Zhu Xian Lun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references (leaves 83-103). / ACKNOWLEDGEMENT --- p.1 / ABSTRACT --- p.2 / Chapter CHAPTER 1 --- INTRODUCTION --- p.4 / Chapter CHAPTER 2 --- TREATMENT METHODS OF INTRACRANIAL ANEURYSMS OTHER THAN CLIPPING --- p.6 / Chapter CHAPTER 3 --- EXPERIMENTAL ANEURYSM MODELS --- p.24 / Chapter CHAPTER 4 --- A SUITABLE ANEURYSM MODEL FOR THE STUDY --- p.30 / Introduction / Materials and methods --- p.31 / Results --- p.37 / Discussion --- p.46 / Conclusion --- p.56 / Chapter CHAPTER 5 --- REINFORCEMENT AND FILLING TREATMENT IN EXPERIMENTAL ANEURYSMS --- p.57 / Introduction / Materials and methods --- p.58 / Results --- p.63 / Discussion --- p.71 / Conclusion --- p.77 / Chapter CHARTER 6 --- SUMMARY --- p.79 / Chapter APPENDIX I --- REFERENCES --- p.83 / Chapter APPENDIX II --- TABLES --- p.104 / Chapter APPENDX III --- FIGURES --- p.115

Ho Siu-ying, Salina. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 51-59). / Abstract and appendix in English and Chinese. / List of Tables --- p.v / List of Figures --- p.vi / Introduction --- p.1 / Method --- p.10 / Results --- p.15 / Discussion --- p.42 / References --- p.51 / Appendices --- p.60

Cerebral Cavernous Malformations (CCM) and Intracranial Aneurysms (IA) are cerebrovascular disorders that can lead to a hemorrhagic stroke and other neurological problems. CCMs are characterized by abnormally enlarged capillary cavities while IAs are saccular outpouchings of intracranial arteries. CCM is found in approximately 0.4% to 0.9% of the population, while IA is more common (3-6%). / This dissertation aimed to add to the body of research for CCM and IA and was divided into two parts. Initial work focused on the characterization and identification of the genes involved in CCM; the second phase focused on the identification of a susceptibility gene for IA. / In the first phase, the CCM1, CCM2 and CCM3 genes were characterized in families and in sporadic cases of CCM. In both cohorts, a causative mutation was identified in 71% of the cases. Subsequent MLPA analysis of subjects with no CCM mutations revealed that large genomic deletions and duplications are a common cause of CCM. In addition, investigation of CCM1 point mutations revealed that these were not simple missense mutations but that they rather activated cryptic splice-donor sites and caused aberrant splicing. Furthermore, the genetic predisposition to CCM in sporadic cases with a single lesion was determined to be different from sporadic cases with multiple malformations. Investigation into the loss of heterozygosity demonstrated a plausible mechanism for CCM pathogenesis involving a second somatic hit at the site of the lesion, suggesting that CCM may be caused by a complete loss of CCM protein function. / In the second phase, a genome-wide scan of a large family and subsequent linkage analysis using a monogenic approach identified a susceptibility locus for IA (ANIB4). / As a result of this research, we have greatly contributed to the field of CCM, most specifically to its clinical diagnosis. A greater understanding of the genetics involved in CCM will facilitate and permit better management care for patients. Furthermore, the possibility of identification of a gene with a major effect for IA will give us more insight into which pathways are involved in IA formation.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22827号 / 医博第4666号 / 新制||医||1047(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 髙橋 良輔, 教授 Shohab YOUSSEFIAN / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Abstract Subarachnoid haemorrhage (SAH) is a life-threatened disease with poor outcome. It is usually caused by an intracranial aneurysm (IA) rupture and rapid diagnosis and treatment are of great importance. Computed tomography (CT) is a reliable method to detect the blood in the subarachnoid (SA) spaces. Digital subtraction angiography (DSA) offers dynamic and morphological information of a ruptured IA. The treatment options for excluding an aneurysm from the main circulation are neurosurgical clipping and endovascular procedures. The purpose of the present study was to evaluate the risk factors of acute hydrocephalus (HC) and the reliability to localize the ruptured aneurysm based on non-contrast CT. The aim was also to compare the effect of neurosurgical and endovascular treatment on the development of chronic HC, and evaluate the incidence and the risk factors of early rebleeding (<  30 days) after coiling. The data of 180 operated patients with a ruptured IA were checked. Two neuroradiologists separately located the IAs based on non-contrast CT. The analyses of blood amount and distribution was a reliable method for estimating the location of ruptured middle cerebral artery (MCA) aneurysms and anterior communicate artery (ACoA) aneurysms. Intracerebral haemorrhage (ICH) was a predictor for detecting the precise site. The results confirmed that intraventricular haemorrhage (IVH) was the most consistent single risk factor for the development of acute HC. Haemorrhage in the basal region and the large total blood amount in the SA spaces were strong predictors. The effect of early treatment modality for ruptured IAs on the development of chronic HC with 102 clipped and 107 coiled patients was compared. The treatment method used was not significantly associated with the occurrence of chronic HC or the need for shunt operation. The incidence and risk factors of early rebleeding after coiling were investigated in 194 consecutive acutely (within 3 days) coiled patients with ruptured IAs. The incidence of early rehaemorrhage was 3.6%. The presence of ICH at admission and poor clinical condition were significant predictors for rebleeding. An early rehaemorrhage appeared as an enlargement of the ICH in all of these patients. In conclusion, the non-contrast CT is a reliable method to detect the location of ruptured IA in patients with MCA and ACoA aneurysms. The risk factor for the development of acute HC is IVH. Other predictors are the total SA blood amount and blood in the basal regions. The treatment method used for acutely ruptured IA has no significant effect on the occurrence of chronic HC. The incidence of early rebleeding after coiling is low. The risk factors of rebleeding are the presence of ICH and poor clinical condition. Rehaemorrhage appears often as an enlargement of the ICH.

Abstract The purpose of the study was to analyze the angiographic and clinical results of endovascularly treated intracranial aneurysms in Oulu University Hospital, Finland. The study population consisted of 416 consecutive patients (467 aneurysms, 332 ruptured), who were referred for endovascular treatment of intracranial aneurysm(s) between December 1993 and July 2004. Technical failures were analyzed for an assesment of technical feasibility. Angiographic results were assessed using modified Raymond Classification. Clinical results were analyzed from patient files using the Glasgow Outcome Scale (GOS). Patient, aneurysm, and procedure related variables were tested with an intention to find the predictors of the angiographic and clinical outcome. The clinical effects on presenting symptoms were analyzed for a subgroup of patients with a symptomatic unruptured aneurysm (n = 30). The mean results on technical feasibility, complications, and angiographic results were separately assessed for three time periods (1993–1997, 1998–2000 and 2001–2004) to demonstrate potential significant changes in outcome. Endovascular treatment of saccular aneurysms was technically feasible in 91.4% of the treatments. Initially, 25.7% of the aneurysms were completely occluded, 57.9% had a neck remnant, and 16.3% remained incompletely occluded. In follow-up, the rates for complete occlusions, neck remnants and incomplete occlusions were 37.6%, 49.7% and 12.7%, respectively. Small aneurysm size predicted complete aneurysm occlusion, while a wide aneurysm neck and location in the posterior circulation predicted incomplete occlusion. In follow-up (mean 38.2 months), 78.1% of the patients with a ruptured aneurysm and 92.3% of the patients with an unruptured aneurysm had resumed independent life (GOS 4-5). The predictors of good outcome were young age, good preprocedural clinical condition, small amount of blood in CT scan, and uncomplicated procedure. Ten of the treated aneurysms involved intracranial bleeding in follow-up, and the annual risk for bleeding after endovascular treatment was 0.95% among the patients with ruptured aneurysms and 0.33% among those with unruptured aneurysms. The risk of bleeding was associated with larger aneurysm size and lower occlusion grade. In the subgroup of symptomatic unruptured aneurysms, 53.4% of the patients showed either resolution or improvement of the symptoms after treatment. The rates of procedural complications, morbidity, and mortality were 16.5%, 6.7%, and 1.7%, respectively. The risk for procedural complications was higher when the balloon remodeling technique was used and lower in retreatments. Technical feasibility (85.6%, 90.6%, and 95.7%, respectively) and the percentage of complete occlusions (initially 16.5%, 23.0%, and 32.9%, respectively) were significantly improved by increased experience, while no statistical difference was detected in the total procedural complication rates (15.4%, 15.7%, and 18.3%, respectively) or the combined procedural morbidity and mortality rates (8.0%, 8.3%, and 9.1%, respectively). All six dissecting aneurysms treated with parent artery occlusion or the stent remodeling technique resulted in complete occlusions. The present results confirmed endovascular treatment of intracranial aneurysms as a feasible, safe, and effective method in preventing further bleeding of aneurysms. Increased experience in a single center improved the feasibility of the treatment as well as the angiographic results.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23371号 / 医博第4740号 / 新制||医||1051(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 安達 泰治, 教授 YOUSSEFIAN Shohab / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19397号 / 医博第4048号 / 新制||医||1012(附属図書館) / 32422 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邊 直樹, 教授 小泉 昭夫, 教授 木村 剛 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24785号 / 医博第4977号 / 新制||医||1066(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 金子 新, 教授 YOUSSEFIAN Shohab, 教授 阪上 優 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM