Association Of Intracranial Artery Stenosis And Extracranial Atherosclerosis With White Matter Hyperintensities

Background:White matter hyperintensities(WMHs)are frequently found on brain MRI of older individuals and substantially predict an increased risk of dementia,stroke,mortality and physical disability.Evidence exist considered WMHs as small-vessel disease-related lesions,but the exact etiology underlying is poorly understood.Proposed mechanisms including chronic hypoperfusion,diffuse cerebrovascular endothelial failure,and blood-brain barrier alterations,alone or simultaneously contribute to the damage of cerebral vessels and parenchyma.Postmortem studies have shown that WMHs correlate with various degrees of demyelination,arteriolosclerosis and mild gliosis.As regards the pathology,there is little doubt that great majority of WMHs lesions are ischaemic in origin.An inefficient blood supply to brain due to luminal narrowing by atherosclerotic arterial stenosis in the upstream may be a potential impact of the presence and development of WMHs.Numerous efforts have been made to identify the correlation between carotid arteriosclerosis with WMHs and resulted controversial consequences,while most of which showed no direct association for the co-relevance with vascular risk factors(VRFs).Intracranial-and Extracranial atherosclerosis(ICAS and ECAS)have been suggested to have distinct pathogeneses,as the former might have less opportunity to be compensated by the circle of Willis hemodynamically and is less elastic in cerebral autoregulation resulting in pressure-passive cerebral blood flow.Cross-sectional studies performed in Koreans with stroke cohorts alone reported the association between WMHs severity and ICAS rather than ECAS,whereas other studies failed to demonstrate the relevance.Additionally,WMHs may progress insidiously rather than stay unalterable and risk factors for progression are uncertain.There has been only one study assessing the effects of statins on the progression of WMHs incidentally mentioned a negative association between ICAS and WMHs.Further exploration of ICAS in relation to WMHs is warranted.We therefore sought to conduct the current study in acute stroke free patients,aiming to determine whether ICAS and ECAS have relation to WMHs severities and ICAS could serve as predictors for WMHs progression during 5 years.Section One Association of intracranial-and extracranial atherosclerosis with white matter hyperintensitiesObjects: To study the relationship of intracranial-and extracranial atherosclerosis with white matter hyperintensities(PVWMHs)and subcortical white matter hyperintensities(SCWMHs).Methods:Seven hundred and nine in-patients with their age ?60 years who underwent head MRI and CTA examination were included in this study.We assessed the severity of PVWMHs and SCWMHs using Fazekas and LADIS scores,and measured the stenosis of major intracranial-and extracranial arteries by CTA.Individuals with more than 50% artery stenosis were considered as positive.Results:1.PVWMHs were found in 433 patients(mild 192,moderate 151,severe 90),and SCWMHs were found in 424 patients(mild 184,moderate 150,severe 90),as well as 64 patients were found with co-existence of PVWMHs and SCWMHs.There were 138 ICAS,31 ECAS and 64 Co-CAS.Patients with both PVWMHs and SCWMHs were older,with higher systolic pressure,and had higher prevalence of male,hypertension,coronary heart disease,previous stroke,antihypertensive use,intracranial-and extracranial atherosclerosis than those without WMHs(P<0.05).Diabetes was more prevalent in PVWMHs patients than SCWMHs patients.2.Fazekas scores for PVWMHs patients and SCWMHs petients were 1.76±0.77 and 1.77±0.77.Compared with NCAS patients,ICAS patients with single and multiple stenosis had higher PVWMHs scores(P>0.05),ECAS patients with multiple stenosis had higher SCWMHs,Co-CAS patients with single and multiple stenosis had both higher PVWMHs and SCWMHs scores.3.Binary logistic regression was used to analyze the effect of ICAS,ECAS and other potential risk factors on PVWMHs and SCWMHs prevalence.After adjustment of age,sex,BMI,hypertension,diabetes,coronary heart disease,dyslipidaemia,atrial fibrillation,previous stroke,current smoking and daily alcohol use,ICAS was independently associated with PVWMHs(OR: 3.11,95%CI: 1.80-5.37)and SCWMHs(OR: 1.83,95%CI: 1.13-2.97)(P<0.05),while ECAS and Co-CAS had no relation to WMHs(P>0.05).4.Multinomial logistic regression was used to analyze the relation of ICAS and ECAS to WMHs severities.After adjustment of age,sex,BMI,hypertension,diabetes,coronary heart disease,dyslipidaemia,atrial fibrillation,previous stroke,current smoking and daily alcohol use,ICAS had relation to mild,moderate and severe PVWMHs with ORs as 2.07,3.10 and 4.24(P<0.05),while ICAS were associated with only moderate and severe PVWMHs with ORs as 2.05 and 2.97(P<0.05).Conclusions:ICAS rather than ECAS had more close relationship to WMHs,with ORs of 3.1 and 1.8 for PVWMHs and SCWMHs,respectively.Additionally,ICAS was associatied with WMHs severities and showed more WMHs scores in patients with multiple stenosis than those with single ones.Section Two Association of intracranial atherosclerosis with progression of white matter hyperintensitiesObjects: To study the relationship of ICAS with progression of PVWMHs and SCWMHs.Methods:In this retrospective longitudinal study,we enrolled the patients who had undergone cerebral MRI scans twice with a 5-years gap and had been examined by CTA in the first MRI scan.We assessed the severity of baseline PVWMHs and SCWMHs using Fazekas and LADIS scores,and evaluated the progression of WMHs using the modified Rotterdam Progression scale(m RPS),as well as measured the stenosis of major intracranial arteries by CTA.Individuals with more than 50% artery stenosis were considered as positive.Results:1.A total of 72 patients were enrolled,of which 55.6% occurred WMHs progression(47.2% for PVWMHs progression,50.0% for SCWMHs progression).Patients with both progression of PVWMHs and SCWMHs were older,with higher Fazekas scores,and had higher prevalence of hypertension and ICAS than those without WMHs(P<0.05).2.Binary logistic regression was used to analyze the effect of ICAS on PVWMHs and SCWMHs progression.ICAS had ORs of 9.43 and 5.59 for PVWMHs and SCWMHs progression,separately.After adjustment of age,sex,BMI,hypertension,diabetes,coronary heart disease,dyslipidaemia,atrial fibrillation,previous stroke,current smoking and daily alcohol use,ICAS was independently associated with PVWMHs(OR: 5.09,P<0.05),while not for SCWMHs(P>0.05).After additional adjustment of baseline Fazekas scores ICAS had no relation to WMHs progression(P>0.05).Conclusions:The progressions of WMHs in 5 years measured by m RPS were 47.2% and 50.0% for PVWMHs and SCWMHs respectively.ICAS was independently associated with PVWMHs after adjustment of age,sex,BMI and vascular risk factors,while the relation was disappeared after additional adjustment of baseline Fazekas scores.Further prospective studies with a larger sample size are needed to confirm the relationship of ICAS and WMHs progression.