Stroke

Markers for Diagnosis and Progression of Ischemic Stroke

Ischemic stroke is a cardiovascular disease that affects over 700,000 people every year and over 75% of patients will go on to have long-term disabilities. There are two classifications of the disease: ischemic stroke and hemorrhagic stroke. Ischemic is the most common and is caused by a decrease in blood flow to a specific part of the brain whereas a hemorrhagic stroke is caused by an inter-cranial hemorrhage.

Symptoms can vary in severity; some disappear following rehabilitation, but other symptoms may last indefinitely. Symptoms include paralysis, usually down one side of the body, visual difficulties and problems with speech.

Currently the main emergency ‘test’ used is the face, arm, speech test - FAST. In a clinical setting MRI and CT scans are routine but there is no blood test currently available for determining a stroke. However researchers have, over the past few years, discovered a number of biomarkers which may help to predict cause and long-term outcome and survival following a stroke. Developing routine tests such as these would be of huge benefit as they would help to increase survival rates, and help prevent future cardiovascular disorders.

Brain Natriuretic Peptide or B-type Natriuretic Peptide (BNP) is a hormone which is secreted by heart ventricles in humans. Levels of BNP are significantly increased in the incident of an acute heart attack or stroke when compared directly to healthy individuals. This marker may also be useful in predicting the likelihood of death following a stroke.

C-Reactive Protein (CRP) is a protein which is secreted by the liver and found in the serum of patients with acute inflammation. It has been described as a marker of prognostic importance in ischemic strokes. High levels of CRP in the serum of stroke patients have correlated with an increased risk of future cardiovascular events and fatality after an ischemic stroke has occurred. However, it has limited use as a prognostic tool for diagnosing an ischemic stroke itself, as CRP is a general marker of inflammation, and is not specific to a particular condition.

D-Dimer is a small protein fragment which is broken down by fibrin. It is often found in the blood following a clot. This marker is thought to have uses in predicting the progression of an ischemic stroke. Research has shown that high levels can be seen in those patients that are at a high risk of early clinical progression, which indicates a poor prognosis.

IL-6 and MMP9 are both inflammatory molecules seen at high levels in inflamed areas of the brain in stroke patients. Again they are general markers of inflammation and therefore would not be used alone to determine a stroke but, instead, in a panel of biomarkers.

S100b is a protein which is present in glial cells in the brain, and has been implicated in inflammation. Levels of this protein have been shown to correlate with the extent of tissue damage in ischemic stroke victims, and although it is not a sole biomarker it may be a useful in the diagnosis of acute stroke.

Von willebrand factor (vWF) is an important blood glycoprotein which binds to factor VIII to aid blood clotting. It has been identified as a predictive marker for mortality following acute stroke. Elevated levels have been seen in patients who have suffered an acute stroke and it is a fairly easy protein to measure in blood so could be very useful as a routine diagnosis marker.

References:

1. Napoli, M. et al (2001) Stroke 32:917-924
2. Reynolds, M. A et al (2003) Clinical Chemistry 49: 1733-1739
3. Makikallio, A.M et al (2005) Stroke 36:1016:1020
4. Laskowitz, D.T et al (2005) Ann. N.Y. Acad. Sci. 30:1053
5. Lynch, J.R et al (2004) Stroke 35:57-63
6. Barber, M et al (2006) Stroke 37:1113-1115
7. Carter, A.M (2007) Stroke 38:1873-1880