Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Centre for Individualised Infection Medicine, Feodor-Lynen-Str. 15, 30625 Hannover, Germany.
Int J Mol Sci. 2019 Jan 15;20(2):337. doi: 10.3390/ijms20020337.
Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis ( 10), and subdivided them into those with elevated ( 5) and normal ( 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell's palsy and normal pressure hydrocephalus ( 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other Central nervous system (CNS) infections.
肠道病毒是病毒性脑膜炎最常见的病因之一。肠道病毒性脑膜炎仍然具有诊断挑战性，因为多达 15%的患者脑脊液 (CSF) 细胞数（一种经过充分验证的诊断筛选工具）可能正常。我们旨在确定肠道病毒性脑膜炎的潜在 CSF 生物标志物，特别是对于 CSF 细胞计数正常的病例。使用靶向液相色谱-质谱法，我们从肠道病毒性脑膜炎患者（10 例）中确定了代谢物图谱，并将其分为白细胞计数升高（5 例）和正常（5 例）的患者。将贝尔氏面瘫和正常压力脑积水患者的非炎症性 CSF 样本（19 例）用作对照。对 91 种代谢物的分析显示，脑膜炎样本中存在相当大的代谢重编程。它确定了磷脂酰胆碱 PC.ae.C36.3、天冬酰胺和甘氨酸作为肠道病毒脑膜炎的准确（AUC，0.92）综合分类器，而犬尿氨酸则是 CSF 细胞计数增加的肠道病毒性脑膜炎的完美生物标志物（AUC，1.0）。值得注意的是，PC.ae.C36.3 本身就是 CSF 细胞计数正常的肠道病毒性脑膜炎的单一准确（AUC，0.87）生物标志物，而包含 PC.ae.C36.3、PC.ae.C36.5 和 PC.ae.C38.5 的组合分类器则达到了近乎完美的分类（AUC，0.99）。总之，这项分析表明 CSF 代谢物作为肠道病毒性脑膜炎和可能其他中枢神经系统（CNS）感染的额外诊断工具的潜力。
