NMR‐based metabolomic analysis of cerebrospinal fluid and serum in neurological diseases – a diagnostic tool?

Abstract

We sought to evaluate the diagnostic accuracy of metabolomic biomarker profiles in neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) compared to controls with either no neurological disease or mixed neurological diseases). Spectra of CSF (n = 87) and serum (n = 72) were acquired using (1)H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease-specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a second cohort of patients (n = 25). CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity:specificity of 63:75% and 67:75%, respectively). These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease-unique metabolites may also impart information on disease pathology.

Metabolomics in the Analysis of Inflammatory Diseases

“…Oxaloacetate levels were also increased in IIH and this, together with reduced citrate, suggests alterations in the citric acid cycle. Overall the observations suggest a predominantly anaerobic environment deficient in carbohydrate substrate in patients with IIH, a conclusion supported by the presence of elevated ketone bodies 3-hydroxybutyrate (Sinclair et al, 2010) often observed in hypoxic tissues.…”

“…In a study of metabolite fingerprints in the CSF from patients with a range of neurological conditions we have been able to differentiate between some of these conditions by comparing the metabolites found (Sinclair et al, 2010). In particular we were able to identify some novel features of idiopathic intracranial hypertension (IIH) a neurological condition, the pathogenesis of which is poorly understood (Sinclair et al, 2008).…”

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…Metabolomics provides information downstream of other techniques (e.g., genomics, transcriptomics) as well as insights into the gut microbiota and environmental exposures (4,5). The few studies that have used metabolomics in MS either examined limited metabolites or were technically unable to definitively identify many metabolites (6)(7)(8).…”

Analysis of Cerebrospinal Fluid in Diagnosis of Bacterial Meningitis; Using Nuclear Magnetic Resonance Spectroscopy: A Systematic Review

“…Establishing biomarkers of the diseases affecting central nervous system is an important goal in diagnosis and inform therapy. Metabolomics is available to define accurate disease-specific biomarkers in neurology (13).…”