Stroke / Brain Attack
Thrombolytic Therapy in Acute Stroke

The Role of Imaging in Acute Stroke Patients- by Dr. Ph Demaerel in Current Approach to Acute Stroke Management 1996

CT is currently the modality of choice in acute stroke patients in part due to its ready availablity. It is usually requested to exclude a hemorrhage, or other lesions. Although early large vessel infarct can be detected when images are carefully reviewed, CT has relatively poor sensitivity in detecting ischemia- the sensitivity of unenhanced CT ranges from 30% to 79% according to the literature. MRI is can detect 82-95% of early ischemic stroke , due to its superiority in detecting changes in tissue water content. Potential problems with MRI are the monitoring of patients, motion, claustrophobia and not as readily available.

From the viewpoint of therapu, it is important to detect hemorrhagic changes in an infarct and to exclude a hemorrhage. CT can easily detect these due to their hyperdense appearance and therefore can be differentiated from the surrounding gray and white matter.

In the near future, combined diffusion weighted and perfusion imaging are likely to further elucidate the pathophysilogy of infarcts.

Thrombolytic therapy In Ischemic Stroke by Dr. W. Hacke et al in Current Approach to Acute Stroke Management 1996

Acute intervention for ischemic stroke is currently the subject of intensive research. Two such approaches are under investigation: the use of thrombolytic agents to restore perfusion to ischemic tissue, and the development of neuroprotective agents to limit neuronal damage. This article reviews the use of thrombolysis in stroke.

Large-scale trials have shown that thrombolytic therapy reduces mortality and preserves left ventricular function in patients with acute myocardial infarction. As most ischemic strokes are thromboembolic in origin, thereappears to be a rationale for the use of thrombolysis in ischemic stroke.

Early angiographic studies show that a high proportion of patients with hyperacute ischemic stroke have a corresponding cerebral artery occlusion. Some strokes may result from occlusion of vessels too small to be detected byangiography." Early thrombolytic therapy during ischemic stroke could potentially restore perfusion to the affected area. However, CT is necessary to identify patients whose stroke is hemorrhagic, rather than ischemic before treatment can begin.

The timing of thrombolytic therapy is important. Following occlusion of a cerebral artery, the infarct is surrounded by an expanding area of poorly perfused tissue (the ischemic penumbra), which can be salvaged if perfusion is restored within a critical time period. Studies in animals suggest that this period lasts no more than 1 -- 3 hours. It has been discussed that the duration in humans may be a little bit longer. Thrombolytic therapy is, therefore, rarely started after 6 hours and should begin as early as possible.

Data from open uncontrolled trials of thrombolysis in stroke report the occurrence of hemorrhage as between 0 -- 18%. In view of the risk of intracerebral hemorrhage associated with thrombolytic drugs, CT is advisable to exclude bleeding, and identify patients with major infarcts or hemispheric ischemia who appear to be at increased risk of hemorrhagic complications.

In the National Institute Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, 624 patients were treated with rt-PA, 0.9 mg/kg, or placebo within 3 hours of the onset of symptoms (half of the patients were treated within 90 minutes). There was no significant difference in early clinical effect, as indicated by either an improvement of four points on the National Institutes of Health Stroke Scale (NIHSS) or resolution of the neurological deficit within 24 hours, but there was a significant improvement in median NIHSS. Most importantly, there was a significant improvement in outcome after 3 months in patients treated with rt-PA; this group were at least 30% more likely to show no disability (12% absolute increase), as measured by the Barthel Index, Modified Rankin Scale, Glasgow Coma Score and NIHSS. This benefit was seen in all stroke subtypes. Symptomatic intracerebral hemorrhages occurred within 36 hours in 6.4% of patients receiving rt-PA, compared with only 0.6% of placebo-treated patients (P < 0.001), but there was no significant difference in 3-month mortality between the groups.

Conclusions:

Thrombolytic treatment may have an important role in the management of acute stroke, but the studies to-date highlight the importance of early intervention and careful patient selection. In the NINDS trial, treatment within 3 hours was associated with an improved functional outcome without an increase in mortality. In ECASS, treatment of eligible patients resulted in improved neurologic and functional outcome. In the MAST-E and ASK trials, later intervention was associated with an increased risk of cerebral hemorrhage and poor outcome. Successful use of thrombolytic therapy, therefore, depends on rapid assessment to exclude patients with hemorrhagic stroke or those at risk of hemorrhagic complications. At present, though thrombolysis cannot be recommended for all patients with acute stroke, it has been shown to be beneficial in patients treated within 3 hours who conform to the strict inclusion and exclusion criteria of the NINDS trial.

Additional readings:

Haley EC Jr. Thrombolytic therapy for acute ischemic stroke. Clin Neuropharmacol 1993; 16: 179 -- 94.

Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017 -- 25.

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581 -- 7.

The multicenter Acute Stroke Trial --Europe Study Group. Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med 1996; 335: 145-50.

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