Buchhalter Jeffrey R, D'Alfonso Sabrina, Connolly Mary, Fung Ernest, Michoulas Aspasia, Sinasac David, Singer Rachel, Smith Jacklyn, Singh Narender, Rho Jong M
Department of Pediatrics Cumming School of Medicine University of Calgary Calgary Alberta Canada.
Clinical Neurosciences Cumming School of Medicine University of Calgary Calgary Alberta Canada.
Epilepsia Open. 2017 May 19;2(3):317-321. doi: 10.1002/epi4.12058. eCollection 2017 Sep.
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.
生酮饮食（KD）已被证实可用于治疗儿童和青少年的耐药性（DR）癫痫发作。然而，癫痫发作控制与该饮食中最常检测的代谢物——酮体d-β-羟基丁酸（D-BHB）之间的关系存在争议。进行本研究是为了阐明这种关系，因为特定的酮体可能作为饮食疗效的生物标志物。
当加拿大西部两家儿童医院将患有DR癫痫发作的儿童家庭转诊接受KD治疗时，邀请他们参与这项开放标签的前瞻性研究。纳入标准包括记录DR癫痫发作，不基于年龄、性别、癫痫发作或综合征类型进行排除。如果患者因独立于癫痫发作的代谢紊乱而被转诊治疗，则被排除。通过家长报告对癫痫发作进行量化，并标准化为每28天的癫痫发作频率。根据病历确定癫痫综合征。通过串联质谱法测定血液中的D-BHB。
两个研究地点共招募了23名患者。由于5名个体的癫痫发作呈簇状发生，其数据被排除，最终18名患者纳入初步分析。在后者组中，癫痫发作频率测量值与D-BHB浓度之间存在明显的正相关。然而，这一结果未达到统计学意义，可能是因为样本数量相对较少。
癫痫发作频率与D-BHB水平之间显然存在一种趋势，因此我们不应因缺乏统计学意义而却步，因为这可能是由方法技术导致的，尤其是样本量。这些结果呼吁开展一项更大规模的前瞻性研究，以标准化方式在护理点评估癫痫发作频率，从而确定D-BHB是否可作为KD疗效的可靠生物标志物。
