Vagus nerve stimulation for medication-resistant generalized epilepsy. E04 VNS Study Group

We treated 24 generalized epilepsy patients with vagus nerve stimulation (VNS), comparing seizure rates during a 1-month baseline with 3 months of VNS. Median seizure rate reduction was -46%. Sixteen of the 24 patients had better than a -30% reduction and 11 of the 24 patients had better than a -50% reduction in seizure rate. A mild cough during stimulation occurred in six patients. Patients with higher baseline seizure rates and later ages at epilepsy onset had the best responses to VNS. Our findings suggest VNS is an effective treatment for medication-resistant generalized epilepsy even in patients as young as 4 years.     

Health-related quality of life and seizure control in temporal lobe epilepsy

We conducted a prospective study over 24 months to compare health-related quality of life in surgically and medically treated patients with intractable temporal lobe epilepsy. Seizure frequency and health-related quality of life were assessed in 81 patients before and 6, 12, and 24 months after treatment. Using the Epilepsy Surgery Inventory 55 (ESI-55), we compared (1) different seizure outcome groups and (2) temporal lobectomy with continuing medical management. Follow-up was satisfactory in 72 patients (89%), 51 treated with temporal lobectomy and 21 with no surgery. Pretreatment seizures and health-related quality of life were comparable in the two groups. Seizure outcome was significantly better at 6, 12, and 24 months after surgery. At 24 months, seizure-free patients and those with at least a 90% reduction in seizure frequency reported significant improvements in health-related quality of life (on 5 of 10 subscales and overall Epilepsy Surgery Inventory 55 scale). Deterioration in quality of life occurred with less than 90% seizure reduction. Only one Epilepsy Surgery Inventory 55 subscale at 6 months and two subscales at 12 months showed a significant difference. Patients with good seizure outcome experience improved health-related quality of life after treatment. Since temporal lobectomy results in considerably better seizure control than continued medical management, the findings support surgery as the preferred treatment, although changes in health-related quality of life may not be evident until the second postoperative year.     

Quality-of-Life Assessment in Patients Treated with Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a novel therapy used in patients with medically intractable epilepsy. We administered a Quality of Life in Epilepsy-10 (QOLIE-10) questionnaire consisting of questions designed to assess the patients' rating of their memory, level of physical and mental well-being, energy, depression, worries about seizures and work, social limitations, and overall quality of life on VNS treatment. The questionnaire was administered before and at 1-3 weeks, 5-7 weeks, 3 months, 6 months, and 9-12 months after the initiation of VNS in 17 patients. QOLIE-10 scores were significantly better after the initiation of the therapy as compared with baseline (P < 0.01). There was no correlation between the improvement in QOLIE-10 scores and the reduction in seizure frequency, decreased severity of seizures, or increased level of energy/alertness. We conclude that VNS therapy is associated with a significant improvement in subjective quality of life.     

Exploration of Changes in Health-Related Quality of Life after 3 Months of Vagus Nerve Stimulation

Purpose. The goal of this work was to explore changes in health-related quality of life (HRQOL) and reductions in seizure frequency among patients initiating vagus nerve stimulation (VNS) for medication-refractory epilepsy.Methods. Patients receiving VNS completed the Quality of Life in Epilepsy-10 (QOLIE-10) at baseline and after 3 months of stimulation. Patients were categorized as responders (>/=50% seizure reduction) and nonresponders (<50% seizure reduction). Data were analyzed for change from baseline to 3 months within each group and between groups.Results. Both groups reported improvements in almost all aspects of HRQOL. Statistically significant improvements were reported by responders in energy, memory, social aspects, mental effects, and fear of seizures; and by nonresponders in downheartedness and overall QOL. Responders improved significantly more than nonresponders in energy.Conclusions. These exploratory analyses showed little difference in HRQOL between responders and nonresponders, with both reporting improvements after 3 months of VNS. Follow-up may determine whether improvements are sustained or attributable to placebo effect.     

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.     

Outcomes of vagal nerve stimulation in a pediatric population: A single center experience

ObjectiveTo evaluate the efficacy of vagus nerve stimulation (VNS) in pediatric patients with medically refractory epilepsy.MethodWe 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.ResultsComplete 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.ConclusionVNS provides significant seizure reduction, in particular in pediatric patients with a higher baseline seizure frequency.     

Contribution of depression and anxiety to impaired quality of life in survivors of myocardial infarction

Objective. To quantify the adverse influence of depression and anxiety assessed at the time of myocardial infarction, on the quality of life 5 years after the infarction. Methods. The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were completed in a group of 196 patients admitted in the hospital following non-fatal myocardial infarction, and the SF-12 quality of life questionnaire was administered during the 5- year follow-up. Results. Regression analysis showed a strong association between baseline depression and QoL in both the physical and mental domains; the higher the depression scores, the poorer the QoL. However, anxiety present at the time of myocardial infarction did not predict later QoL. Conclusions. Depression but not anxiety following MI predicts longer-term quality of life in myocardial infarction survivors.     

Effect of Long-Term Treatment with Vagus Nerve Stimulation on Mood and Quality of Life in Korean Patients with Drug-Resistant Epilepsy

Background and PurposeThis study aimed to determine the long-term effects of vagus nerve stimulation (VNS) treatment on suicidality, mood-related symptoms, and quality of life (QOL) in patients with drug-resistant epilepsy (DRE). We also investigated the relationships among these main effects, clinical characteristics, and VNS parameters.MethodsAmong 35 epilepsy patients who underwent VNS implantation consecutively in our epilepsy center, 25 patients were recruited to this study for assessing the effects of VNS on suicidality, mood-related symptoms, and QOL. The differences in these variables between before and after VNS treatment were analyzed statistically using paired t-tests. Multiple linear regression analyses were also performed to determine how the patients'' demographic and clinical characteristics influenced the variables that showed statistically significant changes after long-term VNS treatment.ResultsAfter VNS, our patients showed significant improvements not only in the mean seizure frequency but also in suicidality, depression, and QOL. The reduction in depression was associated with the improvement in QOL and more-severe depression at baseline. The reduction in suicidality was associated with higher suicidality at baseline, smaller changes in depression, and less-severe depression at baseline. Improved QOL was associated with lower suicidality at baseline.ConclusionsThis study found that VNS decreased the mean seizure frequency in patients with DRE, and also improved their depression, suicidality, and QOL. These results provide further evidence for therapeutic effect of VNS on psychological comorbidities of patients with DRE.     

Comparison of efficiency between VNS and ANT-DBS therapy in drug-resistant epilepsy: A one year follow up study

Vagus nerve stimulation (VNS) and anterior thalamic deep brain stimulation (ANT-DBS) have both been used for treatments of drug-resistant epilepsy (DRE). However, there is no comparative study on the effectiveness of two methods from one single center. 17 patients with DRE who underwent VNS therapy and 18 patients who underwent DBS were enrolled. A retrospective study was performed starting from baseline before operation extending to 12 months after operation. The seizure types, duration of epilepsy, age at implantation, failed numbers of antiepileptic drugs (AEDs) before operation, history of craniotomy, stimulation parameters and response rate were described. The analysis of liner regression on the age of onset, duration of epilepsy, numbers of AEDs, and the seizure reduction at 12 months after operation was applied. The mean seizure reduction in patients with DBS at 3, 6, 9 and 12 months after the operation was 57.22%, 61.61%, 63.94% and 65.28%, and that in cases with VNS was 36.06%, 39.94%, 45.24% and 48.35%, respectively. At 1 year after the operation, the patients with older operation age, focal seizures and older age of onset responded better to VNS; and those older operation age, focal generalized seizures, history of craniotomy and longer duration of disease responded better to DBS. The efficiency of ANT-DBS was higher than that of VNS at each follow up time point. Patients can choose the appropriate treatment according to the individual clinical characteristics.     

成年癫痫患者抑郁、焦虑状况及生活质量调查

目的调查成年癫痫患者抑郁、焦虑的患病率及可能的危险因素;评价抑郁及焦虑对癫痫患者生活质量的影响。方法采用Beck抑郁问卷(BDI)、贝克焦虑量表(BAI)及癫痫患者生活质量量表-31(QO-LIE-31中文版),对200例成年癫痫患者的抑郁、焦虑情况及生活质量进行评估。结果在200例癫痫患者中43.5%伴发抑郁,28.5%伴发焦虑,23%伴发抑郁及焦虑。发作频繁、无有薪职业是癫痫患者伴发抑郁的重要危险因素,无有薪职业是癫痫患者伴发焦虑的危险因素。抑郁组及抑郁伴焦虑组的QOLIE-31总分及各项评分均低于非抑郁非焦虑组(P=0.000);焦虑组的QOLIE-31总分(P=0.004)及发作的担忧(P=0.019)、认知功能(P=0.009)方面的得分均低于非抑郁非焦虑组。结论抑郁和焦虑是癫痫患者常见的精神共病,严重影响了癫痫患者的生活质量。积极控制发作、为癫痫患者提供更多的就业机会是改善癫痫患者生活质量的重要因素。     

Efficacy of vagus nerve stimulation as a treatment for medically intractable epilepsy in brain tumor patients. A case-controlled study using the VNS therapy Patient Outcome Registry

PurposeVagus 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.MethodsData 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.ResultsIn 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.ConclusionsVNS 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.     

迷走神经刺激对癫痫患者生活质量影响的临床研究

目的评估迷走神经刺激对癫痫患者生活质量的影响。方法 14例药物难治性全身性癫痫患者进行迷走神经刺激术治疗,比较其术前及术后癫痫患者生活质量量表-31(QOLIE-31)评分的变化。结果平均随访12月,患者发作频率平均减少61.0%,其中5例发作频率减少<50%,6例发作频率减少≥50%,3例发作停止。癫痫患者生活质量量表总分从术前的50.5上升至术后的57.1,平均增加6.6(P=0.0276)。各个分量表中得分均有一定程度增加,其中认知功能、情绪两项改善有统计学意义。癫痫患者生活质量量表总分及7个分量表得分改善与发作减少均无相关性。结论迷走神经刺激是一种治疗药物难治性癫痫安全、有效的方法。其作用不仅体现在癫痫发作的减少,对生活质量也有一定的改善作用。而且这两者之间无相关性,提示生活质量改善是迷走神经刺激独立的临床疗效评价指标之一。     

Self-Reported Mood Changes following 6 Months of Vagus Nerve Stimulation in Epilepsy Patients

Vagus nerve stimulation (VNS) for treatment of drug-resistant epileptic seizures has been reported to have additional positive mood effects as obtained by psychiatric ratings. To avoid rater bias effects, this study used self-report questionnaires and examined changes in self-reported mood and health-related quality of life following 6 months of VNS treatment. From 40 adult patients treated with VNS since the beginning of the study, 28 patients (mean age: 35.4 years) with unchanged medication were included. Repeated-measures MANOVA revealed a significant general mood improvement. Post hoc univariate tests obtained improvements of tenseness and dysphoria but not of depression, level of activity, or health-related quality of life. Mood and seizure outcome were correlated. VNS may improve unspecific states of indisposition and dysphoria. Absolute seizure reduction contributes to this antidysphoric effect. Since baseline depression scores were low, findings do not contradict but complement earlier reports of an antidepressive effect of VNS.     

Multiple sclerosis and depression: influence of interferon beta therapy

BACKGROUND AND OBJECTIVES: Depression is frequently part of the clinical picture of multiple sclerosis (MS). Major depression affects one in two patients with MS during the course of their lifetime. Our objectives were to determine first, whether interferon beta-1a (IFNbeta-1a) treatment increases the risk or level of depression and, secondly, whether depression status and depression evolution are related to the clinical characteristics of the disease. PATIENTS AND METHODS: We investigated 106 consecutive patients with relapsing remitting MS treated with IFNbeta-1a (Avonex). Patients with evidence of severe depression were excluded. The depression status, scored on the Beck Depression Inventory (BDI-II) (stratified as minimum, mild, moderate or severe level), and disability, scored on the Expanded Disability Status Scale (EDSS), were evaluated before and after 12 months of IFNbeta-1a treatment. RESULTS: At baseline, 85% of patients had a minimum or a mild depression status and after 12 months of treatment most of them (83%) retained their baseline status. Beck scores before and after treatment were not significantly different (P = 0.63). There was no correlation between age, gender, duration of illness or EDSS score and Beck score at baseline (P = 0.696). Patients with disability progression after one year of IFNbeta-1a treatment had a significantly higher Beck score at baseline than patients without disability progression (P = 0.003). CONCLUSION: IFNbeta-1a (Avonex) does not seem to significantly influence the depression status of MS patients even in those with disability progression.     

Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05

OBJECTIVE: To perform an open-label, long-term efficacy and safety/tolerability study of vagus nerve stimulation (VNS) of 454 patients with refractory epilepsy. METHODS: Subjects were enrolled from five clinical trials of VNS between 1988 and 1995 after undergoing an implantation of a pulse generator in the chest and a left cervical vagus nerve-stimulating lead coil. Patients were assessed at 6-month intervals until device approval. Seizure frequencies, medication treatment, and adverse events (AEs) were recorded and entered into a database. RESULTS: A total of 454 patients were implanted, and 440 patients yielded assessable data. A > or =50% seizure reduction postimplantation occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years. Median seizure reductions compared with baseline were 35% at 1 year, 44.3% at 2 years, and 44.1% at 3 years. Most common AEs postimplantation at 1 year were hoarseness (28%) and paraesthesias (12%), at 2 years were hoarseness (19.8%) and headache (4.5%), and at 3 years was shortness of breath (3.2%). Continuation rates were 96.7% at 1 year, 84.7% at 2 years, and 72.1% at 3 years. CONCLUSION: Long-term, open-label vagus nerve stimulation (VNS) provided seizure reduction similar to or greater than acute studies, for median reductions and for those reaching a > or =50% seizure reduction. VNS remained safe and well tolerated, with nearly three-quarters of the patients choosing to continue therapy.     

Influence of fatigue, depression, and demographic, socioeconomic, and clinical variables on quality of life of patients with epilepsy

The purpose of this study was to define the influence of fatigue, depression, and clinical, demographic, and socioeconomic factors on the quality of life of patients with epilepsy. The study was performed on 103 adult patients who visited Erciyes University Epilepsy Outpatient Clinic between 2004 and 2005. Patients were evaluated with the Form of Negotiation, Quality of Life in Epilepsy Inventory (QOLIE-89), Beck Depression Inventory, and Fatigue Severity Scale. Mean age of the patients was 34.3+/-12.6, and mean duration of disease was 12.6+/-9.3 years. Among these patients, 52.4% were men, 49.5% were married, 15.5% had a university education, 53.4% had low incomes, 45.6% had generalized seizures, and 35.0% had experienced one or more seizures per month during the preceding year. The most significant variables in the domain of Overall quality of life were seizure frequency (P<0.001), depression (P<0.001), and fatigue (P<0.001); the variables in the domain of Mental Health were seizure frequency (P<0.001) and fatigue (P<0.001); the variable in the Cognitive domain was fatigue (P<0.001); the variables in the domain of Physical Health were social insurance coverage (P<0.01), fatigue (P<0.01), and age (P<0.01); the variables in the Epilepsy Targeted domain were depression (P<0.001), seizure frequency (P<0.001), and fatigue (P<0.01). Although quality of life has multiple determinants, seizure frequency, fatigue, and depression are the most important factors affecting quality of life in patients with epilepsy. One or more seizures per month, severe fatigue, and depression are associated with lower quality of life in some but not all domains. Partial correlations demonstrated that fatigue was a significant independent predictor of quality of life. The present study confirms that fatigue can be a powerful predictor of quality of life.     

Wednesday July 5, 200613:30–15:00Poster Session 3Surgical Treatment/VNS

¹ M. Trimble (   ¹ Institute of Neurology, London, UK )
Purpose: Intractable seizures are common in patients with learning disability (LD), and the seizures may contribute to the LD. Control of seizures in LD represents a clinical challenge, but vagus nerve stimulation (VNS) is one option.
Method: Data from 396 cognitively challenged patients i.e., institutionalised, with LD or developmental delay treated with (VNS) therapy in addition to their regular medication were analysed from the VNS Therapy Patient Outcome Registry at 3, 12, and 24 months. Data on seizure reduction and quality of life (QoL) were analysed at 3, 12 and 24 months after implant.
Results: of 396 patients, 153 (38.6%) were < 18 years, with 80 patients (20.2%) < 12 years of age. Mean age was 24.5 years (range, 2–63). There was a median seizure reduction of 41% after 3 months, 54% at 12 months and 54% at 24 months. Seizure reduction ≥ 50% was reported in 47%, 55% and 55% of the patients after 3, 12 and 24 months, respectively. Seizure reduction ≥ 75% occurred in 26%, 33% and 37% of patients after 3, 12 and 24 months, respectively. Seizure reduction ≥ 90% was observed in 13%, 17% and 23% of patients after 3, 12 and 24 months, respectively. Regarding QoL, the percentage classified as "better" or "much better" were: alertness, 62%, 68% and 66%; mood, 41%, 48% and 45%; and achievements, 24%, 34% and 29%.
Conclusion: VNS Therapy is associated with seizure and QoL improvements in this population of cognitively challenged patients.     

Vagus Nerve Stimulation for Treatment of Partial Seizures: 1. A Controlled Study of Effect on Seizures

Summary: Vagus nerve stimulation (VNS) was shown to reduce seizure frequency in refractory epilepsy patients in two pilot studies. Based on these results, a multicenter, prospectively randomized, parallel, double-blind study of patients with refractory partial seizures was initiated. After a 12–week baseline period, identical vagus nerve stimulators were implanted and patients randomized to either a high or low 14–week VNS treatment paradigm. The primary objective was to demonstrate that high VNS (therapeutic parameters) was more effective in reducing partial seizure frequency than was low VNS (less or noneffective parameters). Patients continued receiving antiepileptic drugs (AEDs) with plasma concentrations held constant throughout the study. We report results of the first 67 patients to exit the 14-week acute phase. After 14 weeks of VNS, 31 patients receiving high VNS experienced a mean seizure frequency percentage reduction of 30.9%, which was statistically significant as compared with the mean seizure frequency percentage reduction of 11.3% in 36 patients receiving low VNS (p = 0.029, t test; p = 0.036, Wilcoxon rank-sum test). In addition to the significant intra group p-values, mean seizure frequency percentage change reached statistical significance for high VNS (p < 0.001) but not low VNS (p = 0.072) as compared with baseline. Twelve of 31 (38.7%) patients receiving high VNS achieved at least 50% reduction in seizure frequency whereas 7 of 36 (19.4%) patients receiving low VNS experienced at least 50% reduction after 14 weeks. The implant procedure and VNS therapy were well tolerated. Our study confirmed the effectiveness of VNS as treatment for epilepsy patients with refractorypartial seizures.     

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.     

Improvement in quality of life and sexual functioning in a comorbid sample after the unified protocol transdiagnostic group treatment

Patients with multiple mental disorders often experience sexual dysfunction and reduced quality of life. The unified protocol (UP) is a transdiagnostic treatment for emotional disorders that has the potential to improve quality of life and sexual functioning via improved emotion management. The present study evaluates changes in quality of life and sexual functioning in a highly comorbid sample treated with the UP in a group format. Forty-eight patients were randomly assigned to either a UP active-treatment group or a medication-only control group. Treatment was delivered in 14 sessions over the course of 4 months. Symptoms of anxiety and depression were assessed using the Beck Anxiety Inventory and Beck Depression Inventory. Sexual functioning was assessed by the Arizona Sexual Experience Scale (ASEX), and quality of life was assessed by the World Health Organization Quality of Life-BREF scale (WHOQOL-BREF). Quality of life, anxiety and depression all significantly improved among participants treated with the UP. Some improvement in sexual functioning was also noted. The results support the efficacy of the UP in improving quality of life and sexual functioning in comorbid patients.