Dataset Information

Progressive Multifocal Leukoencephalopathy Diagnosed by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid in an HIV Patient.

ABSTRACT: Metagenomic next-generation sequencing (mNGS) is a novel approach to identify pathogens undetected by conventional methods. Herein, we report a case in which mNGS was used to identify JC virus from the cerebrospinal fluid sample of an HIV positive patient with progressive multifocal leukoencephalopathy (PML).

SUBMITTER: Xia H

PROVIDER: S-EPMC6882502 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Progressive Multifocal Leukoencephalopathy Diagnosed by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid in an HIV Patient.

Xia Huan H Guan Yuanlin Y Zaongo Silvère D SD Xia Han H Wang Ziyu Z Yan Zhongfang Z Ma Ping P

Frontiers in neurology 20191121

Metagenomic next-generation sequencing (mNGS) is a novel approach to identify pathogens undetected by conventional methods. Herein, we report a case in which mNGS was used to identify JC virus from the cerebrospinal fluid sample of an HIV positive patient with progressive multifocal leukoencephalopathy (PML). ...[more]

PMID: 31824396

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Project description:The implementation of a variety of immunosuppressive therapies has made drug-associated progressive multifocal leukoencephalopathy (PML) an increasingly prevalent clinical entity. The purpose of this study was to investigate its diagnostic characteristics and to determine whether differences herein exist between the multiple sclerosis (MS), neoplasm, post-transplantation, and autoimmune disease subgroups. Reports of possible, probable, and definite PML according to the current diagnostic criteria were obtained by a systematic search of PubMed and the Dutch pharmacovigilance database. Demographic, epidemiologic, clinical, radiological, cerebrospinal fluid (CSF), and histopathological features were extracted from each report and differences were compared between the disease categories. In the 326 identified reports, PML onset occurred on average 29.5 months after drug introduction, varying from 14.2 to 37.8 months in the neoplasm and MS subgroups, respectively. The most common overall symptoms were motor weakness (48.6 %), cognitive deficits (43.2 %), dysarthria (26.3 %), and ataxia (24.1 %). The former two also constituted the most prevalent manifestations in each subgroup. Lesions were more often localized supratentorially (87.7 %) than infratentorially (27.4 %), especially in the frontal (64.1 %) and parietal lobes (46.6 %), and revealed enhancement in 27.6 % of cases, particularly in the MS (42.9 %) subgroup. Positive JC virus results in the first CSF sample were obtained in 63.5 %, while conversion after one or more negative outcomes occurred in 13.7 % of cases. 52.2 % of patients died, ranging from 12.0 to 83.3 % in the MS and neoplasm subgroups, respectively. In conclusion, despite the heterogeneous nature of the underlying diseases, motor weakness and cognitive changes were the two most common manifestations of drug-associated PML in all subgroups. The frontal and parietal lobes invariably constituted the predilection sites of drug-related PML lesions.

Project description:PurposeThe application of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains poorly characterized. Here, we retrospectively analyzed data from patients with TBM who had taken both mNGS and conventional tests including culture of Mycobacterium tuberculosis (MTB), polymerase chain reaction (PCR) and acid-fast bacillus (AFB) stain, and the sensitivity and specificity of these methods were compared.MethodsWe retrospectively recruited TBM patients admitted to the hospital between December 2015 and October 2018. The first collection of cerebrospinal fluid (CSF) samples underwent both mNGS and conventional tests. In addition, patients with bacterial/cryptococcal meningitis or viral meningoencephalitis were mNGS positive controls, and a patient with auto-immune encephalitis was an mNGS negative control.ResultsTwenty three TBM patients were classified as 12 definite and 11 clinical diagnoses, which were based on clinical manifestations, pathogen evidence, CSF parameters, brain imaging, and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MBTC) from 18 samples (18/23, 78.26%). In patients with definite TBM, the sensitivity of mNGS, AFB, PCR, and culture to detect MTB in the first CSF samples were 66.67, 33.33, 25, and 8.33%, respectively. The specificity of each method was 100%. Among the four negative mNGS cases (4/23, 17.39%), three turned out positive by repeated AFB stain. The agreement of mNGS with the total of conventional methods was 44.44% (8/18). Combination of mNGS and conventional methods increased the detection rate to 95.65%. One patient was diagnosed as complex of TBM and cryptococcal meningitis, in which AFB stain and cryptococcal antigen enzyme immunoassay were positive and the DNA of Cryptococcus neoformans was detected by mNGS.ConclusionOur study indicates that mNGS is an alternative method to detect the presence of mycobacterial DNA in CSF samples from patients with TBM and deserves to be applied as a front-line CSF test.

Dataset Information

Progressive Multifocal Leukoencephalopathy Diagnosed by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid in an HIV Patient.

Publications

Progressive Multifocal Leukoencephalopathy Diagnosed by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid in an HIV Patient.

Similar Datasets

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