Reduction in glutamine/glutamate levels in the cerebral cortex after adrenocorticotropic hormone therapy in patients with west syndrome.
Reduction in glutamine/glutamate levels in the cerebral cortex after adrenocorticotropic hormone therapy in patients with west syndrome.
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DOI：
10.1620/tjem.232.277
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发表时间：
2014-04
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通讯作者：
M. Munakata;N. Togashi;O. Sakamoto;K. Haginoya;Yasuko Kobayashi;Akira Onuma;K. Iinuma;S. Kure
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作者：
M. Munakata;N. Togashi;O. Sakamoto;K. Haginoya;Yasuko Kobayashi;Akira Onuma;K. Iinuma;S. Kure
West综合征（WS）是一种婴儿期难治性癫痫脑病，许多抗癫痫药物难以治疗，而促肾上腺皮质激素（ACTH）是治疗WS的有效药物。我们使用（1）H磁共振波谱（<$H-MRS）检查了使用合成ACTH类似物四糖丙肽（TCS）治疗对WS患者脑代谢的影响。在6例隐源性WS患者中，我们在枕叶皮质进行了单体素1H-MRS。在TCS治疗前、治疗后几天和治疗后几个月进行测量。数据还与只有轻度精神延迟的受试者进行了比较。测定的代谢物为谷氨酰胺+谷氨酸（Glx）、N-乙酰天冬氨酸（NAA）、胆碱（Cho）和肌醇（mI）;每种代谢物均表示为肌酸+磷酸肌酸的比值（总肌酸：tCr）。TCS治疗后Glx/tCr比值显著降低。与对照组相比，治疗后NAA/tCr比值也显著降低，尽管患者之间NAA信号的变化是不均匀的，与各自的结果相关。TCS治疗对Cho/tCr和mI/tCr比值无影响。Glx的减少表明谷氨酸-谷氨酰胺循环的减少，谷氨酸-谷氨酰胺循环在合成神经递质如谷氨酸和GABA中起关键作用。TCS诱导的Glx减少可能会引起突触信号转导的变化，从而解释TCS对WS的影响。NAA的变化表明神经元活性改变，这可能与WS患者的结局相关。
West syndrome (WS), an intractable epileptic encephalopathy of infancy, is refractory to many antiepileptic drugs; however, adrenocorticotropic hormone (ACTH) is an effective treatment for WS. The mechanism behind the efficacy of ACTH is mediated by biochemical processes that remain unknown. We examined the effects of ACTH therapy with tetracosactide (TCS), a synthetic ACTH analogue, on brain metabolism in patients with WS, using (1)H magnetic resonance spectroscopy (¹H-MRS). In six patients with cryptogenic WS, we performed single-voxel ¹H-MRS at the occipital lobe cortex. Measurements were taken prior to TCS treatment, a few days after therapy, and several months after therapy. Data were also compared with subjects having only mild psychomotor delays. The metabolites measured were glutamine plus glutamate (Glx), N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI); each was expressed as a ratio with creatine plus phosphocreatine (total creatine: tCr). The Glx/tCr ratio was significantly reduced after the TCS treatment. The NAA/tCr ratio was also significantly reduced after the treatment compared with the control group, although the change in NAA signal was heterogeneous among patients, correlating with respective outcomes. The Cho/tCr and mI/tCr ratios were not affected by TCS treatment. The reduction in Glx suggests a decrease in the glutamate-glutamine cycle, which plays a pivotal role in synthesizing neurotransmitters such as glutamate and GABA. TCS-induced Glx reduction may induce changes in synaptic signal transduction, thereby accounting for the effect of TCS on WS. The change in NAA indicates altered neuronal activity, which may be correlated with outcome in WS patients.