Tianjin Medical University, Tianjin, China.
Department of Neurology, Tianjin Medical University General Hospital, 154 Anshan Street, Tianjin 300052, China.
Epilepsy Behav. 2021 Feb;115:107683. doi: 10.1016/j.yebeh.2020.107683. Epub 2020 Dec 23.
To explore the changes of gamma-aminobutyric acid (GABA) levels in the bilateral hippocampus and anterior cingulate cortex (ACC) of healthy control subjects and patients with temporal lobe epilepsy (TLE) and the correlation of GABA levels with the clinical symptoms by quantitative magnetic resonance spectroscopy (MRS).
N-acetylaspartate (NAA), creatine (Cr) as well as choline (Cho) and GABA levels in the bilateral hippocampus and ACC were measured in 40 patients with TLE and 26 healthy control (NC) subjects with quantitative Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS). The NAA/(Cho + Cr) and GABA/Cr ratios were compared between the NC and TLE groups. Comparisons were also made between the subgroups with lateralization (left TLE, right TLE and uncertain), short (<10 years) and longer (≥10 years) clinical seizure history (CSH), low (<1/month) and higher (≥1/month) seizure frequency (SF), with and without cognitive impairment (CI) in the patients with TLE, and by antiepileptic medications. Further analyses of the clinical information and metabolite ratios between the patients with TLE with and without CI were preformed.
The GABA/Cr ratio was significantly decreased in the bilateral hippocampus (left: P = 0.028, right: P = 0.035), while the NAA/(Cho + Cr) ratio was decreased only in the right hippocampus (RH) (P = 0.004) in patients with TLE compared with that of the NCs. Whereas the NAA/(Cho + Cr) ratio showed a consistent decreasing trend in bilateral hippocampus during the CSH, it only showed a significant difference in the RH. The GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased in the short seizure history (<10 years) patients with TLE compared with NCs (left: P = 0.018, right: P = 0.012), whereas the long seizure history (≥10 years) patients with TLE showed no difference with the NCs. However, in the ACC, the GABA/Cr ratio of the CI group was significantly decreased compared with that of NCs (P = 0.015). Further analysis showed that the patients with TLE with CI had obvious atrophy of the gray matter volume (GMV) and total parenchymal brain volume (PBV); GABA/Cr ratio was decreased in ACC, but increased in bilateral hippocampus compared with that of the no cognitive impairment (NOCI) group.
The GABA/Cr ratio was more valuable than the NAA/(Cho + Cr) ratio in evaluating the dynamic metabolite changes in patients with TLE. Importantly, the GABA changes in the hippocampal and ACC regions were not consistent during different stages of the disease. In the bilateral hippocampus, the GABA/Cr ratio was decreased at the early stage, but recovered to normal levels later. The decreased GABA/Cr ratio in the ACC might indicate more cerebral cortex was involved, resulting in more CI in patients with TLE.
通过定量磁共振波谱（MRS）探索健康对照组和颞叶癫痫（TLE）患者双侧海马和前扣带回（ACC）中γ-氨基丁酸（GABA）水平的变化，以及GABA 水平与临床症状的相关性。
采用 Meshcher-Garwood 点分辨波谱（MEGA-PRESS）定量测量 40 例 TLE 患者和 26 例健康对照（NC）受试者双侧海马和 ACC 中的 N-乙酰天门冬氨酸（NAA）、肌酸（Cr）、胆碱（Cho）和 GABA 水平。比较 NC 组和 TLE 组的 NAA/（Cho+Cr）和 GABA/Cr 比值。还比较了 TLE 患者中侧化（左 TLE、右 TLE 和不确定）、短（<10 年）和长（≥10 年）临床癫痫发作史（CSH）、低（<1/月）和高（≥1/月）癫痫发作频率（SF）、有和无认知障碍（CI）亚组之间的比值，以及 TLE 患者的抗癫痫药物。对 TLE 患者中伴有和不伴有 CI 的临床资料和代谢物比值进行了进一步分析。
与 NC 相比，TLE 患者双侧海马（左侧：P=0.028，右侧：P=0.035）的 GABA/Cr 比值显著降低，而只有右侧海马（RH）的 NAA/（Cho+Cr）比值降低（P=0.004）。尽管 NAA/（Cho+Cr）比值在 CSH 期间在双侧海马中呈持续下降趋势，但仅在 RH 中存在显著差异。疾病不同阶段，海马和 ACC 区域的 GABA 变化不一致。在双侧海马中，与 NC 相比，TLE 患者中短癫痫发作史（<10 年）的 GABA/Cr 比值降低（左侧：P=0.018，右侧：P=0.012），而长癫痫发作史（≥10 年）的 TLE 患者与 NC 之间无差异。然而，在 ACC 中，CI 组的 GABA/Cr 比值明显低于 NC（P=0.015）。进一步分析表明，伴有 CI 的 TLE 患者灰质体积（GMV）和总脑实质体积（PBV）明显萎缩；ACC 中的 GABA/Cr 比值降低，但双侧海马中的 GABA/Cr 比值升高，与无认知障碍（NOCI）组相比。
与 NAA/（Cho+Cr）比值相比，GABA/Cr 比值在评估 TLE 患者的动态代谢物变化方面更有价值。重要的是，在疾病的不同阶段，海马和 ACC 区域的 GABA 变化不一致。在双侧海马中，GABA/Cr 比值在早期降低，但后来恢复正常水平。ACC 中 GABA/Cr 比值的降低可能表明更多的皮质参与，导致 TLE 患者更多的 CI。
