevier]

Abstract: Purpose: In the treatment of epilepsy, the recommendation to add vagus nerve stimulation (VNS) to the best available drug therapy (BDT) mostly relies on uncontrolled studies which provide limited information about VNS-specific benefits. We report findings from a retrospective matched pairs case–control study comparing the long-term (>2 years) outcomes of BDT with or without VNS. Methods: Included were adult patients with therapy-refractory epilepsy who had undergone the pre-surgical work-up (baseline) and subsequently received BDT with VNS (BDT+VNS) or BDT alone (BDT group). Patients were matched in pairs for age, gender and follow-up. Health outcomes were assessed at least 24 months after the baseline by comprehensive postal surveys and included established psychometric scales. Results: We obtained data from 20 matched pairs of case and control patients. In both groups, seizures, health-related quality of life and mood improved over time. More BDT patients experienced a complete cessation of “major” seizures (12/20 vs. 4/20) whereas, in non-seizure free patients, BDT+VNS patients showed better seizure frequency reduction (>50% reduction: 12/19 vs. 7/16). BDT+VNS patients experienced equal drug related and additional VNS related side effects. No clinically relevant effect of VNS treatment was found on any psychological/psychosocial outcome measure. Conclusion: This retrospective study provided no positive evidence for therapeutic benefits of adding VNS to BDT. The follow-up health status of BDT+VNS patients was slightly worse than in patients receiving BDT alone. Despite minor group differences at baseline the two patient groups who had failed presurgical evaluation were comparable. Therapeutic improvements during long-term BDT alone are often underestimated resulting in a misattribution of positive changes to VNS in uncontrolled studies and reviews. Currently, there is no incontrovertible evidence for the clinical effectiveness of adding VNS to BDT. [Copyright &y& Elsevier]

Abstract: Purpose: Lennox–Gastaut syndrome (LGS) is an epileptogenic disorder that arises in childhood and is typically characterized by multiple seizure types, slow spike-and-wave complexes on EEG and cognitive impairment. If medical treatment fails, patients can proceed to one of two palliative surgeries, vagus nerve stimulation (VNS) or corpus callosotomy (CC). Their relative seizure control rates in LGS have not been well studied. The purpose of this paper is to compare seizure reduction rates between VNS and CC in LGS using meta-analyses of published data. Methods: A systematic search of Pubmed, Ovidsp, and Cochrane was performed to find articles that met the following criteria: (1) prospective or retrospective study, (2) at least one patient diagnosed with Lennox–Gastaut syndrome, and (3) well-defined measure of seizure frequency reduction. Seizure reduction rates were divided into seizure subtypes, as well as total seizures, and categorized as 100%, >75%, and >50%. Patient groups were compared using chi-square tests for categorical variables and t-test for continuous measures. Pooled proportions with 95% confidence interval (95% CI) of seizure outcomes were estimated for total seizures and seizure subtypes using random effects methods. Results: 17 VNS and 9 CC studies met the criteria for inclusion. CC had a significantly better outcome than VNS for >50% atonic seizure reduction (80.0% [67.0–90.0%] vs. 54.1% [32.1–75.4%], p <0.05) and for >75% atonic seizure reduction (70.0% [48.05–87.0%] vs. 26.3% [5.8–54.7%], p <0.05). All other seizure types, as well as total number of seizures, showed no statistically significant difference between VNS and CC. Conclusions: CC may be more beneficial for LGS patients whose predominant disabling seizure type is atonic. For all other seizure types, VNS offers comparable rates to CC. [Copyright &y& Elsevier]

Abstract: Purpose: The effectiveness of VNS was evaluated in thirty-nine encephalopatic patients with drug-resistant epilepsy characterized by multiple seizures and drop attacks. Twenty-five patients were affected by severe epilepsy with multiple independent spike foci (SE-MISF) and fourteen patients by Lennox–Gastaut syndrome (LGS). Method: Changes in seizure frequency, cognition, adaptive behaviour and quality of life were assessed before and after VNS implant until three years. Outcome assessment for all seizure types included the number of seizures/month and the reduction in seizure frequency rate at each follow-up. Moreover, the effect of VNS on frequency, duration and intensity of drop attacks was separately addressed by a modification of McHugh scale. Results: VNS produced a mean seizure rate reduction of 41% at six months, 50% at twelve months, and 54% at thirty-six months. After one year of stimulation, thirteen patients with SE-MISF (52%) and three patients with LGS (21%) showed a reduction above 50% in all seizures’ frequency rate. As for drop attacks, eight patients (20%) gained a reduction above 50%, while seven patients (17%) showed a reduction only in intensity and duration. Cognitive level and adaptive behaviour were unchanged, while a better quality of life was reported in half out of the patients. Conclusions: VNS had a greater effect in reducing seizures frequency and drop attacks’ intensity and duration in SE-MISF patients than LGS patients. An improved quality of life was observed also in those patients who only reduced the intensity and duration of drop attacks. [Copyright &y& Elsevier]

Abstract: Optimal candidates for VNS as a treatment for refractory epilepsy have not been identified. In this retrospective two-center study, we used the Engel classification for evaluating seizure outcome, and tried to identify predictive factors for outcome by means of subgroup analysis. The medical records of patients who have been treated with VNS for at least one year at Dartmouth–Hitchcock Medical Center and Ghent University Hospital were evaluated. Seizure frequency outcome was assessed using the Engel classification for the study population as a whole, and for patient subgroups with regard to mental functioning, seizure type, predisposing factors for developing epilepsy, age at time of VNS implantation and epilepsy duration. 189 patients (102M/87F) were included in the study (mean FU: 41 months). 6% had a class I outcome (seizure-free), 13% a class II outcome (almost seizure-free), 49% a class III outcome (worthwhile improvement) and 32% had a class IV outcome (no improvement). When patients were divided into specific subgroups, a statistically significant better outcome was found patients with normal mental functioning (p =0.029). In our series, results for VNS are clearly inferior to resective surgery, but comparable to other treatment modalities for refractory epilepsy. With combined class I and II outcomes around 20%, and another 50% of patients having worthwhile improvement, VNS is a viable alternative when resective surgery is not feasible. [Copyright &y& Elsevier]

Abstract: The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 50 patients with epilepsy and learning disabilities. Mean observation time was 4.6 years. At follow-up, none of the patients was seizure-free, 25% had more than 50% seizure reduction, and 46% had some seizure reduction, but less than 50%. The discontinuation rate was 18%. Our results indicate that, like antiepileptic drugs, VNS does not have such a good seizure-reducing effect in patients with epilepsy and learning disabilities compared with the general epilepsy population. [ABSTRACT FROM AUTHOR]

Abstract: Rationale: Vagus nerve stimulation (VNS) is a frequently used treatment for patients with refractory epilepsy who are unsuitable candidates for epilepsy surgery. There has been a steady evolution in VNS technology, as generators’ volumes have become smaller and battery life expectancy longer. This pilot study is an open-label retrospective study that describes our experience with the latest commercially available generator, i.e. the VNS Therapy™ Demipulse Model 103. Treatment efficacy and side effects, as well as technical and practical enhancements useful for the patient and for the medical staff are discussed in this study. Methods: Twenty patients (11F/9M) with a mean age of 40 years (range 8–61), who were considered unsuitable candidates for resective surgery, were implanted with a VNS Therapy™ Demipulse Model 103. Mean monthly seizure frequency reduction and side effects were evaluated 1 year after implantation. Results: Mean monthly seizure frequency decreased significantly from 54 seizures/month (SEM 30; range 1–555) before treatment to 33 (SEM 24, range 0–445) following 12 months of treatment (p <0.05). Seven patients (39%) were considered responders with a reduction in seizure frequency of more than 50%. One of those seven patients became seizure free. Side effects were stimulation-related tingling sensation in the throat and/or hoarseness, a painful sensation in the left neck or ear region and a lead breakage In addition; one case of SUDEP was reported. Conclusion: Patients treated with VNS Therapy™ Demipulse generators proved to have a significant decrease in seizure frequency. In this patient group, VNS was well tolerated. The main technical advances are the decrease in size and improved options for battery life follow-up. [ABSTRACT FROM AUTHOR]

Abstract: We performed a retrospective, multicenter, open-label study to evaluate the efficacy of vagus nerve stimulation (VNS) in all patients in the Czech Republic who have received this treatment for at least 5 years (n =90). The mean last follow-up was 6.6±1.1 years (79±13 months). The median number of seizures among all patients decreased from 41.2seizures/month in the prestimulation period to 14.9seizures/month at 5 years follow-up visit. The mean percentage of seizure reduction was 55.9%. The responder rate in these patients is in concordance with the decrease of overall seizure frequency. At 1 year after beginning the stimulation, 44.4% of patients were responders; this percentage increased to 58.7% after 2 years. At the 5 years last follow-up 64.4% of patients were responders, 15.5% experienced ≥90% seizure reduction, and 5.5% were seizure-free. A separate analysis of patients younger than 16 years of age showed lower efficacy rates of VNS in comparison to the whole group. Complications and chronic adverse effects occurred in 13.3% of patients. VNS is an effective and safe method to refractory epilepsy in common clinical practice. [Copyright &y& Elsevier]

Summary: Purpose: To unravel the mechanism of action of neurostimulation as a treatment for seizures, functional neuroimaging tools allow minimally invasive research in humans. We performed single-photon emission computed tomography (SPECT) in patients with epilepsy, treated with vagus nerve stimulation (VNS). Changes in regional cerebral blood flow (rCBF) at the time of initial stimulation as well as after chronic treatment were correlated with long-term clinical efficacy. Methods: In this pilot study, 27 patients (14 female and 13 male) who were treated with VNS at Ghent University Hospital for refractory epilepsy underwent a 99mTc-ECD (ethyl cystein dimer) SPECT activation study at the time the first stimulation train was administered. 12 patients underwent an additional 99mTc-ECD SPECT activation study 6 months later. Image acquisition was performed on a high-resolution triple-headed gamma camera. Significant rCBF changes were correlated with prospectively assessed clinical efficacy data. Results: Significant rCBF changes were found in the thalamus, the hippocampus and the parahippocampal gyrus. Acute limbic hyper-perfusion and chronic thalamic hypo-perfusion correlate with positive clinical efficacy. Conclusions: Acute and chronic electrical stimulation of the vagus nerve induces rCBF changes that can be measured by SPECT on a group-basis. The thalamus and the limbic system are thought to play a key role in the mechanism of action of VNS. [Copyright &y& Elsevier]

Summary: Introduction: Vagus nerve stimulation (VNS) is thought to have a cumulative effect in time on seizure frequency reduction. There also might be other variables than reduction of seizure frequency in order to determine VNS efficacy. In this study we describe the long-term outcome of the first group of vagus nerve stimulation patients with pharmacoresistant epilepsy at the Medisch Spectrum Twente, The Netherlands. Methods: This long-term descriptive prospective study included 19 patients, 11 males and 8 females, aged 17–46 years with pharmacoresistant epilepsy. They had received 3–16 (mean 9) different anti-epileptic drugs and were not eligible for surgical resection of an epileptic focus. A vagus nerve stimulator was implanted in the period April 1999–October 2001. Follow-up ranges from 2 to 6 years (mean 4 years). Efficacy was measured as the percentage change in seizure rate during 1 year and then after each year follow-up of VNS compared to 5 months baseline before implantation. Results: Mean seizure reduction at 1–6 years was, respectively, 14% (n =19), 25% (n =19), 29% (n =16), 29% (n =15), 43% (n =9) and 50% (n =7). Because of VNS two patients were able to start living without supervision. One patient died after 2 years of follow-up possibly as a result of SUDEP. Four patients had no apparent reduction in seizure frequency. Two of them had their stimulator removed. The other two patients however had significantly reduced post-ictal periods and seizure time and received a new pulse generator when the battery was depleted. One stimulator was switched off due to adverse effects, even though there was a positive effect on his seizure reduction. In six patients the medication regimen was changed during VNS by adding one anti-epileptic drug, however without significant change in seizure reduction. Adverse effects were hoarseness and coughing during stimulation. One patient had a temporary paralysis of his left vocal cord. Conclusion: We think that VNS is an effective treatment for pharmacoresistant epilepsy and its positive effect persists during the years of follow-up. Our results suggest that seizure reduction should not be considered as the only variable of importance to describe the outcome of VNS on epilepsy and it is worthwhile to look at other outcome measures. [Copyright &y& Elsevier]

Summary: Purpose: To evaluate the effects of two cycles of vagus nerve stimulation (VNS), 30s/5min and 7s/18s on the interictal epileptiform discharges (IEDs). Methods: Twenty patients were studied, 12 with generalized and 8 with partial seizures. An EEG of 120 channels was performed during 3 different conditions, each one lasting 30min: basal state (BS), 30s/5min and 7s/18s VNS cycles. The number and duration of IEDs, time of IEDs in 1min (TIEDM), IEDs/NIEDs index and the spike-free period (SFP) were determined. Results: In 16 patients (80%), IED decreased during 30s/5min cycle (Group 1) and increased in 4 (Group 2). In Group 1, during the 30s/5min cycle the following variables showed a decrease: TIEDM, from 12.64s to 9.62s (p =0.001); IED/NIED index, from 0.53 to 0.31 (p =0.021), and IED duration, from 1.57s to 1.05s (p =0.015); whereas SFP duration increased from 20.06s to 37.73s (p =0.008). The decrease in IED was 41% and the increase in SFP 88%. In the 7s/18s cycle, only SFP had an increase, 72% (p <0.043). In Group 2, an increase in IED during both cycles was found. In the 30s/5min cycle, TIEDM increased 56% (p =0.042) and IED/NIED index 259% (p =0.040). Conclusion: VNS modifies IED in an acute form, in 80% of patients the 30s/5min cycle decreases the epileptiform activity and it is not modified by 7s/18s cycle. In 20% of patients, both cycles increase the epileptiform activity. [Copyright &y& Elsevier]

Summary: Purpose: To retrospectively review our experience with VNS in pediatric patients with pharmacoresistant epilepsy and examine the seizure-frequency outcome and rates of discontinuation in two age groups: adolescent and pre-adolescent children. Results: Complete pre- and post-VNS data were available for 46/49 patients. Median age at implantation was 12.1 (range 2.3–17.9) and median duration of epilepsy 8.0 (1.9–16.9) years. Twenty-one patients (45.6%) were under 12 years at the time of surgery. Median follow-up was 2 years; follow-up exceeded 4 years in 9/46 patients. As compared to baseline, median seizure-frequency reduction in the setting of declining numbers was 56% at 3 months, 50% at 6, 63% at 12, 83% at 24 and 74% at 36 months. When a last observation carried forward analysis was employed median seizure-frequency reduction in the range of 60% was observed at 1, 2 and 3 years post-VNS. Twenty patients (43.5%) had >75% seizure-frequency reduction. No response (increase or <50% reduction) was observed in 19/46 (41.3%). Five patients (10.1%) were seizure-free for more than 6 months by their last follow-up. There was no difference in the number of AEDs used before and after VNS. The long-term discontinuation rate was 21.7% and reflected a lack of clinical response or infection. Conclusions: In this series VNS was well-tolerated and effective as add-on therapy for refractory seizures in children of all ages. Response was even more favorable in the younger group (<12 years at implantation). Infection and lack of efficacy were the most common reasons for discontinuation of long-term VNS therapy in this group. [Copyright &y& Elsevier]

Summary: Purpose: We report long-term effects of vagus nerve stimulation (VNS) on epileptiform activity in 15 children, and how these changes are related to activity stage and to clinical effects on seizure reduction, seizure severity (NHS3) and quality of life (QOL). Methods: Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with 24h ambulatory EEG monitoring for spike detection. The number of interictal epileptiform discharges (IEDs) and the inter spike intervals (ISIs) were analysed during 2h in the awake state, and 1h of rapid eye movement (REM)-, spindle- and delta-sleep, respectively. Total number and duration of electrographic seizure episodes were also analysed. Results: At 9 months the total number of IEDs was significantly reduced (p =0.04). There was a tendency of reduction in all activity stages, and significantly so in delta-sleep (p =0.008). Total electrographic seizure number was significantly reduced in the 24h EEG at 3 and 9 months (p =0.03, 0.05). There was a significant concordance in direction of changes in epileptiform activity and electrographic seizures at 9 months (p =0.04). Concordance in direction of changes was seen in 9 of 15 children between clinical seizures and IED (p >0.3), in 10 of 15 children between QOL and IED (p =0.3) and in 8 of 15 children between NHS3 and IED (p >0.3). There was no direct correlation between the extent of improvement in these clinical data and the degree of spike reduction. Conclusion: This study shows that VNS reduces IEDs especially in REM and delta sleep, as well as the number of electrographic seizures. It also shows a concordance between reduction in IEDs and electrographic seizures. [Copyright &y& Elsevier]

Summary: Purpose:: Vagus nerve stimulation (VNS) is a neurophysiologic treatment for patients with refractory epilepsy. There is growing evidence of additional quality of life (QOL) benefits of VNS. We report the effects of VNS on seizure frequency and severity and how these changes are related to cognitive abilities, QOL, behaviour and mood in 15 children with medically refractory and for surgery not eligible epilepsy. Methods:: Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with Bayley Scales of Infant Development (BSID), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R), Wechlser Intelligence Scales for Children (WISC-III) depending on the child''s level of functioning, a Visual Analogue Scale for validating QOL, Child Behaviour Checklist (CBCL) for quantifying behaviour problems, Dodrill Mood Analogue Scale and Birleson Depression Self-Rating Scale, and the National Hospital Seizure Severity Scale (NHS3). A diary of seizure frequency was collected. Results:: Six of 15 children showed a 50% or more reduction in seizure frequency; one of these became seizure-free. Two children had a 25–50% seizure reduction. Two children showed increased seizure frequency. In 13 of 15 children there was an improvement in NHS3. The parents reported shorter duration of seizure and recovery phase. There were no changes in cognitive functioning. Twelve children showed an improvement in QOL. Eleven of these also improved in seizure severity and mood and five also in depressive parameters. Conclusion:: This study has shown a good anti-seizure effect of VNS, an improvement in seizure severity and in QOL and a tendency to improvement over time regarding behaviour, mood and depressive parameters. The improvement in seizure severity, QOL, behaviour, mood and depressive parameters was not related to the anti-seizure effect. [Copyright &y& Elsevier]