腦淀粉樣血管病-趙元立（英文）課件

1、Cerebral Amyloid Angiopathy腦淀粉樣血管病趙元立北京天壇醫(yī)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病理機制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病理特點受累血管壁常規(guī)染色在光鏡下呈不成形的，強嗜伊紅的玻璃樣即淀粉樣改變剛果紅染色呈粉紅陽性物質(zhì)在血管及其周圍沉積，即嗜剛果紅血管病腦膜及皮質(zhì)中、小血管受累淀粉樣物質(zhì)多沉積于血管中膜及外膜血管壁增厚，管腔狹窄腦淀粉樣血管病腦膜表面大血管硬化，管腔狹窄附近小動脈亦明顯變性 x50腦實質(zhì)內(nèi)可見大量淀粉樣小體形成腦實質(zhì)小血管管壁增厚、變性中等量淀粉樣小體形成 x100HE VS Congo RedPathology由皮層向皮層下過度的

13、區(qū)域中受累血管的分布情況高倍鏡下典型的嗜剛果紅染色的血管壁，呈現(xiàn)“雙環(huán)”狀標本中可見不同程度受累的血管由低倍到高倍示A(+)的腦血管，集中分布在皮層及皮層下區(qū)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建立規(guī)范化的微創(chuàng)外科診斷治療標準 （新增樣本2000例）規(guī)范試驗標準 多中心大樣本研究 小骨窗手術(shù)大骨瓣減壓手術(shù)其它微創(chuàng)手段病理學檢查高血壓動脈硬化性淀粉樣血管病療效分析自然史研究新增2000例既往2764例篩選疾病相關(guān)危險因素建立預(yù)警體系衛(wèi)生經(jīng)濟學研究建立關(guān)于成本/效益的數(shù)學模型社區(qū)干預(yù)淀粉樣變腦血管病研究-技術(shù)路線數(shù)據(jù)庫網(wǎng)絡(luò)平臺現(xiàn)有病例分析67例確診為自發(fā)性腦出血開顱手術(shù)獲取出血灶周圍病理標本剛果紅染色和A免疫組化染色結(jié)果 病理學證實8例為淀粉樣血管病占11.9男:女48:19 (CAA男:女6:2)40-49歲組15.8% (3/19)50-59歲組13.0% (3/23)60-69歲組占9.1%(1/11)70歲以上組11.1% (1/9)典型病例典型復(fù)發(fā)性、多發(fā)腦出血女性，73歲主因“突發(fā)意識喪失1小時”于2008年4月22日急診入院3年前曾因“突發(fā)頭痛、頭暈、嘔吐1天”急診收入我院神經(jīng)內(nèi)科否認高血壓病、糖尿病、高血脂、冠心病等病史無服用抗凝藥物史此次入院時深昏迷，去腦強直狀態(tài)