Metabolic Abnormalities in Patients with Chronic Disorders of Consciousness.

Fanxia Meng,Benyan Luo,Fangping He,Jian Gao,Fei Chen,Jie Yu,Yamei Yu,Wangxiao Bao,Yao Yao,Woo-Ping Ge,Jintao Zhou,Jingqi Li

doi:10.14336/ad.2020.0812

Abstract

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.

Highlights

There are two major different groups of patients with chronic disorders of consciousness [1]: the vegetative state (VS) and minimally conscious state (MCS) [2, 3]
To investigate the potential relationships among different samples in the three groups, we performed a correlation analysis and observed that there was a high correlation among the samples within each group (Fig. 1A), which is consistent with the results of our unsupervised Principal component analysis (PCA) analysis: the samples from the MCS group were located between the healthy controls (HCs) and VS groups but were closer to those of the VS group (Fig. 1C)
We identified metabolites and lipids significantly altered in the VS/MCS groups compared with the HC group and those differentially regulated between the VS and MCS groups

Summary

Introduction

There are two major different groups of patients with chronic disorders of consciousness [1]: the vegetative state (VS) and minimally conscious state (MCS) [2, 3]. Metabolomics and lipidomics are high-throughput techniques for the systematic analysis of a comprehensive metabolic profiling They can effectively detect changes in lipid classes and even particular lipid species and predict their potential mechanisms and functions in various biological processes [20]. The application of metabolomics and lipidomics to the understanding of the pathogenesis of DoC is rare To address this knowledge gap, we examined both metabolite and lipid changes specific to different levels of consciousness with the ultimate goal of exploring the potential mechanisms of DoC. We did comparison of DoC patients with Alzheimer's disease (AD) and Emerged from Minimally Conscious State (EMCS) in metabolic profiling Using both untargeted and targeted lipidomic analyses, we identified potential biomarkers that can distinguish between VS and MCS patients and assessed the specificity and sensitivity of those biomarkers

Methods

Results

Conclusion