【作者】 徐文苑；

【导师】 楼小亮；

【作者基本信息】 南昌大学医学院 ， 神经病学（专业学位）， 2012， 博士

【摘要】 目的：通过对急性脑梗死患者血压、血糖、血脂、生活习惯、中风史、家族史等因素的调查分析,研究颅内动脉狭窄的危险因素,探讨颅内动脉狭窄的好发部位、颅内动脉狭窄相关性脑梗死的临床预后及影响因素。材料和方法：选取2008年10月至2012年6月在我科住院的急性脑梗死患者148例。所有患者诊断均符合全国第四届脑血管病学术会议修订的诊断标准,其中84例急性脑梗死患者经颅脑磁共振血管成像(MRA)证实合并颅内动脉狭窄,另64例MRA正常。将合并颅内动脉狭窄的急性脑梗死患者设为研究组,其中男性74例,女性10例,年龄41-80岁,平均年龄(61±9)岁；无颅内动脉狭窄的急性脑梗死患者作为对照组。其中男性48例,女性16例,年龄38-77岁,平均年龄(56±4.8)岁。两组均排除心源性栓塞、大动脉炎、合并感染、肿瘤、严重心肺疾病。入院第二天清晨空腹抽取静脉血测定血糖、甘油三脂(TG)、胆固醇(TC)、载脂蛋白A (ApoA)、载脂蛋白B (ApoB)、脂蛋白a、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、监测血压、完善心电图检查、询问并记录抽烟、酗酒史、高血压史、中风史及家族史。研究组和对照组比较分析危险因素；所纳入研究的颅内动脉包括：颈内动脉颅内段、椎动脉颅内段、基底动脉、大脑中动脉、大脑前动脉、大脑后动脉。通过对研究组颅脑MRA的分析,获得颅内动脉单支狭窄和多支狭窄的分布特征。两组患者在入院第一周每天上午、第十天上午分别进行美国国立卫生研究院脑卒中量表(NIHSS)评分,观察疾病短期的进展及预后。将可能影响预后的因素：梗死面积、梗死类型、动脉狭窄部位、动脉狭窄范围、体温、血糖、血压进行分析。结果：1、颅内动脉狭窄的危险因素经过单因素分析后,根据单因素分析结果,结合专业知识,用多因素分析方法对某些可能引起混杂作用的变量进行调整。年龄、性别、吸烟、饮酒、糖尿病、高血脂、高血压、冠心病、家族史、脂蛋白a, APO-B、 HDL-C进入多因素分析,最后性别、吸烟、糖尿病、高血脂、高血压、脂蛋白-a、 APO-B、 HDL-C变量有统计学意义。2、颅内动脉狭窄与血脂的关系经过卡方检验(χ2=4.24,P<0.05),两组脑梗死患者高血脂的比例有统计学意义,狭窄组的高血脂患者比例大于非狭窄组,脑梗死患者中有高血脂者发生颅内动脉狭窄危险性是没有高血脂者的2.05倍。血脂各项指标中,脂蛋白a、APO-B、 HDL-C进入多因素分析,脂蛋白a的OR值为2.21、 APO-B的OR值为1.86、HDL-C的OR值为0.48。3、颅内动脉闭塞性脑梗死临床预后经多因素Cox回归分析,RR值点值提示；高龄、男性、合并糖尿病、梗死面积>80cm3、多发病灶、颅内动脉狭窄、发热是危险的预后因素。但是95%的置信区间都包含1,提示都没有统计学意义。可能与只收集21例终点为进展的患者有关。4、颅内动脉狭窄的好发部位图6显示：84例患者中77例(91.6%)为颈内动脉系统狭窄、7例(8.4%)为椎动脉系统狭窄。最多见为大脑中动脉狭窄33例(39.3%),其次为大脑前+大脑中动脉狭窄12(14.3%)例。结论：1、吸烟、糖尿病、高血脂、高血压、男性是颅内动脉狭窄的危险因素,其中吸烟是第一位的、最重要的危险因素。2、在血脂指标中,脂蛋白a、APO-B、HDL-C与颅内动脉狭窄相关,HDL-C是颅内动脉狭窄的保护性因素,而脂蛋白a、APO-B值越高,越易产生颅内动脉狭窄。3、合并的危险因素越多,颅内动脉狭窄程度越重。.4、颅内动脉狭窄最多出现在大脑中动脉,年龄与动脉狭窄的分布无关。目的：颅内动脉粥样硬化性狭窄是全球缺血性卒中最常见的原因,我们应对颅内动脉狭窄性脑梗死的影像学资料的特点及发病机制有完善、系统的认识,本课题拟利用磁共振的弥散成像序列(DWI),对颅内动脉狭窄性脑梗死在DWI上的病灶特点进行细致、深入的分析。并结合TCD加栓子监测及心电图结果,对颅内动脉狭窄所导致的急性脑梗死作发病机制上的探讨。材料和方法：发病一周内的急性脑梗死患者84例,其诊断均符合全国第四届脑血管病学术会议修订的诊断标准,且已经MRA证实存在颅内动脉狭窄或闭塞,其中77例为前循环动脉闭塞,7例为后循环动脉闭塞。利用MRI的DWI成像分析患者的梗死特点,利用TCD栓子监测功能结合血流灌注异常探讨各种梗死类型的可能发病机制。结果：1颈内动脉系统77例患者中：根据DWI上的表现,梗死特点可按如下归类：1)完全性梗死9例(10.4%)；2)皮层梗死11例(14.3%)：其中皮层多发梗死8例(10.4%)、皮层大的单发梗死3例(3.9%)；3)半卵园中心区梗死11例(14.3%)：单发梗死2例(62.6%)、多发髓质区梗死9例(11.7%)：4)皮层、半卵园中心都累及的多发性梗死18例(23.4%)；5)深部小梗死10例(13.0%)；6)分水岭梗死18例(23.4%)：前后分水岭1例(1.3%)、内分水岭梗死17例(22.1%)。2椎动脉系统7例患者中：根据DWI上的表现,梗死特点可按如下归类：1)深部单发梗死2例(28.6%)；2)皮层单发梗死2例(28.6%)；3)多发脑梗死3例(43.9%)。3多发脑梗死58例,栓子阳性21例,阳性率36.2%；单发脑梗死26例,栓子阳性2例,阳性率7.7%。二者具有明显差异(P<0.05)458例多发性脑梗死,18例心电图显示窦性心动过缓(31.0%),26例单发性脑梗死,只有3例心电图显示窦性心动过缓(11.5%),二者具有显著性差异(P<0.05)。结论：1梗死特点颅内动脉狭窄所致的急性脑梗死在DWI上主要表现为多发性脑梗死；其中以皮层、半卵园中心都累及的多发性梗死及内分水岭梗死最多见。2发病机制颅内动脉狭窄发生脑梗死的发病机制包括：动脉-动脉栓塞、血流灌注不足、原位病变。多发性脑梗死的发病机制主要为动脉-动脉栓塞和血流灌注不足,其中,窦性心动过缓参与了低灌注导致脑梗死的过程；原位病损致血栓形成是基底节区单发梗死的主要发病机制。更多还原

【Abstract】 Purpose:To study the hazards of intracranial artery stenosis and discuss the parts liable to intracranial artery stenosis and clinical prognosis affecting factors of the cerebral infarction related to intracranial artery stenosis through the investigation and analysis of various factors including the blood pressure, blood sugar, blood fat, living habits, history of stroke and family medical history of the patients suffering from acute cerebral infarction.Materials and Methods:148cases of acute cerebral infarction are selected from the patients admitted to our hospital from October2008to June2012. All the patients satisfy the diagnostic criteria amended at the4th National Academic Conference on Cerebral Vascular Diseases and intracranial artery stenosis was confirmed in84cases of acute cerebral infarction by magnetic resonance angiography (MRA) while the result of MRA of the other64cases is normal. We targeted the patients suffering from acute cerebral infarction with intracranial artery stenosis as the object group to be studied, which include74male patients and10female patients aged between41and80(average age:61±9) while the patients suffering from acute cerebral infarction without intracranial artery stenosis are considered as contrast, including48male patients and16female patients aged between38and77(average age:56±4.8). The two groups of patients have no cardiogenic embolism, aorto-arteritis, concurrent infection, tumour and severe cardiopneumatic diseases. In the early morning of the second day when the patients were admitted to the hospital, the venous blood was drawn with an empty stomach to test the blood sugar, triglyceride (TG), cholesterol (TC), apolipoprotein A (ApoA), apolipoprotein B (ApoB), lipoprotein a, high density lipoprotein (HDL), low density lipoprotein (LDL) and we also monitored the blood pressure, improved the electrocardiographic examination, asked about the history of smoking, alcoholism, high blood pressure, history of stroke and family medical history. A comparison and analysis was made for the dangerous factors between the research group and comparison group. Intracerebral arteries to be studied include the intracranial internal carotid artery, intracranial vertebral artery, basilar artery, middle cerebral artery, anterior cerebral artery and posterior cerebral artery. Based on the analysis of the cerebral MRA of the research group, the distribution characteristics of intracranial single artery stenosis and intracranial multiple arteries stenosis are evident. The patients of the two groups were scored according to the National Institute of Health Stroke Scale (NIHSS) every morning of the first week and in the morning of the10th day to observe the short-term progress and prognosis. Those factors which may affect the prognosis are analyzed, including the infarct size, infarct type, arteriostenosis part, arteriostenosis range, body temperature, blood sugar and blood pressure.Results:Hazards of intracranial artery stenosisAfter the analysis of any single factor and based on the result of the analysis and professional knowledge, the multiple factor analyzing method is used to adjust the variables that may cause the hybridism. Among those variables like ag(?) gender, smoking, alcoholism, diabetes, hyperlipidemia, high blood pressure, coronary heart disease, family medical history, lipoprotein a(mg/L), APO-B, HDL-C, it is found out that gender, smoking, diabetes, hyperlipidemia, high blood pressure, lipoprotein a(mg/L), APO-B, HDL-C are of great significance to the statistics.Relation between intracranial artery stenosis and blood fatAccording to the chi-square test (x2=4.24,P<0.05), the proportion of hyperlipidemia in the two groups of patients suffering from hyperlipidemia is also significant to the statistics. The proportion of hyperlipidemia in the group with intracranial artery stenosis is larger than that of the group with no intracranial artery stenosis. The risk of intracranial artery stenosis for the patients suffering from cerebral infarction is2.05times of that of patients without hyperlipidemia. The index of blood fat such as lipoprotein a (mg/L), APO-B, HDL-C entry are all included in the multiple factors analysis, OR value of lipoprotein a is2.21, OR value of APO-B is1.86and OR value of HDL-C is0.48.Clinical prognosis of cerebral arterial occlusive cerebral infarctionAccording to Cox regression analysis of multiple factors, RR value suggests that older age, male, concurrent diabetes, infarct size>80cm3, multiple focus, stenosis and fever are prognosis factors; however,95%of the confidence interval include1, the suggestion has no significance to the statistics. Perhaps it is because only21cases were selected.Vulnerable parts of intracranial artery stenosisAccording to Diagram6, among the84cases, patients of77cases (91.6%) suffer from diseases of internal carotid system while7cases (8.4%) are about the vertebral artery. The middle cerebral artery stenosis accounts for the largest part (39.3%with33cases) and anterior cerebral artery plus middle cerebral artery stenosis comes after that (14.3%with12cases).Conclusion:Smoking, diabetes, hyperlipidemia and high blood pressure are especially dangerous factors of intracranial artery stenosis and smoking is the first and most important dangerous factor.Among the index of blood fat, lipoprotein a (mg/L), APO-B, HDL-C are related to intracranial artery stenosis; HDL-C is the protective factor for intracranial artery stenosis; the larger value of lipoprotein a (mg/L) and APO-B will cause the intracranial artery stenosis more easily.The more dangerous factors are combined; the intracranial artery stenosis will be caused more easily.The intracranial artery stenosis exists in the cerebral artery in most cases, irrelevant to the distribution of age and stenosis. Purpose:Intracranial atherosclerotic stenosis (ICAS) is the most common cause of ischemic stroke in the world. We should have a better and comprehensive understanding of the characteristics and pathogenesis of iconography data of intracranial artery stenosis related cerebral infarction. In this essay, the diffusion weighted imaging (DWI) of magnetic resonance is utilized to analyze the characteristics of the focus of intracranial artery stenosis related cerebral infarction as suggested on DWI and explore the pathogenesis of acute cerebral infarction caused by the intracranial artery stenosis based on TCD emboli-monitoring and electrocardiogram result.Materials and Methods:84cases of acute cerebral infarction are selected who were attacked by the disease in less than one week and the diagnosis of these patients all satisfy the diagnostic criteria amended at the4th National Academic Conference on Cerebral Vascular Diseases. Magnetic resonance angiography (MRA) confirmed that intracranial artery stenosis or occlusion exists, among which,77cases are anterior circulation arterial occlusion while7cases are posterior circulation arterial occlusion. MRI and DWI images are used to analyze the characteristics of the infarct of the patients and TCD emboli-monitoring functions and abnormal hemoperfusion helps to explore the probable pathogenesis of all kinds of infarcts.Results:Among the77patients suffering from diseases of internal carotid artery:According to the result of DWI, the characteristics of infarcts can be classified as follows,1)9cases of complete infarction (10.4%);2)11cases of cortical infarction (14.3%) including8cases of multiple cortical infarction (10.4%) and3cases of large single cortical infarction (3.9%);3)11cases of semiovale centrum zone infarction (14.3%):2case of single infarction (62.6%),9cases of multiple infarction in medullary substance (11.7%);4)18cases of multiple infarction involved in cotical and semiovale centrum zones (23.4%);5)10cases of deep and small infarction (13.0%);6)18cases of cerebral watershed infarction (23.4%) including1case of front and rear watershed (1.3%),17cases of inner watershed infarction (22.1%).Among the7patients suffering from diseases of vertebral artery, According to the lesions on DWI, the infarction patterns are categorized as1)2cases of deep single infarction (28.6%);2)2cases of single cotical infarction (28.6%);3)3cases of multiple cerebral infarction (43.9%);58cases of multiple cerebral infarction, positive features are found in21cases and the positive rate is36.2%;26cases of single cerebral infarction, positive features are found in2cases and positive rate is7.7%. There are big differences between the two situations (P<0.05).There are58cases of multiple cerebral infarction, among which, the electroc-ardiogram suggests sinus bradycardia in18cases (31.0%) while among the26cases of single cerebral infarction, the electrocardiogram suggests sinus bradycardia in only3cases (11.5%). The difference is quite significant.(P<0.05)Conclusion:1. Characteristics of infraction:When performing DWI, the acute cerebral infarction caused by intracranial artery stenosis is multiple cerebral infarction in most of cases. The multiple infarction involved in cotical and semiovale centrum zones as well as the inner watershed infarction are most common. 2. Pathogenesis:The pathogenesis of cerebral infarction due to intracranial artery stenosis includes:artery-artery occlusion, inadequate hemoperfusion, pathological changes in home position. The pathogenesis of multiple cerebral infarction includes: artery-artery occlusion and inadequate hemoperfusion. Moreover, the sinus bradycardia plays a role in the process leading to cerebral infarction caused by low hemoperfusion while the thrombogenesis caused by in-situ lesion is the main pathogenesis of single infarction in basal ganglia zone.更多还原