title: 1H-NMR metabolic profiling of cerebrospinal fluid in patients with complex regional pain syndrome-related dystonia.
abstract: In complex regional pain syndrome (CRPS)-related dystonia, compelling evidence points to the involvement of the central nervous system, but the underpinning pathobiology is still unclear. Thus, to enable a hypothesis-free, unbiased view of the problem and to obtain new insight into the pathobiology of dystonia in CRPS, we applied an exploratory metabolomics analysis of cerebrospinal fluid (CSF) of patients with CRPS-related dystonia. (1)H-NMR spectroscopy in combination with multivariate modeling were used to investigate metabolic profiles of a total of 105 CSF samples collected from patients with CRPS-related dystonia and controls. We found a significantly different metabolic profile of CSF in CRPS patients compared to controls. The differences were already reflected in the first two principal components of the principal component analysis model, which is an indication that the variance associated with CRPS is stronger than variance caused by such classical confounders as gender, age, or individual differences. A supervised analysis generated a strong model pinpointing the most important metabolites contributed to the metabolic signature of patients with CRPS-related dystonia. From the set of identified discriminators, the most relevant metabolites were 2-keto-isovalerate, glucose, glutamine, and lactate, which all showed increased concentrations, and urea, which showed decreased concentration in CRPS subjects. Our findings point at a catabolic state in chronic CRPS patients with dystonia that is likely associated with inflammation.
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands Department of Anesthesiology, Reinier de Graaf Gasthuis, PO Box 5011, 2600 GA Delft, The Netherlands.
authors.forename: Axel
authors.initials: A
authors.lastname: Meissner
authors.forename: Anton A
authors.initials: AA
authors.lastname: van der Plas
authors.forename: Nick T
authors.initials: NT
authors.lastname: van Dasselaar
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Mayboroda
mesh_terms: D000328:Adult; D000368:Aged; D001931:Brain Mapping; D020918:Complex Regional Pain Syndromes / Q000134:cerebrospinal fluid* / Q000150:complications; D004421:Dystonia / Q000134:cerebrospinal fluid* / Q000150:complications; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D012372:ROC Curve; D014316:Tritium
chemical_list: D014316:Tritium
keywords: CSF analysis; Complex regional pain syndromes; Metabolomics; NMR