Categorizing Monogenic Epilepsies by Genetic Mechanisms May Predict Efficacy of the Ketogenic Diet

IF 3.2 3区 医学 Q2 CLINICAL NEUROLOGY
Jeong-A Kim MD , Stephanie Schimpf RD , Sho T. Yano MD, PhD , Douglas Nordli Jr MD , Chalongchai Phitsanuwong MD
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Abstract

Background

The ketogenic diet (KD) is an effective treatment for epilepsy. In recent years, studies have shown favorable efficacy of KD in epilepsy from genetic disorders. In this study, we propose an approach to KD in monogenic epilepsy: we evaluate the utility of categorizing genetic variants based on rational associations with the known mechanisms of KD.

Methods

Patients with monogenic epilepsy treated with KD were reviewed. The genetic etiologies were categorized into five groups: (1) conditions causing cellular energy impairment, (2) GABA-pathies, (3) mToR-pathies, (4) ion channelopathies, and (5) no known mechanisms associated with KD mechanisms. Treatment response was defined as a median reduction in seizure frequency of greater than 50%.

Results

Of 35 patients, 24 (69%) were responders at three months. Based on categories, Group 1 had the highest response rate with seven of seven (100%), followed by Group 2, six of seven (86%), and Group 3, two of three (67%). Patients in Groups 4 and 5 had poorer responses with three of seven (43%) and four of 11 (36%) response rates, respectively (P < 0.01). Median percentage of seizure reduction showed Group 1 with the highest reduction of 97.5%, Group 2 at 94%, and Groups 3, 4, and 5 at 62.5%, 30%, and 40%, respectively (P = 0.036).

Conclusion

Our findings show a favorable response to KD in patients with monogenic epilepsy (69% at three months) with the highest response in patients with conditions involving cellular energy impairment and GABA-pathies. The KD, therefore, should be considered early in patients with monogenic epilepsy, especially those involving genes associated with cellular energy impairment or GABA-pathies.

根据遗传机制对单源性癫痫进行分类可预测生酮饮食的疗效
背景:生酮饮食(KD)是治疗癫痫的有效方法。近年来,研究表明生酮饮食对遗传性癫痫具有良好疗效。在本研究中,我们提出了一种针对单基因癫痫的生酮饮食方法:我们评估了根据基因变异与已知生酮饮食机制的合理关联进行基因变异分类的效用:我们对接受 KD 治疗的单基因癫痫患者进行了回顾。遗传病因被分为五组:(1) 导致细胞能量损伤的病因;(2) GABA-病因;(3) mToR-病因;(4) 离子通道病因;(5) 与 KD 机制无关的已知机制。治疗反应的定义是癫痫发作频率减少的中位数超过 50%:在 35 名患者中,24 人(69%)在三个月后出现应答。根据类别,第 1 组的反应率最高,7 人中有 7 人(100%),其次是第 2 组,7 人中有 6 人(86%),第 3 组,3 人中有 2 人(67%)。第 4 组和第 5 组患者的反应较差,分别为 7 例中的 3 例(43%)和 11 例中的 4 例(36%)(P 结论:我们的研究结果表明,KDK 治疗的反应良好:我们的研究结果表明,单基因癫痫患者对 KD 的反应良好(三个月时反应率为 69%),其中细胞能量受损和 GABA 病变患者的反应最高。因此,单基因癫痫患者,尤其是涉及细胞能量损伤或 GABA 病变相关基因的患者,应尽早考虑接受 KD 治疗。
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来源期刊
Pediatric neurology
Pediatric neurology 医学-临床神经学
CiteScore
4.80
自引率
2.60%
发文量
176
审稿时长
78 days
期刊介绍: Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.
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