Stroke occurs when the blood flow to a part of the brain is suddenly blocked by occlusion (ischemic stroke, responsible for about 90% of strokes). The acute death of brain cells is caused by reduced delivery of oxygen. Within the ischemic core zone, most of the affected cells are neurons, because they show the highest vulnerability to oxygen deprivation. Surrounding the ischemic core zone, there is an area of moderately ischemic brain tissues called penumbra where surviving cells are exposed to secondary deleterious phenomena, such as excitotoxicity, spreading depolarization and inflammation. Thus the prime goal of neuroprotection is to rescue the penumbra. Clincially, depending on the part of the brain that is affected, strokes can result in weakness or paralysis of the arms, legs and/or facial muslces, loss of vision or speech, and imparied walking.
The two most common forms of ischemia (deficiency of oxygen in a part of the body causing metabolic changes) are cardiovascular and crebrovascular. Cardiovascular ischemia, in which the body’s capacity to provide oxygen to the heart is diminished, is the leading cause of illness and death in the US. Crerebral ischemia is a precursor to cerebrovascular accident (stroke) which is the third leading cause of death in the US. Bar-Or (US 7,449,338)
Signs and Symptoms :
Timely receipt of appropriate treatments for stroke requires prompt recognition of stroke signs and sumptoms and activaiton of EMS. The five major signs and symptoms of stroke include 1) sudden severe headache; 2) sudden loss of vision in one or both eyes, 3) sudden weakness in an arm, a leg, or the face, 4) sudden confusion, trouble speaking, or understanding, and 5) sudden trouble walking, dizziness, or loss of balance or coordination.
Full-blown strokes are often preceded by transient ischemic attachs (TIA)
Pathological mechanisms/Risk factors:
The continum of ischemic disease includes (1) elevated blood levels of cholesterol and other blood lipids; (2) subsequent narrowing of the arteries, (3) reduced blood flow to the body organ (as a result of arterial narrowing), (4) cellular damage to an organ caused by a lack of oxygen and (5) death of organ tissue caused by sustained oxygen depreivation. (3-5) above are collectively referred to as “ischemic disease” while (1-2) are considered its precursors.
Risk factors for ischemic heart disease indclude being over age 50, smoking, diabetes mellitus, obesity, high blood pressure, elevated low density lipoproteins, high cholesterol and strong family history of cardiac disease.
Diagnosis:
It is known that immediately folloiwng an ischemic event, proteins such as creatine kinase (CK),serum glutamic oxalacetic transaminase (SGOT) and lactic dehydrogenase (LDH) are released, and these proteins have been used for evaluating the occurrence of past ischemic heart events (US 4,492,753).
Bar-Or (US 7,449,338) teaches a method of testing for the existence of ischemia based on detecting the existence of an alteration of the serum protein albumin which occurs folloiwng an ischemic event.
Treatment:
Early treatment is very important with stroke. Among persons with onset of stroke, less than half arrived at the hosptial within 2 hours of symptom onset. Rapid removal of a thrombus (i.e., bloot clot) after ischemic stroke can greatly reduce the risk of the loss of brain fnction.
— TPA (issue plasminogen activator): is the only treatment approved by the FDA for use with ischemic stroke patients and is only approved for use within 3 hours of symptom onset. Patients treated with tPA are 30%-50% more likely to have good functional outcomes than those who do not receive tPA. However, intravenous recombinant tissue plasminogen activator (rtPA) is associated with increased risk of intracerebral hemorrhage.
–A CT scan is a crucial component of optimal stroke care for all stroke patients. The National Institutes of Neurological Disorders and Stroke recommends that stroke patients receive an initial CT scane within 25 minutes of hospital arrival.
–Mechanical removal: Blood clots can also be mechanically removed using a system called Mechanical Embolus Removal in Cerebral Ischemia (MERCI®). Ultrasound may also be used to enhance the effectivenss of the tPA or to physically remove the thrombus. Magnetci partciles either conjugated to biomolecules which allows specific attachment to thrombus tissue (US 12/403,124) or which can be directed to the thrombus and disrupt it with the assistance of a magetic wave (see Drug Delivery) have also been used.
Complications from Stroke:
Thromboysis (dissolution of blood clots) relies upon the administration of exogenous plasinogen activators that lyse fibrin. However, significant risks include uncontrolled bleeding. The most feared complication of thromobytic therapty is symptomatic intracranial hemorrhage (SICH).
Clopidogrel bisulfate sold as Plavix was introduced in the U.S. in 1998.