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Insulin-Like Growth Factor-1 as a Prognostic Marker in Patients with Acute Ischemic Stroke  [PDF]
Jian-Hua Tang, Li-Li Ma, Tian-Xia Yu, Juan Zheng, Hui-Juan Zhang, Hui Liang, Peng Shao
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099186
Abstract: Objective Insulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 levels in patients with acute ischemic stroke (AIS). Methods All patients with first-ever AIS from August 1, 2012 to August 31, 2013 were recruited to participate in the study. Clinical data were collected. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to serum IGF-1 levels. For the assessment of functional outcome at 90 days Modified Rankin Scale (mRS) was used. On admission, serum IGF-1 levels were determined by chemiluminescence immunoassay. The influence of IGF-1 levels on functional outcome and death was assessed by multivariate logistic regression analysis. Results Patients with an unfavorable outcomes and non-survivors had significantly decreased serum IGF-1 levels on admission (P<0.0001 for both). IGF-1 was an independent prognostic marker of functional outcome and death [odds ratio 0.89 (0.84–0.93) and 0.90 (0.84–0.95), respectively, P<0.0001 for both, adjusted for age, NIHSS score and other predictors] in patients with ischemic stroke. Serum IGF-1 levels ≤130 ng/mL was as an value indicator for unfavorable functional outcome (OR 3.31, 95% CI:1.87–5.62; P<0.0001), after adjusting for other significant confounders. Conclusions We reported a significant association between low serum IGF-1 levels and unfavorable functional outcome and death.
Prognostic value of copeptin in patients with acute ischemic stroke  [cached]
Tu Wen-Jun,Chen Hui,Cui Li-Hua
Iranian Journal of Neurology , 2011,
Abstract: Stroke is the second leading cause of mortality in the Chinaand one of the leading causes of severe morbidity. An earlyrisk assessment with estimate of the severity of disease andprognosis is pivotal for optimized care and allocation ofhealthcare resources. Reliable prognostic markers availableduring the initial phase after acute stroke may aid clinicaldecision-making.Vasopressin (AVP) is a potent synergistic factor ofcorticotropin-releasing hormone as hypothalamic stimulator ofthe hypothalamo-pituitary-adrenal axis.1 Some studies foundincreased AVP levels in patients with ischemic stroke werecorrelated with stroke severity2 and outcome.3 Copeptin isreleased in an equimolar ratio to AVP, and is more stable inthe circulation and easy to measure.4We designed a preliminary prospective cohort study toevaluate the prognostic value of copeptin in acute strokepatients. Adult patients with a persistent neurological deficitdue to ischemic stroke were eligible. Sixty-ninenonconsecutive patients admitted at 3 hospitals with adiagnosis of acute ischemic stroke confirmed by CT scanningwere evaluated. All patients provided informed consent. Inpatients who died within 24 hours after admission or inpatients who were discharged, data from admission or untildischarge were collected. The National Institute of HealthStroke Scale (NIHSS) score was assessed on admission.Functional outcome was obtained on days 90 according to themodified Rankin Scale (mRS) blinded to copeptin levels. Poorfunctional outcome at 3 months was considered as a mRSscore > 2. Blood samples were collected on admission andimmediately centrifuged and sera stored at –70°C. Copeptinwas measured with a sandwich immunoluminometricassay.1 Discrete variables are summarized as counts(percentage), and continuous variables as medians andinterquartile ranges (IQRs). Two-group comparison of notnormally distributed data was performed using Mann–Whitney U test, and a Kruskal–Wallis one-way analysis ofvariance was used for multi-group comparisons.The median age of the 69 patients was 62 years (IQR,55 to 84), 61% were men and the median NIHSS score onadmission was 7 points (IQR, 3 to 12). In 38 patients(55%) with a poor functional outcome (13 patients died),copeptin levels were higher compared with those inpatients with a favorable outcome (23.5; IQR, 10.6 to 64.3pmol/L vs. 7.5; IQR, 3.8 to 13.6 pmol/L; P < 0.0001).Multivariate logistic regression analysis adjusted for ageand NIHSS score showed that copeptin was anindependent predictor of poor functional outcome (oddsratio = 3.12; 95%CI, 1.54–6.46). The area under the
Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke  [PDF]
Shufen Chen,Na Li,Milani Deb-Chatterji,Qiang Dong,Jan T. Kielstein,Karin Weissenborn,Hans Worthmann
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms131215983
Abstract: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is known as mediator of endothelial cell dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. Accordingly, clinical studies found evidence that increased ADMA levels are associated with a higher risk of cerebrovascular events. After the acute event of ischemic stroke, levels of ADMA and its analog symmetric dimethylarginine (SDMA) are elevated through augmentation of protein methylation and oxidative stress. Furthermore, cleavage of ADMA through dimethylarginine dimethylaminohydrolases (DDAHs) is reduced. This increase of dimethylarginines might be predictive for adverse clinical outcome. However, the definite role of ADMA after acute ischemic stroke still needs to be clarified. On the one hand, ADMA might contribute to brain injury by reduction of cerebral blood flow. On the other hand, ADMA might be involved in NOS-induced oxidative stress and excitotoxic neuronal death. In the present review, we highlight the current knowledge from clinical and experimental studies on ADMA and its role for stroke risk and ischemic brain injury in the hyperacute stage after stroke. Finally, further studies are warranted to unravel the relevance of the close association of dimethylarginines with stroke.
Selected acute phase CSF factors in ischemic stroke: findings and prognostic value
Maia Beridze, Tamar Sanikidze, Roman Shakarishvili1, Nino Intskirveli, Natan M Bornstein
BMC Neurology , 2011, DOI: 10.1186/1471-2377-11-41
Abstract: Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0.At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P < 0.05). Cerebrospinal fluid Electron Paramagnetic Resonance signal of nitric oxide was increased in patients against controls. Severe stroke group had an elevated Electron Paramagnetic Resonance signal of lipoperoxiradical compared to less severe stroke. Cerebrospinal fluid nitrate levels in less severe stroke patients were higher than those for severe stroke and control. Positive correlation was established between the initial interleukin-6 content and ischemic lesion size as well as with National Institute Health Stroke Scale score on the seventh day. Initial interleukin-6 and nitrate levels in cerebrospinal fluid found to be significant for functional outcome of stroke at one month.According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.Modern concepts of acute cerebral ischemia highlight the role of neurovascular units and emphasize the importance of integrative tissue responses that result from dynamic interactions of endothelial cells, vascular sooth muscles, matrix elements, astroglia, microglia and neurons. By means of infla
The Prognostic Value of Serum Uric Acid Level in Acute Ischemic Stroke
Journal of Neurological Sciences , 2009,
Abstract: Introduction and Objective: Uric acid is a natural anti-oxidant that plays a role in acute oxidative stress reactions like acute ischemic stroke. In this study, we aimed to search the relation between serum uric acid level, length of hospital stay and severity of stroke in acute stroke patients, and consequently, the prognostic value of serum uric acid level.Patients and Methods: We performed a retrospective study on 100 patients who had presented to the emergency department with the findings of acute ischemic stroke. All the laboratory, radiological and clinical investigations were recorded. All the risk factors, National Institute of Health Stroke Scale (NIHSS), laboratory values, clinical findings, length of hospital stay of the patients and the treatment modalities were recorded.Results: The median serum uric acid level was 5.25±2.03 mg/dl. The median level in females was found to be higher than that in males. The length of hospital stay varied from 2 to 57 days and the median value was 13±8.66 days. In the multivariate analysis, increases in the levels of serum uric acid measured were significantly associated with decreased length of hospital stay. We detected a low value correlation between NIHSS and serum uric acid levels, but it was statistically insignificant. According to our results, there was a strong negative correlation between serum uric acid levels and the length of hospital stay, and a weak correlation between the serum uric acid level and the severity of stroke.
Prognostic Value of Dehydroepiandrosterone-Sulfate and Other Parameters of Adrenal Function in Acute Ischemic Stroke  [PDF]
Claudine A. Blum, Cornelia Mueller, Philipp Schuetz, Felix Fluri, Michael Trummler, Beat Mueller, Mira Katan, Mirjam Christ-Crain
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063224
Abstract: Background and Purpose Acute stroke has a high morbidity and mortality. We evaluated the predictive value of adrenal function testing in acute ischemic stroke. Methods In a cohort of 231 acute ischemic stroke patients, we measured dehydroepiandrosterone (DHEA), DHEA-Sulfate (DHEAS), cortisol at baseline and 30 minutes after stimulation with 1 ug ACTH. Delta cortisol, the amount of rise in the 1 ug ACTH-test, was calculated. Primary endpoint was poor functional outcome defined as modified Rankin scale 3–6 after 1 year. Secondary endpoint was nonsurvival after 1 year. Results Logistic regression analysis showed that DHEAS (OR 1.21, 95% CI 1.01–1.49), but not DHEA (OR 1.01, 95% CI 0.99–1.04), was predictive for adverse functional outcome. Neither DHEA (OR 0.99, 95% CI 0.96–1.03) nor DHEAS (OR 1.10, 95% CI 0.82–1.44) were associated with mortality. Baseline and stimulated cortisol were predictive for mortality (OR 1.41, 95% CI 1.20–1.71; 1.35, 95% CI 1.15–1.60), but only basal cortisol for functional outcome (OR 1.20, 95% CI 1.04–1.38). Delta cortisol was not predictive for functional outcome (OR 0.86, 95% CI 0.71–1.05) or mortality (OR 0.92, 95% CI 0.72–1.17). The ratios cortisol/DHEA and cortisol/DHEAS discriminated between favorable outcome and nonsurvival (both p<0.0001) and between unfavorable outcome and nonsurvival (p = 0.0071 and 0.0029), but are not independent predictors for functional outcome or mortality in multivariate analysis (adjusted OR for functional outcome for both 1.0 (95% CI 0.99–1.0), adjusted OR for mortality for both 1.0 (95% CI 0.99–1.0 and 1.0–1.01, respectively)). Conclusion DHEAS and the cortisol/DHEAS ratio predicts functional outcome 1 year after stroke whereas cortisol levels predict functional outcome and mortality. Trial Registration ClinicalTrials.gov NCT00390962 (Retrospective analysis of this cohort).
The Etiologic and Prognostic Importance of High Leukocyte and Neutrophil Counts in Acute Ischemic Stroke
Journal of Neurological Sciences , 2010,
Abstract: Objectives: Inflammatory mechanisms play an important role in the pathogenesis of cerebral ischemia and in the risk of stroke. In several studies, elevated leukocyte count has been associated with cardiovascular and cerebrovascular events. The aim of this study is to investigate the relationship between the leukocyte and neutrophil counts and stroke severity, short term prognosis and stroke subtypes of the patients with acute ischemic stroke.Materials/Methods: Leukocyte and neutrophil counts were measured in 166 consecutive acute ischemic stroke patients in the first 24 hour of admission. Clinical findings, stroke risk factors and brain imagings were evaluated. According to their etiology, patients were classified by using the TOAST criteria. Stroke severity was assessed by the modified Rankin Scale(mRS) on admission and discharge, National Institutes of Health Stroke Scale (NIHSS) was used on admission.Results: While 51(%30.72) patients had leukocyte ≥10000/μl and 115(%69.28) patients had leukocyte <10000/ μl, 70(%42.17) patients had neutrophil ≥6100/μl and 96(%57.83) patients had neutrophil<6100/μl. leukocyte and neutrophil counts were significantly higher in severe stroke (p<0.001) hence short term prognosis was significantly poor in these patients. (p<0.001) We found a strong correlation between large vessel disease and high leukocyte count (p<0.05) and also between small vessel disease and normal leukocyte count. (p<0.05) Results were similar for neutrophil levels of patients according to stroke subtypes.Conclus on: According to our study; high leukocyte and neutrophil levels on admission correlate with large vessel disease and therefore could be a predictor of stroke severity and unfavourable outcome.
Prognostic Value of Complete Blood Count and Electrolyte Panel during Emergency Department Evaluation for Acute Ischemic Stroke  [PDF]
Latha Ganti,Rachel M. Gilmore,Amy L. Weaver,Robert D. Brown Jr.
ISRN Stroke , 2013, DOI: 10.1155/2013/974236
Abstract: Objective. To determine whether routine laboratory parameters are predictors of early mortality after acute ischemic stroke (AIS). Methods. The cohort consisted of 522 consecutive patients with AIS presenting to the emergency department (ED) at a tertiary referral center during a 27-month period, residing within the surrounding ten counties. Serum laboratory values were obtained for all patients and categorized according to whether the levels were low, normal, or high. These laboratory results were evaluated as potential predictors of 90-day mortality using Cox proportional hazards models. The associations were summarized by calculating risk ratios (RRs) and 95% confidence intervals (CI). Results. The presence of elevated white blood cell count (RR 2.2, 95% CI 1.5–3.4), low bicarbonate (RR 4.2, 95% CI 2.6–6.7), low calcium (RR 2.9, 95% CI 1.4–5.9), and high glucose (RR 1.3, 95% 1.1–1.6) were each univariately associated with significantly higher mortality within the first 90 days. Based on fitting a multivariate Cox regression model, elevated white blood cell count, low bicarbonate, and high glucose were each identified as being jointly associated with early mortality ( ). Conclusion. Early leukocytosis, acidosis, and hyperglycemia and hypocalcemia in AIS appear to be associated with early mortality. Whether addressing these factors will impact survival remains to be investigated. 1. Introduction For patients who present with chief complaint of acute ischemic stroke, the American Stroke Association recommends a set of diagnostic studies [1] to be done at presentation, with the intent of optimizing and expediting the care of these patients. From the Emergency Physicians’ perspective many tests are simply part of a routine battery, often without direct impact on emergency department (ED) management, diagnostic or prognostic value. In this study, we sought to determine whether the routine complete blood count (CBC) and electrolyte panel include any components that are markers of early mortality in acute ischemic stroke. Specifically, the parameters of interest were those obtained as part of routine clinical investigation. 2. Methods 2.1. Study Design This study was an observational study using a consecutive sample of local residents presenting to the ED with acute ischemic stroke (AIS). The primary outcome measure was death at 90 days. This study was approved by the Mayo Clinic Institutional Review Board. 2.2. Study Population and Setting This study was conducted at the Saint Marys Hospital, a tertiary referral academic medical center with an annual ED
Ubiquitin Fusion Degradation Protein 1 as a Blood Marker for The Early Diagnosis of Ischemic Stroke
Laure Allard,Natacha Turck,Pierre R. Burkhard,Nadia Walter
Biomarker Insights , 2007,
Abstract: Background: Efficacy of thrombolysis in acute ischemic stroke is strongly related to physician’s ability to make an accurate diagnosis and to intervene within 3–6 h after event onset. In this context, the discovery and validation of very early blood markers have recently become an urgent, yet unmet, goal of stroke research. Ubiquitin fusion degradation protein 1 is increased in human postmortem CSF, a model of global brain insult, suggesting that its measurement in blood may prove useful as a biomarker of stroke.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to measure UFD1 in plasma and sera in three independent cohorts, European (Swiss and Spanish) and North-American retrospective analysis encompassing a total of 123 consecutive stroke and 90 control subjects.Results: Highly significant increase of ubiquitin fusion degradation protein 1 (UFD1) was found in Swiss stroke patients with 71% sensitivity (95% CI, 52–85.8%), and 90% specificity (95% CI, 74.2–98%) (N = 31, p < 0.0001). Significantly elevated concentration of this marker was then validated in Spanish (N = 39, p < 0.0001, 95% sensitivity (95% CI, 82.7–99.4%)), 76% specificity (95% CI, 56.5–89.7%)) and North-American stroke patients (N = 53, 62% sensitivity (95% CI, 47.9–75.2%), 90% specificity (95% CI, 73.5–97.9%), p < 0.0001). Its concentration was increased within 3 h of stroke onset, on both the Swiss (p < 0.0001) and Spanish (p = 0.0004) cohorts.Conclusions: UFD1 emerges as a reliable plasma biomarker for the early diagnosis of stroke, and in the future, might be used in conjunction with clinical assessments, neuroimaging and other blood markers.Abbreviations: AUC: area under curve; BBB: blood–brain barrier; CO: cut-off; CSF: cerebrospinal fluid; CT: computerized tomography; H-FABP: heart-fatty acid binding protein; MMP9: matrix metalloproteinase 9; MRI: magnetic resonance imaging; NDKA: nucleotide diphosphate kinase A; OR: odds ratio; RFU: relative fluorescence units; ROC: receiver operating characteristic; rtPA: recombinant tissue plasminogen activator; SE: sensitivity; SP: specificity; TIA: transient ischemic attack; UFD1: ubiquitin fusion degradation protein 1
A simple slide test to assess erythrocyte aggregation in acute ST-elevated myocardial infarction and acute ischemic stroke: Its prognostic significance  [cached]
Lakshmi Atla,Uma Prasad,Venkatachalam Ch,Nageswar Rao G
Indian Journal of Pathology and Microbiology , 2011,
Abstract: A simple slide test and image analysis were used to reveal the presence of an acute-phase response and to determine its intensity in subjects of acute myocardial infarction and acute ischemic stroke. Erythrocytes tend to aggregate during an inflammatory process. Evaluation of erythrocyte adhesiveness/aggregation is currently available to the clinicians indirectly by erythrocyte sedimentation rate (ESR), but ESR correlates poorly with erythrocyte aggregation, hence a simple slide technique using citrated blood was used to evaluate erythrocyte aggregation microscopically and also by using image analysis. Aims: (1) To study erythrocyte aggregation/adhesiveness by a simple slide test in subjects with acute ST-elevated myocardial infarction (STEMI), acute ischemic stroke and healthy controls. (2) To study the prognostic significance of ESR and erythrocyte aggregation/adhesiveness test (EAAT) in predicting the outcome after 1 week in subjects of acute myocardial infarction and acute ischemic stroke. Patients and Methods: Three groups of subjects were included in the study; 30 patients of acute STEMI, 30 patients of acute ischemic stroke, and 30 subjects with age- and gender-matched healthy controls. Citrated blood was subjected to simple slide test and ESR estimation by Westergren′s method. Stained smears were examined under 400Χ and graded into four grades. Images were taken from nine fields; three each from head, body, and tail of the smear. The degree of erythrocyte aggregation was quantified using a variable called erythrocyte percentage (EP), by using the software MATLAB Version 7.5. A simple program was used to count the number of black and white pixels in the image by selecting a threshold level. Results: The mean ESR of the subjects with acute myocardial infarction (29 + 17.34) was significantly higher (P = 0.001) than the mean ESR of the control group (15.5 + 12.37). The mean EP of the subjects with acute myocardial infarction (69.91 + 13.25) was significantly lower (P < 0.001) than the mean EP of the control group (85.16 + 8.41). The mean ESR of the subjects with acute stroke (40.46 + 33.75) was significantly higher (P = 0.0005) than that of the controls (15.5 + 12.37). The mean EP of the stroke patients (70.59 + 11.30) was significantly lower (P < 0.001) than the mean EP of the controls (85.16 + 8.41). In subjects with acute myocardial infarction there was a significant negative correlation (r = 0.623) between ESR and EP. In acute stroke patients there was a significant negative correlation (r = 0.69) between ESR and EP. On performing standard er
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