Assessment of enlarged perivascular spaces and their relation to target organ damage and mild cognitive impairment in patients with hypertension.

BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) have been recently considered a feature of cerebral small vessel disease. They have been related to aging, hypertension and dementia but their relationship with hypertension related variables (i.e. target organ damage, treatment compliance) and mild cognitive impairment (MCI) is not fully elucidated. Our aims were to investigate the relation between basal ganglia (BG) and centrum semiovale (CSO) EPVS with vascular risk factors, hypertension related variables and MCI. METHODS: In all, 733 hypertensive individuals free of stroke and dementia from the Investigating Silent Strokes in Hypertensives, a magnetic resonance imaging Study (ISSYS) underwent brain magnetic resonance imaging and cognitive testing to diagnose MCI or normal cognitive aging. RESULTS: The numbers of participants presenting high grade (>10) EPVS at the BG and CSO were 23.3% and 40.0%, respectively. After controlling for vascular risk factors, high grade BG EPVS were associated with age (odds ratio 1.68; 95% confidence interval 1.37, 2.06), poor antihypertensive compliance (1.49; 1.03, 2.14) and the presence of microalbuminuria (1.95; 1.16, 3.28), whereas in the CSO only age (1.38; 1.18, 1.63) and male sex were associated with EPVS (1.73; 1. 24, 2.42). MCI was diagnosed in 9.3% of the participants and it was predicted by EPVS in the BG (1.87; 1.03, 3.39) but not in the CSO. This last association was greatly attenuated after correction for lacunes and white matter hyperintensities. CONCLUSIONS: Basal ganglia EPVS are associated with the presence of microalbuminuria and poor adherence to antihypertensive drugs. The BG EPVS relation with MCI is not independent of the presence of other cerebral small vessel disease markers.

Low ankle-brachial index predicts new vascular events and functional outcome after 1 year in patients with non-cardioembolic stroke: our experience and review.

BACKGROUND AND PURPOSE: The ankle-brachial index (ABI) has been defined as an important factor associated with vascular events. Our objective was to analyze the prognostic value of the ABI as a predictive factor of new vascular events and functional status at 1 year in patients with non-cardioembolic ischaemic stroke. METHODS: A prospective, longitudinal, observational and multicenter study was performed, including consecutive patients ≥ 50 years old who had suffered from a non-cardioembolic ischaemic stroke. Pathological ABI (PI) was defined when the value was ≤ 0.9. The logistic regression model, survival analysis and the Cox proportional hazard regression model were used to identify factors independently associated with functional outcome and occurrence of new vascular events, including recurrent stroke. RESULTS: In all, 977 patients were evaluated. The mean age was 69.1 ± 9.5 years. 40.5% patients had PI. Stroke recurrence and new vascular events global rates were 9% and 20% respectively at 1 year. PI was independently associated with new vascular events [hazard ratio 1.764 (1.274-2.444), P = 0.001]. A cut-off point of ABI ≤ 0.8 (14% vs. 7%, P = 0.002) independently predicted stroke recurrence in an adjusted regression model [hazard ratio 1.807 (1.102-2.963), P = 0.019]. PI was also associated with functional dependence [odds ratio 1.490 (1.011-2.196), P = 0.044]. CONCLUSIONS: In non-cardioembolic ischaemic stroke patients, PI was an independent predictive factor of new vascular events and functional outcome after 1 year of follow-up.

Cognitive assessment protocol design in the ISSYS (Investigating Silent Strokes in hYpertensives: a magnetic resonance imaging Study).

Hypertension and silent cerebrovascular lesions (SCL) detected by brain magnetic resonance imaging (MRI) are associated with an increased risk of cognitive decline. In a prospective observational study in 1000 hypertensive patients, aged 50-70 years, with no prior history of stroke or dementia, we will study the presence of mild cognitive impairment (MCI) and the relationship between SCL and cognition. All participants will be assessed by means of the Dementia Rating Scale-2 (DRS-2) and will undergo a brain MRI. In order to better characterize MCI and future dementia risk in our cohort, those patients that are suspected to be cognitively impaired according to the DRS-2 results will have a further neurological evaluation and complete neuropsychological testing. Follow-up for the entire cohort is planned to last for at least 3 years.

Biomarker level improves the diagnosis of embolic source in ischemic stroke of unknown origin.

The risk of recurrent stroke is likely related to etiology. Therefore it is important to identify which patients are at highest early risk. We evaluated whether selected blood biomarkers may aid in the diagnosis of stroke etiology. We studied consecutive non-lacunar stroke patients between November 2006 and January 2007, and selected undetermined origin strokes. Blood samples were drawn at arrival to test brain natriuretic peptide (BNP), D-dimer, CK-MB, myoglobin, and troponin. Second harmonic transthoracic echocardiography (SHTTE) and ECG-24 h monitoring were also performed within the first 24 h. We evaluated 294 patients with ischemic stroke; 89 had an initial undetermined origin. After a cardiological work-up, 49 were diagnosed as embolic including atrial fibrillation (4), severe aortic arch atheromatosis (24), severe wall abnormalities (12), valve disease (3), dilated cardiomyopathy (1), and patent foramen (5). Higher levels of CK-MB, BNP, and myoglobin were found in patients with embolic source in SHTTE, but only CK-MB >1.5 ng/ml and BNP >64 pg/ml remained as independent predictors: BNP (OR 8.86; CI 95 % 2.79-28.09), CK-MB (OR 6.28; CI 95 % 1.66-23.69). BNP showed specificity of 75 %, sensitivity of 63.4 %, and positive predictive value (PPV) of 75.6 %. CK-MB had specificity of 85 %, sensitivity of 47.9 %, and PPV of 79.3 %. Measuring both biomarkers improves the finding of embolic source, increasing specificity to 95 % and PPV to 88.2 %. High-level CK-MB and BNP during the acute phase of ischemic stroke are associated with an embolic source. Measurement of both biomarkers may improve the diagnosis, guiding the need to perform a heart exploration.

The gender gap in stroke: a meta-analysis.

UNLABELLED: Several studies have indicated that gender differences might exist in stroke. OBJECTIVES AND METHODS: Our goal was to perform a comprehensive meta-analysis in order to evaluate and quantify stroke gender disparities through a systematic search of relevant articles published up to October 2009 and addressing gender related differences in ischemic stroke risk factors, stroke subtype and severity, diagnostic tests, and acute phase and secondary prevention treatments. RESULTS: Forty-five articles were included in the analysis, representing a total of 673,935 patients. Women were globally older than men (+5.2 years) and suffered more hypertension (P = 0.017) and atrial fibrillation (P < 0.001), although they were less likely to drink alcohol (P < 0.001), smoke cigarettes (P < 0.001), present hyperlipidemia (P = 0.033) or diabetes (P = 0.003) than men. Baseline stroke severity was not different between genders. Women suffered more cardioembolic strokes, while men had more atherothrombotic strokes. Moreover, women were less likely to receive stroke-related treatments, such as antiplatelets (P < 0.001), statins (P < 0.001), and tPA (P < 0.001) than men. Although meta-regression did not identify age or stroke etiology as sources of heterogeneity, caution should be taken as that analysis was possible only for gender differences in secondary prevention with antiplatelets because of limited data for other end points. CONCLUSIONS: Gender differences have been identified on the risk factors profile and diagnostic and therapeutic management of patients with ischemic stroke. Active measures should thus be taken to avoid bias in clinical practice.

Reperfusion after stroke sonothrombolysis with microbubbles may predict intracranial bleeding.

BACKGROUND: Although ultrasound-activated microbubbles (MB) accelerate clot lysis, MB activation has shown to promote blood barrier disruption and bleeding in animal models. We conducted a case-control study aimed to investigate the risk of hemorrhagic transformation (HT) after MB-enhanced sonothrombolysis in acute stroke. METHODS: We evaluated a total of 296 patients with acute stroke treated with IV tissue plasminogen activator (tPA) <3 hours after stroke onset. One hundred eighty-eight patients received continuous 2-hour TCD monitoring plus 3 doses of 2.5 g of MB after tPA bolus (MB group). These patients were compared with 98 historic stroke patients (control group). The presence and extent of HT on 24-hour CT were blindly assessed. RESULTS: Recanalization rates were higher in the MB compared with the control group at 1, 2, 6, and 12 hours (p < 0.05). MB administration was associated with an increased risk of hemorrhagic infarction (HI)1-HI2 (21% vs 12%, p = 0.026) and a higher degree of clinical improvement at 24 hours (54.9% vs 31.1%, p = 0.004). Parenchymal hematoma (PH)1-PH2 and symptomatic intracranial hemorrhage rates were similar in both groups. Moreover, the extent of bleeding after MB-enhanced sonothrombolysis was correlated with the time to reperfusion. Early (<6 hours) recanalization independently predicted HI in the MB group (odds ratio 6.3, 95% confidence interval 2.3-56) but not in the control group. Delayed (>6 hours) or no recanalization was associated with PH1-PH2 in both the MB group (p = 0.024) and the control group (p = 0.045). CONCLUSION: This hypothesis-generating study shows that microbubble administration was associated with early recanalization and a high rate of hemorrhagic transformation but does not seem to increase the risk of symptomatic intracranial hemorrhage. However, definitive conclusions cannot be made based on these data.

Prognostic significance of blood pressure variability after thrombolysis in acute stroke.

OBJECTIVE: To evaluate the impact of early blood pressure (BP) changes on diffusion-weighted imaging (DWI) lesion evolution and clinical outcome in patients with stroke treated with IV tissue plasminogen activator (tPA). METHODS: We prospectively evaluated 80 patients with stroke with a documented middle cerebral artery occlusion treated with IV tPA. Multiple repeated systolic (SBP) and diastolic (DBP) BP measurements were obtained during 24 hours after admission. All patients underwent DWI, perfusion-weighted imaging, and magnetic resonance angiography before and 36-48 hours after thrombolysis. Recanalization was assessed on transcranial Doppler at 6 hours of stroke onset. NIH Stroke Scale scores were recorded at baseline and 24 hours. Modified Rankin Scale was used to assess 3-month outcome. RESULTS: Recanalization occurred in 44 (55%) patients. BP variability, estimated as the SD of the mean, was associated with DWI lesion growth (r = 0.46, p = 0.0003 for SBP and r = 0.26, p = 0.02 for DBP), early clinical course (p = 0.06 for SBP and p = 0.01 for DBP), and 3-month outcome (p = 0.002 for SBP and 0.07 for DBP). However, the prognostic significance of BP changes differed depending on the presence of recanalization. SBP variability emerged as an independent predictor of DWI lesion growth (beta: 6.9; 95% CI, 3.2 to 10.7, p = 0.003) and worse stroke outcome (OR: 11; 95% CI: 2.2 to 56.1; p = 0.004) in patients without recanalization, but not in recanalized patients. CONCLUSION: Blood pressure variability is associated with greater diffusion-weighted imaging lesion growth and worse clinical course in patients with stroke treated with IV tissue plasminogen activator. However, its impact varies depending on the occurrence of early recanalization after thrombolysis.