MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept study

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research Pub Date : 2024-11-08 DOI:10.1016/j.eplepsyres.2024.107478

Raquel Samões , Ana Cavalheiro , Cristina Santos , Joana Lopes , Catarina Teixeira , Maria Manuel Tavares , Cláudia Carvalho , Carolina Lemos , Paulo Pinho e Costa , Sara Cavaco , João Chaves , Bárbara Leal

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引用次数: 0

Abstract

Background

Accurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD.

Methods

Patients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR.

Results

Thirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17–100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %.

Conclusions

A panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.

查看原文本刊更多论文

微RNA是治疗成人耐药性癫痫的改良阿特金斯饮食反应的潜在生物标志物：概念验证研究

背景：需要准确预测对改良阿特金斯饮食（MAD）的反应。微RNA是癫痫的潜在生物标志物。本研究旨在探索循环miR-146a、miR-155、miR-22、miR-21和miR-134水平在预测MAD反应中的价值：从MAD专科门诊随访的DRE成人前瞻性队列中挑选出完成3个月MAD治疗的患者。如果随访时癫痫发作频率有所减少（通过癫痫发作日历计算），则将患者归类为应答者。此外，还探讨了癫痫发作减少 >50% 的分界线。此外，还分析了癫痫发作和认知能力方面的定性优势。在启动 MAD 之前采集了血液样本，并通过 qRT-PCR 对 microRNA 进行了量化：共纳入 39 名患者（56% 为男性，平均年龄（33.1±8.5）岁，62% 为局灶性癫痫，59% 为结构性病因）：20名患者（51%）为应答者[癫痫发作频率平均减少54%（17-100%）；10名患者减少≥50%]；25名患者（64%）报告了癫痫发作的质量效益，21名患者（54%）报告了认知效益。在治疗前的基线上，结合所有研究的微RNA血清水平的小组预测了癫痫发作的减少（AUC=0.839，p结论：在治疗前的基线上，结合所有研究的微RNA血清水平的小组预测了癫痫发作的减少（AUC=0.839，p结论）：将治疗前血清中的 miR-146a、miR-155、miR-134、miR-21 和 miR-22 水平组合在一起，可预测罹患 DRE 的成人在接受 MAD 治疗 3 个月后癫痫发作的减少情况。该研究小组可能是一种很有前景的生物标志物，也是选择患者的有用工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epilepsy Research 医学-临床神经学

CiteScore

0.10

自引率

4.50%

发文量

143

审稿时长

62 days

期刊介绍： Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.