Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity
Cerebral cortex and the clinical expression of Huntington's disease: complexity and heterogeneity
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DOI：
10.1093/brain/awn025
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发表时间：
2008-04-01
期刊：
影响因子：
14.5
通讯作者：
Hersch, Steven M.
中科院分区：
文献类型：
--
作者：
Rosas, H. Diana;Salat, David H.;Hersch, Steven M.
亨廷顿病（HD）的临床表型远比描述它作为一种以新纹状体病理为主的进行性运动障碍复杂和多变。新的神经成像方法的可用性使我们能够评估HD的大脑皮层变化，我们发现这种变化发生得早，并且具有地形选择性。然而，尚不清楚的是，这些变化如何影响该疾病的临床表现。在这项研究中，我们使用基于高分辨率表面的体内MRI数据分析来测量33名HD患者的皮质厚度，这些患者跨越了疾病谱系和22名年龄和性别匹配的对照组。我们发现特定功能和认知测量与拓扑特异性皮质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。皮质变薄与HD临床特征的选择性地形关联表明，我们并不是简单地将全局恶化与全局皮质变性联系起来。我们的研究结果表明，皮层受损伤有助于重要的症状，包括那些主要归因于纹状体的症状，并且皮层的拓扑选择性改变可能解释HD临床异质性的大部分原因。此外，区域皮质变薄和总功能容量之间的显著关联，目前用于HD神经保护试验的主要结局指标，确立了皮质MRI形态测量作为疾病进展的潜在生物标志物。
The clinical phenotype of Huntingtons 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.