Intracranial large artery disease in Alzheimer’s disease and vascular dementia among ethnic Asians

Background and purpose: An underlying vascular etiology underpins vascular dementia (VaD) and possibly Alzheimer’s disease (AD). Intracranial large artery disease (ICLAD) is a common site of disease among ethnic Asians, and carries a poor prognosis. We studied the prevalence of ICLAD among ethnic Asian patients with AD and VaD. Methods: We recruited patients with AD and VaD from a retrospective review of consecutive ethnic Asian patients presenting to our dementia clinic. ICLAD was evaluated by visual inspection of brain magnetic resonance angiography by two observers in consensus, and defined as >50% luminal narrowing. Results: There were 56 patients with probable AD and 47 with probable VaD. ICLAD was prevalent among 53% of VaD patients and 18% of AD patients. Conclusions: There is a relatively high burden of ICLAD among AD and VaD patients of Asian ethnicity. We suggest that ethnic Asian dementia patients are a potential group to investigate if ICLAD is associated with clinical symptoms or prognosis and if treatment strategies targeted at ICLAD retard the progression of cognitive impairment.     

Correlation between symptomatic, radiological and etiological diagnosis in acute ischemic stroke

OBJECTIVES: The aim of this study was to correlate with the symptomatic, radiological and etiological diagnosis in acute ischemic stroke. SUBJECTS AND METHODS: Two hundred and fifty patients with first-ever ischemic stroke within 24 h of onset were prospectively studied with 3-step diagnoses: 1) symptomatic diagnosis based on the Oxfordshire Community Stroke Project criteria (OCSP), 2) radiological diagnosis (CT or MRI) and 3) etiological diagnosis based on the Lausanne Stroke Registry criteria. RESULTS: Most of the patients with symptoms of total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI) and posterior circulation infarcts (POCI) had corresponding lesions on CT or MRI, while only 68% of lacunar infarcts (LACI) patients had small subcortical infarction (SSI). More than 60% of patients with TACI were classified into cardioembolism in the third diagnosis, while the etiology of PACI was either CE or large-artery atherosclerosis (LAA) in equal numbers. Only 58% of LACI patients were classified into small-artery disease (SAD) and 29% of them (30 cases) into LAA, of which 23 patients had lesions other than SSI. The positive predictive value of SAD in the combination of LACI and SSI was 0.78. The etiology of POCI was variable. CONCLUSION: Except for LACI, the symptomatic classification by OCSP corresponds well to the radiological diagnosis. The etiological diagnosis can be predicted by OCSP in TACI and PACI, but it is hard in POCI, and a number of LACI are due to LAA.     

Cognitive and functional impairments in ischemic stroke patients with concurrent small vessel and large artery disease

Background and purpose

Concurrent small vessel, intracranial and extracranial large artery disease (SLAD) is common in Asian but its impact on cognitive and functional outcomes is unclear. We aimed to evaluate the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD.

Methods

Chinese ischemic stroke patients with diffuse white matter lesions (WMLs) were recruited as part of the VITATOPS Trial. They were studied with MRI and MRA of brain. Various neuropsychiatric batteries were used to assess the cognitive functions.

Results

Totally 97 patients with acute ischemic stroke and diffuse WMLs were included, of whom 44 (45%) had SLAD. Patients with SLAD had lower Mini Mental State Examination (MMSE) when compared with the patients without SLAD. They had more behavioral symptoms and caused more stress in caregivers as assessed by the Neuropsychiatric Inventory (NPI). Multivariate regression analysis showed SLAD contributed significantly to MMSE, NPI Patient (NPI P) and NPI Care Giver (NPI CG). Among 44 patients with SLAD, 30 (68%) had severe cognitive impairment. They were older and less educated. They had more diabetes and poorer performance in neuropsychiatric tests including Mattis Dementia Rating Scale Initiation/Perseveration subset (MDRS I/P) and Clinical Dementia Rating (CDR). They also had poorer functional outcomes as assessed by Barthel Index (BI) and Instrumental activities of daily living (IADL).

Conclusions

This was the first MRA-based study to take into consideration the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD. Patients with SLAD had poorer cognitive and functional outcomes when compared to patients without SLAD.     

急性缺血性卒中血清超敏C-反应蛋白与改良TOAST分型和OCSP分型关系的研究

探讨急性缺血性卒中患者血清超敏C-反应蛋白(hs-CRP)表达变化与改良TOAST分型和OCSP分型之间的关系。实验室检测显示,缺血性卒中组患者血清hs-CRP表达水平高于正常对照组[(13.68±6.92)mg/L对(3.98±0.76)mg/L;t=6.922,P=0.002]。TOAST分型中以心源性栓塞型患者血清hs-CRP水平[(16.82±6.16)mg/L]最高,然后依次为动脉粥样硬化血栓形成型[(15.71±5.68)mg/L]、不明病因型[(10.06±3.89)mg/L]和小动脉型[(9.86±3.75)mg/L,P=0.027];OCSP分型由高至低分别为完全前循环梗死型[(17.02±6.98)mg/L]、后循环梗死型[(15.91±7.12)mg/L]、部分前循环梗死型[(12.83±4.95)mg/L]和腔隙性梗死型[(10.61±5.73)mg/L,P=0.005]。提示急性缺血性卒中患者血清hs-CRP表达水平在改良TOAST分型和OCSP分型各亚型中存在差异,可以此指导临床治疗和判断预后。     

Extracranial carotid artery disease in nasopharyngeal carcinoma patients with post-irradiation ischemic stroke

Objective

Irradiation induced extracranial carotid occlusive disease has been recognized as a potential cause of post-irradiation stroke in nasopharyngeal carcinoma (NPC) patients. Our study aims to investigate the prevalence of extracranial CA disease in post-irradiated Taiwanese NPC ischemic stroke patients.

Methods

Forty-three NPC patients with ischemic stroke were retrospectively selected from the stroke registration of the study hospital and compared with 276 first-ever ischemic stroke patients from the same database, of which 31 patients underwent carotid duplex sonography (CDS). Significant atherosclerotic lesions of the carotid arteries were defined as a >50% stenosis or an occlusion according to CDS.

Results

Significant carotid lesions occurred in 13 of 31 (42%) NPC patients. Stroke was more frequently caused by large artery disease (44% versus 23%; p < 0.01) in NPC patients than in first-ever stroke patients without NPC. Carotid artery disease (odds ratio 7.22, 95% confidence interval 2.51–20.77; p < 0.0001) and absence of diabetes mellitus (odds ratio 0.26, 95% confidence interval 0.07–0.93; p = 0.039) were the strongest independent discriminators between NPC stroke patients and non-NPC stroke patients in a multivariate logistic regression analysis.

Conclusion

Patients who received neck irradiation are at risk for the delayed development of diffused atherosclerosis but also for carotid occlusion within years, although the mechanism remains elusive and probably multifactorial.     

Subgroup differences in psychosocial factors relating to coronary heart disease in the UK South Asian population

Objectives

To explore the differences in psychosocial risk factors related to coronary heart disease (CHD) between South Asian subgroups in the UK. South Asian people suffer significantly higher rates of CHD than other ethnic groups, but vulnerability varies between South Asian subgroups, in terms of both CHD rates and risk profiles. Psychosocial factors may contribute to the excess CHD propensity that is observed; however, subgroup heterogeneity in psychosocial disadvantage has not previously been systematically explored.

Methods

With a cross-sectional design, 1065 healthy South Asian and 818 white men and women from West London, UK, completed psychosocial questionnaires. Psychosocial profiles were compared between South Asian religious groups and the white sample, using analyses of covariance and post hoc tests.

Results

Of the South Asian sample, 50.5% was Sikh, 28.0% was Hindu, and 15.8% was Muslim. Muslim participants were more socioeconomically deprived and experienced higher levels of chronic stress, including financial strain, low social cohesion, and racial discrimination, compared with other South Asian religious groups. In terms of health behaviors, Muslim men smoked more than Sikhs and Hindus, and Muslims also reported lower alcohol consumption and were less physically active than other groups.

Conclusion

This study found that Muslims were exposed to more psychosocial and behavioral adversity than Sikhs and Hindus, and highlights the importance of investigating subgroup heterogeneity in South Asian CHD risk.     

大动脉粥样硬化型与小动脉闭塞型青年缺血性卒中高危因素相关分析

目的探讨青年缺血性卒中两种不同病因分类亚型的高危因素的差别。方法收集北京大学第一医院神经内科(2006-2011年,18～45岁)缺血性卒中病人。入选66例,分为大动脉粥样硬化组(46例)及小动脉闭塞组(20例)。以性别、年龄、既往病史(包括高血压、糖尿病、长期大量吸烟、饮酒史)以及周围血检测(甘油三脂、低密度脂蛋白、高密度脂蛋白、同型半胱氨酸)研究变量。结果单变量分析发现大动脉粥样硬化组低密度脂蛋白升高率及甘油三酯升高率与小动脉闭塞组比较有显著性差异(P<0.05)。小动脉闭塞组血压升高率与大动脉粥样硬化组比较有显著性差异(P<0.05),其他高危因素比较差异无显著性意义(P>0.05)。logistic回归分析发现甘油三酯升高率(wald=4.372,95%CI 0.089-0.925,p=0.037)与大动脉粥样硬化性青年缺血性卒中有关。高血压(wald=4.764,95%CI 1.196-21.986,p=0.029)与小动脉闭塞性青年缺血性卒中有关。结论两种不同病因的青年缺血性卒中主要致病高危因素不同,大动脉粥样硬化型需要更好的调控血脂,尤其是甘油三酯,而小动脉闭塞型需要更好的控制血压。     

Frontal lobe atrophy is associated with small vessel disease in ischemic stroke patients

Background

The pathogenesis of frontal lobe atrophy (FLA) in stroke patients is unclear. We aimed to ascertain whether subcortical ischemic changes were more associated with FLA than with parietal lobe atrophy (PLA) and temporal lobe atrophy (TLA).

Methods

Brain magnetic resonance images (MRIs) from 471 Chinese ischemic stroke patients were analyzed. Lobar atrophy was defined by a widely used visual rating scale. All patients were divided into non-severe, mild–moderate, and severe atrophy of the frontal, parietal, and temporal lobe groups. The severity of white matter lesions (WMLs) was rated with the Fazekas’ scale. Clinical and radiological features were compared among the groups. Subsequent logistic regressions were performed to determine the risk factors of atrophy and severe atrophy of the frontal, parietal and temporal lobes.

Results

The frequency of FLA in our cohort was 36.9% (174/471). Severe FLA occurred in 30 (6.4%) patients. Age, previous stroke, and periventricular hyperintensities (PVH) (odds ratio (OR) = 1.640, p = 0.039) were independent risk factors of FLA. Age and deep white matter hyperintensities (DWMH) (OR = 3.634, p = 0.002) were independent risk factors of severe FLA. PVH and DWMH were not independent risk factors of PLA and TLA.

Conclusion

Frontal lobe atrophy in ischemic stroke patients may be associated with small vessel disease. The association between WMLs and FLA was predominant over atrophy of the parietal and temporal lobes, which suggests that the frontal lobe may be vulnerable to subcortical ischemic changes.     

Effects of cerebral small vessel disease on the outcome of patients with ischemic stroke caused by large artery atherosclerosis

Objective: Cerebral small vessel disease (CSVD) describes a syndrome of neuroimaging, pathological, and associated clinical features caused by small intracranial vascular lesions, which commonly coexists with large artery atherosclerosis (LAA) and has been identified as a major cause of motor impairment over time. In this review, we aim to summarize the relationship between CSVD and LAA, and discuss the effects of CSVD on the clinical outcome of patients with ischemic stroke caused by LAA.

Methods: We searched and scanned all the literature with the keyword cerebral small vessel disease, cerebral microbleeds, white matter hyperintensity, silent lacunar infarcts, enlarged perivascular spaces and stroke in the database of Pubmed and MEDLINE (from inception to 1 February 2015).

Results: Various imaging phenotypes of CSVDs have different influences on the clinical outcome of patients with LAA stroke. The total brain burden of CSVD can represent the cumulative effects of different MRI features of CSVD, which has predictive value for recurrent stroke after ischemic stroke. Better quantification of the total brain burden of CSVD may help stratify patients more effectively in clinical practice.

Discussion: CSVD can significantly influence the clinical outcome of stroke in patients with cerebral infarction caused by LAA, and the methods to capture whole brain CSVD burden cross the spectrum of changes in CSVD imaging features may be useful for patient stratification in clinical trials. Further studies should be performed to validate the relationship between CSVD related brain damage and LAA stroke.     

彩色多普勒超声分析缺血性脑血管病患者颈内动脉狭窄血流动力学改变的临床价值

目的应用彩色多普勒超声(CDUS)分析缺血性脑血管病(ICVD)患者颈内动脉狭窄血流动力学改变的临床价值。方法对50例健康成人和48例ICVD患者,常规行颈动脉彩色多普勒超声检查,通过二维灰阶超声检查(2D)、彩色多普勒血流成像(CDFI)计算颈内动脉(ICA)最狭窄处直径狭窄率,脉冲多普勒(PD)测量颈动脉收缩期峰值流速(PSV)、舒张末期流速(EDV)、阻力指数(RI),计算ICA与颈总动脉(CCA)收缩期峰值流速比值(ICA-PSV/CCA-PSV)。诊断ICA狭窄程度与磁共振血管成像(MRA)进行对比。结果 ICA组ICA-PSV、ICA-PSV/CCA-PSV与对照组无明显差异(P>0.05);ICA-EDV明显低于对照组(P<0.05),而RI明显高于对照组(P<0.05)。本研究诊断ICA中、重度狭窄和闭塞的结果 ,与MRA诊断结果比较无明显统计学差别(χ2=0.1557,P>0.05)。结论 CDUS通过ICA血流动力学变化反映脑血管病变,有助于ICVD的鉴别诊断及预后判断,为早期采取有效的预防和治疗措施提供依据。     

Combination oral antiplatelet therapy may increase the risk of hemorrhagic complications in patients with acute ischemic stroke caused by large artery disease

Introduction

The association between the frequency or severity of bleeding complications and combination antiplatelet therapy for acute stroke treatment is not understood in detail. This retrospective study investigated whether combination oral antiplatelet therapy for cases with acute ischemic stroke due to large artery disease increased the incidence of hemorrhagic complications.

Materials and Methods

We reviewed 1335 consecutive patients who were admitted to our department within 7 days of the onset of an ischemic stroke or transient ischemic attack between April 2005 and November 2009. We enrolled 167 patients with > 50% stenosis or occlusion in culprit major vessels and who were administered oral antiplatelet agents within 48 hours of admission. Hemorrhagic complications were classified according to the bleeding severity index. We studied the association between the incidence and severity of hemorrhagic complications during hospitalization and the clinical characteristics, including antiplatelet therapy.

Results

Fifty-nine and 108 patients were treated with only 1 antiplatelet agent and combination antiplatelet agents, respectively. Fourteen patients developed bleeds (3 major and 11 minor), and all of the major bleeds occurred in those given combination agents. The proportion of patients receiving combination agents was significantly higher in those with significant bleeds. Multivariate logistic regression analysis revealed that being older and receiving combination agents were independent predictors for significant bleeds during hospitalization.

Conclusions

Despite the retrospective nature of this study, our findings suggest that the incidence of hemorrhagic complications increases in patients with acute ischemic stroke treated with combination antiplatelet agents.     

合并小血管病的颅内大动脉狭窄患者的预后

目的 探讨合并的小血管病(SVD)对颅内大血管动脉粥样硬化(ILAA)性卒中患者的远期预后影响.方法 前瞻性随访293例症状性ILAA患者,将之分为4组(组1为单个ILAA不伴SVD;组2为多个ILAA不伴SVD;组3为单个ILAA伴SVD;组4为多个ILAA伴SVD),观察随访期的卒中复发率和死亡率.结果 4组患者3年的累积卒中复发风险分别为18%、38%、21%和34%;3年累积死亡风险分别6%、7%、21%和22%.与组1相比,组2和组4的卒中复发率显著增高(P分别为0.05和0 014),组4的死亡率显著增高(P=0.002).Cox回归分析提示伴SVD是多发ILAA患者卒中复发和死亡的预示因子.结论SVD常与ILAA合并且与不良预后相关.     

缺血性脑血管病患者脑动脉狭窄与血压变异性的相关性

目的 探讨缺血性脑血管病患者脑动脉粥样硬化性狭窄与血压变异性的关系. 方法 选择自2006年11月至2010年6月在淮南市第一人民医院神经内科住院的206例缺血性脑血管病患者为研究对象,对患者进行连续主动脉弓+全脑血管造影检查,并作动脉血压监测.根据造影结果分组,并对其临床资料进行回顾性分析. 结果 (1)206例患者中75例颅内外动脉无狭窄,131例存在脑动脉狭窄,其中42例仅有颅外动脉狭窄,38例仅有颅内动脉狭窄,51例颅内外狭窄并存;颅外动脉狭窄的发生率(71.0％,93例)高于颅内动脉(67.9％,89例).(2)与颅内外动脉无狭窄组比较.单纯颅外动脉狭窄组、单纯颅内动脉狭窄组、颅内外动脉狭窄并存组24h平均收缩压、舒张压标准差,白昼平均收缩压、舒张压标准差,夜间平均收缩压、舒张压标准差均明显增大,差异有统计学意义(P＜0.05).(3)收缩压变异系数与脑动脉狭窄患病率成正相关(r=0.918,P=0.002),而舒张压变异系数与脑动脉狭窄发患病率无明显相关性(P＞0.05);24 h平均收缩压与脑动脉狭窄患病率成正相关(r=0.936,P=0.001),而24 h平均舒张压与脑动脉狭窄患病率无明显相关性(P＞0.05).(4)多元回归分析显示:24h平均收缩压、收缩压变异系数与颅内外动脉狭窄患病率呈明显正相关.(5)血脂异常是单纯颅内动脉狭窄的独立危险因素;高龄是单纯颅外动脉狭窄的独立危险因素;吸烟是单纯颅内动脉狭窄及单纯颅外动脉狭窄的独立危险因素;高血压是单纯颅外动脉狭窄及颅内外动脉狭窄并存的独立危险因素. 结论 在缺血性脑血管病患者中,脑动脉狭窄与平均血压标准差、收缩压变异系数独立相关.高血压、高脂血症、冠心病、吸烟、高龄、糖尿病和高同型半胱氨酸血症等危险因素与脑动脉狭窄的分布模式有一定关系.动脉血压变异性是缺血性脑血管病患者颅内外狭窄的独立危险因素,但与狭窄的分布模式无相关性.     

急性缺血性脑卒中患者脑白质病变与HbA1c水平的相关性分析

目的探讨初发急性缺血性脑卒中患者脑白质病变(cerebral white matter disease,WMD)的血管危险因素,及其与Hb A1c水平的相关性。方法纳入初发急性缺血性脑卒中患者,收集患者入院当时及入院后第2天的影像学资料和血生化检查资料,根据患者WMD分级标准将患者分为4级。详细记录患者的人口统计学资料,血管危险因素和FLAIR序列显示的WMD影像资料并进行比较和分析。结果共纳入512例首发急性缺血性脑卒中患者,其中男性320(62.5%)例,460(89.8%)例患者存在WMD,其中无WMD患者52例,轻度WMD患者205例,中度WMD患者139例,重度WMD患者116例。单变量分析显示,高龄、高血压、肾小球滤过率降低,Hb A1c水平降低,男性与WMD呈正相关(P0.05)。进一步的多变量Logistic回归发现,高龄、高血压和Hb A1c增高是WMD的独立危险因素。结论急性缺血性脑卒中患者Hb A1c增高是WMD的独立危险因素之一。     

缺血性脑血管病患者脑主要供血动脉狭窄分布的DSA分析

目的探讨缺血性脑血管病(ICVD)患者脑主要供血动脉狭窄分布特征。方法对2007-2009年诊治的脑主要供血动脉狭窄92例ICVD患者的临床和DSA资料进行回顾性分析。结果脑主要供血动脉颅外段病变发生率(82.6%)高于颅内段动脉(66.3%);多支动脉及前后循环同时病变的发生率较高(79.3%、57.6%);颈动脉系统常见狭窄部位是颈内动脉颅外段(57.6%)、大脑中动脉(34.8%),椎基底动脉系统常见狭窄部位是椎动脉颅外段(57.6%)、椎动脉颅内段(20.7%)。可干预危险因素越多,颅外合并颅内动脉狭窄的发生率越高,但无显著性差别(χ2=7.1;P=0.069)。结论 ICVD患者以颅外段动脉狭窄多见;颈动脉系统狭窄好发于颈内动脉颅外段、大脑中动脉,椎基底动脉系统好发于椎动脉颅外段。伴不同可干预危险因素组颅内合并颅内动脉狭窄的发生率无显著差异。     

Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study

BACKGROUND: Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD. METHODS: Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80-300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493). FINDINGS: Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index >or=85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and 73%vs 75%, respectively). INTERPRETATION: Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.     

Long-term mortality in ischemic stroke patients with concomitant chronic obstructive pulmonary disease

BackgroundLong-term mortality in ischemic stroke patients with concomitant COPD has been largely unexplored. This study aimed to compare long-term all-cause mortality in ischemic stroke patients with and without COPD.MethodsThis was a retrospective cohort study of ischemic stroke patients with and without COPD in the Geisinger Neuroscience Ischemic Stroke database to examine all-cause mortality up to 3 years using Kaplan-Meier estimator and Cox proportional hazards model.ResultsOf the 6,589 ischemic stroke patients included in this study, 5,525 (83.9%) did not have COPD (group A). Group B (n=1,006) consisted of patients with COPD diagnosis by ICD-9/10-CM codes. COPD patients in Group C (n=233) were diagnosed by spirometry, and in Group D (n=175) by both ICD-9/10-CM codes and spirometry confirmation. The survival probabilities at three years in Group B, C, and D were significantly lower than in Group A. Group B (HR=1.262, 95% CI 1.122–1.42, p<0.001) and group C (HR=1.251, 95% CI 1.01–1.55, p=0.041) had significantly lower hazard of mortality compared to group A. There was no significant difference in survival between COPD subtypes of chronic bronchitis and emphysema. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 stage had an increased mortality hazard compared to the GOLD 1 stage.ConclusionsWhile ischemic stroke patients with preexisting COPD have worse long-term survival than those without COPD, the results largely depended on the definition of COPD used. These results suggest that ischemic stroke patients with COPD need more personalized medical care to decrease long-term mortality.