脑淀粉样血管病-赵元立（英文）课件

1、Cerebral Amyloid Angiopathy脑淀粉样血管病赵元立北京天坛医院What is CAA?amyloid deposition aged (=50-60y)arteries of the cortical, subcortical areasM & F in incidenceRecurrent, Multiple HemorrhagePrada et al., J. Neurosci., 2007 BackgroundCerebral amyloid angiopathy (CAA) - deposition of -amyloid in the media and ad

2、ventitia of small- and mid-sized arteriesICH - most recognized result ofCAARelation with Alzheimer diseaseCerebral Amyloid angiopathyTwo-photon projection of a z-series about 150 um deep into the brain of a living 20-mo-old transgenic mouse expressing a mutant human amyloid precursor protein. This a

3、nimal had amyloid deposits surrounding some cerebral vessels. Brian J. Bacskai, Massachusetts General Hospital, USAEpidemiologyUnited States up to 15% of all ICH 60up to 50% of nontraumatic lobar ICH 70 15-20 per 100,000 population / yeara series of 400 autopsies: CAA in 18.3% of men 28% of women (a

4、ge 40-90) a series of 117 confirmed AD: 83% CAAGreenberg SM, Stroke 28 (7): 141822 July 1997 Sex and AgeSexmaybe more commonly in womenincidence of ICH is sameAgeage relatedSporadic ICH occurs 60 Familial CAA at younger agesIcelandic form 30-40, Dutch 50-60Transaxial T2-weighted gradient-echo MR ima

5、ges show innumerable microhemorrhages predominantly at cerebral graywhite matter junction. Microhemorrhages are not present in basal ganglia, pons, or cerebellum. Large focal hemorrhages are present in bilateral parietal lobe Marisa Kastoff BlitsteinAJR 2007; 189:720-725Guideline for diagnosisBoston

6、 Group - Four levelsDefinite CAA: lobar, cortical, or subcortical hemorrhage evidence of severe CAAProbable CAA with supporting pathological evidence: clinical data + some degree of vascular amyloid depositionProbable CAA: clinical data + MR, no pathological specimenmultiple hematomas in patient 60

7、Possible CAA: patient 60 clinical + MR: single lobar, cortical, or corticosubcortical hemorrhage, no other causemultiple hemorrhages with a possible but not a definite causeor some hemorrhage in an atypical locationKnudsen KA, Neurology 2001; 56: 5379. Bhomraj Thanvi Age and Ageing 2006 35(6):565-57

8、1 The cause of amyloid deposits in blood vessels in the brain in sporadic CAA is not knownIn hereditary CAA, genetic defects, typically on chromosome 21, allow accumulation of amyloid, a protein made up of units called beta-pleated sheet fibrils. The fibrils tend to clump together, so that the amylo

9、id cannot be dissolved and builds up in the brain blood vessel walls. One form of amyloid fibril subunit proteins is the amyloid beta protein. Steven Greenberg Geriatrics and aging, 2008 11(5): 15-17 Systemic theoryamyloid beta protein in blood deposited in blood vessels in the brainbreakdown blood-

10、brain barrieramyloid beta protein deposited in brain substanceforms neuritic plaqueSecond theoryamyloid fibrils produced by perivascular microgliaThird theoryboth nerve cells and glia produce amyloid precursor protein, increases with aging病理机制Amyloid damages the media and adventitialeading to thicke

11、ning of the basal membranestenosis of the vessel lumenfragmentation of the internal elastic laminaresult in fibrinoid necrosis and microaneurysm formationSome evidence suggests that the amyloid is produced in the smooth muscle cells of the tunica media as a response to damage of the vessel wall (per

12、haps by arteriosclerosis or hypertension)Amyloid Family: AACysATTRAGelPrPScABriADan病理特点受累血管壁常规染色在光镜下呈不成形的，强嗜伊红的玻璃样即淀粉样改变刚果红染色呈粉红阳性物质在血管及其周围沉积，即嗜刚果红血管病脑膜及皮质中、小血管受累淀粉样物质多沉积于血管中膜及外膜血管壁增厚，管腔狭窄脑淀粉样血管病脑膜表面大血管硬化，管腔狭窄附近小动脉亦明显变性 x50脑实质内可见大量淀粉样小体形成脑实质小血管管壁增厚、变性中等量淀粉样小体形成 x100HE VS Congo RedPathology由皮层向皮层下过度的

13、区域中受累血管的分布情况高倍镜下典型的嗜刚果红染色的血管壁，呈现“双环”状标本中可见不同程度受累的血管由低倍到高倍示A(+)的脑血管，集中分布在皮层及皮层下区域gradingMortality and MorbidityCAA ICH associated with lower mortality rate (11-32%) and better functional outcome25-40% have a recurrence, with the highest risk in the first year, associated with a high mortality rate (u

14、p to 40%)Cognitive impairment is common建立规范化的微创外科诊断治疗标准 （新增样本2000例）规范试验标准 多中心大样本研究 小骨窗手术大骨瓣减压手术其它微创手段病理学检查高血压动脉硬化性淀粉样血管病疗效分析自然史研究新增2000例既往2764例筛选疾病相关危险因素建立预警体系卫生经济学研究建立关于成本/效益的数学模型社区干预淀粉样变脑血管病研究-技术路线数据库网络平台现有病例分析67例确诊为自发性脑出血开颅手术获取出血灶周围病理标本刚果红染色和A免疫组化染色结果 病理学证实8例为淀粉样血管病占11.9男:女48:19 (CAA男:女6:2)40-49岁组15.8% (3/19)50-59岁组13.0% (3/23)60-69岁组占9.1%(1/11)70岁以上组11.1% (1/9)典型病例典型复发性、多发脑出血女性，73岁主因“突发意识丧失1小时”于2008年4月22日急诊入院3年前曾因“突发头痛、头晕、呕吐1天”急诊收入我院神经内科否认高血压病、糖尿病、高血脂、冠心病等病史无服用抗凝药物史此次入院时深昏迷，去脑强直状态