伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（附l例报道）

目的 探讨伴有皮层下梗死和白质脑病(Cerebral autonomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)的常染色体显性遗传性脑动脉病的临床特点和诊断方法。方法 对1例CADASIL患者的临床表现、影像学(MRI、CT )特点及皮肤活检等方面进行了探讨。结果 患者临床表现为反复发作的缺血性脑卒中、记忆力减退、假性球麻痹、MRI、CT见皮质下梗死和白质脑病的改变，皮肤活检显示小动脉含糖原颗粒，管腔狭窄，血管内皮下黑色嗜锇颗粒。结论 通过本病的临床特点、影像学和皮肤活检，可在生前进行诊断。     

CADASIL患者的临床、影像和Notch3基因突变特点及我国研究现状

常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病（cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL）是一种较为少见的遗传性小动脉病,致病基因为Notch3。我国患者主要表现为皮层下缺血及认知障碍,伴有先兆的偏头痛极少见。影像学特点为多发皮质下梗死灶,侧脑室旁白质多发斑点状异常信号,外囊、前颞区和胼胝体为特征性受累部位。Notch3基因突变热区分布在第11、4和3号外显子,可能存在热点突变。     

遗传因素导致的脑小血管病变-CADASIL研究进展

<正>CADASIL是伴有皮质下梗死和白质脑病的常染色体显性遗传性的血管性脑病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL),是一种非动脉硬化性、非淀粉样变的全身性动脉病,其自然病程为:常在20~40岁之间出现偏头痛,40~60岁之间出现反复发作的缺血性卒中,60岁以后出现进行性智力障碍,以记忆力减退和额叶功能障碍为主,常伴有情感障碍,平     

伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病(附1例报道)

目的　探讨伴有皮层下梗死和白质脑病 (Cerebralautonomicdominantarteriopathywithsubcorti calinfarctsandleukoencephalopathy ,CADASIL)的常染色体显性遣传性脑动脉病的临床特点和诊断方法。 方法　对 1例CADASIL患者的临床表现、影像学 (MRI、CT)特点及皮肤活检等方面进行了探讨。结果　患者临床表现为反复发作的缺血性脑卒中、记忆力减退、假性球麻痹、MRI、CT见皮质下梗死和白质脑病的改变 ,皮肤活检显示小动脉含糖原颗粒 ,管腔狭窄 ,血管内皮下黑色嗜锇颗粒。结论　通过本病的临床特点、影像学和皮肤活检 ,可在生前进行诊断。     

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(附一例报告及文献复习)

目的 提高对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(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy，CADASIL)临床特点和诊断方法的认识。方法 对2003年4月7日收治的1例CADASIKL患的临床表现、影像学特点及皮肤活检结果等临床资料进行回顾性分析。结果 主要临床表现为偏头痛、记忆力下降，头部MRI检查可见皮质下梗死、脑白质变性；皮肤活检电子显微镜显示小血管内皮下出现嗜锇酸颗粒。结论 对出现反复发作性偏头痛的中年人，MRI检查示皮质下白质或基底节区长T1、长T2异常信号，应高度怀疑为CADASIL，需进一步行皮肤活检及基因检测，以明确诊断。     

表现为家族性偏头痛的CADADASIL家系临床及病理研究

目的 探讨以偏头痛为主要临床特征的伴皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autonomic dominant arteriopathy with subeortical infarcts and leukoencephalopathy,CADASIL)的病理学改变、影像学特征以及诊断方法.方法 选取一临床确诊的CADASIL家系,调查先证者及其家族的发病情况、病程变化及误诊情况;对其临床表现、病理学及影像学等方面进行研究.结果 先证者青年起病,早期临床主要表现为反复发作的先兆型偏头痛,进而出现波动渐进性记忆、认知功能减退以及反复发作的缺血性脑卒中.磁共振显示皮层下多发腔隙性或小灶性梗死,以及特征性的颞极白质损害.皮肤血管活检:电镜下见小动脉基底膜增厚,其中存在嗜锇颗粒物质沉积.全家系4代中,已有4代6人呈临床或亚临床发病,符合常染色体显性遗传.结论 青年期发病的家族性先兆型偏头痛可能是CADASIL的早期表现,影像学磁共振的特征性表现和皮肤活检发现嗜锇颗粒是确诊该病的重要途径.     

伴有皮层下梗塞和白质脑病的常染色体显性遗传脑动脉病

伴有皮层下梗塞和白质脑病的常染色体显性遗传脑动脉病王拥军卢德宏伴有皮层下梗塞和白质脑病的常染色体显性遗传脑动脉病（ｃｅｒｅｂｒａｌａｕｔｏｓｏｍｅｄｏｍｉｎａｎｔａｒｔｅｒｉｏｐａｔｈｙｗｉｔｈｓｕｂｃｏｒｔｉｃａｌｉｎｆａｒｃｔｓａｎｄｌｅｕｋｏｅ...     

以硬膜下出血为首发症状的常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病1例

常染色体显性遗传性脑动脉病伴皮质下梗死和白质脑病(CADASIL)是19p13的Notch3基因突变导致的常染色体显性遗传性脑动脉病,确诊是需在小动脉平滑肌细胞表面发现嗜锇性颗粒状致密沉积物( GOM )或者Notch3 基因检查发现突变.患者多在中年起病,以偏头痛、反复发作的缺血性卒中为特点,晚期出现进行性皮质下痴呆...     

伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病的临床、影像和病理学一例分析

目的探讨伴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)的临床特点、影像和病理学特征,提高对CADASIL的认识。方法对一例CADASIL患者的临床表现、影像学表现及皮肤活检进行总结。结果患者妊娠晚期发病,表现为反复的缺血性卒中发作,头颅MRI见皮质下梗死和白质脑病的改变,皮肤活检提示微小动脉的平滑肌细胞表面出现颗粒样嗜锇物质(GOM)。结论有阳性家族史,无常见脑血管病危险因素且发病年龄较早的缺血性脑血管病患者要考虑到CADASIL的可能,同时妊娠可能会对促进本病的发展有一定的影响。     

常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病研究进展

常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病（Cerebral autosomal dominantarteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL）是一种在成人时发病且以显性方式遗传的小动脉血管病变。它的临床特征主要为反复性的脑皮质下梗死及痴呆症,在少数的患者身上同时可见先兆性偏头痛及精神疾病方面的症状。它的致病基因是NOTCH3。CADASIL是最常见的因为单基因变异所造成的遗传性脑血管病变。该文简单介绍CADASIL的临床症状、分子遗传致病机制、诊断方法、在台湾的现况以及治疗与预防建议。     

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a Chinese pedigree A case report using brain magnetic resonance imaging and biospy

The present study enrolled a Chinese family that comprised 34 members and spanned three generations. Eight members were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and disease diagnoses corresponded with autosomal incomplete dominance inheritance. The primary clinical manifestations included paralysis, dysarthria, and mild cognitive deficits. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes, in particular the pons. In addition, multiple cerebral infarction was identified in the proband. Sural nerve biopsy findings of the proband revealed granular osmophilic material deposits in the extracellular matrix, which were adjacent to smooth muscle cells of dermal arterioles. Screening exons 2-4 for NOTCH 3 mutations by direct sequencing did not reveal any abnormalities.     

Clinical autosomal dominating arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a diffuse disease of small arteries, predominating in the brain. It starts during mid-adulthood and is characterized by recurrent ischaemic events (transient or permanent), attacks of migraine with aura, severe mood disorders, subcortical dementia and at MRI white periventricular leukoencephalopathy. CADASIL is an autosomal dominant disease. The gene Notch3 on which the mutation was detected is located on chromosome 19. There is so far no specific treatment and death occurs after a mean of twenty years.     

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and skin biopsy features.

We describe the clinical, radiological, genetic and skin biopsy findings of the first Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family tree extending over three generations, eight had typical clinical features of CADASIL with recurrent ischemic stroke. In the three surviving affected family members, brain MRI showed extensive leukoaraiosis. Genotyping revealed heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical features were cerebellar infarction as a presenting complaint and a late age of onset with mild symptoms at age 69. A novel finding is the suggestion of a direct correlation between clinical disease severity and the quantity of ultrastructural pathognomonic granular osmophilic material (GOM) seen on skin biopsy.     

Migraine with aura and white matter abnormalities: Notch3 mutation

The authors report on an Italian family with eight affected members who show autosomal dominant migraine with prolonged visual, sensory, motor, and aphasic aura. These symptoms are associated with white matter abnormalities on brain MRI. All living affected members carry a Notch3 mutation (Arg153Cys) previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). White matter abnormalities occur in a variable percentage of the general migraine population; CADASIL should be suspected in migraineurs with prolonged atypical aura and white matter abnormalities.     

Dominant autosomal cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A review

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial condition caused by a mutation of the Notch3 gen in chromosome 19. Accumulation of osmiophilic granular material (GOM) on the middle layer of small and medium-sized cerebral arteries leads to progressive narrowing of the blood vessels. As a result, clinical findings include migraine, cerebrovascular ischemic events, vascular dementia and a number of neuropsychiatric disorders associated to an extensive leukoencephalopathy readily shown by MRI studies. GOM deposits, however, are systemic and maybe shown ultrastructuraly on skin vessels by means of a biopsy. Detection of mutations of the Notch3 gen by molecular genetics may also allow accurate diagnosis during life. So far, there is no effective treatment for this disorder.     

CADASIL presenting with a movement disorder: a clinical study of a Chilean kindred.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular disease that usually begins with migraine, followed by repeated strokes and progressive dementia. We describe an unusual clinical presentation of this condition in members of a Chilean family with an established NOTCH3 mutation. We report early clinical, neuropsychological, transcranial ultrasound, magnetic resonance imaging (MRI), cerebral blood flow, and skin biopsy findings on these patients. Of the patients, 2 presented with facial dystonia, 1 of whom had abnormal single photon emission computed tomography and transcranial ultrasound studies after normal brain MRI scans. Our report emphasizes that CADASIL must be considered in the study of patients with secondary dystonia.     

A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), diagnosed in the age of puberty

We report a 13-year-old boy with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) at an early stage. He showed migraine, cognitive deficits, depressive episodes and areas of white matter hyperintensity on MRI. There were no first-degree relatives accompanied with similar symptoms. T2-and fluid-attenuated inversion recovery (FLAIR)--weighted brain MRI revealed areas of apparently symmetric high intensity in the deep white matter and periventicular caps. On ultrastructural studies of the biopsied skin, there were free granular osmiophilic materials (GOM) between vascular smooth muscle cells in the cutaneous vessels. But there were no excavations in the cell membranes that contained GOM. On immunostaining with Notch3 monoclonal antibodies, granular staining was not observed in vessels of the skin. No mutation was detected on DNA analysis of the Notch3 gene (exon 4 and part of exon 5) in peripheral leukocytes. Although the frequencies of migraine episodes and depressive episodes decreased with amitriptyline and ibuprofen, the cognitive deficits (delayed-recall impairment) and areas of white matter hyperintensity on MRI have been unchanged for the past four     

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): a morphological study of a German family

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized clinically by recurrent cerebral infarcts, subcortical dementia and pseudobulbar palsy, and morphologically by a granular degeneration of cerebral and, to a lesser degree, extracerebral blood vessels. We present morphological findings in a further German family affected by CADASIL. The index case showed the typical periodic acid-Schiff-positive granular degeneration of vascular smooth muscle cells (VSMC) in cerebral vessels, which did not react with antibodies against various immunoglobulins or complement factors. Ultrastructurally, granular osmiophilic material (GOM) covered the VSMC in different cerebral regions as well as in extracerebral organs (muscle, nerve, skin, small and large intestine, liver, kidney and heart). Skin biopsy samples from other family members of the last two generations also revealed GOM irrespective of the clinical symptomatology (CADASIL, migraine only or asymptomatic). Patients in the third generation had higher amounts of GOM in skin vessels than did asymptomatic or migraine patients in the fourth generation. We conclude that skin biopsy is a useful and less-invasive screening method for the differential diagnosis of CADASIL. Received: 9 February 1996 / Revised, accepted: 24 April 1996