Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections

Abstract

The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis (n = 32), viral meningitis/encephalitis (n = 34), and noninflamed controls (n = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly (p = 1.2 × 10−25–1.5 × 10−4) higher than in controls. Indeed, all biomarkers for bacterial meningitis vs. viral meningitis/encephalitis with an AUC ≥ 0.86 (ROC curve analysis) were phosphatidylcholines. Four of the five most accurate (AUC ≥ 0.9) phosphatidylcholine biomarkers had higher sensitivity and negative predictive values than CSF lactate or cell count. Concentrations of the 10 most accurate phosphatidylcholine biomarkers were lower in meningitis due to opportunistic pathogens than in meningitis due to typical meningitis pathogens, and they correlated most strongly with parameters reflecting blood–CSF barrier dysfunction and CSF lactate (r = 0.73–0.82), less so with CSF cell count, and not with blood CRP. In contrast to the elevated phosphatidylcholine concentrations in CSF, serum concentrations remained relatively unchanged. Taken together, these results suggest that increased free CSF phosphatidylcholines are sensitive biomarkers for bacterial meningitis and do not merely reflect inflammation but are associated with local disease and a shift in CNS metabolism.

Ventriculitis: Infection or Inflammation

“…Investigations based on metabolomics may have a role in distinguishing neuroinflammation from infection [57]. Of particular interest are lipid-based biomarkers, such as free phosphatidyl choline levels [58,59]. The CNS contains high concentrations of lipids, including phosphatidyl choline, ceramides, and sphingomyelins, all of which have important roles in the inflammatory response.…”

Metabolomic Characterization of Cerebrospinal Fluid from Intracranial Bacterial Infection Pediatric Patients: A Pilot Study

“…Therefore, further efforts are needed to dissect the co-metabolism of host and pathogen. Moreover, while our work focused on polar metabolites, it has been reported that certain lipid classes, such as phosphatidylcholines, sphingolipids and ceramides, play an important role in CNS infection [52,53]. Multi-omics characterization of CSF, as well as peripheral blood are expected for an integrated and detailed regulatory landscape regarding CNS infection.…”

Elevated acylcarnitines C4 and C5 in cerebrospinal fluid distinguish viral CNS infections from autoimmune neuroinflammation

“…We have previously applied a targeted metabolomics approach to measure 188 small molecules in CSF from 221 patients with infectious, autoimmune, and non-in ammatory CNS disorders. In previous publications we reported the identi cation of accurate biomarkers for CNS involvement in varicella-zoster virus reactivation (10), for enterovirus meningitis in patients without CSF pleocytosis (11), and for the differentiation between bacterial and viral meningitis (12,13). We have now expanded the analysis of this cohort to screen for CSF metabolite biomarkers that can accurately distinguish between viral CNS infections and autoimmune meuroin ammation and may reveal pathophysiological differences between the two.…”