According to the literature, MRI has been applied to characterize the atherosclerosis in coronary and extracranial internal carotid artery. The cross-sections of MCA were scanned by Magnetic Resonance Imaging (MRI) to assess the accuracy of MRI in identifying MCA stenosis with histopathology as a golden standard, which was performed in the same post-mortem brains as in the second part. The sensitivity and specificity of MRI in detecting more than 30% MCA stenosis were 38.6% and 92.2%, with a positive predictive value of 87.2% and negative predictive value of 52.2%, and the corresponding values of MRI in identifying more than 50% MCA stenosis were 57.1%, 90.8%, 50% and 83.0%, respectively. Stenotic lesions >30% and >50% identified by MRI were found to be associated with infarctions in corresponding MCA territory. / After verification of potential relationship between ischemic stroke and intracranial artery calcification, the incidence of intracranial artery calcification was assessed in the ischemic stroke. One hundred and seventy-five ischemic stroke patients and 182 controls were enrolled. There was a higher prevalence of intracranial artery calcification in ischemic stroke patients than in controls. Hypertension, diabetes, smoking, intracranial artery calcification, hyperlipidemia, and atrial fibrillation were found to be independently associated with ischemic stroke. / Atherosclerotic stenosis is a heterogeneous disorder. The studies performed in extracranial carotid artery and coronary artery showed that the genes associated with lipoprotein metabolism may be associated with atherosclerosis. Thus, we speculated that the genes concerned with lipid metabolism may also be risk factors for MCA atherosclerotic stenosis. In the part of genetic analysis, clinical parameters and the genotypes of polymorphisms in the apolipoprotein E (ApoE), lipoprotein lipase (LPL), and paraoxonase (PON1) genes were compared in patients with and without MCA stenosis. Two hundred and ninety-four ischemic stroke patients were recruited, 136 cases with and 158 without MCA stenosis. Systolic blood pressure (SBP), rather than ApoE, LPL, and PON1 polymorphism was found to be a risk factor of MCA stenosis. / Calcification of intracranial artery, as a common complication of atherosclerosis, was investigated by multi-detector-row computed tomography (MDCT). By this advanced technique, the prevalence and location of calcification in intracranial arteries were determined, and its potential risk factors were also investigated. Four hundred and ninety patients were recruited. The incidence of intracranial artery calcification was 69.4%. The highest prevalence of intracranial artery calcification was seen in internal carotid artery (60%), followed by vertebral artery (20%), middle cerebral artery (5%) and basilar artery (5%). Age, a history of ischemic stroke, and white blood cell count were shown to be independently associated with intracranial artery calcification. / In the present study, genetic, pathological, imaging characterizations and prognosis of MCA stenosis were investigated. The effect of candidate genes has not been confirmed in the present study, but SBP and hypertension appears to contribute a lot to the occurrence of MCA stenosis among Chinese populations. As for the pathology of MCA atherosclerotic plaques, luminal stenosis and also the morphology of atherosclerotic plaque seem to play a cooperative role in leading to ischemic stroke. Imaging studies demonstrated the agreement between ex vivo MRI and histopathology in identifying MCA stenosis, and the correlation between the MCA stenosis identified by MRI and ischemic events. Calcification of intracranial artery, as a common complication of atherosclerosis, may be associated with age, history of ischemic stroke. High incidence of ischemic stroke has been demonstrated in Chinese type 2 diabetes patients. The presence of asymptomatic MCA stenosis plays an important role in the occurrence of ischemic stroke. / Lastly, using a cohort-study, we aimed to investigate stroke incidence of asymptomatic MCA stenosis and its risk factors in Chinese type II diabetic population. Transcranial Doppler was performed to define MCA stenosis. Incident strokes between 1996 and 2006 were ascertained by the database of Clinical Management System of the Hong Kong Hospital Authority. Anthropometric parameters (waist circumference and body mass index), blood pressure, and baseline plasma biochemical profile (lipid and glucose) were recorded to find the risk factors of ischemic stroke in asymptomatic MCA stenosis patients. Totally, 2,197 type II diabetic patients without symptoms of cerebrovascular disease were recruited. The evidence of MCA stenosis was identified in 272 subjects (12.4%), including 146 (53.7%) subjects with single-vessel involvement. Ischemic stroke occurred in one hundred and eighty-four (8.4%, 184/2197) patients. History of ischemic heart disease, MCA stenosis, the presence of retinopathy, lipid total cholesterol and age were independently associated with ischemic stroke. / Secondly, the pathological features of MCA stenosis and their relationship with cerebral infarcts were investigated in a series of post-mortem adults aged 45 years or above. The morphological features of the MCA atherosclerotic plaques were described in detail. The results demonstrated that the degree of luminal stenosis, the percentage of the plaques containing more than 40% lipid area, the values of cap-lipid, cap-lipid-stenosis, and the prevalence of intraplaque hemorrhage, neovasculature and thrombus were higher in the group of plaques associated with infarction. And the mean index of both CD45RO and CD68 were higher in the group of plaques associated with infarction. Binary logistic regression showed that stenosis, lipid area and presence of neovasculature were independent risk factors of MCA infarcts. / Stroke is one of the leading causes of death, disability, and dementia throughout the world. The stenosis of the intracranial large artery, especially the middle cerebral artery (MCA), is common in Chinese, Hispanic, and African populations. But MCA stenosis has been understudied due to its infrequency in the white population and its relative inaccessibility and invasiveness involved in its investigations. The purpose of the study was to investigate the genetic, pathological, imaging characteristics and prognosis of MCA atherosclerotic stenosis in Chinese population. / Chen Xiang-yan. / "September 2006." / Adviser: MH Ng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1460. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 193-212). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Object Rupture of intracranial arteriovenous malformations is a leading cause of stroke in children and young adults. Treatment options include surgery and highly focused radiation (stereotactic radiosurgery). For large and deep seated lesions, the risks of surgery may be prohibitively high, while radiosurgery has a disappointingly low efficacy and long latency. Radiosurgery carries the most promise for significant advances, however the process by which radiosurgery achieves obliteration is incompletely understood. Inflammation and thrombosis are likely to be important in the radiation response and may be amenable to pharmacological manipulation to improve radiosurgical efficacy. Materials and methods Immunohistochemistry and electron microscopy were used to study normal cerebral vessels, cavernous malformations and AVMs, some of which had previously been irradiated. An attempt was made to culture AVM endothelial cells to study the immediate response of AVM endothelium to radiosurgery. The effects of radiosurgery in a rat model of AVM were studied using immunohistochemistry and the results used to determine the choice of a pharmacological strategy to enhance the thrombotic effects of radiosurgery. Results Vascular malformations have a different endothelial inflammatory phenotype than normal cerebral vessels. Radiosurgery may cause long term changes in inflammatory molecule expression and leads to endothelial loss with exposure of pro-thrombotic molecules. Ultrastructural effects of irradiation include widespread cell loss, smooth muscle cell (SMC) proliferation and thrombosis. Endothelial culture from AVMs proved difficult due to SMC predominance in initial cultures. Radiosurgery upregulated several endothelial inflammatory molecules in the animal model and may induce pro-thrombotic cell membrane alterations. The administration of lipopolysaccharide and soluble tissue factor to rats following radiosurgery led to selective thrombosis of irradiated vessels. Conclusions Inflammation and thrombosis are important in the radiosurgical response of AVMs. Lumen obliteration appears to be mediated by proliferation of cells within the vessel wall and thrombosis. Upregulation of inflammatory molecules and perhaps disruption of the normal phospholipid asymmetry of the endothelial and SMC membranes are some of the earliest responses to radiosurgery. The alterations induced by radiation may be harnessed to selectively initiate thrombus formation. Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing treatable lesion size and reducing latency.

Introdução: O risco do tratamento das malformações arteriovenosas encefálicas (MAVEs) é proporcional à sua graduação. O processo de seleção da técnica empregada depende, além da natureza e localização das MAVEs, das condições clínicas e idade dos doentes e da disponibilidade de profissionais treinados e de equipamentos apropriados no ambiente onde o doente é tratado. Objetivo: Avaliar a eficácia da radiocirurgia e da embolização prévia ao tratamento radiocirúrgico das MAVEs classificadas como graus 3A, 3B, 4 ou 5. Métodos e Resultados: O trabalho baseou-se na observação retrospectiva de prontuários clínicos e de arquivos de imagens de 90 doentes com diagnóstico de MAVEs classificadas como graus 3A, 3B, 4 ou 5 submetidos a tratamento com radiocirurgia precedida ou não de embolização no Departamento de Radioterapia e Radioterapia Estereotáctica, Neuroradiologia Intervencionista e Neurocirugia da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, de outubro de 1993 a outubro de 2008. As idades dos doentes variaram de sete a 60 anos (média de 30,6 anos ± 11,59 anos, mediana de 28 anos). Eram do sexo feminino 46 (51,1%) doentes. Todos foram submetidos a três exames de ressonância magnética (RM) ou tomografia computadorizada (TC) no primeiro ano de acompanhamento e a um exame de RM ou TC do encéfalo no segundo e terceiro anos. Quando um dos exames sugeriu oclusão da MAVE ou o período de acompanhamento foi maior que três anos, os doentes foram submetidos à angiografia digital do encéfalo. Em 51 (56,7%) dos 90 doentes tratados ocorreu oclusão completa da MAVE após a primeira radiocirurgia (1ª Rc), em 21 (23,3%) foram evidenciadas complicações clínica em 36 (40,0%), foram visibilizadas anormalidades no exame de RM. Em 30 (33,3%) doentes evidenciou-se hipersinal no encéfalo em T2 na RM xvi e, em seis (6,7%), radionecrose. Trinta e dois(82,0%) dos 39 doentes que não apresentaram oclusão completa da MAVE após a 1ª Rc foram submetidos à segunda radiocirurgia (2ª Rc). Ocorreu oclusão completa em 12 (37,5%) destes doentes, instalaram-se complicações clínicas em cinco (15,6%) e, anormalidades no exame de RM em oito (25,0%), ou seja, hipersinal em T2 na RM em três (9,5%) e radionecrose em cinco (15,6%). Conclusão: Concluiu-se que a radiocirurgia foi eficaz no tratamento das MAVEs graus 3A, 3B, 4 e 5, que as MAVEs classificadas como grau 3B devem tratadas, preferencialmente, apenas com radiocirurgia e que as MAVEs classificadas como 3A, 4 e 5 devem ser submetidas à embolização previamente à radiocirugia para reduzir-se sua graduação e seu fluxo sanguíneo / Introduction: The risk of treatment of the cerebral arteriovenous malformations (AVM) is proportional to their grade and is affected by the method used. The selection of the AVM therapeutic method depends of the vascular pattern and anatomical site, clinical condition and age of the patient, experience of the treating team and of the equipment available. Objectives: This study aimed the evaluation of the efficacy of the radiosurgical treatment of Grade 3A, 3B, 4 and 5 cerebral AVMs in patients previosly treated or not with embolization. Methods and Results: The data of the clinical notes and the computed tomography (CT) and magnetic ressonance (RM) images of the brain of 90 patients with Grade 3A, 3B, 4 or 5 cerebral embolised or not AVMs treated with radiosurgery at the Department of Radiotherapy, Stereotactic Radiotherapy, Interventional Neuroradiology and Neurosurgery at Real e Benemerita Associação Portuguesa de Beneficência de São Paulo were retrospectively reviewed. The ages of the patients ranged from 7 to 60 years of (average = 30.6 ± 11.59 years; median = 28 years) and 46 (51.1%) were female. During the first year after treatment three MR or CT scans of the brain were evaluated and one at the end of the 2nd and 3rd years after the treatment one MR or CT scan were re-evaluated respectively. When the brain scans suggest AVM occlusion, cerebral angiography was performed. In 51 of the 90 patients (56.7%) there was complete occlusion of the AVM after one radiosurgical treatment; 21 of the patients (23.3%) had clinical complications. In 36 patients (40.0%) new abnormalities of the MR became evident. Thirty (33.3%) presented T2 hypersignal and six (6.7%), had radionecrosis. From the 39 patients who did not had complete occlusion of the AVM, 32 (82.0%) had a second radiosurgical course of treatment; in 12 xviii (37.5%) the AVM became completely occluded but five (15.6%) had clinical complications. Eight (25.0%) of these patients presented new abnormalities at the MR scan of the brain; three (9.5%) had T2 hypersignal and five (15.6%) radionecrosis. Conclusions: Radiosurgery was effective in the treatment of Grade 3A, 3B, 4 and 5 cerebral AVMs , Grade 3B cerebral AVM should be treated only with radiosurgery without previous embolization, and Grade 3A, 4 and 5 AVMs should be treated with embolization to reduce their AVM grade and blood flow prior to radiosurgery

Introdução: O risco do tratamento das malformações arteriovenosas encefálicas (MAVEs) é proporcional à sua graduação. O processo de seleção da técnica empregada depende, além da natureza e localização das MAVEs, das condições clínicas e idade dos doentes e da disponibilidade de profissionais treinados e de equipamentos apropriados no ambiente onde o doente é tratado. Objetivo: Avaliar a eficácia da radiocirurgia e da embolização prévia ao tratamento radiocirúrgico das MAVEs classificadas como graus 3A, 3B, 4 ou 5. Métodos e Resultados: O trabalho baseou-se na observação retrospectiva de prontuários clínicos e de arquivos de imagens de 90 doentes com diagnóstico de MAVEs classificadas como graus 3A, 3B, 4 ou 5 submetidos a tratamento com radiocirurgia precedida ou não de embolização no Departamento de Radioterapia e Radioterapia Estereotáctica, Neuroradiologia Intervencionista e Neurocirugia da Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, de outubro de 1993 a outubro de 2008. As idades dos doentes variaram de sete a 60 anos (média de 30,6 anos ± 11,59 anos, mediana de 28 anos). Eram do sexo feminino 46 (51,1%) doentes. Todos foram submetidos a três exames de ressonância magnética (RM) ou tomografia computadorizada (TC) no primeiro ano de acompanhamento e a um exame de RM ou TC do encéfalo no segundo e terceiro anos. Quando um dos exames sugeriu oclusão da MAVE ou o período de acompanhamento foi maior que três anos, os doentes foram submetidos à angiografia digital do encéfalo. Em 51 (56,7%) dos 90 doentes tratados ocorreu oclusão completa da MAVE após a primeira radiocirurgia (1ª Rc), em 21 (23,3%) foram evidenciadas complicações clínica em 36 (40,0%), foram visibilizadas anormalidades no exame de RM. Em 30 (33,3%) doentes evidenciou-se hipersinal no encéfalo em T2 na RM xvi e, em seis (6,7%), radionecrose. Trinta e dois(82,0%) dos 39 doentes que não apresentaram oclusão completa da MAVE após a 1ª Rc foram submetidos à segunda radiocirurgia (2ª Rc). Ocorreu oclusão completa em 12 (37,5%) destes doentes, instalaram-se complicações clínicas em cinco (15,6%) e, anormalidades no exame de RM em oito (25,0%), ou seja, hipersinal em T2 na RM em três (9,5%) e radionecrose em cinco (15,6%). Conclusão: Concluiu-se que a radiocirurgia foi eficaz no tratamento das MAVEs graus 3A, 3B, 4 e 5, que as MAVEs classificadas como grau 3B devem tratadas, preferencialmente, apenas com radiocirurgia e que as MAVEs classificadas como 3A, 4 e 5 devem ser submetidas à embolização previamente à radiocirugia para reduzir-se sua graduação e seu fluxo sanguíneo / Introduction: The risk of treatment of the cerebral arteriovenous malformations (AVM) is proportional to their grade and is affected by the method used. The selection of the AVM therapeutic method depends of the vascular pattern and anatomical site, clinical condition and age of the patient, experience of the treating team and of the equipment available. Objectives: This study aimed the evaluation of the efficacy of the radiosurgical treatment of Grade 3A, 3B, 4 and 5 cerebral AVMs in patients previosly treated or not with embolization. Methods and Results: The data of the clinical notes and the computed tomography (CT) and magnetic ressonance (RM) images of the brain of 90 patients with Grade 3A, 3B, 4 or 5 cerebral embolised or not AVMs treated with radiosurgery at the Department of Radiotherapy, Stereotactic Radiotherapy, Interventional Neuroradiology and Neurosurgery at Real e Benemerita Associação Portuguesa de Beneficência de São Paulo were retrospectively reviewed. The ages of the patients ranged from 7 to 60 years of (average = 30.6 ± 11.59 years; median = 28 years) and 46 (51.1%) were female. During the first year after treatment three MR or CT scans of the brain were evaluated and one at the end of the 2nd and 3rd years after the treatment one MR or CT scan were re-evaluated respectively. When the brain scans suggest AVM occlusion, cerebral angiography was performed. In 51 of the 90 patients (56.7%) there was complete occlusion of the AVM after one radiosurgical treatment; 21 of the patients (23.3%) had clinical complications. In 36 patients (40.0%) new abnormalities of the MR became evident. Thirty (33.3%) presented T2 hypersignal and six (6.7%), had radionecrosis. From the 39 patients who did not had complete occlusion of the AVM, 32 (82.0%) had a second radiosurgical course of treatment; in 12 xviii (37.5%) the AVM became completely occluded but five (15.6%) had clinical complications. Eight (25.0%) of these patients presented new abnormalities at the MR scan of the brain; three (9.5%) had T2 hypersignal and five (15.6%) radionecrosis. Conclusions: Radiosurgery was effective in the treatment of Grade 3A, 3B, 4 and 5 cerebral AVMs , Grade 3B cerebral AVM should be treated only with radiosurgery without previous embolization, and Grade 3A, 4 and 5 AVMs should be treated with embolization to reduce their AVM grade and blood flow prior to radiosurgery