The treatment of patients with acute stroke is reviewed. Evidence of the existence of an ischemic penumbra in humans is presented. Different approaches to treatment of acute stroke include restoring blood flow by thrombolysis, neuroprotection, and early secondary prevention with aspirin. The evidence for each of these approaches is reviewed. Organization of stroke services, and particularly the use of stroke units, have been shown to significantly improve stroke outcome and these data are presented.

Acute Stroke

The ischaemic penumbra has been documented in the laboratory animal as a severely hypoperfused, non-functional, but still viable cortex surrounding the irreversibly damaged ischaemic core; with elapsing time, more penumbra gets recruited into the core, while tissue reperfusion is able to stop this deleterious process until a certain point in time As saving the penumbra should improve clinical outcome, it should constitute the main target of acute stroke therapy In a series of PET studies performed 5-18 h after stroke onset, we were able to (i) document, for the first time in man, the existence of tissue fulfilling operational criteria for penumbra in about one third of the cases; (ii) show that long-term neurological recovery is proportional to the volume of penumbra that eventually escapes infarction, and (iii) detect penumbral tissue as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in such cases Mapping the penumbra in the individual patient with neuroimaging procedures should allow to formulate a pathophysiological diagnosis, and thus to design a rational management of the stroke patient and to improve the selection of candidates for therapeutic trials

Mapping the ischaemic penumbra with PET: implications for acute stroke treatment.

The Cochrane Database of Systematic Reviews summarizes all the existing randomized evidence of all treatments for all diseases, so that doctors can quickly access the most up-to-date information. The trials for the Cochrane systematic review of thrombolytic therapy in acute ischemic stroke were identified from extensive searching of the literature and contact with trial investigators. Data on several prespecified outcomes (death and symptomatic intracranial hemorrhages within the first 7 to 10 days after treatment, and death and poor functional outcome at long-term follow-up) were sought in each identified randomized, controlled trial. There have thus far been 17 completed randomized, controlled trials of thrombolytic therapy versus control in 5,216 patients (including the provisional data from the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke [ATLANTIS] A and B and Recombinant Prourokinase in Acute Cerebral Thromboembolism [PROACT] II trials). Of these, eight trials tested recombinant tissue plasminogen activator (rt-PA) in 2,889 patients (56% of all data). Overall, there was an increase in the odds of death within the first 10 days (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.48 to 2.32) and symptomatic intracranial hemorrhage (OR 3.53, 95% CI 2.79 to 4.45) with thrombolysis (slightly less with rt-PA). The odds of death at the end of follow-up were also slightly increased with thrombolysis (OR 1.31, 95% CI 1.13 to 1.52), although this increase was not significant in patients receiving rt-PA. Despite this, overall there was a significant reduction in the number of patients with a poor functional outcome (combined death or dependency) at the end of follow-up (OR 0.83, 95% CI 0.73 to 0.94), which was slightly better in patients receiving rt-PA. Most of the data came from trials testing thrombolysis up to 6 hours after stroke, but the subgroup of patients treated within 3 hours showed a greater reduction in poor functional outcome with thrombolysis (OR 0.58, 95% CI 0.46 to 0.74) with a less adverse effect on death. The available data do not allow much further subgroup analysis, although there is reasonable evidence to indicate that aspirin or heparin given within 24 hours of thrombolytic therapy causes a significant increase in intracranial hemorrhage and death. It is hoped that a meta-analysis using individual patient data may be able to address the effect of thrombolysis in further specific subgroups and examine the interaction between the severity of stroke and the effect of thrombolysis.

Overview of Cochrane thrombolysis meta-analysis.

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Mapping the ischaemic penumbra with PET: implications for acute stroke treatment.

Overview of Cochrane thrombolysis meta-analysis.