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宏基因组二代测序在单纯疱疹病毒性脑炎快速诊断及预后评估中的临床应用

Clinical application of metagenomic next-generation sequencing in rapid diagnosis and prognostic assessment of herpes simplex encephalitis.

作者信息

Tang Jin, Li Ping, Xu Haoming, Han Jingzhe

机构信息

Department of General Practice, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Department of Geriatric Respiratory, Hebei General Hospital, Shijiazhuang, Hebei, China.

出版信息

Front Microbiol. 2025 Mar 25;16:1534513. doi: 10.3389/fmicb.2025.1534513. eCollection 2025.

Abstract

PURPOSE

Herpes simplex encephalitis (HSE) ranks among the most common causes of severe viral encephalitis. It leads to meningitis or encephalitis, with patients frequently encountering adverse outcomes. In this study, we utilized metagenomic next-generation sequencing (mNGS) to rapidly and accurately detect and identify the HSV pathogen directly from cerebrospinal fluid (CSF) samples, aiming to achieve a definitive diagnosis for encephalitis patients.

METHODS

From 2018 to 2023, we prospectively identified and enrolled 28 patients diagnosed with HSE at Hengshui People's Hospital. CSF samples were subjected to mNGS to facilitate the diagnosis and characterization of HSE in this cohort. We compiled the clinical characteristics, supplementary examinations, and outcomes of HSE patients, with prognosis assessed using the Glasgow Outcome Scale (GOS) scores at discharge, 1 month post-discharge, and 3 months thereafter.

RESULTS

In this cohort of 28 patients, 12 were females and 16 males, with a mean age of 41.82 ± 18.23. HSE manifested with a variety of clinical symptoms, the most prevalent being headaches (67.9%), fever exceeding 38°C (60.7%), and altered consciousness (60.7%). Seizures (42.9%), vomiting (35.7%), and speech deficits (35.7%) were frequently observed, with a minority of patients displaying personality changes (28.6%). CSF analysis revealed pleocytosis and a mild increase in protein levels. Magnetic resonance imaging (MRI) abnormalities (28.6%) were primarily confined to the frontal and temporal lobes as well as limbic regions, with no indications of cerebral hemorrhage. Half of the patients exhibited Electroencephalogram (EEG) changes suggestive of encephalitis. HSE was confirmed through mNGS analysis of CSF within 3 days of admission. All patients received empirical treatment with ganciclovir, with 46.4% undergoing hormonotherapy and 32.1% receiving immunoglobulin therapy. At the three-month follow-up, 32.1% had GOS scores <5.

CONCLUSION

HSE often presents with nonspecific signs of encephalitis, and it's not easy for traditional CNS examinations to confirm the diagnosis. mNGS serves as a cutting-edge diagnostic tool for the rapid and precise identification of HSE, facilitating timely clinical diagnosis and intervention to prevent the progression of the disease.

摘要

目的

单纯疱疹病毒性脑炎(HSE)是严重病毒性脑炎最常见的病因之一。它可导致脑膜炎或脑炎,患者常出现不良后果。在本研究中,我们利用宏基因组下一代测序(mNGS)直接从脑脊液(CSF)样本中快速、准确地检测和鉴定HSV病原体,旨在为脑炎患者实现明确诊断。

方法

2018年至2023年,我们前瞻性地识别并纳入了衡水市人民医院28例诊断为HSE的患者。对CSF样本进行mNGS检测,以协助该队列中HSE的诊断和特征分析。我们汇总了HSE患者的临床特征、辅助检查及结局,出院时、出院后1个月及此后3个月使用格拉斯哥预后量表(GOS)评分评估预后。

结果

在这28例患者队列中,女性12例,男性16例,平均年龄41.82±18.23岁。HSE表现出多种临床症状,最常见的是头痛(67.9%)、体温超过38°C(60.7%)和意识改变(60.7%)。经常观察到癫痫发作(42.9%)、呕吐(35.7%)和言语缺陷(35.7%),少数患者表现出人格改变(28.6%)。CSF分析显示有细胞数增多和蛋白质水平轻度升高。磁共振成像(MRI)异常(28.6%)主要局限于额叶、颞叶及边缘区域,无脑出血迹象。一半患者脑电图(EEG)有提示脑炎的改变。入院3天内通过CSF的mNGS分析确诊为HSE。所有患者均接受更昔洛韦经验性治疗,46.4%接受激素治疗,32.1%接受免疫球蛋白治疗。在3个月随访时,32.1%的患者GOS评分<5。

结论

HSE常表现为脑炎的非特异性体征,传统的中枢神经系统检查不易确诊。mNGS是快速、精确鉴定HSE的前沿诊断工具,有助于及时进行临床诊断和干预,以防止疾病进展。

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