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Abstract：
BACKGROUND: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Paraplegia Type 7 (SPG7) are paradigmatic spastic ataxias (SPAX) with suggested white matter (WM) involvement. Aim of this work was to thoroughly disentangle the degree of WM involvement in these conditions, evaluating both macrostructure and microstructure via the analysis of diffusion MRI (dMRI) data.
METHODS: In this multi-center prospective study, ARSACS and SPG7 patients and Healthy Controls (HC) were enrolled, all undergoing a standardized dMRI protocol and a clinimetrics evaluation including the Scale for the Assessment and Rating of Ataxia (SARA). Differences in terms of WM volume or global microstructural WM metrics were probed, as well as the possible occurrence of a spatially defined microstructural WM involvement via voxel-wise analyses, and its correlation with patients\' clinical status.
RESULTS: Data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years), 37 SPG7 (M/F = 24/13; 55.7 ± 10.7 years), and 29 HC (M/F = 13/16; 42.1 ± 17.2 years) were analyzed. While in SPG7, only a mild mean microstructural damage was found compared to HC, ARSACS patients present a severe WM involvement, with a reduced global volume (p < 0.001), an alteration of all microstructural metrics (all with p < 0.001), without a spatially defined pattern of damage but with a prominent involvement of commissural fibers. Finally, in ARSACS, a correlation between microstructural damage and SARA scores was found (p = 0.004).
CONCLUSIONS: In ARSACS, but not SPG7 patients, we observed a complex and multi-faced involvement of brain WM, with a clinically meaningful widespread loss of axonal and dendritic integrity, secondary demyelination and, overall, a reduction in cellularity and volume.
METHODS: In this multi-center prospective study, ARSACS and SPG7 patients and Healthy Controls (HC) were enrolled, all undergoing a standardized dMRI protocol and a clinimetrics evaluation including the Scale for the Assessment and Rating of Ataxia (SARA). Differences in terms of WM volume or global microstructural WM metrics were probed, as well as the possible occurrence of a spatially defined microstructural WM involvement via voxel-wise analyses, and its correlation with patients\' clinical status.
RESULTS: Data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years), 37 SPG7 (M/F = 24/13; 55.7 ± 10.7 years), and 29 HC (M/F = 13/16; 42.1 ± 17.2 years) were analyzed. While in SPG7, only a mild mean microstructural damage was found compared to HC, ARSACS patients present a severe WM involvement, with a reduced global volume (p < 0.001), an alteration of all microstructural metrics (all with p < 0.001), without a spatially defined pattern of damage but with a prominent involvement of commissural fibers. Finally, in ARSACS, a correlation between microstructural damage and SARA scores was found (p = 0.004).
CONCLUSIONS: In ARSACS, but not SPG7 patients, we observed a complex and multi-faced involvement of brain WM, with a clinically meaningful widespread loss of axonal and dendritic integrity, secondary demyelination and, overall, a reduction in cellularity and volume.
摘要：
背景：Charlevoix-Saguenay常染色体隐性遗传性痉挛性共济失调（ARSACS）和7型痉挛性截瘫（SPG7）是典型的痉挛性共济失调（SPAX），提示涉及白质（WM）。这项工作的目的是彻底解开WM参与这些情况的程度，通过扩散MRI（dMRI）数据分析评估宏观结构和微观结构。
方法：在这项多中心前瞻性研究中，纳入ARSACS和SPG7患者和健康对照（HC），所有患者均接受了标准化的dMRI方案和包括共济失调评估和评定量表(SARA)在内的临床计量学评估.探测了WM体积或全球微观结构WM指标的差异，以及通过逐体素分析可能发生的空间定义的微结构WM参与，及其与患者临床状况的相关性。
结果：37个ARSACS数据（M/F=21/16；33.4±12.4年），37SPG7（M/F=24/13；55.7±10.7年），分析了29例HC（M/F=13/16；42.1±17.2年）。而在SPG7中，与HC相比，仅发现了轻度的平均微观结构损伤，ARSACS患者出现严重的WM受累，随着全球交易量的减少(p<0.001)，所有微观结构指标的改变(均为p<0.001)，没有空间定义的损伤模式，但连合纤维明显参与。最后,在ARSACS中,发现微结构损伤与SARA评分之间存在相关性(p=0.004).
结论：在ARSACS中，但不是SPG7患者，我们观察到大脑WM的复杂和多面的参与，具有临床意义的轴突和树突完整性的广泛丧失，继发性脱髓鞘和,总的来说,细胞数量和体积的减少。
方法：在这项多中心前瞻性研究中，纳入ARSACS和SPG7患者和健康对照（HC），所有患者均接受了标准化的dMRI方案和包括共济失调评估和评定量表(SARA)在内的临床计量学评估.探测了WM体积或全球微观结构WM指标的差异，以及通过逐体素分析可能发生的空间定义的微结构WM参与，及其与患者临床状况的相关性。
结果：37个ARSACS数据（M/F=21/16；33.4±12.4年），37SPG7（M/F=24/13；55.7±10.7年），分析了29例HC（M/F=13/16；42.1±17.2年）。而在SPG7中，与HC相比，仅发现了轻度的平均微观结构损伤，ARSACS患者出现严重的WM受累，随着全球交易量的减少(p<0.001)，所有微观结构指标的改变(均为p<0.001)，没有空间定义的损伤模式，但连合纤维明显参与。最后,在ARSACS中,发现微结构损伤与SARA评分之间存在相关性(p=0.004).
结论：在ARSACS中，但不是SPG7患者，我们观察到大脑WM的复杂和多面的参与，具有临床意义的轴突和树突完整性的广泛丧失，继发性脱髓鞘和,总的来说,细胞数量和体积的减少。
