Abstract：
BACKGROUND: The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale to assess cerebellar ataxia but faces some criticisms about the relevancy of all its items.
OBJECTIVE: To prepare for future clinical trials, we analyzed the progression of SARA and its items in several polyQ spinocerebellar ataxias (SCA) from various cohorts.
METHODS: We included data from patients with SCA1, SCA2, SCA3, and SCA6 from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) for a total of 850 carriers and 3431 observations. Longitudinal progression of the SARA and its items was measured. Cohort, stage and genetic effects were tested. We looked at the respective contribution of each item to the total scale. Sensitivity to change of the scale and the impact of item removal was evaluated by calculating sample sizes needed in various scenarios.
RESULTS: Longitudinal progression was significantly different between cohorts in SCA1, SCA2 and SCA3, the EUROSCA cohort having the fastest progression. Advanced-stage patients were progressing slower in SCA2 and SCA6. Items were not contributing equally to the full scale through ataxia severity: gait, stance, hand movement, and heel-shin contributed the most in the early stage, and finger-chase, nose-finger, and sitting in later stages. Few items drove the sensitivity to the change of SARA, but changes in the scale structure could not improve its sensitivity in all populations.
CONCLUSIONS: SARA and its item\'s progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately.
OBJECTIVE: To prepare for future clinical trials, we analyzed the progression of SARA and its items in several polyQ spinocerebellar ataxias (SCA) from various cohorts.
METHODS: We included data from patients with SCA1, SCA2, SCA3, and SCA6 from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) for a total of 850 carriers and 3431 observations. Longitudinal progression of the SARA and its items was measured. Cohort, stage and genetic effects were tested. We looked at the respective contribution of each item to the total scale. Sensitivity to change of the scale and the impact of item removal was evaluated by calculating sample sizes needed in various scenarios.
RESULTS: Longitudinal progression was significantly different between cohorts in SCA1, SCA2 and SCA3, the EUROSCA cohort having the fastest progression. Advanced-stage patients were progressing slower in SCA2 and SCA6. Items were not contributing equally to the full scale through ataxia severity: gait, stance, hand movement, and heel-shin contributed the most in the early stage, and finger-chase, nose-finger, and sitting in later stages. Few items drove the sensitivity to the change of SARA, but changes in the scale structure could not improve its sensitivity in all populations.
CONCLUSIONS: SARA and its item\'s progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately.
摘要：
背景：共济失调评估和评级量表（SARA）是一种广泛用于评估小脑共济失调的临床量表，但对其所有项目的相关性面临一些批评。
目的：为未来的临床试验做准备，我们分析了来自不同队列的多个polyQ脊髓小脑共济失调(SCA)中SARA及其项目的进展情况.
方法：我们纳入了来自四个队列的SCA1，SCA2，SCA3和SCA6患者的数据（EUROSCA，RISCA,CRC-SCA,和SPATAX）共850个运营商和3431个观测值。测量SARA及其项目的纵向进展。队列,阶段和遗传效应进行了测试。我们查看了每个项目对总规模的各自贡献。通过计算各种情况下所需的样本量来评估对量表变化和项目删除影响的敏感性。
结果：SCA1、SCA2和SCA3队列的纵向进展有显著差异，EUROSCA队列进展最快。晚期患者SCA2和SCA6进展较慢。通过共济失调的严重程度，项目对全面的贡献不相等：步态，立场，手部运动,胫骨在早期贡献最大，和手指追逐，鼻子-手指,坐在后面的阶段。很少有项目驱动对SARA变化的敏感性，但是尺度结构的变化并不能提高其在所有人群中的敏感性。
结论：SARA及其项目的进展速度显示出不同队列和SCA的高度异质性。然而,在所有SCA或单独研究的人群中,没有项目组合可提高反应性.
目的：为未来的临床试验做准备，我们分析了来自不同队列的多个polyQ脊髓小脑共济失调(SCA)中SARA及其项目的进展情况.
方法：我们纳入了来自四个队列的SCA1，SCA2，SCA3和SCA6患者的数据（EUROSCA，RISCA,CRC-SCA,和SPATAX）共850个运营商和3431个观测值。测量SARA及其项目的纵向进展。队列,阶段和遗传效应进行了测试。我们查看了每个项目对总规模的各自贡献。通过计算各种情况下所需的样本量来评估对量表变化和项目删除影响的敏感性。
结果：SCA1、SCA2和SCA3队列的纵向进展有显著差异，EUROSCA队列进展最快。晚期患者SCA2和SCA6进展较慢。通过共济失调的严重程度，项目对全面的贡献不相等：步态，立场，手部运动,胫骨在早期贡献最大，和手指追逐，鼻子-手指,坐在后面的阶段。很少有项目驱动对SARA变化的敏感性，但是尺度结构的变化并不能提高其在所有人群中的敏感性。
结论：SARA及其项目的进展速度显示出不同队列和SCA的高度异质性。然而,在所有SCA或单独研究的人群中,没有项目组合可提高反应性.
