生酮饮食治疗小儿癫痫的系统评价再评价

Ketogenic Diet for the Treatment of Pediatric Epilepsy: An Overview of Systematic Reviews

摘要: 目的：通过系统评价再评价，整合证据评估生酮饮食(KD)治疗小儿癫痫的有效性、耐受性及证据质量，为临床研究提供依据。方法：检索Web of Science、PubMed等中英文数据库，纳入2023年10月前相关系统评价(SRs)与Meta分析(MAs)，用AMSTAR-2、ROBIS工具评估质量，分析发作频率、无发作状态、保留率及不良反应。结果：纳入7篇SRs (含107项RCTs)，均显示KD可显著减少发作：7篇SRs中患儿发作减少≥50%，3篇SRs中患儿发作减少≥90%，4篇SRs中患儿达无发作；改良阿特金斯饮食(MAD)与经典KD (CKD)疗效相当(RR = 0.83, 95% CI: 0.49~1.41)，耐受性良好，需关注胃肠紊乱、胆固醇升高等短期副作用。7篇SRs间存在显著潜在异质性，各研究在纳入人群的癫痫亚型划分、患儿年龄分层标准、KD干预的具体剂量配比、疗程时长及随访周期方面均存在明显差异，且部分研究对发作减少、无发作等核心结局的定义与评估方法不统一，这些方法学与研究设计层面的差异，是导致各SRs效应量存在波动、结论细节略有分歧的核心原因，也是本次再评价需重点剖析的关键内容。结论：KD对小儿癫痫(尤其难治性)疗效明确，MAD可替代传统KD；现有证据受方法学缺陷与短期随访限制，本次质量评价显示7篇SRs中有4篇为低或极低质量，存在未明确排除文献合理性、未报告研究资助来源、偏倚风险评估不全面等突出问题，此类严重质量缺陷直接降低了整体证据的可信度，若直接据此得出KD疗效明确的结论过于绝对，临床应用需结合证据质量谨慎参考，不可过度依赖现有结论开展诊疗。临床需个体化制定方案并定期监测不良反应。

Abstract: Objective: To assess the efficacy, tolerability and evidence quality of ketogenic diet (KD) for pediatric epilepsy via an overview of systematic reviews, and provide evidence for clinical practice and research. Methods: Chinese and English databases (e.g., Web of Science, PubMed) were searched to include relevant systematic reviews (SRs) and meta-analyses (MAs) before October 2023. AMSTAR-2 and ROBIS tools were used for quality assessment. Seizure frequency, seizure-free status, retention rate and adverse reactions were analyzed. Results: 7 systematic reviews (SRs) encompassing 107 randomized controlled trials (RCTs) consistently demonstrated that the ketogenic diet (KD) significantly reduces seizure frequency: ≥50% seizure reduction was observed in patients across the 7 SRs, ≥90% seizure reduction in 3 SRs, and seizure freedom in 4 SRs. The modified Atkins diet (MAD) showed comparable efficacy to the classic ketogenic diet (CKD) (RR = 0.83, 95% CI: 0.49~1.41) with good tolerability. Short-term side effects such as gastrointestinal disturbances and elevated cholesterol levels require attention. There is significant potential heterogeneity among the 7 SRs, including obvious differences in epilepsy subtype classification, pediatric age stratification, specific KD dose ratio, treatment course and follow-up period, as well as inconsistent definitions and evaluation methods of core outcomes such as seizure reduction and seizure freedom in some studies. These differences in methodology and study design are the core reasons for the fluctuation of effect sizes and slight differences in conclusion details among various SRs, which is also the key content to be analyzed in this overview. Conclusion: KD is effective for pediatric epilepsy (especially refractory cases), and MAD can replace traditional CKD. Current evidence is limited by methodological flaws and short-term follow-up. The quality evaluation shows that 4 of the 7 SRs are low or very low quality, with prominent problems such as unclear justification for excluded literature, unreported research funding sources, and incomplete bias risk assessment. Such serious quality defects directly reduce the credibility of the overall evidence, and it is too absolute to draw a conclusion that KD has clear efficacy based on this alone. Clinical application needs to be carefully referenced combined with evidence quality, and should not rely excessively on existing conclusions for diagnosis and treatment. Individualized clinical plans and regular adverse reaction monitoring are needed.