Effect of coincidence of severe extracranial and intracranial artery stenosis or occlusion on cerebral small vessel disease

Effect of coincidence of severe extracranial and intracranial artery stenosis or occlusion on cerebral small vessel disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of coincidence of severe extracranial and intracranial artery stenosis or occlusion on cerebral small vessel disease Pei Dai, Ya-na Fang, Hui-xian Yu, Zhao-xia Wang, Si-hao Liu, Da-wei Zang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4825369/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: There was a significant correlation between the large atherosclerotic extracranial artery stenosis (ECAS) or intracranial artery stenosis (ICAS) and the neuroimaging markers of cerebral small vessel disease (CSVD). Our objective was to investigate the effect of coexistence of severe extracranial and intracranial arterial stenosis or occlusion on CSVD in patients with ischemic stroke. Methods: A total of 222 patients with LAA infarction with CSVD were included in this retrospective study, including 160 males and 62 females. All enrolled patients were divided into four groups: ECAS, ECAS+ICAS, ICAS and None. The differences between the four groups were evaluated by total CSVD scores, total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores. Results: There were significant differences between the four groups in terms of total CSVD scores ( P < 0.05). But there was no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores. Further pairwise comparison shows that only the ECAS+ICAS group and the none group had a significant difference in total CSVD scores ( P < 0.05). Conclusion: The coincidence of severe stenosis or occlusion of the extracranial and intracranial artery may increase the incidence of CSVD and aggravate the performance of CSVD in patients with ischemic stroke and mainly reflected in the total CSVD scores. If ECAS and/or ICAS are found in patients, the total CSVD burden should be also actively assessed. To reduce the incidence of stroke and improve outcomes, active clinical intervention should be undertaken for these patients. Severe extracranial or intracranial artery stenosis Occlusion Large atherosclerotic cerebral infarction Total cerebral small vessel disease scores Fazekas scores Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Cerebral small vessel disease (CSVD) is recognized as a risk factor for stroke and dementia. Atherosclerotic extracranial or intracranial artery stenosis or occlusion is a crucial cause and pathology of ischemic stroke. The evaluation of CSVD mainly depends on MRI image features. With the advancement of MRI technology, especially with the support of high-field MRI technology, more subtle abnormal changes in brain tissue related to CSVD injury can be revealed. These neuroimaging markers have been found in many studies to be associated with the prognosis of LAA stroke [ 2 ] . Imaging findings of CSVD are generally considered to include lacunae, new subcortical infarction, blood-derived white matter lesions (WML), enlarged perivascular space (EPVS), cerebral microbleeds (CMBs) and cerebral atrophy [ 3 ] . Extracranial artery stenosis (ECAS) and intracranial artery stenosis (ICAS) have been showed to be associated with the development of CSVD and usually share common vascular risk factors such as hypertension and aging [ 4 – 6 ] , both of these common risk factors affect the outcome of stroke. Previous studies have found that ICAS was associated with lacunes, increased white matter hyperintensities volume and brain atrophy [ 6 ] . Other studies have suggested that ICAS may be associated with arteriolar lesions, radiographically manifested as white matter lesions or small chronic infarcts, which are pathologically defined as CSVD [ 7 ] . Xue-yang Wang [ 8 ] et al. also founded that severe centrum semiovale perivascular space (CS-PVS) and lacunes were associated with severe stenosis of intracranial large artery disease. In recent years, many studies have explored the relationship between ECAS and total CSVD score or different imaging markers of CSVD from different perspectives. Ultrasound evidence recently described by Lu et al. suggests that severe ECAS in patients with ischemic stroke suspected to have originating in small or large arteries is associated with the presence of concurrent progressive CSVD [ 9 ] . Müjdat Deniz Benli et al. founded that compared with the 50–69% ICA stenosis group, the number of patients with silent brain infarcts (SBIs) and the number of SBIs in the ipsilateral hemisphere were higher in stenosis ≥ 70% group [ 10 ] . Another study showed that patients with severe ECAS or occlusion had a significantly higher total CSVD score than those without [ 11 ] . However, the effect of extracranial or intracranial vascular stenosis, especially coincidence of severe extracranial and intracranial arterial stenosis or occlusion on CSVD in patients with ischemic stroke has yet to be addressed. Therefore, in the present study, we divided four groups according to the presence or absence of severe intracranial or extracranial arterial stenosis to investigate their influence on CSVD. MATERIALS AND METHODS Recruitment period This study was designed as a retrospective study and was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University. The ethics review number is KY 2021-039-01. All participants provided signed and informed consent. We enrolled patients between April 1, 2021 and November 1, 2023. Study Population We collected clinical data from 222 patients in our rehabilitation department for analysis. Inclusion criteria ① Aged between 50 and 80 years; ② According to the TOAST classification scheme, the patients were diagnosed as ischemic stroke caused by atherosclerosis of the large arteries [ 1 ] ; ③ Patients with onset within 2 to 4 weeks when admission; ④ All patients signed informed consent when admission. Exclusion criteria ① Cardiogenic embolism, arteriole occlusion, et al. other types of TOAST etiological classification scheme were not included; ② Patients with leukoencephalopathy due to multiple sclerosis, genetic diseases, Alzheimer's disease (AD) and other factors were excluded; ③ Patients who were unable to provide all sequences of head MRIs were also excluded. Imaging Assessment All enrolled patients underwent brain MRIs before admission. The patient's bilateral ECASs were assessed by color Doppler ultrasonography, including the common carotid arteries, the extracranial internal carotid arteries and the proximal vertebral arteries (ostium, V2-3). Bilateral ICASs were assessed by MR Angiography or CT angiography, including the middle cerebral arteries, anterior cerebral arteries, posterior cerebral arteries and distal vertebral arteries (segment V4). We used the total CSVD score and the Fazekas score to evaluate the CSVD burden. As there are some differences between periventricular WMH and deep WMH, we further evaluated the Fazekas scores of periventricular WMH and deep WMH respectively in this study. Assessment of Total CSVD Score It mainly included lacunes, EPVS, CMBs and WML scores. The score ranges from 0 to 4, and higher scores indicated more severe CSVD [ 12 ] . The scoring method involved several aspects: (1) Lacunae: 1 point was given when 1 or more asymptomatic lacunes were present. (2) CMBs: 1 point was awarded when there is 1 or more microbleeds. (3) EPVS: based on the number of EPVS in the basal ganglia, a semi-quantitative scale from 0 to 4 points is used: grade 0, no EPVS; grade 1, 10 or fewer EPVS; grade 2, 11–20 EPVS; grade 3, 21–40 EPVS; grade 4, more than 40 EPVS. 1 point is given for moderate to severe EPVS (grade 2–4) [ 13 ] . (4): WML: WMLs are graded according to the Fazekas scale. 1 point is awarded for a Fazekas score of 3 for periventricular white matter lesions (irregular hyperintensities extending into deep white matter) and/or a Fazekas score of 2 or 3 for deep WMLs (confluent WMH) [ 14 ] . The Fazekas Scale (0–6) The Fazekas score ranges from 0 to 6 and is the sum of scores for periventricular and deep WMLs. Periventricular hyperintensity scores: 0 indicates no obvious white matter change; 1 indicates that WMLs are cap-like or pencil-like thin-layer lesions; 2 refers to a smooth halo; and 3 indicates that the irregular periventricular hyperintensities extended into the deep WM. Deep WM scores: 0 indicates no obvious WML; 1 indicates punctate WML; 2 indicates the fusion of WMLs; and 3 indicates large lesion fusion [ 14 ] . In the North American Symptomatic Carotid Endarterectomy (NASCET) criteria [ 15 ] , vascular stenosis was classified into the following five grades: no stenosis, mild stenosis (less than 30%), moderate stenosis (30%-69%), severe stenosis (70%-99%), or occlusive (100%). Grouping The study design was showed in Fig. 1 and we performed several different comparisons as following: First, we compared total CSVD scores, total Fazekas scores and Fazekas scores of periventricular WMH and deep WMH respectively between the four groups (including ECAS, ECAS + ICAS, ICAS and None). Next, we made further pairwise comparison between ECAS and ECAS + ICAS, ECAS and ICAS, ECAS and None, ECAS + ICAS and ICAS, ECAS + ICAS and None, ICAS and None for total CSVD scores. Statistical Analysis We compared baseline factors (including age, sex, the history of hypertension, diabetes and stroke) between patients of group ECAS, group ECAS + ICAS, group ICAS and group None. The comparison of age was performed with t test; other comparisons were performed with Fisher’s exact test (for percentages). Statistical analysis and graphing were performed by GraphPad Prism 8.0 (GraphPad Software, Inc., San Diego, California, USA). All data in this study basically conform to normal distribution, and continuous variables such as age are expressed as mean ± standard deviation; independent sample t test was applied for comparison between groups. A P value < 0.05 was considered statistically significant. RESULTS In all the 222 patients with LAA cerebral infarctions, 160 were males and 62 were females. 35 patients had severe ECAS or occlusion, 28 patients had both severe extracranial and intracranial arterial stenosis or occlusion, 39 patients had severe ICAS or occlusion and 120 patients didn’t have any severe extracranial or intracranial arterial stenosis or occlusion. Among the four groups (ECAS, ECAS+ICAS, ICAS and None), there was no significant differences in terms of age, gender, the history of hypertension, diabetes or stroke ( P > 0.05) (Table 1). 1. Total CSVD scores，total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores between the four groups. We found significant difference between the four groups in terms of total CSVD scores ( P = 0.048, Figure 2A); but there was no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores. 2. Pairwise comparisons between the groups (including ECAS and ECAS+ICAS, ECAS and ICAS, ECAS and NONE, ECAS+ICAS and ICAS, ECAS+ICAS and NONE, ICAS and NONE). Further pairwise comparison shows that only the ECAS+ICAS and NONE group had a significant difference in total CSVD scores ( P =0.026, Figure 3E). DISCUSSION In our study, we found that there were significant differences between the four groups (including ECAS, ECAS+ICAS, ICAS and None) in terms of total CSVD scores. But no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores were found. The main results of the present study show that with severe stenosis or occlusion of extracranial or intracranial artery can promote the occurrence and development of CSVD and mainly reflected in the total CSVD score rather than total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores. Further pairwise comparison shows that only the ECAS+ICAS group and the none group had a significant difference in total CSVD scores. But there was no significant difference in group ECAS and ECAS+ICAS, ECAS and ICAS, ECAS and None, ECAS+ICAS and ICAS, and also, ICAS and None. The imaging hallmarks of CSVD include lacunae, small new subcortical infarcts, WML, EPVS, CMBs and brain atrophy [16] . Staals et al. proposed that total CSVD scores is more powerful and persuasive in assessing the overall impact of CSVD on brain function than a single imaging phenotype [12] . Many studies explored the relationships between total CSVD scores and clinics. Total CSVD scores were found to be independently associated with cognitive impairment in patients with CSVD [17] . Xuanting Li et al. [18] also found that total CSVD scores was associated with the overall cognitive impairment among middle-aged and elderly Chinese adults. In a study, total CSVD scores were also shown to be independently associated with clinical outcomes in patients with acute ischemic stroke (AIS) treated with intra-arterial thrombectomy (IAT), and a higher total CSVD score may be a reliable predictor of poor outcomes in AIS patients treated with IAT [19] . It appears that ECAS or/and ICAS may affect stroke outcomes by affecting CSVD. Based on some previous studies on the relationships between ECAS or/and ICAS and CSVD, in our study, severe intracranial or/and extracranial arterial stenosis or occlusion was shown to be more associated with total CSVD scores than the Fazekas scores (including total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores). WML is the most common manifestation compared with other hallmarks of CSVD such as lacunae, small new subcortical infarcts, EPVS and CMBs. Many studies confirmed the relationship between extracranial or/and intracranial arterial stenosis and WMH [20,21] . However, in our study, we didn’t find any significant difference in the Fazekas scores between the four groups. This may be because ECAS or/and ICAS are more likely to cause varying degrees of brain function impairment by affecting multiple CSVD imaging phenotypes, rather than just white matter damage. Further pairwise comparisons were made for exploring the relationship between severe extracranial or/and intracranial arterial stenosis or occlusion and CSVD. It showed that only the ECAS+ICAS group had higher total CSVD scores than NONE group. There was no significant difference between other groups (ECAS and ECAS+ICAS, ECAS and ICAS, ECAS and NONE, ECAS+ICAS and ICAS, ECAS+ICAS and NONE, ICAS and NONE), however. We speculated that this may be because both severe extracranial and intracranial arterial stenosis or occlusion have contributed to the occurrence and development of CSVD in various degrees. Compared with group NONE, the coexistence of severe extracranial and intracranial arterial stenosis or occlusion might lead to more severe CSVD burden. This result is consistent with previous studies. For example, Lu et al. found that high levels of ECAS were associated with coexisting advanced CSVD in ischemic stroke patients [9] . Wang et al. concluded that in multivariate analysis of their study, severe centrum semiovale centrum semiovale PVS and lacunes were associated with severe stenosis of intracranial large artery disease [8] . CSVD has a significant effect on the occurrence, development, prognosis and recurrence of LAA cerebral infarction. Clinically, active, appropriate and effective intervention for extracranial and/or intracranial arterial stenosis may help to reduce or prevent the occurrence and progression of CSVD, and further reduce the adverse effects of CSVD on brain function. However, our study still has some limitations that need to be addressed. First, we performed a retrospective analysis of 222 patients with ischemic stroke. But the occurrence and development of CSVD are long-term and chronic. Many factors may affect the development and change of CSVD. As a cross-sectional or baseline analysis alone, it may not provide the most accurate description of the relationship between ECAS or/and ICAS and CSVD. Thus, longitudinal follow-up in the future should be involved. Second, few of the enrolled patient received active intravascular intervention. We speculate that the severity of CSVD will improve in the future after appropriate ECAS and/or ICAS intervention. In fact, given that severe extracranial or intracranial arterial stenosis or occlusion may increase the incidence of CSVD or exacerbate the presentation of CSVD, active intravascular intervention of ECAS and/or ICAS in such patients may be beneficial for the improvement of overall brain function. Third, severe stenosis or occlusion of the extracranial or intracranial artery may be closely related to a specific phenotype of CSVD. However, this study only focused on the total CSVD scores and the Fazekas scores, which only represents white matter lesions. The influence of ECAS or/and ICAS on other phenotypes of CSVD should also be concerned in the future. In conclusion, the coexistence of severe stenosis or occlusion of the extracranial and intracranial artery may increase the incidence or exacerbate the presentation of CSVD in patients with LAA cerebral infarction. active intravascular intervention of ECAS and/or ICAS in such patients may be beneficial for the improvement of overall brain function. If ECAS and/or ICAS are found in patients, the total CSVD burden should be also actively assessed. Intervention at the early stage of CSVD may have an important impact on stroke treatment, prognosis and recurrence, and may also reduce morbidity and mortality, especially for patients with both severe extracranial and intracranial arterial stenosis or occlusion. Abbreviations ECAS extracranial artery stenosis ICAS intracranial artery stenosis CSVD cerebral small vessel disease WML blood-derived white matter lesions EPVS enlarged perivascular space CMBs cerebral microbleeds CS-PVS centrum semiovale perivascular space SBIs silent brain infarcts AD Alzheimer's disease NASCET North American Symptomatic Carotid Endarterectomy Declarations Ethical statement and consent to participate This research was conducted in agreement with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University. All participants provided signed and informed consent. The ethics review number is KY 2021-039-01. The informed consent was obtained from all subjects and/or their legal guardian(s) for minor and uneducated participants. Consent for publication Not applicable Availability of data and materials The data that support the findings of this study are available from the corresponding author. Conflict of interest The authors declare that there is no conflict of interest. Funding This research was supported by the National Natural Science Foundation of China (grant number: 82072532). Acknowledgment The authors wish to thank their colleagues for mentorship, help and guidance in experimental design. Author contributions Pei Dai: Conceptualization, Methodology, Formal analysis, Data Curation, Writing - Original Draft; Ya-na Fang: Formal analysis; Hui-xian Yu: Methodology; Zhao-xia Wang: Methodology, Data Curation; Si-hao Liu: Data Curation; Da-wei Zang: Writing-Review & Editing, supervision, funding. All authors read and approved the final manuscript. 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Identification of Metabolomics Biomarkers in Extracranial Carotid Artery Stenosis[J]. Cells. 2022,11(19):3022. Atticus H Hainsworth, Hugh S Markus, Julie A Schneider. Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia[J]. Hypertension. 2024,81(1):75-86. Zhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England) 2019;394:1145-1158. Xue-yang Wang, Jin-hao Lyu, Sen-hao Zhang, et al. Severity of Intracranial Large Artery Disease Correlates With Cerebral Small Vessel Disease. J Magn Reson Imaging. 2022;56(1):264-272. Tao Lu, Jiahui Liang, Ninglin Wei, Liya Pan, Hong Yang, Baohui Weng, Jinsheng Zeng. Extracranial Artery Stenosis Is Associated With Total MRI Burden of Cerebral Small Vessel Disease in Ischemic Stroke Patients of Suspected Small or Large Artery Origins. Front Neurol. 2019,10:243. Müjdat Deniz Benli, Bülent Güven , Hayat Güven, et al. Silent brain infarcts and white matter lesions in patients with asymptomatic carotid stenosis[J]. Acta Neurol Belg, 2021,121(4):983-991. Pei Dai, Hui-Xian Yu, Zhao-Xia Wang, et al. The relationship between severe extracranial artery stenosis or occlusion and cerebral small vessel disease in patients with large artery atherosclerotic cerebral infarction. Front Neurol. 2022,13:1008319. Staals J, Makin SD, Doubal FN, et al. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden[J]. Neurology,2014,83(14): 1228-1234. Doubal, F.N., MacLullich, A.M., Ferguson, K.J., Dennis, M.S., Wardlaw, J.M.. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease[J]. Stroke,2010,41:450-454. Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A.. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging[J]. AJR Am. J. Roentgenol,1987,149:351-356. North American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, et al. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis[J]. N Engl J Med,1991,325:445–53. Berrocal-Izquierdo N，Bioque M，Bemardo M．Is cerebrovascular disease a silent condition in patients with chronic schizophrenia-related disorders [J]. Int Clin Psychopharmacol，2017, 32(2):80-86. Zhihua Xu, Fangfei Li, Dengxiang Xing, Hongyan Song, Jingshu Chen, Yang Duan, Benqiang Yang. A Novel Imaging Biomarker for Cerebral Small Vessel Disease Associated With Cognitive Impairment: The Deep-Medullary-Veins Score. Front Aging Neurosci. 2021, 13:720481. Xuanting Li, Junliang Yuan, Wei Qin, Lei Yang, Shuna Yang, Yue Li, Wenli Hu. Total Burden of Cerebral Small Vessel Disease on MRI May Predict Cognitive Impairment in Parkinson's Disease. J Clin Med. 2022,11(18):5381. Mengqi Yang, Jiahui Liang, Baohui Weng, Jinghong Liang, Tao Lu, Hong Yang. Total Cerebral Small Vessel Disease Burden Predicts the Outcome of Acute Stroke Patients after Intra-Arterial Thrombectomy. Cerebrovasc Dis. 2023,52(6):616-623. Sedat Yasin, Rabia Tasdemir. An Investigation of the Relationship Between Carotid Artery Stenosis and White Matter Hyperintensitie. Cureus. 2023,15(5): e39468. Tingting Zhong, Yunwen Qi, Rui Li, Huadong Zhou, Boli Ran, Jiao Wang, ZhiYou Cai. Front Neurol. 2022,13:922320. Tables Table 1 Patient comparisons Group Age（±𝑠） Sex（n） Hypertension（n） Diabetes（n） Stroke（n） M F Yes No Yes No Yes No ECAS 62.80±9.83 28 7 28 7 20 15 10 25 ECAS+ICAS 65.07±8.76 24 4 22 6 17 11 4 24 ICAS 62.92±8.50 30 9 32 7 25 14 14 25 NONE 62.17±9.74 78 42 98 22 52 68 27 93 ECAS, extracranial arterial stenosis; ICAS, intracranial artery stenosis; M, male, F, female. P＞0.05 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4825369","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":337504170,"identity":"6c35217b-0a7c-47a0-8169-fcaa540b2710","order_by":0,"name":"Pei Dai","email":"","orcid":"","institution":"Beijing Tian Tan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pei","middleName":"","lastName":"Dai","suffix":""},{"id":337504171,"identity":"037927a2-5096-469d-976d-06d010b6889f","order_by":1,"name":"Ya-na Fang","email":"","orcid":"","institution":"Beijing Electric Power Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ya-na","middleName":"","lastName":"Fang","suffix":""},{"id":337504172,"identity":"b39c367d-f86f-43b5-b764-c91e9102f53a","order_by":2,"name":"Hui-xian Yu","email":"","orcid":"","institution":"Beijing Tian Tan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hui-xian","middleName":"","lastName":"Yu","suffix":""},{"id":337504173,"identity":"02176b4e-43b2-4010-b1b2-ecd071bd270c","order_by":3,"name":"Zhao-xia Wang","email":"","orcid":"","institution":"Beijing Tian Tan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhao-xia","middleName":"","lastName":"Wang","suffix":""},{"id":337504174,"identity":"9213e594-9f5b-4001-ad94-79a3b121fdee","order_by":4,"name":"Si-hao Liu","email":"","orcid":"","institution":"Beijing Tian Tan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Si-hao","middleName":"","lastName":"Liu","suffix":""},{"id":337504175,"identity":"4b3d5fff-2c60-4cb9-931a-2269e4736b6a","order_by":5,"name":"Da-wei Zang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYDCCA0CcUPFPjp+Z+fADErScOWAs2c6WZkC8FsaWA4kG53kUJIjSwXf8jOGDhw13EowP8zAYMNTYRBPUInkmx9ggccezPLPDvAceMBxLy20gpMXgQO42icQzzMVmh/kSDBgbDhOh5fzb7T8S25gTNzfzGEgQp+VG7jaGxLbDiRuYidUieeP9Z4mEM2nGEoeBgZxAjF/4zqclfvxRYSPH33/48IMPNTaEtaCCBNKUj4JRMApGwSjABQADikdCbPqmJAAAAABJRU5ErkJggg==","orcid":"","institution":"Beijing Tian Tan Hospital","correspondingAuthor":true,"prefix":"","firstName":"Da-wei","middleName":"","lastName":"Zang","suffix":""}],"badges":[],"createdAt":"2024-07-30 03:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4825369/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4825369/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63126184,"identity":"8a44c320-2c73-4203-8673-8dd91234f034","added_by":"auto","created_at":"2024-08-23 12:19:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1249681,"visible":true,"origin":"","legend":"\u003cp\u003eEnrollment and Outcomes. CSVD, cerebral small vessel disease; ECAS, extracranial artery stenosis; ICAS, intracranial arterial stenosis.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4825369/v1/d0a4251ac787318f86c879c1.png"},{"id":63126185,"identity":"d994e2a8-a3b2-41bf-956e-dab228f802ba","added_by":"auto","created_at":"2024-08-23 12:19:51","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":255105,"visible":true,"origin":"","legend":"\u003cp\u003eTotal CSVD scores，total Fazekas scores, periventricular WMH Fazekas scores\u003cem\u003e \u003c/em\u003eand deep WMH Fazekas scores between the four groups. We found significant difference between the four groups in terms of total CSVD scores (P = 0.048, Figure 2A); but there was no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4825369/v1/57159a88cfa00e7f50ed4270.jpg"},{"id":63126186,"identity":"d1451ec5-aa82-4c61-abe4-d2c3ef98a565","added_by":"auto","created_at":"2024-08-23 12:19:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":214009,"visible":true,"origin":"","legend":"\u003cp\u003ePairwise comparisons between the groups (including ECAS and ECAS +ICAS, ECAS and ICAS, ECAS and NONE, ECAS+ICAS and ICAS, ECAS+ICAS and NONE, ICAS and NONE). Further pairwise comparison shows that only the ECAS+ICAS and NONE group had a significant difference in total CSVD scores(P =0.026, Figure 3E).\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4825369/v1/739dfa323da265d033da8c8e.jpg"},{"id":64175564,"identity":"68b17e7a-31d2-4553-bfbb-3141dffe7deb","added_by":"auto","created_at":"2024-09-09 12:48:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1925034,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4825369/v1/1b779385-66e5-4aa3-8ff4-1f54e029ee9a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of coincidence of severe extracranial and intracranial artery stenosis or occlusion on cerebral small vessel disease","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCerebral small vessel disease (CSVD) is recognized as a risk factor for stroke and dementia. Atherosclerotic extracranial or intracranial artery stenosis or occlusion is a crucial cause and pathology of ischemic stroke. The evaluation of CSVD mainly depends on MRI image features. With the advancement of MRI technology, especially with the support of high-field MRI technology, more subtle abnormal changes in brain tissue related to CSVD injury can be revealed. These neuroimaging markers have been found in many studies to be associated with the prognosis of LAA stroke \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eImaging findings of CSVD are generally considered to include lacunae, new subcortical infarction, blood-derived white matter lesions (WML), enlarged perivascular space (EPVS), cerebral microbleeds (CMBs) and cerebral atrophy \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Extracranial artery stenosis (ECAS) and intracranial artery stenosis (ICAS) have been showed to be associated with the development of CSVD and usually share common vascular risk factors such as hypertension and aging \u003csup\u003e[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, both of these common risk factors affect the outcome of stroke. Previous studies have found that ICAS was associated with lacunes, increased white matter hyperintensities volume and brain atrophy \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Other studies have suggested that ICAS may be associated with arteriolar lesions, radiographically manifested as white matter lesions or small chronic infarcts, which are pathologically defined as CSVD \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Xue-yang Wang \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e et al. also founded that severe centrum semiovale perivascular space (CS-PVS) and lacunes were associated with severe stenosis of intracranial large artery disease. In recent years, many studies have explored the relationship between ECAS and total CSVD score or different imaging markers of CSVD from different perspectives. Ultrasound evidence recently described by Lu et al. suggests that severe ECAS in patients with ischemic stroke suspected to have originating in small or large arteries is associated with the presence of concurrent progressive CSVD \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. M\u0026uuml;jdat Deniz Benli et al. founded that compared with the 50\u0026ndash;69% ICA stenosis group, the number of patients with silent brain infarcts (SBIs) and the number of SBIs in the ipsilateral hemisphere were higher in stenosis\u0026thinsp;\u0026ge;\u0026thinsp;70% group \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Another study showed that patients with severe ECAS or occlusion had a significantly higher total CSVD score than those without \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, the effect of extracranial or intracranial vascular stenosis, especially coincidence of severe extracranial and intracranial arterial stenosis or occlusion on CSVD in patients with ischemic stroke has yet to be addressed. Therefore, in the present study, we divided four groups according to the presence or absence of severe intracranial or extracranial arterial stenosis to investigate their influence on CSVD.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eRecruitment period\u003c/h2\u003e \u003cp\u003e This study was designed as a retrospective study and was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University. The ethics review number is KY 2021-039-01. All participants provided signed and informed consent. We enrolled patients between April 1, 2021 and November 1, 2023.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eWe collected clinical data from 222 patients in our rehabilitation department for analysis.\u003c/p\u003e \u003cp\u003eInclusion criteria\u003c/p\u003e \u003cp\u003e \u003cb\u003e①\u003c/b\u003e Aged between 50 and 80 years;\u003c/p\u003e \u003cp\u003e② According to the TOAST classification scheme, the patients were diagnosed as ischemic stroke caused by atherosclerosis of the large arteries \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e;\u003c/p\u003e \u003cp\u003e③ Patients with onset within 2 to 4 weeks when admission;\u003c/p\u003e \u003cp\u003e④ All patients signed informed consent when admission.\u003c/p\u003e \u003cp\u003eExclusion criteria\u003c/p\u003e \u003cp\u003e① Cardiogenic embolism, arteriole occlusion, et al. other types of TOAST etiological classification scheme were not included;\u003c/p\u003e \u003cp\u003e② Patients with leukoencephalopathy due to multiple sclerosis, genetic diseases, Alzheimer's disease (AD) and other factors were excluded;\u003c/p\u003e \u003cp\u003e③ Patients who were unable to provide all sequences of head MRIs were also excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eImaging Assessment\u003c/h2\u003e \u003cp\u003eAll enrolled patients underwent brain MRIs before admission. The patient's bilateral ECASs were assessed by color Doppler ultrasonography, including the common carotid arteries, the extracranial internal carotid arteries and the proximal vertebral arteries (ostium, V2-3). Bilateral ICASs were assessed by MR Angiography or CT angiography, including the middle cerebral arteries, anterior cerebral arteries, posterior cerebral arteries and distal vertebral arteries (segment V4).\u003c/p\u003e \u003cp\u003eWe used the total CSVD score and the Fazekas score to evaluate the CSVD burden. As there are some differences between periventricular WMH and deep WMH, we further evaluated the Fazekas scores of periventricular WMH and deep WMH respectively in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of Total CSVD Score\u003c/h2\u003e \u003cp\u003eIt mainly included lacunes, EPVS, CMBs and WML scores. The score ranges from 0 to 4, and higher scores indicated more severe CSVD \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The scoring method involved several aspects: (1) Lacunae: 1 point was given when 1 or more asymptomatic lacunes were present. (2) CMBs: 1 point was awarded when there is 1 or more microbleeds. (3) EPVS: based on the number of EPVS in the basal ganglia, a semi-quantitative scale from 0 to 4 points is used: grade 0, no EPVS; grade 1, 10 or fewer EPVS; grade 2, 11\u0026ndash;20 EPVS; grade 3, 21\u0026ndash;40 EPVS; grade 4, more than 40 EPVS. 1 point is given for moderate to severe EPVS (grade 2\u0026ndash;4) \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. (4): WML: WMLs are graded according to the Fazekas scale. 1 point is awarded for a Fazekas score of 3 for periventricular white matter lesions (irregular hyperintensities extending into deep white matter) and/or a Fazekas score of 2 or 3 for deep WMLs (confluent WMH) \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eThe Fazekas Scale (0\u0026ndash;6)\u003c/h2\u003e \u003cp\u003eThe Fazekas score ranges from 0 to 6 and is the sum of scores for periventricular and deep WMLs. Periventricular hyperintensity scores: 0 indicates no obvious white matter change; 1 indicates that WMLs are cap-like or pencil-like thin-layer lesions; 2 refers to a smooth halo; and 3 indicates that the irregular periventricular hyperintensities extended into the deep WM. Deep WM scores: 0 indicates no obvious WML; 1 indicates punctate WML; 2 indicates the fusion of WMLs; and 3 indicates large lesion fusion \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the North American Symptomatic Carotid Endarterectomy (NASCET) criteria \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, vascular stenosis was classified into the following five grades: no stenosis, mild stenosis (less than 30%), moderate stenosis (30%-69%), severe stenosis (70%-99%), or occlusive (100%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGrouping\u003c/h2\u003e \u003cp\u003eThe study design was showed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and we performed several different comparisons as following:\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFirst, we compared total CSVD scores, total Fazekas scores and Fazekas scores of periventricular WMH and deep WMH respectively between the four groups (including ECAS, ECAS\u0026thinsp;+\u0026thinsp;ICAS, ICAS and None).\u003c/p\u003e \u003cp\u003eNext, we made further pairwise comparison between ECAS and ECAS\u0026thinsp;+\u0026thinsp;ICAS, ECAS and ICAS, ECAS and None, ECAS\u0026thinsp;+\u0026thinsp;ICAS and ICAS, ECAS\u0026thinsp;+\u0026thinsp;ICAS and None, ICAS and None for total CSVD scores.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eWe compared baseline factors (including age, sex, the history of hypertension, diabetes and stroke) between patients of group ECAS, group ECAS\u0026thinsp;+\u0026thinsp;ICAS, group ICAS and group None. The comparison of age was performed with t test; other comparisons were performed with Fisher\u0026rsquo;s exact test (for percentages). Statistical analysis and graphing were performed by GraphPad Prism 8.0 (GraphPad Software, Inc., San Diego, California, USA). All data in this study basically conform to normal distribution, and continuous variables such as age are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; independent sample t test was applied for comparison between groups. A P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eIn all the 222 patients with LAA cerebral infarctions, 160 were males and 62 were females. 35 patients had severe\u0026nbsp;ECAS\u0026nbsp;or occlusion, 28 patients had both severe\u0026nbsp;extracranial and intracranial arterial stenosis\u0026nbsp;or occlusion, 39 patients had severe\u0026nbsp;ICAS\u0026nbsp;or occlusion and 120 patients didn’t have any severe\u0026nbsp;extracranial or intracranial arterial stenosis\u0026nbsp;or occlusion. Among the four groups (ECAS, ECAS+ICAS, ICAS and None), there was no significant differences in terms of age, gender, the history of hypertension, diabetes or stroke (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05) (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.\u0026nbsp; \u0026nbsp;Total CSVD scores，total Fazekas scores, periventricular WMH Fazekas scores\u003c/p\u003e\n\u003cp\u003eand deep WMH Fazekas scores between the four groups. We found significant difference between the four groups in terms of total CSVD scores\u0026nbsp;(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.048, Figure 2A);\u0026nbsp;but there was no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp;Pairwise comparisons between the groups (including\u0026nbsp;ECAS and ECAS+ICAS,\u003c/p\u003e\n\u003cp\u003eECAS and ICAS, ECAS and NONE, ECAS+ICAS and ICAS, ECAS+ICAS and NONE, ICAS and NONE). Further pairwise comparison shows that only the ECAS+ICAS and NONE group had a significant difference in total CSVD scores\u0026nbsp;(\u003cem\u003eP\u003c/em\u003e =0.026, Figure 3E).\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn our study, we found that\u0026nbsp;there were significant differences between the four groups (including ECAS, ECAS+ICAS, ICAS and None) in terms of total CSVD scores. But no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores were found.\u0026nbsp;The main results of the present study show that with\u0026nbsp;severe stenosis or occlusion of extracranial or intracranial artery can\u0026nbsp;promote the occurrence and development of CSVD and mainly reflected in the total CSVD score rather than\u0026nbsp;total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores.\u0026nbsp;Further pairwise comparison shows that only the ECAS+ICAS group and the none group had a significant difference in total CSVD scores. But there was no significant difference in group ECAS and ECAS+ICAS, ECAS and ICAS, ECAS and None, ECAS+ICAS and ICAS, and also, ICAS and None.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe imaging hallmarks of CSVD include lacunae, small new subcortical infarcts, WML, EPVS, CMBs and brain atrophy \u003csup\u003e[16]\u003c/sup\u003e. Staals et al. proposed that total CSVD scores is more powerful and persuasive in assessing the overall impact of CSVD on brain function than a single imaging phenotype \u003csup\u003e[12]\u003c/sup\u003e. Many studies explored the relationships between total CSVD scores and clinics. Total CSVD scores were found to be independently associated with cognitive impairment in patients with CSVD \u003csup\u003e[17]\u003c/sup\u003e.\u0026nbsp;\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Li+X\u0026amp;cauthor_id=34322013\"\u003eXuanting Li\u003c/a\u003e et al. \u003csup\u003e[18]\u003c/sup\u003e also found that total CSVD scores was associated with the overall cognitive impairment among middle-aged and elderly Chinese adults. In a study, total CSVD scores were also shown to be independently associated with clinical outcomes in patients with acute ischemic stroke (AIS) treated with intra-arterial thrombectomy (IAT), and a higher total CSVD score may be a reliable predictor of poor outcomes in AIS patients treated with IAT \u003csup\u003e[19]\u003c/sup\u003e. It appears that ECAS or/and ICAS may affect stroke outcomes by affecting CSVD. Based on some previous studies on the relationships between ECAS or/and ICAS and CSVD, in our study, severe intracranial or/and extracranial arterial stenosis or occlusion was shown to be more associated with total CSVD scores than the Fazekas scores (including total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores). WML is the most common manifestation compared with other hallmarks of CSVD such as lacunae, small new subcortical infarcts, EPVS and CMBs. Many studies confirmed the relationship between extracranial or/and intracranial arterial stenosis and WMH \u003csup\u003e[20,21]\u003c/sup\u003e. However, in our study, we didn’t find any significant difference in the Fazekas scores between the four groups. This may be because ECAS or/and ICAS are more likely to cause varying degrees of brain function impairment by affecting multiple CSVD imaging phenotypes, rather than just white matter damage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurther pairwise comparisons were made for exploring the relationship between severe extracranial or/and intracranial arterial stenosis or occlusion and CSVD. It showed that only the ECAS+ICAS group had higher total CSVD scores than NONE group. There was no significant difference between other groups (ECAS and ECAS+ICAS, ECAS and ICAS, ECAS and NONE, ECAS+ICAS and ICAS, ECAS+ICAS and NONE, ICAS and NONE), however. We speculated that this may be because both severe extracranial and intracranial arterial stenosis or occlusion have contributed to the occurrence and development of CSVD in various degrees. Compared with group NONE, the coexistence of severe extracranial and intracranial arterial stenosis or occlusion might lead to more severe CSVD burden. This result is consistent with previous studies. For example, Lu et al. found that high levels of ECAS were associated with coexisting advanced CSVD in ischemic stroke patients \u003csup\u003e[9]\u003c/sup\u003e.\u0026nbsp;\u003ca href=\"https://pubmed.ncbi.nlm.nih.gov/?term=Wang+XY\u0026amp;cauthor_id=34797007\"\u003eWang\u003c/a\u003e et al. concluded that in multivariate analysis of their study, severe centrum semiovale centrum semiovale PVS and lacunes were associated with severe stenosis of intracranial large artery disease \u003csup\u003e[8]\u003c/sup\u003e. \u0026nbsp;CSVD has a significant effect on the occurrence, development, prognosis and recurrence of LAA cerebral infarction. Clinically, active, appropriate and effective intervention for extracranial and/or intracranial arterial stenosis may help to reduce or prevent the occurrence and progression of CSVD, and further reduce the adverse effects of CSVD on brain function.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, our study still has some limitations that need to be addressed. First, we performed a retrospective analysis of 222 patients with ischemic stroke. But the occurrence and development of CSVD are long-term and chronic. Many factors may affect the development and change of CSVD. As a cross-sectional or baseline analysis alone, it may not provide the most accurate description of the relationship between ECAS or/and ICAS and CSVD. Thus, longitudinal follow-up in the future should be involved. Second, few of the enrolled patient received active intravascular intervention. We speculate that the severity of CSVD will improve in the future after appropriate ECAS and/or ICAS intervention. In fact, given that severe extracranial or intracranial arterial stenosis or occlusion may increase the incidence of CSVD or exacerbate the presentation of CSVD, active intravascular intervention of ECAS and/or ICAS in such patients may be beneficial for the improvement of overall brain function. Third, severe stenosis or occlusion of the extracranial or intracranial artery may be closely related to a specific phenotype of CSVD. However, this study only focused on the total CSVD scores and the Fazekas scores, which only represents white matter lesions. The influence of ECAS or/and ICAS on other phenotypes of CSVD should also be concerned in the future.\u003c/p\u003e\n\u003cp\u003eIn conclusion, the coexistence of severe stenosis or occlusion of the extracranial and intracranial artery may increase the incidence or exacerbate the presentation of CSVD in patients with LAA cerebral infarction. active intravascular intervention of ECAS and/or ICAS in such patients may be beneficial for the improvement of overall brain function. If ECAS and/or ICAS are found in patients, the total CSVD burden should be also actively assessed. Intervention at the early stage of CSVD may have an important impact on stroke treatment, prognosis and recurrence, and may also reduce morbidity and mortality, especially for patients with both severe extracranial and intracranial arterial stenosis or occlusion.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eECAS \u0026nbsp; \u0026nbsp; \u0026nbsp; extracranial artery stenosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eICAS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;intracranial artery stenosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCSVD \u0026nbsp; \u0026nbsp; \u0026nbsp; cerebral small vessel disease\u003c/p\u003e\n\u003cp\u003eWML \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;blood-derived white matter lesions\u003c/p\u003e\n\u003cp\u003eEPVS \u0026nbsp; \u0026nbsp; \u0026nbsp; enlarged perivascular space\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCMBs \u0026nbsp; \u0026nbsp; \u0026nbsp; cerebral microbleeds\u003c/p\u003e\n\u003cp\u003eCS-PVS \u0026nbsp; \u0026nbsp; centrum semiovale perivascular space\u003c/p\u003e\n\u003cp\u003eSBIs \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;silent brain infarcts\u003c/p\u003e\n\u003cp\u003eAD \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Alzheimer's disease\u003c/p\u003e\n\u003cp\u003eNASCET \u0026nbsp; \u0026nbsp;North American Symptomatic Carotid Endarterectomy\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical statement and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was conducted in agreement with the Declaration of Helsinki and was approved by\u0026nbsp;the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University. All participants provided signed and informed consent. The ethics review number is KY 2021-039-01. The informed consent was obtained from all subjects and/or their legal guardian(s) for minor and uneducated participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the National Natural Science Foundation of China (grant number: 82072532).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to thank their colleagues for mentorship, help and guidance in experimental design.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePei Dai: Conceptualization, Methodology, Formal analysis, Data Curation, Writing - Original Draft; Ya-na Fang: Formal analysis; Hui-xian Yu: Methodology; Zhao-xia Wang: Methodology, Data Curation; Si-hao Liu: Data Curation; Da-wei Zang: Writing-Review \u0026amp; Editing, supervision, funding. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZeena Mohamed Fuad, Hazlina Mahadzir, Syed Zulkifli Syed Zakaria, et al. Frequency of cognitive impairment among malaysian elderly patients following first ischemic stroke\u0026mdash;a case control study[J]. Front Public Health,2020,12 (8):577940.\u003c/li\u003e\n\u003cli\u003eCunsheng Wei, Tingwen Shen, Xuelian Tang, Yuanyuan Gao, Xiaorong Yu and Xuemei Chen. Cerebral small vessel disease combined with cerebral collaterals to predict the prognosis of patients with acute large artery atherosclerotic stroke[J]. Front Neurol. 2022,13:969637.\u003c/li\u003e\n\u003cli\u003eWardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration[J]. Lancet Neurol, 2013,12(8): 822-838.\u003c/li\u003e\n\u003cli\u003eRuijun Liu , Jing Shao. Research progress on risk factors related to intracranial artery, carotid artery, and coronary artery stenosis[J]. Front Cardiovasc Med. 2022,9:970476.\u003c/li\u003e\n\u003cli\u003eChia-Ni Lin, Kai-Cheng Hsu, Kuo-Lun Huang, Wen-Cheng Huang, Yi-Lun Hung, Tsong-Hai Lee. Identification of Metabolomics Biomarkers in Extracranial Carotid Artery Stenosis[J]. Cells. 2022,11(19):3022.\u003c/li\u003e\n\u003cli\u003eAtticus H Hainsworth, Hugh S Markus, Julie A Schneider. Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia[J]. Hypertension. 2024,81(1):75-86.\u003c/li\u003e\n\u003cli\u003eZhou M, Wang H, Zeng X, et al. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England) 2019;394:1145-1158.\u003c/li\u003e\n\u003cli\u003eXue-yang Wang, Jin-hao Lyu, Sen-hao Zhang, et al. Severity of Intracranial Large Artery Disease Correlates With Cerebral Small Vessel Disease. J Magn Reson Imaging. 2022;56(1):264-272.\u003c/li\u003e\n\u003cli\u003eTao Lu, Jiahui Liang, Ninglin Wei, Liya Pan, Hong Yang, Baohui Weng, Jinsheng Zeng. Extracranial Artery Stenosis Is Associated With Total MRI Burden of Cerebral Small Vessel Disease in Ischemic Stroke Patients of Suspected Small or Large Artery Origins. Front Neurol. 2019,10:243.\u003c/li\u003e\n\u003cli\u003eM\u0026uuml;jdat Deniz Benli, B\u0026uuml;lent G\u0026uuml;ven , Hayat G\u0026uuml;ven, et al. Silent brain infarcts and white matter lesions in patients with asymptomatic carotid stenosis[J]. Acta Neurol Belg, 2021,121(4):983-991.\u003c/li\u003e\n\u003cli\u003ePei Dai, Hui-Xian Yu, Zhao-Xia Wang, et al. The relationship between severe extracranial artery stenosis or occlusion and cerebral small vessel disease in patients with large artery atherosclerotic cerebral infarction. Front Neurol. 2022,13:1008319.\u003c/li\u003e\n\u003cli\u003eStaals J, Makin SD, Doubal FN, et al. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden[J]. Neurology,2014,83(14): 1228-1234.\u003c/li\u003e\n\u003cli\u003eDoubal, F.N., MacLullich, A.M., Ferguson, K.J., Dennis, M.S., Wardlaw, J.M.. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease[J]. Stroke,2010,41:450-454.\u003c/li\u003e\n\u003cli\u003eFazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A.. MR signal abnormalities at 1.5 T in Alzheimer\u0026rsquo;s dementia and normal aging[J]. AJR Am. J. Roentgenol,1987,149:351-356.\u003c/li\u003e\n\u003cli\u003eNorth American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, et al. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis[J]. N Engl J Med,1991,325:445\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eBerrocal-Izquierdo N，Bioque M，Bemardo M．Is cerebrovascular disease a silent condition in patients with chronic schizophrenia-related disorders [J]. Int Clin Psychopharmacol，2017, 32(2):80-86.\u003c/li\u003e\n\u003cli\u003eZhihua Xu, Fangfei Li, Dengxiang Xing, Hongyan Song, Jingshu Chen, Yang Duan, Benqiang Yang. A Novel Imaging Biomarker for Cerebral Small Vessel Disease Associated With Cognitive Impairment: The Deep-Medullary-Veins Score. Front Aging Neurosci. 2021, 13:720481.\u003c/li\u003e\n\u003cli\u003eXuanting Li, Junliang Yuan, Wei Qin, Lei Yang, Shuna Yang, Yue Li, Wenli Hu. Total Burden of Cerebral Small Vessel Disease on MRI May Predict Cognitive Impairment in Parkinson\u0026apos;s Disease. J Clin Med. 2022,11(18):5381.\u003c/li\u003e\n\u003cli\u003eMengqi Yang, Jiahui Liang, Baohui Weng, Jinghong Liang, Tao Lu, Hong Yang. Total Cerebral Small Vessel Disease Burden Predicts the Outcome of Acute Stroke Patients after Intra-Arterial Thrombectomy. Cerebrovasc Dis. 2023,52(6):616-623.\u003c/li\u003e\n\u003cli\u003eSedat Yasin, Rabia Tasdemir. An Investigation of the Relationship Between Carotid Artery Stenosis and White Matter Hyperintensitie. Cureus. 2023,15(5): e39468.\u003c/li\u003e\n\u003cli\u003eTingting Zhong, Yunwen Qi, Rui Li, Huadong Zhou, Boli Ran, Jiao Wang, ZhiYou Cai. Front Neurol. 2022,13:922320.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Patient comparisons\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"574\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.679442508710801%\" valign=\"top\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.466898954703833%\" valign=\"top\"\u003e\n \u003cp\u003eAge（\u0026plusmn;𝑠）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.89198606271777%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eSex（n）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.73170731707317%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHypertension（n）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.80836236933798%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes（n）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.421602787456447%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eStroke（n）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.679442508710801%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.466898954703833%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.923344947735192%\" valign=\"top\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.278745644599303%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452961672473867%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.839721254355401%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.536585365853659%\" valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.885017421602788%\" valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.679442508710801%\" valign=\"top\"\u003e\n \u003cp\u003eECAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.466898954703833%\" valign=\"top\"\u003e\n \u003cp\u003e62.80\u0026plusmn;9.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.923344947735192%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.278745644599303%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452961672473867%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.839721254355401%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.536585365853659%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.885017421602788%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.679442508710801%\" valign=\"top\"\u003e\n \u003cp\u003eECAS+ICAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.466898954703833%\" valign=\"top\"\u003e\n \u003cp\u003e65.07\u0026plusmn;8.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.923344947735192%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.278745644599303%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452961672473867%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.839721254355401%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.536585365853659%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.885017421602788%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.679442508710801%\" valign=\"top\"\u003e\n \u003cp\u003eICAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.466898954703833%\" valign=\"top\"\u003e\n \u003cp\u003e62.92\u0026plusmn;8.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.923344947735192%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.278745644599303%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452961672473867%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.839721254355401%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.536585365853659%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.885017421602788%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.679442508710801%\" valign=\"top\"\u003e\n \u003cp\u003eNONE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.466898954703833%\" valign=\"top\"\u003e\n \u003cp\u003e62.17\u0026plusmn;9.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.923344947735192%\" valign=\"top\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.278745644599303%\" valign=\"top\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.452961672473867%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.839721254355401%\" valign=\"top\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.968641114982578%\" valign=\"top\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.536585365853659%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.885017421602788%\" valign=\"top\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eECAS, extracranial arterial stenosis; ICAS, intracranial artery stenosis; M, male, F, female.\u003c/p\u003e\n\u003cp\u003eP＞0.05\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Severe extracranial or intracranial artery stenosis, Occlusion, Large atherosclerotic cerebral infarction, Total cerebral small vessel disease scores, Fazekas scores","lastPublishedDoi":"10.21203/rs.3.rs-4825369/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4825369/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e There was a significant correlation between the large atherosclerotic extracranial artery stenosis (ECAS) or intracranial artery stenosis (ICAS) and the neuroimaging markers of cerebral small vessel disease (CSVD). Our objective was to investigate the effect of coexistence of severe extracranial and intracranial arterial stenosis or occlusion on CSVD in patients with ischemic stroke.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA total of 222 patients with LAA infarction with CSVD were included in this retrospective study, including 160 males and 62 females. All enrolled patients were divided into four groups: ECAS, ECAS+ICAS, ICAS and None. The differences between the four groups were evaluated by total CSVD scores, total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e There were significant differences between the four groups in terms of total CSVD scores (\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05). But there was no significant difference in the total Fazekas scores, periventricular WMH Fazekas scores and deep WMH Fazekas scores. Further pairwise comparison shows that only the ECAS+ICAS group and the none group had a significant difference in total CSVD scores (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe coincidence of severe stenosis or occlusion of the extracranial and intracranial artery may increase the incidence of CSVD and aggravate the performance of CSVD in patients with ischemic stroke and mainly reflected in the total CSVD scores. If ECAS and/or ICAS are found in patients, the total CSVD burden should be also actively assessed. To reduce the incidence of stroke and improve outcomes, active clinical intervention should be undertaken for these patients.\u003c/p\u003e","manuscriptTitle":"Effect of coincidence of severe extracranial and intracranial artery stenosis or occlusion on cerebral small vessel disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-23 12:19:47","doi":"10.21203/rs.3.rs-4825369/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a261e996-88bc-4a3f-82aa-cefd36fd49b8","owner":[],"postedDate":"August 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-09T12:40:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-23 12:19:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4825369","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4825369","identity":"rs-4825369","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}