Glutamate in pyridoxine-dependent epilepsy: neurotoxic glutamate concentration in the cerebrospinal fluid and its normalization by pyridoxine.
Glutamate in pyridoxine-dependent epilepsy: neurotoxic glutamate concentration in the cerebrospinal fluid and its normalization by pyridoxine.
复制标题
吡哆醇依赖性癫痫中的谷氨酸：脑脊液中的神经毒性谷氨酸浓度及其通过吡哆醇的正常化。
作者：
Friedrich A. M. Baumeister;Yoon S. Shin;Joseph Egger;Wieland Gsell
背景
吡哆醇依赖性癫痫是一种罕见的常染色体隐性遗传疾病。未经治疗的患者患有进行性脑病，伴有智力低下、顽固性癫痫以及进行性神经系统体征和症状。终身补充维生素 B6 是治疗的首选。然而，尽管进行了早期治疗，许多患者仍出现智力低下。
目标
评估谷氨酸作为兴奋性神经递质和神经毒素在吡哆醇依赖性癫痫中的作用。
方法
我们检查了一名吡哆醇依赖性患者在接受和停止维生素 B6 治疗期间的脑脊液 (CSF) 中谷氨酸、γ-氨基丁酸和 5'-磷酸吡哆醛的水平。
结果
没有维生素 B6 时，谷氨酸水平是正常水平的 200 倍。中等剂量的维生素 B6（5 毫克/公斤体重/天）可使脑电图正常化并缓解癫痫发作，但脑脊液谷氨酸浓度仍是正常值的十倍。使用较高剂量的吡哆醇（10 毫克/千克体重/天），脑脊液谷氨酸恢复正常。
结论
结果表明，控制癫痫可能不足以作为治疗吡哆醇依赖的治疗目标。鉴于兴奋性氨基酸在破坏中枢神经系统神经细胞中的作用的证据，最佳治疗必须抵消脑脊液谷氨酸水平的升高，并且必须相应调整维生素 B6 的剂量。理论上，可以通过调整维生素 B6 的剂量来预防精神发育迟滞的发生，不仅可以缓解癫痫，还可以使脑脊液谷氨酸正常化。
BACKGROUND
Pyridoxine-dependent epilepsy is a rare autosomal recessive disorder. Untreated patients suffer from a progressive encephalopathy with mental retardation, intractable epilepsy, and progressive neurological signs and symptoms. Lifelong supplementation with vitamin B6 is the treatment of choice. However, despite early treatment, many patients develop mental retardation.
OBJECTIVES
To assess the role of glutamate as an excitatory neurotransmitter and neurotoxin in pyridoxine-dependent epilepsy.
METHODS
We examined cerebrospinal fluid (CSF) levels of glutamate, gamma-aminobutyric acid, and pyridoxal-5'-phosphate in a patient with pyridoxine dependency while on and off vitamin B6 treatment.
RESULTS
Off vitamin B6 the glutamate level was two hundred times normal. An intermediate dose of vitamin B6 (5 mg/kg BW/day) caused normalization of the EEG and remission of the seizures, but the CSF glutamate concentration was still ten times normal. With a higher dose of pyridoxine (10 mg/kg BW/day) the CSF glutamic acid normalized.
CONCLUSIONS
The results indicate that control of epilepsy might not suffice as the therapeutic aim in treating of pyridoxine dependency. In view of the evidence for the role of excitatory amino acids in destruction of CNS nerve cells, the optimal treatment must counteract the raised levels of CSF glutamate and the dosage of vitamin B6 must be adjusted accordingly. The development of mental retardation might theoretically be prevented by adjusting the dose of vitamin B6 to achieve not only remission of epilepsy but also normalization of CSF glutamate.