mNGS技术诊断11例人类免疫缺陷病毒相关进行性多灶性白质脑病及其临床特征

Diagnosis and clinical characteristics of 11 cases of human immunodeficiency virus associated progressive multifocal leukoencephalopathy by mNGS technique

目的总结经脑脊液宏基因组二代测序(metagenomic next-generation sequencing,mNGS)技术诊断人类免疫缺陷病毒(human immunodeficiency virus,HIV)相关进行性多灶性白质脑病(progressive multifocal leukoencephalopathy,PML)患者的临床特征,为诊断PML提供参考。方法回顾性分析2019年1月至2021年6月本市公共卫生医疗救治中心感染科收治的HIV感染者且通过mNGS技术诊断为PML患者临床资料,并复习相关文献。结果11例HIV相关PML患者纳入分析,其中男7例,女4例,年龄(45.9±10.9)岁。CD4^(+)T淋巴细胞计数的中位值为52(20~146)个/μL。除2例患者外,其余9例均在入院后才确诊HIV感染;患者最常见的临床表现为肢体乏力、认知功能下降和头晕,分别占10/11、8/11和5/11。头颅MRI提示颅内广泛病变,可见多发条片、斑片状异常信号。11例患者脑脊液总蛋白及细胞数正常或轻度升高,糖、氯化物均正常;mNGS检测脑脊液JC病毒序列数为1~467条不等。患者确诊HIV后均接受高效抗逆转录病毒疗法(highly active antiroviral therapy,HARRT)治疗。至最后随访时间(2021年12月),有6例患者存活,其中3例症状好转,3例病情稳定;3例死亡,确诊PML至死亡时间为4~13个月;2例失访。结论PML临床表现多样且不具特异性,影像学表现以脱髓鞘为主,脑脊液JC病毒DNA阳性可做出诊断,运用mNGS技术对诊断PML有一定优势,可作为早期诊断的补充手段。HIV相关PML治疗无特效药,一旦确诊,建议尽快启动HARRT治疗。

Objective The study aimed at summarizing the clinical characteristics of patients with HIV related progressive multifocal leukoencephalopathy(PML)diagnosed by metagenomic next-generation sequencing(mNGS),to provide reference for the diagnosis of PML.Methods The clinical data of patients with human immunodeficiency virus(HIV)who were admitted to the department of infection disease from January 2019 to June 2021 and diagnosed as PML by mNGS were retrospectively analyzed,and the relevant literature was reviewed.Results Eleven patients with HIV related PML were included in the analysis,including 7 males,with an average age of 45.9±10.9 years.The median value of CD4^(+)T lymphocyte count was 52(20~146)/μL.Nine cases were diagnosed with HIV after admission.The most common clinical manifestations of patients were limb fatigue,cognitive decline and dizziness,accounting for 10/11,8/11 and 5/11,respectively.MRI of the head showed extensive intracranial lesions,with multiple clockwork and patchy abnormal signals.The total protein and cell number of cerebrospinal fluid in 11 patients were normal or slightly increased,while CSF sugar and chloride were normal.The number of JC virus sequences detected by mNGS ranged from 1 to 467.After HIV was confirmed,all patients received highly active antiretroviral therapy(HARRT).Up to the last follow-up(December 2021),6 patients survived,of which 3 were improved and 3 were stable.Three patients died,and the time from diagnosis of PML to death was 4~13 months.Two cases were lost to follow-up.Conclusion The pathogen can be quickly detected by mNGS,and the technology has advantages in the diagnosis of PML,and can be used as a supplementary means of early diagnosis.