腦淀粉樣血管病趙元立（英文）

CerebralAmyloidAngiopathy

腦淀粉樣血管病趙元立北京天壇醫(yī)院WhatisCAA?amyloiddepositionaged(>=50-60y)arteriesofthecortical,subcorticalareasM&FinincidenceRecurrent,MultipleHemorrhagePradaetal.,J.Neurosci.,2007BackgroundCerebralamyloidangiopathy(CAA)-depositionofβ-amyloidinthemediaandadventitiaofsmall-andmid-sizedarteriesICH-mostrecognizedresultof

CAARelationwithAlzheimerdiseaseCerebralAmyloidangiopathy

Two-photonprojectionofaz-seriesabout150umdeepintothebrainofaliving20-mo-oldtransgenicmouseexpressingamutanthumanamyloidprecursorprotein.Thisanimalhadamyloiddepositssurroundingsomecerebralvessels.

BrianJ.Bacskai,MassachusettsGeneralHospital,USA

EpidemiologyUnitedStates~upto15%ofallICH>60upto50%ofnontraumaticlobarICH>70~15-20per100,000population/yearaseriesof400autopsies:CAAin18.3%ofmen28%ofwomen(age40-90)aseriesof117confirmedAD:83%CAAGreenbergSM,Stroke

28(7):1418–22July1997SexandAgeSexmaybemorecommonlyinwomenincidenceofICHissameAgeagerelatedSporadicICHoccurs>60FamilialCAAatyoungeragesIcelandicform30-40,Dutch50-60DiagnosisCCheadache,vomiting,hemiplegia…PHwithouthypertension,asymptomaticPEICHrelatedfindingsCT/MRIlobar/cortical/subcorticalSAH,ventricularhemorrhage

梯度回聲MR:sensitivetomicrohemorrhagePathologyCongoRed(+),Aβ(+)TransaxialT2-weightedgradient-echoMRimagesshowinnumerablemicrohemorrhagespredominantlyatcerebralgray–whitematterjunction.Microhemorrhagesarenotpresentinbasalganglia,pons,orcerebellum.LargefocalhemorrhagesarepresentinbilateralparietallobeMarisaKastoffBlitsteinAJR2007;189:720-725

GuidelinefordiagnosisBostonGroup-FourlevelsDefiniteCAA:lobar,cortical,orsubcorticalhemorrhageevidenceofsevereCAAProbableCAAwithsupportingpathologicalevidence:clinicaldata+somedegreeofvascularamyloiddepositionProbableCAA:clinicaldata+MR,nopathologicalspecimenmultiplehematomasinpatient>60PossibleCAA:patient>60clinical+MR:singlelobar,cortical,orcorticosubcorticalhemorrhage,noothercausemultiplehemorrhageswithapossiblebutnotadefinitecauseorsomehemorrhageinanatypicallocationKnudsenKA,Neurology2001;56:537–9.BhomrajThanviAgeandAgeing200635(6):565-571SpecialtypeofCAADutchtypeofhereditarycerebralhemorrhage:autosomaldominant,withmutationofamyloidprecursorprotein,atage40–60,mayproduceanabnormalanti-coagulant,whichmakeshemorrhagemorelikely.FamilialAlzheimer'sdisease:autosomaldominant,5–10%ofallADIcelandictype:autosomaldominant,withmutationinthegenecodingforcystatinC,beginat30–40withmultiplebrainhemorrhages,mostinvolvethebasalgangliaDownSyndrome:trisomy21Britishtypeoffamilialamyloidosis:autosomaldominant,associatedwithprogressivedementia,spasticity,andataxia.Brainstem,spinalcord,andcerebellumallexhibitamyloiddeposits,buthemorrhagetypicallydoesnotoccur.WhybleedingBleedingintobrainoccurastinybloodvesselscarryingamyloiddepositsbecomeheavierandmorebrittlemorelikelytoburstwithminortraumaorwithfluctuatingbloodpressureAneurysmsmaydevelop,andmayalsoruptureAmyloiddepositsmaydestroysmoothmusclecellsorcauseinflammationinthebloodvesselwall,causebloodvesseltobreakmoreeasilySethLove,FrontiersinBioscience14,4778-4792,January,2021ThecauseofamyloiddepositsinbloodvesselsinthebraininsporadicCAAisnotknownInhereditaryCAA,geneticdefects,typicallyonchromosome21,allowaccumulationofamyloid,aproteinmadeupofunitscalledbeta-pleatedsheetfibrils.Thefibrilstendtoclumptogether,sothattheamyloidcannotbedissolvedandbuildsupinthebrainbloodvesselwalls.Oneformofamyloidfibrilsubunitproteinsistheamyloidbetaprotein.StevenGreenbergGeriatricsandaging,202111(5):15-17Systemictheoryamyloidbetaproteininblooddepositedinbloodvesselsinthebrainbreakdownblood-brainbarrieramyloidbetaproteindepositedinbrainsubstanceformsneuriticplaqueSecondtheoryamyloidfibrilsproducedbyperivascularmicrogliaThirdtheorybothnervecellsandgliaproduceamyloidprecursorprotein,increaseswithaging病理機制AmyloiddamagesthemediaandadventitialeadingtothickeningofthebasalmembranestenosisofthevessellumenfragmentationoftheinternalelasticlaminaresultinfibrinoidnecrosisandmicroaneurysmformationSomeevidencesuggeststhattheamyloidisproducedinthesmoothmusclecellsofthetunicamediaasaresponsetodamageofthevesselwall(perhapsbyarteriosclerosisorhypertension)病理機制severalkeyprocessesareinvolved:productionofamyloidprecursorproteins(APP),processingofprecursorproteins,aggregationofprotein,andfibrilformation.

Impairedeliminationandaccumulationofsolubleandinsolubleβ-amyloidpeptidemayunderliethepathogenesisofCAAandexplainthelinkbetweenCAAandAD.ElectronmicroscopydemonstratesfibrilsofamyloidintheouterbasementmembraneintheinitialstageofCAAManytypesofamyloidproteinarepresentinthebody,butsomeareuniquetothebrain.β-amyloidisauniquecerebrovascularamyloidproteinAmyloidFamily:AβACysATTRAGelPrPScABriADan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在血管及其周圍沉積，即嗜剛果紅血管病腦膜及皮質中、小血管受累淀粉樣物質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外表大血管硬化，管腔狹窄附近小動脈亦明顯變性x50腦實質內可見大量淀粉樣小體形成腦實質小血管管壁增厚、變性中等量淀粉樣小體形成x100HEVSCongoRedPathology由皮層向皮層下過度的區(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Aβ(+)的腦血管，集中分布在皮層及皮層下區(qū)域gradingMortalityandMorbidityCAAICHassociatedwithlowermortalityrate(11-32%)andbetterfunctionaloutcome25-40%havearecurrence,withthehighestriskinthefirstyear,associatedwithahighmortalityrate(upto40%)Cognitiveimpairmentiscommon建立標準化的微創(chuàng)外科診斷治療標準〔新增樣本2000例〕標準試驗標準多中心大樣本研究

小骨窗手術大骨瓣減壓手術其它微創(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