Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan University, Chengdu, China.
Epilepsia. 2024 Oct;65(10):2959-2972. doi: 10.1111/epi.18098. Epub 2024 Aug 27.
To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug-resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice.
Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre-KD and post-KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non-genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation.
Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti-seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non-genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post-KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD.
Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug-resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re-evaluation of KD decision-making paradigms.
确定影响儿童耐药性癫痫酮饮食（KD）治疗效果的关键因素，并阐明它们之间的相互关系，以优化临床实践。
本研究选取 2015 年 9 月至 2023 年 10 月在四川大学华西第二医院接受 KD 治疗的患儿为研究对象。采用分析框架系统分析 KD 前（治疗前 3 个月）和 KD 后（治疗后第 3 个月）的临床因素。对全队列及遗传病因（通道病）和非遗传病因（结构性病因和未知病因）亚组进行描述性分析、单变量分析和多变量回归分析，从而确定每个相关因变量的最显著预测因素。通过路径分析图进行可视化展示。
在 156 例患儿中，遗传病因较为常见（38.5%）。在遗传病因亚组中，通道病预测基线发作频率较低，KD 后无发作的机会增加。发作频繁和抗癫痫药物（ASM）治疗史复杂预测基线精神运动异常严重。KD 起始年龄越小，精神运动改善越好。在非遗传病因亚组中，基线发作频率越低，KD 后无发作的可能性越大。同时使用多种 ASM 有助于达到≥50%的发作减少。男孩更有可能出现精神运动改善。两个亚组中均发现≥50%的发作减少与精神运动改善之间存在显著相关性。KD 起始延迟（KD 起始时癫痫持续时间较长）与使用更多的 ASM、发作不频繁和癫痫发病年龄较大有关。此外，患有通道病的患者 KD 起始延迟。
遗传性癫痫患儿表现出更明显的癫痫性脑病特征。对于通道病，尤其是 SCN1A 变异，早期 KD 干预至关重要。对于其他耐药性癫痫病例，KD 联合多种 ASM 可能改善发作控制和发育结局。然而，从 KD 中获益最多的患者人群往往开始治疗较晚，这促使我们重新评估 KD 决策模式。
