Belousova E D
Department of Psychoneurology and Epileptology ,Research and Clincal Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(6):106-110. doi: 10.17116/jnevro201711761106-110.
Antiepileptic drugs (AEDs) have long been known to affect carnitine metabolism, dropping the plasma free carnitine. Valproate (VPA) was considered to be the strongest carnitine-reducing agent. VPA-induced hyperammonemic encephalopathy and hepatotoxicity are well known, and pre-existing carnitine deficiency can be a predisposing factor, especially in congenital metabolic disorders. Several studies have shown that carnitine supplementation in patients receiving VPA to result in subjective and objective improvements and to prevent VPA-induced hepatotoxicity and encephalopathy, in parallel with increases in carnitine serum concentrations. Level of free plasma carnitine <20 micromol/l (syn. carnitine deficiency) in patients with epilepsy (in 15-30% of cases) may occur not only with administration of VPA but with administration of other AEDs (phenobarbital, phenytoin, carbamazepine) and low nutritional intake of carnitine. Some findings indicate that the number of AEDs used is a risk factor for carnitine deficiency. It was established that body weight, height and multidrug therapy are significantly associated with low level of free plasma in epileptic patients. Carnitine deficiency can have severe consequences; but most epileptic patients suffering from it are asymptomatic. Although carnitine deficiency is not uncommon among patients receiving AEDs, it seems not necessary to routinely monitor carnitine levels in epileptic ambulatory patients, this is reasonable only in groups of risk. L-carnitine supplementation is clearly indicated in case of VPA-induced hepatotoxicity (i.v. administration) VPA overdose (i.v. administration), primary carnitine-transporter defect and is strongly recommended in specific secondary carnitine deficiency syndromes, symptomatic VPA-associated hyperammonemia, infants and young children receiving VPA, especially those younger than 2 years, patients with a complex neurologic disorder, who are receiving multiple AEDs, patients who have risk factors for hepatotoxicity and carnitine insufficiency. In the absence of double blind trials, clinical practice is based on empiric observation, clinical experience, and theory. Well-designed studies of specific and general uses of L-carnitine replacement therapy in patients with epilepsy are needed.
长期以来，人们都知道抗癫痫药物（AEDs）会影响肉碱代谢，降低血浆游离肉碱水平。丙戊酸盐（VPA）被认为是最强的降低肉碱的药物。VPA诱导的高氨血症性脑病和肝毒性是众所周知的，而预先存在的肉碱缺乏可能是一个诱发因素，尤其是在先天性代谢紊乱中。几项研究表明，在接受VPA治疗的患者中补充肉碱可带来主观和客观的改善，并预防VPA诱导的肝毒性和脑病，同时血清肉碱浓度会升高。癫痫患者（15% - 30%的病例）血浆游离肉碱水平<20微摩尔/升（即肉碱缺乏）不仅可能在使用VPA时出现，在使用其他AEDs（苯巴比妥、苯妥英、卡马西平）以及肉碱营养摄入不足时也可能出现。一些研究结果表明，使用AEDs的数量是肉碱缺乏的一个危险因素。已证实体重、身高和多药治疗与癫痫患者血浆游离肉碱水平低显著相关。肉碱缺乏可能会产生严重后果；但大多数患有肉碱缺乏的癫痫患者并无症状。虽然肉碱缺乏在接受AEDs治疗的患者中并不罕见，但对于癫痫门诊患者似乎没有必要常规监测肉碱水平，仅在高危人群中这样做才合理。在VPA诱导的肝毒性（静脉给药）、VPA过量（静脉给药）、原发性肉碱转运体缺陷的情况下，明确需要补充L - 肉碱，在特定的继发性肉碱缺乏综合征、有症状的VPA相关高氨血症、接受VPA治疗的婴幼儿（尤其是2岁以下者）、患有复杂神经系统疾病且正在接受多种AEDs治疗的患者、有肝毒性和肉碱不足危险因素的患者中强烈推荐补充L - 肉碱。在缺乏双盲试验的情况下，临床实践基于经验观察、临床经验和理论。需要针对癫痫患者中L - 肉碱替代疗法的具体和一般用途进行精心设计的研究。
