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

• Published in: NMR in biomedicine 2010-02, Vol.23 (2), p.123-132
• Main Authors: Sinclair, Alexandra J., Viant, Mark R., Ball, Alexandra K., Burdon, Michael A., Walker, Elizabeth A., Stewart, Paul M., Rauz, Saaeha, Young, Stephen P.
• Format: Article
• Language: English
• Subjects: 1H NMR spectroscopy; Adult; biomarkers; cerebrospinal fluid and serum; Cohort Studies; diagnosis; Discriminant Analysis; Female; Humans; Least-Squares Analysis; Magnetic Resonance Spectroscopy - methods; Male; metabolic profiling; Metabolome; metabolomics; Metabolomics - methods; Middle Aged; Multivariate Analysis; Nervous System Diseases - blood; Nervous System Diseases - cerebrospinal fluid; Nervous System Diseases - diagnosis; neurology
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.1428

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 1H 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. Copyright © 2009 John Wiley & Sons, Ltd. 1H NMR spectroscopic analysis of cerebrospinal fluid (CSF) and serum from three pathologically distinct neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD)) defined distinct disease specific metabolite profiles. CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and for MS. The CVD serum metabolite profile was 75% sensitive and specific. Metabolomics may have the potential to be developed into a clinically useful diagnostic tool in neurology.