Vagus nerve stimulation in children with intractable epilepsy: indications,complications and outcome

Purpose  To analyze the indication, complications and outcome of vagus nerve stimulation in intractable childhood epilepsy. Materials and methods  We retrospectively reviewed the data of 69 children who had insertion of vagal nerve stimulator (VNS) between June 1995 and August 2006 for medically intractable epilepsy. Outcome was based on the Engel's classification. Statistical analysis of the data was also done to see if any of the parameters significantly influenced the outcome. Result  Thirty-eight patients (55.08 %) had a satisfactory outcome (Engel class I, II or III), and in 31 patients (44.92 %), there was no worthwhile improvement of seizures (Engel class IV). There was no statistical significance between the type of seizure and outcome (Fisher's exact test, p = 0.351). Statistical analysis also showed that the following parameters did not significantly influence the outcome (p > 0.05): age at insertion of VNS, age of first fit, duration between first fit and insertion of VNS and the length of follow-up. Complications included infection, lead fracture, fluid collection around the stimulator, neck pain and difficulty swallowing. Conclusion  Vagus nerve stimulation is a relatively safe and potentially effective treatment for children with medically intractable epilepsy.     

Vagus nerve stimulation for refractory epilepsy in children: More to VNS than seizure frequency reduction

Purpose :  Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy for refractory epilepsy. Studies of VNS in children report mainly seizure frequency reduction as a measure of efficacy and clinical details are often scanty. We report our experience with VNS in children with refractory epilepsy and emphasize the positive effects of VNS in terms of seizure severity.
Methods :  We reviewed 26 consecutive children who had VNS with a minimum follow-up period of 18 months. We examined their clinical characteristics, seizure types, seizure frequency, epilepsy syndrome diagnosis, and response to VNS in terms of seizure frequency and seizure severity.
Results :  Fifty-four percent of patients responded to VNS with ≥50% seizure frequency reduction. Patients with Lennox-Gastaut syndrome (LGS) and tonic seizures had a higher responder rate; 78% (seven of nine patients) (p < 0.01). Status epilepticus (SE) episodes were reduced or ceased in the four patients with recurrent SE. Seizure severity, duration, and recovery time decreased in all responders. Increased alertness was reported in all responders and three nonresponders.
Conclusion :  Decreased seizure severity, recovery time, abolition of daytime drop attacks, and reduced hospitalization due to SE improved patients' lives over and above the benefit from seizure frequency reduction.     

Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome

PURPOSE: Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox-Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS. METHODS: A six-center, retrospective study evaluated the effectiveness of VNS therapy in patients with LGS at 3 and 6 months and compared preimplant and postimplant seizure frequency. Adverse effects and quality of life (QOL) were included as secondary measures. RESULTS: Fifty patients, median age 13 years, with medically refractory epilepsy, were implanted. Median age at onset of seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been tried before implantation. Data-collection forms were designed for retrospectively gathering data on each patient's preimplant history, seizures, implants, device settings, QOL, and adverse events. Median reductions in total seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most common adverse events reported were voice alteration and coughing during stimulation. Other uncommon adverse events included increased drooling and behavioral changes. Investigators noted that QOL had improved for some patients in the study. CONCLUSIONS: VNS is an effective treatment for medically refractory epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.     

Effects of vagus nerve stimulation on sleep-related breathing in epilepsy patients

PURPOSE: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients. METHODS: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21-58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial. RESULTS: Baseline PSGs: One of 16 patients had an apnea-hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels. CONCLUSIONS: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.     

Sleep disordered breathing in children receiving vagus nerve stimulation therapy

ObjectiveThe effects of vagus nerve stimulation (VNS) on sleep disordered breathing (SDB) have been reported in limited case series. Detailed studies, particularly in the pediatric population, have not been performed. The primary purpose of this study is to describe clinical characteristics, polysomnographic findings, and management of children treated with VNS.MethodsA retrospective review of medical records and polysomnography data was performed in patients ages 0–20 years old receiving VNS therapy for refractory epilepsy at Cincinnati Children's Hospital Medical Center.Results22 subjects met the inclusion criteria. 50% were male. The mean age at the time of VNS insertion was 8.4 ± 4.0 years. The mean age at the first PSG was 10.6 ± 4.3 years. Common presentations to sleep clinics included snoring (77.3%), frequent nighttime awakening (68.1%), and parasomnias (63.6%). The median apnea-hypopnea index (AHI) was 4.5/hr (IQR 3.0–13.1) and the median obstructive index (OI) was 4.1/hr (1.5–12.8). Obstructive sleep apnea (OSA) was diagnosed after VNS insertion in 19 patients (86.4%), 8 of which (36.3%) had severe OSA. Six patients (27.3%) had significant hypoventilation. For management, 6 patients (27.2%) were treated with bilevel PAP, 3 patients (13.6%) with CPAP, 2 patients (9.1%) with ventilator, 4 patients (18.2%) with upper airway surgeries, and 9 patients (40.9%) received medications only.ConclusionsSDB is common in pediatric patients with medically refractory epilepsy managed with VNS who were referred to sleep medicine clinics. Both OSA and nocturnal alveolar hypoventilation are relatively common in this population. Management of SDB often involves the use of positive airway pressure therapy or upper airway surgeries. Further studies are needed to assess the prevalence, risk factors, and the effect of treatments on epilepsy control. This study highlights the need for screening of SDB prior to and following VNS implantation.     

Vagus nerve stimulation elevates seizure threshold in the kindling model

Purpose: Vagus nerve stimulation (VNS) provides partial relief of medically refractory partial seizures in a subset of patients. The optimal pattern of stimulation and the mechanism of the antiseizure effects are uncertain. Establishing the efficacy of VNS in an animal model of epilepsy would provide an experimental preparation with which to address these questions. We sought to determine whether VNS exerted antiseizure effects in the kindling model of epilepsy. Methods: We implanted adult rats with bipolar stimulating electrodes in the right amygdala and VNS devices around the left vagus nerve. Following induction of kindling, electrographic seizure threshold (EST) was determined by quantifying the amygdala electrode current required to evoke a seizure. Once stable ESTs were established, VNS devices were programmed to deliver U.S. Food and Drug Administration (FDA)–approved, clinically used (standard) or an experimental (microburst) pattern of stimulation of variable intensity. VNS devices were programmed identically in control animals except that no current was delivered. EST was examined at 60 min and 1 week in the control and vagus nerve stimulated groups. Key Findings: Significant reductions of EST values were detected in control animals when tested both 60 min and 1 week following device programming. Both clinically used and experimental patterns of VNS prevented the reduction of EST evident in control animals when tested either 60 min or 1 week after device programming. Significance: These findings establish an experimental preparation with which to elucidate the antiseizure mechanisms of VNS and to determine patterns of VNS most effective at elevating seizure threshold.     

Vagus nerve stimulation therapy induces changes in heart rate of children during sleep

PURPOSE: This study analyzed changes in the heart rates of children receiving vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. METHODS: Changes in the heart rates of ten children receiving VNS therapy for pharmacoresistant epilepsy were evaluated with polysomnographic recordings, including electrocardiogram (ECG), EEG, thoraco-abdominal distension, nasal airflow, and VNS artifacts. Measurements during stimulation were compared with those at baseline for each patient. RESULT: While the VNS therapy pulse generator was delivering stimulation, the heart rates of four children increased significantly (p < 0.01), decreased for one child, and increased at the end of the stimulation for one child. The heart rates of four children did not change. Changes in heart rate varied during VNS, within stimulation cycles for individual children and from one child to another. Changes in heart rate differed between rapid eye movement (REM) and non-REM (NREM) sleep states. Respiratory changes (increases in frequency and decreases in amplitude) were concomitant with the changes in heart rate. CONCLUSION: In this case series of children with pharmacoresistant epilepsy, cardiorespiratory variations occurred while the VNS therapy pulse generator was delivering stimulation. Understanding these variations may allow further optimization of VNS parameters.     

Vagus nerve stimulation therapy: 5-year or greater outcome at a university-based epilepsy center

OBJECTIVE: This retrospective study documented long-term outcome of patients receiving vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. METHODS: Medical charts of 28 patients implanted for 5 years or longer were reviewed for changes in seizure frequency after 1 year of VNS therapy and at follow up, which ranged from 5 to 7 years. Numbers of antiepileptic drugs (AEDs) taken by the patients were also computed at 1 year and follow up. One patient had died and one had discontinued VNS therapy; data were available for 26 patients. Results: The median percent change in seizure frequency from baseline increased from -28% (P = 0.0053, Wilcoxon signed-rank test) at 12 months to -72% (P < 0.0001) at follow up. Some patients whose seizure frequency was not reduced during the initial 12 months of VNS therapy did experience reductions in seizure frequency during the follow-up period. CONCLUSION: In this retrospective study, the effectiveness of VNS therapy increased over time. Physicians should be aware that response to VNS therapy may be delayed for some patients.     

Vagus nerve stimulation induces concomitant respiratory alterations and a decrease in SaO2 in children

PURPOSE: To analyze respiratory alterations and effects on SaO(2) caused by vagus nerve stimulation (VNS) in children with epilepsy. METHODS: Polysomnographic recordings, including electroencephalography, thoracoabdominal distention, nasal airflow, SaO(2), and VNS artifact were evaluated in 10 children with pharmacoresistant epilepsy treated with VNS. RESULTS: Each VNS caused a significant increase in respiratory frequency (p < 0.05) throughout the stimulation period and a decrease in thoracoabdominal-distention amplitude (p < 0.05), especially at the beginning of the stimulation. These respiratory alterations induced a decrease in SaO(2) from 1 to 5%. The effects of VNS on respiration differed significantly between rapid-eye-movement (REM) and non-REM (NREM) sleep states. CONCLUSIONS: VNS caused a pronounced change in respiration in children with epilepsy, and this induced a decrease in SaO(2). It is possible that VNS has a neuroprotective effect, and this possibility calls for further investigation.     

迷走神经刺激术早期不同程控方案在儿童难治性癫痫中的应用效果

目的通过比较迷走神经刺激术(VNS)早期不同程控方案在儿童难治性癫痫中的应用效果和安全性,寻找最佳早期程控方案。方法回顾性分析首都儿科研究所附属儿童医院神经外科2016年8月至2018年12月行VNS治疗的54例难治性癫痫患儿的临床资料。根据术后程控方案的刺激电流幅度,分为低参数组(≤1 mA,28例)和高参数组(>1 mA,26例)。术后6个月行临床随访,对比两组的治疗有效率和治疗相关并发症的发生率。结果VNS治疗6个月,54例患儿的无发作率为13.0%(7/54),总体有效率为66.7%(36/54)。其中低参数组的有效率(82.1%,23/28)高于高参数组(50.0%,13/26)(χ^2=6.268,P=0.012)。54例患者术后总体并发症的发生率为7.4%(4/54)。低参数组治疗相关并发症的发生率(0%)与高参数组(15.4%,4/26)之间的差异无统计学意义(χ^2=4.652,P=0.102)。结论VNS是治疗儿童难治性癫痫的有效手段,相对于高参数程控方案,患儿可能从低参数程控方案获益更多。     

Acute single photon emission computed tomographic study of vagus nerve stimulation in refractory epilepsy

PURPOSE: Left-sided vagus nerve stimulation (VNS) is an efficacious treatment for patients with refractory epilepsy. The precise mechanism of action remains to be elucidated. Only limited data on VNS-induced changes in regional cerebral blood flow (rCBF) are available. The aim of this study was to investigate rCBF changes during initial VNS with single-photon emission computed tomography (SPECT). METHODS: In 12 patients (8 women, 4 men) with mean age of 32 years and mean duration of epilepsy of 19 years, VNS-induced rCBF changes were studied by means of a 99mTc-ethyl cysteinate dimer activation study with a single-day split-dose protocol before and immediately after initial stimulation. Images were acquired on a triple-head camera with fan-beam collimators and were reconstructed with scatter and attenuation correction. After coregistration to a standardized template, both a semiquantitative analysis using predefined volumes-of-interest (VOIs) as well as voxel-by-voxel analysis of the intrasubject activation were performed. During follow-up, efficacy of VNS in terms of seizure-frequency reduction was studied. RESULTS: The semiquantitative analysis, with reference to the total counts in all VOIs, revealed a significant decrease of activity in the left thalamus immediately after the initial stimulation train. These results agreed with voxel-by-voxel analysis. In our study ipsilateral thalamic hypoperfusion was the most significant finding. Mean frequency of complex partial seizures was reduced from 30 per month before implantation to six per month after implantation. CONCLUSIONS: VNS induces rCBF changes immediately after initial stimulation that can be studied with SPECT. VNS-induced changes in the thalamus may play an important role in suppression of seizures. However, no significant relation between the level of hypoperfusion and subsequent clinical efficacy was found.     

迷走神经刺激术在难治性癫痫领域的临床进展

迷走神经刺激术(vagus nerve stimulation,VNS)是通过躯体性刺激治疗神经-精神疾病的一种方法.自1883年以来,许多学者对VNS的抗癫痫作用进行了研究,最终认为VNS是治疗难治性癫痫的新途径[1-3].1997年7月VNS首次通过美国食品药物管理局(FDA)认证,用于成人和年龄大于12岁青少年癫痫的辅助治疗.目前为止全球已经有超过100 000的患者接受了VNS治疗[4].     

迷走神经刺激术治疗顽固性癫痫初步探讨

目的 探讨迷走神经刺激术治疗顽固性癫痫的治疗效果.方法 对21例顽固性癫痫患者进行迷走神经刺激手术治疗,术后2周开机,分次调试参数,脉冲发生器输出电流从0.25 mA逐渐增加,但不超过3.0 mA,刺激时间为30 s,间歇5 min,信号频率为20～30 Hz,脉宽为250～1000μs.对治疗效果进行随访,分析治疗效果.结果 经4-16个月刺激,McHugh Ⅰ级3例,Ⅱ级7例,Ⅲ级9例,Ⅴ级2例.其中10例患者癫痫发作减少50%以上.结论 迷走神经刺激术治疗顽固性癫痫是一种相对安全、有效的治疗方法 .     

Vagus nerve stimulation for the treatment of bilateral independent temporal lobe epilepsy

PURPOSE: We studied the effect of vagus nerve stimulation (VNS) on seizure reduction in patients with intractable epilepsy with bilateral independent temporal lobe foci. METHODS: Ten patients who met the criterion of the presence of two distinctive clinical and ictal EEG seizure patterns were identified and followed up for 1 year. RESULTS: Six patients had >50% reduction in their seizure frequency that persisted up to > or =1 year of follow-up, whereas four patients reported small or no reduction in their partial seizures. CONCLUSIONS: VNS is often effective and well tolerated in this select group of intractable epilepsy patients.     

Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans

PURPOSE: We present three children who underwent right-sided vagus nerve stimulation (R-VNS). This treatment option for people with refractory epilepsy has not been described in children. METHODS: We reviewed our database of >350 patients implanted with vagus nerve stimulators and now describe our experience in three patients with R-VNS for the treatment of intractable seizures. All three patients improved dramatically with left-sided vagus nerve stimulation (L-VNS), but the devices had to be removed because of infection. The patients were thought to be at high risk for nerve injury if they were reapproached for L-VNSs; therefore R-VNSs were implanted. RESULTS: All three patients with an R-VNS had a reduction in seizures. Our first patient has had an R-VNS for 5 years; he has been seizure free for >2 years on R-VNS monotherapy. The second patient had an R-VNS for 8 months. His seizure control improved slightly, but not as dramatically as with L-VNS. The third child has had an R-VNS for >7 months and has cessation of his most disabling seizure type (generalized tonic-clonic seizures). None of the patients had cardiac side effects from therapeutic R-VNS. However, two of the three patients had respiratory events with R-VNS. CONCLUSIONS: VNS is known to be an effective treatment in pharmacoresistant epilepsy. R-VNS should be considered if a patient has significant benefit from L-VNS but is unable to continue with L-VNS. R-VNS appears also to have antiepilepsy effects. Additionally, our case report suggests that in some patients, a differential response is found regarding seizure control with R-VNS or L-VNS, raising the question whether L-VNS failures should pursue a trial of R-VNS. Patients should be cautioned and monitored for reactive airway disease if they undergo R-VNS. More research is needed to compare the effects of right- and left-sided VNS on cardiac and pulmonary function in humans and to determine which has the best antiseizure effect.     

迷走神经刺激术治疗药物难治性癫痫的价值

尽管目前癫痫的药物治疗已取得较大进展,但仍有20％～30％的患者对癫痫药物治疗反应差,部分癫痫发作难以有效控制,即所谓的药物难治性癫痫。癫痫病灶切除术是治疗药物难治性癫痫的有效方法,但并非所有患者均能找到确切病灶,而且部分患者手术后效果不佳。1988年,迷走神经刺激术(vagus nerve stimulation,VNS)开始应用于治疗药物难治性部分性癫痫,为药物难治性癫痫提供了一种新的治疗方法。     

迷走神经刺激术治疗药物难治性癫痫的初步研究

目的 探讨迷走神经刺激术治疗药物难治性癫痫的方法及效果. 方法 回顾性分析上海交通大学医学院附属仁济医院神经外科自2007年1月至2011年1月收治的14例药物难治性、全身性癫痫患者临床资料,其中脑炎后继发癫痫6例,外伤后继发癫痫3例,原因不明5例,所有患者均行左侧迷走神经刺激术治疗.术后3周内开机,初始刺激参数为:刺激电流0.25 mA,频率30 Hz,刺激时间30 s,间歇时间5 min,脉宽500 μs.刺激电流强度以0.25 mA为一调整单位逐渐递增,并综合其他参数调控以到达满意疗效. 结果 随访3月以上,14例患者术后发作频率平均减少63.6％,其中3例发作频率减少＜50％,11例发作频率减少≥50％,6例发作频率减少＞80％,2例发作停止.5例患者使用磁铁后发作控制得到改善. 结论 迷走神经刺激术是一种治疗药物难治性癫痫有效、安全的方法,对全身性癫痫发作患者同样有效.     

Vagus nerve stimulation in children less than 5 years old

Introduction Vagus nerve stimulation (VNS) has been used in both adults and older children with varying success.Materials and methods We retrospectively reviewed our experience with VNS in very young children (below 5 years old). The mean age at stimulator implantation was 20.5 months. Two patients were below 2 years old at implantation and two patients were below 1 year old at their initial surgery. The average follow up time for this group was 22 months.Results Of the six patients (three males and three females) with long-term follow up, 83% had a significant decrease in the frequency of their seizure. Of these, two are seizure-free (33%), three are improved (50%), and one (17%) has had no change in seizure status at their most recent clinical examination. Age at implantation of the vagus nerve stimulator did not seem to correlate with patient success. In this group, atonic seizures were found to best respond to VNS with cessation of this type of seizure in two patients. No patients were made worse by the procedure and no morbidity was observed related to VNS.Conclusions Based on our small patient cohort, it appears that VNS in very young children with life-threatening epilepsy can be efficacious. Larger groups and other institutional experiences are now needed to verify our findings.