| Background: Intracranial arterial dolichoectasia(IADE)is an extracranial remodeling form of intracranial blood vessels.Mainly involves the posterior circulation,also known as vertebral basilar dolichoectasia(VBD).Studies have shown that IADE is not uncommon in the clinic,and its incidence in stroke population is about 12%.IADE can be asymptomatic,and also could cause severe neurological diseases such as cerebral infarction,cerebral hemorrhage,subarachnoid hemorrhage,cranial nerve compression,hydrocephalus,dementia,etc..;however,the pathogenesis of IADE is poorly understood,IADE is mainly manifested as outward dilation of blood vessels,pathological manifestations of interrupted inner elastic layer,sparse reticular fibers,and studies have shown that IADE is not related to carotid atherosclerosis;IADE and intracranial atherosclerosis stenosis(ICAS)is two different forms of vascular disease,whether the risk factors and the effects on downstream small vessels of the two vasculopathy are different remains unknown.In addition,some studies have found that IADE is closely related to imaging markers of cerebral small vessel disease(CSVD),such as lacuna,white matter hyperintensity(WMH),enlarged perivascular space(EPVS),and cerebral microbleeds(CMBs).We hypothesis that intracranial arteries degeneration(manifested as increased diameter)may lead to more conduction of systemic hemodynamic pressure to terminal small blood vessels,leading to CSVD.There is currently no systematic study to evaluate the diameter of intracranial arteries and its correlation with markers of CSVD and the total burden of CSVD.Finally,due to the lack of effective treatments,the expected risk of stroke recurrence in IADE patients is relatively high,but the studies about predictors of stroke recurrence in IADE patients is limited,especially in the Chinese population.Objective: Therefore,the purpose of our research is mainly in the following three aspects: 1)The first part is to study whether the risk factors between IADE and intracranial atherosclerotic stenosis and the impact on downstream small vessels are different;2)the second part of the study aimed to find the correlation of intracranial arterial outward remolding with markers of CSVD and total burden of CSVD;3)The third part aimed to evaluate the risk factors of stroke recurrence in IADE patients.Methods: 1)case inclusion and exclusion: in the first part of the study,patients were retrieved from the Nanjing Stroke Registration System and continuously included from September 1,2015 to August 31,2016.Patients with acute ischemic stroke were confirmed by magnetic resonance imaging(MRI)or computed tomography(CT)scanning;at the second part of the study,patients with acute lacuna infarction came from the Nanjing Stroke Registry System and the Stroke Registry Database of the Affiliated Hospital of Nanjing University of Chinese Medicine;in the third part,patients with first acute ischemic stroke were included from the Nanjing Stroke Registration System and the Stroke Registration Database of the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine.Cases were excluded depending on the purpose of the study,and are described separately in three parts of this research;2)we measured the diameters of seven major intracranial arteries including the basilar artery,the bifurcation height and lateral position of the basilar artery,and use the documented standards to diagnose IADE;the blood vessel diameter were standardized and to calculate the Z-score of intracranial arterial diameter,called cerebral arterial remodeling(BAR)score.Baseline demographics,laboratory data,vascular risk factors,and medical records were collected,and data on intracranial atherosclerotic stenosis were recorded.The imaging markers of cerebral small vessel disease were recorded,including lacuna,WMH,EPVS,CMBs,and then calculate the total CSVD burden.The risk factors of IADE were identified through binary logistic regression analysis;the relationship between the BAR score and the total burden of CSVD was observed through ordered logistic regression analysis;finally,the recurrence of ischemic stroke was tracked through planned clinical visits or telephone follow-up,baseline characteristics and vascular morphological changes with statistically significant parameters in patients with and without stroke recurrence were introduced into the COX proportional hazard model to detect possible predictors of stroke recurrence.Results: Part I: Of the 469 patients enrolled,61(13%)had IADE and 218(46%)had ICAS.Multivariate analysis found that ICAS(+)patients were associated with age(P = 0.002),hypertension(P = 0.027),history of stroke(P = 0.009),LDL cholesterol(P = 0.002),and WBC levels(P = 0.003);however,IADE was only correlated with age(adjusted OR = 1.03;95% CI 1.00-1.06;P = 0.034)and hypertension(adjusted OR = 2.01;95% CI 1.03-3.93;P = 0.042);IADE was not correlated with extracranial(internal carotid artery)atherosclerosis(adjusted OR = 0.618;95% CI,0.280-1.367;P = 0.235).The incidence of multiple infarcts was higher in IADE(+)patients(adjusted OR = 2.142;95% CI 1.158-3.964;P = 0.015);white matter hyperintensity were also more frequent(adjusted OR = 2.782;95% CI 1.522-5.085;P = 0.001).However,patients with ICAS(+)had no significant difference with multiple lacuna infarcts and white matter hyperintensity compared with ICAS(-)patients.Part Ⅱ: A total of 312 patients were involved in this study,patients with BAR score >1 SD were older(P = 0.039),and more prone to having a history of myocardial infarction(P = 0.033).The Spearman’s rank correlation coefficient between the BAR score and total CSVD score is 0.320(P < 0.001).Binary logistic regression found that BAR score >1 SD was correlated with lacuna(OR = 1.987;95% CI,1.037-3.807;P = 0.039);severe WMH(OR = 1.994;95% CI,1.003-3.964;P = 0.049);severe EPVS(OR = 2.544; 95% CI,1.299-4.983;P = 0.006)and CSVD(OR = 2.997;95% CI 1.182-7.599;P = 0.021).IADE was also correlated with lacuna(OR = 2.565;95% CI,1.317-4.996;P = 0.006);severe WMH(OR = 2.983;95% CI,1.499-5.937;P = 0.002);severe EPVS(OR = 2.648;95% CI,1.338-5.238;P = 0.005)and CSVD(OR = 2.931;95% CI,1.155-7.438;P = 0.024).Ordinal logistic regression analysis found that BAR score >1 SD(OR = 2.418;95% CI,1.350-4.330;P = 0.003)were correlated with the total CSVD score.Part Ⅲ: A total of 115 stroke patients with vertebrobasilar dolichoectasia were enrolled,of which 22(19.1%)had recurrence during 22 ± 6 months follow-up.Basilar artery diameter ≥ 5.3 mm(HR = 4.744;95% CI,1.718-13.097;P = 0.003),diffuse intracranial dolichoectasia(HR = 3.603;95% CI,1.367-9.496;P = 0.010)and ischemic heart disease history(HR = 4.095;95% CI,1.221-13.740;P = 0.022)had increased risk of recurrence.Conclusions: 1)IADE and ICAS had different risk factors and associated with different small vessel signs,suggesting different underlying mechanisms.2)Patients with intracranial arterial outward remolding may have heavier CSVD burden.The mechanisms of this association warrant further study.3)Stroke patients with vertebrobasilar dolichoectasia may have a high risk of recurrence.Basilar artery diameter ≥5.3mm or diffuse intracranial dolichoectasia were independent riskfactors of stroke recurrence. |
PDF Full Text Request