Clinical,Radiological And Pathological Study In Patients With Cerebral Amyloid Angiopathy

Objective To observe the clinical、radiological and radiological features and mechanical of hemorrhage in cerebral amyloid angiopathy（CAA）patients.Methods 1.35 CAA patients（14 definite CAA patients、21 probable CAA）patients were enrolled.Demographic and clinical data,including clinical symptoms,Analysis the position of the lobar hemorrhage demonstrated on CT.2.Observe the CMB or SS on SWI in 18 patients,analysis the number as well as the position relationship with lobar hemorrhage in the follow up study.3.21 CAA patients with complete imaging from the first part were involved in this study.10pathology proven non-CAA patients were the control group.Analysis the position of the white matter hyperintensity and DPVS demonstrated on MRI.4.10 non-demential CAA patients were evaluated together with 10cases of normal controls and 11 Alzheimer disease（AD）patients were assessed with ¹¹C-PIB PET MRI with as well as SWI.5.Analysis the relationship between PIB and CMB and the distribution of amyloid protein in CAA、AD and control group.Results 1.14 definite CAA,21 probable CAA patients were enrolled in our study.14 patients were encountered in 54 autopsied cases at the PLA General hospital over the past 20 years.The CAA incidence was 30.4%in the pathological series.Patients were 70 to 99 years old.Large-and medium-sized leptomeningeal and cortical arteries showed the characteristic pattern of medial and intimal involvement,with luminal stenosis.The amyloid nature of the infiltrate was confirmed by electron microscopic examination in all cases.Multiple,small cortical infarcts and hemorrhages were regularly present.Larger lobar hemorrhage was present in 6 cases.The main clinical manifestations included,limb paralysis（n=12）,headache（n=7）,disturbance of consciousness（n=6）,aphasia（n=5）,convulsions（n=3）,ransient neurological loss（n=1）.A total of 26 cases（74.3%）developed lobar hemorrhage,Among them,8 were multiple lobar hemorrhages.Three broke into the subarachnoid space,and 2 cases broke into the ventricle.The sites of lobar hemorrhage were recorded for patients with multiple lobar hemorrhage,including 12 cases of occipital lobe hemorrhage,10 cases of frontal lobe hemorrhage,8 cases of temporal lobe hemorrhage,and 5 cases of parietal hemorrhage.and there was no statistical significance between the groups.2.The detection rate of CAA in brain autopsy cases was 25.9%（14/54）.42.9%（6/14）of CAA patients were pathologically diagnosed as asymptomatic intracranial hemorrhage,42.9%（6/14）of CAA patients were pathologically diagnosed as lobe hemorrhage,and 14.3%（2/14）of CAA patients were bleeding from other sites（1 case was cerebral hemorrhage in basal ganglia region and 1 case was tumor stroke hemorrhage）.The incidence of microscopic severe vascular lesions in CAA patients was 83.3%（5/6）higher than 37.5%（3/8）in the group without lobar hemorrhage（P=0.038）.Microscopically,the incidence of microhemorrhage and microinfarction in cerebral lobes in CAA group was higher than that in non-CAA group（P=0.013 and 0.047,respectively）.3.18 CAA patients underwent susceptibility-weighted imaging（SWI）examination,and all of them were found to have cerebral microbleeds（CMB）,6 patients were found to have multiple CMB,2 patients had CMB in basal ganglia region,and 3 patients had convexity superficial siderosis（SS）.The site of the cerebral hemorrhage is not consistent with the location of the CMB that existed before.All patients with SS had cerebral hemorrhage on the same side of SS.4.Sever centrum semiovale DPVS were detected in 13（61.9%）of patients with CAA but in none of the control with non-CAA patients（p=0.004）.Occipital dominant white matter hyperintensity was found in CAA patients（p=0.029）5.The whole brain SUVR in CAA group（1.8±0.35）and AD group（1.9±0.35）were significantly higher than those in NC group（1.2±0.12）（P=0.028 and 0.031,respectively）.Using Boston criteria as a reference,¹¹0%（6/6）sensitive and 90%（9/10）specific for CAA diagnosis.Under visual observation,the cerebral microhemorrhage in CAA patients was consistent with the space of high PIB uptake.PIB uptake at the old bleeding site was negative.6.Compared with the healthy control group,there were 11 voxins in the AD group,which were higher than those in the healthy control group.The differences were concentrated in the temporal pole,putamen,superior middle frontal gyrus and superior frontal gyrus,which were basically symmetrical on both sides（P<0.05）.CAA has higher PIB retention in Temporal-Mid（1334）、Calcarine（1643）and Frontal-Mid（74）（p<0.05）compared with health control group.7.AD has higher PIB retention in Precuneus（338）、Paracentral-Lobule（249）Supper-Moter-Area（226）、Lingual（210）、Postcentral（113）、Parietal-Inf（72）Parietal-Sup（77）（p<0.05）compared with CAA group.Conclusion1.Nearly half patients with pathologically confirmed cerebral amyloid angiopathy were clinically silent.The probable CAA patients may have variable clinical symptoms according to different site of hemorrhage.Lobar hemorrhage may be associated with severe vascular disease.The pathology of patients without lobar hemorrhage may include microhemorrhage,subarachnoid hemorrhage or lacunar infarction.2.The location of cerebral hemorrhage in CAA patients was not consistent with the CMB in the cerebral lobes.However,cerebral hemorrhage may tend to occur on the same side of SS in the middle stage of CAA.The amyloid deposition theory can explain this asymmetry of bleeding distribution.3.There are both cerebral hemorrhage and non-hemorrhage manifestations in CAA patients,and Aβdeposition may be the pathological basis.11C-PIB can bind to Aβdeposition in CAA patients.Lobar CMB patients with punctate distribution of white matter in subcortical area or significant occipital white matter osteoporosis,severe semi-ovale center with enlarged perivascular space,and positive 11C-PIB PET would support the diagnosis of CAA.4.In CAA patients,amyloid protein was more easily deposited in the Temporal-Mid、Calcarine and Frontal-Mid gyrus.CMB may be associated with local vascular Aβdeposition.The distribution of amyloid deposition in the brain of CAA patients and AD patients may not be consistent.