title: Serum lactate as a novel potential biomarker in multiple sclerosis.
abstract: Multiple sclerosis (MS) is a primary inflammatory demyelinating disease associated with a probably secondary progressive neurodegenerative component. Impaired mitochondrial functioning has been hypothesized to drive neurodegeneration and to cause increased anaerobic metabolism in MS. The aim of our multicentre study was to determine whether MS patients had values of circulating lactate different from those of controls. Patients (n=613) were recruited, assessed for disability and clinically classified (relapsing-remitting, secondary progressive, primary progressive) at the Catholic University of Rome, Italy (n=281), at the MS Centre Amsterdam, The Netherlands (n=158) and at the S. Camillo Forlanini Hospital, Rome, Italy (n=174). Serum lactate levels were quantified spectrophotometrically with the analyst being blinded to all clinical information. In patients with MS serum lactate was three times higher (3.04±1.26mmol/l) than that of healthy controls (1.09±0.25mmol/l, p<0.0001) and increased across clinical groups, with higher levels in cases with a progressive than with a relapsing-remitting disease course. In addition, there was a linear correlation between serum lactate levels and the expanded disability scale (EDSS) (R(2)=0.419; p<0.001). These data support the hypothesis that mitochondrial dysfunction is an important feature in MS and of particular relevance to the neurodegenerative phase of the disease. Measurement of serum lactate in MS might be a relative inexpensive test for longitudinal monitoring of "virtual hypoxia" in MS and also a secondary outcome for treatment trials aimed to improve mitochondrial function in patients with MS.
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry Largo F. Vito 1, 00168 Rome, Italy. Electronic address: angela.amorini@rm.unicatt.it.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Amorini
authors.affiliation: Institute of Neurology, Catholic University of Rome, Largo F. Vito 1, 00168 Rome, Italy; Fondazione Don C. Gnocchi, Onlus, Piazzale Morandi 6, 20121 Milano, Italy. Electronic address: viv.nociti@libero.it.
authors.forename: Viviana
authors.initials: V
authors.lastname: Nociti
authors.affiliation: Department of Neurology, VU Medical Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: a.petzold@ion.ucl.ac.uk.
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.affiliation: Department of Neurosciences, S Camillo Forlanini Hospital, Circonvallazione Gianicolense 87 00152 Rome, Italy. Electronic address: c.gasperini@libero.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
authors.affiliation: Department of Neurosciences, S Camillo Forlanini Hospital, Circonvallazione Gianicolense 87 00152 Rome, Italy. Electronic address: e.quartuccio@libero.it.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Quartuccio
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry Largo F. Vito 1, 00168 Rome, Italy. Electronic address: g.lazzarino@libero.it.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Lazzarino
authors.affiliation: Neurotrauma and Neurodegeneretion Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston B15 2TT, Birmingham, UK. Electronic address: v.dipietro@bham.ac.uk.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Pietro
authors.affiliation: Neurotrauma and Neurodegeneretion Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston B15 2TT, Birmingham, UK; National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Edgbaston B15 2TH, Birmingham, UK. Electronic address: a.belli@bham.ac.uk.
authors.forename: Antonio
authors.initials: A
authors.lastname: Belli
authors.affiliation: Department of Neurosciences, S Camillo Forlanini Hospital, Circonvallazione Gianicolense 87 00152 Rome, Italy. Electronic address: stefano.signoretti@tiscali.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Department of Biomedicine and Prevention, Section of Neurosurgery, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy. Electronic address: vagnozzi@uniroma2.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vagnozzi
authors.affiliation: Department of Biology, Geology and Environmental Sciences, Division of Biochemistry and Molecular Biology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. Electronic address: lazzarig@unict.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lazzarino
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry Largo F. Vito 1, 00168 Rome, Italy. Electronic address: btavazzi@rm.unicatt.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tavazzi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007773:Lactates / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology; D009103:Multiple Sclerosis / Q000097:blood* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000097:blood / Q000473:pathology
chemical_list: D015415:Biomarkers; D007773:Lactates
keywords: Clinical disability; Energy penalty; Mitochondrial dysfunction; Multiple sclerosis; Serum lactate