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脑脊液病原菌二代测序在α疱疹病毒颅内感染诊断中的应用 被引量:13

Validation ofα-herpes viruses in cerebrospinal fluid from patients with intracranial infection by next-generation sequencing
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摘要 目的探讨脑脊液病原菌二代测序(NGS)技术对α疱疹病毒性脑膜炎或脑炎的诊断价值。方法选择北京协和医院神经科牵头的脑炎多中心临床登记研究中自2015年7月至2018年7月确诊的15例α疱疹病毒性脑膜炎或脑炎患者的临床资料进行研究。患者分别来源于南京脑科医院与北京协和医院,均采用脑脊液病原菌NGS技术鉴定诊断。观察15例患者进一步行脑脊液病毒PCR或抗体检测的验证结果,腰穿及脑电图、MRI检测结果,以及背景细菌核酸序列分析结果。结果15例患者中单纯疱疹病毒(HSV)-1感染8例,HSV-2感染2例,水痘-带状疱疹病毒(VZV)感染5例。4例进一步行脑脊液病毒PCR检测,8例进一步行抗体IgM检测,结果均为阳性。脑脊液生化检查结果中蛋白质含量轻度升高,达到(0.91±0.50)g/L。9例患者脑电图出现异常;HSV-1脑炎中6例患者MRI异常,表现为颞叶内侧、海马、扣带回及岛叶MRIT2相上异常高信号,可一侧受累为主或双侧同时受累。15例患者中11例发热,最高体温为(38.6±0.61)℃;头痛13例,精神行为异常8例,意识水平降低7例。所有患者检测结果中均不同程度出现可疑背景微生物,最常见的背景菌为痤疮丙酸杆菌(13.7%),其次为表皮葡萄球菌(9.59%),假单胞菌(8.22%),食酸菌(6.85%)等。结论脑脊液病原菌NGS技术可有效鉴定颅内α疱疹病毒感染,是目前已有检测方法的有效补充。 Objective To investigate the diagnostic value of next-generation sequencing(NGS)inα-herpes virus meningitis or encephalitis.Methods A multicenter clinical registration study of encephalitis based on Department of Neurology of Peking Union Hospital from July 2015 to July 2018 was performed;15 patients with meningitis or encephalitis caused byα-herpes virus in Nanjing Brain Hospital and Peking Union Hospital were identified by NGS of cerebrospinal fluid(CSF).The verification results of further CSF virus PCR or antibody detection,the results of lumbar puncture,electroencephalogram and MRI detection,and the nucleic acid sequence analysis results of background bacteria in these 15 patients were observed.Results In these 15 patients with CSFα-herpes virus infection,8 were with herpes simplex virus(HSV)-1 infection,two with HSV-2 infection and 5 with varicella zoster virus(VZV)infection;four were further tested by CSF virus PCR,and 8 were further tested by antibody IgM,and the results were all positive.The protein content in CSF biochemical examination was slightly increased to(0.91±0.50)g/L.EEG abnormalities were observed in 9 patients;MR imaging abnormalities were observed in 6 patients with HSV-1 encephalitis,presenting as abnormal high signals in MR imaging T2 phase in the medial temporal lobe,hippocampus,cingulate gyrus and insula,which could be mainly involved in one side or both sides simultaneously.Eleven patients had fever,and the highest temperature was(38.6±0.61)℃;13 patients had headache,8 had abnormal mental behavior and 7 had decreased consciousness.All patients showed different levels of suspicious background microorganisms;the most common background bacteria were propionibacterium acacne(13.7%),staphylococcus epidermidis(9.59%),pseudomonas(8.22%)and acid-eating bacteria(6.85%).Conclusion CSF NGS could be used in diagnosis of intracranialα-herpes virus infection,which can be a supplement diagnostic method currently.
作者 陆杰 关鸿志 王多浩 祝东林 尹俊雄 任海涛 石静萍 Lu Jie;Guan Hongzhi;Wang Duohao;Zhu Donglin;Yin Junxiong;Ren Haitao;Shi JingPing(Department of Neurology,Affiliated Brain Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Neurology,Peking Union Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China)
出处 《中华神经医学杂志》 CAS CSCD 北大核心 2019年第4期387-391,共5页 Chinese Journal of Neuromedicine
基金 国家自然科学基金青年项目(81500969) 江苏省青年医学人才(QNRC2016052).
关键词 二代测序 脑脊液 α疱疹病毒 病毒性脑炎 病毒性脑膜炎 Next-generation sequencing Cerebrospinal fluid α-herpes viruse Encephalitis Meningitis
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