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Patients with an acute basilar artery occlusion (BAO) have a high risk of long-lasting disability and death. Only limited data are available on functional outcome in elderly patients with BAO. Using data from the Basilar Artery International Cooperation Study, we aimed to determine outcomes in patients ≥75 years. Primary outcome measure was poor functional outcome (modified Rankin scale score 4-6). Secondary outcomes were death, insufficient vessel recanalization (defined as thrombolysis in myocardial infarction score 0-1) and symptomatic intracranial hemorrhage (SICH). Patients were divided into four age-groups, based on quartiles: 18-54, 55-64, 65-74, and ≥75 years. Outcomes were compared between patients ≥75 years and patients aged 18-54 years. Risk ratios with corresponding 95 % confidence intervals (CI) were calculated and Poisson regression analyses were performed to calculate adjusted risk ratios (aRR). We included 619 patients [18-54 years n = 153 (25 %), 55-64 years n = 133 (21 %), 65-74 years n = 171 (28 %), and ≥75 years n = 162 (26 %)]. Compared with patients aged 18-54 years, patients ≥75 years were at increased risk of poor functional outcome [aRR 1.33 (1.14-1.55)] and death [aRR 2.47 (1.75-3.51)]. Nevertheless, 35/162 (22 %, 95 % CI 15-28 %) of patients ≥75 years had good functional outcome. No significant differences between age groups were observed for recanalization rate and incidence of SICH. Although patients ≥75 years with BAO have an increased risk of poor outcome compared with younger patients, a substantial group of patients ≥75 years survives with a good functional outcome.

Background and Purpose: Improving stroke management, guideline adherence, and outcome is a global priority. Our aim was to examine trends in nationwide use of reperfusion therapy, stroke in-hospital management, and outcome., Methods: Data were based on the triennial 2-month period of the National Acute Stroke Israeli registry (February to March 2004, March to April 2007, April to May 2010). The registry includes unselected patients admitted to all hospitals nationwide. There were in total 6279 patients: ischemic stroke, 4452 (70.9%); intracerebral hemorrhage, 485 (7.7%); undetermined stroke, 97 (1.6%); and transient ischemic attacks, 1245 (19.8%)., Results: Overall use of reperfusion therapy for acute ischemic stroke increased from 0.4% in 2004% to 5.9% in 2010 (P<0.001; adjusted OR, 17.0; 95% CI, 7.5-38.7). Use of CT or MR angiography for ischemic events increased from 2.1% in 2004% to 16.6% in 2010 (P<0.001; adjusted OR, 9.7; 95% CI, 6.8-13.9). Overall use of antithrombotics and anticoagulation for atrial fibrillation did not differ between periods, whereas clopidogrel use increased nearly 3-fold to 41% and statin use nearly 2-fold to 68%. The relative odds of providing reperfusion therapy, using CT or MR angiography, and prescribing anticoagulants for atrial fibrillation were higher among hospitals with large as compared with small stroke patient volumes. In-hospital mortality after acute ischemic stroke decreased from 7.2% in 2004 to 3.9% in 2010 (P<0.001; adjusted OR, 0.7; 95% CI, 0.4-1.0), whereas there was no significant change in odds of poor functional outcome., Conclusions: Based on a nationwide stroke registry, use of reperfusion therapy, vascular imaging, and statins is steadily increasing, whereas in-hospital mortality is decreasing.

Background: Frontal-type cognitive deficits are common in patients with Parkinson disease (PD). The Frontal Assessment Battery (FAB) was developed to assess frontal lobe functions. However, many studies found that it also correlated with a variety of other general neuropsychological tests., Objectives: To evaluate whether the FAB has an added value over the Mini-Mental State Examination (MMSE) and other bedside neuropsychological tests in reflecting cognitive deficits in patients with PD., Methods: Seventy-two consecutive patients with PD underwent cognitive assessment including the FAB, the MMSE, and a variety of other neuropsychological tests. Correlations were examined using the Spearman's r., Results: Highly significant correlations were found between the total FAB score and tests of attention, executive functions, and memory. To evaluate the contribution of the FAB beyond that of the MMSE, partial correlation was used. Analyses revealed that the FAB still correlated with most of the tests. Dividing the patients according to the median MMSE score revealed that the high correlation between the FAB and the MMSE was preserved in the low MMSE group, while in the high MMSE group the correlation was relatively low. In the high MMSE group, the FAB correlated with 11 tests compared to the MMSE that correlated with one (P < .001), while in the low MMSE group the number of correlations was 13 versus 7, respectively (P = .05)., Conclusions: In our sample of patients with PD, the FAB correlated with dysfunction in a variety of cognitive domains including attention, memory, and executive functions. The FAB has an added value over the MMSE, particularly among nondemented patients, an advantage that can be used in clinical practice.

Background: The effect of combination of fibrate with statin on major adverse cardiovascular events (MACE) following acute coronary syndrome (ACS) hospitalization is unclear. The main aim of this study was to investigate the 30-day rate of MACE in patients who participated in the nationwide ACS Israeli Surveys (ACSIS) and were treated on discharge with a fibrate (mainly bezafibrate) and statin combination vs. statin alone., Methods: The study population comprised 8,982 patients from the ACSIS 2000, 2002, 2004, 2006, 2008 and 2010 enrollment waves who were alive on discharge and received statin. Of these, 8,545 (95%) received statin alone and 437 (5%) received fibrate/statin combination. MACE was defined as a composite measure of death, recurrent MI, recurrent ischemia, stent thrombosis, ischemic stroke and urgent revascularization., Results: Patients from the combination group were younger (58.1±11.9 vs. 62.9±12.6 years). However, they had significantly more co-morbidities (hypertension, diabetes), current smokers and unfavorable cardio-metabolic profiles (with respect to glucose, total cholesterol, triglyceride and HDL-cholesterol). Development of MACE was recorded in 513 (6.0%) patients from the statin monotherapy group vs. 13 (3.2%) from the combination group, p = 0.01. 30-day re-hospitalization rate was significantly lower in the combination group: 68 (15.6%) vs. 1691 (19.8%) of patients, respectively; p = 0.03. Multivariable analysis identified the fibrate/statin combination as an independent predictor of reduced risk of MACE with odds ratio of 0.54, 95% confidence interval 0.32-0.94., Conclusion: A significantly lower risk of 30-day MACE rate was observed in patients receiving combined fibrate/statin treatment following ACS compared with statin monotherapy. However, caution should be exercised in interpreting these findings taking into consideration baseline differences between our observational study groups.

Background: High cholesterol has been associated with better stroke outcomes. Conversely, a protective effect of prestroke statin use in the acute phase of stroke has been reported. The effect of low cholesterol on outcome in patients with and without prestroke statin treatment has not been studied. We assessed the association between low cholesterol and ischemic stroke short- and long-term outcomes and studied potential interactions with statin treatment in patients with a first-ever ischemic stroke in a prospective national registry., Methods: Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry with a first-ever stroke and no previous disability, dementia or cancer admitted in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were included (n = 1,895). Cholesterol levels ≤155 mg/dl (1st quintile) were defined as low cholesterol and patients treated with statins for at least 7 days before stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS ≥11), total anterior circulation infarction, poor functional outcome (defined as discharged to a nursing facility or modified Rankin Scale >3 or death), and mortality at discharge and at 3 years were the study outcomes. Associations between low cholesterol and outcomes at discharge were assessed separately in patients with and without prestroke statin treatment using multiple logistic regression analyses. Mortality at 3 years was assessed in a subset of 681 patients with Cox proportional hazard models., Results: Patients were 67.4 ± 13.5 years old on average; 43.1% were women. Low cholesterol was associated with higher rates of stroke risk factors. Controlling for age, sex, hypertension, diabetes, current smoking, ischemic heart disease, congestive heart failure and atrial fibrillation, low cholesterol was significantly associated with severe stroke, total anterior circulation infarction and poor functional outcome in patients with and without statin treatment. There were no interactions between low cholesterol and prestroke statin therapy in association with outcomes. Short- and long-term mortality rates were increased for patients with low cholesterol (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at discharge and 20.5% at 3 years). Adjusted mortality risks were increased for patients with low cholesterol; however, this finding was statistically significant only for patients not on statins before the stroke., Conclusions: Low cholesterol is associated with increased stroke severity and poorer functional outcome in patients with and without prestroke statin use. Low-cholesterol statin-naive patients show increased risks of mortality. 'Reverse epidemiology' in the association between cholesterol and outcome is possible in patients with ischemic stroke., (Copyright © 2012 S. Karger AG, Basel.)

Background: Reports on differences between patients with and without wake-up stroke are inconsistent. We studied the proportion, characteristics, and outcomes of wake-up ischemic stroke (IS) and estimated the number of potential candidates for reperfusion therapy in a national registry of hospitalized patients., Methods: IS patients in all three National Acute Stroke ISraeli (NASIS) registry periods (2004, 2007, and 2010; 2 months each) were included. In-hospital neurological complications, poor functional outcome (death, modified Rankin scale ≥ 2, or discharge to a nursing home), and in-hospital mortality were the study outcomes. Risks of poor outcomes were estimated with logistic regression analysis., Results: Wake-up IS was reported for 820/4,408 (18.6%) patients. Baseline characteristics were similar for patients with and without wake-up IS. ORs (95% CIs) for wake-up compared to non-wake-up IS were 1.2 (0.9-1.6) for neurological complications, 0.8 (0.7-0.98) for poor functional outcome, and 0.8 (0.5-1.2) for death. According to an estimated 20-40% prevalence of penumbra, wake-up stroke patients could add 3.7-7.4% to the number of patients potentially eligible for reperfusion therapy., Conclusions: Stroke on awakening is present in almost one fifth of IS patients. Characteristics and stroke outcomes are similar for patients with and without wake-up IS. Confirmation of a valid approach for the detection of wake-up stroke patients who can potentially benefit from reperfusion therapy is essential., (Copyright © 2012 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF) is a major risk factor of ischemic stroke. We tested whether the adoption of the CHADS(2) score in clinical guidelines has impacted treatment strategies for stroke prevention, and examined how AF affects stroke outcome., Methods: In the setting of two national surveys [National Acute Stroke Israeli Surveys; all patients hospitalized for stroke in Israel during February-March 2004, and March-April 2007] data of patients with and without AF were analyzed with respect to patient characteristics, use of anticoagulation, stroke severity, clinical course, and long-term outcome., Results: Of 3040 patients with acute ischemic stroke, 586 patients (19%) had a history of AF. Severe strokes on admission were significantly more frequent in patients with AF, as was the proportion of total anterior circulation strokes. Ischemic stroke associated with AF predicted poor outcome at discharge (adjusted OR 1.56; 95%CI 1.24-1.96) and higher mortality rates throughout follow-up. Among patients with a CHADS(2) score ≥ 2 prior to the index stroke and without known contraindications, 41% received anticoagulation. This proportion increased to only 62% after the index stroke, even after excluding patients with severe disability and no significant increase between 2004 and 2007 was detectable. Increasing age, in-hospital infectious complications, and unfavorable functional status at discharge were independently associated with decreased likelihood of receiving anticoagulation., Conclusions: In deviation from current recommendations and in spite of the introduction of CHADS(2) criteria, anticoagulation for stroke prevention remains underutilized, despite the particularly poor outcome of strokes associated with AF., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: A number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC., Methods: The study population comprised 510 patients with stable angina pectoris, mean age of 63 ± 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up., Results: CL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups (p=0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 ± 63 from baseline in the 1st (upper) quartile, and by 350 ± 44, 403 ± 41 and 480 ± 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes (p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups (p=0.4). Multivariate analysis demonstrated that only baseline TCS (p < 0.001), body mass index (p = 0.007) and age (p = 0.006) were independent predictors for the TCS changes., Conclusions: Longitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Intravenous tissue plasminogen activator (IV t-PA) for acute stroke is dosed by weight, which is typically estimated, and requires a multistep infusion, which may lead to administration errors. We evaluated the impact of dosing errors on outcome in the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Study. Using logistic regression, we investigated the relationship between actual weight-based dose (administered dose divided by actual weight, capped at 100 kg) and intracerebral hemorrhage (ICH) at 36 hours and likelihood of good recovery (modified Rankin score of 0 or 1) at 3 months. Estimated weight, actual weight, and total t-PA dose administered were available for 311 of 312 patients; 3 received only the bolus and were excluded. In multivariable logistic regression, there was no association between the risk of any ICH using actual dose as a continuous variable (P = .65), or when comparing the highest quintile of actual dose (>0.944 mg/kg) to the lower 4 quintiles (9.8% vs 10.9%; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.22-1.61; P = .31), adjusting for age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and changes on baseline computed tomography. Similarly, there was no association between likelihood of good outcome and actual dose as a continuous variable (P = .87), or when comparing the lowest quintile (<0.879 mg/kg) of actual dose to the 4 higher quintiles (44.3% vs 42.5%; OR, 1.08; 95% CI, 0.55-2.09; P = .83), adjusting for age, baseline NIHSS score, and time of onset to treatment. Our findings indicate that it is reasonable to estimate weight when administering IV t-PA for acute stroke, because dosing errors did not have a major impact on the risk of ICH or the likelihood of good outcome in the NINDS t-PA Stroke Study., (Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Two clinical risk scores, the Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores, have been proposed to predict the risk of intracerebral haemorrhage following thrombolysis in acute ischaemic stroke., Aims: To validate Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores as predictors of post-tissue plasminogen activator symptomatic intracerebral haemorrhage and asymptomatic intracerebral haemorrhage in an independent cohort., Methods: Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores were calculated for the cohort of tissue plasminogen activator-treated patients enrolled in the placebo arms of the SAINT-I and SAINT-II trials. The absolute risk of symptomatic intracerebral haemorrhage and asymptomatic intracerebral haemorrhage associated with each scoring system was determined. The overall predictive value was assessed using c-statistics., Results: Symptomatic intracerebral haemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator in the SAINT cohorts. The risk of symptomatic intracerebral haemorrhage was modestly greater, with higher Haemorrhage After Thrombolysis scores (0: 4.1%, 1: 4.1%, 2: 8.8%, 3: 12.5%, 4: 0%, 5: no subjects). Similar results were seen with the Multicentre Stroke Survey score (0: 0%, 1: 4.8%, 2: 2.3%, 3: 7.3%, 4: 6.3%). In logistic regression, the Haemorrhage After Thrombolysis score was associated with the risk of symptomatic intracerebral haemorrhage (odds ratio = 1.41 per point, 95% confidence interval: 1.05-1.89, P = 0.021) and asymptomatic intracerebral haemorrhage (odds ratio = 1.59 per point, 95% confidence interval: 1.33-1.92, P< 0.001). The Multicentre Stroke Survey score was modestly associated with the risk of symptomatic intracerebral haemorrhage (odds ratio = 1.43 per point, 95% confidence interval: 0.95-2.15, P = 0.084) and asymptomatic intracerebral haemorrhage (odds ratio = 1.63 per point, 95% confidence interval: 1.27-2.08, P < 0.001). The c-statistic was 0.59 for predicting symptomatic intracerebral haemorrhage and 0.61 for asymptomatic intracerebral haemorrhage for both the Haemorrhage After Thrombolysis and the Multicentre Stroke Survey scores., Conclusions: While both the Haemorrhage After Thrombolysis and Multicentre Stroke Survey scores were associated with a risk of symptomatic intracerebral haemorrhage, discriminatory ability was limited., (© 2010 The Authors. International Journal of Stroke © 2010 World Stroke Organization.)

C-reactive protein (CRP) is a plasma protein involved in inflammation. While its levels have been associated with stroke, cognitive impairment and depression, the association with clinical characteristics of Parkinson's disease (PD) is unknown. A total of 73 consecutive patients with PD (46 males, age 68.8 ± 11.5 years) were evaluated regarding motor as well as cognitive and psychiatric features of PD. Plasma CRP levels were determined and tests for associations with disease parameters were performed. The average level of CRP was 3.9 ± 4.1 μmol/L, and 45.2% of the patients (n = 33) had a level above 3.0 μmol/L. Patients in the high CRP group tended to be older (71.4 ± 9.2 vs. 66.7 ± 12.9 years; p = 0.08) and coronary artery disease (CAD) was more common (36 vs. 10%, p < 0.05) in the high CRP group, but no differences were found between the groups regarding gender, disease duration, levodopa dose, motor scores or most of the neuropsychiatric complications such as severity of depression, psychosis, dementia, cognitive decline or frontal lobe dysfunction. Reported depression (at present or in the past) was more common in the high CRP group (54.5 vs. 25%, p = 0.01). CRP levels in patients with PD are associated with a higher prevalence of CAD, but are not associated with PD duration or severity, or with neuropsychiatric complications other than reported depression.

Background: Data linking neighborhood socioeconomic status (SES) to stroke risk are scarce. We examined long-term stroke incidence according to neighborhood SES in a population-based cohort of patients hospitalized with first myocardial infarction (MI)., Methods: Consecutive patients aged 65 years or less, discharged from 8 hospitals in central Israel after incident MI in 1992-1993, were followed for stroke through 2005. Individual demographic, socioeconomic, and clinical data were obtained at study entry. We estimated neighborhood SES through a composite census-derived index developed by the Israel Central Bureau of Statistics., Results: During a median follow-up of 13 years, 196 incident ischemic strokes occurred in 1410 patients. Accounting for death as a competing risk, patients residing in disadvantaged neighborhoods had higher rates of ischemic stroke (cumulative survival estimates: 81%, 88%, and 89% in increasing tertiles of neighborhood SES). Upon multivariable adjustment for individual SES measures (including income, education, and employment), cardiovascular risk factors, MI characteristics and severity indices, and acute management, the overall hazard ratio for stroke in the lower versus upper tertile of neighborhood SES was 1.5 (95% confidence interval [CI] = 1.0-2.3); after 13 years, the adjusted absolute risk difference was 7.9 incident stroke cases per 100 participants with MI (95% CI = 1.7-14.1)., Conclusions: Poor neighborhood SES is associated with increased risk of ischemic stroke post-MI. The association is only partly attributable to individual SES and other baseline characteristics. The potential mechanisms for this association require further study.

Purpose of Review: Hyperglycemia is frequent in patients with cerebrovascular disease. This review article aims to summarize the recent evidence from observational studies that examined the adverse cerebrovascular effects of dysglycemic states as well as interventional studies assessing intensive management strategies for hyperglycemia., Recent Findings: In recent years, diabetes, prediabetic states and insulin resistance and their association with cerebrovascular disease were an important focus of research. The cerebrovascular consequences of these metabolic abnormalities were found to extend beyond ischemic stroke to covert brain infarcts, other structural brain changes and to cognitive impairment with and without dementia. Interventional studies did not reveal that more intensive management of chronic hyperglycemia and of hyperglycemia in the setting of acute stroke improves outcome. There is clear evidence, however, that the overall management of multiple risk factors and behavior modification in patients with dysglycemia may reduce the burden of cerebrovascular disease., Summary: Observational studies reveal the growing burden and adverse cerebrovascular effects of dysglycemic states. Currently available interventional studies assessing more intensive strategies for the management of hyperglycemia did not prove, however, to be effective. We discuss the current evidence, pathophysiological considerations and management implications.

Background: Chronic kidney disease (CKD) is associated with both a risk of adverse vascular outcome and a risk of bleeding. We have tested the hypothesis that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated with poor outcome and with larger hematoma volume., Methods: We examined the association between CKD and ICH characteristics and outcome within a prospective cohort study of consecutive patients hospitalized with an acute stroke and followed for 1 year. CKD was categorized by the estimated baseline glomerular filtration rate into moderate/severe impairment (<45), mild impairment (45-60) and no impairment (>60 ml/min/1.73 m(2))., Results: Among 128 patients with an ICH (mean age = 71.7 ± 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7% moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69-10.90) compared to patients with no impairment. The hematoma volumes [median (25-75%)] were 15.3 ml (5.4-37.5) in patients with no impairment, 16.6 (6.8-36.9) in mild impairment and 50.2 (10.4-109.1) in moderate/severe impairment (p = 0.009). The location of the hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39% with moderate/severe impairment (p = 0.02). Patients with moderate/severe impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold higher odds of lobar location (95% CI = 1.59-24.02) as compared to no impairment. Further adjustment for antiplatelet use and for presence of leukoaraiosis attenuated the association with hematoma volume (p = 0.15), while moderate/severe impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18-24.14) for lobar location., Conclusions: Presence of moderate/severe CKD among patients with ICH is associated with larger, lobar hematomas and with poor outcome., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To examine the feasibility, safety and effectiveness of an early aerobic rehabilitation program for patients after minor ischemic stroke., Design: Randomized control trial., Methods: Twenty-eight patients, 1-3 weeks post minor ischemic stroke (modified Rankin scale; mRS ≤ 2), were randomly assigned to intervention or control groups. Measures were taken at weeks 1 and 6. All participants were instructed in home practice to achieve strength and flexibility, and were asked to continue their normal community routine. Intervention group participants performed a supervised exercise training program twice a week for 6 weeks. Exercise capacity was evaluated by the 6-minute walk distance test (6MWD), and the modified Bruce treadmill test., Results: Eight subjects out of 14 participated in all 12 training sessions, one at less than 50% of the sessions, while five reached the highest stage of the program. No adverse events were noted during the intervention period. In the intention to treat analysis a significant improvement over time was seen for the functional parameters only. No interaction (group*time) was found. According to the per protocol analysis a significant interaction effect was found; only the intervention group participants showed a significant clinical change in the 6MWD test (412 ± 178 meters to 472 ± 196 meters, vs the control group 459 ± 116 meters to 484 ± 122 meters, p< 0.01)., Conclusions: An early supervised aerobic training after minor ischemic stroke is feasible and well tolerated and, in a per-protocol analysis, was associated with improved walking endurance. Further studies with a larger sample size are needed to assess the effect of such a program on functional abilities, prevention of risk factors, and recurrent stroke.

Background: Calcium concentrations in serum are maintained within an exquisitely narrow range. Our aim was to examine the association between serum calcium and albumin-adjusted calcium (calcium(adj)) levels and stroke outcome in a cohort of unselected patients with acute stroke., Methods: Consecutive patients hospitalized due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large medical center were systematically assessed and followed for 1 year. Baseline total calcium and calcium(adj) levels were collapsed into groups of low (<8.6 mg/dl), normal (8.7-9.9 mg/dl) and high (>10 mg/dl) levels and linear and quadratic relations with outcome were examined., Result: Among 784 patients (mean age 70.7 ± 12.5 years, 42.5% females), the mean ± SD total calcium level was 9.3 ± 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all-cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22-2.75] among patients with low versus normal levels. For calcium(adj), the adjusted HR for all-cause death among women was over 3-fold higher among patients with high calcium(adj) levels versus those with normal levels (3.31; 95% CI 1.70-6.46), while no such associations were observed among men. In models developed to estimate the linear and quadratic relations, each unit increment in total calcium squared was associated with an increased adjusted HR of all-cause death over 1 year (p = 0.02) confirming nonlinear associations, and each unit increment in calcium(adj) squared was associated with an increased adjusted HR of all-cause death over 1 year among women (p < 0.001) but not among men (p = 0.70)., Conclusions: Serum calcium concentrations are a marker of mortality in acute stroke patients, but the associations are not linear, increasing at both extremes of calcium levels. Our findings suggest that long-term survival is optimal in a distinct range of serum calcium levels., (Copyright © 2010 S. Karger AG, Basel.)

Background: We intended to determine ethnic differences in the characteristics, management and outcome of acute ischemic stroke between the Israeli Arab and Jewish populations., Methods: A national survey was conducted in 2004 at all 28 hospitals in Israel. Information on demographics, transportation, risk factors, clinical presentation, stroke severity, type and subtype, management and clinical outcome was obtained. Mortality during the 36 months after hospitalization was assessed by matching with national mortality data., Results: Of the 1,540 patients, 169 (11%) were Arabs and 1,371 (89%) were Jews. The mean age of Arab patients was 9 years younger than in Jewish patients (63 ± 11 vs. 72 ± 12 years). Also, Arabs were more likely to be obese (OR = 1.72; 95% CI: 1.19-2.50) and have diabetes (OR = 1.41; 95% CI: 1.01-1.96), while Jews were more likely to have dyslipidemia (OR = 1.56; 95% CI: 1.11-2.17). A greater percentage of the Arab patients arrived at the hospital independently (OR = 3.85; 95% CI: 2.56-5.56) and were less likely to arrive within 3 h of symptom onset (OR = 2.33; 95% CI: 1.39-3.85). Arabs suffered increased rates of lacunar stroke (OR = 1.67; 95% CI: 1.14-2.43) and were discharged home more often (OR = 2.40; 95% CI: 1.35-4.25). No differences in severity of stroke, management, complications, disability or mortality were found between the 2 groups., Conclusions: The unique characteristics of the Arab and Jewish populations should be considered when planning stroke-care services and culturally oriented public education programs., (Copyright © 2011 S. Karger AG, Basel.)

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

Background: Multiple case series, mostly highly selected, have demonstrated a very high mortality following acute basilar artery occlusion. The more widespread availability and use of non-invasive vascular imaging over recent years has increased the rate of ABAO diagnosis., Objectives: To estimate the proportion of diagnosed ABAO among all-cause ischemic stroke in an era of increasing use of non-invasive vascular imaging and to compare the characteristics and outcomes between these two groups., Methods: We compared 27 consecutive cases of ABAO identified in a university hospital between 2003 and 2007 with 311 unselected cases of ischemic stroke from two 4 month surveys., Results: ABAO diagnosis increased from 0.3% of all-cause ischemic stroke (2003-2004) to 1.1% (2007), reflecting the increased use of non-invasive vascular imaging. In comparison to all-cause ischemic stroke, ABAO patients were younger (mean age 60 vs. 71 years), were more likely to be male (89% vs. 60%), had less atrial fibrillation (7% vs. 26%), more severe strokes (baseline NIHSS over 20: 52% vs. 12%), higher admission white cell count (12,000 vs. 9000 cells/ mm3), lower admission systolic blood pressure (140 +/- 24 vs. 153 +/- 27 mmHg), higher in-hospital mortality rates (30% vs. 8%) and worse functional outcome (modified Rankin scale < or = 3, 22% vs. 56%) (P< 0.05 for all). Rates of reperfusion therapy for ABAO increased from 0 in 2003-2004 to 60% in 2007., Conclusions: In this study, ABAO patients represented approximately 1% of all-cause ischemic stroke and were about a decade younger than patients with all-cause ischemic stroke. We report a lower ABAO mortality compared to previous more selected case series; however, most survivors had a poor functional outcome. Given the marked clinical heterogeneity of ABAO, a low threshold for non-invasive vascular imaging with a view to definitive reperfusion treatment is needed.

Background and Purpose: Randomized trials suggested a different benefit of intravenous thrombolysis (IVT) and intra-arterial thrombolysis (IAT) between men and women with anterior circulation stroke because of a worse outcome of women in the control group., Methods: We compared outcome and recanalization in men and women with basilar artery occlusion treated with antithrombotic treatment alone, IVT or combined IVT-IAT, or IAT in the Basilar Artery International Cooperation Study., Results: Overall, 389 male and 226 female patients were analyzed. In the antithrombotic treatment group, 68 of 111 (61%) men and 47 of 70 (67%) women had a poor outcome defined as a modified Rankin Scale score of 4 to 6 (adjusted risk ratio [aRR], 0.96; 95% CI, 0.75 to 1.24), in the IVT/combined IVT-IAT group, 47 of 77 (61%) men and 24 of 43 (56%) women (aRR, 1.19; 95% CI, 0.89 to 1.60), and in the IAT group, 142 of 185 (77%) men and 71 of 102 (70%) women (aRR, 1.01; 95% CI, 0.88 to 1.17). Mortality was not different between men and women in the antithrombotic treatment group (aRR, 0.80; 95% CI, 0.55 to 1.16), the IVT/combined IVT-IAT group (aRR, 1.11; 95% CI, 0.72 to 1.73), or in the IAT group (aRR, 1.01; 95% CI, 0.75 to 1.36). Insufficient recanalization after combined IVT-IAT or IAT was similar in men and women (23% versus 22%; aRR, 0.92; 95% CI, 0.58 to 1.46)., Conclusions: In patients with acute basilar artery occlusion, no significant gender differences for outcome and recanalization were observed, regardless of treatment modality.

Doppler echocardiography remains the most extended clinical modality for the evaluation of left ventricular (LV) function. Current Doppler ultrasound methods, however, are limited to the representation of a single flow velocity component. We thus developed a novel technique to construct 2D time-resolved (2D+t) LV velocity fields from conventional transthoracic clinical acquisitions. Combining color-Doppler velocities with LV wall positions, the cross-beam blood velocities were calculated using the continuity equation under a planar flow assumption. To validate the algorithm, 2D Doppler flow mapping and laser particle image velocimetry (PIV) measurements were carried out in an atrio-ventricular duplicator. Phase-contrast magnetic resonance (MR) acquisitions were used to measure in vivo the error due to the 2D flow assumption and to potential scan-plane misalignment. Finally, the applicability of the Doppler technique was tested in the clinical setting. In vitro experiments demonstrated that the new method yields an accurate quantitative description of the main vortex that forms during the cardiac cycle (mean error for vortex radius, position and circulation). MR image analysis evidenced that the error due to the planar flow assumption is close to 15% and does not preclude the characterization of major vortex properties neither in the normal nor in the dilated LV. These results are yet to be confirmed by a head-to-head clinical validation study. Clinical Doppler studies showed that the method is readily applicable and that a single large anterograde vortex develops in the healthy ventricle while supplementary retrograde swirling structures may appear in the diseased heart. The proposed echocardiographic method based on the continuity equation is fast, clinically-compliant and does not require complex training. This technique will potentially enable investigators to study of additional quantitative aspects of intraventricular flow dynamics in the clinical setting by high-throughput processing conventional color-Doppler images.

Background: Length of stay (LOS) is the main cost-determining factor of hospitalization of stroke patients. Our aim was to derive and validate a simple score for the assessment of the risk of prolonged LOS for acute stroke patients in a national setting., Methods: Ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients in the National Acute Stroke Israeli Surveys (NASIS 2004 and 2007) were included. Predictors of prolonged LOS (LOS > or =7 days) in the NASIS 2004 (n = 1,700) were identified with logistic regression analysis and used for the derivation of the Prolonged Length of Stay (PLOS) score. The score was validated in the NASIS 2007 (n = 1,648)., Results: Median (interquartile range) LOS was 6 (3-10) days in the derivation cohort (42.3% prolonged LOS) and 5 (3-8) in the validation cohort (35.7% prolonged LOS). The derivation cohort included 54.8% men, 90.8% IS and 9.2% ICH, with a mean (SD) age of 71.2 (12.5) years. Stroke severity was the strongest multivariable predictor of prolonged LOS: odds ratio (95% confidence interval [CI]) increased from 2.6 (2.0-3.3) for NIH Stroke Scale score (NIHSS) 6-10 to 4.9 (3.0-8.0) for NIHSS 16-20, compared with NIHSS < or =5. Stroke severity and type, decreased level of consciousness on admission, history of congestive heart failure, and prior atrial fibrillation were used for the derivation of the PLOS score (c statistics 0.692, 95% CI 0.666-0.718). The score performed similarly well in the validation cohort (c statistics 0.680, 95% CI 0.653-0.707)., Conclusion: A simple prolonged length of stay score, based on available baseline information, may be useful for tailoring policy aimed at better use of resources and optimal discharge planning of acute stroke patients.

Background: In the setting of an acute stroke, anemia has the potential to worsen brain ischemia, however, the relationship between the entire range of hemoglobin to long-term outcome is not well understood., Methods: We examined the association between World Health Organization-defined admission anemia status (hemoglobin<13 in males, <12 g/dl in women) and hemoglobin concentration and 1-year outcome among 859 consecutive patients with acute stroke (ischemic or intracerebral hemorrhage)., Results: The mean baseline hemoglobin concentration was 13.8 +/- 1.7 g/dl (range 8.1 - 18.7). WHO-defined anemia was present in 19% of patients among both women and men. After adjustment for differences in baseline characteristics, patients with admission anemia had an adjusted OR for all-cause death at 1-month of 1.90 (95% CI, 1.05 to 3.43) and at 1-year of 1.72 (95% CI, 1.00 to 2.93) and for the combined end-point of disability, nursing facility care or death of 2.09 (95% CI, 1.13 to 3.84) and 1.83 (95% CI, 1.02 to 3.27) respectively. The relationship between hemoglobin quartiles and all-cause death revealed a non-linear association with increased risk at extremes of both low and high concentrations. In logistic regression models developed to estimate the linear and quadratic relation between hemoglobin and outcomes of interest, each unit increment in hemoglobin squared was associated with increased adjusted odds of all-cause death [at 1-month 1.06 (1.01 to 1.12; p = 0.03); at 1-year 1.09 (1.04 to 1.15; p < 0.01)], confirming that extremes of both low and high levels of hemoglobin were associated with increased mortality., Conclusions: WHO-defined anemia was common in both men and women among patients with acute stroke and predicted poor outcome. Moreover, the association between admission hemoglobin and mortality was not linear; risk for death increased at both extremes of hemoglobin.

Although the benefit of antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is well recognized, its potential effect on stroke severity and outcome is less well established. Our objective was to examine the effect of preadmission antithrombotic therapy on stroke severity and outcome in patients with AF within a large comprehensive nationwide stroke survey. The data from consecutive patients with AF admitted with acute ischemic stroke or transient ischemic attack during a 2-month period were collected. The patients were categorized into 4 groups according to the use of preadmission antithrombotic therapy: no antithrombotic therapy, antiplatelet therapy, warfarin with an admission international normalized ratio (INR) <2 and INR of > or = 2. Of 1,938 patients presenting with acute brain ischemia, 329 (17%) had AF. The age-adjusted rate of more severe stroke (baseline National Institutes of Health stroke scale score >5) stratified by antithrombotic therapy use was 70% for no antithrombotic therapy use, 55% for antiplatelet therapy use, 59% for warfarin with an INR <2, and 38% for warfarin with an INR of > or = 2 (p = 0.01). Compared to warfarin therapy with an admission INR of > or = 2, the adjusted odds ratio for more severe strokes was 4.0 (95% confidence interval [CI] 1.7 to 10.0) for no antithrombotic therapy, 2.2 (95% CI 1.0 to 9.4) for antiplatelet therapy, and 2.7 (95% CI 1.1 to 6.7) for warfarin therapy with an INR of <2. Similarly, graded associations of antithrombotic medication were observed with severe disability (modified Rankin Scale score >3) or death at discharge, with corresponding adjusted odds ratios of 4.1 (95% CI 1.8 to 9.9), 2.1 (95% CI 1.0 to 4.6), and 1.5 (95% CI 0.6 to 3.5), and 1-year mortality, with corresponding adjusted ORs of 2.4 (95% CI 0.9 to 6.7), 1.9 (95% CI 0.8 to 5.0), and 2.2 (95% CI 0.8 to 6.2). In conclusion, in addition to its established benefit for stroke prevention, effective anticoagulation therapy is associated with decreased stroke severity and better functional outcome and survival in patients with AF presenting with acute brain ischemia., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Despite declining age-adjusted stroke mortality rates, the disease remains the third most common cause of death in Israel. Based on a national survey, we examined mortality rates during the first 3 years after a first-ever acute ischemic stroke (IS) and the major predictors of short-term (1 month) and long-term (3 years) mortality., Methods: In the National Acute Stroke Israeli Survey (NASIS 2004), data were collected on all hospitalized stroke patients in Israel during a 2-month period. Mortality rates for first-ever IS were assessed at 1 month and 3 years and predictors of death were evaluated using the Cox proportional hazard model., Results: A total of 1,079 first-ever IS patients were included. Survival data were complete for over 99% of patients. Cumulative mortality rates were 9.9% at 1 month and 31.1% at 3 years. Of the survivors at 1 month, 23.5% did not survive for 3 years. At 1 month, the hazard ratio (HR) for death significantly increased with stroke severity. One-month mortality was also associated with a decreased level of consciousness (HR 2.9, 95% CI 1.7-5.1), total anterior circulation infarction (TACI); HR 4.9, 95% CI 1.6-15.2), temperature on admission (HR 1.5, 95% CI 1.1-2.1 per 1 degrees C), age (HR 1.04, 95% CI 1.02-1.07 per year) and glucose levels on admission (HR 1.003, 95% CI 1.001-1.006 per 1 mg/dl). Age-adjusted proportions of diabetes and chronic heart failure were considerably higher in the deceased compared with survivors at 3 years (48 vs. 38 and 21 vs. 9%, respectively). In the multivariate survival analyses, predictors of death at 1 month also predicted death at 3 years; however, history of dementia (HR 1.5, 95% CI 1.0-2.4), diabetes (HR 1.6, 95% CI 1.0-2.4), peripheral artery disease (HR 1.7, 95% CI 1.1-2.8), chronic heart failure (HR 1.6, 95% CI 1.1-2.4) and malignancy (HR 1.7, 95% CI 1.1-2.7) were additional predictors of long-term mortality for patients surviving the first month after stroke., Conclusions: Approximately one third of patients did not survive 3 years after the first-ever IS. While age and markers of severe stroke were the major predictors of death at 1 month, comorbidities and variables associated with atherosclerotic vascular disease predicted long-term mortality. Improved control of these factors can potentially reduce long-term mortality in stroke victims., (Copyright 2009 S. Karger AG, Basel.)

Background and Purpose: Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events., Methods: Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction > or =6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles., Results: Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile (P = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94-1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97-1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category., Conclusions: Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease.

Background: The incidence of stroke varies among ethnically and culturally diverse groups., Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke., Methods: Patients with documented coronary heart disease were followed for 6-8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measurements of blood lipids. Among 15,052 patients, 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack., Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000), but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin resulting from factors that remain unrecognized, or with variables unassessed in this study., Conclusions: We identified an ethnic diversity in stroke risk among the Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.

Objective: We tested the hypothesis that impaired kidney function in the elderly is associated with a more rapid rate of cognitive decline., Methods: Baseline serum was used to calculate estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula, for 886 elderly without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. Kidney function was also dichotomized into impairment or no impairment based on eGFR < or >or=60 mL/min/1.73 m(2). Structured cognitive testing was performed at baseline and at annual evaluations, using a battery of 19 cognitive tests summarized into global cognition and 5 cognitive domains., Results: In mixed-effects models adjusted for age, sex, and education, a lower eGFR at baseline was associated with a more rapid rate of cognitive decline (estimate 0.0008, SE <0.001, p = 0.017). The increased rate of cognitive decline associated with a 15-mL/min/1.73 m(2) lower eGFR at baseline (approximately 1 SD) was similar to the effect of being 3 years older at baseline. Impaired kidney function at baseline was associated with a more rapid rate of cognitive decline (estimate -0.028, SE <0.009, p = 0.003). The increased rate of cognitive decline associated with impaired kidney function at baseline was approximately 75% the effect of ApoE4 allele on the rate of cognitive decline. Baseline kidney function was associated with declines in semantic memory, episodic memory, and working memory but not visuospatial abilities or perceptual speed., Conclusion: Impaired kidney function is associated with a more rapid rate of cognitive decline in old age.

Background and Purpose: A number of factors have been associated with postthrombolysis intracerebral hemorrhage, but these have varied across studies., Methods: We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post-tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of > or =4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days., Results: Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P<0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS < or =7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P<0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome., Conclusions: Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post-tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.

Background: Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO., Methods: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes., Findings: 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22)., Interpretation: Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial., Funding: Department of Neurology, University Medical Center Utrecht.

Background and Purpose: Intracerebral hemorrhage (ICH) is a deadly form of stroke. Pretreatment with statins exerts protective effects in patients with ischemic stroke, but their effects in patients with ICH remains unclear., Methods: The National Acute Stroke Israeli Surveys (NASIS) included all patients admitted with acute stroke to any of the 28 hospitals nationwide during February through March 2003 and March through April 2007. We compared stroke severity and outcomes of ICH patients who received statins before the index event with those who did not, using multivariable logistic regression models adjusting for the propensity to use statins before the event., Results: Among 3212 stroke patients, 312 had ICH and 89 of them were receiving statins at the time of the ICH. Patients on statins before ICH had lower baseline NIHSS scores, less systemic complications, higher proportions of good outcome (modified Rankin scale 0 to 3), lower death rates, and higher rates of discharge home or to a rehabilitation facility. On logistic regression analyses statin use before the event was associated with odds ratios of 0.46 for having a severe stroke defined as baseline NIHSS >15 (95% CI; 0.23 to 0.93), 2.97 for having good outcome (95% CI; 1.25 to 7.35) at discharge, and 0.25 for death or nursing facility disposition (95% CI; 0.09 to 0.63)., Conclusions: Use of statins before ICH is associated with reduced mortality and neurological disability and with a higher chance for good outcome, suggesting that statins may be protective in the setting of ICH.

Background and Purpose: Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (GFR) and stroke outcome and to assess whether CKD and its severity affect stroke outcome in a large cohort of unselected patients with acute stroke., Methods: We examined the association between baseline estimated GFR and CKD and 1-year outcomes in 821 consecutive patients with acute stroke (ischemic or hemorrhagic). GFR was estimated by 2 methods: the Modification of Diet in Renal Disease and the Mayo Clinic quadratic equation. An estimated GFR rate 60 mL/min/1.73 m(2), whereas those based on the Mayo Clinic equation were 2.3 (1.1 to 4.7) and 3.3 (1.6 to 7.1), respectively. The adjusted ORs for Barthel Index

Background: Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to bezafibrate is independently associated with subsequent long-term mortality., Methods: The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (< or =8 mg/dL) on-treatment HDL-C change., Results: Multivariate analysis demonstrated that patients allocated to bezafibrate therapy experienced a significant 11% reduction (P = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among bezafibrate-allocated patients was related to a significant 22% (P = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group (P = .57)., Conclusion: Our findings suggest that HDL-C level-raising therapy with bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

Background and Purpose: Cerebral leukoaraiosis is frequently observed in patients with acute stroke, but its clinical consequences on functional recovery remain incompletely defined. We evaluated the clinical correlates of leukoaraiosis, and its association with stroke-outcome in a cohort of consecutively hospitalized patients., Methods: One-thousand twenty-four consecutive patients with acute stroke or transient ischemic attack (TIA) undergoing brain CT were included in this single-center study. Patients were systematically evaluated at hospitalization and followed-up for 1 year. Mortality, functional outcome, quality of life (QoL), psychological distress, community integration, and patient perception of recovery were evaluated by leukoaraiosis severity. Adjusted ORs (95%CI) were calculated., Results: Moderate/severe leukoaraiosis was diagnosed in 177 patients (17.3%) and mild leukoaraiosis in 362 patients (35.3%). After 1 year, adjusted ORs for moderate/severe leukoaraiosis compared with no leukoaraiosis were 2.0 (95%CI 1.1-4.0) for Barthel Index

Low high-density lipoprotein (HDL) cholesterol is a strong independent predictor of cardiovascular risk. The present study was designed to assess the relation between the clinical response to HDL cholesterol modification and serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary artery disease (CAD). The risk for a major cardiac event (defined as nonfatal myocardial infarction or cardiac death) during a median 7.9-year follow-up period in 3,020 patients with CAD enrolled in the Bezafibrate Infarction Prevention (BIP) trial was related to changes in lipid levels during the study. Baseline LDL cholesterol levels were categorized according to National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariate analysis demonstrated that the benefit of HDL cholesterol increase was most pronounced in patients with low baseline LDL cholesterol (or=160 mg/dl; hazard ratio 0.94, 95% confidence interval 0.75 to 1.17, p = 0.14). A similar relation was shown for risk reduction-associated triglyceride decrements, whereas the benefit of LDL cholesterol reduction was more pronounced in patients with baseline LDL cholesterol >or=130 mg/dl. In conclusion, these data suggest that the clinical response to HDL cholesterol and triglyceride modification is inversely related to baseline LDL cholesterol levels. Thus, combined assessment of baseline and follow-up lipid levels to direct therapeutic goals in patients with CAD may provide incremental prognostic information to secondary prevention that is based solely on LDL cholesterol modification.

This Practice Point commentary discusses a study by Kastrup et al. that demonstrates that the early detection of blood-brain barrier (BBB) disruption as detected on post-contrast enhanced T1-weighted MRI after thrombolysis for acute ischemic stroke predicts subsequent intracerebral hemorrhage. No parenchymal enhancements were detected on scans before thrombolysis; however, after thrombolysis, 3 of 48 patients had parenchymal enhancement in the areas of the initial insult and these patients later developed symptomatic hemorrhages at these sites. These data suggest that assessment of BBB integrity might be a useful addition to a multimodal MRI study, potentially improving the overall efficacy of thrombolysis and broadening the effective time window. Further work is needed to optimize an imaging sequence that will be short and sufficiently sensitive to detect early damage to the BBB before treatment. Meanwhile, prudent clinicians should select patients for therapy on the basis of accepted guidelines and best clinical judgment.

Background: Ability to predict risk of postthrombolysis intracerebral hemorrhage (ICH) is currently limited., Methods: Using data from the Multicenter Recombinant Tissue Plasminogen Activator Stroke Survey Group, we developed a score to predict this risk. One point was assigned for the presence of each of 4 variables: age older than 60 years, baseline National Institutes of Health Stroke Scale score greater than 10, glucose greater than 8.325 mmol/L, and platelet count less than 150,000/mm(3)., Results: Rate of any ICH increased with higher scores: 0 points, 2.6%; 1 point, 9.7%; 2 points, 15.1%; and greater than or equal to 3 points, 37.9%. The model had reasonable discriminatory capability (C-statistic 0.69). A similar pattern was seen with symptomatic and asymptomatic ICH separately, and with radiographically defined parenchymal hemorrhage., Conclusion: A simple risk score may be useful for predicting postthrombolysis ICH.

Stroke is the third most common cause of death in Israel. Stroke is a leading cause of severe long-term disability and is associated with staggering economic costs. Ethnic variations observed in stroke mortality rates support that undetermined inherent genetic or sociocultural differences act to increase stroke mortality rates in immigrants from Asia and North Africa over that predicted from their profile of traditional risk factors. In accordance with other Western countries, there has been a decline in mortality rates from stroke, concomitantly with a decline observed in coronary heart disease mortality. With the aging of the population, the burden of stroke is projected to further increase. Moreover, brain infarcts detected by brain imaging are 5-times more common than the clinical syndrome of acute stroke, detected in about 20% of healthy elderly and up to 50% of high risk patients. Estimates of the incidence of stroke, characteristics of patients, management and outcome became available from the tri-annual national acute stroke Israeli survey (NASIS) program, initiated during 2004. The annual incidence of hospitalized acute cerebrovascular events is approximately 13,000 and rates, particularly in women, seem even higher than those observed for acute myocardial infarction. Findings also highlight critical deficiencies in acute stroke units and systems for urgent evaluation and intervention in acute stroke. Action plans are urgently required, in accordance with the experience from other countries, in order to upgrade the stroke infrastructure nationwide for more effective prevention and management of acute stroke.

Background: Calcification of the thoracic aorta is associated with atherosclerotic risk factors, yet its pathogenesis and clinical implications are not yet elucidated. The goal of the present study was to assess whether thoracic aorta calcification is associated with an increased risk of cardiovascular events and death in patients with stable angina pectoris., Methods and Results: A prospective cohort of 361 stable angina pectoris patients (307 men, 54 women; age range, 37 to 83 years) underwent chest spiral computed tomography and were evaluated for aortic calcification. We recorded the incidence of cardiovascular events and death during a 4.5- to 6-year follow-up. Aortic calcification was documented in 253 patients (70% of patients; 213 men, 40 women). Patients with aortic calcification were older (mean age, 65+/-7 versus 55+/-9 years; P<0.001), and fewer were classified as smokers (13% versus 26%; P=0.014) compared with patients without aortic calcification. Significant correlation was found between patients with and those without aortic calcification for the presence of aortic valve calcification (28% versus 11%; P<0.001), mitral annulus calcification (29% versus 4%; P<0.001), and coronary calcification as expressed by coronary calcium score. (P<0.001). During 4.5 to 6 years of follow-up, 19 patients died, all of whom were in the aortic calcification group. Age-adjusted hazard ratios for total events and cardiovascular events by aortic calcification were 2.84 (95% CI, 1.52 to 5.30; P=0.001) and 2.70 (95% CI, 1.33 to 5.47; P=0.006), respectively. In multivariable analysis, hazard ratios for total events and cardiovascular events were 2.79 (95% CI, 1.46 to 5.20; P=0.002) and 4.65 (95% CI, 1.19 to 18.26; P=0.028), respectively., Conclusions: Calcification of the thoracic aorta is age related and associated with coronary calcification and valvular calcification. Thoracic aortic calcification is associated with an increased risk of death and cardiovascular disease.

Stroke is the third most common cause of death in Israel, similar to the United States and Europe. A decline in stroke mortality rates for the Israeli population is evident in the last decades. However, stroke is still a major health and economical burden in Israel and has recently been recognized by the Israeli health-care policy planners as a top priority disease. Action plans are being taken in order to establish a comprehensive infrastructure for the treatment of acute stroke patients.

Background and Purpose: The role of blood lipids and lipoprotein-related variables in the prediction of ischemic stroke is less clear than that for coronary heart disease. Apolipoprotein B (Apo B), which reflects the concentration of potentially atherogenic lipoprotein particles, and apolipoprotein AI (Apo A-I), which reflects the corresponding concentration of the anti-atherogenic HDL, represent additional lipoprotein-related variables that may indicate vascular risk. We examined the association between serum concentrations of Apo B, Apo A-I, and the Apo A-I/Apo B ratio and the risk of incident ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease., Methods: Patients with documented chronic coronary heart disease and measured Apo B and Apo A-I concentration, screened for but not included in a clinical trial of lipid modification were followed over 4.8 to 8.1 years for hospitalized incident cerebrovascular events., Results: Among 3,434 patients 266 (7.7%) developed an incident ischemic cerebrovascular event. Adjusting for potential confounders, the hazard ratios (HR) for incident ischemic cerebrovascular events associated with the top versus bottom quartile of Apo B was 1.68 (95%CI, 1.18-2.40), of Apo A-I 0.71 (95%CI, 0.50-1.00), and of Apo A-I/Apo B ratio 0.51 (95%CI, 0.35-0.74)., Conclusions: These findings support the hypothesis that Apo B, Apo A-I and the Apo A-I/Apo B ratio predict incident ischemic stroke among patients with preexisting atherothrombotic disease. The potential clinical role of measuring these apolipoproteins for ischemic stroke prediction warrants further study.

Individuals involved in intense resistance training present with increased absolute left ventricular (LV) wall thickness and mass and show good systolic responses to isometric exercise. There is no consensus regarding diastolic features and no available information regarding diastolic function in athletes during isometric exertion itself. Therefore, the main aim of this study was to assess diastolic LV function at baseline and during exercise in athletes. The population consisted of 96 men (mean age 29 +/- 7 years): 48 weight lifters who trained for 15 to 20 hours/week and 48 sedentary men. All weight lifters had been active for >6 years, including the 6 months before the study. Ultrasound was performed using a commercially available Doppler echocardiographic system. Isometric exercise was performed in the supine position using a standard 2-hand bar dynamometer. The man end-diastolic volumes at rest were 97 +/- 6 ml in sedentary subjects and 101 +/- 5 ml in weight lifters, increasing to 100 +/- 6 and 118 +/- 11 ml during exercise (p = 0.06 and p <0.01, respectively). End-systolic volumes at rest were similar in the 2 groups, showing significantly greater reductions during exercise in the weight lifters. The mean absolute LV mass was 167 +/- 30 g in sedentary subjects and 202 +/- 32 g in weight lifters (p <0.0001). The mean stroke volume increased from 65 +/- 7 to 86 +/- 7 ml in sedentary subjects and from 70 +/- 6 to 107 +/- 11 ml in weight lifters (intergroup significance p = 0.05 and p <0.01, respectively). A similar pattern of response was documented for the ejection fraction (i.e., significantly greater increases during exercise in weight lifters). Regarding diastolic indexes, in the weight lifters, the mean peak early velocity at rest was 68 +/- 7 cm/s, the mean acceleration rate was 1,242 +/- 176 cm/s/s, and the mean deceleration rate was 414 +/- 44 cm/s/s. All these values were significantly higher than in sedentary subjects, with further increases during exercise (p <0.0001). In weight lifters, the mean peak atrial velocity at rest was 37 +/- 6 cm/s, the mean acceleration time was 55 +/- 4 ms, the mean isovolumic relaxation time was 63 +/- 3 ms, and the mean deceleration time was 164 +/- 4 ms; these values were lower than in sedentary subjects (p <0.0001 for all). In conclusion, intense resistance training leads to enhanced LV diastolic function at rest and during isometric exercise despite the markedly increased LV mass.

Background: Epidemiologic studies have suggested that hypertriglyceridemia and insulin resistance are related to the development of colon cancer. Nuclear peroxisome proliferator-activated receptors (PPAR), which play a central role in lipid and glucose metabolism, had been hypothesized as being involved in colon cancerogenesis. In animal studies the lipid-lowering PPAR ligand bezafibrate suppressed colonic tumors. However, the effect of bezafibrate on colon cancer development in humans is unknown. Therefore, we proposed to investigate a possible preventive effect of bezafibrate on the development of colon cancer in patients with coronary artery disease during a 6-year follow-up., Methods: Our population included 3011 patients without any cancer diagnosis who were enrolled in the randomized, double blind Bezafibrate Infarction Prevention (BIP) Study. The patients received either 400 mg of bezafibrate retard (1506 patients) or placebo (1505 patients) once a day. Cancer incidence data were obtained by matching a subject's identification numbers with the National Cancer Registry. Each matched record was checked for correct identification., Results: Development of new cancer (all types) was recorded in 177 patients: in 79 (5.25%) patients from the bezafibrate group vs. 98 (6.51%) from the placebo group. Development of colon cancer was recorded in 25 patients: in 8 (0.53%) patients from the bezafibrate group vs. 17 (1.13%) from the placebo group, (Fisher's exact test: one side p = 0.05; two side p = 0.07). A difference in the incidence of cancer was only detectable after a 4 year lag and progressively increased with continued follow-up. On multivariable analysis the colon cancer risk in patients who received bezafibrate tended to be lower with a hazard ratio of 0.47 and 95% confidence interval 0.2-1.1., Conclusion: Our data, derived from patients with coronary artery disease, support the hypothesis regarding a possible preventive effect of bezafibrate on the development of colon cancer.

Stroke is a major cause of morbidity and mortality in Israel and the main cause for neurological disability among adults. Continued efforts for its prevention and treatment began a long time ago and currently persist. During the last decade, these efforts have resulted in a number of significant breakthroughs. Consequently, several new guidelines and consensus statements from Europe and North America have been published. In Israel, up to date, guidelines have been published only for acute stroke treatment, as well as for its prevention by medical means. The present guideline is supplemental to the previous papers and focuses on the invasive options to treat specific risk factors and conditions, when appropriate, for primary and secondary stroke prevention.

Inherited disorders of hemostasis are natural models for investigating mechanisms of thrombosis and development of antithrombotic therapy. Because mice with total factor XI deficiency are protected against ischemic stroke and do not manifest excessive bleeding, we investigated the incidence of ischemic stroke in patients with severe inherited factor XI deficiency. Incidence of ischemic stroke in 115 patients aged 45 years or more with severe factor XI deficiency (activity less than 15 U/dL) was compared with incidence in the Israeli population as estimated from a stroke survey of 1528 patients. Adjustment for major risk factors of stroke (hypertension, diabetes mellitus, hypercholesterolemia, current smoking) was based on comparison of their prevalence in the stroke survey to an Israeli health survey of 9509 subjects. Incidence of myocardial infarction in the factor XI cohort was also recorded. After adjustment for the 4 major risk factors of ischemic stroke, the expected incidence of ischemic stroke was 8.56 compared with one observed (P = .003). The reduced 1:115 incidence of ischemic stroke contrasted with a 19:115 incidence of myocardial infarction, similar to the expected incidence. Thus, severe factor XI deficiency probably is protective against ischemic stroke but not against acute myocardial infarction.

Experimental antiphospholipid syndrome (eAPS) induced by immunization with beta(2)-glycoprotein I (beta(2)-GPI) causes behavioral hyperactivity. We assessed the role of thrombotic and inflammatory perivascular factors and standard APS therapies for CNS manifestations. Groups of mice (n=10 per group) were immunized once with beta(2)-GPI (eAPS) or adjuvant (controls) and treated daily from 1 month after immunization with either sham injections, aspirin (1.2 mg/kg) or enoxaparin (1 mg/kg) for 3 months. Serum antiphospholipid antibodies (aPL) and brain levels of tissue necrosis factor-alpha (TNF-alpha) and prostaglandin E (PGE) were then measured by ELISA and thrombin inhibitors by immunoblot. Behavioral hyperactivity was assessed by the staircase test. The eAPS mice had higher levels of aPL than adjuvant immunized controls. Inflammatory markers were found to be twofold higher and intrinsic brain thrombin inhibitors 50% lower in eAPS brains compared to controls. aPL titers were unaffected by treatment. Both aspirin and enoxaparin normalized brain concentrations of PGE and TNF-alpha and elevated thrombin inhibitors, the latter effect being more pronounced for enoxaparin. The increased activity and rearing exploratory behavior in eAPS (138.6+/-13.6 and 141.9+/-13.9% of controls, respectively) were attenuated significantly more by treatment with enoxaparin (91.5+/-12.3 and 95.0+/-9.8%) than by aspirin (167.0+/-18.4 and 114.7+/-13.1%, p<0.01, ANOVA). Together, these results demonstrate that eAPS is associated with significant brain inflammation and thrombosis that are well treated with both standard therapies for human APS. Enoxaparin attenuates behavior better than aspirin possibly by reducing thrombosis or stabilization of the blood brain barrier, suggesting an advantage for similar drugs in CNS APS.

Inflammation plays a critical role in the pathogenesis of atherothrombosis. Our aim was to examine the association between plasma concentrations of inflammatory biomarkers and severity and outcome of acute brain ischaemia. Plasma samples were collected within 36 h of symptom onset in patients with acute brain ischaemia, and assessed by conventional ELISA kits for concentration of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). Patients were assessed serially for stroke severity (National Institute of Health stroke scale) and outcome during follow-up (modified Rankin Scale, mRS; and Stroke Impact Scale-16, SIS). Patients (n = 113, 65% men, mean age 64 +/- 12 years) had a mean IL-6 concentrations of 5.1 +/- 5.0 pg/ml and sICAM-1 of 377 +/- 145 ng/ml. IL-6, but not sICAM-1, concentrations were strongly associated with stroke severity (P < 0.01 at all serial assessments). Ln-transformed IL-6 levels (per 1 SD) were associated with disability (mRS > or = 2, OR = 1.7; 95% CI 1.1-3.0) and poor physical function (SIS < or = 85, OR = 1.7; 95% CI 1.0-2.8). Further adjustment for baseline stroke severity, however, eliminated these associations. Our results suggest that high plasma concentrations of the inflammatory biomarker IL-6 but not sICAM-1 are associated with stroke severity and poorer functional outcome. IL-6 does not add, however, additional prognostic information for stroke outcome beyond that conveyed by the stroke severity.