伴皮质下梗死及白质脑病的常染色体显性遗传脑动脉病2例及文献复习

Two cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and literature review

目的分析伴有皮质下梗死及白质脑病的常染色体显性遗传脑动脉病(CADASIL)的临床特点、影像和病理学特征,提高对CADASIL的认识。方法收集2011年11月—2015年8月解放军第161医院神经内科收治的CADASIL患者2例,对其临床表现、家系分析、影像学表现、Notch3基因检测及皮肤活检进行总结,并结合国内外文献对该病特点进行分析。结果例1患者中年起病,有家族史,反复发作性头痛、右侧肢体乏力,逐渐出现右侧肢体瘫痪,认知功能障碍,头颅MR示双侧基底节区及半卵圆区多发腔隙性梗死及缺血灶,脑白质稀疏。MRA未见异常。Notch3基因检测提示3号和4号外显子中发现了1个碱基突变。例2患者中年起病,进行性头晕、记忆力减退,头颅MR双侧大脑半球、丘脑、脑干、小脑广泛异常信号。皮肤活检血管内皮细胞胞浆表面和平滑肌的表面见嗜锇颗粒(GOM)沉积。结论 CADASIL的诊断应结合患者的临床表现、家族史及MR检查结果,Notch3基因检测和/或皮肤活检是明确诊断的金标准。

Objective To study the clinical features, the image manifestations and pathological characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy（CADASIL）, and to improve the recognition about it. Methods Two cases of CADASIL were diagnosed after biopsy of skin, Notch3 gene were detected. Family history, clinical manifestations and brain MRI were investigated, and the cases were analyzed by reviewing the related literature domestic and abroad. Results Cases 1 was a female who had a positive family history, was onset at middle age. She presented with repeating paroxysmal headache, weakness of the right extremities, and gradually her right extremities paralyzed. Cognitive dysfunction was developed, and MRI displayed multiple infarctions and ischemic focuses in bilateral basal ganglia, centrum ovale region, MRA was normal. Mutations were found in the third and fourth exon of Notch3 gene. Cases 2 was also a female, at first onset at middle age, presented with progressive dizziness and cognitive dysfunction. MRI displayed widespread abnormal signals in bilateral hemisphere, thalamus, brain stem and cerebellum. Skin biopsy found granules of osemophylic （GOM） in plasma of vascular endothelium and smooth muscles. Conclusion Diagnosis of CADASIL should be made in combination with clinical manifestations, family history and MRI. Notch3 gene detection and /or skin biopsy was the golden standard in the diagnosis of CADASIL.