Background:

Metagenomic next-generation sequencing offers an unbiased approach to identifying viral pathogens in cerebrospinal fluid of patients with meningoencephalitis of unknown etiology.

Methods:

In an 11-month case series, we investigated the use of cerebrospinal fluid metagenomic next-generation sequencing to diagnose viral infections among pediatric hospitalized patients presenting with encephalitis or meningoencephalitis of unknown etiology. Cerebrospinal fluid from patients with known enterovirus meningitis were included as positive controls. Cerebrospinal fluid from patients with primary intracranial hypertension were included to serve as controls without known infections.

Results:

Cerebrospinal fluid metagenomic next-generation sequencing was performed for 37 patients. Among 27 patients with encephalitis or meningoencephalitis, 4 were later diagnosed with viral encephalitis, 6 had non–central nervous system infections with central nervous system manifestations, 6 had no positive diagnostic tests, and 11 were found to have a noninfectious diagnosis. Metagenomic next-generation sequencing identified West Nile virus (WNV) in the cerebrospinal fluid of 1 immunocompromised patient. Among the 4 patients with known enterovirus meningitis, metagenomic next-generation sequencing correctly identified enteroviruses and characterized the viral genotype. No viral sequences were detected in the cerebrospinal fluid of patients with primary intracranial hypertension. Metagenomic next-generation sequencing also identified sequences of nonpathogenic torque Teno virus in cerebrospinal fluid specimens from 13 patients.

Conclusions:

Our results showed viral detection by cerebrospinal fluid metagenomic next-generation sequencing only in 1 immunocompromised patient and did not offer a diagnostic advantage over conventional testing. Viral phylogenetic characterization by metagenomic next-generation sequencing could be used in epidemiologic investigations of some viral pathogens, such as enteroviruses. The finding of torque Teno viruses in cerebrospinal fluid by metagenomic next-generation sequencing is of unknown significance but may merit further exploration for a possible association with noninfectious central nervous system disorders.

中文翻译：

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通过宏基因组下一代测序对小儿脑炎的病毒进行脑脊液分析：尚未准备好迎接黄金时段？

背景：

宏基因组下一代测序提供了一种公正的方法来识别病因不明的脑膜脑炎患者脑脊液中的病毒病原体。

方法：

在一个为期 11 个月的病例系列中，我们研究了脑脊液宏基因组二代测序在诊断患有未知病因的脑炎或脑膜脑炎的儿科住院患者中的病毒感染的情况。来自已知肠道病毒性脑膜炎患者的脑脊液作为阳性对照。来自原发性颅内高压患者的脑脊液被包括作为没有已知感染的对照。

结果：

对 37 名患者进行了脑脊液宏基因组下一代测序。27 例脑炎或脑膜脑炎患者中，4 例后来被诊断为病毒性脑炎，6 例有中枢神经系统表现的非中枢神经系统感染，6 例无阳性诊断试验，11 例被发现具有非感染性诊断。宏基因组下一代测序在 1 名免疫功能低下患者的脑脊液中鉴定出西尼罗河病毒 (WNV)。在 4 名已知肠道病毒性脑膜炎患者中，宏基因组二代测序正确识别了肠道病毒并表征了病毒基因型。在原发性颅内高压患者的脑脊液中未检测到病毒序列。

结论：

我们的结果表明，脑脊液宏基因组下一代测序仅在 1 名免疫功能低下的患者中检测到病毒，与传统检测相比，并没有提供诊断优势。通过宏基因组下一代测序进行的病毒系统发育表征可用于某些病毒病原体（如肠道病毒）的流行病学调查。通过宏基因组下一代测序发现脑脊液中的扭矩 Teno 病毒具有未知的意义，但可能值得进一步探索与非感染性中枢神经系统疾病的可能关联。