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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.
Abstract:
Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell's palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other Central nervous system (CNS) infections.
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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