Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL.
Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL.
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DOI：
10.1161/strokeaha.108.528299
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发表时间：
2009-06
期刊：
影响因子：
8.3
通讯作者：
Kalaria RN
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Ihara M;Tham C;Low RW;Slade JY;Moss T;Oakley AE;Polvikoski T;Kalaria RN
磁共振成像（MRI）显示白色物质（WM）高信号或脑白质疏松是中风综合征的特征。前颞极MRI信号增加被认为是常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病（CADASIL）的诊断依据，其敏感性为90%，特异性为100%。在CADASIL颞极T2加权和FLAIR序列上看到的这些特定WM高信号的结构相关性尚不清楚。我们评估了颞极死后组织的病理变化，以揭示CADASIL特异性WM高信号的原因。结合染色和免疫染色方法以及体外成像方法来量化血管周围间隙（PVS）的程度，动脉硬化被确定为硬化指数（SI），在9例CADASIL和8例散发性皮质下缺血性血管性痴呆（SIVD）的前颞极样本中，WM髓鞘形成作为髓鞘指数（MI），WM内的损伤作为累积的降解髓鞘碱性蛋白（dMBP）5例年龄相近的青年对照组和5例老年对照组。对一例CADASIL病例进行Luxol坚牢蓝（LFB）染色连续切片，重建颞极，然后与MR图像进行比较。用于重建颞极的LFB切片显示WM中有大量扩大的PVS，其在地形上表现为模糊不清的不透明区域。CADASIL组PVS/WM面积的平均面积和总面积（%PVS）显著大于对照组。与SIVD和对照样品相比，CADASIL中的MI严重降低，这与dMBP的免疫反应性增加一致，表明髓鞘变性。与年轻对照组相比，CADASIL受试者中与PVS相关的脑微血管显示嗜碱性（透明化）血管数量增加4.5倍，SI值增加57%。玻璃样变血管的数量与SI值也有显著相关性（P<0.05）。我们的研究结果表明，CADASIL患者颞极的MRI高信号是由PVS扩大和髓鞘变性伴间质液缺乏引流而不是腔隙性梗死解释的。与老年SIVD受试者颞极缺乏MR高信号一致，我们的观察结果表明CADASIL患者的病理变化进展更大。
White matter (WM) hyperintensities upon magnetic resonance imaging (MRI) or leukoaraiosis is characteristic of stroke syndromes. Increased MRI signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with 90% sensitivity and 100% specificity. The structural correlates of these specific WM hyperintensities seen on T2-weighted and FLAIR sequences in the temporal pole of CADASIL are unclear. We assessed pathological changes in post-mortem tissue from the temporal pole to reveal the cause of CADASIL specific WM hyperintensities. A combination of tinctorial and immunostaining approaches and in vitro imaging methods were used to quantify the extent of perivascular space (PVS), arteriosclerosis determined as the sclerotic index (SI), WM myelination as the myelin index (MI) and damage within the WM as accumulated degraded myelin basic protein (dMBP) in samples of the anterior temporal pole from 9 CADASIL and 8 sporadic subcortical ischaemic vascular dementia (SIVD) cases, and 5 similar age (young) and 5 older controls. Luxol fast blue (LFB) stained serial sections from a CADASIL case were also used to reconstruct the temporal pole, which was then compared to the MR images. LFB sections used to reconstruct the temporal pole revealed an abundance of enlarged PVS in the WM that topographically appeared as indistinct opaque regions. The mean and total areas of the PVS per WM area (%PVS) were significantly greater in CADASIL compared to the controls. The MI was severely reduced in CADASIL in relation to the SIVD and control sample that was consistent with increased immunoreactivity of dMBP, indicating myelin degeneration. Cerebral microvessels associated with the PVS exhibited a 4.5 fold greater number of basophilic (hyalinised) vessels and a 57% increase in the SI values in CADASIL subjects compared to young controls. A significant correlation between the quantity of hyalinised vessels and SI values was also apparent (P<0.05). Our findings suggest that MRI hyperintensities in the temporal pole of CADASIL patients are explained by enlarged PVS and degeneration of myelin accompanied by lack of drainage of the interstitial fluid rather than lacunar infarcts. Consistent with the lack of MR hypersignals in the temporal pole of older SIVD subjects, our observations imply greater progression of pathological changes in CADASIL patients.