Longitudinal metabolite changes in Huntington's disease during disease onset

Previous cross-sectional magnetic resonance spectroscopy (MRS) studies in Huntington's disease (HD) have demonstrated differences in metabolite concentrations in several regions of interest, especially the putamen and caudate nucleus.

To assess metabolite changes in both premanifest and early HD over a two year follow up period using MRS at 7 Tesla in several regions of interest.

In 13 HD gene carriers (10 premanifest and 3 manifest HD) proton MRS was performed at baseline and after 24 months. 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 Wilcoxon signed rank tests.

Across all subjects, a longitudinal decrease in the caudate nucleus in creatine (p = 0.038) and myo-inositol (p = 0.015) concentrations was found. A significant decrease in the putamen was seen in the total N-acetylaspartate (tNAA) (p = 0.028) and choline concentrations (p = 0.028). For premanifest HD converters, a non-significant high rate of tNAA decrease in the putamen was found compared to non-converting premanifest HD.

Over a two year period we have demonstrated metabolite changes in the caudate nucleus and putamen of HD gene carriers around disease onset. This demonstrates the potential of MRS for providing a biomarker of disease progression and for evaluating future therapeutic interventions.