Rosas H Diana, Salat David H, Lee Stephanie Y, Zaleta Alexandra K, Pappu Vasanth, Fischl Bruce, Greve Doug, Hevelone Nathanael, Hersch Steven M
Center for Neuro-imaging of Aging and Neurodegenerative Diseases, 149 13th Street Room 2275, Charlestown, MA 02129, USA.
Brain. 2008 Apr;131(Pt 4):1057-68. doi: 10.1093/brain/awn025. Epub 2008 Mar 12.
The clinical phenotype of Huntington's disease (HD) is far more complex and variable than depictions of it as a progressive movement disorder dominated by neostriatal pathology represent. The availability of novel neuro-imaging methods has enabled us to evaluate cerebral cortical changes in HD, which we have found to occur early and to be topographically selective. What is less clear, however, is how these changes influence the clinical expression of the disease. In this study, we used a high-resolution surface based analysis of in vivo MRI data to measure cortical thickness in 33 individuals with HD, spanning the spectrum of disease and 22 age- and sex-matched controls. We found close relationships between specific functional and cognitive measures and topologically specific cortical regions. We also found that distinct motor phenotypes were associated with discrete patterns of cortical thinning. The selective topographical associations of cortical thinning with clinical features of HD suggest that we are not simply correlating global worsening with global cortical degeneration. Our results indicate that cortical involvement contributes to important symptoms, including those that have been ascribed primarily to the striatum, and that topologically selective changes in the cortex might explain much of the clinical heterogeneity found in HD. Additionally, a significant association between regional cortical thinning and total functional capacity, currently the leading primary outcome measure used in neuroprotection trials for HD, establishes cortical MRI morphometry as a potential biomarker of disease progression.
亨廷顿舞蹈症（HD）的临床表型远比将其描述为以新纹状体病理为主导的进行性运动障碍更为复杂和多变。新型神经成像方法的出现使我们能够评估HD患者大脑皮层的变化，我们发现这些变化出现得很早且具有地形学选择性。然而，尚不清楚的是这些变化如何影响该疾病的临床症状表现。在本研究中，我们对33例HD患者（涵盖疾病的各个阶段）以及22例年龄和性别匹配的对照者的活体MRI数据进行了基于高分辨率表面的分析，以测量皮层厚度。我们发现特定的功能和认知指标与拓扑学上特定的皮层区域之间存在密切关系。我们还发现不同的运动表型与皮层变薄的离散模式相关。皮层变薄与HD临床特征的选择性拓扑学关联表明，我们并非简单地将整体病情恶化与整体皮层退化相关联。我们的结果表明，皮层受累会导致重要症状，包括那些主要归因于纹状体的症状，并且皮层的拓扑学选择性变化可能解释了HD中发现的许多临床异质性。此外，区域皮层变薄与总功能能力之间存在显著关联，而总功能能力是目前HD神经保护试验中使用的主要主要结局指标，这确立了皮层MRI形态测量作为疾病进展潜在生物标志物的地位。
