Longitudinal magnetic resonance spectroscopy in premanifest and early Huntington disease

Content Provider	Semantic Scholar
Author	Russell-Schulz, Bretta Kay, Alex L. Mac Leavitt, Blair R.
Copyright Year	2012
Abstract	Introduction Huntington disease (HD) is a neurodegenerative disease that currently has no cure and leads to severe cognitive and physical impairment which requires full-time care as the disease progresses, ultimately leading to death. The purpose of this study was to examine brain metabolites using H magnetic resonance spectroscopy (MRS) as possible biomarkers for disease progression. A previous study using a single timepoint, compared metabolite concentrations in the putamen between controls and premanifest HD (subjects possessing genetic predisposition to HD) and early-HD subjects. This study found decreased N-acetyl aspartate (NAA) and glutamate (Glu) and increased myo-inositol (mI) in early HD compared to premanifest HD. Another MRS study at 7T found significantly decreased NAA and creatine (tCr) in the putamen of manifest HD patients. The current study longitudinally examines changes in putamen metabolites across 36 months to assess the ability of MRS metabolites to be used as biomarkers and to compare the metabolite concentrations to control. It is the first study of its kind and is a part of the Track-HD cohort. Methods All subjects, early (n=30), pre-HD (n=25) and control (n=30), were recruited for TrackHD. However, only subjects that had been scanned at all four timepoints (0, 12, 24, 36 months) were included in the longitudinal analysis lowering the analyzed subject groups to: early (n=15), pre-HD (n=19) and control (n=22). A 3T MRI (Philips Healthcare) was used to collect a single voxel MR spectra on the left putamen were obtained (3.5cm x 1cm x 1.5 cm) with TR=2000ms, TE=35ms, 1024 samples and 128 averages. The spectra were analyzed using LCModel, and were normalized to the unsuppressed water spectral area as well as water concentration. Metabolites that could be fitted with a %SD of <20% were included. Seven metabolites (total NAA (tNAA), NAA, tCr, glutamate (Glu), choline (tCho), (mI), and Glu + glutamine (Glx)) were examined for each subject group and compared over the four visits. A Student’s t-test was used to compare the metabolite concentrations between subject groups within each visit, a p<0.05 was considered to be significant. Results The average metabolite concentrations for four metabolites over the four visits are shown in Figure 1 for all three patient groups. tNAA was significantly lower in earlyHD at all four time points compared to controls and pre-HD. NAA showed a similar trend to tNAA (not shown). tCr was lower in early-HD vs controls at all time points. tNAA and tCr showed the same pattern of concentrations at all time points: [Control] > [pre-HD] > [early-HD]. Glu (not shown) also showed this pattern across the four visits, but Glx was not as consistent across the timepoints (not shown). mI was found to be significantly increased compared to controls for Visits 2-4 and significantly increased from pre-HD for Visits 1-3 but not Visit 4. No significant differences in tCho concentration could be found between the three subject groups at any of the time points.
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Language	English
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Content Type	Text
Resource Type	Article