Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution

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 (H-1-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 H-1-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 H-1-MRS quantities were significantly associated with the disease DIT over the study period. Conclusion: 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.