Vagus nerve stimulation for medically refractory absence epilepsy

PurposeA 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.MethodsPatients 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.ResultsNine 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%.ConclusionVNS may be considered as a therapeutic option in patients with medically refractory absence epilepsy.     

Vagus nerve stimulation for refractory epilepsy.

Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with medically or surgically refractory epilepsy. Since the first human implant in 1989, more than 10 000 patients have been treated with VNS. Two randomized controlled studies have shown a statistically significant decrease in seizure frequency during a 12-week treatment period versus a baseline period when 'high stimulation' mode was compared with 'low stimulation' mode. The efficacy appears to increase over time. In general, one third of the patients show a >50% reduction of seizure frequency; one third show a 30-50% seizure reduction, and one third of patients show no response. Few patients become seizure-free. Side effects during stimulation are mainly voice alteration, coughing, throat paraesthesia and discomfort. When studied on a long-term basis, VNS is an efficacious, safe and cost-effective treatment not only in adults but also in children and the elderly. The precise mechanism of action remains to be elucidated. In recent years much progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in animals and patients treated with VNS. Further elucidation of the mechanism of action of VNS may increase its clinical efficacy and our general understanding of some physiopathological aspects of epilepsy. Finally, VNS may become an alternative treatment for other conditions such as depression and pain.     

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience.

Vagus nerve stimulation (VNS) is an alternative treatment for medically or surgically refractory epilepsy. The long-term efficacy and safety of VNS were evaluated in a large patient series at Ghent University Hospital and Dartmouth-Hitchcock Medical Center. Between March 1995 and February 2003, seizure frequency and type as well as prescribed antiepileptic drugs and side effects were prospectively assessed in 131 patients treated with VNS in either center. Patients with a minimum follow-up duration of 6 months were included in the efficacy and safety analysis. A total of 118 of 131 implanted patients had a minimum postimplantation follow-up period of 6 months (mean, 33 months). The mean age of these patients was 32 years and the mean duration of refractory epilepsy was 22 years. The mean reduction in monthly seizure frequency in all patients was 55% (range, 0-100; SD = 31.6). Seven percent of patients were free of seizures with impaired consciousness, 50% of patients had a seizure frequency reduction of more than 50%, and 21% of patients were nonresponders. Fifteen patients reported stimulation-related side effects such as hoarseness or gagging. In a large patient series from two geographically distinct epilepsy centers located in two different continents, VNS proved to be efficacious and safe during long-term follow-up.     

Vagus nerve stimulation for refractory idiopathic generalised epilepsy.

We reviewed our experience with vagus nerve stimulation (VNS) in 165 patients with medically refractory epilepsy (138 partial epilepsy (PE), 13 symptomatic generalised epilepsy (SGE), 14 idiopathic generalised epilepsy (IGE)). Average duration of VNS therapy was 21.6 months. A 50% or greater reduction in seizure frequency was achieved in 47.1% of the PE group, 46.1% of the SGE group, and 57.1% of the IGE group. A 50% or greater reduction in seizure frequency and reduced antiepileptic drug (AED) regimen were achieved in: PE (9.4%), SGE (7.7%), and IGE (35.7%). These preliminary results suggest that VNS is an effective therapy for some patients with medically refractory IGE.     

Vagus nerve stimulation for epilepsy: a review.

Vagus nerve stimulation is an empirically based method for treatment of epilepsy by repeated stimulation of the left vagus nerve through implanted electrodes. Despite studies in animals and man, which show changes in brain electrophysiology, metabolism and neurochemistry, the mode of action remains unknown. Clinical testing has presented methodological challenges, as it is difficult to assess under double blind conditions a treatment which requires surgery and produces a sensation every time the stimulator comes on. This has nevertheless been successfully addressed in parallel design, controlled trials comparing high and low stimulation schedules. These have been performed in adults with medically intractable partial seizures, and demonstrated efficacy, safety and good tolerability. Efficacy, both in the controlled trials and in numerous reports arising from the considerable post-marketing experience is modest. Some 30% of patients achieve a 50% seizure reduction after 3 months of treatment, but this proportion progressively increases to about 50% after 18 months. Side-effects comprise: discomfort in the face or neck when the stimulator is activated, coughing, breathlessness on exertion and hoarseness of voice. All are related to intensity of stimulation and rapidly habituate in most subjects. In those patients who respond, a stimulus level can therefore generally be found which is acceptable to the subject. No indication other than refractory partial seizures in adults has been the subject of controlled trials, but post-marketing experience and uncontrolled reports indicate comparable efficacy and safety in a wide range of epilepsies, partial and generalized, idiopathic, cryptogenic, or symptomatic, in patients of all ages.     

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study.

This six-center, retrospective study evaluated the effectiveness, tolerability, and safety of vagus nerve stimulation in children. Data were available for 125 patients at baseline, 95 patients at 3 months, 56 patients at 6 months, and 12 patients at 12 months. The typical patient, aged 12 years, had onset of seizures at age 2 years and had tried nine anticonvulsants before implantation. Collected data included preimplant history, seizures, implant, device settings, quality of life, and adverse events. Average seizure reduction was 36.1% at 3 months and 44.7% at 6 months. Common adverse events included voice alteration and coughing during stimulation. Rare adverse events, unique to this age group, included increased drooling and increased hyperactivity. Quality of life improved in alertness, verbal communication, school performance, clustering of seizures, and postictal periods. We concluded that vagus nerve stimulation is an effective treatment for medically refractory epilepsy in children.     

Vagus nerve stimulation in the treatment of refractory epilepsy

Many patients with epilepsy suffer from persistent seizures despite maximal anti-epileptic drug therapy. Chronic, intermittent vagus nerve stimulation has been proven to be an effective option for many patients suffering from refractory seizures who are not candidates for surgical resection. Although only a small minority of patients will be entirely seizure-free, vagus nerve stimulation, as an adjunct to medical therapy, may result in significant improvements in quality of life. Vagus nerve stimulation is generally well-tolerated, as device implantation is associated with a low rate of perioperative complications, and the majority of side effects are stimulation-dependent and thus reversible.     

迷走神经刺激术-程控电刺激治疗难治性癫痫

目的 应用迷走神经刺激术(vagus nerve stimulation,VNS)治疗难治性癫痫,并探讨其治疗机制和方法。方法 个体化的VNS疗效预测和精确无误的VNS植入,适时恰当的刺激参数程控调校,并以长程脑电图、SPECT观测VNS带来的脑功能改变。结果 接受VNS术3个月后,3例病患的发作频次均减少50％以上,2例在应急磁铁的辅助下基本不再表现复杂性发作,1例不再表现全身失张性发作,而以部分性发作为主,偶有复杂发作,生活质量提高。脑电图原有的棘波、尖波消失或减少,阵发性异常消失或时间缩短。发作间期SPECT表现为原有的低代谢灶缩小。结论 恰当地应用VNS能够为难治性癫痫提供一种有效、微创、副作用极少的治疗手段。     

Vagus nerve stimulation for treatment of medically intractable seizures. Evaluation of long-term outcome

Vagus nerve stimulation (VNS) constitutes an adjunctive, modern management of medically intractable seizures, especially when surgery is inadvisable. OBJECTIVE: To evaluate the long-term results as regards efficacy, safety and tolerability of VNS in epileptic subjects, with focal and/or generalised seizures, refractory to old and new AEDs, without indication for resective surgery. PATIENTS: 51 epileptic subjects (30 males, 21 females), aged 7-49 years, have been implanted so far. RESULTS: The results refer to the 47 subjects with a follow-up longer than 6 months. 22 (46.8%) of them had a greater than 50% reduction in seizure frequency, with a more than 75% reduction in 6. No significant difference was found in relation to type of seizures. The efficacy maintained steadily over time during the follow-up (mean 26.4 months). Twelve out of the 47 subjects had an improvement in alertness, attention and psychomotor activity. Complications were observed in 5 cases, leading to removal of the stimulator in 2. A moderate vocal hoarseness (40.4%), paresthesia (6.3%), pharingodinia and cough (4.3%) were the registered adverse events. CONCLUSIONS: Our results confirm that VNS is effective, safe and well tolerated and constitutes an alternative treatment for pharmacoresistant epileptic seizures.     

Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study.

PURPOSE: To establish the long-term efficacy and tolerability of vagus nerve stimulation (VNS) in children with a Lennox-like syndrome. METHOD: This study was a longitudinal observational prospective cohort analysis. Baseline: 6 months. Follow-up: 24 months. Screening (baseline and every 6 months): MRI (baseline only), EEG, neuropsychological evaluation, ECG and blood sampling for antiepileptic drug levels. Nineteen children are included. RESULTS: A seizure frequency reduction of 20.6% was found at the end of the follow-up period. No relationship was detected between the length of the stimulation period and the reduction in the seizure frequency. 21% of the patients showed a reduction in seizure frequency of 50% or more. The seizure severity showed improvement in the first 12 months of treatment. The largest seizure reduction was found in the patients with highest frequency of background activity at the baseline EEG. Neuropsychological findings: no negative impact on behaviour, moderate improvement in function, behaviour and mood. Largest seizure reduction was found in the group with the highest baseline mental function. The scores for mental age improved independently of the seizure control. Twelve patients (63%) experienced minor side effects, which subsided after 1 month. CONCLUSION: (1) There was a significant reduction in seizure frequency and severity. (2) No serious side effects were recorded. (3) No negative effects on cognition or quality of life were apparent. (4) Patients with highest baseline mental functioning showed the highest seizure reduction. (5) Those patients with less disturbed EEG (high background activity and less interictal epileptic activity) showed the highest seizure reduction.     

Vagus nerve stimulation for the treatment of refractory epilepsy. State of the art

The vagus nerve stimulation (VNS) therapy is a new neurostimulation technique used for treating pharmacoresistant epilepsy. It can be considered an effective and safe alternative for the treatment of refractory epilepsy patients. In the present review, we describe the surgical implantation technique, its indications and results achieved until now. We will also summarize the possible mechanisms of action of VNS therapy. Finally, we will comment on the difficulties and inconveniences that did not allow this antiepileptic surgical technique to become more widely used.     

Vagus nerve stimulation in refractory epilepsy: New indications and outcome assessment

Although vagus nerve stimulation (VNS) is an effective alternative option for patients with refractory epilepsy unsuitable for conventional resective surgery, predictors of a better control of seizure frequency and severity are still unavailable. This prospective study reports on 39 patients, including 4 children affected by epilepsia partialis continua (EPC), who underwent VNS for refractory epilepsy. The overall seizure frequency outcome was classified into three groups according to reduction rate: ≥ 75%, ≥ 50%, and < 50%. Engel and McHugh classifications were also used. The median follow-up period was 36 months. A seizure reduction rate ≥ 50% or EPC improvement was observed in 74% of the patients. Twenty-one out of 35 cases (60%) resulted in Engel classes II and III. Outcome, as defined by the McHugh scale, showed a responder rate of 71%.These results suggest that younger patient age and focal or multifocal epilepsy are related to a better seizure control and cognitive outcome. Vagus nerve stimulation could also be considered as an effective procedure in severe conditions, such as drug-refractory EPC.     

Vagus nerve stimulation in pediatric epilepsy: a review

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.     

Vagus nerve stimulation has a positive effect on mood in patients with refractory epilepsy

Background

Preliminary research on the efficacy of vagus nerve stimulation (VNS) indicated additional effects on neuropsychological variables like mood and quality of life (QOL).

Objectives

The objectives of this prospective longitudinal observational cohort study were to assess the effects of VNS on mood, QOL and cognition in patients with refractory epilepsy and to determine whether these effects occur dependent of seizure control.

Methods

We included 41 patients with refractory epilepsy; treated with VNS as part of usual patient care. A neuropsychological battery was performed during baseline and repeated after 6 months of VNS in order to compare neuropsychological variables before and after VNS. All patients completed seizure diaries.

Results

Significant improvements were observed for both mood and QOL after 6 months of VNS; based on the results in the POMS and QOLIE-89 questionnaires (p < 0.05). There was no significant change in cognition. Mean percentage change in seizure frequency was −9.0%, while 20% of the patients achieved a seizure frequency reduction of 50% or more. No significant correlation was found between changes in seizure frequency and improvements in mood or QOL.

Conclusions

VNS is associated with improvements in both mood and QOL in patients with refractory epilepsy. Since these improvements appeared to be independent of seizure control, the results of this study indicate an additional antidepressant effect of VNS, which can be of extra value in view of the high co-morbidity of mood disturbances in patients with epilepsy.     

Vagus nerve stimulation: Outcome and predictors of seizure freedom in long-term follow-up

ObjectivesTo present long-term outcome and to identify predictors of seizure freedom after vagus nerve stimulation (VNS).MethodsAll patients who had undergone VNS implantation in the Epilepsy Centre Bethel were retrospectively reviewed. There were 144 patients who had undergone complete presurgical evaluation, including detailed clinical history, magnetic resonance imaging, and long-term video-EEG with ictal and interictal recordings. After implantation, all patients were examined at regular intervals of 4 weeks for 6–9 months. During this period the antiepileptic medication remained constant. All patients included in this study were followed up for a minimum of 2 years.ResultTen patients remained seizure-free for more than 1 year after VNS implantation (6.9%). Seizures improved in 89 patients (61.8%) but no changes were observed in 45 patients (31.3%). The following factors were significant in the univariate analysis: age at implantation, multifocal interictal epileptiform discharges, unilateral interictal epileptiform discharge, cortical dysgenesis, and psychomotor seizure. Stepwise multivariate analysis showed that unilateral interictal epileptiform discharges (IEDs), P = 0.014, HR = 0.112 (95% CIs, 0.019–0.642), cortical dysgenesis P = 0.007, HR = 0.065 (95% CIs, 0.009–0.481) and younger age at implantation P = 0.026, HR = 7.533 (95% CIs 1.28–44.50) were independent predictors of seizure freedom in the long-term follow-up.ConclusionVNS implantation may render patients with some forms of cortical dysgenesis (parietooccipital polymicrogyria, macrogyria) seizure-free. Patients with unilateral IEDs and earlier implantation achieved the most benefit from VNS.     

Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for intractable epilepsy. However, the optimal range of device duty-cycles [on/(on + off times)] is poorly understood. The authors performed a multicenter, randomized trial of three unique modes of VNS, which varied primarily by duty-cycle. The results indicate that the three duty-cycles were equally effective. The data support the use of standard duty-cycles as initial therapy.