title: Inflammatory multiple-sclerosis plaques generate characteristic metabolic profiles in cerebrospinal fluid.
abstract: BACKGROUND
  Multiple sclerosis (MS), an inflammatory disease of the central nervous system, manifests itself in numerous forms and stages. A number of brain metabolic alterations have been reported for MS patients vs. control subjects. However, metabolite profiles of cerebrospinal fluid (CSF) are not consistent among the published MS studies, most probably due to variations in the patient cohorts studied. We undertook the first investigation of highly homogeneous MS patient cohorts to determine characteristic effects of inflammatory MS plaques on the CSF metabolome, including only patients with clinically isolated syndrome (CIS) with or without inflammatory brain plaques, and controls.
  
  
  RESULTS
  CSF obtained by lumbar puncture was analyzed by proton magnetic resonance spectroscopy. 27 metabolites were quantified. Differences between groups of control subjects (n = 10), CIS patients with (n = 21) and without (n = 12) inflammatory plaques were evaluated by univariate statistics and principal component analysis (PCA). Seven metabolites showed statistically significant inter-group differences (p<0.05). Interestingly, a significant increase in beta-hydroxyisobutyrate (BHIB) was detected in CIS with vs. without active plaques, but not when comparing either CIS group with control subjects. Moreover, a significant correlation was found, for the first time, between CSF lactate concentration and the number of inflammatory MS brain plaques. In contrast, fructose concentrations were equally enhanced in CIS with or without active plaques. PCA based on all 27 metabolites yielded group-specific clusters.
  
  
  CONCLUSIONS
  CSF metabolic profiles suggest a close link between MS plaque activity in CIS patients on the one hand and organic-acid metabolism on the other. Our detection of increased BHIB levels points to a hitherto unsuspected role for this compound in MS with active plaques, and serves as a basis for further investigation. The metabolic effects described in our study are crucial elements in the explanation of biochemical mechanisms involved in specific MS manifestations.
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale, UMR CNRS 6612, Faculté de Médecine de la Timone, Université de la Méditerranée, Marseille, France. Norbert.Lutz@medecine.univ-mrs.fr
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Lutz
authors.forename: Angèle
authors.initials: A
authors.lastname: Viola
authors.forename: Irina
authors.initials: I
authors.lastname: Malikova
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cozzone
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D001921:Brain / Q000473:pathology; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006462:Hemolytic Plaque Technique; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013577:Syndrome
chemical_list: D000596:Amino Acids; D005632:Fructose; D003404:Creatinine; D005947:Glucose