期刊
NEUROLOGY
卷 75, 期 19, 页码 1702-1710出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3181fc27e4
关键词
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资金
- CHDI Foundation, Inc. (CHDI)
- NIH [20R-03189]
- CHDI/High Q Foundation, Inc.
- European Huntington's Disease Network
- High Q Foundation, Inc.
- Wellcome Trust
- MRC
- Genzyme Corporation
- Teva Pharmaceutical Industries Ltd.
- Multiple Sclerosis Society of Canada
- Natural Sciences and Engineering Research Council
- Canadian Institutes of Health Research
- Michael Smith Foundation
Objectives: To evaluate in vivo brain metabolite differences in control subjects, individuals with premanifest Huntington disease (pre-HD), and individuals with early HD using H-1 magnetic resonance spectroscopy (MRS) and to assess their relationship with motor performance. Methods: Eighty-five participants (30 controls, 25 pre-HD, and 30 early HD) were recruited as part of the TRACK-HD study. Eighty-four were scanned at 3 T with single-voxel spectroscopy in the left putamen. Disease burden score was >220 among pre-HD individuals. Subjects underwent TRACK-HD motor assessment including Unified Huntington's Disease Rating Scale (UHDRS) motor scoring and a novel quantitative motor battery. Statistical analyses included linear regression and one-way analysis of variance. Results: Total N-acetylaspartate (tNAA), a neuronal integrity marker, was lower in early HD (similar to 15%) vs controls (p < 0.001). N-acetylaspartate (NAA), a constituent of tNAA, was lower in pre-HD (similar to 8%) and early HD (similar to 17%) vs controls (p < 0.05). The glial cell marker, myo-inositol (mI), was 50% higher in early HD vs pre-HD (p < 0.01). In early HD, mI correlated with UHDRS motor score (R-2 = 0.23, p < 0.05). Across pre-HD and early HD, tNAA correlated with performance on a tongue pressure task (R-2 = 0.30, p < 0.0001) and with disease burden score (R-2 = 0.17, p < 0.005). Conclusions: We demonstrate lower putaminal tNAA in early HD compared to controls in a cross-section of subjects. A novel biomarker role for mI in early HD was also identified. These findings resolve disagreement in the literature about the role of MRS as an HD biomarker. We conclude that putaminal MRS measurements of NAA and mI are promising potential biomarkers of HD onset and progression. Neurology(R) 2010;75:1702-1710
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