The Clinical Features, Radiological Findings And Follow-up Study Of Cerebral Microbleeds In Patients With Symptomatic Cerebral Artery Stenosis

Cerebral microbleeds (CMBs) are hemosiderin deposits in macrophages related to bleeding-prone microangiopathy, which appear as small (generally 2-10 mm in diameter) round or oval hypointensities on gradient-echoT2*-weighted imaging (GRE-T2*WI) or susceptibility weighted imaging (SWI). However, the cause and clinical significance of CMBs remains uncertain.The risk factors of CMBs were varied in different studies. Previous studies had shown that age, hypertension, diabetes, smoking, low serum cholesterol, anticoagulation and antiplatelet drug use, leukoaraiosis (LA), lacunar infarction (LI) were a risk factor for CMBs. It is reported that CMBs often located in the cortical, subcortical white matter, thalamus, basal ganglia, brain stem, and cerebellum. CMBs are associated with the occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis. CMBs are associated with an increased risk of recurrent stroke after ischemic stroke or transient ischemic attack. Patients with symptomatic cerebral artery stenosis have a risk of recurrence and poor prognosis. It is important to investigate the clinical features for CMBs in patients with symptomatic cerebral artery stenosis. However, there was a lack of studies on clinical features of CMBs in patients with symptomatic cerebral artery stenosis in Chinese population. In this study, we investigate the prevalence, distribution, risk factors for CMBs in patients with symptomatic cerebral artery stenosis, providing a theoretical basis for the secondary prevention of patients with symptomatic cerebral artery stenosis.Hemorrhagic transformation (HT) is bleeding into an area of ischemic brain after stroke. SWI is different from traditional MRI imaging. Hemorrhage is more sensitively detected by SWI compared with traditional MRI imaging. SWI played an important role in early detection of HT in patients with ischemic stroke.Previous studies have found that HT may be closely related to massive cerebral infarction, cerebral embolism, hyperglycemia, low cholesterol levels, lower platelet count, poor collateral circulation, use of rt-PA and hyperdense middle cerebral artery on CT and so on. HT is common in patients with LAA. Symptomatic and asymptomatic HT was associated with poor clinical outcome in patients with ischemic stroke. CMBs may be a potential risk factor for hemorrhagic transformation after ischemic stroke. However, it has been questioned whether the presence of CMBs is a risk factor for HT. In this study, we use SWI to detect HT, and investigate the relationship beween HT and CMBs in patients with LAA, providing a theoretical basis for the secondary prevention of patients with LAA.CMBs showed dynamic temporal change. CMBs may develop rapidly after certain critical events, such as ischemic stroke, tPA infusion treatment and carotid artery stenting (CAS). CMBs represent the perivascular extravasation of blood resulting from advanced cerebral microangiopathy. However, it is reported that the count of CMBs could decrease in long-term follow-up GREs. However, the cause and clinical significance of newly developed CMBs remains uncertain. Previous studies had shown that blood pressure, baseline CMBs and small vessel diseases appear to act as risk factors while in contrast, a high level of LDL cholesterol may act as a protective factor against CMBs increase. CMBs may be associated with the use of antiplatelet. Patients who received endovascular stent-assisted angioplasty treatment should receive aspirin and clopidogrel in the prevent of stent thrombosis. As a imaging biomarkers of prone to bleeding, whether CMBs could increase the risk of cerebral hemorrhage, ischemic stroke and other vascular events in patients who received endovascular stent-assisted angioplasty treatment remained uncertain. In this follow-up MRI study, we observed temporal changes of CMBs in patients who received endovascular stent-assisted angioplasty treatment, and attempted to determine factors associated with the development of new CMBs shortly after endovascular stent-assisted angioplasty treatment. We also explore whether CMBs could increase the risk of cerebral hemorrhage, ischemic stroke and other vascular events in patients who received endovascular stent-assisted angioplasty treatment.Part I:Risk Factors for Cerebral Microbleeds in Patients with Symptomatic Cerebral Artery StenosisObjective:To investigate the potential risk factors for CMBs in patients with symptomatic cerebral artery stenosis.Methods:We retrospectively recruited 337 consecutive patients with symptomatic cerebral artery stenosis in our Hospital between August 2013 and February 2015. Vascular risk factors (age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking) and laboratory parameters (triglyceride, cholesterol, low-density hpoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, uric acid) were recorded during hospital stay, the CMBs was assessed with use of the microbleed anatomical rating scale (MARS), the LA was assessed with use of the age related white matter changes (ARWMC), the LI was also recoreded. The patients with risk factors were analyzed by the univariate and multivariate logistic regression analysis. A total of 337 patients were divided into non-CMBs group and CMBs group according to SWI. The patients were divided into strictly lobar microbleeds and deep microbleeds based on CMBs location. We performed univariate and multiple logistic regression in this study. Patients with CMBs were divided into 4 groups-0 (no CMBs),1,2 to 4, and≥5 lesions. Patients with LA were divided into 4 groups depending on ARWMC score-0 (no LA),1 to 4,5 to 7, and>7 lesions. Patients with LI were divided into 4 groups-0 (no LI),1-2,3 to 4, and≥5 lesions. Pearson correlation was used to analyze the corelation between the severity of CMBs and the extent of LA and LI.Results:337 patients with symptomatic cerebral artery stenosis (240 men; mean age 64.4±10.5 years) were studied, of whom 117 (34.7%) had CMBs. In a multivariate analysis, CMBs was associated with hypertension (OR,3.494; 95%CI 1.835-6.654; P<0.001),previous ischemic stroke (OR,2.219; 95%CI 1.197-4.114; P=0.011),LA (OR,1.100; 95%CI 1.037-1.168; P=0.002) and LI (OR,1.402; 95%CI 1.191-1.651; P<0.001). Deep microbleeds was associated with hypertension (OR,3.858; 95%CI 1.634-9.109; P=0.002), diabetes mellitus (OR,1.987; 95%CI 1.069-3.692; P=0.030), previous ischemic stroke (OR,2.283; 95%CI 1.154-4.516; P=0.018),LA(OR,1.135; 95%CI 1.064-1.212; P<0.001) and LI (OR,1.443; 95%CI 1.220-1.707; P<0.001). Strictly lobar microbleeds was associated with antiplatelet use (OR,2.083; 95%CI 1.058-4.103; P=0.034). There was a correlation between the number of microbleeds and the number of LI (P< 0.001) and the severity of LA (P< 0.001).Conclusion:In conclusion, our results suggest that CMBs was associated with hypertension, previous ischemic stroke, LA and LI. CMBs in deep locations are etiologically different from those that are strictly lobar in location. Deep microbleeds was associated with hypertension, diabetes mellitus, previous ischemic stroke, LA and LI. Strictly lobar microbleeds was associated with antiplatelet use. CMBs was related to LA and LI, both markers of cerebral small vessel disease. Our results suggest that all three may have a shared pathogenesis such as advanced microangiopathy.Part Ⅱ:Analysis of Relationship beween Hemorrhagic Transformation and Cerebral Microbleeds in Patients with Large Artery AtherosclerosisObjective:To investigate the relationship beween HT and CMBs in patients with large artery atherosclerosis (LAA).Methods:We retrospectively recruited 286 consecutive patients with LAA in our Hospital between August 2013 and February 2015. Vascular risk factors (age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking) and laboratory parameters (triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, uric acid) were recorded during hospital stay, the CMBs was assessed with use of the MARS, the LA was assessed with the use of the ARWMC, the number of LI and the site and size of acute infarction were also recoreded. All the 286 patients were divided into non-HT group and HT group according to SWI. We performed univariate and multiple logistic regression in this study.Results:The positive rates of HT was 21.0% with the diagnosis of SWI and 16.4% with the diagnosis of T1WI. HI-1 accounted for 30.0%, and HI-2, PH-1, PH-2 for 56.7%,8.3% and 5.0%, respectively. Univariate analyses revealed a significant association between HT and INR (P=0.031), the size of infarcts (P<0.001). After logistic regression, only the size of infarcts (OR,3.352; 95%CI 1.859-6.045; P<0.001) remained independently associated with the presence of HT.Conclusion:The positive rates of HT evaluated by SWI was higher than T1WI in patients with LAA can be sensitively. HT was related to the size of infarcts and had no relationship with CMBs.Part Ⅲ:Progression of Cerebral Microbleeds in Patients with Endovascular Stent-Assisted Angioplasty of Intracranial and Extracranial ArteriesObjective:To investigate changes of CMBs and potential risk factors associated with the changes in patients with endovascular stent-assisted angioplasty of intracranial and extracranial arteries. We also expored the impact of CMBs on occurrence of cerebral hemorrhage, ischemic stroke and other vascular events in patients who received endovascular stent-assisted angioplasty treatment.Methods:We prospectively enrolled 80 consecutive patients with endovascular stent-assisted angioplasty of intracranial and extracranial arteries, and followed-up their brain MRIs with an interval 3 month in our Hospital between August 2013 and November 2014.Vascular risk factors (age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking) and laboratory parameters (triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, uric acid) were recorded during hospital stay. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of CMBs.Results:Six patients were lost to follow-up and a patient died of myocardial infarction during follow-up. A total of 73 patients completed the follow-up examinations (mean,109 days). During follow-up, one patient had an ischemic stroke, two patients had a transient ischemic attack. We found new CMBs in 7 patients (9.6%) on follow-up MRI. Patients had new CMBs were significantly higher LI (P=0.034) and elevated systolic blood pressure (P<0.001). After logistic regression, only the elevated systolic blood pressure (OR,1.070; 95%CI 1.012-1.130; P=0.017) remained independently associated with the development of new CMBs.Conclusion:Elevated systolic blood pressure was associated with the development of new CMBs, it remains to be uncertain whether effective blood pressure control can slow down the progression of CMBs.