Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study.

BACKGROUND AND PURPOSE: The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. METHODS: ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0-2) or unfavorable (score of 3-6). Safety outcomes were death and any intracranial bleeding. RESULTS: Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03-3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36-3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87-58.71; P=0.068) in the cases than in the controls. CONCLUSIONS: In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study.

BACKGROUND AND PURPOSES: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. METHODS: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. RESULTS: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days. CONCLUSIONS: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.

Risk of recurrent cerebrovascular events in patients with cryptogenic stroke or transient ischemic attack and patent foramen ovale: the FORI (Foramen Ovale Registro Italiano) study.

BACKGROUND: The optimal management of patients with cryptogenic ischemic stroke found to have a patent foramen ovale (PFO) at diagnostic workup remains unclear. The aims of this observational multicenter study were to evaluate: (1) the risk of recurrent cerebrovascular events in patients with cryptogenic minor ischemic stroke or transient ischemic attack (TIA) and PFO who either underwent percutaneous PFO closure or received only medical treatment, and (2) the risk factors associated with recurrent events. METHODS: Consecutive patients (aged 55 years or less) with first-ever cryptogenic minor ischemic stroke or TIA and PFO were recruited in 13 Italian hospitals between January 2006 and September 2007 and followed up for 2 years. RESULTS: 238 patients were included in the study (mean age 42.2 ± 10.0 years; 118 males); 117 patients (49.2%) received only antithrombotic therapy while 121 patients underwent percutaneous PFO closure (50.8%). Stroke as the qualifying event was more common in the medical treatment group (p = 0.01). The presence of atrial septal aneurysm and evidence of 20 bubbles or more on transcranial Doppler were more common in the PFO closure group (p = 0.002 and 0.02). Eight patients (6.6%) experienced a nonfatal complication during PFO closure. At the 2-year follow-up, 17 recurrent events (TIA or stroke; 3.6% per year) were observed; 7 of these events (2.9% per year) occurred in the percutaneous PFO closure group and 10 events (4.2% per year) in the medical treatment group. The rate of recurrent stroke was 0.4% per year in patients who underwent percutaneous closure (1 event) and 3.4% per year in patients who received medical treatment (8 events). On multivariate analysis, percutaneous closure was not protective in preventing recurrent TIA or stroke (OR = 0.1, 95% CI = 0.02-1.5, p = 0.1), while it was barely protective in preventing recurrent stroke (OR = 0.1, 95% CI = 0.0-1.0, p = 0.053). CONCLUSIONS: The results of this observational, nonrandomized study suggest that PFO closure might be superior to medical therapy for the prevention of recurrent stroke. Periprocedural complications were the trade-off for this clinical benefit. Controlled randomized clinical trials comparing percutaneous closure with medical management are required.

Acute hyperglycemia and early hemorrhagic transformation in ischemic stroke.

BACKGROUND: Hyperglycemia has been claimed to be associated with hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis. The aim of this study was to assess whether the admission blood glucose level is related to HT in a prospective study in consecutive patients with acute ischemic stroke. METHODS: Consecutive patients admitted for ischemic stroke to 4 Italian hospitals were included in this prospective cohort study. RESULTS: Among 1,125 consecutive patients included in the analysis, 98 (8.7%) had HT: 62 (5.5%) had hemorrhagic infarction (HI) and 36 (3.2%) parenchymal hematoma (PH). A blood glucose level >110 mg/dl was found in 42.4% of the patients, a level between 110 and 149 mg/dl in 25.2%, and a level >150 mg/dl in 17.2%. At 3 months, 7 patients were lost at follow-up, 326 patients (29.2%) were disabled (modified Rankin score > or = 3) and 129 died (11.5%). PH was associated with an increased risk of death or disability (OR 15.29, 95% CI 2.35-99.35). However, this was not the case for HT overall and HI. At logistic regression analysis, PH was predicted by high levels of admission blood glucose (OR 1.01, 95% CI 1.00-1.01 for 1 added mg/dl). The rate of PH was 2.1% in patients with <110 mg/dl, 3.6% in patients with a level between 110 and 149 mg/dl and 6.4% in patients with a level >150 mg/dl. The curve estimation regression model showed a significant linear increase in the risk of PH related to an increase in blood glucose levels (R(2) = 0.007, p = 0.007). CONCLUSIONS: Hyperglycemia during acute ischemic stroke predisposes to PH, which in turn determines a non-favorable outcome at 3 months. This relationship seems to be linear.

Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study.

BACKGROUND AND PURPOSE: Early hemorrhagic transformation (HT) is a complication of ischemic stroke but its effect on patient outcome is unclear. The aims of this study were to assess: (1) the rate of early HT in patients admitted for ischemic stroke, (2) the correlation between early HT and functional outcome at 3 months, and (3) the risk factors for early HT. METHODS: Consecutive patients with ischemic stroke were included in this prospective study in 4 study centers. Early HT was assessed by CT examination performed at day 5+/-2 after stroke onset. Study outcomes were 3-month mortality or disability. Disability was assessed using a modified Rankin score (> or = 3 indicating disabling stroke) by neurologists unaware of the occurrence of HT in the individual cases. Outcomes in patients with and without early HT were compared by chi(2) test. Multiple logistic regression analysis was used to identify predictors for HT. RESULTS: Among 1125 consecutive patients (median age 76.00 years), 98 (8.7%) had HT, 62 (5.5%) had hemorrhagic infarction, and 36 (3.2%) parenchymal hematoma. At 3 months, 455 patients (40.7%) were disabled or died. Death or disability was seen in 33 patients with parenchymal hematoma (91.7%), in 35 patients with hemorrhagic infarction (57.4%) as compared with 387 of the 1021 patients without HT (37.9%). At logistic regression analysis, parenchymal hematoma, but not hemorrhagic infarction, was independently associated with an increased risk for death or disability (OR 15.29; 95% CI 2.35 to 99.35). At logistic regression analysis, parenchymal hematoma was predicted by large lesions (OR 12.20, 95% CI 5.58 to 26.67), stroke attributable to cardioembolism (OR 5.25; 95% CI 2.27 to 12.14) or to other causes (OR 6.77; 95% CI 1.75 to 26.18), high levels of blood glucose (OR 1.01; 95% CI 1.00 to 1.01), and thrombolytic treatment (OR 3.54, 95% CI 1.04 to 11.95). CONCLUSIONS: Early HT occurs in about 9% of patients. Parenchymal hematoma, seen in about 3% of patients, is associated with an adverse outcome. Parenchymal hematoma was predicted by large lesions attributable to cardioembolism or other causes, high blood glucose, and treatment with thrombolysis.

Airborne pollutants and lacunar stroke: a case cross-over analysis on stroke unit admissions.

Particulate air pollution is known to be associated with cardiovascular disease. The relation of particulate air pollution with cerebrovascular disease (CVD) has not been extensively studied, particularly in relation to different subtypes of stroke. A time-series study was conducted to evaluate the association between daily air pollution and acute stroke unit hospitalizations in Mantua, Italy. We analyzed 781 CVD consecutive patients living in Mantua county admitted between 2006-08. Data on stroke types, demographic variables, risk factors were available from the Lombardia Stroke Registry. Daily mean value of particulate matter with a diameter <10 µm (PM(10)), carbon monoxide, nitric oxide, nitrogen dioxide, sulphur dioxide, benzene and ozone were used in the analysis. The association between CVD, ischemic strokes subtypes and pollutants was investigated with a case-crossover design, using conditional logistic regression analysis, adjusting for temperature, humidity, barometric pressure and holidays. Among the 781 subjects admitted 75.7% had ischemic stroke, 11.7% haemorrhagic stroke 12.6% transient ischemic attack. In men admission for stroke was associated with PM(10) [odds ratio (OR) 1.01, 95%; confidence interval (CI) 1.00-1.02; P<0.05]. According to the clinical classification, lacunar anterior circulation syndrome stroke type was related to PM(10) level registered on the day of admission for both genders (OR: 1.01, 95%; CI: 1.00-1.02; P<0.05) while for total anterior circulation syndrome stroke only in men (OR: 1.04, 95%; CI 1.01-1.07; P<0.05).In conclusion, our study confirms that air pollution peaks may contribute to increase the risk of hospitalization for stroke and particulate matter seems to be a significant risk factor, especially for lacunar stroke.

Risk factors for cerebral ischemic events in patients with atrial fibrillation on warfarin for stroke prevention.

BACKGROUND AND PURPOSES: Patients with atrial fibrillation (AF) on treatment with oral anticoagulants may still suffer ischemic cerebrovascular events. The aim of this study was to evaluate the risk factors for cerebral ischemic events in warfarin-treated AF patients with an International Normalized Ratios (INR) above 1.8 on admission. METHODS: In a case-control study, cases were consecutive patients with AF who were on warfarin and who were admitted to four Italian hospitals after an acute cerebrovascular ischemic event (ischemic stroke or transient ischemic attack) with an INR above 1.8. Controls were selected from a single anticoagulation clinic and were patients with AF on adequate warfarin treatment who did not suffer cerebrovascular events. RESULTS: Cases were identified among 4785 consecutive patients with an ischemic cerebral event. 148 cases (3.1%, 21 with transient ischemic events and 127 with ischemic strokes) had AF and were taking warfarin with an INR above 1.8 on admission. On multivariate analysis, diabetes (OR 3.8; 95% CI 1.09-13.82, p=0.025), hyperlipidemia (OR 4.5; 95% CI 1.11-18.23, p=0.035) and carotid/vertebral atherosclerosis on ultrasound (OR 3.0; 95% CI 1.13-8.41, p=0.028) were independent predictors for ischemic cerebral events. The use of statins was inversely correlated with an ischemic event (OR 0.1; 95% CI 0.06-0.47. p=0.001). CONCLUSIONS: Carotid/vertebral atherosclerosis, diabetes and hyperlipidemia are associated with an increased risk for ischemic events in patients with AF on adequate warfarin treatment. Statins significantly reduce the risk of ischemic events.

Gender differences in patients with acute ischemic stroke.

Stroke has a greater effect on women than men owing to the fact that women have more stroke events and are less likely to recover. Age-specific stroke rates are higher in men; however, because of women's longer life expectancy and the much higher incidence of stroke at older ages, women have more stroke events than men overall. The aims of this prospective study in consecutive patients were to assess whether there are gender differences in stroke risk factors, treatment or outcome. Consecutive patients with ischemic stroke were included in this prospective study at four study centers. Disability was assessed using a modified Rankin Scale score (>or=3 indicating disabling stroke) in both genders at 90 days. Outcomes and risk factors in both genders were compared using the chi(2) test. Multiple logistic regression analysis was used to identify any independent predictors of outcome. A total of 1136 patients were included in this study; of these, 494 (46%) were female. Women were statistically older compared with men: 76.02 (+/- 12.93) and 72.68 (+/- 13.27) median years of age, respectively. At admission, females had higher NIH Stroke Scale scores compared with males (9.4 [+/- 6.94] vs 7.6 [+/- 6.28] for men; p = 0.0018). Furthermore, females tended to have more cardioembolic strokes (153 [30%] vs 147 [23%] for men; p = 0.004). Males had lacunar and atherosclerotic strokes more often (146 [29%] vs 249 [39%] for men; p = 0.002, and 68 [13%] vs 123 [19%] for men; p = 0.01, respectively). The mean modified Rankin Scale score at 3 months was also significantly different between genders, at 2.5 (+/- 2.05) for women and 2.1 (+/- 2.02) for men (p = 0.003). However, at multivariate analysis, female gender was not an indicator for negative outcome. It was concluded that female gender was not an independent factor for negative outcome. In addition, both genders demonstrated different stroke pathophysiologies. These findings should be taken into account when diagnostic workup and treatment are being planned.

Effect of carotid stenosis on the prognostic value of admission blood pressure in patients with acute ischemic stroke.

BACKGROUND: Data on the correlation between blood pressure (BP) on admission and clinical outcome in patients with acute stroke are conflicting. The aims of the present study in consecutive patients with acute ischemic stroke were to evaluate: (a) the relationship between systolic or diastolic BP on admission and mortality at 3 months; (b) the role of carotid artery disease ipsilateral to the index stroke on this relationship. METHODS: Consecutive patients admitted to four Italian hospitals with objectively diagnosed ischemic stroke were included in this prospective study. RESULTS: A total of 1467 patients (mean age 72.6+/-13.2 years; males 53.3%) with acute ischemic stroke were evaluated. At 3 months, 13 patients were lost at follow-up and 133 had died (9.2%). In patients with systolic BP <140mmHg, mortality was 11% (40/362), in patients with systolic BP between 140 and 179mmHg 8.3% (68/823) and in patients with systolic BP >or=180mmHg 9.2% (25/269). Patients with systolic BP <140mmHg were more likely to die within 90 days (OR 3.4; 95% CI 1.4-8.5, p=0.008, after adjusting for other risk factors) when compared to those with systolic BP between 140 and 179mmHg (reference group with OR=1.0). Systolic BP >or=180mmHg was not associated with increased mortality (OR 0.4; 95% CI 0.1-1.3, p=0.13). Two-hundred and thirty patients out of 1278 with anterior circulation stroke had a stenosis (>or=50% on ultrasonography) or an occlusion of the internal carotid ipsilateral to the index stroke. At 3 months, 29 patients had died (12.7%). In patients with systolic BP <140mmHg, mortality was 20.4% (11/54), in those with systolic BP between 140 and 179mmHg 13.0% (16/123) and in those with systolic BP >or=180mmHg 3.9% (2/51). Patients with systolic BP >or=180mmHg were less likely to die within 90 days (OR 0.1; 95% CI 0.0-0.5, p=0.022 after adjusting for other risk factors) compared to those with systolic BP between 140 and 179mmHg. Systolic BP <140mmHg was not associated with increased mortality (OR 6.3; 95% CI 0.8-48.0, p=0.08). CONCLUSIONS: In the overall population, low BP was an independent risk factor for mortality. In patients with stenosis >/=50% or occlusion of the carotid ipsilateral to the index stroke, high BP was associated with a lower mortality at 3 months.