Consistent neurodegeneration and its association with clinical progression in Huntington's disease: a coordinate-based meta-analysis.
Consistent neurodegeneration and its association with clinical progression in Huntington's disease: a coordinate-based meta-analysis.
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DOI：
10.1159/000339528
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Reetz K
中科院分区：
文献类型：
--
作者：
Dogan I;Eickhoff SB;Schulz JB;Shah NJ;Laird AR;Fox PT;Reetz K
亨廷顿病 (HD) 的神经病理学特征是在临床发病前几年开始进行性纹状体丧失。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。为了综合当前的形态测量 MRI 结果并研究临床和遗传特征对结构变化的影响，我们对 HD 中基于体素的形态测量 (VBM) 研究进行了基于坐标的荟萃分析。分析中整合了来自 17 项研究的 20 个 HD 样本，比较了总共 685 名 HD 突变携带者 [345 名症状前 (pre-HD) 和 340 名有症状 (symp-HD) 受试者] 和 507 名对照者。使用解剖可能性估计方法描述了各项研究的趋同结果。通过相关分析计算遗传和临床参数对观察 VBM 结果的可能性的影响。 HD 前的研究提供了基底神经节、杏仁核、丘脑、岛叶和枕叶区域神经退行性变的证据。在症状 HD 中，脑萎缩更加明显，并扩散到皮质区域（即额下皮质、运动前皮质、感觉运动皮质、扣带回中部、额顶皮质和颞顶皮质）。较高的胞嘧啶-腺苷-鸟苷重复序列与纹状体变性有关，而疾病进展和运动损伤的参数还与皮质萎缩相关，尤其是在感觉运动区域。 HD 的首次定量荟萃分析证明了临床转化前纹状体萎缩的程度以及进一步一致的纹状体外变性。感觉运动区似乎是症状 HD 受影响的核心区域，加上广泛的皮质萎缩，可能是 HD 临床异质性的原因。
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.