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Neuropathological correlates of cortical superficial siderosis in cerebral amyloid angiopathy.
Brain ( IF 10.6 ) Pub Date : 2020-09-16 , DOI: 10.1093/brain/awaa266
Andreas Charidimou 1, 2 , Valentina Perosa 1 , Matthew P Frosch 3 , Ashley A Scherlek 4 , Steven M Greenberg 1 , Susanne J van Veluw 1, 4
Affiliation  

Cortical superficial siderosis is an established haemorrhagic neuroimaging marker of cerebral amyloid angiopathy. In fact, cortical superficial siderosis is emerging as a strong independent risk factor for future lobar intracerebral haemorrhage. However, the underlying neuropathological correlates and pathophysiological mechanisms of cortical superficial siderosis remain elusive. Here we use an in vivo MRI, ex vivo MRI, histopathology approach to assess the neuropathological correlates and vascular pathology underlying cortical superficial siderosis. Fourteen autopsy cases with cerebral amyloid angiopathy (mean age at death 73 years, nine males) and three controls (mean age at death 91 years, one male) were included in the study. Intact formalin-fixed cerebral hemispheres were scanned on a 3 T MRI scanner. Cortical superficial siderosis was assessed on ex vivo gradient echo and turbo spin echo MRI sequences and compared to findings on available in vivo MRI. Subsequently, 11 representative areas in four cases with available in vivo MRI scans were sampled for histopathological verification of MRI-defined cortical superficial siderosis. In addition, samples were taken from predefined standard areas of the brain, blinded to MRI findings. Serial sections were stained for haematoxylin and eosin and Perls’ Prussian blue, and immunohistochemistry was performed against amyloid-β and GFAP. Cortical superficial siderosis was present on ex vivo MRI in 8/14 cases (57%) and 0/3 controls (P = 0.072). Histopathologically, cortical superficial siderosis corresponded to iron-positive haemosiderin deposits in the subarachnoid space and superficial cortical layers, indicative of chronic bleeding events originating from the leptomeningeal vessels. Increased severity of cortical superficial siderosis was associated with upregulation of reactive astrocytes. Next, cortical superficial siderosis was assessed on a total of 65 Perls’-stained sections from MRI-targeted and untargeted sampling combined in cerebral amyloid angiopathy cases. Moderate-to-severe cortical superficial siderosis was associated with concentric splitting of the vessel wall (an advanced form of cerebral amyloid angiopathy-related vascular damage) in leptomeningeal vessels (P < 0.0001), but reduced cerebral amyloid angiopathy severity in cortical vessels (P = 0.048). In terms of secondary tissue injury, moderate-to-severe cortical superficial siderosis was associated with the presence of microinfarcts (P = 0.025), though not microbleeds (P = 0.973). Collectively, these data suggest that cortical superficial siderosis on MRI corresponds to iron-positive deposits in the superficial cortical layers, representing the chronic manifestation of bleeding episodes from leptomeningeal vessels. Cortical superficial siderosis appears to be the result of predominantly advanced cerebral amyloid angiopathy of the leptomeningeal vessels and may trigger secondary ischaemic injury in affected areas.

中文翻译:

脑淀粉样血管病皮质浅层铁沉积的神经病理学相关性。

皮质浅表铁沉积症是脑淀粉样血管病的出血性神经影像学标志物。事实上,皮质浅表铁质沉着症正在成为未来脑叶出血的一个强大的独立危险因素。然而,皮层浅表铁质沉着症的潜在神经病理学相关性和病理生理机制仍然难以捉摸。在这里,我们使用体内MRI,离体MRI,组织病理学方法,用于评估皮层表面铁沉积症的神经病理学相关性和血管病理学。14 例脑淀粉样血管病尸检病例(平均死亡年龄 73 岁,9 名男性)和 3 例对照(平均死亡年龄 91 岁,1 名男性)被纳入研究。在 3 T MRI 扫描仪上扫描完整的福尔马林固定的大脑半球。在体外梯度回波和涡轮自旋回波 MRI 序列上评估皮质表面铁沉积,并与可用的体内MRI发现进行比较。随后,4个案例中的11个代表性区域与体内MRI 扫描被取样用于 MRI 定义的皮质浅表铁沉积的组织病理学验证。此外,样本取自大脑的预定义标准区域,对 MRI 结果不知情。连续切片染色苏木精和伊红以及 Perls 普鲁士蓝,并针对淀粉样蛋白-β 和 GFAP 进行免疫组织化学。皮质浅表铁质沉着症存在于离体MRI在8/14例(57%)和0/3对照组(P = 0.072)。在组织病理学上,皮质浅层铁沉积对应于蛛网膜下腔和浅层皮质层中铁阳性含铁血黄素沉积,表明源自软脑膜血管的慢性出血事件。皮质浅表铁沉积的严重程度增加与反应性星形胶质细胞的上调有关。接下来,对来自 MRI 靶向和非靶向采样的总共 65 个 Perls 染色切片在脑淀粉样血管病病例中进行了评估。中度至重度皮质浅层铁沉积与软脑膜血管中的血管壁同心分裂(一种与脑淀粉样血管病相关的血管损伤的晚期形式)有关(P < 0.0001),但降低了皮质血管中脑淀粉样血管病的严重程度(P =  0.048)。在继发性组织损伤方面,中度至重度皮质浅层铁沉积与微梗死的存在(P =  0.025)有关,但与微出血无关(P =  0.973)。总的来说,这些数据表明 MRI 上的皮质浅层铁质沉积对应于浅层皮质层中的铁阳性沉积物,代表了软脑膜血管出血的慢性表现。皮质浅表铁沉积似乎是软脑膜血管晚期脑淀粉样血管病的结果,可能引发受影响区域的继发性缺血性损伤。
更新日期:2020-09-16
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