Abstract：
OBJECTIVE: To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations.
METHODS: A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age ≤ 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with ≤ 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran\'s Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher\'s exact, and chi-squared tests. This systematic review was not registered.
RESULTS: Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures\' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient\'s sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality.
CONCLUSIONS: RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.
METHODS: A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age ≤ 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with ≤ 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran\'s Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher\'s exact, and chi-squared tests. This systematic review was not registered.
RESULTS: Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures\' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient\'s sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality.
CONCLUSIONS: RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.
摘要：
目的：评估耐药癫痫患儿的反应性神经刺激（RNS）疗效，比较两个或两个以下发作灶的患者与多灶性或全身性癫痫患者之间的反应率（发作频率降低≥50％）。这项研究旨在解决有关儿科人群RNS有效性的知识差距。
方法：系统综述和荟萃分析包括来自PubMed，Embase,和WebofScience到2023年11月，包括17项回顾性研究和24例患者的病例系列，来自我们的实践，总共105名患者。患者的纳入标准为年龄≤18岁，诊断为DRE。排除标准是非人类受试者和未使用RNS治疗DRE的情况。研究纳入标准是详细说明RNS的使用，并将≤2个病灶的患者与其他病灶进行比较。研究排除标准是未能指定RNS导线放置或癫痫类型。对于所有非随机研究，使用ROBINS-I工具评估偏倚风险。将效果大小和方差汇总，以提供RNS疗效的综合衡量标准，使用I2统计和Cochran'sQ检验评估研究结果的一致性。使用IBMSPSS进行统计分析。我们分析了人口统计，癫痫病史,治疗结果，和RNS细节使用描述性和推理统计，包括Wilcoxon-Mann-Whitney,费希尔的精确,和卡方检验。该系统审查未注册。
结果：17项回顾性研究和单机构病例系列，包括105名儿科患者，进行了分析。计算效果大小和置信区间以量化治疗效果。分析显示，RNS降低了一系列小儿癫痫综合征的癫痫发作频率，无论癫痫发作如何，多焦点,或广义起源。RNS的有效性不受患者性别的影响，癫痫发作的年龄，或者神经和精神合并症的存在。先前的迷走神经刺激手术和癫痫综合征的存在是与RNS几乎完全缓解癫痫发作的可能性较低相关的因素。强调治疗患有全身性癫痫或先前介入失败的患者的复杂性。电极特征与应答率的混合结果强调了进一步研究患者个性化手术策略的必要性。我们研究的局限性包括对回顾性研究的依赖，这引入了潜在的偏差，限制了推断因果关系的能力。
结论：RNS是一种安全有效的治疗儿童DRE患者，合并症，和焦点可变性。FDA年龄和病灶限制，伴随着病人和医生的犹豫，可能限制了用RNS有效治疗小儿DRE的潜力。建议进行前瞻性随机试验来验证这些发现。
方法：系统综述和荟萃分析包括来自PubMed，Embase,和WebofScience到2023年11月，包括17项回顾性研究和24例患者的病例系列，来自我们的实践，总共105名患者。患者的纳入标准为年龄≤18岁，诊断为DRE。排除标准是非人类受试者和未使用RNS治疗DRE的情况。研究纳入标准是详细说明RNS的使用，并将≤2个病灶的患者与其他病灶进行比较。研究排除标准是未能指定RNS导线放置或癫痫类型。对于所有非随机研究，使用ROBINS-I工具评估偏倚风险。将效果大小和方差汇总，以提供RNS疗效的综合衡量标准，使用I2统计和Cochran'sQ检验评估研究结果的一致性。使用IBMSPSS进行统计分析。我们分析了人口统计，癫痫病史,治疗结果，和RNS细节使用描述性和推理统计，包括Wilcoxon-Mann-Whitney,费希尔的精确,和卡方检验。该系统审查未注册。
结果：17项回顾性研究和单机构病例系列，包括105名儿科患者，进行了分析。计算效果大小和置信区间以量化治疗效果。分析显示，RNS降低了一系列小儿癫痫综合征的癫痫发作频率，无论癫痫发作如何，多焦点,或广义起源。RNS的有效性不受患者性别的影响，癫痫发作的年龄，或者神经和精神合并症的存在。先前的迷走神经刺激手术和癫痫综合征的存在是与RNS几乎完全缓解癫痫发作的可能性较低相关的因素。强调治疗患有全身性癫痫或先前介入失败的患者的复杂性。电极特征与应答率的混合结果强调了进一步研究患者个性化手术策略的必要性。我们研究的局限性包括对回顾性研究的依赖，这引入了潜在的偏差，限制了推断因果关系的能力。
结论：RNS是一种安全有效的治疗儿童DRE患者，合并症，和焦点可变性。FDA年龄和病灶限制，伴随着病人和医生的犹豫，可能限制了用RNS有效治疗小儿DRE的潜力。建议进行前瞻性随机试验来验证这些发现。
