Study On The Pathogenesis,Correlative Factors Of Cerebral Microbleed And Its Relationship With Retinal Vessels

Cerebral microbleed(CMB)is a common subtype of cerebral small vessel disease(CSVD),which is not only an important factor leading to cognitive impairment and progressive brain function damage,but also a factor that should be considered of when the doctor decisided to use antiplatelet and anticoagulant drugs to prevent or treat cerebrovascular diseases.CSVD is one of the hot spots of cerebrovascular disease research in recent years.How to prevent and identify it earlier has always been a huge clinical challenge.We already knew that CMB was caused by small vascular lesions in the brain,but how about its incidence?What risk factors are involved in it?Retinal blood vessels have the same embryological origin as the brain.They are nerve endings extending outward from the brain and can reflect the situation of cerebrovascular to some extent.Optical coherence tomography angiography(OCTA)has been widely used in recent years to investigate the retinal structure and microvascular circulation.Can it provide a reference basis for CMB evaluation of vascular information other than MRI morphology?Therefore,this study aims to investigate the incidence of CMB and its related factors in hospitalized patients,and to analyze the correlation between CMB and retinal microvascular structure and perfusion by OCTA.Research Methods:Part Ⅰ:The study of the incidence and related factors of CMB1.All patients admitted to the Department of Neurology of the First Affiliated Hospital of Guangdong Pharmaceutical University from January 2019 to March 2021 who were over 40 years old and met the inclusion criteria were admitted.All patients need to undertook 3.0T cerebral magnetic resonance(MRI)routine sequence and magnetic sensitivity weighted imaging(SWI)sequence detection.2.Patients with CMB found on the SWI sequence were considered as the CMB group,and it was divided into three groups from grade 1 to 3 according to the number of CMB.Patients without CMB were enrolled in the control group.General clinical data,blood biochemical results and the degree of other types of CSVD,including white matter heperintensity(WMH),recent small subcortical infarct(RSSI),lacune and enlarged perivascular space(EPVS)in both groups were collected.SPSS23.0 software was used for statistical analysis to explore the related factors of CMB and its relationship with other types of CS VD,Part Ⅱ:Studies of the relationship between CMB and retinal.1.OCT A examination was undertook for the patients in the CMB group and the control group who met the inclusion criteria and could cooperate with ophthalmic examination.They were divided into the CMB group and the control group.All enrolled patients were detected by the same skilled ophthalmologist using the Optovoue OCTA apparatus.2.Retinal blood flow density,retinal thickness,fovea avascula area(FAZ),PERIM,non-circular index(AI),fovea density(FD)and other indexes were analyzed in the two groups and the different severity grades of CMB,and to discuss the relationship of these indexes and the incidence or the severity of CMB.Results:Part Ⅰ:The study of the incidence and related factors of cerebral microbleed.1.A total of 549 patients were enrolled.There were 163 patients who had CMB(26.7%),the mean age was 69.96±12.09 years old,the ratio of gender was 98:65(male/female).In the control group,there were 386 patients,with an average age of 67.16±13.63 years old,including 209 males and 177 females.The average age of CMB group was significantly higher than the control group(P<0.05),meanwhile,there was no significant difference in sex ratio between them.2.The differences were significant in the history of cerebral infarction,cerebral hemorrhage and hypertension between CMB group and control group(P<0.05).Comparing these two groups:systolic blood pressure(SBP),the total load of CSVD,the midbrain EPVS,basal ganglia EPVS,centrum semiovale EPVS,next to the ventricle WMH,deep WMH,RSSI,lacuna(LI),LDL,sdLDL,TC,Hcy,Cr,BUN,UA,FT3,CK-MB had statistically significant differences(P<0.05),in which LDL,TC and sdLDL were negatively correlated with the occurrence of the CMB,the rest of them were positive correlation with it.Midbrain EPVS,deep WMH,RSSI,Hcy,FT3,among with the history of cerebral hemorrhage and hypertension,were the independent risk factors of CMB(P<0.05,OR value>1).3.The results shown that through the comparison of three levels of CMB,we found that CSVD total load rating,the midbrain EPVS and basal ganglia region EPVS,DWMH,cerebral hemorrhage history,PVWMH,Lacune and PTA,APTT,LDL,TC and sdLDL were correlated between the different grades of CMB(P<0.05);Among them,PTA,LDL,TC and sdLDL were negatively correlated with CMB,while the others were positively correlated.There were significant differences in TC between grade 1 and grade 2 and between grade 1 and grade 3 in the CMB group(P<0.05),and showed a decreasing trend with the increase of the severity of CMB.The difference of TG between CMB grade 1 and grade 2 was statistically significant(P<0.05).Part Ⅱ:Study on the relationship between CMB and retinal1.A total of 52 patients were included,including 63 eyes of 32 patients in the CMB group and 39 eyes of 20 patients in the control group.Through the analysis of the results of OCTA examination between these two groups,it was found that there were no significant differences in inner retinal thickness,full retinal thickness,superficial blood flow density,deep blood flow density,FAZ area,circumference and FD between the two groups.There were significant differences in AI between the two groups,and the AI of CMB group was lower than the control group.2.It was found that there was no significant difference in the thickness of the inner retina and the full retina among different grades of CMB group.The superficial blood flow density in Perifovea,T2,N2 and S2 regions was statistically different among different grading groups.Pair comparison shows differences in Perifovea and S2 regions between grade 1 and 2,1 and 3,and in T2 regions between grade 1 and 2,N2 regions between grade 1 and 3(P<0.05).With the increase of grade of CMB,the superficial blood flow density showed a decreasing trend.3.Comparing the deep blood flow density in different grades of CMB,we found significant differences in Parafovea,S1,N1 and S2 regions.Pair comparison showed that deep blood flow density in Parafovea,S1,N1 and S2 had statistical difference between grade 1 and 3(P<0.05),and the deep blood flow density showed a decline trend with the increase of grade.Research Conclusions:1.The detection rate of CMB accounted for 26.7%of the included patients,and the incidence increased with the increase of age,suggesting that CMB is a common age-related disease.2.The incidence of CMB was correlated with previous history of cerebrovascular diseases,common risk factors of cerebrovascular diseases and non-cerebrovascular risk factors such as Cr,BUN,CK-MB and FT3,among which LDL and TC were negatively correlated.3.The incidence of CMB is closely related to the total load of CSVD,EPVS,WMH,RSSI and other types of CSVD,which often exist in combination.4.The OCTA study found significant differences in AI between the CMB group and the control group.With the increase of the severity of CMB,the blood flow density in surpeificial and deep layers declined significantly in some areas.It suggested that OCTA is worth exploring as an indirect method to evaluate the structure and function of the small vessels in CMB and other CSVD.