The relationship between d-beta-hydroxybutyrate blood concentrations and seizure control in children treated with the ketogenic diet for medically intractable epilepsy.
The relationship between d-beta-hydroxybutyrate blood concentrations and seizure control in children treated with the ketogenic diet for medically intractable epilepsy.
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DOI：
10.1002/epi4.12058
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发表时间：
2017-09
期刊：
影响因子：
3
通讯作者：
Rho JM
中科院分区：
文献类型：
--
作者：
Buchhalter JR;D'Alfonso S;Connolly M;Fung E;Michoulas A;Sinasac D;Singer R;Smith J;Singh N;Rho JM
生酮饮食(KD)是治疗儿童和青少年耐药(DR)癫痫的一种有效方法。然而，癫痫发作控制与饮食中最常见的代谢物--酮体D-β-羟基丁酸酯(D-BHB)之间的关系存在争议。这项研究是为了阐明这种关系，因为特定的酮体可能是有用的饮食疗效的生物标志物。当两家加拿大西部儿童医院转介患有DR癫痫的儿童的家庭时，他们被要求参加这项开放的前瞻性研究。纳入标准包括不排除基于年龄、性别、癫痫发作或综合征类型的DR癫痫的记录。如果患者被转介接受独立于癫痫发作的代谢紊乱的治疗，则排除在外。癫痫发作通过父母报告进行量化，并标准化为每28天的癫痫发作频率。癫痫综合征是在病历的基础上确定的。采用串联质谱法测定全血D-BHb。共有23名患者从这两个地点招募。来自五个人的数据被排除在外，因为这些癫痫发作是成群发生的，留下18名患者进行初步分析。在后一组中，癫痫发作频率与D-BHb浓度呈明显正相关。然而，这一数字未能达到统计意义，可能是因为数字相对较小。癫痫发作频率和D-BHb水平之间存在明显的趋势，因此我们不应因缺乏统计学意义而却步，因为这可能是方法技术，特别是样本量的结果。这些结果要求进行更大规模的前瞻性研究，以标准化的方式在护理点评估癫痫发作频率，以确定D-BHb是否可以作为KD疗效的可靠生物标志物。
The ketogenic diet (KD) is a proven treatment for drug‐resistant (DR) seizures in children and adolescents. However, the relationship between seizure control and the most commonly measured metabolite of the diet, the ketone body d‐beta‐hydroxybutyrate (D‐BHB), is controversial. This study was performed to clarify the relationship because specific ketone bodies may be useful as biomarkers of diet efficacy. Families of children with DR seizures were approached for participation in this open‐label, prospective study when they were referred for the KD at two western Canadian children's hospitals. Inclusion criteria included documentation of DR seizures without exclusion based on age, sex, seizure, or syndrome type. Patients were excluded if they were referred for treatment of a metabolic disorder independent of seizures. Seizures were quantified via parental report and standardized as seizure frequency per 28 days. Epilepsy syndromes were identified on the basis of the medical record. Blood D‐BHB was determined by tandem mass spectrometry. A total of 23 patients were recruited from both sites. Data from five individuals were excluded because these seizures occurred in clusters, leaving 18 patients for the primary analysis. In the latter group, a clear positive correlation was present between measures of seizure frequency and D‐BHB concentrations. However, this failed to reach statistical significance, likely because of the relatively small numbers. A trend clearly exists between seizure frequency and D‐BHB levels, so we should not be dissuaded by the lack of statistical significance because it possibly results from methodological techniques, especially sample size. These results call for a larger prospective study in which seizure frequency is assessed at the point of care in a standardized fashion so as to determine whether D‐BHB can be used as a reliable biomarker of KD efficacy.