title: Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution.
abstract: OBJECTIVE
  To define the nature and the temporal evolution of neuronal/axonal injury in patients at the earliest clinical stage of multiple sclerosis (MS), using whole brain N-acetylaspartate (WBNAA) proton MR spectroscopy (1H-MRS).
  
  
  METHODS
  Thirty-five patients at presentation with clinically isolated syndromes (CIS) and MRI evidence of disease dissemination in space were studied. The following scans of the brain were acquired within 3 months from the onset of the disease and after 12 months: 1) dual-echo; 2) WBNAA 1H-MRS; 3) pre- and postcontrast T1-weighted. The same scans were obtained in 12 age-matched healthy subjects, without contrast administration. In patients, conventional MRI scans were also repeated 3 months after the first scanning session, to assess the presence of early disease dissemination in time (DIT).
  
  
  RESULTS
  Over the study period, 24 patients showed MRI evidence of disease DIT, thus fulfilling the criteria for a diagnosis of MS. The average WBNAA amount was lower in CIS patients than in controls both at baseline (13.7 vs 16.9 mM, p < 0.001) and at 1-year follow-up (12.6 vs 16.2 mM, p < 0.001), but the average yearly percentage change of WBNAA did not differ between the two groups. No MRI or 1H-MRS quantities were significantly associated with the disease DIT over the study period.
  
  
  CONCLUSIONS
  Irreversible brain damage associated with axonal dysfunction occurs at a very early stage in patients with clinically isolated syndromes, but it does not seem to be related with the disease evolution in the subsequent short-term period.
authors.affiliation: Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rovaris
authors.forename: A
authors.initials: A
authors.lastname: Gambini
authors.forename: A
authors.initials: A
authors.lastname: Gallo
authors.forename: A
authors.initials: A
authors.lastname: Falini
authors.forename: A
authors.initials: A
authors.lastname: Ghezzi
authors.forename: B
authors.initials: B
authors.lastname: Benedetti
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.forename: V
authors.initials: V
authors.lastname: Martinelli
authors.forename: G
authors.initials: G
authors.lastname: Comi
authors.forename: M
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D014855:Wallerian Degeneration / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology