Clinically Meaningful Magnetic Resonance Endpoints Sensitive to Preataxic Spinocerebellar Ataxia Types 1 and 3
Clinically Meaningful Magnetic Resonance Endpoints Sensitive to Preataxic Spinocerebellar Ataxia Types 1 and 3
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DOI：
10.1002/ana.26573
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发表时间：
2022-12-29
影响因子：
11.2
通讯作者：
Oz, Gulin
中科院分区：
文献类型：
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作者：
Chandrasekaran, Jayashree;Petit, Emilien;Oz, Gulin
目的：在多点试验环境中，使用先进的多模式磁共振成像(MRI)方案，确定对脊髓小脑性共济失调1型(SCA1)和3型(SCA3)的早期脑变化最敏感的磁共振(MR)指标。方法：在美欧READISCA研究中，对SCA1或SCA3突变携带者和对照组(n=107)进行磁共振扫描，使用先进的3T方案获得结构、弥散磁共振和磁共振波谱数据。对形态计量学、显微结构和神经化学指标进行盲法分析，并在共济失调前期组(n=11，n=28)、共济失调组(n=14，n=37，SCA3)和对照组(n=17)之间进行比较。使用受试者操作特征(ROC)分析确定对共济失调前异常最敏感的MR指标。结果：两组共济失调前期患者临床表现与对照组无明显差异，但脑干和小脑脚的萎缩和微结构损害以及脑桥的神经化学异常均较明显。MR指标与共济失调症状、日常生活能力和估计的共济失调持续时间密切相关。神经化学指标是SCA1(ROC曲线下面积[AUC]=0.95)中对共济失调前改变最敏感的指标，微结构指标是SCA3中共济失调前变化最敏感的指标(AUC=0.92)。解释：小脑传入和传出通路的改变是两种SCA最早症状的基础。在多点试验环境中，使用协调的先进方案收集的MR指标允许在共济失调发病之前检测个体的疾病影响，并具有潜在的临床试验用途，可用于受试者分层。Ann Neurol 2022
Objective: This study was undertaken to identify magnetic resonance (MR) metrics that are most sensitive to early changes in the brain in spinocerebellar ataxia type 1 (SCA1) and type 3 (SCA3) using an advanced multimodal MR imaging (MRI) protocol in the multisite trial setting. Methods: SCA1 or SCA3 mutation carriers and controls (n = 107) underwent MR scanning in the US-European READISCA study to obtain structural, diffusion MRI, and MR spectroscopy data using an advanced protocol at 3T. Morphometric, microstructural, and neurochemical metrics were analyzed blinded to diagnosis and compared between preataxic SCA (n = 11 SCA1, n = 28 SCA3), ataxic SCA (n = 14 SCA1, n = 37 SCA3), and control (n = 17) groups using nonparametric testing accounting for multiple comparisons. MR metrics that were most sensitive to preataxic abnormalities were identified using receiver operating characteristic (ROC) analyses. Results: Atrophy and microstructural damage in the brainstem and cerebellar peduncles and neurochemical abnormalities in the pons were prominent in both preataxic groups, when patients did not differ from controls clinically. MR metrics were strongly associated with ataxia symptoms, activities of daily living, and estimated ataxia duration. A neurochemical measure was the most sensitive metric to preataxic changes in SCA1 (ROC area under the curve [AUC] = 0.95), and a microstructural metric was the most sensitive metric to preataxic changes in SCA3 (AUC = 0.92). Interpretation: Changes in cerebellar afferent and efferent pathways underlie the earliest symptoms of both SCAs. MR metrics collected with a harmonized advanced protocol in the multisite trial setting allow detection of disease effects in individuals before ataxia onset with potential clinical trial utility for subject stratification. ANN NEUROL 2022