Diffusion Tensor Imaging in Male Premutation Carriers of the Fragile X Mental Retardation Gene
Diffusion Tensor Imaging in Male Premutation Carriers of the Fragile X Mental Retardation Gene
复制标题
DOI：
10.1002/mds.23646
复制
发表时间：
2011-06-01
影响因子：
8.6
通讯作者：
Rivera, Susan M.
中科院分区：
文献类型：
--
作者：
Hashimoto, Ryu-ichiro;Srivastava, Siddharth;Rivera, Susan M.
老年男性FMR 1基因前突变携带者与发生迟发性神经退行性疾病、脆性X相关震颤/共济失调综合征的风险相关。虽然以前的尸检和体内磁共振成像研究表明白色物质病理，区域选择性异常，以及它们与FMR 1基因的分子变量的关系，还没有被调查。在这项研究中，我们使用扩散张量成像研究男性前突变携带者，有和没有脆性X相关震颤/共济失调综合征和健康的性别匹配的控制。我们对小脑-脑干和边缘系统的主要白色物质束的各向异性分数和轴向和径向扩散率进行了感兴趣的分析。与健康对照组相比，脆性X相关震颤/共济失调综合征患者在多个白色物质束中表现出明显的各向异性分数降低，包括小脑中脚、小脑上级脚、大脑脚、穹窿和终纹。分数各向异性在这些道显着减少证实了体素分析，使用基于道的空间统计。轴向和径向弥散系数的分析表明，这些措施在小脑中脚显着升高，即使在没有脆性X相关震颤/共济失调综合征的前突变携带者。此外，回归分析表明，CGG重复序列大小与小脑中脚的轴向和径向扩散率之间存在明显的倒U形关系。这些结果提供了新的证据，从扩散张量成像的白色物质异常的小脑脑干和边缘系统与脆性X前突变的个人，并建议参与的分子机制相关的FMR 1基因在他们的白色物质病理。(C)2011年运动障碍学会
Older male premutation carriers of the FMR1 gene are associated with the risk of developing a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. Although previous postmortem and in vivo magnetic resonance imaging studies have indicated white matter pathology, the regional selectivity of abnormalities, as well as their relationship with molecular variables of the FMR1 gene, has not been investigated. In this study, we used diffusion tensor imaging to study male premutation carriers with and without fragile X-associated tremor/ataxia syndrome and healthy sex-matched controls. We performed a tract of interest analysis for fractional anisotropy and axial and radial diffusivities of major white matter tracts in the cerebellar-brain stem and limbic systems. Compared with healthy controls, patients with fragile X-associated tremor/ataxia syndrome showed significant reductions of fractional anisotropy in multiple white matter tracts, including the middle cerebellar peduncle, superior cerebellar peduncle, cerebral peduncle, and the fornix and stria terminalis. Significant reduction of fractional anisotropy in these tracts was confirmed by voxel-wise analysis using tract-based spatial statistics. Analysis of axial and radial diffusivities showed significant elevation of these measures in middle cerebellar peduncle, even among premutation carriers without fragile X-associated tremor/ataxia syndrome. Furthermore, regression analyses demonstrated a clear inverted U-shaped relationship between CGG-repeat size and axial and radial diffusivities in middle cerebellar peduncle. These results provide new evidence from diffusion tensor imaging for white matter abnormalities in the cerebellar-brain stem and limbic systems among individuals with the fragile X premutation and suggest the involvement of molecular mechanisms related to the FMR1 gene in their white matter pathology. (C) 2011 Movement Disorder Society