Sara Micheli

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 (≥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 &khgr;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.

Efficacy and Safety of Anticoagulant Treatment in Acute Cardioembolic Stroke A Meta-Analysis of Randomized Controlled Trials

Background and Purpose— The role of anticoagulant treatment for acute cardioembolic stroke is uncertain. We performed an updated meta-analysis of all randomized trials to obtain the best estimates of the efficacy and safety of anticoagulants for the initial treatment of acute cardioembolic stroke. Methods— Using electronic and manual searches of the literature, we identified randomized trials comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids), started within 48 hours, with other treatments (aspirin or placebo) in patients with acute ischemic cardioembolic stroke. Two reviewers independently selected studies and extracted data on study design, quality, and clinical outcomes, including death or disability, all strokes, recurrent ischemic stroke, and cerebral symptomatic bleeding. Odds ratios for individual outcomes were calculated for each trial and data from all the trials were pooled using the Mantel-Haenszel method. Results— Seven trials, involving 4624 patients with acute cardioembolic stroke, met the criteria for inclusion. Compared with other treatments, anticoagulants were associated with a nonsignificant reduction in recurrent ischemic stroke within 7 to 14 days (3.0% versus 4.9%, odds ratio 0.68, 95% CI: 0.44 to 1.06, P=0.09, number needed to treat=53), a significant increase in symptomatic intracranial bleeding (2.5% versus 0.7%, odds ratio 2.89; 95% CI: 1.19 to 7.01, P=0.02, number needed to harm=55), and a similar rate of death or disability at final follow up (73.5% versus 73.8%, odds ratio 1.01; 95% CI: 0.82 to 1.24, P=0.9). Conclusions— Our findings indicate that in patients with acute cardioembolic stroke, early anticoagulation is associated with a nonsignificant reduction in recurrence of ischemic stroke, no substantial reduction in death and disability, and an increased intracranial bleeding.

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 ≥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 (R2 = 0.007, p = 0.007). Conclusions: Hyperglycemia during acute ischemic stroke predisposes to PH, which in turn determines a nonfavorable outcome at 3 months. This relationship seems to be linear.

First-Ever Stroke and Outcome in Patients Admitted to Perugia Stroke Unit: Predictors for Death, Dependency, and Recurrence of Stroke within the First Three Months

Predictors of poor outcome after first-ever stroke within 3 months in consecutive patients admitted to our Stroke Unit were defined. Factors included age, sex, risk factors, occurrence of transient ischemic attacks, extension of cerebral infarction, presumed cause of stroke, clinical findings, and demographic characteristics. Multiple regression models were used to analyze predictors of mortality, dependency and stroke recurrence. A total of 435 patients with first-ever stroke were included. Of these, 358 patients had ischemic stroke and 77 hemorrhagic stroke. Three-month mortality rate was 20.5%. After the same period, 24.6% of survivors were dependent (mRS ≥3) and 5.0% of patients had recurrent stroke. Age, the presence of atrial fibrillation, impaired consciousness on admission, and stroke severity were related to mortality. The presence of stroke due to an undetermined cause or small vessel disease was associated with lower mortality. Partial anterior circulation syndrome or lacunar syndrome were both related to better outcome. The best predictors for dependency after 3 months were age and stroke severity. The only variable identified as the best predictor for recurrence was the presence of diabetes mellitus.

Need for extensive diagnostic work-up for patients with lacunar stroke

ObjectiveSmall-vessel disease is the most frequent cause of lacunar stroke. The aims of this study were to evaluate: 1) alternative causes of lacunar stroke other than small-vessel disease; 2) functional outcome of lacunar strokes due to small vessel disease compared to lacunar strokes due to alternative causes.MethodsConsecutive patients with first-ever ischemic lacunar stroke were prospectively followed-up for at least 3 months. At discharge patients were divided into 2 groups: lacunar stroke due to small vessel disease (L-SVD) and lacunar stroke due to possible other etiologies (L-non SVD) (e. g. cardioembolism, atherosclerosis or other causes). Main outcome measures were the combined end point of death or disability (mRS ≥ 3) and recurrent stroke at the end of follow-up.Results535 patients with acute stroke were seen during the study period. Out of these, 196 patients (126 males) with a mean age of 71.6 years (SD = 10) had lacunar stroke. L-SVD was seen in 142 patients (72.4 %) and L-nonSVD in 54 patients (27.6 %). After 16.4 months, 12 patients had died (6.2%; annual mortality rate 4.4 %), 63 were disabled (32.5 %) and 27 had stroke recurrence (13.9%; annual recurrence rate 9.9 %). Forty-nine patients with L-SVD (34.7 %) and 26 with L-nonSVD (49%) had died or become disabled. Sixteen patients with L-SVD (11.3 %) and 11 with L-nonSVD (20.4 %) had stroke recurrence. On multivariate analysis, L-nonSVD (OR = 2.87, 95% CI 1.08–7.65; p = 0.034) and age (OR = 1.07, 95 % CI 1.02–1.12; p = 0.01) were associated to more severe outcome. L-nonSVD was independently associated with recurrence (OR = 5.03, 95% CI 1.54–16.44; p = 0.006).ConclusionsTwenty-seven percent of patients with lacunar stroke have causes other than small vessel disease. These patients have a severe outcome in terms of recurrence,mortality or disability. These findings support the need for a comprehensive diagnostic work-up for patients with lacunar stroke.

Clinical Benefit of Early Anticoagulation in Cardioembolic Stroke

Background: Nonvalvular atrial fibrillation is the most common source of cardiac embolism with a high reported risk of stroke and a high stroke-related mortality. A common clinical dilemma in patients with acute stroke is whether the detection of one of the major cardiac sources of emboli requires an early anticoagulation to reduce early stroke recurrence and mortality. Methods: In this review, we report on the results of clinical trials that have investigated the efficacy of early treatment for acute cardioembolic stroke. Results: Large clinical trials demonstrate that there is no evidence supporting the administration of heparin in patients with acute ischemic stroke within 48 h from stroke onset. Conclusions: The results of recent studies showing an advantage of the very early administration of heparin (<3 h from stroke onset) should encourage clinicians to perform further trials on the efficacy of an early administration of heparin in acute cardioembolic stroke.

Lacunar versus Non-Lacunar Syndromes

Small-vessel disease is the accepted most frequent cause of lacunar stroke. The main clinical features seen with lacunar infarcts are motor and/or sensitive deficit, ataxic sign, without cortical involvement. A lacunar syndrome is generally the result of a small deep infarct within the territory of a single perforating artery with the maximum diameter on imaging of 15 mm. Recent studies have demonstrated alternative causes of lacunar stroke other than small-vessel disease (e.g. cardio embolism, atherosclerosis or other causes), especially in large lacunae, with a potential relevance on functional outcome. These findings suggest that lacunar stroke is not always a benign disease. Moreover, clinical features may be significant in terms of disability in lacunae in close proximity to crucial anatomical site. The following chapter reports the classical lacunar syndrome and discusses the debated etiology of lacunar stroke.

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.

Angiographic findings of moyamoya vessels in a patient with rheumatoid arthritis.

and subcortical multiple ischemic lesions. Conventional angiography (CA) showed occlusion of the right internal carotid artery (ICA) in the terminal portion and stenosis of the proximal right ICA with occlusion of the proximal portion of the right middle cerebral artery. Moreover, the patient suffered from symmetrical aching and shoulder, knee and hand stiffness responsive to low-dose corticosteroid therapy (prednisone 25 mg per day). ESR was 117, reactive C protein (RCP) 10.5 mg/dl and rheumatoid factor 650 UI/l. High ESR, RCP and rheumatoid factor values were present before ischemic events and confi rmed during follow-up. Search for other infl ammatory and immunitary parameters was negative as well as antiphospholipid antibodies. Nineteen months later, after new ischemic events involving the left occipital cortex with persistent right lateral homonymous hemianopia, a second cerebral CA was performed. CA demonstrated occlusion of the left cerebral posterior artery, right ICA terminal portion tight stenosis, left ICA proximal tract irregular profi les and occlusion of the same vessel in the terminal portion with newly developed moyamoya vessels prevalent in the left basal area where they appeared in the shape of smoke spirals ( fi g. 1 ). Prednisone was increased (75 mg per day) and anticoagulation was continued. After 6 months of follow-up the patient remained asymptomatic. This is the fi rst report in the literature of a patient with moyamoya vessels associated with RA. Cerebrovasc Dis 2005;20:415–416 DOI: 10.1159/000088666

Response to Letter by Guedes and Ferro

Response: We appreciate the attention of Guedes and Ferro to our meta-analysis of randomized controlled trials on the efficacy and safety of anticoagulant treatment in acute cardioembolic stroke.1 Indeed, our paper was submitted to Stroke on April 26, 2006, and thus before the ENS meeting held in September 2 to 5, 2006. After updating the meta-analysis by adding the ARGIS-1 study,2 Guedes and Ferro confirmed that the routine use of anticoagulants in the first …