title: Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression.
abstract: BACKGROUND
  Altered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS).
  
  
  METHODS
  One-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one-hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored.
  
  
  RESULTS
  CSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein.
  
  
  CONCLUSIONS
  Measurement of CSF lactate may be helpful, in conjunction with other biomarkers of tissue damage, as an early predictor of disease severity in RRMS patients. A better understanding of the alterations of mitochondrial metabolic pathways associated to RRMS severity may pave the way to new therapeutic targets to contrast axonal damage and disease severity.
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.|IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, 86077, Pozzilli, IS, Italy.
authors: Maria
authors: M
authors: Albanese
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.|Clinica di Neurologia, Università Politecnica delle Marche, 60100, Ancona, Italy.
authors: Sara
authors: S
authors: Zagaglia
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.|IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, 86077, Pozzilli, IS, Italy.
authors: Doriana
authors: D
authors: Landi
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.
authors: Laura
authors: L
authors: Boffa
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.
authors: Carolina G
authors: CG
authors: Nicoletti
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.
authors: Maria Grazia
authors: MG
authors: Marciani
authors: IRCCS Fondazione Santa Lucia, 00143, Rome, Italy.
authors: Georgia
authors: G
authors: Mandolesi
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.|IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, 86077, Pozzilli, IS, Italy.
authors: Girolama A
authors: GA
authors: Marfia
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.|IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, 86077, Pozzilli, IS, Italy.
authors: Fabio
authors: F
authors: Buttari
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy.|IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, 86077, Pozzilli, IS, Italy.
authors: Francesco
authors: F
authors: Mori
authors: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy. centonze@uniroma2.it.|IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, 86077, Pozzilli, IS, Italy. centonze@uniroma2.it.
authors: Diego
authors: D
authors: Centonze
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009460:Neurologic Examination; D018709:Statistics, Nonparametric; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins; D019344:Lactic Acid