【作者】 王娜；

【导师】 陈晓虹；

【作者基本信息】 大连医科大学 ， 神经病学（专业学位）， 2020， 硕士

【摘要】 目的:脑微出血(cerebral microbleeds,CMBs)是常见的脑小血管病之一,与未来发生缺血性和出血性卒中相关。非瓣膜性房颤(non-valvular atrial fibrillation,NVAF)是脑卒中发生的重要危险因素,是心源性卒中重要的病因之一。NVAF患者需要长期口服抗凝药来预防栓塞事件,但同时也增加了颅内出血(intracranial hemorrhage,ICH)发生的风险。CMBs作为ICH的先兆,目前有研究证实在NVAF患者中CMBs的检出率更高,NVAF的存在与CMBs的发生具有相关性。本研究以伴NVAF的缺血性卒中(ischemic stroke,IS)患者为研究对象,回顾性收集临床资料包括既往史、脑血管危险因素、实验室检查,经头部磁敏感加权成像(susceptibility weighted imaging,SWI)对CMBs进行诊断,探讨伴NVAF的IS患者CMBs的危险因素。方法:本研究收集在2016年4月-2019年9月于辽宁省人民医院神经内科住院,并完成头核磁共振常规序列和SWI序列检查的伴NVAF的IS患者的临床资料。排除标准:动脉粥样硬化性卒中等其他非心源性卒中者、其他严重疾病或影响观察指标的各种因素、其他原因引起的SWI低信号的患者。将纳入患者按SWI诊断分为CMBs(+)组和CMBs(-)组。收集的临床资料主要有性别、年龄;血管性危险因素:高血压病、糖尿病、吸烟史、饮酒史、既往卒中史(缺血性和出血性)、既往服用抗栓药物史、抗凝药物史及他汀类药物史;抗凝评分(CHA2DS2-VASc)和出血风险评分(HAS-BLEDS);急性IS患者的NIHSS评分、既往IS患者的MRS评分;相关实验室血液化验指标:血常规、凝血功能、脑利钠肽(brain natriuretic peptide,BNP)等;心电图及心脏超声等。CMBs的诊断:在SWI序列上病灶直径≤10 mm(一般为2-5mm)的类圆形、界限清楚、均质的、低信号区域,病灶为脑实质围绕;除外其他原因引起的SWI低信号。依据SWI序列显示的部位和数量对CMBs进行进一步分组。采用SPSS21.0软件进行统计分析,用多因素Logistic回归分析探讨伴NVAF的IS患者CMBs发生的独立危险因素。结果:连续收集2016年4月-2019年9月于辽宁省人民医院医院神经内科住院的伴NVAF的IS患者的临床资料,结果共117例符合条件纳入本研究,患者的平均年龄为76.22±8.12岁,男性67例(57.3%),CMB(+)组69例(59.0%)。CMBs根据部位可分为脑叶21例(17.9%)、深部或幕下18例(15.4%)和混合30例(25.6%);根据严重程度(CMBs数量),CMBs组又分为轻度(1-2个CMBs)25例(21.4%)、中度(3-10个CMBs)28例(23.9%)和重度(>10个CMBs)16例(13.7%)。基线资料各组间比较::在CMBs(+)组和CMBs(-)组间,卒中史、高血压、他汀类药物服用史的构成比及纤维蛋白原(fibrinoge,Fg)水平和BNP水平升高患者的比例,前者高于后者,其差异具有统计学意义(P<0.05)。不同部位的CMBs组间,其出血性卒中史的构成比由高至低依次为:混合>深部或幕下>脑叶>无CMBs;高血压病史的构成比由高至低依次为:深部或幕下>脑叶>混合>无CMBs,二者在不同CMBs部位组间都有显著差异(P<0.05);在不同严重程度CMBs组间,其卒中史、高血压、BNP水平存在显著差异(P<0.05)(出血性卒中史构成比由高至低依次为:重>中>轻>无CMBs;高血压史构成比由高至低依次为:中>轻>重>无CMBs;高BNP水平构成比由高至低依次为:重>轻>中>无CMBs)。多因素logistic回归分析:以单因素分析有统计学意义的(P<0.05)的变量为自变量,分别以CMBs、CMBs分布部位和严重程度为因变量。结果显示高血压和BNP与NVAF的IS患者CMBs的发生独立相关(P=0.007,P=0.047)。高血压、卒中史、他汀药物史与CMBs的部位独立相关:高血压与NVAF的IS患者深部或幕下CMBs的发生独立相关(P=0.049);出血性卒中史除与NVAF的IS患者脑叶CMBs发生独立相关(P<0.05),还与深部或幕下CMBs发生独立相关(P<0.05);他汀类药物使用史与NVAF的IS患者混合部位CMBs的发生独立相关(P=0.036)。在不同严重程度CMBs的组间,高血压、出血性卒中史、BNP的异常升高的比例不同,其差异有统计学意义(P<0.05),这些因素的单独存在都会增加CMBs的负荷。结论:伴NVAF的IS患者有半数以上的患者较高的CMBs的发生率,高血压与CMBs的发生相关,主要影响深部或幕下的CMBs,并且会增加CMBs的负荷;他汀类药物使用史主要与混合部位CMBs的发生独立相关;BNP与CMBs的发生相关,并且与CMBs的严重程度成正相关,但在不同部位的CMBs中无显著差异。更多还原

【Abstract】 Objective: Cerebral microbleeds(CMBs)is one of the common small cerebral vascular diseases,which is associated with ischemic and hemorrhagic strokes.Non-valvular atrial fibrillation(NVAF)is an important risk factor of stroke,especially cardiogenic stroke.NVAF patients usually need long-term oral anticoagulant treatment to prevent embolization,and such treatment increases the incidence of intracranial hemorrhage(ICH).CMBs are the precursor of ICH,and many studies have confirmed the correlation between NVAF and CMBs.The detection rate of CMBs is higher in patients with NVAF,so it is necessary to find the risk factors related to the occurrence of CMBs in patients with NVAF.In this study,the clinical data includig previous history,cerebrovascular risk factors,and laboratory examinations of the enrolled ischemic stroke(IS)patients with NVAF was collected retrospectively.The susceptibility weighted imaging(SWI)was used to diagnose CMBs.We explored the risk factors of CMBs in IS patients with NVAF.Methods: We collected clinical data of IS patients with NVAF who were admitted to the neurology department of People’s Hospital of Liaoning Province from April 2016 to September 2019,which completed routine brain magnetic resonance sequence and SWI tests.Patients with non-cardiogenic stroke,other serious diseases or factors that affect the outcome were excluded.The enrolled patients were divided into CMBs(+)group and CMBs(-)group based on SWI results,and the clinical data collected mainly including gender and age.Vascular risk factors and previous history of drugs;anticoagulation score(CHA2DS2-VASc)and bleeding risk score(HAS-BLEDS);NIHSS of acute IS patients and MRS of previous IS patients;related blood test indexes,such as blood routine test,coagulation function,brain natriuretic peptide(BNP)etc;cardiac ultrasound,etc.CMBs was diagnosed as lesions on the SWI sequence with a diameter of no more than 10 mm,generally round,well-bounded,homogeneous andlow-signal region of 2-5mm,with lesions surrounding the brain parenchyma,except for SWI low-signal caused by other reasons.CMBs were devided into different groups according to the location and numbers in SWI imagings.SPSS21.0 software was used for statistical analysis.Analyse the independent risk factors of CMBs in IS patients with NVAF by using multivariate Logistic regression analysis.Results: In this study,117 NVAF patients were enrolled.The average age of the patients was 76.22±8.12 years old,with 67 males(57.3%)and 69 patients(59.0%)in the CMB(+)group.According to the location of CMBs,21 cases(17.9%)were in cerebral lobe,18 cases(15.4%)in deep or subtensive zone,and 30 cases(25.6%)in mixed locations.According to the severity(numbers of CMBs),the CMBs(+)group are subdivided into 25 cases(21.4%)of mild group(1-2 CMBs),28 cases(23.9%)of moderate group(3-10 CMBs)and 16 cases(13.7%)of severegroup(>10 CMBs).Variables with statistical significance in univariate analysis(P< 0.05)were used as independent variables,and CMBs,CMBs distribution location and severity were used as dependent variables in multivariate logistic regression analysis.The result shows that hypertension and BNP were independently correlated with CMBs in NVAF IS patients(P=0.007,P=0.047).The history of hypertension,stroke and statins were independently correlated with the location of CMBs in IS patients with NVAF: hypertension was independently correlated with the occurrence of deep or subtentorial CMBs in IS patients with NVAF(P=0.049);the history of hemorrhagic stroke was not only independently correlated with the occurrence of cerebral lobe CMBs in IS patients with NVAF(P<0.05),but also independently correlated with the occurrence of deep or subtentorial CMBs(P<0.05);the statin use history was independently associated with the occurrence of mixed location CMBs in IS patients with NVAF(P=0.036).In different severity CMBs groups of IS patientswith NVAF,the difference of the proportion of hypertension,hemorrhagic stroke history and BNP level was statistically significant(P<0.05).The presence of these factors alone would increase the load of CMBs.Conclusions: Hypertension are related to the occurrence of CMBs in IS patientswith NVAF,it mainly affects the deep CMBs or subtentorial CMBs,and increases the load of CMBs.Statin use history was independently related to the occurrence of CMBs in the mixed site of NVAF patients.BNP was correlated with the occurrence of CMBs in patients with NVAF,and was positively correlated with CMBs severity,but there was no significant difference in CMBs at different location.更多还原