الفهرس 
PHYSIOLOGY AND PATHOPHYSIOLOGY OF ACUTE ISCHEMIC STROKEOnly 14 pages are availabe for public view
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Abstract
S
troke is a global epidemic and a major public health-care concern, it is usually associated with a detrimental impact on survival and quality of life of the patient, and a high economic cost. Worldwide, stroke is the second most common cause of mortality and the third most common cause of disability, the global burden of stroke-related disability is high and increasing. While the incidence of stroke is decreasing in high-income countries, the incidence is increasing in low-income countries (Shrivastava et al., 2013). Official national statistics indicate that diseases of the circulatory system, including stroke, are the primary cause of death in Egypt and account for one third of all deaths. Stroke accounts for 6.4% of all deaths and thus ranks 3rd after heart disease and gastrointestinal (especially liver) diseases. Deaths attributable to stroke have remained relatively unchanged during the past 10 years (CAPMAS, 2013).
Risk factors for ischemic stroke include modifiable and non-modifiable conditions. Identification of risk factors in each patient can uncover clues to the cause of the stroke and the most appropriate treatment and secondary prevention plan (Sacco et al., 1997).
Non modifiable risk factors include age, race sex while modifiable risk factors include the following hypertension, diabetes mellitus, cardiac disease, hypercholesterolemia, TIAs, carotid stenosis, excessive alcohol intake, tobacco use, physical inactivity and obesity (Sacco et al., 1997).
Inflammation appears to play an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Clinically, the susceptibility of the patients to stroke and the subsequent prognosis are influenced by systemic inflammatory processes. Stroke patients with systemic inflammation exhibit clinically poorer outcomes (Jin et al., 2010).
Carotid artery intima-media thickness (IMT) measurements are recognized as a surrogate measure of atherosclerosis. The measurement is performed on high-resolution ultrasound images of the carotid artery. It is considered as Non-invasive imaging of the carotid arteries has been suggested to be a valid “window” or indicator site for general atherosclerosis in epidemiological studies (Rosvall et al., 2005).
Increased IMT values indicate a higher likelihood of having had a stroke or transient ischemic attack. In epidemiological studies, IMT measurements made in asymptomatic individuals also predict future cerebrovascular events. IMT measurements have been used in clinical trials as a means of gauging the effects of interventions that modify cardiovascular risk factors, a positive response to the intervention is defined as a measurable difference in IMT values of the treated group as compared with a control group (Polak et al., 2010).
An ideal blood biomarker for stroke would be reliable, rapidly measured, and readily available, and might assist with diagnosis, determination of stroke subtype or mechanism, or prediction of outcome or response to therapy. The development of diagnostic blood biomarkers for stroke, which might help distinguish stroke from mimics, faces tremendous challenges given the heterogeneity of stroke, the presence of the blood-brain-barrier, and the complexity of brain injury. Once validated, such biomarkers could be useful for choosing specific primary and secondary prevention strategies (Jickling and Sharp, 2011).
Numerous biomarkers are associated with stroke outcome, including the risk of first or recurrent stroke, though how to incorporate these markers into clinically meaningful prognostic tools remains controversial. Markers may also predict risk of early complications in stroke patients, allowing closer monitoring and earlier intervention. However, it remains uncertain how much additive value is provided beyond traditional risk assessment (Jickling and Sharp, 2011). In this study, it was focused on the Hs-CRP as a blood biomarker.
CRP is an acute-phase protein, which was synthesized and released into the peripheral blood by the liver in response to inflammation. Normally, CRP level in plasma is very low. When the acute inflammatory response or tissue injury occurred, its level rapidly increased within several hours and reached a peak after 2 days of stroke (Di Napoli et al., 2005). Data demonstrated that elevated CRP in plasma could predict not only future vascular events in healthy individuals, but also an increased risk of fatal or nonfatal cerebrovascular events in ischemic stroke patients (Seo et al., 2012). Elevated CRP levels at admission are significantly associated with early neurologic deterioration (Chan et al., 2012) poorer functional outcome, both short- and long-term mortality after stroke and predict a larger infarct size (Dewan et al., 2011).
Stroke is a global health-care concern, for improving the short-term and long-term prognosis of stroke, every attempt should be taken toward a comprehensive approach for the best possible outcome (Shrivastava et al., 2013). Primary prevention includes lifestyle associated with the risk for stroke in the form of promoting a healthy diet, physical activity, and cessation of tobacco, is a must in bringing down the incidence of stroke to a significant extent, including use of antiplatelet and statins for high risk personnel. Secondary prevention is indispensable in ascertaining long-term outcome of patient survival, disability, and quality of life (Shrivastava et al., 2013).
In this study it was focused on the use of statins as several large clinical trials of statins have shown a significant reduction in ischemic stroke in patients with coronary artery disease. However, the reduction in serum cholesterol does not seem to entirely explain the protective effect. Anti-inflammatory and neuroprotective properties of statins, in addition to their lipid-lowering effects, have therefore been proposed (Liao and Laufs, 2005). Pravastatin lowers CRP levels in a manner largely independent of effects on LDL cholesterol in subjects with and without a history of cardiovascular disease. Statin use after ischemic stroke is associated with CRP reduction and improved prognosis independent of lipid lowering, with the greatest risk reduction seen in patients with higher CRP levels. Pleiotropic effects of statins upon the vasculature are reported to include antithrombotic actions, improvement of endothelial function, and atherosclerotic plaque stabilization (Albert et al., 2001).
This study was conducted among sixty four patients who suffered first-ever recent anterior circulation ischemic stroke, Patients were recruited from Ain Shams University hospitals. Patients who suffered, recurrent stroke, TIA, ICH, stroke of posterior circulation origin, evidence of confounding inflammatory process, evidence of cardio embolic source of stroke, receiving thrombolytic therapy were excluded.
The study subjects were investigated by basic laboratory data including quantitative Hs-CRP, full lipid profile, including Low-density lipoprotein (LDL), High-density lipoprotein (HDL), Triglycerides, Total cholesterol, carotid duplex with assessment of carotid Intimal Media Thickness in addition to the size of the subjects’ stroke was estimated using the ABC/2 method calculated from the MRI diffusion weighted film. The initial burden and the prognosis of subjects’ ischemic strokes were estimated using the NIHSS on admission, after 1 month and the MRS conducted 3 months after the onset of their insults.
The results showed there is significant positive correlation between Hs –CRP with IMT on asymptomatic side yet no correlation between Hs-CRP and IMT on symptomatic side.
While comparing Hs-CRP value in large vessel stroke and small vessel stroke, it was found no significant difference, yet mean CRP was slightly higher in large vessel stroke.
Moreover, No significant correlation was found between the volume of infarction and the intimal medial thickness on both the symptomatic and asymptomatic side.
Correlations between Hs-CRP as a prognostic blood biomarker and NIH on admission, NIH after one month and MRS were done, it showed there was a positive significant correlation between Hs-CRP and MRS while no significant correlations were found as regards Hs-CRP and NIH on admission, NIH after one month suggesting the value of Hs-CRP can affect the patient’s prognosis after 3 month more than shorter term follow up as a prognostic blood biomarker.
In this study patient’s serum Magnesium was also correlated with Hs-CRP values, and it was found that a significant correlation as patients with high serum Magnesium had high Hs- CRP value. While patients with low serum Magnesium had low value of Hs- CRP, opposite to some studies.
At the end of the study, it was concluded that Hs-CRP could serve as prognostic blood biomarker in longer follow up of stroke patients rather than shorter ones, and Hs-CRP was correlated to CIMT on asymptomatic side of the lesion with no significant correlation to size of stroke.