Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis

Dominica Ratuszny1, Kurt-Wolfram Sühs2,3, Natalia Novoselova4,5

  • 1Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Ratuszny.Dominica@mh-hannover.de.

Insights

New cerebrospinal fluid (CSF) biomarkers, including phosphatidylcholine PC.ae.C36.3, can improve enteroviral meningitis diagnosis, especially when CSF cell counts are normal. This aids in identifying central nervous system (CNS) infections.

Area of Science:

  • Neurovirology
  • Clinical Diagnostics
  • Metabolomics

Background:

  • Enteroviruses are a leading cause of viral meningitis, posing diagnostic challenges.
  • Cerebrospinal fluid (CSF) leukocyte counts, a standard diagnostic tool, can be normal in up to 15% of enteroviral meningitis cases.
  • The need for reliable biomarkers in diagnosing enteroviral meningitis, particularly in cases with normal cell counts, is critical.

Purpose of the Study:

  • To identify novel CSF biomarkers for enteroviral meningitis.
  • To specifically target biomarkers for enteroviral meningitis cases presenting with normal CSF leukocyte counts.
  • To investigate metabolic reprogramming in the CSF during enteroviral meningitis.

Main Methods:

  • Targeted liquid chromatography-mass spectrometry was employed to analyze CSF metabolite profiles.
  • Patients with enteroviral meningitis (n=10) were categorized based on CSF leukocyte counts (elevated vs. normal).
  • CSF samples from patients with Bell's palsy and normal pressure hydrocephalus (n=19) served as controls.

Main Results:

  • Metabolite profiling revealed significant metabolic reprogramming in meningitis samples.
  • Phosphatidylcholine PC.ae.C36.3, asparagine, and glycine formed an accurate combined classifier (AUC, 0.92) for overall enteroviral meningitis.
  • PC.ae.C36.3 alone was an accurate biomarker (AUC, 0.87) for enteroviral meningitis with normal cell counts.

Conclusions:

  • CSF metabolites show potential as supplementary diagnostic tools for enteroviral meningitis.
  • PC.ae.C36.3 is a promising biomarker for diagnosing enteroviral meningitis, especially in cases with normal CSF cell counts.
  • These findings may extend to the diagnosis of other central nervous system (CNS) infections.

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