Craggs Lucinda J L, Yamamoto Yumi, Deramecourt Vincent, Kalaria Raj N
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Brain Pathol. 2014 Sep;24(5):495-509. doi: 10.1111/bpa.12177.
Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology.
随着老龄人口的增加，脑小血管疾病（SVDs）可能会变得越来越普遍。近年来，神经影像学和病理学研究为散发性SVD以及几种易患皮质下中风和弥漫性白质疾病的单基因（孟德尔）疾病的发病机制提供了信息。然而，研究SVD的局限性之一在于临床和病理测量缺乏一致的评估标准和病变负担。动脉硬化和弥漫性白质改变是散发性和遗传性SVD的标志性特征。动脉病变的发病机制是理解各种SVD中疾病不同进展的关键。值得注意的是，散发性和遗传性SVD中微血管异常的量化表明，与遗传性疾病如伴有皮质下梗死和白质脑病的脑常染色体动脉病变（CADASIL）相比，散发性SVD中小动脉变性所涉及的过程在定性上基本相似。脑内病变位置的重要显著区域差异可能使人们能够区分SVD，其中几乎每种SVD都始终出现额叶受累，但其他SVD在其他脑叶有特定的病理学表现，如CADASIL中的颞极以及脑桥常染色体显性遗传性微血管病和白质脑病（PADMAL）中的脑桥。此外，在遗传性疾病中，血管平滑肌细胞、脑内皮细胞和基膜的退行性变化通常更快且更具侵袭性。需要进一步量化其他微血管成分甚至神经元细胞，以全面表征SVD的发病机制，并区分血管干预和治疗对所产生病理的有效性。
