Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma
Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma
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DOI：
10.3171/2014.6.jns132775
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发表时间：
2014-09-01
影响因子：
4.1
通讯作者：
Bertalanffy, Helmut
中科院分区：
文献类型：
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作者：
Jakimovski, Dejan;Schneider, Hannah;Bertalanffy, Helmut
object.在脑海绵状血管畸形（CM）中，内皮细胞紧密连接（TJ）的表达大多缺失，这会导致病灶周围红细胞和液体渗出增加。然而，在CM病变的一个子集中，沿内皮细胞接触观察到保留的TJ染色灶。该发现的临床相关性尚不清楚。本研究探讨了TJ蛋白表达的相关性及其与CM出血倾向的关系。对2008 - 2010年期间切除的32个CM标本进行TJ蛋白claudin-5、occludin和ZO-1的免疫组织化学染色。根据TJ蛋白的表达将患者分为2组，分析比较两组患者侵袭性的临床和影像学指标。在20例标本中发现完全不存在TJ表达，在12例标本中发现局灶性TJ蛋白表达。无TJ免疫反应性的CM显著更大（p = 0.022），并具有显著更大的发展明显血肿（p = 0.028）和病灶周围水肿（p = 0.013）的倾向。症状的严重程度、多样性、发育性静脉异常（DVA）的存在和CM的位置没有显示出显著差异，这取决于TJ的表达。在一项单变量分析中，作者观察到，与无TJ表达的CM相比，有局灶性TJ表达的CM病变中明显血肿和病灶周围水肿的倾向显著更低，且尺寸更小。观察到的TJ蛋白表达的差异可能是CM病变出血倾向差异的原因。虽然这一发现不能用于预测的方式在这个时候，它是一个基础，进一步多变量分析可能的CM生物学预测。
Object. Endothelial tight junction (TJ) expression is mostly absent in cerebral cavernous malformations (CMs), which causes increased perilesional erythrocyte and fluid oozing. However, in a subset of CM lesions, foci of preserved TJ staining are observed along endothelial cell contacts. The clinical relevance of this finding is unclear. This study investigates the relevance of the focal TJ protein expression and its association with CM bleeding propensity.Methods. Immunohistochemical staining for the TJ proteins claudin-5, occludin, and ZO-1 was performed on 32 CM specimens that were resected during 2008-2010. The patients were allocated to 2 groups according to TJ protein expression, and the clinical and radiological parameters of aggressiveness were analyzed and compared.Results. Complete absence of TJ expression was identified in 20 specimens, and focal TJ protein expression in 12. CMs without TJ immunoreactivity were significantly larger (p = 0.022) and had a significantly greater propensity for development of frank hematomas (p = 0.028) and perilesional edema (p = 0.013). Symptom severity, multiplicity, developmental venous anomaly (DVA) presence, and CM location did not show a significant difference depending on TJ expression.Conclusions. In a univariate analysis the authors observed significantly less propensity for frank hematomas and perilesional edema as well as smaller size in CM lesions with focal TJ expression compared with CMs without TJ expression. The observed difference in TJ protein expression might be the reason for differences in bleeding propensity of the CM lesions. Although this finding cannot be used in predictive manner at this time, it is a basis for further multivariate analyses of possible CM biological predictors.