| Part Ⅰ Association between white matter hyperintensities,intracranial pulsatility and asymptomatic intracranial arterial stenosis:A population-based study in Shandong,ChinaBackground:White matter hyperintensities(WMH),described as hyperintense in the subcortical white matter displayed on T2-weighted magnetic resonance imaging(MRI)and fluid-attenuated inversion recovery(FLAIR)images,are commonly observed in older adults and considered one of the manifestations of cerebral small vessel disease(CSVD).Several studies have suggested that arterial stiffening results in increased aortic pulsatility and its transmission to the cerebral circulation may play a pathophysiological role in the development of WMH.Increased intracranial pulsatility,measured by transcranial Doppler sonography(TCD)or phase-contrast MRI,might therefore be an important underlying mechanism of CSVD.Thus,data on the association between the pulsatility index(PI)and WMH in individuals with severe atherosclerosis are still lacking.Most studies suggest WMH to be a direct result of local microvascular abnormalities,but the effect of intracranial arterial stenosis on WMH remains unclear.The purpose of this study was to investigate the relationship between WMH,PI and intracranial arterial stenosis in a natural population,which will help in better understanding the underlying pathogenesis of WMH and provide a basis for prevention and delaying the progression of WMH.Objective:We aimed to investigate the relationship between WMH,PI and intracranial arterial stenosis in a natural population.Methods:All participants were recruited from the Kongcun Town asymptomatic intracranial atherosclerotic stenosis(aICAS)Study,including a total of 103 participants with aICAS and 98 healthy controls(age-and sex-matched).PI was assessed using transcranial Doppler ultrasound.The WMH volume(WMHV)was calculated through the lesion segmentation tool system for the Statistical Parametric Mapping package based on magnetic resonance imaging.The association between WMH,PI and intracranial arterial stenosis were analyzed by linear regression models adjusting for demographics,lifestyle,and vascular risk factors.Results:The alCAS group was more likely to have hypertension,diabetes,dyslipidemia,increased triglyceride/high-density lipoprotein ratio,increased systolic blood pressure,and decreased high-density lipoprotein(P<0.05).There were no significant differences in age,gender,current smoking,current drinking,total cholesterol,low density lipoprotein,diastolic blood pressure,carotid intima-media thickening and carotid plaque between aICAS group and control group(P>0.05).In a multivariable model,age≥60 years and male sex(P=0.000 and 0.006,respectively)were significant predictors of lnWMHV in the aICAS group.In the control group,age≥60 years(P=0.000)and systolic blood pressure(P=0.010)were significant predictors of lnWMHV.In sex-stratified analyses,there was a significant association between PI and lnWMHV in males with aICAS(P=0.038).The median WMH volume was 0.97ml(IQR 0.19-3.82)in the control group and 1.34ml(IQR 0.30-4.75)in the aICAS group.There was no significant difference in WMHV between the two groups(P=0.171).There were 47 cases of severe stenosis with a median WMHV of 1.81ml(IQR 0.16-5.89)in the aICAS group,and the WMHV of the severe stenosis group was not significantly different from the control group(P>0.05).After adjusting for covariates in multiple linear regression analysis,we found no significant correlation between severe intracranial arterial stenosis and lnWMHV(P=0.544).Conclusion:This study suggests that there might be a likely association between increased intracranial pulsatility and WMH burden in males with aICAS,while there were no significant correlation between intracranial artery stenosis and WMH burden.Part Ⅱ White matter hyperintensities combined with hemodynamic parameters predict hyperperfusion after carotid artery stentingBackground:Cerebral hyperperfusion syndrome(CHS)is a serious complication after carotid revascularization.Initial hyperperfusion-associated cerebral edema is reversible,and early detection and intervention can prevent progression to severe or even life-threatening symptoms.Carotid stenosis often coexists with white matter hyperintensities(WMH).Cerebral autoregulatory dysfunction is associated with WMH and as a main mechanism of cerebral hyperperfusion(CH)after carotid artery stenting.Therefore,we hypothesize that preoperative WMH may have adverse effects on CH.However,few studies have examined WMH as a risk factor for hyperperfusion after carotid artery stenting(CAS).Objective:This study aims to combine WMH imaging markers with hemodynamic parameters to predict hyperperfusion after CAS.Methods:A total of 171 CAS procedure treated for carotid artery stenosis in the Department of Neurology from 2018 to 2020 were retrospectively enrolled.WMH severity was rated visually on axial FLAIR images using the Fazekas rating scale.The hemodynamic parameters of bilateral MCA were detected by TCD one day before and 2 hours after CAS.Univariate and multivariate logistic regression models were used to analyze preoperative risk factors for CH after stenting.Receiver Operating Characteristic(ROC)curves were drawn to determine the appropriate limit to predict CH,and the risk factors for the development of CHS were analyzed.Results:CH occurred in 28(16.4%)of 171 CAS procedure.Binary Logistic regression analysis showed that WMH≥3(OR=4.000,95%CI:1.249-12.805,P=0.020),preoperative mean flow velocity Vm of the affected middle cerebral artery(OR=0.926,95%CI:0.878-0.976,P=0.004),preoperative bilateral middle cerebral artery mean flow velocity asymmetry index Vm AI(OR=2.308,95%CI:1.125-4.736,P=0.023),preoperative pulsatile index(OR=0.018,95%CI:0.001-0.437,P=0.013),hypertension(OR=0.134,95%CI:0.039-0.459,P=0.001)and contralateral stenosis≥70%(OR=6.030,95%CI:1.720-21.135,P=0.005)were independent risk factors for CH after CAS.The area under the curve(AUC)of WMH combined with TCD in predicting CH was 0.888(95%CI:0.821-0.955)with a sensitivity of 92.9%,a specificity of 79.0%,a positive predictive value of 46.4%,a negative predictive value of 98.3%.A total of 8 patients(4.6%)developed CHS,and 2 of them(1.2%)developed cerebral hemorrhage.Preoperative Vm(P=0.000)and Vm AI(P=0.000)were risk factors for CHS.There were no significant differences in WMH score between CHS group and non-CHS group.Conclusion:WMH is an independent risk factor for CH after CAS,which can be used as an effective imaging marker for CH.WMH combined with TCD hemodynamic parameters can accurately predict CH before surgery,which would be beneficial to clinical decision-making.Preoperative TCD mean velocity and bilateral asymmetry index are associated with CHS,while WMH is not significantly associated with CHS.Further large-sample analysis is needed to verify the correlation.Part Ⅲ Effect of white matter hyperintensities on long-term outcomes after carotid artery stentingBackground:Patients with white matter hyperintensities(WMH)have chronic cerebral blood flow insufficiency,blood-brain barrier disruption and decreased cerebrovascular reactivity,which may have adverse effects on long-term prognosis of patients with carotid artery stenting(CAS).WMH are associated with an increased perioperative risk of stroke in patients undergoing carotid artery stenting(CAS).However,there are few data showing their impact on postoperative long-term stroke recurrence,restenosis or survival.Objective:We tried to assess the effects of WMH on long-term outcomes after CAS in patients with carotid artery stenosis.Methods:Consecutive patients who had undergone CAS for symptomatic and asymptomatic carotid artery stenosis from 2018 to 2020 were included.WMH severity was rated visually on axial FLAIR images using the Fazekas rating scale.The 90-day modified Rankin Scale(mRS)was assessed.The primary end point events included any stroke,myocardial infarction,all-cause death and stent restenosis after perioperative period(30 days after CAS surgery),while the composite end point was a composite of any stroke,myocardial infarction and all-cause death.We analyzed the association between WMH and long-term outcomes after CAS through clinic follow-ups and telephone interviews,with a median follow-up time of 32 months.Results:161 patients with an average age of 65.5 years fulfilled the inclusion criteria,while 3 patients were lost to follow-up after 3 months.In our cohort,87.6%of the participants were male.The mean age of severe WMH group was significantly higher than that of mild WMH group(66.9 vs 64.3,P=0.035).Seventeen patients(10.6%)had poor functional prognosis(mRS≥3)at 90 days.During the follow-up period,10 cases(6.2%)had any stroke,4 cases(2.5%)had myocardial infarction,10 cases(6.2%)had all-cause death,19 cases(11.8%)had composite end point events(stroke,myocardial infarction or all-cause death),and 10 cases(6.2%)had restenosis.The 3-year cumulative incidence of stroke recurrences was significantly different between the severe WMH and mild WMH groups(10.8%vs 2.3%,p=0.028),whereas the 90-day mRS,cumulative incidence of all-cause death,myocardial infarction,composite end point events(stroke,myocardial infarction,or all-cause death)and restenosis did not differ significantly between the groups(p>0.05).Cox regression analysis showed that WMH was a risk factor for recurrent stroke in patients aged ≤65 years(HR=9.24,95%CI 1.11-76.74,P=0.040),but not in patients aged>65 years(HR=1.83,95%CI 0.17-20.17,P=0.622).After adjusting for age,gender and symptomatic status,WMH was not independently associated with increased risk of composite end point events(P>0.05).Conclusion:The presence of white matter lesions should be considered in patients undergoing CAS surgery.The 3-year cumulative incidence of stroke with severe WMH is 4～5 times higher than that in patients with mild WMH.WMH was an independent risk factor for stroke recurrence in relatively young patients after CAS,but not for 90-day good functional outcome,myocardial infarction,all-cause death,composite end point event and restenosis during long-term follow-up.Larger studies are warranted to confirm this finding and explore the potential clinical impact of WMH so as to better determine treatment strategies for patients with severe carotid artery stenosis. |
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