NMR metabolomics of cerebrospinal fluid differentiates inflammatory diseases of the central nervous system

PLoS Negl Trop Dis. 2018 Dec 17;12(12):e0007045. doi: 10.1371/journal.pntd.0007045. eCollection 2018 Dec.

Abstract

Background: Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample.

Methodology/principal findings: 1H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity.

Conclusions/significance: These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Central Nervous System / immunology
  • Central Nervous System Diseases / cerebrospinal fluid*
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / immunology
  • Cerebrospinal Fluid / chemistry*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Metabolomics / methods*
  • Young Adult

Grants and funding

This work was supported by an NIH grant 1R01AI093369 (RW), and the Zach Jones Memorial Fund (http://www.zachjonesmemorial.org) (RW). CS received no specific funding for this work, but is supported through a USDA National Institute of Food and Agriculture Hatch Project 1005945. The Bruker Advance 600 MHz NMR is supported by NIH grant RR011973. The sponsors had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.