| Part one:Clinical Analysis of Intracranial or Extracranial Atherosclerotic Artery StenosisBackground:Intracranial or extracranial atherosclerotic stenosis is common cause of ischemic stroke. Stroke patients with atherosclerotic artery stenosis also have higher risk for stroke recurrence than cardioembolic and small vessel origins. Cerebral artery stenosis can be classified to intracranial artery stenosis (IAS), extracranial artery stenosis (EAS) and combined artery stenosis (IC-EC), with variant epidemiology and prognosis in different locations. Previous studies have found significant ethnic variation in atherosclerotic stenosis. Extracranial stenosis is common in Whites, while intracranial stenosis is more prevalent among Asians, Blacks and Spanish. These differences may be caused by both genetic susceptibility and environment. Studies investigating this area often reported different results, probably caused by varying examinational means and diagnostic criteria. Exploring the epidemiologic characteristics and risk factors of these three distribution patterns with advanced examinational technologies is warranted. This study was aimed at analyzingthe vessel distribution characteristics in patients with atherosclerotic stenosis, and investigating different risk factors in these three distribution patterns.Methods:Acute ischemic stroke patient caused by large artery atherosclerosis (LAA) within 7 days of onset were included from Nanjing Stroke Registry Program (NSRP) between January 2013 and December 2014. All patients underwent digital subtraction angiography (DSA) to confirm the LAA diagnosis. Clinical characteristics, such as age, sex, BMI, hypertension, diabetes, TIA history, smoking and imaging data were collected.Results:A total of 711 patients were analyzed and 1607 stenosis lesions were identified, with 57.6% in anterior circulation and 69.8% in posterior circulation. The most often seen location was middle cerebral artery (22.7%), followed by intracranial internal carotid artery (ICA) and extracranial ICA. Combined stenosis was identified in 64.4% of patients. Compared with combined stenosis group, patients with single stenosis had higher rate of IAS (72.7% vs 54.8%, P<0.001). Univariate analysis found that age and diabetes were significantly different among IAS, EAS and IC-EC group (P<0.05). Ordinal logistic regression revealed that hyperhomocysteinemia was independent predictor for EAS, while diabetes was independent predictor for IC-EC. Conclusion:Our study found that IAS was prevalent in stroke patients caused by LAA in NSRP, with MCA stenosis most often seen. Age, diabetes and hyperhomocysteinemia were linked to different distribution patterns of stenosis. Based on golden diagnostic criteria (DSA) for cerebral artery, our study revealed the distribution models and risk factors of LAA in China. Our findings may be helpful to clinical diagnosis for LAA using advanced imaging technology.Part Two:Clinical Analysis of Symptomatic Vertebrobasilar Artery Stenosis and OcclusionBackground:Posterior circulation stroke caused by vertebrobasilar artery stenosis and occlusion accounted for 10-20% of all ischemic stroke. Posterior stoke has high mortality, especially for acute basilar occlusion. With the untypical, varying presentation and imaging difficulty for subtentorial lesions, studies of posterior stroke were far behind the anterior stroke. This situation has been improved with technology progress nowadays. However, studies investigating posterior stroke are limited in China. This study was aimed at analyzing the clinical characteristics, prognosis and risk factors of symptomatic vertebrobasilar artery stenosis and occlusion and to evaluate the predicting values of different scores for acute posterior stroke.Methods:Acute posterior stroke patient within 24 hours of symptom onset were included from Nanjing Stroke Registry Program (NSRP) between January 2013 and October 2015. All patients underwent MRI and cerebral angiograph to confirm the existence of vertebrobasilar artery stenosis or occlusion qualifying for the stroke event. The clinical characteristics and stenosis distribution were analyzed. The vertebrobasilar occlusion patients confirmed by DSA were further analyzed and divided into good and poor outcome group (90-day mRS<2 and>2). Risk factors, onset to presentation time, baseline NIHSS score, dual anti-platelet, pc-ASPECT score and posterior artery score were included for analysis. Predictive ability of different scores was evaluated with Receiver operating characteristic (ROC) curve.Results:A total of 297 patients were included for final analysis, with 78.5% presented with hypertension,43.4% with smoking history and 36.5% with diabetes. The most-often seen symptom was dizziness with/without visual rotation (44.1%), followed by limb weakness (37.4%) and speech difficulty (22.6%). Totally,440 stenosis or occlusion lesions were found, in which the three most prevalent locations were extracranial vertebral stenosis, intracranial vertebral stenosis and posterior cerebral artery. In secondary analysis,129 patients with vertebral or basilar occlusion were divided into good outcome group (70.5%) and poor outcome group (29.5%). Univariate analysis showed that baseline NIHSS, DWI-pc-ASPECT score and Posterior Circulation Vascular Score (PCVS) had statistic significance between the two groups. Multivariate regression model revealed that all the three factors were independently associated with 90-day outcome. The ROC-AUC analysis showed that both DWI-pc-ASPECT and PCVS had good predictive abilities in posterior stroke.Conclusion:Our study found that posterior circulation stroke caused by vertebrobasilar artery stenosis and occlusion were often presented with untypical and varying symptoms, confusing the patients’awareness and diagnosis. In patient with vertebral or basilar occlusion, baseline NIHSS, DWI-pc-ASPECT score and PCVS were independently associated with 90-day outcome. And DWI-pc-ASPECT and PCVS had good predictive abilities in posterior stroke. These results may be helpful in diagnosis and treatment for acute posterior stroke in clinical reality.Part Three:Gene Polymorphism in Intracranial or Extracranial Atherosclerotic Artery StenosisBackgrounds:Intracranial or extracranial atherosclerotic stenosis is prevalent in China, in which intracranial stenosis accounted for 33 to 50% of all ischemic stroke. Compared with extracranial atherosclerotic artery stenosis, intracranial stenosis is linked with higher mortality. Ethnic difference between intracranial or extracranial atherosclerotic stenosis indicated that genetic factor played an important role in this disease. Genetic susceptibility studies may help diagnosis and prevention of intracranial or extracranial atherosclerotic stenosis and lowering the incidence of acute cerebral events. This study was to investigate the association of RNF213 gene and risk and clinical characteristics of intracranial/extracranial atherosclerotic stenosis in Han population in China.Methods:Acute ischemic stroke patient within 7 days of symptom onset were included from Nanjing Stroke Registry Program (NSRP) between January 2013 and December 2014. All patients underwent digital subtraction angiography (DSA) to confirm the existence of large artery stenosis. Blood samples of all patients were collected for gene analysis, with three SNPs were selected (RNF213, rs11273543 and rsl48731719). Cases were matched for sex. age and region and compared by two subgroups:Large atherosclerotic stenosis/occlusion group vs. control group; intracranial atherosclerotic stenosis/occlusion group vs. control group.Results:In the large atherosclerotic stenosis/occlusion group vs. control group,711 patients and 677 control cases were included. Logistic regression model did not find any association between large atherosclerotic stenosis and RNF213, rs11273543 or rs148731719. In the intracranial atherosclerotic stenosis/occlusion vs. control group, 331 patients and 335 control cases were analyzed. Also, Logistic regression model showed that RNF213, rs11273543 or rs148731719 were non-significant between the two groups.Conclusion:This study did not found any correlation between RNF213, rs11273543 or rs148731719 SNPs and intracranial/extracranial atherosclerotic stenosis/occlusion in China. However, selecting high-risk patients for cerebral artery stenosis by genetic susceptibility may be helpful for monitoring and preventing acute ischemic events. Further studies are needed in this area. |
