G12From premanifest to manifest Huntington's disease: a 2-year follow-up study with magnetic resonance spectroscopy at 7 Tesla

BackgroundPrevious cross-sectional magnetic resonance spectroscopy (MRS) studies in Huntington's disease (HD) have demonstrated differences in metabolite concentrations compared to controls in several regions of interest, especially the putamen and caudate nucleus. It has been suggested that metabolite changes could be used as biomarker in future therapeutic trials. The aim of the present study was to assess metabolite changes in both premanifest and early HD over a 2year follow-up period using MRS at 7 Tesla.MethodsIn 13 HD gene carriers (10 premanifest and 3 manifest HD) proton MRS was performed at baseline and after 24months. At follow-up, four of the premanifest HD gene carriers had progressed into manifest HD, as assessed by clinical measures. 7T MR proton spectroscopy was performed in three regions of interest; the caudate nucleus, putamen and prefrontal cortex. Six metabolites were quantified for each region at each time point. Statistical analysis was performed using paired t-tests.ResultsIn the caudate nucleus a decrease in creatine (p=0.032) and myo-inositol (p=0.006) concentrations was observed. A significant decrease in the putamen was seen in the total N-acetylaspartate (tNAA) (p=0.022) and choline concentrations (p=0.007). Premanifest HD converters showed higher rates of tNAA decrease in the putamen (p