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Background: Pre-treatment collateral status may be associated with the rates of successful revascularization in acute ischemic stroke patients receiving endovascular treatment (EVT). We conducted a systematic review and meta-analysis to synthesize relevant evidence currently available. Methods: Relevant full-text articles published in English since January 1, 2000, reporting associations between collateral status and successful reperfusion and/or recanalization in acute ischemic stroke patients receiving EVT in cohort or case-control studies, or randomized clinical trials, were retrieved through search of PubMed. Study selection, data extraction and study quality assessment were carried out by 2 investigators. Risk ratios (RR) were pooled for good vs. poor collaterals for the outcomes of successful reperfusion and recanalization, based on random-effects models. Subgroup analyses were conducted to explore for potential factors that might interfere with the effects of pre-treatment collateral status on reperfusion by EVT. Results: In total, 27 studies (2,366 subjects) were included in qualitative analysis, among which 24 studies (2,239 subjects) were quantitatively analyzed. Overall, good pre-treatment collaterals significantly increased the rate of both successful reperfusion (RR 1.28, 95% CI 1.17-1.40; p < 0.001) and recanalization (RR 1.23, 95% CI 1.06-1.42; p = 0.006), as compared with poor collaterals. Subgroup analyses revealed that the effects of collateral status on successful reperfusion by EVT might be different between populations with different ethnicities. Conclusions: Good pre-treatment collaterals may enhance the rates of successful reperfusion and recanalization in EVT for acute ischemic stroke. This may partly explain the favorable effects of good pre-treatment collaterals on clinical outcomes of stroke patients receiving EVT. Thus, it would be valuable to assess the collateral status prior to EVT in acute ischemic stroke. But studies are needed to further verify if the positive effects of good collaterals on revascularization by EVT are restricted to certain subgroups of patients.

Background: Apathy is common in stroke survivors. Unlike poststroke depression, apathy after stroke has not been extensively investigated and the significance of the location of infarcts in the development of apathy following a stroke is unknown. This study examined the association between poststroke apathy (PSA) and the location of infarcts. Methods: A cohort of 185 patients with acute ischemic stroke admitted to the Stroke Unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a psychiatrist administered the Apathy Evaluation Scale (AES). PSA was defined as an AES score of 37 or above. The presence and location of infarcts were evaluated with magnetic resonance imaging. Results: Altogether 185 patients met the entry criteria and formed the study sample; 20 (10.8%) had PSA. PSA patients were older and had higher stroke severity and more depressive symptoms. The PSA group also had lower levels of physical and cognitive functioning. Compared with the non-PSA group, PSA patients were more likely to have acute pontine infarcts (35.0% vs. 11.5%; p = 0.011). They had a higher mean number (0.5 ± 0.7 vs. 0.1 ± 0.3; p = 0.003) and larger volume (0.6 ± 1.4 vs. 0.1 ± 0.3 ml; p = 0.002) of acute pontine infarcts. Six variables were entered into the predictive regression model: age, the presence, number and volume of acute pontine infarcts, the number of old infarcts and periventricular white matter hyperintensities scores. The volume of infarcts remained an independent predictor of PSA in the multivariate analysis, with an odds ratio of 3.9 (p = 0.007). The Geriatric Depression Scale, National Institutes of Health Stroke Scale, Barthel Index and Mini-Mental State Examination scores were also entered into the subsequent associative regression model; the volume of acute pontine infarcts remained a significant predictor (odds ratio = 3.8). Conclusions: This is the first report of an association between pontine infarcts and the risk of PSA. The results suggest that pontine infarcts may play a role in the development of PSA. The importance of acute pontine infarcts in the pathogenesis of PSA warrants further investigation.

Background and Purpose: The purpose of this study was to evaluate the effect of metabolic syndrome on ischemic stroke in Chinese subjects with type 2 diabetes. Methods: Anthropometric parameters (waist circumference and body mass index), blood pressure, and plasma biochemical (lipid and glycemic profiles) were collected. Subjects with type 2 diabetes were categorized by the criteria of the updated Adult Treatment Panel III (ATP III) with the modified definitions of obesity in Asians. Transcranial Doppler was performed to define middle cerebral artery stenosis. Results: Of 2,197 patients (age 55.4 ± 11.3 years; male 40.8%; median follow-up period 8.7 years, interquartile range 7.8–9.5 years) without symptoms of cerebrovascular disease, evidence of middle cerebral artery stenosis was identified in 272 subjects (12.4%). According to NCEP ATP III criteria, 1,324 (60.3%) patients had MetS at baseline. Ischemic stroke occurred in 184 (8.4%, 184/2197) patients during follow-up. Patients with incident stroke had a higher prevalence of MetS compared with those without stroke (p = 0.004), and the number of components of MetS was also significantly increased in patients with stroke (p = 0.001). Cox regression demonstrated that MetS was not associated with incident stroke. Conclusions: In Chinese type 2 diabetic patients, metabolic syndrome does affect stroke occurrence with a higher stroke incidence among those with metabolic syndrome, but stroke occurrence seems to be better explained by other vascular risk factors than by metabolic syndrome.

Background and Purposes: Until now, limited data are available about the potential effect of coexisting small vessel disease (SVD) on the long-term outcome of stroke patients with intracranial large artery atherosclerosis (ILAA). Methods: A prospective study was performed on 293 patients with symptomatic ILAA, who were divided into 4 groups (group I, single intracranial large artery atherosclerosis (SILAA) without SVD; group II, multiple intracranial large arteries atherosclerosis (MILAA) without SVD; group III, SILAA with SVD; group IV, MILAA with SVD) and followed up for recurrent stroke or death. Results: The 3-year cumulative risks of recurrent stroke were 18% for SILAA without SVD, 38% for MILAA without SVD, 21% for SILAA with SVD and 34% for MILAA with SVD. The 3-year cumulative risks of death were 6, 7, 20 and 22%, respectively. Compared with SILAA without SVD, more recurrent stroke occurred in MILAA without SVD (log-rank 3.83; p = 0.050) and MILAA with SVD (log-rank 7.79; p = 0.014), and the higher risk of death (log-rank 9.472; p = 0.002) was found in group MILAA with SVD. A Cox proportional-hazards regression model showed that MILAA with SVD may be a predictor of recurrent stroke (hazard ratio 2.001; 95% CI 1.108–3.934; p = 0.044), and a borderline predictor for death (hazard ratio 3.180; 95% CI 0.895–10.987; p = 0.073). Conclusion: Coexisting SVD is very common and may predict poor outcome in stroke patients with symptomatic ILAA.

Background: Subclinical brain infarct (SBI) is associated with subsequent stroke and cognitive decline. A longitudinal epidemiological study suggests that statins may prevent development of SBI. We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis (ROCAS) study. Methods: The ROCAS study is a randomized, double-blind, placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years. A total of 227 subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study. The primary outcome measure was the number of new brain infarcts at the end of the study. Results: Among the 227 randomized subjects, 33 (14.5%) had SBI at baseline. At the end of the study, significantly fewer subjects in the active group (n = 1) had new brain infarcts compared with the placebo group (n = 8; p = 0.018). The new brain infarcts of subjects in the active group were subclinical. Among the placebo group, the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical. Among putative variables, multivariate regression analysis showed that only the baseline number of SBIs (OR = 6.27, 95% CI 2.4–16.5) and simvastatin treatment (OR = 0.09, 95% CI 0.01–0.82) independently predicted the development of new brain infarcts. Conclusions: Consistent with findings of the epidemiological study, our study suggests that statins may prevent the development of a new brain infarct.

Background: The progression of cerebral atherosclerosis increases the risk of stroke and vascular events. Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression, we studied the effects of statins on asymptomatic middle cerebral artery (MCA) stenosis progression. Methods: We conducted a randomized, double-blind, placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol (3.0–5.0 mmol/l). Two hundred and twenty-seven subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The severity of MCA stenosis at baseline and at the end of the study was graded by MRA into normal, minimal (90%). The primary outcome was the change in grading of MCA stenosis over 2 years. Results: At the end of the study, the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups, respectively (p < 0.001). There was no significant difference in the proportion of patients having stable, progressive and regressive MCA stenosis between the placebo (72, 22 and 6%) and active groups (78.6, 15.5 and 5.8%). The all-cause mortality was significantly lower in the active group (n = 0) relative to the placebo group (n = 7, p = 0.014). Any clinical events were also lower in the active group (n = 5) than in the placebo group (n = 13, p = 0.052). Conclusions: Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years.

Background: In Chinese populations, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion, and has been shown to be associated with an increased risk of secondary stroke mortality, but has yet to be reported for primary events. We assess whether asymptomatic MCA stenosis is associated with mortality in Chinese type 2 diabetic patients. Methods: The presence of MCA stenosis was determined by transcranial Doppler and mortality data were collated in the Hong Kong Death Registry. Cox proportional hazards regression was used to determine if the MCA stenosis (n = 272, 53.7% 2-vessel disease) in 2,197 diabetics was associated with all-cause or vascular disease mortality, including after adjustment for conventional vascular risk factors. Anthropometric and fasting biochemical parameters were compared between diabetic patients with MCA stenosis and without evidence of stenosis. Results: A total of 191 deaths were identified (30.9% of vascular disease origin) during a follow-up of 18,279 patient years over 8.32 years. After adjustment for age, gender and diabetes duration, the hazard ratios for vascular mortality for 1- and 2-vessel disease were 2.47 (95% CI = 1.13–5.38) and 4.47 (95% CI = 2.24–8.82), p < 0.001 for trend, for increasing vascular mortality with increasing severity of cerebrovascular involvement, but 0.81 (95% CI = 0.45–1.47) and 2.23 (95% CI = 1.45–1.47), p = 0.001 for trend, for all-cause mortality. For vascular mortality, further adjustments for anthropometric and fasting biochemical parameters, or existing disease and treatment history increased the hazard ratios for 1-vessel disease slightly but attenuated the risk for 2-vessel disease evidently, 2.81 (95% CI = 1.10–7.16) and 2.85 (95% = CI 1.11–7.33), p = 0.026. Conclusion: The presence of MCA stenoses was an independent predictor of vascular mortality in these diabetics. More aggressive treatment of risk factors in these subjects merits further evaluation.

Background: Atherosclerotic stenosis of large intracranial arteries, especially the middle cerebral artery (MCA), is a common cause of stroke in Chinese patients. We aimed to describe the morphological features of atherosclerotic stenosis in the MCA and to investigate their relationship with cerebral infarcts from a postmortem series. Methods: We studied the morphological features of the MCAs in consecutive postmortem adults aged 45 years or above. The following parameters were evaluated by a single observer blinded to the clinical history: (1) thickness of fibrous cap; (2) extent of lipid area; (3) degree of luminal stenosis; (4) presence of intraplaque hemorrhage, neovasculature, thrombus and calcification. A semiquantitative assessment of macrophage and T lymphocyte infiltration was made by immunohistochemical staining for CD68 and CD45RO. Results: Seventy-six cases were recruited. Atherosclerotic plaques of more than 40% cross-sectional area luminal narrowing stenosis were found in 69 MCAs (45.4%, 69/152). The results demonstrated that the degree of luminal stenosis, the percentage of the plaques containing more than 40% lipid area and the prevalence of intraplaque hemorrhage, neovasculature and thrombus were higher in those plaques associated with infarct, and the mean index of both CD45RO and CD68 was higher among those associated with infarct (p < 0.01). Binary logistic regression showed that stenosis (p = 0.003; odds ratio, OR = 1.050), lipid area (p = 0.048, OR = 1.698) and presence of neovasculature (p = 0.040, OR = 3.471) were independent risk factors of MCA infarcts. Conclusions: Luminal stenosis caused by atherosclerotic plaque, percentage of lipid area and presence of intraplaque neovasculature may play a key role in leading to ischemic stroke.

Backgrounds: Intracranial atherosclerosis is the commonest vascular lesion for ischemic stroke in Asians. Most research on risk factors for middle cerebral artery (MCA) stenosis has been conducted in symptomatic patients with ischemic stroke or transient ischemic attack. The present study aimed to investigate risk factors for MCA stenosis in an asymptomatic population in Rongqi County in Southern China. Methods: We assessed 1,068 asymptomatic subjects over 50 years of age by transcranial Doppler. Medical history documentation and investigation of biochemical markers were performed for each subject. Multivariant, unconditioned, logistic regression analyses were employed to assess the risk factors associated with MCA stenosis. Results: MCA stenosis was found in 63 subjects (5.9%). Male gender, advancing age, hypertension, diabetes and systolic blood pressure were significant risk factors for MCA stenosis (p < 0.001). Based on logistic regression analyses, 4 factors emerged as independent risk factors (p < 0.001) of MCA stenosis: male gender [95% confidence interval (CI) = 1.49–4.66, OR = 2.63], age (95% CI = 1.01–1.06, OR = 1.04), hypertension (95% CI = 4.57–18.35, OR = 9.16) and diabetes mellitus (95% CI = 3.09–11.29, OR = 5.9). Conclusion: MCA stenosis is relatively common among asymptomatic Chinese subjects. Male gender, advanced age, hypertension and diabetes mellitus are risk factors for MCA stenosis.

Background and Purpose: Cerebral vasoreactivity and collateral circulation are important protective mechanisms against cerebral ischemia. Previous studies suggest that the efficiency of these mechanisms can be reflected by extracranial arterial blood flow volume. Brain damage leading to neurological impairments can influence patients’ functional recovery after stroke. This study attempted to explore the potential value of poststroke extracranial arterial blood flow volume in the prediction of stroke patients’ functional outcome. Methods: We prospectively studied 362 consecutive patients who were hospitalized for recent acute strokes. All patients underwent extracranial arterial blood flow volume measurement of the carotid and vertebral arteries by color velocity imaging quantification within 3 days after admission. Their functional recovery was assessed 6 months after stroke. The effect of poststroke extracranial arterial blood flow volume on patients’ functional outcome was tested by multivariate ordinal regression after controlling for other independent variables. Significance was at p < 0.05. Results: Poststroke extracranial arterial blood flow volume together with age, prestroke modified Rankin scale, the National Institutes of Health Stroke Scale and diabetes mellitus had significant effects on the patients’ 6-month functional outcome as measured by the modified Rankin scale after controlling for other independent variables (p < 0.05). Conclusions: Poststroke extracranial arterial blood flow volume is an independent outcome predictor. The graded predictive power of this parameter is potentially more superior than other outcome predictors by allowing classification of stroke outcome according to the degree of severity. A large prospective study is thus warranted to investigate its clinical value in the management of stroke patients.

The presence of microembolic signals (MES) may indicate an increased risk of recurrent ischemic events in patients with stroke. The optimal management of such patients is uncertain. We report the effect of clopidogrel in addition to aspirin on the number of MES in a series of patients with ischemic stroke and transient ischemic attack (TIA) due to large-vessel disease.8 patients with either extracranial or intracranial artery stenosis were identified in 30-min MES studies by transcranial Doppler sonography as having MES. All patients were on antiplatelet therapy prior to baseline transcranial Doppler monitoring. The patients were subsequently treated with clopidogrel in addition to aspirin. Repeat MES studies were performed between day 3 and 7 with aspirin and clopidogrel.All patients were Chinese. The median interval time from symptom onset to initial MES study was 7 days (range of 2-30). MES donor sites included 4 severely stenosed or occluded internal carotid arteries and 4 stenosed middle cerebral arteries. The median MES number at baseline was 8 (range 3-51). Repeat MES studies showed a significant decrease in MES (p = 0.012, Wilcoxon signed ranks test). 4 patients had complete cessation of MES and all patients showed a decline in MES. No patient had recurrent strokes or bleeding complications.The rapid and significant decline of MES in our stroke and TIA patients suggests the possible efficacy of dual antiplatelet therapy with aspirin and clopidogrel in patients with MES and symptomatic large-artery occlusive disease. Randomized controlled trials should be conducted to confirm this preliminary observation.

Background: There are no data concerning the relative representation of clinical vascular risk factors and radiological lesions in cases that have been ruled in and ruled out for probable vascular dementia (VaD) according to NINDS-AIREN criteria. Methods: Three months after their index stroke, a psychiatrist interviewed patients and made a diagnosis of VaD according to both DSM-IV and NINDS-AIREN criteria for probable VaD. Patients who fulfilled the DSM-IV criteria for VaD were divided into two groups: those who were ruled in and ruled out according to NINDS-AIREN criteria as probable VaD. Demographic characteristics, vascular risk factors, clinical features of the index stroke and radiological findings were then compared between the two groups. Results: Of the 297 patients screened, 56 (18.8%) had a DSM-IV diagnosis of dementia. Among these demented patients, 55 (98.2%) and 22 (39.3%) fulfilled DSM-IV and NINDS-AIREN diagnosis of VaD, respectively. The concordance and level of agreement (kappa statistic) between DSM-IV and NINDS-AIREN diagnoses were 40% and 0.02, respectively. Reasons of failure to meet NINDS-AIREN criteria included the lack of temporal relationship between dementia and stroke (n = 20), the absence of focal neurological signs and/or radiological evidence of stroke (n = 6) and both of the above (n = 7). There was no significant difference between the above two groups in terms of demographic data, features of index stroke, vascular risk factors and CT scan findings, except that leukoaraiosis (p = 0.021) and bilateral lesions (p = 0.015) were more frequent in subjects diagnosed according to NINDS-AIREN criteria of probable VaD. The difference between these two groups with respect to the number of lesions was borderline for significance (p = 0.052). Conclusions: The use of NINDS-AIREN criteria for VaD for case selection in poststroke dementia research may exclude a number of subjects with VaD.

Background: The feasibility of a noninvasive evaluation of remodeling of the middle cerebral artery (MCA) by magnetic resonance imaging (MRI) was assessed. The results were correlated with magnetic resonance angiography (MRA) and transcranial color Doppler (TCD) findings. Methods: 26 patients (13 male and 13 female, age ranged from 46 to 82 years) who presented with symptoms of cerebrovascular accidents had TCD, MRA and MRI assessment of the MCA. The TCD and MRA findings of 40 MCAs accessible by TCD were correlated with the ratio of cross-sectional area of the vessel (VA), luminal area of the vessel (LA) and plaque load (PL). Results: The VA ratio and LA showed no correlation with TCD or MRA results. PL however was shown to be associated with both TCD and MRA. Conclusions: MRI could be used to assess remodeling in MCAs. PL was found to be associated with TCD and MRA findings.