Visualization, quantification and correlation of brain atrophy with clinical symptoms in spinocerebellar ataxia types 1, 3 and 6
Visualization, quantification and correlation of brain atrophy with clinical symptoms in spinocerebellar ataxia types 1, 3 and 6
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DOI：
10.1016/j.neuroimage.2009.07.027
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发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Hauser, Till-Karsten
中科院分区：
文献类型：
--
作者：
Schulz, Joerg B.;Borkert, Johannes;Hauser, Till-Karsten
背景与目的：目前缺乏监测常染色体显性遗传性脊髓小脑共济失调（SCA）神经功能障碍的生物标志物。因此，我们的目的是可视化，量化和相关的局部脑萎缩与SCA1，SCA3和SCA6的临床症状。我们比较了SCA1（n = 48）、SCA3（n = 24）、和SCA6（n = 10）与32名对照使用磁共振成像（MRI）在4个不同的扫描仪在8个中心，然后基于体素的形态测定（VBM）结果：SCA1和SCA3患者的全脑干（包括中脑、脑桥脑和延髓）、脑桥、延髓、全小脑、小脑半球和小脑蚓部、壳核和尾状核严重萎缩。小脑半球的萎缩在SCA3中比在SCA1和SCA6中更轻。SCA6的萎缩仅限于小脑灰质（VBM和容量测定法）、全脑干和脑桥（仅容量测定法）。总的来说，我们没有观察到大脑皮层的实质性萎缩。判别分析考虑到数据从脑桥，小脑半球，髓质，中脑和壳核SCA1，SCA3，SCA6实现了重新分类的概率为81.7%。扩展等位基因的重复长度在SCA3中与脑干、脑桥、尾状核和壳核的体积呈弱负相关，在SCA1中与脑桥呈弱相关，而在SCA6中没有发现这种相关性。用共济失调评定量表（SARA）和统一的亨廷顿病评定量表（UHD）评定的临床功能障碍与SCA1中的脑桥萎缩、SCA3中的全脑干萎缩和SCA6中的全小脑萎缩相关性最好。结论：我们的数据提供了强有力的证据，表明MRI是SCA临床研究的一个有吸引力的替代标记物。在每种SCA基因型中，临床功能障碍可能由不同的病理解剖过程引起。(c)2009 Elsevier Inc. All rights reserved.
Background and objective: Biomarkers to monitor neurological dysfunction in autosomal dominant inherited spinocerebellar ataxias (SCA) are lacking. We therefore aimed to visualize, quantify and correlate localized brain atrophy with clinical symptoms in SCA1, SCA3, and SCA6.Methods: We compared patients suffering from SCA1 (n = 48), SCA3 (n = 24), and SCA6 (n = 10) with 32 controls using magnetic resonance imaging (MRI) on four different scanners in eight centers followed by voxel-based morphometry (VBM) and quantitative three-dimensional (3D) volumetry.Results: SCA1 and SCA3 patients presented with severe atrophy in total brainstem (consisting of midbrain, pons, and medulla), pons, medulla, total cerebellum, cerebellar hemispheres and cerebellar vermis, putamen and caudate nucleus. Atrophy in the cerebellar hemispheres was less severe in SCA3 than in SCA1 and SCA6. Atrophy in SCA6 was restricted to the grey matter of the cerebellum (VBM and volumetry), total brainstem and pons (volumetry only). Overall, we did not observe substantial atrophy in the cerebral cortex. A discriminant analysis taking into account data from pons, cerebellar hemispheres, medulla, midbrain and putamen achieved a reclassification probability of 81.7% for SCA1, SCA3, and SCA6. The repeat length of the expanded allele showed a weak negative correlation with the volume of the brainstem, pons, caudate nucleus and putamen in SCA3, and a weak correlation with the pons in SCA1, whereas no such correlation was found in SCA6. Clinical dysfunction as measured by the Scale for the Assessment and Rating of Ataxia (SARA) and the Unified Huntington's Disease Rating Scale functional assessment correlated best with the atrophy of pons in SCA1, with total brainstem atrophy in SCA3 and atrophy of total cerebellum in SCA6.Conclusions: Our data provide strong evidence that MRI is an attractive surrogate marker for clinical studies of SCA. In each SCA genotype clinical dysfunction may be caused by different patho-anatomical processes. (c) 2009 Elsevier Inc. All rights reserved.