| Cerebrovascular amyloidosis is also called Cerebral amyloid angiopathy (CAA). This peculiar cerebral microvasccular lesion is one in which arteriolar media, including its smooth muscle cell component, is gradually replaced by fibrillar amyloid. CAA gives a pathological characteristic of amyloid deposit finding in small vessels of meninges and cerebral cortex, no amyloid angiopathy found in other system. CAA is always considered as an important cause of age-related cerebral hemorrhage, which could lead to stroke, hemorrhage or dementia. The incidence rate, distribution in brain and the clinical pathological characteristic of CAA have been reported detailedly and completely in Europe and Japan. There are many researches of lobar hemorrahge in domestic, but less report related CAA can be found. The present study was emphasized in reporting the distribution, clinical manifestation and sign, pathological characteristic of CAA and its correlation with other related illness. To investigate the characteristic of CAA in our country and detect the inflammatory response in CAA samples undergoing neuropathological examination and immunohistochemical study. The autopsy data was obtained from the department of Neurology of Shenyang General Hospital of PLA during the last more than 20 years. The present study including four parts:Part one is focused on clinical study. The clinical data was obtained from 245 autopsy samples in the department of Neurology of Shenyang General Hospital of PLA since 1983. All samples were stained by hematoxylin and eosin and Congo red,26 cases were diagnosed pathologically with CAA. There were 17 men and 9 women ranging 45 to 78 years with mean 66.5 years old. Of these cases, the number of samples above 60 years was 19(73%) and above 70 years was 11(42.31%), the age of all patients who suffered from cerebral hemorrhage was above 50 years with mean 65.35 years old, which is less than the age in western country and maybe the characteristic of CAA in china. Of the 26 CAA patients,8 patients (30.77%) had the history of hypertension,6 cases (23%) suffered from diabetes,2 patients (7.6%) were taking anticoagulant or antiplatelet agents. There were 20 cases diagnosed as cerebral hemorrhage, include 2 patients with lobe hemorrhage,8 patients with multiple lobe hemorrhage,5 patients with putamen hemorrhage,2 patients with cerebral ganglion hemorrhage,2 patients with cerebellar hemorrhage,1 patient with Brain stem hemorrhage. Of the 26 CAA patients, there were 2 patients with subaracchnoid hemorrhage,1 patient with hemorrhagic cerebral infarction,1 patient with basal ganglia infarction,1 patient with basilar artery occlusion,1 patient with subdural hematoma. All cerebral hemorrhage cases were confirmed CAA related hemorrhages histologically according to the Boston diagnostic criteria of CAA related hemorrhage, small-sized vessels nearby hemorrhagic focus were stained positive by Congo red, and no other pathological change was found. Of the 20 CAA-related cerebral hemorrhage cases,9 patients with headache,15 patients with limb palsy (4 patients fall in coma immediately),8 patients with hyperspasmia,18 patients with unconsciousness,10 patients with uprightness cerebrospinal fluid, which shows CAA always begin as cerebrovascular disease symptoms with uprightness cerebrospinal fluid. The CAA-related hemorrhage often occurs in the lobes of brain, few in basal ganglia, cerebellum and brainstem. In 20 patients with cerebral hemorraghe,8 patients (40%) had the history of hypertension.,14 patients with higer blood pressure than normal when hospitalized (there seem to be more cases that are diagnosed as hypertension before hospitalized and a transient increase in blood pressure at the acute phase of cerebral hemorrhage). In the present study, the concomitance rate of CAA and hypertension was higher than which reported 30% in abroad. Our study suggests that the presence of CAA should generally be taken into account when diagnosing and treating lobar hemorraghe even if hypertension is present and suggests a dominant role for CAA in the pathogenesis of cerebral hemorraghe. In 10 patients with lobar hemorraghe,2 patients had the history of hypertension,5 patients with higher blood pressure than normal when hospitalized, and all these 5 patients’blood pressure had dropped to normal in 1-2 days, which maybe relate to a transient responsive increase in blood pressure at the acute phase of cerebral hemorrhage. CAA was histopathologically confirmed as the origin of hemorrhage in the study, hypertension maybe a contributing factor in causing hemorrhage in patients with CAA, which suggests that different mechanisims might be at work at same time. Only one of 8 patients who suffered from recurrent multiple lobar hemorrhage had history of hypertension, which shows hypertension seems not to be a dangerous factor for recurrent and multiple lobar hemorrhage.We drawed a conclusion of the feature of CAA-related cerebral hemorrhage as follow:①CAA-related hemorrhage often occur in lobe, and influence the superficial area;②CAA-related hemorrhage is characterized by a lobular-shaped hematoma and multiple hemorrhage;③CAA-related hemorrhage break to subarachnoid space easily, on occasion break to cerebral ventricle; In our study,18 of 20 CAA-related hemorrhage breaked into subarachnoid space,2 of 20 breaked into cerebral ventricle;④multiple hemorrhage and repeated hemorrhage;⑤CAA-related hemorrhage often be fatal. Two patients with lobar hemorraghe in our study were taking anticoagulant or antiplatelet agents, serious CAA and multiple hemorrhage were histopathologically confirmed by autopsy, Which shows that anticoagulant or antiplatelet agents maybe a contributing factor for CAA-related hemorrhage.Part two is focused on routine pathological examination. Our study based on the 26 autopsy cases found that the CAA-suffered vessels mainly located in meninges, cortex, subcortical white and hemorrhage focus surroundings, few found in deep kankar and brain stem. Mening involved severvely more than cortex. As the distribution in mengings, CAA located in occiput, temple, forehead and parietal lobes mainly, less found in temple lobe. On the other hand, CAA-related hemorrhage mainly located in parietal, temple and occiput lobes, which differ from the location of vessles with CAA changes and the mechanism is unclear.Amyloid substance deposit in the media and extima of small and medium-sized artery, capillary wall segmentally and symmetricly. The basic histopathologic changes in the CAA under microscope are the invasion of the amyloid substance into the media and extima of artery. Large amount of the amyloid substance is deposited in the media, even taking place of media elastic layer, Which result in the media weaken, anapetia, microaneurysm neoplasia, even vessel rupture and bleeding. A few has external membrane of capillary and perivascular involvement, besides SP and NFT are found in the cerebral cortex. The characteristic staining appearance by HE under light microscope is amorphous, homogenous and intensely hyaline eosinophilic material. The amyloid substance were stained red by Congo red and presented the apple green birefringence under polarizing microscope, which can be used to diagnose CAA specifically. The CAA-AV changes were only found in the severe CAA as follow: microaneurysm, fibrinoid necrosis, double barreling changes, onion skin -liked intima changes, multiple arteriolar clusters and media hyalinization. In all 26 cases, microaneurysm were observed in 3, double barreling change observed in 5, multiple arteriolar clusters observed in 12, obliterative onion skin -liked intima change observed in 7, and fibrinoid necrosis observed in 9. Amyloid deposits were found in small artery of meninges, cerebral cortex, and the periphery of hemorrhage focus in 26 autopsy cases, but severe cerebral arteriosclerosis was observed in 1, moderate observed in 2, mild observed in13, without cerebral arteriosclerosis observed in 10. In 18 severe CAA, without cerebral arteriosclerosis was observed in 7, mild observed in 10, moderate observed in 1, which shows that CAA is not relate to cerebral arteriosclerosis. In addition,2 patients diagnosed as SAH were confirmed that caused by CAA histologically, so it is possible that SAH was caused by CAA in senium.Part three was focused on immunohistochemical study. The expressions of amyloid Aβ40, Aβ42,βAPP and cystatin C were evaluated in the 26 cases. It was suggested that there were the most positive stainings of A640, fewer stainings of Aβ42, and fewest stainings of cystatin C. Aβ40, Aβ42 andβAPP staining were shown in the vessel walls of medium-sized and small-sized arteries, such as cortical and leptomeningeal vascular dilation, thickness and hyalination of vessel wall were also observed.It was suggested that A640 was the main component of amyloid-laden vessel walls, which has important implications for the pathogenesis of CAA, and perhaps provide instruction for the clearance of the targeting Aβfrom vessels. There was fewer staining of cystatin C in our study, only observed in a patient with multiple, severe cerebral hemorrhage (133ml), and mainly seen in the outer membrane of the vessel walls. It was suggested that there were fewer staining of cystain C in the Chinese sporadic cerebral amyloid angiopathy, maybe only observed in a substyle of cerebral amyloid angiopathy.Part four was focused on the study of cerebral amyloid angiopathy related inflammation. Of 26 patients with pathologically diagnosed CAA, a subset of 4(15.38%) cases could be distinguished by pathology finding of pervascular inflammation with lymph cells mainly. In the past, it was considered that lymph cells infiltrated around the amyloid-containing vessels was one of the CAA-AV, now it prones to be a subset of CAA. Pathological examination of the brain samples from these four patients demonstrated moderate to severely advanced CAA together with accumulations of lymph cells around amyloid-laden vessel in cerebral cortex and leptomeninges. All vessel segments with surrounding inflammatory changes stained positive for Aβ. Inflammation with in the vessel wall itself and granuloma formation were not observed. The localization of the lymph cells infiltration response to amyloid -laden vessel segments and the appearance of Aβin close association suggested that it could participate in the deposit of Aβ. T lymphocytes (staining for CD 3) were also present in the perivascular infiltrate, including low numbers of both CD8-positive and CD4-positive T lymphocytes, whereas B lymphocytes (assessed by staining for CD 20) and multinucleated giant cells (assessed by staining for CD20) were absent. All these four patients presented with cerebral lobe hemorrhage clinically and the presenting symptoms were cognitive decline progressing rapidly over a period of months and severe headache. Headache was prominent in 5 of remaining 22 patients. There are new onsets of seizure in three patients, while 5 in the remaining 22 patients, and 3 white matter changes in CT scan. These datas added a syndrome of perivascular inflammation, cerebral lobe hemorrhage, seizure, cognitive decline, headache and leukoencephalopathy to the spectrum of presentations associate with CAA. But because of few cases, we could not carry out statistics analysis in our study.The autopsy brain specimens in our study were so precious, but the brain fixation time was too long, which perhaps influenced the immunohistopathological staining. The limit of the present study was that we did not obtain the fresh brain samples. On the other hand, the patchy nature of the inflammatory response raises the possibility that this pathology might be missed in a small biopsy specimen, thereby causing an underestimate in its frequency. The figure of 15.38%(4/26) for the frequency of CAA-related inflammation observed in our series therefore may represent an overestimate of its true frequency. |
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