Axonal damage in multiple sclerosis plaques: a combined magnetic resonanceimaging and H-1-magnetic resonance spectroscopy study

The purpose of this study was to compare magnetic resonance imaging (MRI) f eatures and proton MR spectroscopy (H-1-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesio n subtypes. Combined MRI and single-voxel LH-MRS investigation was performe d in 54 MS patients (47 relapsing remitting (RR) and seven secondary progre ssive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions wer e Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-cont rast T-1-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypoi ntense on pre- and post-contrast T-1-weighted scans). Choline (Cho), creati ne (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in H-1 spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurolog ical controls. MS lesions of RR patients were characterized by a significan t increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No signific ant metabolite changes were found in lesions of SP patients. Gd enhancing p laques showed lactate signal with higher frequency (37.8%) than Gd unenhanc ing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p<0.01), and to Gd unenhan cing lesions (p<0.05). In particular, there was evidence of a significant i ncrease of Cho/Cr in pre-contrast T-1 hypointense Gd enhancing lesions (p<0 .01 vs. controls). The Gd unenhancing lesions (p<0.01), in particular the T -1 hypointense group (p<0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates k ey pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T-1 hypointense lesions, may re flect increased membrane cell turnover. The T-1 hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/C r. Nevertheless, the lack of statistical differences in NAA/Cr between plaq ue subgroups suggests that axonal impairment might occur even in the early stages. (C) 2001 Published by Elsevier Science B.V.