Department of Neurology, RWTH Aachen University, Aachen.
Institute of Neuroscience and Medicine, Research Center Jülich GmbH, Jülich.
Neurodegener Dis. 2013;12(1):23-35. doi: 10.1159/000339528. Epub 2012 Aug 23.
The neuropathological hallmark of Huntington's disease (HD) is progressive striatal loss starting several years prior to clinical onset. In the past decade, whole-brain magnetic resonance imaging (MRI) studies have provided accumulating evidence for widely distributed cortical and subcortical atrophy in the early course of the disease.
In order to synthesize current morphometric MRI findings and to investigate the impact of clinical and genetic features on structural changes, we performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies in HD.
Twenty HD samples derived from 17 studies were integrated in the analysis comparing a total of 685 HD mutation carriers [345 presymptomatic (pre-HD) and 340 symptomatic (symp-HD) subjects] and 507 controls. Convergent findings across studies were delineated using the anatomical likelihood estimation approach. Effects of genetic and clinical parameters on the likelihood of observing VBM findings were calculated by means of correlation analyses.
Pre-HD studies featured convergent evidence for neurodegeneration in the basal ganglia, amygdala, thalamus, insula and occipital regions. In symp-HD, cerebral atrophy was more pronounced and spread to cortical regions (i.e., inferior frontal, premotor, sensorimotor, midcingulate, frontoparietal and temporoparietal cortices). Higher cytosine-adenosine-guanosine repeats were associated with striatal degeneration, while parameters of disease progression and motor impairment additionally correlated with cortical atrophy, especially in sensorimotor areas.
This first quantitative meta-analysis in HD demonstrates the extent of striatal atrophy and further consistent extrastriatal degeneration before clinical conversion. Sensorimotor areas seem to be core regions affected in symp-HD and, along with widespread cortical atrophy, may account for the clinical heterogeneity in HD.
亨廷顿病（HD）的神经病理学标志是在临床发病前数年开始进行性纹状体丢失。在过去的十年中，全脑磁共振成像（MRI）研究为疾病早期广泛分布的皮质和皮质下萎缩提供了越来越多的证据。
为了综合目前形态磁共振成像（MRI）的发现，并研究临床和遗传特征对结构变化的影响，我们对亨廷顿病的基于体素形态测量学（VBM）研究进行了基于坐标的荟萃分析。
将 17 项研究中的 20 个 HD 样本纳入分析，共比较了 685 名 HD 突变携带者（345 名前驱期（pre-HD）和 340 名有症状期（symp-HD）患者）和 507 名对照。使用解剖似然估计方法描绘研究之间的趋同发现。通过相关分析计算遗传和临床参数对观察 VBM 发现的可能性的影响。
前驱期研究显示基底节、杏仁核、丘脑、脑岛和枕叶区域存在神经退行性变的趋同证据。在有症状的 HD 中，脑萎缩更为明显，并扩展到皮质区域（即额下回、运动前区、感觉运动区、中扣带回、额顶区和颞顶区）。更高的胞嘧啶-腺嘌呤-鸟嘌呤重复与纹状体退化有关，而疾病进展和运动障碍的参数与皮质萎缩相关，尤其是在感觉运动区。
这是 HD 中首次进行的定量荟萃分析，证明了在临床转化前纹状体萎缩的程度以及进一步的一致的纹状体外退化。感觉运动区似乎是 symp-HD 中受影响的核心区域，并且与广泛的皮质萎缩一起，可能解释了 HD 中的临床异质性。
