Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cogniti...Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.展开更多
We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospectiv...We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.展开更多
Thromboxane A synthase 1 （TBXAS1） catalyses the synthesis of thromboxane A2 （TXA2）, which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene ...Thromboxane A synthase 1 （TBXAS1） catalyses the synthesis of thromboxane A2 （TXA2）, which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls （P 〈 0.01 and P = 0.02）. Furthermore, compared with the GG ＋ GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke （odds ratio （OR） = 1.80, 95% confidence interval （CI）： 1.16–2.79, P 〈 0.01）. Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke （OR = 1.94,95% CI ： 1.13–3.33, P = 0.02）. The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis （OR = 1.49, 95% CI： 1.10–2.00, P 〈 0.01）. These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry （registration number： ChiCTR-COC-17013559）.展开更多
Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)iso...Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by prom展开更多
Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of t...Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ),the Shape Trail Test(STT),and the Stroop Color and Word Test(SCWT)to investigate the differences in cognitive performance between these two subtypes of SSI.Methods:Patients with acute SSIs were prospectively enrolled.The differences of MoCA-BJ,STT,and SCWT between the BAD group and CSVD-related SSI group were analyzed.A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function.We investigated the correlations between MoCA-BJ,STT,and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A(STT-A)and STT-B to identify cognitive impairment in patients with SSI.Results:This study enrolled a total of 106 patients,including 49 and 57 patients with BAD and CSVD-related SSI,respectively.The BAD group performances were worse than those of the CSVD-related SSI group for STT-A(83[60.5-120.0]vs.68[49.0-86.5],P=0.01),STT-B(204[151.5-294.5]vs.153[126.5-212.5],P=0.015),and the number of correct answers on Stroop-C(46[41-49]vs.49[45-50],P=0.035).After adjusting for age,years of education,National Institutes of Health Stroke Scale and lesion location,the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.Conclusions:BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language,attention,executive function,and memory.The mechanism of cognitive impairment after BAD remains unclear.展开更多
Using the Trial of Org 10172 in Acute Stroke Treatment （TOAST） classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction wer...Using the Trial of Org 10172 in Acute Stroke Treatment （TOAST） classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.展开更多
The G-protein-coupled purinergic receptor P2Y2(P2RY2) plays an important role in the mechanism of atherosclerosis, which is relevant to ischemic stroke. This retrospective case-control study aimed to assess the relati...The G-protein-coupled purinergic receptor P2Y2(P2RY2) plays an important role in the mechanism of atherosclerosis, which is relevant to ischemic stroke. This retrospective case-control study aimed to assess the relationship between P2RY2 gene polymorphisms and ischemic stroke risk in the northern Han Chinese population. In this study, clinical data and peripheral blood specimens were collected from 378 ischemic stroke patients and 344 controls. The ischemic stroke participants were recruited from the First Affiliated Hospital of China Medical University and the First Affiliated Hospital of Liaoning Medical University. The controls were recruited from the Health Check Center at the First Affiliated Hospital of China Medical University. Ischemic stroke patients were divided into two subgroups according to the Trial of ORG 10172 in Acute Stroke Treatment(TOAST) classification: large-artery atherosclerosis(n = 178) and small-artery occlusion(n = 200) strokes. All subjects were genotyped for three single nucleotide polymorphisms(rs4944831, rs1783596, and rs4944832) in the P2RY2 gene using peripheral venous blood samples. The distribution of the dominant rs4944832 phenotype(GG vs. GA+AA) differed significantly between small-artery occlusion patients and control subjects(odds ratio(OR) = 1.720, 95% confidence interval(CI): 1.203–2.458, P < 0.01). Multivariable logistic regression analysis revealed that the GG genotype of rs4944832 was significantly more prevalent in small-artery occlusion patients than in control subjects(OR = 1.807, 95% CI: 1.215–2.687, P < 0.01). The overall distribution of the haplotype established by rs4944831-rs1783596-rs4944832 was significantly different between ischemic stroke patients and controls(P < 0.01). In ischemic stroke patients, the frequency of the G-C-G haplotype was significantly higher than in control subjects(P = 0.028), whereas the frequency of the T-C-A haplotype was lower than in control subjects(P = 0.047). These results indicate that the G-C-G haplotype of P2RY2 is a susce展开更多
Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the presen...Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.A展开更多
Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric symptoms.The brain damage,seen as focal wh...Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric symptoms.The brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(MRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms.Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of SVD.In this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on MRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions.The core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’approach.This approach should integrate clinical expertise in stroke neurology,cognitive,and physical dysfunctions.It requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions.An essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.展开更多
脑小血管病（cerebral small vessel disease，CSVD）是指颅内小血管病变所致临床、认知、影像学及病理表现的综合征。由于CSVD发病隐匿、病因不明、临床表现多样、短期预后较好，因此易被忽视，造成误诊、漏诊和不规范的诊疗。文章就C...脑小血管病（cerebral small vessel disease，CSVD）是指颅内小血管病变所致临床、认知、影像学及病理表现的综合征。由于CSVD发病隐匿、病因不明、临床表现多样、短期预后较好，因此易被忽视，造成误诊、漏诊和不规范的诊疗。文章就CSVD的临床表现、影像学特征、诊断和治疗进展进行了综述。展开更多
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.A2015160)
文摘Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.
基金supported by the National Key Research and Development Program of China(2016YFB1001402)National Natural Science Foundation of China(81971138)+2 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)(2017-I2M-3-008)Strategic Priority Research Program(Pilot study)“Biological basis of aging and therapeutic strategies”of the Chinese Academy of Sciences(XDPB10)Research Foundation for Young Scholars of Peking Union Medical College Hospital(PUMCH201911275)。
文摘We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.
基金supported by a grant from the National Natural Science Foundation of China,No.81070913
文摘Thromboxane A synthase 1 （TBXAS1） catalyses the synthesis of thromboxane A2 （TXA2）, which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls （P 〈 0.01 and P = 0.02）. Furthermore, compared with the GG ＋ GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke （odds ratio （OR） = 1.80, 95% confidence interval （CI）： 1.16–2.79, P 〈 0.01）. Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke （OR = 1.94,95% CI ： 1.13–3.33, P = 0.02）. The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis （OR = 1.49, 95% CI： 1.10–2.00, P 〈 0.01）. These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry （registration number： ChiCTR-COC-17013559）.
基金supported by the NIH grants,R01 NS111801(to ZGZ)American Heart Association 16SDG29860003(to YZ)。
文摘Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by prom
基金supported by grants from the 1·3·5 project for disciplines of excellence,Clinical Research Incubation Project,West China Hospital,Sichuan University(No.2020HXFH012)the National Natural Science Foundation of China(Nos.82071320 and 81870937)。
文摘Background:Single subcortical infarction(SSI)is caused by two main etiological subtypes,which are branch atheromatous disease(BAD)and cerebral small vessel disease(CSVD)-related SSI.We applied the Beijing version of the Montreal Cognitive Assessment(MoCA-BJ),the Shape Trail Test(STT),and the Stroop Color and Word Test(SCWT)to investigate the differences in cognitive performance between these two subtypes of SSI.Methods:Patients with acute SSIs were prospectively enrolled.The differences of MoCA-BJ,STT,and SCWT between the BAD group and CSVD-related SSI group were analyzed.A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function.We investigated the correlations between MoCA-BJ,STT,and SCWT using Spearman’s correlation analysis and established cut-off scores for Shape Trail Test A(STT-A)and STT-B to identify cognitive impairment in patients with SSI.Results:This study enrolled a total of 106 patients,including 49 and 57 patients with BAD and CSVD-related SSI,respectively.The BAD group performances were worse than those of the CSVD-related SSI group for STT-A(83[60.5-120.0]vs.68[49.0-86.5],P=0.01),STT-B(204[151.5-294.5]vs.153[126.5-212.5],P=0.015),and the number of correct answers on Stroop-C(46[41-49]vs.49[45-50],P=0.035).After adjusting for age,years of education,National Institutes of Health Stroke Scale and lesion location,the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.Conclusions:BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language,attention,executive function,and memory.The mechanism of cognitive impairment after BAD remains unclear.
基金the Natural Science Foundation of Guangdong Province, No. 10151130001000001, S2011010004708the Science and Technology Projects of Guangdong Province, No. 2010Y1-C191
文摘Using the Trial of Org 10172 in Acute Stroke Treatment （TOAST） classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.
基金supported by the National Natural Science Foundation of China,No.81070913(to ZYH)
文摘The G-protein-coupled purinergic receptor P2Y2(P2RY2) plays an important role in the mechanism of atherosclerosis, which is relevant to ischemic stroke. This retrospective case-control study aimed to assess the relationship between P2RY2 gene polymorphisms and ischemic stroke risk in the northern Han Chinese population. In this study, clinical data and peripheral blood specimens were collected from 378 ischemic stroke patients and 344 controls. The ischemic stroke participants were recruited from the First Affiliated Hospital of China Medical University and the First Affiliated Hospital of Liaoning Medical University. The controls were recruited from the Health Check Center at the First Affiliated Hospital of China Medical University. Ischemic stroke patients were divided into two subgroups according to the Trial of ORG 10172 in Acute Stroke Treatment(TOAST) classification: large-artery atherosclerosis(n = 178) and small-artery occlusion(n = 200) strokes. All subjects were genotyped for three single nucleotide polymorphisms(rs4944831, rs1783596, and rs4944832) in the P2RY2 gene using peripheral venous blood samples. The distribution of the dominant rs4944832 phenotype(GG vs. GA+AA) differed significantly between small-artery occlusion patients and control subjects(odds ratio(OR) = 1.720, 95% confidence interval(CI): 1.203–2.458, P < 0.01). Multivariable logistic regression analysis revealed that the GG genotype of rs4944832 was significantly more prevalent in small-artery occlusion patients than in control subjects(OR = 1.807, 95% CI: 1.215–2.687, P < 0.01). The overall distribution of the haplotype established by rs4944831-rs1783596-rs4944832 was significantly different between ischemic stroke patients and controls(P < 0.01). In ischemic stroke patients, the frequency of the G-C-G haplotype was significantly higher than in control subjects(P = 0.028), whereas the frequency of the T-C-A haplotype was lower than in control subjects(P = 0.047). These results indicate that the G-C-G haplotype of P2RY2 is a susce
文摘Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.A
基金This work is supported by the UK Dementia Research Institute(JMW,CA)which receives its funding from DRI Ltd,funded by the UK MRC,Alzheimer's Society and Alzheimer's Research UKthe Fondation Leducq Network for the Study of Perivascular Spaces in Small Vessel Disease(JMW,16 CVD 05)+12 种基金The European Union Horizon 2020,SVDs@Target(JMW,FD,PHC-03-15,project No 666881)The Row Fogo Charitable Trust Centre for Research into Aging and the Brain(JMW)The British Heart Foundation(LACI-2 and Centre for Research Excellence,CS/15/5/31475,RE/18/5/34216)The Chief Scientist Office of Scotland(CZB/4/281,ETM/326,and Clinical Academic Fellowship UC,CAF/18/08)Chest Heart Stroke Scotland(Resl4/A157)NHS Research Scotland(FND)Stroke Association(Garfield Weston Foundation Senior Clinical Lectureship FND,TSALECT 2015/04‘Small Vessel Disease-Spotlight on Symptoms,FD,JMW,UC,SVD-SOSSAPG 19\100068R4VaD,JMW,FD,PMB,16 VAD 07Princess Margaret Research Development Fellowship,UC,2018Stroke Association Professor of Stroke Medicine PMB)PMB is a NIHR Senior Investigator.
文摘Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric symptoms.The brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(MRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms.Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of SVD.In this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on MRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions.The core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’approach.This approach should integrate clinical expertise in stroke neurology,cognitive,and physical dysfunctions.It requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions.An essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.
文摘目的探讨弥散加权成像（diffusion weighted imaging,DWI）阴性的急性缺血性卒中患者的临床特点、影像学表现、病因。方法回顾性分析自2012年1月~2014年7月首都医科大学附属北京天坛医院神经内科急诊溶栓绿色通道就诊的DWI阴性的疑似急性缺血性卒中患者,收集其人口学特征、临床表现、影像数据,进行病因学分类。结果连续收集134例溶栓医生初步判断为DWI阴性的疑似急性缺血性卒中患者,其中男性90例,女性44例,中位数年龄57岁（四分位数间距50~70）,从发病到完成DWI检查的中位数时间266.5 min（四分位数间距205.3~362.5）。中位数美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）评分2（四分位数间距1~3）。33例患者住院进一步诊治。有27例（81.8%）被诊断为缺血性卒中,另有6例（18.2%）诊断为其他疾病。27例诊断为缺血性卒中的住院患者中,9例（33.3%）经重新读片后发现缺血灶,5例（18.5%）症状加重后复查出现缺血灶,1例（3.7%）未加重但复查出现缺血灶,1例（3.7%）症状加重后复查DWI仍无缺血灶但有可以解释症状的磁共振血管成像（magnetic resonance angiography,MRA）大血管闭塞/狭窄或灌注加权成像（perfusion weighted imaging）低灌注区,6例（22.2%）虽DWI阴性但MRA有可以解释症状的大血管闭塞/狭窄或PWI有低灌注区,5例（18.5%）DWI阴性且未见大血管异常。诊断为缺血性卒中的27例患者,根据急性卒中治疗低分子肝素试验病因分型法（Trial of Org 10172 in Acute Stroke Treatment,TOAST）的分型标准,15例（55.6%）为大动脉粥样硬化,11例（40.7%）为小动脉闭塞,1例（3.7%）病因不明。住院患者中,除1例（3.0%）患者出院时明显残疾外,其余32例（97.0%）患者出院时结局良好。101例患者在急诊治疗后出院。其中80例（79.2%）DWI阴性且未见其他异常,5例（5.0%）经重新读片后发现缺血�
文摘脑小血管病（cerebral small vessel disease，CSVD）是指颅内小血管病变所致临床、认知、影像学及病理表现的综合征。由于CSVD发病隐匿、病因不明、临床表现多样、短期预后较好，因此易被忽视，造成误诊、漏诊和不规范的诊疗。文章就CSVD的临床表现、影像学特征、诊断和治疗进展进行了综述。
