PDF(Pubmed)
Abstract：
Glucose is an important fuel for the brain. In glucose transporter 1 deficiency syndrome (GLUT1DS), the transport of glucose across the blood-brain barrier is limited. Most individuals with GLUT1DS present with developmental problems, epilepsy, and (paroxysmal) movement disorders, and respond favorably to the ketogenic diet. Similar to ketones, lactate is an alternative energy source for the brain. The aim of this study is to investigate whether intravenous infusion of sodium lactate in children with GLUT1DS has beneficial effects on their epilepsy.
We performed a proof of principle study with two subjects with GLUT1DS who were not on a ketogenic diet and suffered from absence epilepsy. After overnight fasting, sodium lactate (600 mmol/L) was infused during 120 minutes, under video electroencephalographic (EEG) recording and monitoring of serum lactate, glucose, electrolytes, and pH. Furthermore, the EEGs were compared with pre-/postprandial EEGs of both subjects, obtained shortly before the study.
Fasting EEGs of both subjects showed frequent bilateral, frontocentral polyspike and wave complexes. In one subject, no more epileptic discharges were seen postprandially and after the start of lactate infusion. The EEG of the other subject did not change, neither postprandially nor after lactate infusion. Serum pH, lactate, and sodium changed temporarily during the study.
This study suggests that sodium lactate infusion is possible in individuals with GLUT1DS, and may have potential therapeutic effects. Cellular abnormalities, beyond neuronal energy failure, may contribute to the underlying disease mechanisms of GLUT1DS, explaining why not all individuals respond to the supplementation of alternative energy sources.
We performed a proof of principle study with two subjects with GLUT1DS who were not on a ketogenic diet and suffered from absence epilepsy. After overnight fasting, sodium lactate (600 mmol/L) was infused during 120 minutes, under video electroencephalographic (EEG) recording and monitoring of serum lactate, glucose, electrolytes, and pH. Furthermore, the EEGs were compared with pre-/postprandial EEGs of both subjects, obtained shortly before the study.
Fasting EEGs of both subjects showed frequent bilateral, frontocentral polyspike and wave complexes. In one subject, no more epileptic discharges were seen postprandially and after the start of lactate infusion. The EEG of the other subject did not change, neither postprandially nor after lactate infusion. Serum pH, lactate, and sodium changed temporarily during the study.
This study suggests that sodium lactate infusion is possible in individuals with GLUT1DS, and may have potential therapeutic effects. Cellular abnormalities, beyond neuronal energy failure, may contribute to the underlying disease mechanisms of GLUT1DS, explaining why not all individuals respond to the supplementation of alternative energy sources.
摘要：
葡萄糖是大脑的重要燃料。在葡萄糖转运蛋白1缺乏综合征(GLUT1DS)中,葡萄糖穿过血脑屏障的转运是有限的。大多数患有GLUT1DS的人都存在发育问题，癫痫,和（阵发性）运动障碍，对生酮饮食反应良好。类似于酮，乳酸是大脑的替代能源。这项研究的目的是调查GLUT1DS患儿静脉输注乳酸钠是否对其癫痫有有益影响。我们对两名没有生酮饮食且患有脓肿性癫痫的GLUT1DS受试者进行了原理研究证明。禁食过夜后，在120分钟内输注乳酸钠（600mmol/l），在视频脑电图记录和监测或血清乳酸下，葡萄糖，电解质和pH。此外，将脑电图与两名受试者的餐前/餐后脑电图进行比较，在研究前不久获得的。两个受试者的空腹脑电图显示频繁的双侧，额中央多峰和波复合物。在一名受试者中，餐后和开始输注乳酸后，没有更多的癫痫放电。另一个受试者的脑电图没有变化，无论是餐后还是乳酸输注后。血清pH值,乳酸和钠在研究期间暂时发生变化。这项研究表明，乳酸钠输注在患有GLUT1DS的个体中是可能的，并可能有潜在的治疗效果。细胞异常，除了神经元能量衰竭，可能有助于GLUT1DS的潜在疾病机制，解释为什么不是所有的人都对补充替代能源有反应。
