Department of Neurodegeneration and Restorative Research, Center for Neurological Medicine, University of Göttingen, Göttingen, Germany.
Neuroimage. 2010 Jan 1;49(1):158-68. doi: 10.1016/j.neuroimage.2009.07.027. Epub 2009 Jul 22.
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.
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.
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.
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.
目前缺乏用于监测常染色体显性遗传性小脑共济失调（SCA）中神经功能障碍的生物标志物。因此，我们旨在可视化、量化并将局部脑萎缩与 SCA1、SCA3 和 SCA6 的临床症状相关联。
我们在 8 个中心的 4 台不同的磁共振成像（MRI）扫描仪上比较了 SCA1（n=48）、SCA3（n=24）和 SCA6（n=10）患者与 32 名对照者的情况，随后进行了基于体素的形态计量学（VBM）和定量三维（3D）容积测量。
SCA1 和 SCA3 患者的总脑干（包括中脑、脑桥和延髓）、脑桥、延髓、总小脑、小脑半球和小脑蚓部、壳核和尾状核严重萎缩。SCA3 患者的小脑半球萎缩程度比 SCA1 和 SCA6 患者轻。SCA6 的萎缩仅限于小脑的灰质（VBM 和容积测量）、总脑干和脑桥（仅容积测量）。总的来说，我们没有观察到大脑皮质有明显的萎缩。考虑到脑桥、小脑半球、延髓、中脑和壳核的数据，判别分析实现了对 SCA1、SCA3 和 SCA6 的重新分类概率为 81.7%。SCA3 中扩张等位基因的重复长度与脑干、脑桥、尾状核和壳核的体积呈弱负相关，与 SCA1 中的脑桥呈弱相关，而在 SCA6 中则没有这种相关性。由共济失调评定量表（SARA）和统一亨廷顿病评定量表功能评估测量的临床功能障碍与 SCA1 中的脑桥萎缩、SCA3 中的总脑干萎缩和 SCA6 中的总小脑萎缩相关性最佳。
我们的数据提供了强有力的证据，证明 MRI 是 SCA 临床研究的一种有吸引力的替代标志物。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。
