Reetz Kathrin, Rodríguez-Labrada Roberto, Dogan Imis, Mirzazade Shahram, Romanzetti Sandro, Schulz Jörg B, Cruz-Rivas Edilia M, Alvarez-Cuesta Jose A, Aguilera Rodríguez Raul, Gonzalez Zaldivar Yanetza, Auburger Georg, Velázquez-Pérez Luis
Department of Neurology RWTH Aachen University Pauwelsstr. 3052074 Aachen Germany.
JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging Forschungszentrum Jülich GmbH and RWTH Aachen University 52074 Aachen Germany.
Ann Clin Transl Neurol. 2018 Jan 7;5(2):128-137. doi: 10.1002/acn3.504. eCollection 2018 Feb.
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disease mainly affecting the cerebellum and brainstem. In this Cuban-German research collaboration, we aimed to characterize atrophy patterns and associations with clinical measures in preclinical and manifest SCA2.
In this study, 16 nonmanifest SCA2 mutation carriers, 26 manifest patients with SCA2, and 18 healthy control subjects underwent magnetic resonance imaging, as well as genetic and clinical characterization including assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the cerebellum and brainstem, subdivided into the medulla oblongata, the pontine brainstem, and mesencephalon was performed. Additionally, the anteroposterior diameter of the pontine brainstem was measured.
Analysis of volumetric data revealed degeneration of the cerebellum and brainstem, in particular of pontine volumes and the anteroposterior diameter of the pons, in both manifest SCA2 patients and individuals at risk for SCA2 compared to controls. Comparing patients with nonataxic preclinical SCA2 mutation carriers, we found more pronounced reductions of the pontine brainstem and cerebellum in manifest SCA2. Volumetric data further showed associations with CAG repeat length and predicted age of onset in preclinical SCA2 individuals, and by trend with ataxia signs in patients. Although saccade velocity was associated with reduction in the pontine brainstem in preclinical and manifest SCA2, reduced ability to suppress interfering stimuli measured by the Stroop task was related to cerebellar volume loss in patients.
Preclinical SCA2 mutation carriers exhibit brain abnormalities, which could be targeted as surrogate parameters for disease progression and in future preventive trials.
2型脊髓小脑共济失调（SCA2）是一种常染色体显性遗传的神经退行性疾病，主要影响小脑和脑干。在这项古巴 - 德国的合作研究中，我们旨在描述临床前和显性SCA2患者的萎缩模式及其与临床指标的关联。
在本研究中，16名未表现出症状的SCA2突变携带者、26名显性SCA2患者以及18名健康对照者接受了磁共振成像检查，同时进行了基因和临床特征分析，包括在古巴对共济失调（共济失调评估和分级量表）和扫视速度的评估。对小脑和脑干进行半自动定量容积分析，将脑干细分为延髓、脑桥和中脑。此外，还测量了脑桥的前后径。
容积数据分析显示，与对照组相比，显性SCA2患者和有SCA2患病风险的个体均出现小脑和脑干萎缩，特别是脑桥体积和脑桥前后径的萎缩。将患者与无共济失调的临床前SCA2突变携带者进行比较，我们发现显性SCA2患者的脑桥和小脑萎缩更为明显。容积数据还显示，临床前SCA2个体的脑桥和小脑萎缩与CAG重复序列长度及预测发病年龄相关，并且在患者中与共济失调体征呈趋势性相关。虽然扫视速度与临床前和显性SCA2患者的脑桥体积减小有关，但通过Stroop任务测量的抑制干扰刺激能力下降与患者的小脑体积损失有关。
临床前SCA2突变携带者存在脑部异常，这些异常可作为疾病进展的替代参数，并用于未来的预防性试验。
