The Mechanism Of Vertebrobasilar Dolichoectasia Associated With Posterior Circulation Ischemic And Cerebral Small Vessel Disease

Background:Vertebrobasilar artery dolichoectasia(VBD)was reported to be associated with cerebral small vessel disease(CSVD)and imbalance between matrix metalloproteinases(MMPs)and tissue inhibitor of metalloproteinases(TIMPs)might be the common mechanism of both.Morphology changes of vertebrobasilar arteries subsequently leaded to the change of hemodynamics in vertebrobasilar system.Slow arterial blood flow in VBD patients has been reported in several studies.Hypoperfusion in the areas supplied by the tortuous basilar artery had been confirmed using the CT perfusion imaging.However.hypoperfusion in the areas supplied by vertebrobasilar arteries determined by perfusion weighted imaging(PWI)and posterior circulation ischemic events caused by VBD recognizing with the utilization of PWI,had been reported in few studies.Vertebrobasilar ectasia(VBE),a major type of VBD.was a predictor of stroke and increased the risk of death.However,the relationship between VBE and MMPs remains unclear.Objective:1.To investigate the association between VBD and lacunar infarction(LI)and white matter hyperintensities(WMHs)and test the hypothesis that imbalance between matrix metalloproteinases(MMPs)and tissue inhibitor of metalloproteinases(TIMP)might be the common mechanism of both.2.To examine the association between VBD and hypoperfusion of posterior circulation,and evaluated the values of PWI parameters on predicting the occurrence of posterior circulation ischemic stroke in patients with VBD.3.To investigate the relationship between plasma levels of MMPs and VBE in patients with vertigo or dizziness who also have vascular risk factors,and whether the relationship depends on vertebral artery dominance(VAD).Methods:Information about 524 patients with dizziness or vertigo,hospitalized at the Department of Neurology of Zhengzhou People's Hospital(China)from December 2014 to May 2017,were consecutively collected.Imaging parameters vertebrobasilar arteries,including the maximum diameter,tortuosity index(TI),basilar artery length(BAL)and bending length(BL)were measured by the using of MRA.BL of basilar artery presents its degree of tortuosity.The neuroimaging markers of CSVD including LI and WMH were evaluated with the utilization of T2-weighted and FLAIR images.Serum MMPs and TIMPs levels were measured using enzyme-linked immunosorbent assay.Perfusion parameters of posterior circulation territories including relative cerebral blood volume(rCBV).relative cerebral blood flow(rCBF),mean transit time(MTT)and time to peak(TTP)were evaluated on DSC-PWI images.To investigated the associated mechanism between VBD and CSVD.,differences of MMPs and TIMPs levels were evaluated between different groups of VBD types(ectasia vs non-ectasia group,elongation vs non-elongation group,tortuosity vs non-tortuosity group),and further,the correlation between parameters of vertebrobasilar arteries and MMPs and TIMPs levels were caculated,then differences of vertebrobasilar arteries parameters and MMPs and TIMPs levels were evaluated between CSVD groups(LI vs non-LI group,WMH grade 0?1?2?3 groups).To investigated the association between VBD and perfusion in posterior circulation territories,patients were devided into VBD and non-VBD group and differences of perfusion para,meters in posterior circulation were evaluated between groups,and receiver operating characteristic(ROC)curve analysis were established to evaluated the values of perfusion parameters on predicting the occurrence of posterior circulation ischemic stroke in VBD patients.On the other hand,VBE patients were divided into VAD and non-VAD subgroup and differences of MMPs and TIMPs levels were evaluated between subgroups to investigate whether the association between VBE and MMPs depents on VAD or not.Mann-Whitney U test were performed between two groups and Kruskal-Wall is test were performed among three or more groups.Results:1.MMP-9 level was significantly higher in patients with vertebrobasilar arteries dilation(P = 0.021)and basilar artery elongation(P = 0.004).TIMP-1 level was markedly higher in patients with basilar artery tortuosity(P-0.039).BL of BA was positively correlated with TIMP-1(r = 0.161,P = 0.020).B.AL.BL,TI of BA were greater and TIMP-1 level were higher in patients with higher WMH grades(grade 2 and 3),while as vertebrobasilar arteries diameters,MMP-2,-3,-9,TIMP-2 and cathepsin L were similar in patients with different WMH grades.2.TTP in lower cerebellum,superior cerebellum,pons,and occipital and temporal lobes region of interests was significantly delayed in VBD patients,while rCBF,rCBV,and MTT parameters were not significant differences.TTP in the right temporal lobe delayed by 21.96 ms was the best predictive value and the mean TTP predictive threshold\value in all ROIs was 22.67±1.48 ms.3.Compared with VBE patients without VAD,levels of MMP-2,-3.-9,TIMP-1,-2 and cathepsin L were similar in those with VAD.Conclusion:1.MMP-9 level was higher in patients with vertebrobasilar arteries dilation and basilar artery elongation but TIMP-1 level was higher in those with higher WMH grades and those with basilar artery tortuosity.2.VBD leads to the hypoperfusion of posterior circulation territory characterized by delayed TTP.Delayed TTP in cerebellum,pons,and occipital and temporal lobes fed by vertebrobasilar arteries predicted the occurrence of posterior ischemic stroke in VBD patients.3.High plasma MMP-9 level in VBE patients did not depend on VAD.