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Background Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood–brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. Methods A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVD patients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. Results Of 178 SVD patients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVD patients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls ( P = 0.009, χ 2 test; P = 0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067–6.364; P = 0.036). Conclusion Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, whether ADMA levels are related to the risk of stroke in the Japanese general population remains unclear. Methods: We examined 769 Japanese men (mean age, 47±5years) undergoing health examinations. Each subject's ADMA level and various vascular risk factors were assessed; the predicted 10-year stroke risk was calculated using the point-based prediction model from the Japan Public Health Center Study. Results: In a multiple linear regression analysis, age, body mass index, estimated glomerular filtration rate, and current smoking status were significant independent determinants of ADMA levels. A significant odds ratio (OR) for high predicted stroke risk (10-year risk≥5%)was noted in the highest quartile of ADMA levels (OR, 2.47; 95% CI, 1.002–6.07), compared with the lowest quartile, after adjusting for potential confounding factors. A significant OR for high predicted stroke risk was also found for each standard deviation increment in ADMA level (adjusted OR, 1.46; 95% CI, 1.10–1.92). Conclusion: Elevated ADMA levels were significantly associated with an increased predicted stroke risk, suggesting that measuring ADMA levels may be useful for identifying middle-aged Japanese men with a high risk of stroke. [Copyright &y& Elsevier]

Abstract: Background: The vascular risk factors are associated with an increased risk for vascular cognitive decline (VCD), but also with Alzheimer disease (AD). Objective: To investigate vascular risk factors in relation to AD and VCD, with a non-invasive neurosonological methods in a clinical settings. Results: A total of 296 patients with AD and 237 patients with VCD were included in the study. Hypertension, hyperlipidemia, diabetes mellitus, stroke, and white matter changes (p<0.001) were significantly more prevalent in VCD, although they were also present in AD patients. No statistically significant differences were obtained between groups regarding coronary disease, atrial fibrillation, average degree of carotid artery stenosis and carotid intima-media thickness (cITM). However, the patients with AD had carotid artery stenosis “>50%” (p=0.007) and present plaques (p<0.001) more frequently compared to vascular group. The significant associations between robust cognitive measure and vascular factors, diabetes mellitus, carotid stenosis, cITM, and type of plaques were identified only in VCD, but not in AD group. Conclusions: The vascular risk factors were more prevalent in VCD group, although they were also present in AD. With few treatment options available in AD, it may be important not to neglect the vascular risk factors. [Copyright &y& Elsevier]

Abstract: Background: The CHADS2 score is a stroke risk stratification system for patients with atrial fibrillation (AF). The relationship between the pre-admission CHADS2 score and stroke severity or outcome was examined in AF-related cardioembolic stroke patients. Methods: 423 consecutive AF-related cardioembolic stroke patients (250 men, 173 women; aged 76±10years) were reviewed. Results: Pre-admission CHADS2 scores of 0, 1, 2, 3, 4, 5, and 6 were present in 4.3%, 21.0%, 34.3%, 23.6%, 11.8%, 4.5%, and 0.5% of patients, respectively. There were significant correlations (P<0.001) between CHADS2 and National Institutes of Health Stroke Scale (NIHSS) scores on admission, and CHADS2 and modified Rankin scale (mRS) scores at discharge. The optimal cutoff CHADS2 score for an mRS score ≥3 was ≥2 (sensitivity 84%, specificity 38%). For death, the optimal cutoff CHADS2 score was ≥3 (sensitivity 59%, specificity 62%). On multivariate analysis, a CHADS2 score ≥2 was independently associated with an mRS score ≥3 (OR 1.93, 95% CI 1.39–2.72, P<0.001), and a CHADS2 score ≥3 was independently associated with death (OR 1.46, 95% CI 1.02–2.11, P=0.038). Conclusions: The CHADS2 score is related to severity and outcomes of stroke in patients with AF. [Copyright &y& Elsevier]

Abstract: Background: Chronic kidney disease (CKD) is associated with higher stroke incidence, but little is known about the impact of CKD on mortality during stroke hospitalization, especially by CKD stage and index stroke type. This study assessed the effect of prevalent CKD on risk of dying in the hospital after a stroke. Methods: Data were obtained from all US states that contributed to the Nationwide Inpatient Sample. All patients identified by the International Classification of Diseases, Ninth Revision procedure codes (n=1,127,842) admitted to hospitals between October 2005 and December 2006 with a discharge diagnosis of stroke were included. Independent associations of CKD with in-hospital mortality following stroke were evaluated using multivariable logistic regression. Results: Of the sample, 64,985 (6%) had CKD, of which 5,785 (9%) died in the hospital. In multivariable analyses, CKD was associated with mortality overall (OR 1.63, 95% CI=1.52–1.75) and regardless of stroke type: ischemic stroke (OR 1.70, 95% CI=1.55–1.86), subarachnoid hemorrhage (OR 1.93, 95% CI=1.45–2.58), intracerebral hemorrhage (OR 1.28, 95% CI=1.10–1.49). Association between CKD and greater mortality was more pronounced in younger age groups (CKD*age interaction: p<0.0001) and in women vs. men (CKD*sex interaction: p<0.0001). Higher CKD stage was associated with greater mortality odds, but only with Stages 5 (OR 3.21, 95% CI: 2.09–4.92) and 6 (OR 2.92, 95% CI: 2.62–3.25) was this association of significance. Conclusions: Presence of CKD is independently associated with higher odds of dying during stroke hospitalization regardless of index stroke type. This adverse association is driven by severe CKD and is more pronounced in relatively younger persons and women. [ABSTRACT FROM AUTHOR]

Abstract: Background: Data on the determinants and outcome of ischemic stroke (IS) from the Arabian Gulf countries (AGC) are still scanty. The aim of this study was to characterize IS in six large stroke centers on the Arabian peninsula. Methods: IS subtypes were evaluated in four AGC from January 2006 to December 2007 in a large prospective multicenter hospital-based stroke registry including demographics, baseline risk factors, outcome and management. Results: A total of 780 patients with IS were included. Mean age was 58.9years (63.7% males). Large-artery atherosclerosis (LAA) (38.1%) was the most common subtype followed by lacunar stroke (LS)(34.7%), cardioembolic stroke (CE)(13.5%) and other determined causes (7%). LAA and CE were both more commonly observed over the age of 70. LAA showed a higher male preponderance, and the highest prevalence of hypertension, diabetes, obesity and ischemic heart disease among all subtypes. Obesity was a risk factor for both LAA and CE. Anterior circulation stroke was significantly more affected in LAA (21.2%), CE (19%) and LS (15.1%) subtype of stroke than in posterior circulation strokes (4.4%, 2.9% and 2.8%, respectively) (p<0.05). Only 0.8% of patients received thrombolysis. The 90-day outcome was worst in LAA and least affected in LS. The over-all 90-day mortality was 2.1%. Conclusions: Demographically, our data are different from those in Western registries but the distribution of stroke subtypes is comparable. Compared to Asian registries the ratio LS versus LAA was much lower. For the first time these data allow to study the IS profile in this population. [Copyright &y& Elsevier]

Abstract: Background: Uric acid has been known to exert neuroprotective effects by acting as a free radical scavenger; however, several observational studies indicated that high levels of serum uric acid increased the risk of cardiovascular events or stroke. We sought to determine whether increased levels of uric acid are associated with the presence of silent brain infarction (SBI). Methods: We recruited a consecutive series of non-stroke individuals who visited the Healthcare System in our hospital and underwent brain MRI (n=1577). We conducted intensive interviews and laboratory examinations, including serum uric acid. We examined associations between SBI and vascular risk factors including uric acid by controlling possible confounders. Results: Of the 1577 subjects recruited, 921 were men and 656 were women, and the uric acid level was much higher in the men (6.3±1.3) than in the women (4.7±1.0). There was a strong dose–response relationship between the quartiles of uric acid and the presence of SBI in women (p =0.001), but not in men. Multivariable analysis showed that the highest quartile of uric acid level was an independent risk factor for the presence of SBI in total patients (adjusted OR, 1.79; 95% CI, 1.11–2.91). However, this association remained significant in women (adjusted OR, 2.64; 95% CI, 1.17–5.91), but not in men. Conclusions: Our results suggest that an increased level of uric acid may be a risk factor for the presence of SBI. Serum uric acid level might be a good serum marker of underlying SBI or future stroke, especially in women. [Copyright &y& Elsevier]

Abstract: In order to evaluate progress in preventive therapeutic strategies, and to identify potential targets for improvement, it is essential to assess changes in the risk factors and preventive treatment of stroke over time. All of the strokes occurring within the population of Dijon, France (150,000 inhabitants), were prospectively ascertained from 1985 to 2004. Changes in stroke risk factors and preventive medications were analyzed by stroke subtypes. We recorded 725 lacunar infarcts (LI), 497 cardioembolic (CE) strokes, 2054 ischemic stroke from atheroma of large arteries or from other and undetermined causes (OIS), and 341 primary cerebral haemorrhages (PCH). Over the 20years, the prevalence of hypercholesterolemia increased whatever the stroke subtype (p <0.01) whereas that of diabetes only rose in LI and OIS stroke. The proportion of stroke patients on antiplatelet agents increased overall (p <0.01) and the proportion of patients on anticoagulants rose in CE stroke (p =0.01) and PCH (p <0.01). The proportion of patients on antihypertensive treatment only increased in CE stroke (p =0.01). The risk factor profile and the preventive treatments in stroke patients showed divergent variations over the 20years, according to the stroke subtype considered. These modifications certainly reflect changes in the therapeutic strategies for the preventive management of the population at risk. [Copyright &y& Elsevier]

Abstract: Background: The aims of this study were to clarify the risk factors for stroke, and to investigate the effect of low-density lipoprotein cholesterol (LDL-C) lowering with pravastatin on the risk of stroke, in Japanese mild-to-moderately hypercholesterolemic patients enrolled in the MEGA Study. Methods: Multivariate Cox proportional hazard model was used to determine the baseline risk factors for stroke. The proportion of treatment effect (PTE) explained by on-treatment LDL-C levels was estimated. Results: In 7832 patients at risk, a total of 99 strokes were observed during the 5-year follow-up period. Significant relationships were observed between stroke and traditional risk factors such as male sex, advanced age, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a) (Lp[a]), hypertension, diabetes, obesity, and smoking. In the pravastatin group, hazard ratio (HR) for stroke adjusted by on-treatment lipid level was lower than the unadjusted value versus control (HR [95%CI], 0.48 [0.26–0.87] and 0.59 [0.38–0.92], respectively)—giving a negative PTE of −38.6% and suggesting that the risk reduction could not be explained by LDL-C lowering alone. Conclusions: Male sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin''s LDL-C-lowering effect alone, suggesting pleiotropic effects. [Copyright &y& Elsevier]

Abstract: Background: Vascular localization of symptomatic large artery atherosclerotic (LAA) stroke differs for unknown reasons by race-ethnicity. The metabolic syndrome (MetSD) is associated with higher atherosclerotic stroke risk and comprises abnormal risk factors that can vary by race. Thus, we investigated whether MetSD may contribute to race-ethnic differences in LAA stroke by examining the association of MetSD with symptomatic intra- and extracranial atherosclerosis among a diverse race-ethnic group. Method: We analyzed data prospectively collected over a 4-year period on subjects with ischemic stroke/TIA. Independent vascular risk factor associations with intracranial and extracranial LAA vs. non-LAA mechanism were evaluated in two groups stratified by race-ethnicity; whites and non-whites (Hispanics, African-American, and Asian-American). Results: 1167 patients met study criteria. Intracranial LAA was more prevalent in non-whites vs. whites (20.4% vs. 9.6%, P <0.001), while extracranial LAA had a more frequent point value in whites compared to non-whites (10.7% vs. 7.5%, P =0.267). The presence of MetSD was more prevalent in both intracranial and extracranial LAA group than in non-LAA group: no significant differences were observed in the prevalence of MetSD between intra vs. extracranial LAA or whites vs. non-whites. However, with increasing numbers of abnormal metabolic components, whites were more likely to have experienced extracranial LAA, whereas non-whites were more likely to have experienced intracranial LAA. After adjusting for covariates, MetSD was associated with extracranial LAA in whites (OR, 1.98; 95% CI, 1.13–3.45), while there was a tendency that intracranial LAA was associated with MetSD in non-whites (OR, 1.80; 95% CI, 0.97–3.32). No association was found between MetSD and extracranial LAA in non-whites and between this syndrome with intracranial LAA in whites. Conclusions: Our results showed that the impact of MetSD on the distribution of cervicocephalic atherosclerosis differed by race-ethnicity. This finding may in part explain the well-known differences in race-ethnic predilection to intracranial or extracranial atherosclerosis. [Copyright &y& Elsevier]

Abstract: Background and purpose: Apolipoprotein E (apoE) polymorphism is suggested to be a risk factor in stroke in some populations, either by affecting lipid parameters or independently. Its effect on lipoprotein(a) [Lp(a)] is not known. The roles of apoE polymorphism and of high Lp(a) levels in atherosclerotic stroke (AS) in the Turkish population are unclear. Our aim was to investigate the relationship of apoE alleles and Lp(a) level with AS and the relationship of apoE alleles with Lp(a) and other lipid parameters. Methods: ApoE polymorphisms and lipid parameters were prospectively evaluated in 85 patients and 77 controls with normal brain imaging. Results: Only hypertension, diabetes mellitus, associated vascular diseases and decreased high-density lipoprotein cholesterol levels were found to be independent risk factors for stroke. However, in the presence of apoE/E4 allele, increased low-density lipoprotein cholesterol (LDL-chol), apolipoprotein B (apoB) and Lp(a) levels and in the presence of apo E/E3 allele, only Lp(a) levels were determined as risk factors. Conclusion: This study showed that while apoE polymorphism was not a risk factor itself, high Lp(a), LDL-chol and apoB were determined to be risk factors in E3 or E4 carriers. [Copyright &y& Elsevier]

Abstract: Background: There are conflicting data on the relationship between peripheral arterial disease (PAD) as defined by an ankle–brachial index (ABI) of <0.9 and stroke risk, and these prior data have largely focused on a single race or gender. Furthermore, the association between subsequent ABIs above the established 0.9 threshold for PAD vs. stroke has not been studied. This study assessed stroke occurrence across the full spectrum of ABI values among a broad cohort of stroke survivors. Methods: Data from the National Health and Nutrition Examination Survey from 1999–2004, a nationally representative sample of United States adults, were used to assess prevalence of PAD as evidenced by ABI of <0.9, and to simultaneously identify the independent associations of ABI levels (<0.90, 0.90–0.99, 1.00–1.09, >1.3) with stroke prevalence. Results: Among 6382 adults, 4602 (72%) had full and complete data of which 277 (6%) reported stroke occurrence. Stroke survivors were older and more likely to have diabetes, hypertension, coronary artery disease, elevated blood pressure and glycohemoglobin, than non-stroke respondents. More subjects with ABI <0.9 vs. ≥0.9 had experienced a stroke (12.7% vs. 5.4%, p<0.001). Within the full ABI range, stroke presence rose with decreasing ABI (p =0.0013). After adjustment for potential confounders, only ABI <0.9 (OR 1.9, 95% CI=1.2–3.1) and 0.9–0.99 (OR 2.3, 95% CI=1.4–3.6) compared with the referent group (1.10–1.29) were significantly associated with presence of stroke. Conclusions: Data from this nationally representative cohort support an independent relationship between established PAD and stroke occurrence, but also indicate that even borderline PAD is strongly linked to stroke. [Copyright &y& Elsevier]

Mutations in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) an inherited small vessel disease leading to subcortical strokes and dementia. Since the vascular pathology is clearly defined, CADASIL may provide important insights into the mechanisms underlying lacunar infarcts, ischemic white matter changes, and vascular dementia. Evidence from different sources suggests a central role for vascular smooth muscle cells (VSMC) in the pathophysiology of the disease. This article gives a brief overview on the phenotypic spectrum of the disease and discusses some of the relevant disease mechanisms that lead from Notch3 mutations to ischemic infarcts. [Copyright &y& Elsevier]

Many studies have provided data showing that family history of stroke (FHS) is associated with an increased risk of stroke. The association of the FHS with the various stroke subtypes has not been adequately studied. The purpose of this study was to assess the association of the FHS with the two major stroke types (cerebral haematomas and ischaemic strokes) and the four stroke subtypes (cardioembolic, large artery disease, small artery disease, and undetermined) in a Greek population.The FHS was obtained from 421 consecutive acute stroke patients and from 239 matched control subjects. Positive FHS was observed in 49% of all stroke patients compared with 28% of the control subjects [adjusted OR=2.06 (95% confidence intervals (CI) 1.42–3.00)]. Haematomas, ischaemic strokes, and from the ischaemic strokes, both large and small artery disease strokes were strongly associated with positive FHS compared with the control subjects [adjusted OR=2.06 (95% CI 9–3.04), 2.07 (95% CI 1.09–3.91), 2.05 (95% CI 1.24–3.38), and 2.76 (95% CI 1.55–4.91), respectively]. There was no difference between maternal and paternal heritable contribution.In conclusion, FHS was found in this study to be an independent risk factor for all strokes combined, for each stroke type, and for the large and small-artery disease stroke subtypes, but not for the cardioembolic and undetermined stroke subtypes. [Copyright &y& Elsevier]

Abstract: An association between migraine and ischemic stroke has been observed for many years but exact mechanisms by which migraine can lead to stroke are currently still under investigation. Migraine is related to stroke in several ways. First, ischemic stroke can develop as a complication of an attack of migraine with aura (so called migraineous infarction). Second, epidemiological studies suggest that migraine with aura is a risk factor for ischemic stroke. Third, a patent foramen ovale (PFO) is a well known risk factor for stroke and on the other hand, seems to be associated with migraine with aura. The purpose of this review is to summarize the current literature linking the two neurological diseases: migraine and stroke. For many years, migraine and cerebral ischemic stroke have been linked together. The association between these two diseases is multidimensional and rather complex. [ABSTRACT FROM AUTHOR]

Abstract: The frequency and risk factors for intracerebral haemorrhage (ICH) after ischemic stroke are well-known. ICH frequency is increased by the use of antithrombotic or thrombolytic drugs. Several experimental studies have demonstrated a relationship between ICH and hypertension after fibrinolysis, but the optimal blood pressure levels in patients treated with recombinant tissue plasminogen activator (rTPA) are as yet unknown. We evaluated the role of blood pressure in patients with ischemic stroke treated with rTPA within 3h of symptom onset. We treated 86 consecutive patients admitted to our stroke unit between 2002 and 2008 and prospectively recorded the clinical and instrumental data in our stroke registry. We evaluated haemorrhagic complications by reviewing imaging findings. Blood pressure was recorded before rTPA and at 6, 12, 18, and 32h. Total cerebral haemorrhage occurred in eleven (12.7%) patients, and symptomatic intracerebral haemorrhage occurred in seven (8.1%). We failed to find a correlation between blood pressure levels and stroke severity at admission. High blood pressure levels correlated with a worse outcome. Systolic blood pressure was significantly higher in ICH patients relative to rTPA-treated patients without haemorrhagic complications (p<0.03). This study indicates that rTPA-induced haemorrhage is influenced by systolic blood pressure. More aggressive pharmacological reduction of hypertension during fibrinolysis and the subsequent 32h may reduce this complication. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the role of ACT gene polymorphism in primary spontaneous intracerebral hemorrhage (PSICH) and ischemic stroke (IS). Methods: 193 PSICH, 272 IS and 188 controls were included from the same geographical area. The demographic and clinical stroke risk factors were noted. PSICH was confirmed by CT and IS by MRI. The location of stroke and size were noted. ACT gene polymorphism was analyzed by polymerase chain reaction. The ACT genotype and allele frequency in PSICH, IS and controls were compared. Results: The age of the PSICH was 56.9±13years, IS 54±16.7years and controls 54.8±10years. 134 females were in study and 65 in control groups. In the controls the AA genotype was 30%, AT 51.1% and TT in 16% whereas these were 39.3%, 53% and 7.7% in PSICH and 34.6%, 53.3% and 12.1% in IS. The frequency of T allele in controls was 41.5%, PSICH 34.2% and IS 38.6%. There was no significant difference in genotype and allele frequency in PSICH, IS and controls as well as location and etiology of stroke. Interpretation: The ACT genotype and allele frequency are not different in Indian PSICH and IS compared to controls. [Copyright &y& Elsevier]

Abstract: Migraine is an independent risk factor for ischemic stroke, mainly in the subpopulation of women with migraine with aura who are younger than 45 years, particularly those that use estrogen containing oral contraceptives. Migraine however should be considered a benign condition as the absolute increase of stroke risk is small. Migraine is also associated with a high prevalence of cerebral white matter hyperintensities, occurring in the deep and periventricular white matter as well as infratentorial, mainly pontine. The pathogenesis and clinical significance of these hyperintensities is unclear. We do not know whether migraine may be considered a progressive disorder in a subset of patients because of accumulation of these hyperintensities over time. Studies on the relationship between migraine and cognitive functioning yielded conflicting results. Two recent studies have provided reassuring news for the migraine patient. A population-based twin study showed that a lifetime migraine diagnosis was not associated with cognitive deficits in middle-aged subjects. A long-term prospective study, assessing cognitive and memory changes in ageing individuals with and without a history of migraine, showed that migraineurs do not exhibit more decline on cognitive tests over time versus controls. Migraine is certainly not a recognized risk factor for (vascular) dementia. [Copyright &y& Elsevier]

Abstract: Several reports describe a potential association between prolonged flights and stroke. However, causes of travel-related stroke due to paradoxal embolism other than patent foramen ovale have not been previously reported. We here describe the case of a 44-year-old woman who presented with an acute anterior circulation stroke after a transoceanic flight. The patient received intravenous thrombolytic therapy, with complete recanalization of the anterior and middle cerebral arteries. Contrast transthoracic echocardiography was suggestive of an extracardiac right-to-left shunt. Both cardiothoracic CT and MR angiography revealed a single pulmonary arteriovenous malformation (PAVM) in the lower lobe of the right lung. No cardiac abnormalities were identified. Careful examination of the patient revealed telangiectatic skin lesions, and recurrent epistaxis was reported to occur in first-grade relatives. Genetic testing for hereditary haemorrhagic telangiectasia revealed no mutations in the endoglin and activin receptor-like kinase 1 genes. Intravascular embolization of the PAVM was performed and effective occlusion was later confirmed. To our knowledge, this is the first reported case of travel-related stroke associated with a PAVM. These should be considered in patients with stroke after prolonged flights, particularly when right-to-left shunt is detected and patent foramen ovale is ruled out. [Copyright &y& Elsevier]