Intravenous thrombolysis in young stroke patients: results from the SITS-ISTR.

OBJECTIVE: To assess safety and efficacy of thrombolysis in 18- to 50-year-old patients compared to those aged 51 to 80 years recorded in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). METHODS: A total of 27,671 patients aged 18-80 years treated with IV alteplase within 4.5 hours of symptom onset were enrolled in SITS-ISTR between 2002 and 2010. Main outcome measures were symptomatic intracerebral hemorrhage (SICH; deterioration of ≥4 points on the NIH Stroke Scale [NIHSS] within 24 hours and type 2 parenchymal hematoma), mortality, and functional independence (modified Rankin Scale [mRS] 0-2) at 3 months. RESULTS: In the 3,246 (11.7%) patients aged 18-50, SICH occurred in 0.6% vs 1.9% in those aged 51-80 (adjusted odds ratio [aOR] 0.53; 95% confidence interval [CI] 0.31-0.90, p = 0.02). Three-month mortality was 4.9% and 14.4%, respectively (aOR 0.49; 95% CI 0.40-0.60, p < 0.001) and functional independence was 72.1% vs 54.5%, respectively (aOR 1.61; 95% CI 1.43-1.80, p < 0.0001). In multivariable analysis in young patients, baseline systolic blood pressure (SBP) was the only independent factor associated with SICH (p = 0.04). Baseline NIHSS, baseline glucose, and signs of infarction in baseline imaging scan were associated with higher mortality and poorer functional outcome. Male gender, mRS before stroke, and atrial fibrillation (AF) were associated with higher mortality, and age, SBP, and previous stroke were associated with mRS. CONCLUSIONS: Treatment with IV alteplase is safe in young ischemic stroke patients and they benefit more compared to older patients. We found several factors associated with SICH, mortality, and functional outcome. These can be used to help in the selection of young ischemic stroke patients for thrombolysis. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that younger patients (18-50 years) with ischemic stroke symptoms treated with IV alteplase have lower morbidity and mortality compared to older patients (51-80 years).

Safe implementation of thrombolysis in stroke-monitoring study in Italy.

BACKGROUND AND PURPOSE: The safe implementation of thrombolysis in stroke-monitoring (SITS-MOST) study was an unique opportunity to test in Italy, where only few centres were expert in thrombolytic treatment before, safety and efficacy of i.v. alteplase within 3 h of ischaemic stroke outside the setting of clinical trials. METHODS: In Italy to participate in the study the clinical centres had to possess organizational and structural characteristics certified by Regional Health Authorities. RESULTS: Seventy-one centres were activated, 56 (79%) treated patients of which 41 (73%) had never used thrombolysis before the study. Globally, 586 patients were included. Baseline median National Institute of Health Stroke Scale of Italian patients was 13 vs. 12 in other European centres (P = 0.0001). Symptomatic intracerebral haemorrhage as per the NINDS/Cochrane definition, mortality and independence (modified Rankin Scale 0-2) rates at 3 months occurred respectively in 6.7% (95% CI: 4.8-9.1), 11.7% (9.2-14.6) and 51.6% (47.4-55.7) of Italian patients compared with 7.3% (6.7-8.0) (P = 0.56), 11.2% (10.4-12.1) (P = 0.75) and 55.1% (53.8-56.4) (P = 0.09) in the European patients and in 8.6% (40/65; 6.3-11.6), 17.3% (14.1-21.1) and 50.1% (44.5-54.7) of the patients treated in the pooled randomized controlled trials. CONCLUSIONS: The SITS-MOST study showed that in Italy i.v. alteplase is safe and effective in routine clinical use also in non-expert centres.

The SITS-MOST registry.

In September 2002 the European Medicines Evaluation Agency (EMEA) approved a licence for alteplase (rt-PA) in the treatment of ischaemic stroke within 3 h of symptom onset. One of the conditions required by the EU regulatory authorities for the official definitive approval of thrombolytic therapy was that treatment safety should be monitored over a period of three years by entering all treated patients in the SITS-ISTR (Safe Implementation of Thrombolysis in Stroke -Thrombolysis Register) web register, in accordance with a study protocol, the SITS Monitoring Study - SITS-MOST. The aims of this study are to evaluate the efficacy (in terms of functional independence for activities of daily living at three months after treatment) and safety (in terms of symptomatic intracerebral haemorrhage and death) of the thrombolytic treatment in real routine clinical practice, outside the ideal conditions of an experimental setting, and to compare the results with a systematic review from the randomised clinical trials.

Specific therapies for ischaemic stroke: rTPA and others.

In the last few years there have been several important advances in the understanding of cerebrovascular disorder pathophysiology that have impacted on stroke management. The development of timely and effective treatment strategies was and is still considered a high priority issue. Therapeutic options dramatically increased both in the prevention and overall in the treatment of acute ischaemic stroke (AIS). At present, whereas neuroprotection remains experimental, intravenous (i.v.) thrombolysis is the only specific therapy effective in reducing mortality and disability associated with stroke. The efficacy and safety of the antithrombotic therapy in AIS treatment are not well established, and few issues in clinical stroke management are more controversial. However, some studies have brought new light and new doubts on the roles of these traditional therapies.

Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke.

OBJECTIVES: Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke. METHODS: We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnI) with (a) all-cause mortality over a six month follow up, and (b) in-hospital death or major non-fatal cardiac event (angina, myocardial infarction, or heart failure). RESULTS: cTnI levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10-0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p<0.0001, log rank test for trend). On multivariate analysis, cTnI level was an independent predictor of mortality (low positive cTnI, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnI, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnI also predicted a higher risk of the combined endpoint "in-hospital death or non-fatal cardiac event". Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results. CONCLUSIONS: cTnI positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnI positive patients can reduce cardiac morbidity and mortality should be the focus of future research.

Computed tomography findings in the first few hours of ischemic stroke: implications for the clinician.

In order to evaluate the clinical usefulness of emergency computed tomography (CT) in acute ischemic stroke, we assessed whether CT findings within the first few hours of stroke onset reliably predict type, site and size of the index infarction, and risk of death or disability. For this reason we reviewed clinical and CT findings in a cohort of unselected consecutive patients referred to the stroke unit of a large urban hospital because of a presumed ischemic stroke in the anterior circulation (AC), and submitted to CT within 5 h from onset. Out of 158 total patients, emergency CT revealed parenchymal changes compatible with AC focal ischemia in 77 (49%) and a hyperdense middle cerebral artery (MCA) in 41 (26%). Parenchymal changes and hyperdense MCA predicted an AC territorial infarction respectively in 97% of cases (95% C.I. 93% to 100%) and in 95% of cases (95% C.I. 88% to 100%). Site and size of early changes coincided with those of final lesions in 79% of patients with cortical changes and in 95% of patients with cortico-subcortical changes, but only in 37% of patients with initial subcortical changes, the remainder of whom developed a cortico-subcortical infarction. At logistic regression parenchymal changes were the only independent predictor of an AC territorial infarction. Negative predictive power, however, was only 40% (95% C. I. 29% to 51%) for parenchymal changes, and 35% for hyperdense MCA (95% C.I. 26% to 44%). The odds for death or disability at 1 month associated with parenchymal changes were thrice as high as with negative CT, even after adjustment for clinical severity on admission. These results indicate that CT scan adds significantly to the prediction of outcome made on clinical grounds. The frequent development of a territorial infarction in patients with initially negative CT and the subsequent recruitment of the cortex in those initially exhibiting only subcortical changes suggest that the transition from ischemia to infarction often occurs after the first five h following stroke.

[Nursing documentation in the Stroke Unit]. / Cartella infermieristica nelle stroke units.

The organization of Stroke Unit improved prognosis of stroke patient. The randomized studies emphasized the importance of nursing in such a structure. In order to improve nursing process in our Stroke Unit, we designed a nurse record which includes a neurological scale, to define dependence classes and guidelines based on Virgina Henderson's theoretical model. In this paper, we present this nurse record and we describe the various steps of its design.

Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.

BACKGROUND AND PURPOSE: The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. METHODS: We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. RESULTS: Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. CONCLUSIONS: Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.