Abstract
Meningitis, encephalitis, and myelitis are various forms of acute central nervous system (CNS) inflammation, which can coexist and lead to serious sequelae. Known aetiologies include infections and immune-mediated processes. Despite advances in clinical microbiology over the past decades, the cause of acute CNS inflammation remains unknown in approximately 50% of cases. High-throughput sequencing was performed to search for viral sequences in cerebrospinal fluid (CSF) samples collected from 26 patients considered to have acute CNS inflammation of unknown origin, and 10 patients with defined causes of CNS diseases. In order to better grasp the clinical significance of viral sequence data obtained in CSF, 30 patients without CNS disease who had a lumbar puncture performed during elective spinal anaesthesia were also analysed. One case of human astrovirus (HAstV)-MLB2-related meningitis and disseminated infection was identified. No other viral sequences that can easily be linked to CNS inflammation were detected. Viral sequences obtained in all patient groups are discussed. While some of them reflect harmless viral infections, others result from reagent or sample contamination, as well as index hopping. Altogether, this study highlights the potential of high-throughput sequencing in identifying previously unknown viral neuropathogens, as well as the interpretation issues related to its application in clinical microbiology.
Highlights
Acute central nervous system (CNS) inflammation, encompassing meningitis, encephalitis, myelitis, or any combination of these entities, results either from infection or dysimmunity [1,2].Genes 2019, 10, 625; doi:10.3390/genes10080625 www.mdpi.com/journal/genesAmong infectious causes, viruses are the main culprits clinicians must search for, once pyogenic bacterial meningitis and nonpyogenic agents, such as Mycobacterium tuberculosis or Listeria monocytogenes (Lm), have been excluded [2,3,4]
This study reports the High-throughput sequencing (HTS) analysis results of cerebrospinal fluid (CSF) samples collected from 26 patients presenting with
HTS led to the identification of other sequences assigned to viruses, some of them known to be associated with human infection and diseases but their causal role in CNS inflammation in our cases cannot be ascertained
Summary
Acute central nervous system (CNS) inflammation, encompassing meningitis, encephalitis, myelitis, or any combination of these entities, results either from infection or dysimmunity [1,2]. Viruses are the main culprits clinicians must search for, once pyogenic bacterial meningitis and nonpyogenic agents, such as Mycobacterium tuberculosis or Listeria monocytogenes (Lm), have been excluded [2,3,4]. Despite significant improvements in microbiological investigations in the past decades through implementation of sensitive PCR-based assays performed on cerebrospinal fluid (CSF) or on cerebral biopsy samples, the cause of acute meningo-encephalitis remains unknown in approximately 50% of cases [2,3]. High-throughput sequencing (HTS) represents a tool enabling an unbiased microbial detection [7,8]
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