Clinical Study Of Collateral Circulation In Adult Moyamoya Disease

Objective To investigate the patterns of collateral circulation in adults MMD, the relationship between collateral circulation and stroke subtypes, the value of hyperintense vessel signs (HVS) on fluid-attenuated inversion recovery (FLAIR) sequence assessing the patterns of collateral blood flows in adult MMD, and the correlation of serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9(MMP-9) and Suzuki’s grading system.Method Clinical data of consecutive adult patients with MMD were retrieved from Nanjing Stroke Registry Program in Jinling hospital between August2004and January2010, and following studies were performed:â‘ As the research objects of the extracranial and intracranial collateral circulation of anterior and posterior cerebral circulation ipsilateral to stroke hemisphere, the relationship between collateral distribution patterns in adult MMD and Suzuki’s classification was analyzed;â‘¡According to stroke classification, stroke patients with MMD were divided into different subtypes. The angiographic findings of AChA-PComA were classified into grades1-3:Grade1, normal or mild to moderate dilation, Grade2, exceeding dilation and abnormal extension, and Grade3, disappearance. The relationship between stroke subtypes and angiographic grades of AChA-PcomA was assessed;â‘¢These imaging data of seventy-three non-hernorrhagic hemispheres including digital cerebral angiography and FLAIR sequence were examined. According to the different sites of HVS located in the middle cerebral artery, distributed patterns of HVS in hemisphere with vascular lesions were classified into grades0-3:Grade0, absence of HVS; Grade1, HVS were limited in the cerebral sulci of temporal lobe and Sylvian fissure; Grade2, HVS in the cerebral sulci of fronto-parietal lobe and Sylvian fissure; and Grade3, HVS in the combined territories of Grade1and Grade2. In addition, artery steno-occlusion related intracerebral collateral blood flows were classified as three types:Type1, residual antegrade flow across steno-occlusive lesions; Type2, retrograde flows via leptomeningeal vessels; Type3, the combined collateral blood flows of Type1and Type2. The relationship between the patterns of intracerebral collateral blood flows and the location of HVS was analyzed;â‘£Fifty-two adult MMD patients suffered from transient ischemic attack or stroke were included, and sixteen sex-and age-matched healthy individuals with MMD patients consisted of the control group. Using enzyme-linked immunosorbent assay, serum concentrations of VEGF and MMP-9were compared between adult MMD patients and healthy individuals. By Suzuki’s six-grading system, patients were divided into different subgroups, and the correlation of serum levels of VEGF and MMP-9corresponding to different subgroup and Suzuki’s grading was respectively analyzed. In addition, the correlation of serum levels of VEGF and MMP-9was also evaluated.Resultsâ‘ In117assessed vessel units of the anterior and posterior cerebral circulation ipsilateral to stroke hemisphere, there were a total of200collateral circulation with three different grades. the percentage of number of Grade1collateral (anterior cerebral artery [ACA]â†'meningeal arteries [MLA]â†'middle cerebral artery [MCA]), Grade2collateral (dilating and extensing anterior choroidal artery beyond choroid fissure, patent posterior communicating arteryâ†'posterior cerebral arteryâ†'MLAâ†'ACA and/or MCA, and posterior choroidal arteryâ†'posterior pericallosal arteriesâ†'ACA) and Grade3collateral (collateral originating from the external carotid artery and supplying to cerebral circulation via MLA) was11.5%(23/200),52.0%(104/200) and36.5%(73/200), respectively. The distribution percentage of Grade1collateral circulation was gradually decreased from Suzuki’s â…  to Suzuki’s VI, mainly distributed in the early stage of MMD (Suzuki’s Ⅰ～Ⅱ) and accounted for91.3%(21/23; Z=-7.270, P<0.001). The distribution percentage of Grade3collateral circulation was gradually increased from Suzuki’s â…  to Suzuki’s â…¥, especially in the late stage of MMD (Suzuki’s â…¤-â…¥) and accounted respectively for37.0%(27/73) and63.0%(46/73; Z=-7.270, P<0.001). Compared with the total distribution of Grade1and2collateral circulation, the distribution percentage of Grade2collateral circulation was6.7%(7/104),7.7%(8/104),15.4%(16/104),40.4%(42/104),14.4%(15/104) and15.4%(16/104) from Suzuki’s â…  to Suzuki’s â…¥. Although there was not significant difference, Grade2collateral circulation mainly distributed in the medium stage of MMD (Suzuki’s Ⅲ～Ⅳ);â‘¡The distributed patterns of foci involved in cerebral infarction and hemorrhage were changed with the different grades of AChA-PComA, though the differences were not statistical significance (Z=-1.377; P=0.179). With increasing grade of AChA-PComA, the percentage of cerebral infarction was decreased involved in anterior cerebral circulation and was increased involved in posterior cerebral circulation, and the difference was statistically significant (Z=-5.302; P<0.001). In all ICHs, the percentage of intraventricular hemorrhage was highest (32.5%,25/77), and furthermore,22(88%) of25patients, the ipsolateral AChA-PComA corresponding to intraventricular hemorrhage showed exceeding dilation and abnormal extension (Z=-3.258; P=0.001). Of77ICHs, SAH accounted for23(29.9%). The ipsolateral AChA-PComA corresponding to SAH involving posterior circulation showed exceeding dilation and abnormal extension than the SAH located in anterior circulation (Z=-3.210;P=0.001). Furthermore, in the stage of exceeding dilation and abnormal extension or disappearance of AChA-PComA, aneurysmal rupture-related SAH located in posterior circulation accounted for69.2%(9/13; Z=-2.986; P=0.003);â‘¢Of79non-hemorrhagic hemispheres, there were73hemispheres with the presence of HVS, and therefore, the percentage of the presence of HVS was92.4%(73/79) in hemisphere with vascular lesions. Importantly, the patterns of slow collateral blood flows corresponding to Grade1HVS were all antegrade (100%,7/7); the collateral patterns corresponding to Grade2HVS were mainly retrograde leptomeningeal flows (95%,19/20); and the slow combined collateral blood flows were mainly corresponded to Grade3HVS (84.8%,39/46). Furthermore, with the changing sites of HVS from the cerebral sulci of temporal lobe to the cerebral sulci of fronto-parietal lobe, the directions of collaterals were changed from antegrade to retrograde, which was statistically significant;â‘£Serum VEGF concentrations in ischemic and hemorrhagic MMD patients was respectively289.36±69.20pg/ml and324.32±95.61pg/ml and were significantly higher compared to those in healthy controls (63.48±7.64pg/ml; F=69.43; P<0.001). Similar findings were observed for MMP-9(499.42±76.15ng/and531.21±100.244ng/ml versus257.10±30.72ng/ml; F=66.023; P<0.001). With the increase of Suzuki’s grading, serum levels of VEGF and MMP-9respectively showed a high trend (r=0.879, P<0.001; r=0.838, P<0.001). In addition, A positive correlation between serum levels of VEGF and MMP-9was found in the MMD group.Conclusionâ‘ The patterns of collateral distribution is changing with the progression of adult MMD. The collateral circulation including dilating and extensing anterior choroidal artery beyond choroid fissure, patent posterior communicating arteryâ†'posterior cerebral arteryâ†'MLAâ†'ACA and/or MCA, and posterior choroidal arteryâ†'posterior pericallosal arteriesâ†'ACA accounted for a higher proportion, especially in the medium stage of disease duration, which suggested that these collaterals play an important compensatory role of blood flow;â‘¡Stroke subtypes were related to angiographic characteristics of AChA-PComA in adult moyamoya disease, and the higher the grade of AChA-PComA, the greater the likelihood of stroke involving posterior cerebral circulation. Moreover, the angiographic characteristics may predict certain hemorrhagic stroke subtypes;â‘¢The different location of HVS can reflect the different patterns of collateral blood flow, and the location of HVS may predict the directions of intracerebral collateral blood flows in adult MMD patients;â‘£Serum levels of VEGF and MMP-9in adult MMD were higher than those in healthy controls, which may play a role in neovascularization in MMD, and moreover, serum levels of VEGF and MMP-9showed a high trend with the progression of MMD, which suggest that serum levels of VEGF and MMP-9can reflect the severity of MMD.