Cerebral Circulation Time Is A Potential Predictor Of Disabling Ischemic Cerebrovascular Events In Patients With Non-disabling Middle Cerebral Artery Stenosis

Objective:Patients with nondisabling middle cerebral artery(MCA)stenosis(ND-MCAS)are at risk for disabling ischemic cerebrovascular events(DICE)despite aggressive medical therapy.Cerebral circulation time(CCT)is an important measurement of cerebral vascular reserve.In this study,we aimed to verify whether cerebral circulation time(CCT)was a potential predictor of DICE in patients with ND-MCAS.Methods:From January 2015 to January 2020,46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography(DSA)in this convenience sampling study.They were divided into the DICE(-)and DICE(+)groups based on the occurrence of DICE within 3 months after DSA.Their demographic characteristics,stroke risk factors,clinical symptoms,medications,relevant scale scores(National Institutes of National Institutes of Health Stroke Scale[NIHSS]and Modified Rankin Scale[mRS])and stenosis degree,CCT from the DSA were reviewed by two neurologists.During the angiography procedure,the CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein.The main research indicator of the present study was rCCT(relative CCT),which was calculated with the following formula:rCCT=the CCT of the stenotic side(sCCT)/the CCT of the healthy side(hCCT).All continuous variables were tested for normality and expressed as median(interquartile range).Categorical variables were expressed as numbers(%).The differences in demographic and clinical variables between the DICE(-)and DICE(+)groups were analyzed by Mann-Whitney U tests for continuous variables and Pearson’s χ2 test for categorical variables.Logistic regression analysis was performed to estimate the odds ratio(OR)for DICE with rCCT and other risk factors as independent variables.p<0.05 was considered statistically significant.Receiver operating characteristic(ROC)curve analysis of rCCT was performed to evaluate the predictive accuracy of DICE in the ND-MCAS patients.Results:The DICE appeared in 5 of the 46 patients within 3 months.The rCCT and age in the DICE(+)group were significant difference compared with those in the DICE(-)group(1.08[1.05,1.14]vs.1.30[1.22,1.54],p<0.001;54[47.5,61]vs.69[57.5,77],p=0.026).There was no significant difference in sCCT and Stenosis degree between the two groups(6.83[6.50,7.75]vs.7.67[6.50,10.67],p=0.258;70[30,80]vs.80[60,85],p=0.391).Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE(odds ratio=1.273,p=0.019)after adjustment for potential confounders(age,diabetes,antithrombotic use,and stenosis degree).ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE(+)group from the DICE(-)group among ND-MCAS patients(area under the curve=0.985,p<0.001),with an optimal cut-off point of 1.20(100%sensitivity,97.6%specificity).In contrast,the optimal cut-off point for SCCT was 9.5s(40%sensitivity,100%specificity);The optimal cut-off value of stenosis was 45%(100%sensitivity,43.9%specificity);The cut-off value of stenosis was 72.5%(60%sensitivity,53.7%specificity);The optimal cut-off point for age was 53.5 years(100%sensitivity,48.8%specificity).Conclusions:Our studies suggest that prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify those individuals at the high risk of DICE with a specificity superior to stenosis.In patients with a significantly prolonged CCT,angioplasty or placement of a Wingspan stent may be warranted even when their degree of stenosis is less than 70%.Our findings provide new perspectives into the correlation between rCCT and the prognosis of ND-MCAS.Further exploring the mediators behind this phenomenon may provide new targets for neuroprotection in patients with ND-MCAS.