Κυριότερος σκοπός είναι η αξιολόγηση των συστημάτων Υπολογιστικής Τομογραφίας και Μαγνητικού Συντονισμού κατά την εφαρμογή της τεχνικής Δυναμικής Αιμάτωσης (Perfusion). Επίσης η δημιουργία και εφαρμογή αναλυτικού και αποτελεσματικού πρωτοκόλλου στην οξεία ισχαιμία με σκοπό την άμεση βοήθεια του ισχαιμικού εγκεφάλου. / Thesis MSc in order to highlight the usefulness of CT Brain Perfusion in acute brain ischemia.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Current stroke imaging protocol at Barrow Neurological Institute calls for a noncontrast computed tomography (NCCT), a computed tomography angiography (CTA), and a computed tomography perfusion (CTP) at the time of presentation to the emergency department (ED), and follow up imaging includes magnetic resonance diffusion weighted imaging (MR‐DWI). This information is used to determine the appropriateness and safety of tissue plasminogen activator (tPA) administration. Previous studies have shown the risk for post‐tPA hemorrhagic conversion rises significantly as the size of the infarct core increases. Thus, it is of great importance to have an accurate method of measuring core infarct size in patients presenting with acute ischemic stroke. The purpose of our study is to determine if CTP correctly identifies the infarct core and if post‐tPA hemorrhagic conversion is related to the size of the infarct core and/or the accuracy of CTP in identifying the infarct core. The ultimate goal is to improve patient outcomes by decreasing the morbidity and mortality associated with tPA administration. This study is a retrospective chart review of all patients who presented to the ED during a one year period with signs and symptoms of acute ischemic stroke who then subsequently received tPA. Imaging was also reviewed, including the NCCT, CTA, CTP, and MRDWI for each patient. In this study, MR‐DWI is used as the gold standard for determining the presence or absence of an infarct core. CTP and MR‐DWI are in agreement of the presence of an infarct core in 7 patients, or 10 percent of the time. Similarly, CTP and MR‐DWI are in agreement of the absence of an infarct core in 31 patients, or 44 percent of the time. In the other 32 patients, CTP and MR‐DWI are in disagreement. The percent correlation between CTP and MR‐DWI was found to be 24 percent with a p‐value < 0.05. As for post‐tPA hemorrhagic conversion, 12 percent of patients had hemorrhagic conversion, and when the hemorrhage rate was compared to the size of the infarct core, the odds of post‐tPA hemorrhagic conversion were 56 times higher in the group of patients with infarct cores larger than one‐third of a vascular territory than in patients with smaller infarct cores with a p‐value < 0.001. Although no significant correlation was found between the accuracy of CTP data and the rate of post‐tPA hemorrhagic conversion, patients with concordant CTP and MR data had a 46% lower likelihood of post‐tPA hemorrhagic conversion than did patients with contradictory CTP and MR‐DWI data. Conclusion: Because patients with infarct cores larger than one‐third of a vascular territory are 56 times more likely to hemorrhage than patients with smaller infarct cores and CTP is less accurate than MR‐DWI in identifying the infarct core in patients presenting with acute ischemic stroke, CTP studies should not be part of the acute stroke imaging protocol. Another imaging modality, such as MR‐DWI, may be preferential in the setting of acute ischemic stroke to identify the infarct core.

Orientador: Silméia Garcia Zanati Bazan / Resumo: Introdução: O acidente vascular cerebral (AVC) isquêmico pode ser dividido etiologicamente em cinco tipos de acordo com a classificação TOAST e sua adequada investigação e caracterização pode auxiliar no manejo clínico e prevenção de novos eventos. O ecocardiograma transtorácico (ETT) é peça fundamental na investigação etiológica e cerca de um terço dos pacientes permanece sem definição adequada da etiologia ou são classificados como TOAST indeterminado. Objetivos: Avaliar se o percentual de indeterminação do TOAST diminui em função da realização do ecocardiograma transtorácico; avaliar se o prognóstico após o AVC isquêmico é pior entre pacientes que apresentam TOAST indeterminado e verificar a capacidade preditiva das variáveis ecocardiográficas sobre o prognóstico após AVC isquêmico. Metodologia: Coorte retrospectiva, na qual foram realizadas avaliações clínica, neurológica e ecocardiográfica durante internação por AVC e avaliação da mortalidade intra-hospitalar e da capacidade funcional no momento da alta hospitalar e após 90 dias. Foram realizados modelos de regressão linear múltipla e regressão logística múltipla ajustados pelos fatores confundidores. O nível de significância foi de 5%. Resultados: Foram incluídos 1100 pacientes, maioria do sexo masculino, 606 (55,09%), média de 68,1±13,3 anos de idade, em 977 (88,82%) pacientes foi realizado ETT e 448 (40,7%) tiveram classificação de TOAST indeterminado. Pacientes submetidos ao ecocardiograma transtorácico tiveram 3,1 v... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Ischemic stroke can be divided etiologically into five types according to the TOAST classification, and its adequate investigation and characterization can aid in the clinical management and prevention of new events. Transthoracic echocardiography (TTE) plays a key role in etiological investigation, and about onethird of patients remain without adequate definition of the etiology or are classified as undetermined TOAST. Objectives: To evaluate if the percentage of indetermination of TOAST decreases according to the performance of the transthoracic echocardiography; to evaluate whether the prognosis after ischemic stroke is worse among patients with undetermined TOAST and to verify the predictive capacity of the echocardiographic variables on the prognosis after ischemic stroke. Methods: Retrospective cohort, in which clinical, neurological and echocardiographic evaluations were performed during stroke hospitalization and evaluation of in-hospital mortality and functional capacity at hospital discharge and after 90 days. Multiple linear regression and multiple logistic regression models were adjusted for confounding factors. The level of significance was 5%. Results: A total of 1100 patients were included, mostly male, 606 (55.09%), mean of 68.1 ± 13.3 years of age, and 977 (88.82%) patients were submitted to TTE and 448 (40.7%) had undetermined TOAST classification. Patients submitted to transthoracic echocardiography were 3.1 times less likely to have TOAST class... (Complete abstract click electronic access below) / Mestre

Introdução: O Acidente Vascular Cerebral (AVC) é a maior causa de morte no Brasil e um dos maiores responsáveis por incapacitação e invalidez. Existem informações insuficientes quanto aos principais fatores associados à ocorrência de óbito nos pacientes vítimas desta enfermidade. Alguns escores preditores foram desenvolvidos porém não foram validados em população brasileira até o momento. Uma das ações mais importantes na redução do ônus do AVC é o atendimento sistematizado destes pacientes de forma mulltidisciplinar em Unidades de AVC (UAVC) com potencial aumento do uso da terapia trombolítica, além da estratificação dos pacientes, possibilitando decisões terapêuticas mais precoces. Este estudo traz informações sobre o perfil epidemiológico dos pacientes admitidos na UAVC do Hospital Geral de Fortaleza (HGF), bem como identifica fatores preditores de mortalidade e incapacidade até a alta hospitalar e busca validar o Escore de Risco do Registro da Rede Canadense de AVC (IScore), possibilitando a utilização desta ferramenta na estratificação de risco de morte e incapacidade em uma população distinta daquela originalmente realizada. Objetivos: avaliar perfil clínico-epidemiológico dos pacientes e identificar fatores preditores independentes de mortalidade e incapacidade (primários); validar o iScore para morte ou incapacidade e desenvolver um escore na amostra para morte e incapacidade (secundários). Métodos: Foram selecionados pacientes consecutivos admitidos na Unidade de AVC do HGF entre novembro de 2009 até maio de 2012 com diagnóstico clínico de AVC isquêmico. Os dados foram coletados por equipe treinada e através de um formulário específico. Foi realizada análise univariada (método do quiquadrado) e análise multivariada (com regressão logística, stepwise forwardbackward) para descrição das características e identificação dos fatores associados ao desfecho. Teste de correlação de Pearson e curva ROC foram utilizados para medidas de correlação e desempenho dos escores prognósticos. Resultados: no período entre novembro de 2009 e maio de 2012 foram elegíveis 1433 pacientes, sendo 780 analisados. Houve predomíno do sexo masculino e a média de idade (± desvio padrão) foi de 66,1 anos (± 15,44). A forma de apresentação mais comum foi a fraqueza muscular (653 pacientes, 83,6%). O desfecho combinado ocorreu em 423 pacientes (45,8%) e 40 pacientes (5,1%) morreram. Foram identificados 8 fatores preditores independentes para o desfecho. O iScore apresentou bom desempenho, com AUC de 0,797 e Correlação de Pearson de 0,989. Conclusão: Pacientes com AVCi tem altas taxas de incapacidade ou morte até a alta de uma unidade de AVC. Medidas populacionais de informação tem potencial para reduzir a ocorrência dos desfechos. Foram identificados oito fatores preditores de mortalidade ou incapacidade. O iScore apresentou bom desempenho na amostra e pode ser utilizado com acurácia na população brasileira como ferramenta prognóstica. / Intoduction: Stroke is the leading cause of death and one of the most important disease associated with disability in Brazil. There is insufficient information about factors associated with death in stroke patients. Some death risk score has been developed, but none of them were applied in the Brazilian population yet. One of the most important actions to be done to reduce the burden of the stroke is the multidisciplinary assessment of the patients in stroke units (UAVC), with the potential to improve the thrombolytic therapy utilization and the early stratification of patients, allowing earlier treatment decisions. The present study, provides information on the epidemiological profile of patients admitted to the stroke unit in the Hospital Geral de Fortaleza (HGF), identifies predictors of in-hospital mortality and disability and seeks to validate the IScore, allowing the use of this tool to stratify the risk of death and disability in a population different from that which was originally derived. Objectives: to evaluate patient epidemiologic and clinical patterns and factors independently associated with death and disability at hospital discharge (primary objectives); to validate the iScore fitness to predict mortality and/or disability and to develop a new risk score to predict mortality and disability at discharge (secondary objectives). Methods: all consecutive patients admitted to the Hospital Geral de Fortaleza Stroke Unit since November 2009 until May 2012 were elegible. Data were collected by a trained team and by using a specific clinical research form. Univariable analysis (by chi-square test) followed by multivariable analysis (with logistic regression) were performed to identify and establish the variables associated with the outcome (death or disability at hospital discharge). Additionally, Pearson correlation test and ROC curve to measure the iScore correlation and discrimination ability were conducted. Results: a total of 1433 patients were selected and 781 considered eligible were included for the analysis. Male gender were more frequent; mean age was 66,1 (± 15,44). The most common clinical pattern at hospital arrival was \"weakness\" (653 pacientes, 83,6%). Outcome occurred in 423 patients (58,6%) and 40 patients (5,1%) had died. Eight factors were independently associated with outcome. The iScore had good performance, with AUC of 0,797 and Pearson Correlation Test of 0,985. Conclusion: Stroke patients have substantial rate of death or disability at hospital discharge. Populationbased strategies to inform about the signs and symptoms of stroke have potential to decrease this rate. Eight factors were identified as predictors of death or disability and might be used to support patient risk stratification. The iScore had a good performance in the sample and can be used with accuracy as a prognostic tool in Brazil.

L'aspirine est l'anti-plaquettaire le plus largement prescrit à la phase aiguë de l'accident vasculaire cérébral (AVC) ischémique. Cependant, la survenue de récidives, malgré cette prescription, est fréquente. La description de l'effet de l'aspirine sur l'activité plaquettaire durant cette phase n'a jamais été réalisée. Elle pourrait mettre en évidence une moindre réponse plaquettaire et aider à établir de nouvelles stratégies thérapeutiques. Cinquante patients, ont reçu par voie orale 300 mg d'aspirine, suite à un AVC ischémique. Ensuite, des prélèvements sanguins ont été réalisés : entre 2 et 3 heures (T1), entre 23 et 24 heures (T2) après la prise d'aspirine et, pour des patients déjà traités quotidiennement par une dose inférieure, avant la prise d'aspirine (T0). Les concentrations sériques de thromboxane (TX) B2 ont été mesurées, ainsi que les agrégations induites par l'acide arachidonique, par le collagène à la concentration de 2µg/L (Col2) et 20 µg/L (Col20). Afin de diminuer l'effet des variations de condition d'expérience, les résultats pour Col2 ont été rapportés à ceux pour Col20 (Col2/20). Tous les patients ont présenté une réponse à l?aspirine visible à T1 avec de plus, des concentrations de TXB2 abaissées en comparaison à T0. Il existe une récupération de l'activité plaquettaire à T2 comparée à T1, montrée par les concentrations de TXB2 et le rapport Col2/20. La dose orale de 300 mg d'aspirine, donnée à la phase aiguë de l'AVC, entraîne une inhibition plaquettaire, mais avec une récupération visible sur 24 heures. Pour les patients déjà traités quotidiennement par une dose inférieure, elle permet de compléter l'inhibition de la voie TXA2 dépendante / Aspirin is the most commonly used antiplatelet treatment during the acute phase of cerebral ischemic events. But, despite this protection, early ischemic recurrences are frequent, and considered as clinical failures of this therapy. We studied laboratory parameters of the first 300 mg oral dose of aspirin given, within 48 hours, after ischemic cerebral event. Fifty patients were included. For all patients, two blood sampling were performed, the first, during the third hour after aspirin intake (T1) and the second during the twenty-fourth hour (T2). For patients already treated with a daily dose of aspirin, a supplementary withdrawn was done before aspirin intake (T0). Platelet reactivity was studied on the basis of serum thromboxane (TX) B2 levels and light transmission aggregometry after stimulation of platelet-rich plasma by acid arachidonic and collagen 2µg/mL reported to results with collagen 20 µg/mL (ratio Col2/20). Inhibition of platelet activity was observed, at T1, for all patients. There is a significant increase of TXB2 values, and of relative values of the ratio Col2/20, at T2 as compared to T1. For already aspirin treated patients, there is a significant decrease of TXB2 levels at T1 as compared to T0. There is a platelet reactivity recovery within 24 hours, following the first 300 mg oral dose of aspirin, during the acute phase of a cerebral ischemic event, and demonstrated by TXB2 levels and ratio Col2/20. This fact would favour early ischemic recurrences. However, this dose is able to complete the inhibition of the TXA2 pathway for already aspirin treated patients

No description available.

Stroke is the 5th leading cause of death and the leading cause of disability in the United States, but there are only two available therapies, tissue plasminogen activator and endovascular thrombectomy. As both therapies focus on removal of the clot, the subsequent pathologic processes, i.e. inflammation, cerebrovascular breakdown, ATP depletion, etc. are left untreated, contributing to worsened patient outcome. Many clinical trials have unsuccessfully attempted to address these mechanisms. The blood-brain barrier (BBB), a system of non-fenestrated endothelial cells, extracellular matrix, and astrocytic endfeet, is significantly impacted after ischemic stroke in its role of preventing the free movement of proteins from the blood into the brain. In fact, BBB dysfunction is viewed as one of the major facilitators of damage following ischemic stroke, leading to increased infarct volumes and worsened patient outcomes. Interestingly, a family of endothelial integrins, the b1 integrins, have been shown to regulate tight junction proteins preventing the free movement of molecules. When expression of the tight junctions are decreased, this results in increased BBB permeability. To test this concept, our laboratory has previously shown the knockout of the particular β1 integrin, α5β1, is neuroprotective following ischemic stroke through BBB stabilization. To determine if therapeutically targeting integrin a5b1 was feasible, we first determined if brain integrin a5b1 expression increases after experimental mouse ischemic stroke model, specifically tandem/transient common carotid artery/middle cerebral artery occlusion. We found that integrin a5b1 does increase acutely, by post-stroke day (PSD)2, and continued in an exponential fashion through PSD4. Next, we determined if integrin a5b1 was therapeutically accessible by systemic treatment (i.e. intraperitoneal or intravenous) by being located on the inside (luminal surface) of vasculature. We found that location of integrin a5b1 was dependent on the area relative to the stroke injury. The core, or area of direct impact, demonstrated expression of integrin a5b1 on the outside vasculature (abluminal surface), while per-infarct expression was localized to the lumen. Lastly, to determine the activity of integrin a5b1 following ischemic stroke, we showed that the potential ligands (binding partners), plasma fibronectin, fibrinogen, and amyloid-b, do not bind integrin a5b1 after ischemic stroke. Next, we determined the therapeutic potential of targeting integrin a5b1 with the small peptide, ATN-161. ATN-161 has undergone clinical trials in solid tumors, with limited side effects reported. First, we determined that intraperitoneal (IP) injection of ATN-161 was safe after ischemic stroke, showing no changes in heart rate, pulse distention (blood pressure), or body temperature. Next, we found that IP administration of ATN-161 after experimental ischemic stroke reduced infarct volumes, edema, and functional deficit. Furthermore, these results were due to reduction of BBB permeability and anti-inflammatory effects. Interestingly, ATN-161 reduced cytokine production, prevented leukocyte infiltration, and leukocyte recruitment. Collectively, these results suggest that targeting integrin a5b1 with ATN-161 is 1) feasible, 2) safe and 3) effective, suggesting that ATN-161 may be a novel therapeutic treatment for ischemic stroke.

Ischemic stroke is the leading cause of disability world-wide and affects over 800,000 people per year in the United States. The majority of these strokes are ischemic due to a blockage of blood flow to the brain. Damage to the brain occurs at the onset of stroke, neuronal cell death is irreversible and therefore, quick treatment to remove blockage is critical factor in the recovery from stroke. Mechanical thrombectomy as a treatment for ischemic stroke provides an ideal opportunity to collect blood distal and proximal to the cerebral thrombus to examine neurochemical changes occurring during stroke. The purpose of this dissertation was to explore the trajectory of neurochemical changes that occur in response to ischemic stroke during the first 72 hours and the physiological response from stroke patients to improve stroke outcomes. The specific aims were to: 1) to determine whether venous blood gases predict infarct volume and/or mortality in acute ischemic stroke in young male rats; 2) determine whether venous blood gases predict infarct and edema volume, and/or mortality in acute ischemic stroke in aged male and female rats; 3) compare the presence and relative concentrations of acid/base and electrolytes in static blood distal to thrombus and in peripheral blood drawn from adults who received thrombectomy for ischemic stroke and identify associations to postreperfusion functional outcomes. Specific Aim One was addressed by evaluation of young (three-month old) Sprague-Dawley rats that underwent permanent or transient middle cerebral artery occlusion (MCAO). Pre- and post-MCAO venous samples from permanent and transient models provided pH, carbon dioxide, oxygen, bicarbonate, glucose, hematocrit, hematocrit, and electrolyte values of ionized calcium, potassium and sodium. The analyses indicated that mean differences in the blood gas and electrolytes between pre- to post-MCAO and pH and iCa2+ were predictors of infarct volume in the permanent MCAO model. The second aim was addressed by evaluation of aged (18 month old) male and female rats pre-MCAO, post-MCAO, and at 72 hours of permanent MCAO venous blood gas samples (pH, carbon dioxide, oxygen, bicarbonate, glucose, hematocrit, hematocrit, and electrolyte concentrations of ionized calcium, potassium and sodium). Changes in pH (from pre-MCAO to post-MACO and post-MCAO to 72 hours) and changes in Na+ and iCa2+ (from post-MCAO to 72 hours) were predictors of infarct volume and edema volume, respectively in both sexes. Cox regression revealed there was a 3.25 times increased risk for mortality based on changes (cut-off range within -2.00 to - 7.00) in bicarbonate levels (pre- to post-MCAO). The third aim was addressed by evaluation of acid/base balance (pH, carbon dioxide, oxygen, bicarbonate, ionized calcium, potassium and sodium) of ischemic stroke patients who underwent mechanical thrombectomy. Our results suggests sex differences matter in ischemic stroke populations. Significant differences occur within proximal blood between the sexes. Additionally, females had approximately 2.5 hour increased time between stroke symptom onset to thrombectomy completion time (described as infarct time). Changes in bicarbonate and base deficit were predictors of infarct time, but only in our female population.

Stroke is an important public health problem and the third leading cause of death after coronary heart diesase and all cancers in all over the world. Free radicals and oxidative stress play important role in the pathogenesis of several diseases including atherosclerosis, stroke, cancer, neurodegenerative diseases such as Alzheimer&#039 / s dementia. The activity of paraoxonase (PON1) aganist phenylacetate is known as arylesterase (ARE). Paraoxonase is an esterase associated with high-density lipoprotein (HDL) and contributes to the protective role of this lipoprotein on low-density lipoprotein (LDL) oxidation. Oxidized LDL is known to play a central role in early events in the progression of atherosclerosis which is a risk factor for stroke. Glutathione S-transferases (GSTs) catalyze the conjugation of nonpolar compounds to reduced glutathione (GSH) and detoxify toxic metabolites produced within the cell by oxidative stress to protect cells from oxidant injury. v The maximum ARE enzyme activity was detected at 10 mM Tris-HCl buffer, pH 8.0 and at 45 &deg / C. ARE enzyme was saturated with its substrate phenylacetate around 20 mM concentration. The apparent Km and Vmax values of human blood serum ARE for phenylacetate were found as 1.66 mM and 3300 nmol/min/mg, respectively. The maximum GST enzyme activity was detected at 2 mM potassium phosphate buffer, pH 5.5 and at 65 &deg / C. GST enzyme was saturated with its substrate, CDNB around 4.5 mM concentration and with its cofactor, GSH around 8 mM concentration. The apparent Km and Vmax values of human blood serum GST for CDNB substrate were found as 2.8 mM and 0.43 nmol/min/mg and for GSH were found as 4.11 mM and 0.23 nmol/min/mg, respectively. In addition, effects of three different heavy metal ions, Cd+2, Hg+2 and Ni+2, on human blood serum ARE and GST activity were studied and half maximal inhibitory concentrations (IC50) were determined. The main objective of this study was to investigate the human blood serum ARE and GST activities in patient and control groups using the optimized conditions. For this purpose, blood samples were collected from 172 ischemic stroke patients and 105 controls. Then serum obtained from blood samples were used to determine ARE and GST activities. The mean of ARE activity in patient group (n=172, 109.9 &plusmn / 32.5 U/mL ) was insignificantly lower than the mean of ARE activity in control group (n=105, 113.5 &plusmn / 33.1 U/mL, P=0.284). GST activity of the patients (10.8 &plusmn / 4.4 U/L) was insignificantly higher than that of controls (10.5 &plusmn / 4.2 U/L, P=0.483 ). In addition, statistical analysis showed hypertension, diabetes and HDL as significant risk factors of stroke.

ANALYSIS OF CYTOCHROME P4501A1 GENETIC POLYMORPHISMS IN PATIENTS WITH ISCHEMIC STROKE Adali, Ayse &Ccedil / inar M.Sc., Department of Biochemistry Supervisor: Prof. Dr. Orhan Adali Co-Supervisor: Dr. Birsen Can Demird&ouml / gen January 2011, 179 pages Stroke is the third leading cause of death worldwide and results in serious disabilities. Cytochrome P450 1A1 gene (CYP1A1) is a highly polymorphic gene encoding its corresponding xenobiotic metabolizing enzyme which is responsible from the metabolism of carcinogenic polycyclic aromatic hydrocarbons (PAHs) that are engaged with the formation of free radicals. Atherosclerosis is a major cause of ischemic stroke and this pathology may be associated with the disruption of vascular homeostasis due to the formation of these chemicals. The main objective of this study was to investigate the coding region (A4889G) and non-coding region (T6235C) polymorphisms of the CYP1A1 gene as a risk factor for ischemic stroke. The study group in Turkish population consisted of 226 unrelated ischemic stroke patients and 113 control subjects. There was no statistically significant difference between the groups with respect to age and gender. Total blood samples were obtained from G&uuml / lhane Military Medical Academy Hospital, Neurology Department, Ankara. In stroke patients, hypertension, diabetes mellitus, smoking and obesity were at least 2 times more common and high density lipoprotein cholesterol (HDL-C) was significantly lower than controls. The frequency of mutant allele 4889G was 0.445 in patients and was nearly the same with controls. The frequency of mutant allele 6235C was 0.151 in patients and was significantly higher in controls (0.226, P=0.015). The risk of diabetic, smoker and obese individuals having ischemic stroke was significantly higher in 4889G allele carriers (AG+GG / Odds ratio / OR= 2.1, 2.4 and 3, respectively). The risk of hypertensive and diabetic individuals having ischemic stroke was higher in 6235TT genotypic people (OR= 3 and 2.2, respectively). On the contrary, the risk of smoker and obese individuals having ischemic stroke was significantly higher in 6235 C allele carriers (OR=5.3 and 3.7, respectively). Logistic regression analysis revealed that hypertension, smoking, levels of low density lipoprotein cholesterol (LDL-C) and HDL-C and 6235C allele were significant predictors of stroke. In this analysis, high level of LDL-C was found to be associated with almost 1.5-fold risk of ischemic stroke. On the other hand, HDL-C and having mutant 6235C allele decreased the risk of ischemic stroke 2.5 and 2-fold, respectively. This is the first study investigating the relation between A4889G polymorphism and stroke risk. Additionally, in Turkish population A4889G and T6235C polymorphisms were analyzed for the first time in terms of its relation to ischemic stroke. The present study demonstrated that the frequency of mutant 4889G allele was nearly the same in stroke patients and control subjects / whereas the frequency of mutant 6235 C allele was higher in control subjects than in stroke patients. Consequently, we decided that carrying mutant 4889 G allele does not constitute a risk for ischemic stroke and carrying mutant 6235C allele may have a protective effect against stroke.