AIM To explore the cerebrospinal fluid (CSF) metabolite features in acute neuroinflammatory diseases and identify potential biomarkers to diagnose and monitor neuroinflammation. METHOD A cohort of 14 patients (five females, nine males; mean [median] age 7y 9mo [9y], range 6mo-13y) with acute encephalitis (acute disseminated encephalomyelitis n=6, unknown suspected viral encephalitis n=3, enteroviral encephalitis n=2, seronegative autoimmune encephalitis n=2, herpes simplex encephalitis n=1) and age-matched non-inflammatory neurological disease controls (n=14) were investigated using an untargeted metabolomics approach. CSF metabolites were analyzed with liquid chromatography coupled to high resolution mass spectrometry, followed by subsequent multivariate and univariate statistical methods. RESULTS A total of 35 metabolites could be discriminated statistically between the groups using supervised orthogonal partial least squares discriminant analysis and analysis of variance. The tryptophan-kynurenine pathway contributed nine key metabolites. There was a statistical increase of kynurenine, quinolinic acid, and anthranilic acid in patients with encephalitis, whereas tryptophan, 3-hydroxyanthrnailic acid, and kynurenic acid were decreased. The nitric oxide pathway contributed four metabolites, with elevated asymmetric dimethylarginine and argininosuccinic acid, and decreased arginine and citrulline in patients with encephalitis. An increase in the CSF kynurenine/tryptophan ratio (p<0.001), anthranilic acid/3-hydroxyanthranilic acid ratio (p<0.001), asymmetric dimethylarginine/arginine ratio (p<0.001), and neopterin (p<0.001) strongly predicted neuroinflammation. INTERPRETATION The combination of alterations in the tryptophan-kynurenine pathway, nitric oxide pathway, and neopterin represent a useful potential panel for neuroinflammation and holds potential for clinical translation practice.

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色氨酸-犬尿氨酸和一氧化氮途径中的脑脊液代谢物：急性神经炎症的生物标志物

目的 探索急性神经炎症性疾病的脑脊液 (CSF) 代谢物特征，并确定诊断和监测神经炎症的潜在生物标志物。方法 一组 14 名急性脑炎患者（5 名女性，9 名男性；平均 [中位] 年龄 7 岁 9 个月 [9 岁]，范围 6 个月至 13 岁）患有急性脑炎（急性播散性脑脊髓炎 n=6，未知疑似病毒性脑炎 n=3，肠病毒性脑炎）使用非靶向代谢组学方法研究了 n=2、血清阴性自身免疫性脑炎 n=2、单纯疱疹脑炎 n=1）和年龄匹配的非炎症性神经系统疾病对照（n=14）。CSF 代谢物用液相色谱法与高分辨率质谱联用进行分析，然后是随后的多变量和单变量统计方法。结果 使用监督正交偏最小二乘判别分析和方差分析，总共有 35 种代谢物可以在组间进行统计区分。色氨酸-犬尿氨酸途径贡献了九种关键代谢物。脑炎患者的犬尿氨酸、喹啉酸和邻氨基苯甲酸有统计学意义的增加，而色氨酸、3-羟基邻氨基苯甲酸和犬尿氨酸则减少。一氧化氮途径贡献了四种代谢物，在脑炎患者中，不对称二甲基精氨酸和精氨琥珀酸升高，精氨酸和瓜氨酸降低。脑脊液犬尿氨酸/色氨酸比率（p<0.001）、邻氨基苯甲酸/3-羟基邻氨基苯甲酸比率（p<0.001）、不对称二甲基精氨酸/精氨酸比率（p<0.001）和新蝶呤（p<0. 001）强烈预测神经炎症。解释 色氨酸-犬尿氨酸通路、一氧化氮通路和新蝶呤的改变组合代表了神经炎症的有用潜在面板，并具有临床转化实践的潜力。