Sun Ruitan, Li Yan, Cai Ming, Cao Yunfeng, Piao Xiangyu
Department of Neurology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Department of Instrumentation and Analytical Chemistry, Dalian Institute of Chemical Physics, Dalian, China.
Front Neurol. 2019 Sep 19;10:1011. doi: 10.3389/fneur.2019.01011. eCollection 2019.
Stroke is one of the leading causes of disability all over the world. However, biomarkers for fast differential diagnosis of acute ischemic stroke (AIS) from vertigo or headache, remains lacking. Using a direct-infusion mass spectrometry method, it is possible to establish an efficient method for AIS differential diagnosis that requires only a few minutes. Thirty-eight clearly diagnosed AIS patients and 46 patients with a main complaint of vertigo were enrolled in this study. There was a total of 58 metabolites that were measured by our targeted metabolomics method, and the data were analyzed by pattern recognition algorithms. As a result, a clear classification between AIS and vertigo patients was achieved. Acylcarnitines are the major discriminating metabolites between the two groups. Arginine and its ratio, which is related to urea cycle metabolites, including arginine/ornithine and citrulline/arginine, also accounted for the classification. Interestingly, the levels of these metabolites were also found to be restored among recovering AIS patients ( = 11), which indicated that the metabolic alterations are possibly related to AIS development. Based on the characters from the data pattern reorganization, a novel biomarkers pattern was established using a binary logistic model, which contained arginine, arginine/ornithine, vaccenylcarnitine, and hydroxylbutyrylcarnitine. This biomarkers pattern achieved an area under the receiver operating characteristic curve of 0.89 for the differential diagnosis of AIS. Considering the efficiency and the diagnostic performance of the biomarkers pattern, our method has potential future use for the clinical application.
中风是全球致残的主要原因之一。然而，仍缺乏用于从眩晕或头痛中快速鉴别诊断急性缺血性中风（AIS）的生物标志物。使用直接进样质谱法，有可能建立一种仅需几分钟的AIS鉴别诊断有效方法。本研究纳入了38例明确诊断的AIS患者和46例以眩晕为主诉的患者。通过我们的靶向代谢组学方法共检测了58种代谢物，并采用模式识别算法对数据进行分析。结果，实现了AIS患者与眩晕患者之间的清晰分类。酰基肉碱是两组之间主要的鉴别代谢物。与尿素循环代谢物相关的精氨酸及其比值，包括精氨酸/鸟氨酸和瓜氨酸/精氨酸，也对分类有贡献。有趣的是，在恢复中的AIS患者（n = 11）中也发现这些代谢物水平有所恢复，这表明代谢改变可能与AIS的发展有关。基于数据模式重组的特征，使用二元逻辑模型建立了一种新的生物标志物模式，其中包含精氨酸、精氨酸/鸟氨酸、反式-11-十八烯酰肉碱和羟丁酰肉碱。这种生物标志物模式在AIS鉴别诊断的受试者工作特征曲线下面积为0.89。考虑到生物标志物模式的效率和诊断性能，我们的方法在未来临床应用中具有潜在用途。
