Hazany Saman, DeClouette Brittany, Lowe Jessica, Hwang Darryl H, Kim Paul E, Bluml Stefan, Partikian Arthur
Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Pediatrics & Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
J Epilepsy Res. 2023 Jun 30;13(1):1-6. doi: 10.14581/jer.23001.
Ketogenic diet (KD) improves seizure control in patients with drug-resistant epilepsy. As increased mitochondrial levels of glutathione (GSH) might contribute to a change in seizure susceptibility, we quantified changes of absolute GSH levels in the brain by 1H magnetic resonance spectroscopy (1H MRS) and correlate that with degree of seizure control in patients on KD.
Five cognitively normal adult patients with drug-resistant epilepsy were initially included and 2 completed the study. Each patient was evaluated by a neurologist and registered dietitian at baseline, 1, 3, and 6 months for seizure status and diet adherence after initiation of a modified atkins diet. Multiple metabolites including GSH were quantified using LCModel (version 6.3-1P; Stephen Provencher, Oakville, ON, CA) on a short echo time single-voxel 1H MRS in parieto/occipital grey matter and parietal white matter on a 3 Tesla General Electric magnet prior to starting the ketogenic diet and at 6 months.
Both patients (42-years-old male and 35-years-old female) demonstrated marked increases in absolute GSH level in both gray matter (0.12 to 1.40 and 0.10 to 0.70 international unit [IU]) and white matter (0.65 to 1.50 and 0.80 to 2.00 IU), as well as 50% improvements in seizure duration and frequency. Other metabolites including ketone bodies did not demonstrate consistent changes.
Markedly increased levels of GSH (7-fold and 14-fold) were observed in longitudinal prospective study of two adult patients with intractable epilepsy with 50% seizure improvement after initiation of ketogenic diets. This pilot study supports the possible anticonvulsant role of GSH in the brain.
生酮饮食（KD）可改善耐药性癫痫患者的癫痫控制情况。由于线粒体谷胱甘肽（GSH）水平升高可能会导致癫痫易感性发生变化，我们通过氢质子磁共振波谱（1H MRS）对大脑中GSH的绝对水平变化进行了量化，并将其与接受KD治疗的患者的癫痫控制程度相关联。
最初纳入了5名认知正常的耐药性癫痫成年患者，其中2名完成了研究。在开始改良阿特金斯饮食后，每位患者在基线、1个月、3个月和6个月时由神经科医生和注册营养师对癫痫状态和饮食依从性进行评估。在开始生酮饮食前及6个月时，使用LCModel（版本6.3 - 1P；Stephen Provencher，加拿大安大略省奥克维尔）在3特斯拉通用电气磁体上对顶叶/枕叶灰质和顶叶白质进行短回波时间单体素1H MRS，对包括GSH在内的多种代谢物进行量化。
两名患者（42岁男性和35岁女性）的灰质（从0.12至1.40国际单位[IU]以及从0.10至0.70 IU）和白质（从0.65至1.50以及从0.80至2.00 IU）中的GSH绝对水平均显著升高，癫痫发作持续时间和频率也改善了50%。包括酮体在内的其他代谢物未表现出一致的变化。
在对两名成年难治性癫痫患者进行纵向前瞻性研究中，观察到生酮饮食开始后GSH水平显著升高（分别升高7倍和14倍），癫痫发作改善了50%。这项初步研究支持了GSH在大脑中可能具有的抗惊厥作用。
