Axonal injury and overall tissue loss are not related in primary progressive multiple sclerosis

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 (H-1-MRS) can be used to measure in vivo wholebrain N-acetylaspartate (WBNAA) concentrations, the decrease of whose levels is considered a marker of neuronal-axonal injury. Objectives: To study WBNAA H-1-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) H-1-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. 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 H-1-MRS and atrophy assessment may provide in vivo complementary information about the actual extent of brain damage in PPMS.