脑淀粉样血管病-赵元立(英文)课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Cerebral Amyloid Angiopathy,脑淀粉样血管病,What is CAA?,amyloid deposition,aged (,=50-60y),arteries of the cortical,subcortical areas,M&F in incidence,Recurrent,Multiple Hemorrhage,Prada et al.,J.Neurosci.,2007,Background,Cerebral amyloid angiopathy(CAA)-,deposition of,-amyloid in the media and adventitia of small-and mid-sized arteries,ICH-most recognized result ofCAA,Relation with Alzheimer disease,Epidemiology,United States,up to 15%of all ICH 60,up to 50%of nontraumatic lobar ICH 70,15-20 per 100,000 population/year,a series of 400 autopsies:,CAA in 18.3%of men,28%of women(age 40-90),a series of 117 confirmed AD:83%CAA,Greenberg SM,Stroke,28,(7):141822 July 1997,Sex and Age,Sex,maybe more commonly in women,incidence of ICH is same,Age,age related,Sporadic ICH occurs 60,Familial CAA at younger ages,Icelandic form 30-40,Dutch 50-60,Diagnosis,CC headache,vomiting,hemiplegia,PH without hypertension,asymptomatic,PE ICH related findings,CT/MRI lobar/cortical/subcortical,SAH,ventricular hemorrhage,梯度回声,MR:sensitive to microhemorrhage,Pathology,Congo Red(+),A,(+),Transaxial T2-weighted gradient-echo MR images 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 Blitstein,AJR,2007;189:720-725,Guideline for diagnosis,Boston Group-Four levels,Definite CAA:lobar,cortical,or subcortical hemorrhage,evidence of severe CAA,Probable CAA with supporting pathological evidence:,clinical data+some degree of vascular amyloid deposition,Probable CAA:clinical data+MR,no pathological specimen,multiple hematomas in patient 60,Possible CAA:patient 60 clinical+MR:,single lobar,cortical,or corticosubcortical hemorrhage,no other cause,multiple hemorrhages with a possible but not a definite cause,or some hemorrhage in an atypical location,Knudsen KA,Neurology 2001;56:5379.,Special type of CAA,Dutch type of hereditary cerebral hemorrhage:autosomal dominant,with mutation of amyloid precursor protein,at age 4060,may produce an abnormal anti-coagulant,which makes hemorrhage more likely.,Familial Alzheimers disease:autosomal dominant,510%of all AD,Icelandic type:autosomal dominant,with mutation in the gene coding for cystatin C,begin at 3040 with multiple brain hemorrhages,most involve the basal ganglia,Down Syndrome,:trisomy 21,British type of familial amyloidosis:autosomal dominant,associated with progressive dementia,spasticity,and ataxia.Brain stem,spinal cord,and cerebellum all exhibit amyloid deposits,but hemorrhage typically does not occur.,Seth Love,Frontiers in Bioscience 14,4778-4792,January,2009,The cause of amyloid deposits in blood vessels in the brain in sporadic CAA is not known,In 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 amyloid cannot be dissolved and builds up in the brain blood vessel walls.,One form of amyloid fibril subunit proteins is the amyloid beta protein.,Systemic theory,amyloid beta protein in blood,deposited in blood vessels in the brain,breakdown blood-brain barrier,amyloid beta protein deposited in brain substance,forms neuritic plaque,Second theory,amyloid fibrils produced by perivascular microglia,Third theory,both nerve cells and glia produce amyloid precursor protein,increases with,aging,病理机制,Amyloid damages the media and adventitia,leading to thickening of the basal membrane,stenosis of the vessel lumen,fragmentation of the internal elastic lamina,result in fibrinoid necrosis and microaneurysm formation,Some 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(perhaps by arteriosclerosis or hypertension),病理机制,several key processes are involved:production of amyloid precursor proteins(APP),processing of precursor proteins,aggregation of protein,and fibril formation.Impaired elimination and accumulation of soluble and insoluble-amyloid peptide may underlie the pathogenesis of CAA and explain the link between CAA and AD.,Electron microscopy demonstrates fibrils of amyloid in the outer basement membrane in the initial stage of CAA,Many types of amyloid protein are present in the body,but some are unique to the brain.-amyloid is a unique cerebrovascular amyloid protein,Amyloid Family:,A,ACys,ATTR,AGel,PrPSc,ABri,ADan,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,HE VS Congo Red,Pathology,由皮层向皮层下过度的区域中受累血管的分布情况,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,grading,Mortality and Morbidity,CAA ICH associated with lower mortality rate(11-32%)and better functional outcome,25-40%have a recurrence,with the highest risk in the first year,associated with a high mortality rate(up to 40%),Cognitive impairment is common