DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany.
Department of Neurology, University Hospital Bonn, Bonn, Germany.
Mov Disord. 2021 Oct;36(10):2273-2281. doi: 10.1002/mds.28610. Epub 2021 May 5.
Given that new therapeutic options for spinocerebellar ataxias are on the horizon, there is a need for markers that reflect disease-related alterations, in particular, in the preataxic stage, in which clinical scales are lacking sensitivity.
The objective of this study was to quantify regional brain volumes and upper cervical spinal cord areas in spinocerebellar ataxia type 3 in vivo across the entire time course of the disease.
We applied a brain segmentation approach that included a lobular subsegmentation of the cerebellum to magnetic resonance images of 210 ataxic and 48 preataxic spinocerebellar ataxia type 3 mutation carriers and 63 healthy controls. In addition, cervical cord cross-sectional areas were determined at 2 levels.
The metrics of cervical spinal cord segments C3 and C2, medulla oblongata, pons, and pallidum, and the cerebellar anterior lobe were reduced in preataxic mutation carriers compared with controls. Those of cervical spinal cord segments C2 and C3, medulla oblongata, pons, midbrain, cerebellar lobules crus II and X, cerebellar white matter, and pallidum were reduced in ataxic compared with nonataxic carriers. Of all metrics studied, pontine volume showed the steepest decline across the disease course. It covaried with ataxia severity, CAG repeat length, and age. The multivariate model derived from this analysis explained 46.33% of the variance of pontine volume.
Regional brain and spinal cord tissue loss in spinocerebellar ataxia type 3 starts before ataxia onset. Pontine volume appears to be the most promising imaging biomarker candidate for interventional trials that aim at slowing the progression of spinocerebellar ataxia type 3. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
鉴于新的脊髓小脑共济失调治疗选择即将出现，因此需要有反映疾病相关变化的标志物，特别是在临床量表缺乏敏感性的前期阶段。
本研究旨在定量分析脊髓小脑共济失调 3 型患者在整个疾病过程中的脑区体积和上颈段脊髓面积。
我们应用了一种脑部分割方法，该方法包括小脑的小叶亚分割，对 210 例共济失调和 48 例前期脊髓小脑共济失调 3 型突变携带者以及 63 名健康对照者的磁共振成像进行了分析。此外，还在 2 个水平上确定了颈段脊髓的横截面积。
与对照组相比，前期突变携带者的颈段脊髓 C3 和 C2 节段、延髓、脑桥和苍白球以及小脑前叶的测量值均减小。与非共济失调携带者相比，颈段脊髓 C2 和 C3 节段、延髓、脑桥、中脑、小脑小叶 crus II 和 X、小脑白质和苍白球的测量值均减小。在所研究的所有指标中，脑桥体积在整个疾病过程中的下降幅度最大。它与共济失调严重程度、CAG 重复长度和年龄相关。该分析得出的多元模型解释了脑桥体积变化的 46.33%。
脊髓小脑共济失调 3 型患者的脑和脊髓组织损失在发病前就开始了。脑桥体积似乎是最有前途的影像学生物标志物候选者，可用于旨在减缓脊髓小脑共济失调 3 型进展的干预性试验。© 2021 作者。运动障碍由 Wiley 期刊公司代表国际帕金森病和运动障碍协会出版。
