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Efficacy of the Ketogenic Diet for Pediatric Epilepsy According to the Presence of Detectable Somatic mTOR Pathway Mutations in the Brain

김동석|이정호|김세희|강훈철|김흥동|이준수|양동화|최한솜|고아라|심남석
대한신경과학회 (Korean Neurological Association)|2022.01|Journal of Clinical Neurology|제18권 제1호|pp. 71-78

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epilepsyfocal cortical dysplasiamammalian target of rapamycinmTORopathiessomatic mutationketogenic diet.

초록

Background and Purpose A multifactorial antiepileptic mechanism underlies the ketogenic diet (KD), and one of the proposed mechanisms of action is that the KD inhibits the mammalian target of rapamycin (mTOR) pathway. To test this clinically, this study aimed to determine the efficacy of the KD in patients with pathologically confirmed focal cortical dysplasia (FCD) due to genetically identifiable mTOR pathway dysregulation. Methods A cohort of patients with pathologically confirmed FCD after epilepsy surgery and who were screened for the presence of germline and somatic mutations related to the mTOR pathway in peripheral blood and resected brain tissue was constructed prospectively. A retrospective review of the efficacy of the prior KD in these patients was performed. Results Twenty-five patients with pathologically confirmed FCD and who were screened for the presence of detectable somatic mTOR pathway mutations had received a sufficient KD. Twelve of these patients (48.0%) had germline or somatic detectable mTOR pathway mutations. A response was defined as a ≥50% reduction in seizure frequency. The efficacy of the KD after 3 months of dietary therapy was superior in patients with detectable mTOR pathway mutations than in patients without detectable mTOR pathway mutations, although the difference was not statistically significant (responder rates of 58.3% vs. 38.5%, p=0.434). Conclusions A greater proportion of patients with mTOR pathway responded to the KD, but there was no statistically significant difference in efficacy of the KD between patients with and without detectable mTOR pathway mutations. Further study is warranted due to the smallness of the sample and the limited number of mTOR pathway genes tested in this study.

Abstract

Background and Purpose A multifactorial antiepileptic mechanism underlies the ketogenic diet (KD), and one of the proposed mechanisms of action is that the KD inhibits the mammalian target of rapamycin (mTOR) pathway. To test this clinically, this study aimed to determine the efficacy of the KD in patients with pathologically confirmed focal cortical dysplasia (FCD) due to genetically identifiable mTOR pathway dysregulation. Methods A cohort of patients with pathologically confirmed FCD after epilepsy surgery and who were screened for the presence of germline and somatic mutations related to the mTOR pathway in peripheral blood and resected brain tissue was constructed prospectively. A retrospective review of the efficacy of the prior KD in these patients was performed. Results Twenty-five patients with pathologically confirmed FCD and who were screened for the presence of detectable somatic mTOR pathway mutations had received a sufficient KD. Twelve of these patients (48.0%) had germline or somatic detectable mTOR pathway mutations. A response was defined as a ≥50% reduction in seizure frequency. The efficacy of the KD after 3 months of dietary therapy was superior in patients with detectable mTOR pathway mutations than in patients without detectable mTOR pathway mutations, although the difference was not statistically significant (responder rates of 58.3% vs. 38.5%, p=0.434). Conclusions A greater proportion of patients with mTOR pathway responded to the KD, but there was no statistically significant difference in efficacy of the KD between patients with and without detectable mTOR pathway mutations. Further study is warranted due to the smallness of the sample and the limited number of mTOR pathway genes tested in this study.

참고문헌 (68)

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관련 논문AI추천

The Early Response to Dietary Therapy can Predict the Late Outcome in Children with Intractable Epilepsy고태성, 김민지, 안현지, 염미선, 임수영, 장한나대한신경과학회 · Journal of Clinical Neurology2021 · 제17권 제1호Ketogenic Diet in Infants with Early-Onset Epileptic Encephalopathy and SCN2A MutationJinhong Zhang, Xiaoyu Tian, Xinyi Men, Xiuxia Wang, Yange Zhang, Yan Lu연세대학교의과대학 · Yonsei Medical Journal2021 · 제62권 제4호Brain somatic mutations in MTOR leading to focal cortical dysplasia이정호, 임재석생화학분자생물학회 · BMB Reports2016 · 제49권 제2호Discontinuing Antiepileptic Drugs after Pediatric Epilepsy Surgery for Focal Cortical Dysplasia강훈철, 김동석, 김세희, 김흥동, 서세은, 이준수대한소아신경학회 · 대한소아신경학회지2017 · 제25권 제3호Antiepileptic Drug Withdrawal after Surgery in Children with Focal Cortical Dysplasia: Seizure Recurrence and Its Predictors황희, 김기중, 김수연, 김승기, 김우중, 김훈민, 심영규, 왕규창, 이지연, 임병찬, 정상준, 채종희, 최선아, 최지은, 피지훈대한신경과학회 · Journal of Clinical Neurology2019 · 제15권 제1호Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-AnalysisFang Ye, Hong-Bin Sun, Jie Liu, Wan-Lin Jiang, Xiao-Jia Li대한신경과학회 · Journal of Clinical Neurology2015 · 제11권 제1호

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