Division of Special Neurology, Department of Neurology, Medical University of Graz, Austria.
Acta Neuropathol. 2011 Aug;122(2):171-85. doi: 10.1007/s00401-011-0851-x. Epub 2011 Jun 25.
White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of normal-appearing brain tissue beyond what can be expected from standard MRI scans. There is a need for additional pre- and postmortem studies in humans, including these new imaging techniques.
脑白质病变在老年人的常规磁共振成像（MRI）扫描中普遍存在。脑白质病变的 MRI 表现和组织病理学相关性具有异质性。脑白质病变的 MRI 表现为脑室周围平滑高信号，包括侧脑室角周围的帽状结构、室管膜下和晕轮，这些病变可能是非血管性的。它们与室管膜下破坏有关，导致细胞外空间增宽，需要与皮质下和深部白质异常相鉴别。对于后者，需要区分点状、早期融合和融合性病变。尽管点状脑白质病变通常代表血管周围间隙增宽而没有实质性的缺血性组织损伤，但早期融合和融合性病变与不完全性缺血性破坏相对应。MRI 上的点状病变进展倾向较低，而早期融合和融合性病变进展迅速。散发性与年龄相关的脑白质病变发生的病因和修饰途径仍不完全清楚，但最近的微阵列和全基因组关联方法增加了认为可能作为治疗干预靶点的途径的概念。脑白质病变中差异调节的大多数转录本编码与免疫功能、细胞周期、蛋白水解和离子转运相关的基因。全基因组关联研究确定了六个映射到 17q25 染色体上的 SNP 与普通人群中的脑白质病变负荷相关。我们还报告了初步数据，证明载脂蛋白 E（ApoE）在脑白质病变中有免疫反应性，并支持流行病学研究结果，表明 ApoE 是另一个可能与脑白质病变发生相关的因素。现代 MRI 技术，如弥散张量和磁化传递成像，提供了标准 MRI 扫描之外的正常脑组织特征化的工具，进一步加深了我们的认识。需要在人类中进行更多的生前和死后研究，包括这些新的成像技术。
