Petroff O A, Behar K L, Mattson R H, Rothman D L
Department of Neurology, Yale University, New Haven, Connecticut 06510, USA.
J Neurochem. 1996 Dec;67(6):2399-404. doi: 10.1046/j.1471-4159.1996.67062399.x.
Vigabatrin is a novel antiepileptic drug designed to control seizures by raising brain gamma-aminobutyric acid (GABA) concentrations. Seizure control is not improved significantly when the daily dose is increased beyond 50 mg/kg. Serial, in vivo measurements of GABA levels in human occipital lobe were made using 1H NMR spectroscopy before and after the start of vigabatrin treatment. We used a 2.1-T magnetic resonance imagerspectrometer and an 8-cm surface coll to examine serially a 14-cm3 volume in the occipital lobe of 26 patients with complex partial seizures. Brain GABA content increased following the start of vigabatrin treatment up to a daily dose of 60 mg/kg. Additional increases in dose falled to increase brain GABA content further. GABA synthesis may decrease with sustained elevations of human brain GABA levels. Starting vigabatrin treatment reduced seizure frequency by > 50%, from six to seven per month to three. Improved seizure control was not associated with further increases of vigabatrin dose. Increased brain GABA concentration was associated with improved seizure control. Starting vigabatrin treatment improved seizure control twofold when GABA levels increased above 1.8 mmol/kg. Further increases in brain GABA content above 2.5 mmol/kg provided less protection. Measuring occipital lobe GABA concentrations may predict improved seizure control when using antiepileptic drugs designed to increase brain GABA levels.
氨己烯酸是一种新型抗癫痫药物，旨在通过提高脑内γ-氨基丁酸（GABA）浓度来控制癫痫发作。当每日剂量超过50mg/kg时，癫痫控制效果并无显著改善。在氨己烯酸治疗开始前后，使用1H核磁共振波谱法对人类枕叶中的GABA水平进行了连续的体内测量。我们使用一台2.1-T磁共振成像光谱仪和一个8cm的表面线圈，对26例复杂部分性癫痫患者枕叶中14cm³的体积进行了连续检测。氨己烯酸治疗开始后，直至每日剂量达到60mg/kg，脑内GABA含量均有所增加。剂量的进一步增加未能使脑内GABA含量进一步升高。随着人脑GABA水平的持续升高，GABA合成可能会减少。开始氨己烯酸治疗后，癫痫发作频率降低了50%以上，从每月六至七次降至三次。癫痫控制的改善与氨己烯酸剂量的进一步增加无关。脑内GABA浓度的升高与癫痫控制的改善相关。当GABA水平升高至1.8mmol/kg以上时，开始氨己烯酸治疗使癫痫控制改善了两倍。脑内GABA含量进一步升高至2.5mmol/kg以上时，提供的保护作用较小。在使用旨在提高脑内GABA水平的抗癫痫药物时，测量枕叶GABA浓度可能预测癫痫控制的改善情况。
