Increased number of white matter lesions in patients with familial cerebral cavernous malformations.
Increased number of white matter lesions in patients with familial cerebral cavernous malformations.
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DOI：
10.3174/ajnr.a4200
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Hart BL
中科院分区：
文献类型：
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作者：
Golden MJ;Morrison LA;Kim H;Hart BL
家族性脑海绵状血管畸形是一种常染色体显性遗传病，可导致患病患者的发病率和死亡率过高。这种疾病在美国西南部最普遍，受影响的家庭通常是CCM 1-KRIT 1常见西班牙裔突变的携带者。这些患者的脑和脊髓实质通常受到多发性海绵状血管畸形的影响。以往的研究表明，在脑海绵状血管畸形的内皮细胞连接和血脑屏障的异常。内皮细胞异常也在白色物质高信号的病理学研究中有描述。我们比较了白色高信号在已知家族性脑海绵状血管畸形人群中的患病率。我们检查了191名患有家族性脑海绵状血管畸形的受试者，他们被纳入了一项机构审查委员会批准的研究。所有人都在CCM 1基因中携带相同的常见西班牙裔突变。每例受试者均接受3 TMR成像，包括梯度回波、SWI和FLAIR序列。对海绵状畸形的数量和非出血性白色高信号的数量进行计数。年龄大于60岁的受试者由于该人群中白色病变的高患病率而被排除，年龄小于6岁的儿童由于潜在的镇静需求而被排除。进行逻辑回归分析，以确定与健康对照组或家族性脑海绵状血管畸形组中散发性脑海绵状血管畸形组相比，家族性脑海绵状血管畸形组中异常白色高信号的患病率;还评估了异常白色高信号与年龄、性别、头痛、甲状腺疾病、糖尿病、高血压高脂血症、癫痫发作史或改良兰金量表评分。家族性CCM 1携带者异常白色高信号的患病率（15.4%）高于两个对照人群（分别为2.1%和2.5%）（p<0.05）。Logistic回归分析显示，在家族性脑海绵状血管畸形患者中，性别、头痛、高脂血症、高血压、甲状腺疾病、癫痫发作史、脑海绵状血管畸形数量或改良兰金量表评分均无统计学相关性。显示了与年龄的预期相关性。家族性CCM 1携带者不仅脑海绵状血管畸形的数量增加，而且白色物质T2高信号的数量也增加，在空间上与脑海绵状血管畸形不同，超过了健康人群。临床结果不能解释家族性脑海绵状血管畸形人群中异常白色物质高信号的相关性。据我们所知，这些关系以前没有报道过。这一发现表明，该人群中内皮异常的另一种表现。
Familial cerebral cavernous malformations, an autosomal dominant disorder, result in excess morbidity and mortality in affected patients. The disorder is most prevalent in the Southwest United States, where the affected families are most often carriers of the CCM1-KRIT1 Common Hispanic Mutation. The brain and spinal cord parenchyma in these individuals is usually affected by multiple cavernous malformations. Previous studies have shown abnormalities of endothelial cell junctions and the blood-brain barrier in cerebral cavernous malformations. Endothelial cell abnormalities have also been described in pathologic studies of white matter hyperintensities. We compared the prevalence of white matter hyperintensities in a population with known familial cerebral cavernous malformations. We examined 191 subjects with familial cerebral cavernous malformations who were enrolled into an institutional review board-approved study. All carry the same Common Hispanic Mutation in the CCM1 gene. Each subject underwent 3TMR imaging, including gradient recalled-echo, SWI, and FLAIR sequences. The number of cavernous malformations and the number of nonhemorrhagic white matter hyperintensities were counted. Subjects older than 60 yearsof age were excluded due to the high prevalence of white matter lesions in this population, and children younger than 6 were excluded due to potential sedation requirements. Logistic regression analysis was performed to determine the prevalence of abnormal white matter hyperintensities in those with familial cerebral cavernous malformations compared with healthy controls or those with sporadic cerebral cavernous malformation within the familial cerebral cavernous malformations group; it was also performed to evaluate the associations between abnormal white matter hyperintensities and age, sex, headaches, thyroid disease, diabetes, hypertension, hyperlipidemia, seizure history, or modified Rankin Scale score. Familial CCM1 carriers have a higher prevalence of abnormal white matter hyperintensities (15.4%) compared with both control populations (2.1% and 2.5%, respectively) (p<0.05). Logistic regression showed no statistical association with sex, headaches, hyperlipidemia, hypertension, thyroid disease, seizure history, number of cerebral cavernous malformations, or modified Rankin Scale score among those with familial cerebral cavernous malformation. An expected correlation with age was shown. Familial CCM1 carriers have not only an increased number of cerebral cavernous malformations but also an increased number of white matter T2 hyperintensities, spatially distinct from cerebral cavernous malformations, which exceeded that of a healthy population. Clinical findings did not explain the association with abnormal white matter hyperintensities in the familial cerebral cavernous malformation population. To our knowledge, these relationships have not been previously reported. This finding suggests an additional manifestation of endothelial abnormalities in this population.