Yu Jie, Meng Fanxia, He Fangping, Chen Fei, Bao Wangxiao, Yu Yamei, Zhou Jintao, Gao Jian, Li Jingqi, Yao Yao, Ge Woo-Ping, Luo Benyan
1Department of Neurology and Brain Medical Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
2Children's Research Institute, Department of Neuroscience, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA.
Aging Dis. 2021 Apr 1;12(2):386-403. doi: 10.14336/AD.2020.0812. eCollection 2021 Apr.
The vegetative state (VS) and minimally conscious state (MCS) are two major types of chronic disorders of consciousness (DoC). The assessment of these two consciousness states generally relies on the Coma Recovery Scale-Revised (CRS-R) score, but a high misdiagnosis rate limits the generalized use of this score. To identify metabolites in human plasma that can accurately distinguish VS from MCS patients, comprehensive plasma metabolic profiles were obtained with targeted metabolomics analysis and untargeted and targeted lipidomics analysis. Univariate and multivariate analyses were used to assess the significance of differences. Compared with healthy controls (HCs), the DoC groups, Emerged from Minimally Conscious State (EMCS) group and Alzheimer's disease (AD) group had significantly different metabolic profiles. Purine metabolism pathway differed the most between the DoC (MCS and VS) and HC groups. In this pathway, adenosine, ADP, and AMP, which are the derived products of ATP degradation, were decreased in the MCS and VS groups compared to healthy controls. More importantly, we identified certain lipids for which the levels were enriched in the VS or MCS groups. Specifically, phosphatidylcholine, (38:5)-H (PC(38:5)-H), and arachidonic acid (AA) differed substantially between the VS and MCS groups and may be used to distinguish these two groups of patients. Together, our findings suggest that metabolic profiling is significantly altered in patients with chronic DoC.
植物状态(VS)和微意识状态(MCS)是慢性意识障碍(DoC)的两种主要类型。对这两种意识状态的评估通常依赖于昏迷恢复量表修订版(CRS-R)评分,但高误诊率限制了该评分的广泛应用。为了确定能够准确区分VS患者和MCS患者的人血浆代谢物,采用靶向代谢组学分析以及非靶向和靶向脂质组学分析获得了全面的血浆代谢谱。使用单变量和多变量分析来评估差异的显著性。与健康对照(HC)相比,DoC组、从微意识状态苏醒(EMCS)组和阿尔茨海默病(AD)组的代谢谱有显著差异。DoC(MCS和VS)组与HC组之间嘌呤代谢途径差异最大。在该途径中,与健康对照相比,MCS组和VS组中作为ATP降解衍生产物的腺苷、ADP和AMP减少。更重要的是,我们确定了某些脂质,其水平在VS组或MCS组中富集。具体而言,磷脂酰胆碱、(38:5)-H(PC(38:5)-H)和花生四烯酸(AA)在VS组和MCS组之间有显著差异,可用于区分这两组患者。总之,我们的研究结果表明,慢性DoC患者的代谢谱有显著改变。