Mueller S G, Weber O M, Duc C O, Weber B, Meier D, Russ W, Boesiger P, Wieser H G
Department of Neurology, University Hospital, Zurich, Switzerland.
Epilepsia. 2001 Jan;42(1):29-40. doi: 10.1046/j.1528-1157.2001.077889.x.
Vigabatrin (VGB) is a new antiepileptic drug that increases the human brain gamma-aminobutyric acid (GABA) level by irreversibly inhibiting GABA transaminase. Although some patients respond to VGB with a significant seizure reduction, others do not. The aim of this study was to identify possible responders before or in an early phase of VGB treatment by measuring the GABA and homocarnosine contaminated with macromolecules/creatine and phosphocreatine ratio (GABA+/Cr) signal by means of proton-nuclear magnetic resonance (1H NMR) spectroscopy.
Measurements were performed immediately before and after a titration period of 1 month (2 g/day during the past 2 weeks). A third measurement followed a maintenance period of 3 months (2 or 3 g/day). In 14 patients with drug-resistant temporal lobe epilepsy and 3 patients with occipital lobe epilepsy, GABA+/Cr was measured in the ipsilateral (i.e., epileptogenic) hemisphere and contralateral (i.e., nonepileptogenic) hemisphere in a volume of 8 cm3.
Depending on the therapeutic efficacy of VGB, we defined three groups: (a) full responders (n = 7), (b) nonresponders (n = 7), and (c) partial responders (n = 3). The nonresponders had no significant change in the GABA+/Cr signal during the treatment compared with baseline. The full responders had a significant increase of the GABA+/Cr signal during the whole treatment phase and a lower ipsilateral level at baseline. The partial responders had also a lowered ipsilateral GABA+/Cr signal at baseline and an increase during treatment but a decrease when the seizures started again.
Responders to VGB could be identified by a lower ipsilateral baseline GABA+/Cr signal and a steeper increase during VGB treatment. However, it was not possible to predict the duration of the response (full versus partial responder) with these criteria.
氨己烯酸（VGB）是一种新型抗癫痫药物，它通过不可逆地抑制γ-氨基丁酸转氨酶来提高人脑γ-氨基丁酸（GABA）水平。尽管一些患者使用VGB后癫痫发作显著减少，但另一些患者则不然。本研究的目的是通过质子核磁共振（1H NMR）波谱测量受大分子/肌酸和磷酸肌酸污染的GABA和高肌肽比值（GABA+/Cr）信号，在VGB治疗前或早期阶段识别可能的反应者。
在1个月的滴定期（过去2周每天2克）前后立即进行测量。在3个月的维持期（每天2或3克）后进行第三次测量。对14例耐药性颞叶癫痫患者和3例枕叶癫痫患者，在同侧（即致痫）半球和对侧（即非致痫）半球8立方厘米的体积内测量GABA+/Cr。
根据VGB的治疗效果，我们定义了三组：（a）完全反应者（n = 7），（b）无反应者（n = 7），（c）部分反应者（n = 3）。与基线相比，无反应者在治疗期间GABA+/Cr信号无显著变化。完全反应者在整个治疗阶段GABA+/Cr信号显著增加，且基线时同侧水平较低。部分反应者基线时同侧GABA+/Cr信号也较低，治疗期间增加，但癫痫再次发作时下降。
可以通过较低的同侧基线GABA+/Cr信号和VGB治疗期间更陡峭的增加来识别对VGB有反应者。然而，用这些标准无法预测反应的持续时间（完全反应者与部分反应者）。
