title: Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis.
abstract: BACKGROUND
  There is an increasing body of evidence that magnetic resonance imaging-occult tissue damage is an important component of primary progressive multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury.
  
  
  OBJECTIVE
  To study WBNAA 1H-MRS as a tool to provide information about irreversible brain damage in PPMS and to investigate the relationship between WBNAA and other magnetic resonance imaging measures of MS disease burden, including brain atrophy.
  
  
  METHODS
  The following magnetic resonance pulse sequences of the brain were obtained from 32 patients with PPMS and 16 age-matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin-echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes were measured. Normalized brain volumes were calculated using a fully automated technique. Absolute WBNAA amounts were calculated using a phantom replacement method and were then corrected for individual subjects' brain size.
  
  
  RESULTS
  Levels of WBNAA concentrations and normalized brain volumes were significantly lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively) than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA concentrations and normalized brain volumes were included as independent factors in the final model of a multivariable analysis predicting the subjects' condition. No significant correlations were found between WBNAA values and normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes.
  
  
  CONCLUSIONS
  Axonal-neuronal damage in the brain of patients with PPMS seems to occur, at least partially, independently of the burden of magnetic resonance imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.
authors.affiliation: Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Antonio
authors.initials: A
authors.lastname: Gallo
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.forename: Beatrice
authors.initials: B
authors.lastname: Benedetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Mauro
authors.initials: M
authors.lastname: Comola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scotti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001284:Atrophy; D001369:Axons / Q000000981:diagnostic imaging / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000000981:diagnostic imaging / Q000473:pathology*; D011877:Radionuclide Imaging
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate