Centre for Molecular Medicine & Therapeutics, Vancouver, BC, Canada.
Neurology. 2010 Nov 9;75(19):1702-10. doi: 10.1212/WNL.0b013e3181fc27e4.
To evaluate in vivo brain metabolite differences in control subjects, individuals with premanifest Huntington disease (pre-HD), and individuals with early HD using ¹H magnetic resonance spectroscopy (MRS) and to assess their relationship with motor performance.
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.
Total N-acetylaspartate (tNAA), a neuronal integrity marker, was lower in early HD (∼15%) vs controls (p < 0.001). N-acetylaspartate (NAA), a constituent of tNAA, was lower in pre-HD (∼8%) and early HD (∼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 (R² = 0.23, p < 0.05). Across pre-HD and early HD, tNAA correlated with performance on a tongue pressure task (R² = 0.30, p < 0.0001) and with disease burden score (R² = 0.17, p < 0.005).
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.
使用 ¹H 磁共振波谱（MRS）评估对照组、有前驱亨廷顿病（pre-HD）个体和早期 HD 个体的脑内代谢物差异，并评估其与运动表现的关系。
85 名参与者（30 名对照组、25 名 pre-HD 和 30 名早期 HD）作为 TRACK-HD 研究的一部分被招募。84 名参与者在 3T 下进行单体素波谱左壳核扫描。pre-HD 个体的疾病负担评分＞220。受试者接受了 TRACK-HD 运动评估，包括统一亨廷顿病评定量表（UHDRS）运动评分和新型定量运动电池。统计分析包括线性回归和单向方差分析。
总 N-乙酰天门冬氨酸（tNAA），一种神经元完整性标志物，在早期 HD（约 15%）中低于对照组（p＜0.001）。N-乙酰天冬氨酸（NAA），tNAA 的组成部分，在 pre-HD（约 8%）和早期 HD（约 17%）中低于对照组（p＜0.05）。神经胶质细胞标志物肌醇（mI）在早期 HD 中比 pre-HD 高 50%（p＜0.01）。在早期 HD 中，mI 与 UHDRS 运动评分相关（R²=0.23，p＜0.05）。在 pre-HD 和早期 HD 中，tNAA 与舌压任务的表现相关（R²=0.30，p＜0.0001），与疾病负担评分相关（R²=0.17，p＜0.005）。
我们在横断面研究中发现，与对照组相比，早期 HD 的壳核 tNAA 水平降低。mI 在早期 HD 中也具有新型生物标志物作用。这些发现解决了 MRS 作为 HD 生物标志物的作用在文献中的争议。我们得出结论，壳核 MRS 测量 NAA 和 mI 是 HD 发病和进展的有前途的潜在生物标志物。
