Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL
Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL
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DOI：
10.1007/s00401-004-0887-2
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发表时间：
2004-09-01
影响因子：
12.7
通讯作者：
Colmant, HJ
中科院分区：
文献类型：
--
作者：
Hagel, C;Groden, C;Colmant, HJ
描述了伴有皮质下梗死和白质脑病的脑动脉病，其家系提示为常染色体显性遗传疾病。与缩写为 CADASIL 的血管病变相反，在脉管系统中没有检测到颗粒状嗜锇物质沉积物，也没有发现 NOTCH 3 基因的点突变。这种疾病发生在德国汉堡附近的一个家庭，在过去六代人中影响了 11 名女性和 11 名男性。该病发病年龄在 12 岁至 50 岁之间。临床症状包括步态障碍、构音障碍、感觉运动缺陷和进行性痴呆。各一例中观察到偏头痛样主诉和癫痫发作。颅脑计算机断层扫描和磁共振成像扫描显示白质中存在密度降低的大汇合区，以及脑干、基底神经节和白质中的小坏死。无法证明与血管疾病诱发因素的相关性。对五例病例进行尸检，发现血管病主要影响穿通动脉，伴有连续的腔隙性梗塞、弥漫性脱髓鞘和皮质下白质稀疏以及锥体束变性。组织学上，血管显示同心和偏心内膜增殖、弹性组织变性和玻璃样变性、内弹力层分裂和肌层变性。电子显微镜显示基底层破碎和增厚，但未检测到 CADASIL 特征的电子致密颗粒。
A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.