Brain structure in juvenile-onset Huntington disease
Brain structure in juvenile-onset Huntington disease
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DOI：
10.1212/wnl.0000000000007355
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发表时间：
2019-04-23
期刊：
影响因子：
9.9
通讯作者：
Nopoulos, Peg
中科院分区：
文献类型：
--
作者：
Tereshchenko, Alexander;Magnotta, Vincent;Nopoulos, Peg
目的评价少年型亨廷顿病(JOHD)患者和几种可能代表人类JOHD表型的亨廷顿病(HD)小鼠模型的脑形态计量学。方法尽管成人起病HD具有相同的Huntingtin基因突变，但其特征表现为多动能运动障碍，而JOHD典型表现为运动功能低下的疾病。爱荷华大学的儿童-JHD项目招收已经接受临床诊断的5至25岁的个人。本文对19例幼年先天性心脏病(JHD)患儿(平均CAG=72)进行了研究。采用横断面研究设计，将JHD患者与健康对照组(n=234)进行比较。比较不同组间结构磁共振成像的体积数据。此外，我们使用相同的程序对R6/2、zQ175、HdhQ250 HD小鼠模型的脑形态进行了评估。在控制了较小的颅内体积后，JHD患者皮质下区域(尾状核、壳核、苍白球和丘脑)和皮质白质的体积明显减小。然而，在JHD样本中，小脑按比例增大。大脑皮层基本未受影响。同样，HD小鼠的纹状体体积较小，小脑体积较高，这与人类MRI结果一致。结论JOHD的主要病理范围超出了纹状体体积的变化。小鼠和人类JHD患者的脑形态均显示成比例的小脑增大。这种脑变化模式可能解释了JHD运动障碍症状的独特图景，这在成人起病HD的高动力舞蹈样表型中是看不到的。
ObjectiveTo assess brain morphometry in a sample of patients with juvenile-onset Huntington disease (JOHD) and several mouse models of Huntington disease (HD) that likely represent the human JOHD phenotype.MethodsDespite sharing the mutation in the Huntingtin gene, adult-onset HD characteristically presents as a hyperkinetic motor disorder, while JOHD typically presents as a hypokinetic motor disease. The University of Iowa Kids-JHD program enrolls individuals 5 to 25 years of age who have already received the clinical diagnosis. A total of 19 children with juvenile HD (JHD) (mean CAG = 72) were studied. Patients with JHD were compared to healthy controls (n = 234) using a cross-sectional study design. Volumetric data from structural MRI was compared between groups. In addition, we used the same procedure to evaluate brain morphology of R6/2, zQ175, HdhQ250 HD mice models.ResultsParticipants with JHD had substantially reduced intracranial volumes. After controlling for the small intracranial volume size, the volumes of subcortical regions (caudate, putamen, globus pallidus, and thalamus) and of cortical white matter were significantly decreased in patients with JHD. However, the cerebellum was proportionately enlarged in the JHD sample. The cerebral cortex was largely unaffected. Likewise, HD mice had a lower volume of striatum and a higher volume of cerebellum, mirroring the human MRI results.ConclusionsThe primary pathology of JOHD extends beyond changes in the striatal volume. Brain morphology in both mice and human patients with JHD shows proportional cerebellar enlargement. This pattern of brain changes may explain the unique picture of hypokinetic motor symptoms in JHD, which is not seen in the hyperkinetic chorea-like phenotype of adult-onset HD.