title: The improvement of cognitive functions is associated with a decrease of plasma Osteopontin levels in Natalizumab treated relapsing multiple sclerosis.
abstract: OBJECTIVE
  To investigate the effect of two-years Natalizumab treatment on plasma Osteopontin levels, cognitive performances and fatigue in relapsing multiple sclerosis (RRMS) patients.
  
  
  METHODS
  Forty-nine RRMS patients scheduled for Natalizumab treatment as second-line therapy were enrolled. Plasma samples of twenty-four treatment-naïve RRMS and 22 healthy controls (HCs) were used as controls of baseline Osteopontin levels. Plasma Osteopontin levels, using an enzyme-linked immunosorbent assay, cognitive functions using the brief repeatable battery, and fatigue, by the fatigue severity scale (FSS), were assessed at baseline and every 12months. A global cognitive impairment index (CII) was calculated for each patient.
  
  
  RESULTS
  Patients scheduled for Natalizumab treatment had higher baseline Osteopontin levels (mean [SD] 65.42 [22.20]ng/ml) (p=0.013) than HCs (53.20 [12.68]ng/ml), but not different from those in the treatment-naïve RRMS group (67.70 [24.23]ng/ml); 30.6% of patients showed a cognitive impairment (failure ⩾3 tests) and 47.6% complained fatigue interfering with daily activities(FSS score ⩾4.5). A significant decrease of mean Osteopontin levels (p<0.005), of mean CII values (p<0.005) and of mean FSS score (p<0.05) was found during the treatment. Baseline Osteopontin levels significantly correlated (p=0.002) with baseline CII values, and the reduction of the CII values during Natalizumab treatment significantly correlated with the decrease of the Osteopontin levels (p<0.05). No correlations were found between Osteopontin levels and FSS score before and during Natalizumab treatment.
  
  
  CONCLUSIONS
  Natalizumab treatment reduces plasma Osteopontin levels and improves cognition and fatigue in RRMS patients. The results suggest that the improvement of cognitive functions is associated to a decrease of plasma Osteopontin levels.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Iaffaldano
authors.forename: Maddalena
authors.initials: M
authors.lastname: Ruggieri
authors.forename: Rosa Gemma
authors.initials: RG
authors.lastname: Viterbo
authors.forename: Mariangela
authors.initials: M
authors.lastname: Mastrapasqua
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000069442:Natalizumab; D053495:Osteopontin / Q000097:blood*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D053495:Osteopontin
keywords: Cognition; Multiple sclerosis; Neuropsychology; Psychoneuroimmunology