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儿童多发性硬化症中丘脑损伤的体内梯度:病理窗口。

In vivo gradients of thalamic damage in paediatric multiple sclerosis: a window into pathology.

机构信息

Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Vita-Salute San Raffaele University, Milan, Italy.

出版信息

Brain. 2021 Feb 12;144(1):186-197. doi: 10.1093/brain/awaa379.

Abstract

The thalamus represents one of the first structures affected by neurodegenerative processes in multiple sclerosis. A greater thalamic volume reduction over time, on its CSF side, has been described in paediatric multiple sclerosis patients. However, its determinants and the underlying pathological changes, likely occurring before this phenomenon becomes measurable, have never been explored. Using a multiparametric magnetic resonance approach, we quantified, in vivo, the different processes that can involve the thalamus in terms of focal lesions, microstructural damage and atrophy in paediatric multiple sclerosis patients and their distribution according to the distance from CSF/thalamus interface and thalamus/white matter interface. In 70 paediatric multiple sclerosis patients and 26 age- and sex-matched healthy controls, we tested for differences in thalamic volume and quantitative MRI metrics-including fractional anisotropy, mean diffusivity and T1/T2-weighted ratio-in the whole thalamus and in thalamic white matter, globally and within concentric bands originating from CSF/thalamus interface. In paediatric multiple sclerosis patients, the relationship of thalamic abnormalities with cortical thickness and white matter lesions was also investigated. Compared to healthy controls, patients had significantly increased fractional anisotropy in whole thalamus (f2 = 0.145; P = 0.03), reduced fractional anisotropy (f2 = 0.219; P = 0.006) and increased mean diffusivity (f2 = 0.178; P = 0.009) in thalamic white matter and a trend towards a reduced thalamic volume (f2 = 0.027; P = 0.058). By segmenting the whole thalamus and thalamic white matter into concentric bands, in paediatric multiple sclerosis we detected significant fractional anisotropy abnormalities in bands nearest to CSF (f2 = 0.208; P = 0.002) and in those closest to white matter (f2 range = 0.183-0.369; P range = 0.010-0.046), while we found significant mean diffusivity (f2 range = 0.101-0.369; P range = 0.018-0.042) and T1/T2-weighted ratio (f2 = 0.773; P = 0.001) abnormalities in thalamic bands closest to CSF. The increase in fractional anisotropy and decrease in mean diffusivity detected at the CSF/thalamus interface correlated with cortical thickness reduction (r range = -0.27-0.34; P range = 0.004-0.028), whereas the increase in fractional anisotropy detected at the thalamus/white matter interface correlated with white matter lesion volumes (r range = 0.24-0.27; P range = 0.006-0.050). Globally, our results support the hypothesis of heterogeneous pathological processes, including retrograde degeneration from white matter lesions and CSF-mediated damage, leading to thalamic microstructural abnormalities, likely preceding macroscopic tissue loss. Assessing thalamic microstructural changes using a multiparametric magnetic resonance approach may represent a target to monitor the efficacy of neuroprotective strategies early in the disease course.

摘要

丘脑是多发性硬化症中最早受神经退行性过程影响的结构之一。在儿科多发性硬化症患者中,已经描述了随着时间的推移,其侧脑室脑脊液侧的丘脑体积逐渐减少。然而,其决定因素以及可能在这种现象变得可测量之前发生的潜在病理变化,从未被探索过。使用多参数磁共振方法,我们在儿科多发性硬化症患者中定量地描述了不同的过程,这些过程可以涉及到丘脑的局灶性病变、微观结构损伤和萎缩,并根据其与脑脊液/丘脑界面和丘脑/白质界面的距离进行分布。在 70 名儿科多发性硬化症患者和 26 名年龄和性别匹配的健康对照者中,我们测试了全丘脑和丘脑白质的丘脑体积和定量磁共振指标(包括各向异性分数、平均扩散系数和 T1/T2 加权比)的差异,包括全丘脑和丘脑白质的差异,并在源于脑脊液/丘脑界面的同心带内进行了测试。在儿科多发性硬化症患者中,还研究了丘脑异常与皮质厚度和白质病变之间的关系。与健康对照组相比,患者的全丘脑各向异性分数显著增加(f2 = 0.145;P = 0.03),丘脑白质的各向异性分数降低(f2 = 0.219;P = 0.006),平均扩散系数增加(f2 = 0.178;P = 0.009),且丘脑体积有降低的趋势(f2 = 0.027;P = 0.058)。通过将全丘脑和丘脑白质分割成同心带,我们在儿科多发性硬化症中发现,靠近脑脊液的带(f2 = 0.208;P = 0.002)和靠近白质的带(f2 范围 = 0.183-0.369;P 范围 = 0.010-0.046)的各向异性分数异常明显,而我们发现靠近脑脊液的带的平均扩散系数(f2 范围 = 0.101-0.369;P 范围 = 0.018-0.042)和 T1/T2 加权比(f2 = 0.773;P = 0.001)异常明显。在 CSF/丘脑界面检测到的各向异性分数增加和平均扩散系数降低与皮质厚度减少相关(r 范围 = -0.27-0.34;P 范围 = 0.004-0.028),而在丘脑/白质界面检测到的各向异性分数增加与白质病变体积相关(r 范围 = 0.24-0.27;P 范围 = 0.006-0.050)。总的来说,我们的研究结果支持了这样一种假说,即包括来自白质病变的逆行性变性和脑脊液介导的损伤在内的异质病理过程导致了丘脑的微观结构异常,这可能发生在宏观组织丢失之前。使用多参数磁共振方法评估丘脑的微观结构变化可能代表了一种在疾病早期监测神经保护策略疗效的靶点。

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