HIGH-RESOLUTION PROTON NMR-SPECTROSCOPY OF MULTIPLE-SCLEROSIS LESIONS

Tissue from postmortem multiple sclerosis and normal control brains wa s extracted with perchloric acid and analysed using proton NMR spectro scopy. The content of N-acetyl-derived groups (the sum of N-acetylaspa rtate, acetate, and N-acetylaspartylglutamate) was decreased in multip le sclerosis plaques compared with normal control white matter (mean, 4.36 vs. 6.64 mu mol/g wet weight). In normal appearing white matter a djacent to plaques a corresponding decrease was seen, with no change i n white matter distant from plaques. A decrease in the content of tota l creatine was observed in multiple sclerosis plaques in comparison wi th normal control white matter (mean, 4.64 vs. 6.56 mu mol/g wet weigh t), which correlated strongly with the decrease in N-acetyl-derived gr oups. No changes in other metabolites such as total choline or myo-ino sitol were seen. The decreases in content of N-acetyl-derived groups a re in agreement with observations from in vivo proton NMR spectroscopy in multiple sclerosis patients. The decrease in total creatine is in contrast to most of the observations made in vivo where total creatine is assumed to be unchanged and metabolite levels are often expressed as a total creatine ratio. The use of a total creatine ratio in vivo c ould lead to an underestimation of reductions in N-acetylaspartate and an apparent increase in other metabolites in the multiple sclerosis l esion.