VU University Medical Centre, Department of Neurology, De Boelelaan 1117, Amsterdam, The Netherlands.
J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):126-35. doi: 10.1136/jnnp.2009.204685. Epub 2010 Oct 9.
White matter hyperintensities (WMH), lacunes and microbleeds are regarded as typical MRI expressions of cerebral small vessel disease (SVD) and they are highly prevalent in the elderly. However, clinical expression of MRI defined SVD is generally moderate and heterogeneous. By reviewing studies that directly correlated postmortem MRI and histopathology, this paper aimed to characterise the pathological substrates of SVD in order to create more understanding as to its heterogeneous clinical manifestation.
Postmortem studies showed that WMH are also heterogeneous in terms of histopathology. Damage to the tissue ranges from slight disentanglement of the matrix to varying degrees of myelin and axonal loss. Glial cell responses include astrocytic reactions--for example, astrogliosis and clasmatodendrosis--as well as loss of oligodendrocytes and distinct microglial responses. Lipohyalinosis, arteriosclerosis, vessel wall leakage and collagen deposition in venular walls are recognised microvascular changes. Suggested pathogenetic mechanisms are ischaemia/hypoxia, hypoperfusion due to altered cerebrovascular autoregulation, blood-brain barrier leakage, inflammation, degeneration and amyloid angiopathy. Only a few postmortem MRI studies have addressed lacunes and microbleeds to date. Cortical microinfarcts and changes in the normal appearing white matter are 'invisible' on conventional MRI but are nevertheless expected to contribute substantially to clinical symptoms.
Pathological substrates of WMH are heterogeneous in nature and severity, which may partly explain the weak clinicoradiological associations found in SVD. Lacunes and microbleeds have been relatively understudied and need to be further investigated. Future studies should also take into account 'MRI invisible' SVD features and consider the use of, for example, quantitative MRI techniques, to increase the sensitivity of MRI for these abnormalities and study their effects on clinical functioning.
脑白质高信号（WMH）、腔隙和微出血被认为是脑小血管病（SVD）的典型 MRI 表现，在老年人中非常普遍。然而，MRI 定义的 SVD 的临床表现通常是中度和异质的。通过回顾直接将 MRI 与组织病理学相关联的研究，本文旨在描述 SVD 的病理基础，以便更好地理解其异质性的临床表现。
尸检研究表明，WMH 在组织病理学上也是异质的。组织损伤范围从基质的轻微松解到不同程度的髓鞘和轴突丢失。神经胶质细胞反应包括星形胶质细胞反应，例如星形胶质增生和胶质溶解，以及少突胶质细胞的丧失和明显的小胶质细胞反应。脂质透明样变性、动脉硬化、血管壁漏和小静脉壁胶原沉积是公认的微血管变化。建议的发病机制包括缺血/缺氧、由于脑血管自动调节改变导致的灌注不足、血脑屏障渗漏、炎症、变性和淀粉样血管病。迄今为止，只有少数尸检 MRI 研究涉及腔隙和微出血。皮质微梗死和正常表现的白质变化在常规 MRI 上“不可见”，但预计它们将对临床症状有很大贡献。
WMH 的病理基础在性质和严重程度上是异质的，这可能部分解释了 SVD 中发现的临床影像学关联较弱的原因。腔隙和微出血的研究相对较少，需要进一步研究。未来的研究还应考虑“MRI 不可见”的 SVD 特征，并考虑使用定量 MRI 技术等方法，提高 MRI 对这些异常的敏感性，并研究其对临床功能的影响。
