Dunphy Louise, Rani Amir, Duodu Yaw, Behnam Yousef
Surgery, Milton Keynes University Hospital, Milton Keynes, UK.
Stroke Medicine, Milton Keynes University Hospital, Milton Keynes, UK.
BMJ Case Rep. 2019 Jul 18;12(7):e229609. doi: 10.1136/bcr-2019-229609.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations in the gene which maps to the short arm of chromosome 19 and encodes the NOTCH3 receptor protein, predominantly expressed in adults by vascular smooth muscle cells and pericytes. The receptor has a large extracellular domain with 34 epidermal growth factor-like repeats encoded by exons 2-24, the site at which CADASIL mutations are most commonly found. Migraine with aura is often the earliest feature of the disease, with an increased susceptibility to cortical spreading depression suggested as a possible aetiological mechanism. Stroke, acute encephalopathy and cognitive impairment can also occur. Hypertension and smoking are associated with early age of onset of stroke. It diffusely affects white matter, with distinct findings on T2- weighted MRI, involving the external capsule, anterior poles of the temporal lobe and superior frontal gyri, displaying a characteristic pattern of leucoencephalopathy. Affected individuals have a reduced life expectancy. An effective treatment for CADASIL is not available. The authors describe a 35-year-old manwith an unremarkable medical history, presenting to the emergency department with slurred speech and increased confusion 3 days following a fall. He was a smoker and consumed 16 units of alcohol weekly. He was hypertensive and tachycardic. Physical examination confirmed increased tone in his lower limbs and dysarthria. His CT head showed severe cerebral atrophy, multiple small old infarcts and moderate background microvascular disease. Further investigation with an MRI head confirmed multiple white matter abnormalities with microhaemorrhages. The possibility of a hereditary vasculopathy was rendered as the appearances were thought consistent with a diagnosis of CADASIL. Genetic testing identified the gene thus confirming the diagnosis. This paper provides an overview of the aetiology, clinical presentation, pathogenesis, investigations and management of CADASIL.
伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）由位于19号染色体短臂上的基因突变引起，该基因编码NOTCH3受体蛋白，主要在成人的血管平滑肌细胞和周细胞中表达。该受体有一个大的细胞外结构域，有由外显子2 - 24编码的34个表皮生长因子样重复序列，这是CADASIL突变最常见的位点。有先兆偏头痛通常是该病最早出现的特征，皮质扩散性抑制易感性增加被认为是一种可能的病因机制。中风、急性脑病和认知障碍也可能发生。高血压和吸烟与中风的早发有关。它广泛影响白质，在T2加权磁共振成像上有明显表现，累及外囊、颞叶前极和额上回，呈现出特征性的白质脑病模式。受影响个体的预期寿命缩短。目前尚无治疗CADASIL的有效方法。作者描述了一名35岁男性，既往病史无异常，跌倒3天后因言语不清和意识模糊加重就诊于急诊科。他是吸烟者，每周饮酒16单位。他患有高血压且心动过速。体格检查证实其下肢肌张力增高和构音障碍。他的头颅CT显示严重脑萎缩、多个陈旧性小梗死灶和中度背景微血管病。头颅磁共振成像进一步检查证实有多个伴有微出血的白质异常。由于这些表现被认为与CADASIL诊断一致，故考虑为遗传性血管病。基因检测鉴定出该基因，从而确诊。本文概述了CADASIL的病因、临床表现、发病机制、检查和治疗。
