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The Comprehensive Stroke Center at University Hospital

Treating Acute Ischemic Stroke


Ischemic stroke is caused by a blockage in a blood vessel that stops the flow of blood and deprives the surrounding brain tissue of oxygen. In the absence of oxygen, the brain cells in the immediate area begin to die and release a cascade of toxic chemicals that threaten brain tissue in the surrounding area — the ischemic penumbra.

Angiogram 3D reconstruction showing area of intracranial arterial blockage.

The central goal in treating acute ischemic stroke is to preserve healthy brain tissue surrounding the blockage. This can be accomplished by removing the blockage and restoring blood flow to the area, or by protecting the surrounding tissue.

Interventional Drug Therapy
Thrombolytic drug therapy has helped to change the course of ischemic stroke. It involves the use of a thrombolytic drug — also called a fibronolytic or clot-buster — delivered through the blood vessels to break-up the clot that is disrupting the blood flow.

Currently, tissue Plasminogen Activator (tPA) is the only thrombolytic agent approved by the Food and Drug Administration (FDA) for treating acute ischemic stroke. tPA occurs naturally in the body — it's an enzyme made by cells in blood vessel walls. Stroke specialists use a genetically engineered version, which was first employed in the treatment of blood clots in the heart. Use of tPA offers a 30 percent to 50 percent better chance of cure from stroke disability.

There are two ways to administer tPA — intravenously, or intra-arterially directly at the clot site in the artery. Only the intravenous route has received FDA approval, but comprehensive stroke centers around the country have been using the intra-arterial approach with significant success.

Criteria for tPA Use
There are a number of important criteria that an ischemic stroke patient must meet in order to receive “clot busting” therapy. For instance, there is a narrow (though widening) window of time in which tPA can be used effectively. Failure to recognize stroke and get to a hospital within that window is a primary obstacle to otherwise eligible patients receiving tPA treatment.

In addition, there must be no evidence of bleeding (hemorrhage) because thrombolytic therapy can exacerbate a hemorrhagic stroke. And patients taking blood thinners cannot receive tPA. Other exclusion criteria include severely elevated blood pressure or blood sugar, recent surgery, low platelet count, and end-stage liver or kidney disorders. Currently, tPA therapy is appropriate for about 5 percent to 10 percent of stroke patients.

Intravenous (IV) tPA: When administered intravenously (usually through a vein in the arm), tPA travels from the point of injection through the blood stream until it reaches the blockage. Significant amounts of tPA must be used because the drug becomes diluted in the blood stream as it travels to the site of blockage. A good analogy is a clog in the drain of a bathtub that is full of water. If a clog-dissolving chemical is poured into the water in the tub, it’s going to take a while to make its way down the drain to the blockage, and significant amounts will be required to counter the diluting effect of the water.

To effectively prevent or contain the damage, tPA must be administered intravenously within three hours of the onset of stroke symptoms. In its guidelines for acute ischemic stroke, the National Institute of Health (NIH) calls this the “golden hour” of diagnosis and treatment.

Angiogram showing the microcatheter inserted into a blocked artery prior to administration of the tPA

Intra-arterial tPA: This is a faster way than the intravenous method for delivering clot-busting tPA to the blockage. It is a procedure that cardiologists have been using for years to open clogged vessels in the heart and other areas of the body. In the intra-arterial tPA procedure, the neurovascular specialist inserts a thin, flexible catheter into an artery (usually in the groin area) and steers it up to the area of the clot then administers the tPA through the catheter.

Using the clogged-bathtub drain analogy from above, if a plumbing snake could be threaded down to the point of blockage, and the clog-dissolving chemical sent through it directly to the clog, it could work a lot faster and less of the chemical would be needed.

The intra-arterial method of delivering tPA to the clot can expand the window of treatment opportunity wider than the three hours recommended for IV tPA. It appears that patients can be successfully treated for up to six hours when tPA is administered intra-arterially at the site of the blockage because the blood flow will begin almost immediately. In addition, less tPA is needed when it is delivered directly to the clot, which can reduce the possibility of intracranial hemorrhage.

Mechanical Clot Busting

Many patients arrive at the hospital too late to qualify for intervention with tPA or they have some other contraindications that effectively prohibit the use of the drug. A new potential companion or alternative to thrombolytic therapy is generating excitement among brain experts for speeding up the process of removing clots involved in ischemic stroke. It is an endovascular procedure involving the use of a mechanical device on the end of a catheter to physically pull out all or part of a clot.

Damage Containment

A clot may or may not go away on its own. If it breaks up on its own, smaller pieces may lodge further down in a smaller vessel. While not ideal, at least the area of damage will be smaller. There is a lot of brain that medicine does not recognize as being “eloquent” (associated with a function like movement, forming words, recognizing objects, etc.) If clots lodge in those areas, then the patient effectively suffers no discernible deficits.

Sometimes blood flow will re-route through collateral pathways (like bypasses). The Circle of Willis provides the major form of collateral blood flow to the brain. Other avenues include vessels called pia-pial or leptomeningial collaterals along the convexities of the brain. Some vessels may remain permanently blocked (occluded) and the body will heal them up and form a scar.

When intervention (elimination of the clot) is not possible, the stroke team focuses on preserving as much of the brain as possible. This can be achieved in several ways, including some that are still investigational and not yet widely available.

Drug Therapy: Administration of antiplatelet agents, such as aspirin, has been shown to improve outcome in acute stroke and decrease the risk of stroke recurrence. Hypoglycemia (abnormally low levels of sugar in the blood) and hyperglycemia (excess levels of sugar in the blood) can aggravate stroke damage. So hypoglycemic patients often are given glucose, while hyperglycemic patients receive insulin.

Investigational Therapies: Researchers are looking at a number of “protective measures” such as reducing body or brain temperature (hypothermia). They are also exploring chemicals to bind up white blood cells — which appear to contribute to the extent of stroke damage — and prevent them from doing their job.