CONACYT - Instituto de Neuroetología, Universidad Veracruzana, Veracruz, Mexico.
Laboratorio de Neuropsicología, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico.
Parkinsonism Relat Disord. 2019 Sep;66:182-188. doi: 10.1016/j.parkreldis.2019.08.011. Epub 2019 Aug 19.
Spinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features.
We enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale.
TBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures.
The results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages.
脊髓小脑性共济失调 10 型（SCA10）是一种遗传性神经退行性疾病，由 ATXN10 基因的重复扩展引起。患者常表现为小脑共济失调，常伴有癫痫发作。尽管已经描述了小脑浦肯野神经元的丧失，但其大脑退化模式尚不清楚。我们的目的是描述 SCA10 患者的灰质和白质退化模式及其与临床特征的关系。
我们招募了 18 名经分子诊断为 SCA10 的患者和 18 名年龄和性别匹配的健康对照者。所有参与者均接受了包括高分辨率解剖和弥散成像在内的脑部 MRI 检查。采用全脑基于束流的空间统计学（TBSS）和基于体素的形态学（VBM）分别进行白质和灰质退变分析。在小脑内进行的二次分析确定了无偏的退变模式。使用 SARA 量表评估运动障碍。
患者组的 TBSS 分析显示小脑白质萎缩。VBM 分析显示小脑、脑干、丘脑和壳核广泛灰质退变。发现小脑退变与 SARA 评分之间存在显著相关性。此外，小脑 VI 叶的 GM 和 WM 退变与癫痫发作的存在显著相关。
结果表明，除了小脑和脑干外，SCA10 的脑退变还包括主要的壳核和丘脑；后者的参与与癫痫发作密切相关。小脑无偏退变模式的分析表明，疾病的主要小脑靶区为 VIIIb、IX 和 X 叶，后期扩展至前叶。
