Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study

Neuronal damage and loss is likely to underlie irreversible disability in m ultiple sclerosis (MS). The time of onset, location and extent of neuronal damage in early disease are all uncertain. To explore this issue 16 patient s with short duration, mild relapsing-remitting disease (mean disease durat ion 1.8 years, median EDSS 1) were studied using short echo time proton mag netic resonance spectroscopic imaging (H-1-MRSI) to quantify the concentrat ion of the neuronal marker N-acetyl-aspartate (NAA). The data were compared with those from 12 age-matched controls. H-1-MRSI was obtained from a 1.5- cm-thick slice just above the lateral ventricles. The Linear Combination (L C) Model combined with locally developed software allowed automated measure ment of absolute metabolite concentrations from lesions, normal-appearing w hite matter (NAWM) and cortical grey matter (CGM). MS CGM exhibited signifi cantly lower NAA (P=0.01) and myo-inositol (P=0.04) than control CGM. MS NA WM exhibited a lower concentration of NAA (P=0.01) and increased myo-inosit ol (P=0.03) than control white matter. More marked reductions in NAA and in creases in myo-inositol were seen in lesions. The reduced NAA in MS CGM and NAWM suggest that mild but widespread neuronal dysfunction or loss occurs early in the course of relapsing-remitting MS. This preliminary finding sho uld be confirmed in a larger cohort, and follow-up studies are also needed to determine the prognostic and pathophysiological significance of these ea rly changes.