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A. J. Sinclair, M. R. Viant, G. R. Wallace, A. K. Ball, M. A. Burdon, E. A. Walker, P. M. Stewart, S. P. Young, S. Rauz; NMR-Based Metabolomic Analysis of Cerebrospinal Fluid and Serum in Neuro-Ophthalmological and Neurological Diseases - A Diagnostic Tool?. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4036.
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Establishing biomarkers for conditions affecting the central nervous system have to date proven to be problematic. Processes such as gene transcription, and environmental factors, can affect the metabolic fingerprint of tissues. The recent innovation of metabolomic analysis of biofluids has the capacity to integrate these bio-influences into a single biomarker profile. We therefore sought to define whether metabolomic biomarker profiling of cerebrospinal fluid (CSF) and serum could potentially distinguish between idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) from patients with 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 prospectively collected cohort of patients (n=25).
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. On analysing the second prospective 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.
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