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
|Angiogram showing the microcatheter
inserted into a blocked artery prior to administration
of the 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.
|Picture of the MERCI Retriever
|X-ray showing the MERCI Retriever
System after placement in a patient.
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.
The MERCI retriever (Mechanical Embolus Removal in
Cerebral Ischemia), a cork-screw shaped device, is the
first FDA approved mechanical device for the treatment
of ischemic stroke. It was granted clearance by the
FDA after a thorough review of patient data obtained
in a clinical study at 25 medical centers in the US.
In that study, 40 percent of 141 patients whose blood
clots were successfully removed had positive outcomes.
The major limitation to the retriever device is that
the clot must be visible and accessible in order for
the physician to guide the catheter to the location
of the clot.
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
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.
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.
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.