Vagus Nerve Stimulation in 16 Children with Refractory Epilepsy

Summary: Purpose : Vagus nerve stimulation (VNS) has been reported to produce >90% reduction in the number of seizures in children with intractable epilepsy. These encouraging results need confirmation.
Methods : Sixteen children, 10 boys and 6 girls aged 4-19 years, were treated with VNS (Cyberonics, Webster, TX, U.S.A.) for 12-24 months. Seizure frequency, seizure severity, changes in quality of life (QOL: visual analogue scale), and side effects were recorded. Eight children had partial and 8 had generalized seizures; 4 of the latter had Lennox-Gastaut syndrome (LGS).
Results : During the tenth to twelfth month of VNS, 6 of 16 children experienced ≥50% reduction in seizure frequency. One girl became seizure-free. Seizure severity showed an average decrease in the score from 15 to 11. After 10 months of treatment, QOL was estimated to have improved ≥50% in 6 of 16 children. Reduction in seizure frequency, decreased seizure severity, and reported improvement in QOL did not entirely coincide. Six children experienced hoarseness, 1 had neck pain, 2 had hypersalivation, 2 experienced tiredness, 2 had aspiration episodes during liquid intake, and 6 had electrical transmission problems; in 4 the problem has been surgically corrected. Five stimulators were turned off due to lack of efficacy.
Conclusions : Six of 16 children with refractory epilepsy treated with VNS improved, with a reduction not only in seizure frequency but also in seizure severity and in QOL.     

A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation

Context. Antiepileptic drugs (AEDs) are frequently used for their beneficial mood effects.Objective. We sought to determine if there was a quantifiable effect on mood of the vagus nerve stimulator (VNS) when used as an antiseizure treatment.Design. Mood was assessed before and 3 months after VNS implantation in adult epilepsy patients. A group of adult epilepsy patients on stable AED regimens were used as a comparison group. AED regimens were unchanged during the study. The change in mood scale scores across time was assessed by t test (intragroup) and two-factor repeated-measures ANOVA (intergroup).Setting. An epilepsy center in a university hospital was the setting.Subjects. Twenty consecutive adult epilepsy patients undergoing VNS implantation to improve seizure control and twenty adult seizure patients with no intervention were enrolled.Main outcome measures. The mood scales used were the Cornell Dysthymia Rating Scale (CDRS) and the Hamilton Depression (Ham-D), Hamilton Rating Scale for Anxiety (Ham-A), and Beck Depression Inventory (BDI) scales.Results. The VNS group showed a significant decrease in mood scale scores across time (t test CDRS P = 0.001, Ham-D P = 0.017, BDI P = 0.045), indicating a decrease in depressive symptoms. The Ham-A scores in the VNS group and the comparison group scores did not significantly change across time. There were no significant differences between groups across time, although the BDI approached significance at P = 0.07. The VNS group had a significant decrease in seizure frequency compared with the comparison group (P = 0.01). There was no difference in mood scales over time between the VNS treatment responders (defined by >50% decrease in seizure frequency) and nonresponders, suggesting dissociation between seizure frequency reduction and mood change.Conclusion. VNS treatment is associated with mood improvement as measured by multiple scales, but differences in mood scale scores over time between the VNS and a comparison group were not found.     

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.     

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.     

Vagus Nerve Stimulation for Patients in Residential Treatment Facilities

This analysis compared the effectiveness of vagus nerve stimulation (VNS) therapy among patients with intractable seizures: a group living in residential treatment facilities (RTF) with a group not living in RTFs (non-RTF). Among a constant cohort of patients with baseline, 3-month, and 12-month data, the RTF group had significantly (P < 0.05) larger numbers of patients with generalized seizures, previous callosotomy, psychiatric disorders, behavioral problems, and Rett's syndrome. Median seizure reductions after 3 months were 33% in the RTF group and 49% in the non-RTF group (P < 0.001); after 12 months, 50% (RTF) and 56% (non-RTF). After both 3 and 12 months, alertness, mood, postictal recovery, and cluster seizures improved in more than a third of patients in both groups. Because VNS therapy does not interact with medications and is delivered automatically, it should be seriously considered for patients with intractable epilepsy who reside in RTFs.     

Vagus Nerve Stimulation for Symptomatic Generalized Epilepsy: A Pilot Study

Summary: Purpose: Patients with symptomatic generalized epilepsy (SGE) may have antiepileptic drug (AED)-resistant mixed generalized seizures. Vagus nerve stimulation (VNS) reduces partial seizures and may help SGE.
Methods: We added VNS to stable AED therapy in five SGE patients. Nine-month postoperative VNS treatment seizure rates were compared to a 1 -month preoperative baseline.
Results: All patients had mixed generalized seizures, EEG generalized slow spike-and-wave and behavioral abnormalities. Median number of previous AEDs taken was 6 (range 5–12). Median baseline seizure rate was 75honth (range 29–1 10). VNS produced a median seizure rate production of -41% (range -40%–85%). Adverse events reported in one patient each were: incisional infection, choking sensation and voice change; and coughing (noted by two patients). One patient discontinued VNS due to coughing.
Conclusions: We conclude that VNS may be useful add-on therapy for SGE. A larger, controlled, and blinded trial may be warranted.     

Efficacy and Safety of Vagus Nerve Stimulation in Patients With Complex Partial Seizures

Summary: A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising.     

Vagus Nerve Stimulation for Intractable Epilepsy: Outcomes in Children and Adults

Objectives. Vagus nerve stimulation (VNS) is an accepted treatment for medically intractable epilepsy. However, predictive factors associated with responsiveness to VNS remained unclear. We therefore sought to identify predictive factors that influence responsiveness to VNS in both children and adults. Materials and Methods. We evaluated a retrospective series of 31 patients who underwent VNS for intractable epilepsy at Asan Medical Center from 1998 to 2006. Eighteen patients were younger than 18 years, while 13 patients were aged 18 years or older. We assessed mean seizure frequency, the number of antiepileptic drugs each patient was taking, seizure type, etiology, age at seizure onset, age at implantation, and duration of epilepsy. Results. Forty‐three percent of all patients had a seizure reduction of more than 50%. Ten (59%) children had a 50% reduction in their seizures, while three adults (23%) had such a response. Two factors were significantly different between responders and non‐responders: age at implantation and age of seizure onset. In a logistic regression analysis, however, no factors were independently associated with the response to VNS. Transient hoarseness and cough were observed in eight of all patients and wound infection and generator failure in one patient each. Conclusions. These results suggest that VNS may be a more effective treatment in children with intractable epilepsy than in adults. It remains difficult to predict which patients will respond to VNS therapy.     

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.     

Setting Up a Successful Vagus Nerve Stimulation Service for Patients With Difficult-to-Treat Depression

BackgroundA substantial number of patients with major depressive disorder (MDD) do not sufficiently remit after the first lines of antidepressant treatments, making them vulnerable to poor clinical outcomes. Patients who have not had adequate resolution of their depressive symptoms after four antidepressant treatments and/or have been experiencing their current episode of MDD for two years or more (with insufficient responses to adequate antidepressant treatments) should be evaluated for antidepressant vagus nerve stimulation (VNS Therapy). Adjunctive VNS Therapy is a promising long-term treatment option for patients with difficult-to-treat depression (DTD), offering significantly improved remission rates in comparison with usual treatments. However, VNS Therapy requires specialized treatment centers to support patients.Materials and MethodsIn this narrative review, we aim to outline the necessary steps for setting up an antidepressant VNS Therapy service in an efficient manner.ResultsEstablishing a VNS Therapy service requires several high-level considerations: initiation of a collaborative multidisciplinary team of health care professionals; developing a surgical pathway for implantation; consideration of reimbursement and health care coverage; setting up a specialist clinic to identify optimal candidates for VNS Therapy; educating patients and their families about VNS Therapy; and training health care providers on patient-specific VNS Therapy treatment and long-term treatment management.ConclusionsAntidepressant VNS Therapy is a promising treatment option for the long-term treatment of patients with DTD. We have successfully initiated four VNS Therapy service centers for DTD in the United States, Austria, and Germany. Based on our experiences and lessons learned, herein, we have provided advice to psychiatric centers planning to set up a VNS Therapy service for their patients with DTD.     

Scalp and Limbic P3 Event-Related Potentials in the Assessment of Patients with Temporal Lobe Epilepsy

Auditory oddball scalp and limbic P3s were recorded from 18 patients with unilateral temporal lobe epilepsy (TLE) prior to seizure surgery. Limbic P3s were unilaterally absent ipsilateral to the seizure focus and were present in the nonepileptogenic temporal lobe in all 18 cases studied. Scalp P3s, recorded from C3 and C4, on the other hand, were elicited bilaterally and there was no significant difference in amplitude or latency between the epileptogenic and nonepileptogenic sides. These data concur with studies of scalp P3 performed following surgery and suggest that the assessment of the contribution of limbic P3 to scalp P3 may be masked by volume conduction effects and other generators of P3. We conclude that the P3 recorded from central scalp sites, unlike its limbic counterpart, offers little clinical information in the presurgical assessment of patients with TLE.     

Vagus Nerve Stimulation in the Developmentally Disabled

Vagus nerve stimulation (VNS) with the neuro cybernetic prosthesis (NCP) is an approved treatment of partial seizures for patients 12 years and older. Developmentally disabled or mentally retarded patients with epilepsy may also benefit from VNS; however, their evaluation and management pose greater problems. A retrospective chart review was conducted on all patients diagnosed with mild to severe mental retardation who had an NCP implanted. Records of these 21 patients, ranging in age from 3 to 56 years, were reviewed regarding VNS efficacy, side effects, behavioral changes, and alterations in antiepileptic drugs (AEDs). Seizure types included partial onset and generalized. Sixteen patients had clearly evaluable seizures both pre- and postimplant, with a greater than 50% reduction in seizures noted in 68% (11/16) after 6 months of implant. There were no adverse events that prevented chronic stimulation. Institutional staff and family members were provided with both pre- and postoperative education on VNS and magnet use. VNS appeared to be an effective and well-tolerated therapy in this group of developmentally disabled patients with refractory epilepsy.     

迷走神经刺激治疗难治性癫痫(附11例报告)

目的 探讨迷走神经刺激术治疗顽固性癫痫的治疗效果和机制.方法 2004年4月～2006年12月,11例顽固性癫痫进行了迷走神经刺激治疗,其中3例为脑炎后部分性继发全身发作,3例为Lenonx-Castaut Syndrome(LGS),另外5例为原因不明的全身强直阵挛性发作.手术在全麻下进行,在甲状软骨水平左侧胸锁乳突肌前缘作3cm皮肤切口,分离肌肉并显示左侧迷走神经干约3cm,将螺旋型迷走神经刺激电极缠绕于迷走神经干上,在左腋前线作一皮肤切口,将刺激器置入皮下并与刺激电极相连接及固定.术后2周开机,调试参数,刺激电流从0.25mA逐渐调至1.5mA,刺激模式为:刺激时间为30秒,间歇5分钟,脉宽为500～1000μs,频率为30Hz.结果 术后3个月～2年随访,癫痫发作频率平均减少60%,发作程度减轻,全身强直阵挛性发作明显减少,精神状态明显改善.结论 迷走神经刺激手术创伤小,副作用少,术后能减少病人发作的频率,提高病人生活质量,对不适合开颅手术的难治性癫痫是一种有效的治疗方法.     

Impact of Cardiac-Based Vagus Nerve Stimulation Closed-Loop Stimulation on the Seizure Outcome of Patients With Generalized Epilepsy: A Prospective,Individual-Control Study

ObjectivesWe designed a prospective, individual-controlled study to evaluate the effect of cardiac-based VNS (cbVNS) in a cohort of patients with generalized epilepsy (GE).Materials and MethodsTwenty patients were included. They were followed up for six months under regular VNS (rVNS) and subsequently for six months during cbVNS. Stimulation parameters were 500 μsec, 30 Hz, and up to 2.5 mA. Seizure frequency was documented after two, four, and six months during the rVNS and cbVNS phases. Patients with at least 50% seizure frequency reduction were considered responders. The total and relative amount of stimulation cycles generated by both rVNS and cbVNS activation were documented. Findings during rVNS were compared to baseline and cbVNS data were compared to those during rVNS.ResultsThere was a significant decrease in mean seizure frequency (61% [95% CI, 48-74]; p < 0.001) during the rVNS phase compared to baseline. There was no additional significant (16% [95% CI, 4-35]; p = 0.097) mean seizure frequency reduction during cbVNS compared to the rVNS phase. Fifteen patients (75%) were considered responders after rVNS. Four patients (20%) were considered responders after six months of cbVNS. During the cbVNS phase, the mean total number of cycles/day was 346, 354, and 333 for months two, four, and six, respectively; the cycles generated by rVNS were 142, 138, and 146 for months two, four, and six, respectively; and cycles generated by cbVNS were 204, 215, and 186 for months two, four, and six, respectively. There was no relationship between the mean total number of cycles (−6[95% CI, −85 to 72]; p = 0.431), the mean number of auto-stimulation cycles (27[95% CI,−112 to 166]; p = 0.139), the mean number of regular cycles (−33[95% CI,−123 to 57]; p = 0.122), or the mean percentage of auto-stimulation cycles (13[95% CI,19- 45]; p = 0.109) and outcome during the cbVNS phase. Eight patients showed some decrease in seizure frequency during cbVNS.ConclusionsrVNS was effective in reducing seizure frequency in patients with generalized epilepsy, but activation of the cbVNS feature did not add significantly to rVNS efficacy. On the other hand, although not statistically significant, 40% of the patients showed some reduction in seizure frequency, which might prove useful at an individual level.     

Effects of Vagus Nerve Stimulation on Sleep-Disordered Breathing,Daytime Sleepiness,and Sleep Quality in Patients With Drug-Resistant Epilepsy

Background and PurposeThis study aimed to determine the long-term effects of vagus nerve stimulation (VNS) on sleep-disordered breathing (SDB), daytime sleepiness, and sleep quality in patients with drug-resistant epilepsy (DRE). It also investigated the relationships among these main effects, clinical characteristics, and VNS parameters.MethodsTwenty-four patients were recruited. Paired t-tests and multiple linear regression analyses were performed to determine how the demographic and clinical characteristics of the patients influenced the variables that changed significantly after VNS treatment.ResultsAfter VNS, the patients showed significant increases in the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), apnea index, hypopnea index, and oxygen desaturation index (ODI), as well as a significant decrease in the lowest arterial oxygen saturation (SaO₂ nadir) (p<0.05). The multiple linear regression analyses demonstrated that the predictor of larger increases in AHI and RDI was being older at baseline, and that the predictor of a larger increase in apnea index was a longer epilepsy duration. The strongest predictor of a larger increase in ODI was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration. The strongest predictor of a larger decrease in SaO₂ nadir was a higher frequency of aura episodes at baseline, followed by a longer epilepsy duration.ConclusionsThis study has confirmed that VNS improves seizure control in patients with DRE, whereas it increases obstructive sleep apnea (OSA). Furthermore, the increase in OSA is affected by age and the duration of epilepsy. Therefore, careful observation and monitoring of SDB is recommended in patients who undergo VNS.     

A Comprehensive Review of Vagus Nerve Stimulation for Depression

ObjectivesVagus nerve stimulation (VNS) is reemerging as an exciting form of brain stimulation, due in part to the development of its noninvasive counterpart transcutaneous auricular VNS. As the field grows, it is important to understand where VNS emerged from, including its history and the studies that were conducted over the past four decades. Here, we offer a comprehensive review of the history of VNS in the treatment of major depression.Materials and MethodsUsing PubMed, we reviewed the history of VNS and aggregated the literature into a narrative review of four key VNS epochs: 1) early invention and development of VNS, 2) path to Food and Drug Administration (FDA) approval for depression, 3) refinement of VNS treatment parameters, and 4) neuroimaging of VNS.ResultsVNS was described in the literature in the early 1900s; however, gained traction in the 1980s as Zabara and colleagues developed an implantable neurocybernetic prosthesis to treat epilepsy. As epilepsy trials proceed in the 1990s, promising mood effects emerged and were studied, ultimately leading to the approval of VNS for depression in 2005. Since then, there have been advances in understanding the mechanism of action. Imaging techniques like functional magnetic resonance imaging and positron emission tomography further aid in understanding direct brain effects of VNS.ConclusionsThe mood effects of VNS were discovered from clinical trials investigating the use of VNS for reducing seizures in epileptic patients. Since then, VNS has gone on to be FDA approved for depression. The field of VNS is growing, and as noninvasive VNS quickly advances, it is important to consider a historical perspective to develop future brain stimulation therapies.