The Association Of Remote Diffusion-Weighted-Imaging Lesions With Renal Dysfunction And Cerebral Small Vessel Disease In Primary Intracerebral Hemorrhage

BackgroudPrimary intracerebral hemorrhage(ICH_is the second most common cause of stroke,accounting for about 10-15%of all strokes worldwide each year.ICH has much higher morbidity and mortality compared with ischemic stroke.However,at present,the treatment of ICH is limited,and it is a key task to search new therapeutic targets to effectively improve the prognosis of ICH.Over the last several years,diffusion-restricted lesions on diffusion-weighted imaging(DWI)are detected in 11.1%-41%ICH patients.These lesions are often subclinical,but was reported associating with worsened outcome,as well as predicting higher recurrence of stroke.However,the mechanisms of how remote DWI lesions(R-DWILs)forms and the related factors of formation have not yet been clarified.Small vessel disease in the brain and kidneys may have a common pathogenesis source because these organs are closely related due to similar anatomical and vasoregulatory characters.Therefore,it is suggested that markers for early renal dysfunction may serve as an early indicators of cerebral small vessel damage.Previous studies have suggested a relationship between renal dysfunction and cSVD magnetic resonance imaging(MRI)markers like cerebral microbleeds(CMBs),white matter hyperintensites(WMHs),enlarged perivascular spaces(EPVS)and lacunes.R-DWILs are sometimes considered another potential imaging marker of cSVD.However,the association of renal dysfunction with R-DWILs has been rarely explored before.Besides,it seems that researchers are tend to rely on one marker only,while ignoring the others.Recently,a total cSVD score was proposed,which incorporates four markers of cSVD(CMBs,WMHs,EPVS and lacunes)and aims to capture the overall burden of cSVD.However,to our best knowledge,few studies has aimed to date investigating the association of renal dysfunction with total cSVD burden.Previous studies have suggested that R-DWILs were associated with CMBs,WMHs and EPVS,indicating a potential role of cSVD in the formation of R-DWILs.However,results about each single cSVD marker were conflicting,and most of these studies merely focused on one or two markers,with few of them evaluating four cSVD markers simultaneously in one research,as well as total cSVD burden.Thus,in the first part of my doctoral thesis,we examined the rate of renal dysfunction in primary ICH population and explored the association between the renal dysfunction and R-DWILs and the total burden of cSVD.In the second part,we described the clinic feature of R-DWILs and the total burden of cSVD in patients with primary ICH,and then investigated the relationship between R-DWILs and the total burden of cSVD.Part One Association of Renal Dysfunction with Remote Diffusion-Weighted Imaging Lesions and Total Burden of Cerebral Small Vessel Disease in Patients with Primary Intracerebral HemorrhageObjectiveRemote diffusion-weighted imaging(DWI)lesions(R-DWILs)found in intracerebral hemorrhage(aCH)patients are considered as an additional marker of cerebral small vessel disease(cSVD).This study aimed to investigate the association of renal dysfunction and R-DWIL,as well as the total burden of cSVD on magnetic resonance imaging among patients with primary ICH.MethodsOne hundred and twenty-six consecutive patients were prospectively enrolled.R-DWILs on difiusion-weighted imaging,as well as other imaging markers of cSVD,including lacunes,white matter lesions,cerebral microbleeds,and enlarged perivascular spaces were rated using validated scales.Renal dysfunction was evaluated either by reduced estimated glomerular filtration rate(eGFR)or the presence of protemxiria or increased cystatin C.ResultsAfter adjustments for potential confounders by logistic regression,impaired eGFR(odds ratio[OR]6.00,95%confidence interval[CI]1.73-20.78),proteinuria(OR 3.07,95%CI 1.25-7.54)and:increased cystatin C(OR 2.73,95%CI 1.11-6.72)were correlated with presence of R-DWIL.A similar association was also found between cystatin C levels(OR 3.16,95%CI 1.39-7.19),proteinuria(OR 2.79,95%CI 1.34-5.83)and the comprehensive cSVD burden.ConclusionsRenal dysfunction are associated with the presence of R-DWILs,and total burden of cSVD in patients with primary ICH.Part Two Remote Diffusion-Weighted Imaging Lesions is associated with Cerebral Small Vessel Disease in Primary Intracerebral HemorrhageObjectiveThe aim of this study was to examine the association among remote diffusion-weighted imaging lesions(R-DWILs),imaging markers of cerebral small vessel disease(cSVD),and total cSVD burden in patients with primary intracerebral hemorrhage(ICH).MethodsThree hundred and forty-four consecutive primary ICH patients were enrolled prospectively.RDDWILs on magnetic resonance imaging(MRI),as well as four imaging markers of cSVD,including cerebral microbleeds(CMBs),white matter hbperintensities(WMHs),lacunes,and enlarged perivascular spaces(EPVS)were rated with validated scales.The total cSVD score was calculated by adding up these four markers.Univariate and multivariate analyses were performed.ResultsRemote DWI lesions were detected in 57(16.6%)primary ICH patients.On multivariate logistic regression analysis,presence of CMBs(OR 3.88,95%Cl 1.59-9.46),high-grade WMHs(OR 4.78,95%Cl 2.24-10.20),presence of lacunes(OR 2.55,95%Cl L25-5.22),mixed CMBs(OR 2.66,95%Cl 1.34-5.28),mixed lacunes(OR 2.90,95%Cl 1.09-7.69),PWMHs(OR 2.08,95%Cl 1.39-3.10),DWMHs(OR 1.74,95%Cl 1.19-2.54)and total WMHs(OR 1.45,95%Cl 1.18-1.79)were associated with presence of R-DWILs.High-grade total cSVD score was also independently associated with presence of R-DWILs(OR 2.13,95%Cl 1.53-2.99).This association remained significant in patients stratified by whether or not?60 years.ConclusionsR-DWILs are correlated with the severity of each imaging marker of cSVD,and with the total burden of cSVD.