1.Prognosis And Influencing Factors Of Asymptomatic And Symptomatic Arteriosclerotic Middle Cerebral Artery Stenosis 2.Relationship Between Inflammatory Markers And Arteriosclerotic Intracranial Artery Stenosis And Stable Cerebral Infarction

Part 1 Prognosis and influencing factors of asymptomatic and symptomatic arteriosclerotic middle cerebral artery stenosisBackgroundIntracranial arteriosclerotic stenosis is a critical cause of ischemic stroke in Chinese population.It has been reported that patients with symptomatic intraeranial arterial stenosis are of a high rate of stroke recurrence.However,prognosis and influencing factors of asymptomatic middle cerebral artery(MCA) stenosis have rarely been reported up to date.ObjectiveThe purpose of this study was to determine the incidence rate,recurrence rate and the influencing factors of asymptomatic and symptomatic MCA stenosis.MethodsFrom June 2003 to June 2006,we consecutively and prospectively recruited patients of neurological clinic of PUMCH(77 men,123 women;mean age 63.19 years),who had MCA stenosis confirmed by transcranial Doppler(TCD) of two times or by TCD and MRA at the same time.At baseline stage,demographic data and stroke risk factors were taken.All patients underwent carotid ultrasonography,those of whom with ipsilateral carotid stenosis≥50%were excluded.Mean follow-up is of 38.3±9.9 months.Incidence rate of stroke and influencing factors were analyzed.From September 2004 to January 2007,hospitalized patients of PUMCH neurological department,with cerebral infarct or transcient ischemic infarction(TIA) due to MCA stenosis,were prospectively registered.Demographic data and stroke risk factors were taken at baseline stage.Carotid ultrasonography and ultrasound cardiography were done totally.Patients with ipsilateral carotid stenosis≥50%or with suspected cardioembolism were excluded.According to MRI/DWI,infarct in the territory of MCA was classified as single-lesion and multiple-lesion.Mean follow-up is of 26.1±11.3 months.Cumulative rate of stroke recurrence and annual rate of stroke recurrence were calculated.Influencing factors of stroke recurrence were analyzed through multi-factor Logistic regression.Results200 cases with asymptomatic MCA stenosis were registered.13 patients were lost(6.5%).7 of them developed ischemic stroke,3 of which were in the territory of the narrow MCA,with a cumulative stroke rate of 3.8%.Single factor analysis showed that diabetes mellitus(X~2=9.168,p=0.002) and carotid plaque(X~2= 4.403,p=0.036) were related with stroke.107 cases with symptomatic MCA stenosis,90 cases of cerebral infarction and 17cases of TIA,were included.88 patients of them underwent MRI/DWI,which demonstrated 44 cases had single- lesion and the other 40 cases had multiple-lesion. During follow-up,11 patients were lost.Twenty-three cerebral ischemic events occurred,the cumulative rate of stroke recurrence was 24.7%,annual rate of recurrence was 14%.Multi-factor logistic regression suggested whether anti-platelet drug was regularly taken or not was an independent influencing factor of stroke recurrence(OR=0.154,95%CI 0.039 to 0.618,p=0.008).Patients with multiple-lesion on MRI had much more tendency of stroke recurrence(OR=2.592,95%CI 0.681 to 9.861,p=0.162).Conclusions1,Patients with asymptomatic MCA stenosis had a relative good prognosis,their stroke might develop beyond the territory of the narrow MCA and was related with DM and carotid plaque.Intensive diabetic control and aggressive anti- arteriosclerotic treatment were suggested for them.2,Patients with symptomatic MCA stenosis were at a high risk of stroke recurrence,which was related with whether regularly taking anti-platelet drug or not. Our study showed the significance of the effect of anti-platelet drug for ischemic stroke patients,more education for these patients was needed.3,Patients with multi-lesion on MRI were at high risk of stroke recurrence,which suggested that those with arterio-to-arterial embolism or unstable plaque should receive intensive anti-platelet and anti- arteriosclerotic treatment. Part 2 Relationship between inflammatory markers and arteriosclerotic intracranial artery stenosis and stable cerebral infarctionBackgroundArteriosclerosis is one of the most important pathogenetic factors for cardio-cerebral vascular disorders.It has been demonstrated that inflammatory reaction plays a significant role throughout the whole progress of arteriosclerosis. High-sensitive CRP(hs-CRP),soluble CD40L(sCD40L),matrix metalloproteinases(MMPs)-2 and MMPs-9 are expressed in high levels at the acute stage of cardio-cerebral vascular disorders,which can predict the event in different degree.Their levels and differences between stable cerebral infarct and asymptomatic intracranial artery stenosis,however,haven't been reported.ObjectivePlasma levels of sCD40L,MMPs-2,MMPs-9 and serum level of hs-CRP were detected to investigate their distributions between patients with stable cerebral infarction and those with asymptomatic intracranial artery stenosis and to exploring their clinical significance.MethodsThe study was designed as a case-control study.Subjects were categorized as asymptomatic intracranial artery stenosis(n=46),recurrent ischemic stroke(n=39), stable ischemic stroke(n=37) and healthy control group(n=74).Demographic data, risk factors for stroke,medication and results about the examinations of the cranio-cervical arteries were taken.The plasma levels of sCD40L,MMPs-2,MMPs-9 and the serum level of hs-CRP were detected with the antibody sandwich enzyme-linked immunoadsorbent assay kit of fasting venous blood.ResultsBecause the centrifugation of the control group was apparently delayed,the plasma level of sCD40L of it was obviously higher than those of all the cases and that of the range of the kit.Considering the bias of the concentration of the control group, the result was excluded.1.The mean level of the serum hs-CRP of the group with recurrent ischemic stroke was the highest,followed by that of the group with the stable ischemic stroke and asymptomatic intracranial artery stenosis(p＜0.001).2.The mean level of the plasma sCD40L of the group with stable ischemic stroke was the highest,secondly for that of the group with asymptomatic intracranial artery stenosis and the group with recurrent ischemic stroke(p＜0.001).3.The highest level of the plasma MMPs-2 was in the group with asymptomatic intracranial artery stenosis,then that of the group with stable ischemic stroke was higher than in group with recurrent ischemic stroke(p＜0.001).4.The level of the MMPs-9 was in sequence of recurrent ischemic stroke group＞asymptomatic intracranial artery stenosis group＞stable ischemic stroke group, but no statistical significance was found among groups(P=0.947).5.The spearman analysis for the relationship between the inflammatory factors showed that the concentration of MMPs-9 was positively associated with that of hs-CRP(r=0.299,p=0.001) and that there was a slightly weak relationship between the level of sCD40L and that of MMPs-9(r=0.179,p=0.049).6.Significant differences of the level of MMPs-2 between smokers and nonsmokers was observed(p=0.001),this was also true between patients with and without family history of stroke(p=0.009).Conversely,no differences of the levels of MMPs-9,sCD40L and hs-CRP among groups were shown.Conclusion:1.The measurement of the plasma sCD40L was strongly affected by the time that blood was stored in vitro before centrifuge.Strict controlling the conditions of the experiment was suggested.2.The hs-CRP,as an inflammatory marker of the systemic inflammation,stilly maintained a high level in convalescence phase of stroke.The level of the hs-CRP in patients with the tendency of thrombotic events was the highest,which in patients with vascular stenosis and no thrombotic events was the lowest. Measurement of hs-CRP might be of clinical value and promising prospect in predicting recurrence of cerebral infarction.3.Elevation of the level of sCD40L in group with stable infarction was not shown. Our study demonstrated that sCD40L had a more strong relationship with atherosclerosis and intracranial artery stenosis.4.No significant difference of the MMPs-9 level was found between patients with stable stroke and that with asymptomatic intracranial artery stenosis,but a tendency as the following was observed:the MMPs-9 level of the recurrent ischemic stroke group＞asymptomatic intracranial artery stenosis group＞stable ischemic stroke group.These results implicated that the difference about the level of the MMPs-9 among the groups might have the same relationship as that of the hs-CRP,but the relationship was so inferior to that of the hs-CRP as unable to show by small number sample study.Further study was required.5.The relationship among hs-CRP,MMPs-9 and sCD40L suggested that combined detection of multi-inflammatory marker might predict the arthrosclerosis and the relative events more efficiently and accurately.