TREATMENT OF A CUTE I SCHEMIC

CHEMIC stroke exacts a heavy toll in death and

disability worldwide. In the United States, where

it is the third leading cause of death and the leading

cause of serious long-term disability, approximately

750,000 strokes occur annually, with an annual

mortality rate exceeding 150,000.

In June 1996, the Food and Drug Administration

(FDA) approved tissue plasminogen activator (t-PA)

as a safe and effective treatment for stroke if it is given

within three hours after the onset of symptoms of

stroke.

Subsequently, results of large clinical trials

testing the efficacy of antiplatelet, antithrombotic,

and neuroprotective treatments appeared. More recently,

intraarterial thrombolytic treatment was found

to improve the neurologic outcome in patients with

occlusion of the middle cerebral artery.

More difficult to evaluate have been approaches to treatment

involving integrated stroke-intervention teams and

procedures for rehabilitation during the period of convalescence

immediately after a stroke. Here, we review

data from clinical trials and current treatment options

for patients with acute ischemic stroke.

PATHOPHYSIOLOGY AND TARGETS

FOR INTERVENTION

Acute ischemic stroke results from the abrupt interruption

of focal cerebral blood flow.Angiographically

visible embolic or thrombotic occlusions have

been identified as the cause of stroke in 70 to 80 percent

of patients with symptoms severe enough to warrant

early arteriography.The rate of visible occlusions

is probably lower among all patients with stroke,

such as those with mild strokes or classic lacunar syndromes.

Other causes of decreased cerebral blood flow

include abrupt occlusion of small penetrating arteries

and arterioles, single or multiple high-grade arterial

stenoses with poor blood flow through collateral

vessels, arteritis, arterial dissection, venous occlusion,

and profound anemia or profound hyperviscosity.

The molecular events initiated by acute focal ischemia

can be summarized as a time-dependent cascade,

characterized by decreased energy production; overstimulation

of neuronal glutamate receptors (excitotoxicity);

excessive intraneuronal accumulation of

sodium, chloride, and calcium ions; mitochondrial injury;

and eventual cell death (Fig. 1).The fundamental

goals of intervention are to restore normal cerebral

blood flow as soon as possible and to protect

neurons by interrupting or slowing the ischemic cascade.

Studies using magnetic resonance imaging

(MRI) and positron-emission tomography suggest

that critical ischemia rapidly produces a core of infarcted

brain tissue surrounded by hypoxic but potentially

salvageable tissue.