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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.
Copeptin, Procalcitonin and Routine Inflammatory Markers–Predictors of Infection after Stroke  [PDF]
Felix Fluri, Nils G. Morgenthaler, Beat Mueller, Mirjam Christ-Crain, Mira Katan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048309
Abstract: Background Early predictors for the development of stroke-associated infection may identify patients at high risk and reduce post-stroke infection and mortality. Methods In 383 prospectively enrolled acute stroke patients we assessed time point and type of post-stroke infections (i.e. pneumonia, urinary tract infection (UTI) other infection (OI)). Blood samples were collected on admission, and days 1, and 3 to assess white blood cells (WBC), monocytes, C-reactive protein (CRP), procalcitonin (PCT), and copeptin. To determine the magnitude of association with the development of infections, odds ratios (OR) were calculated for each prognostic blood marker. The discriminatory ability of different predictors was assessed, by calculating area under the receiver operating characteristic curves (AUC). Prognostic models including the three parameters with the best performance were identified. Results Of 383 patients, 66 (17.2%) developed an infection after onset of stroke. WBC, CRP, copeptin and PCT were all independent predictors of any infection, pneumonia and UTI developed at least 24 hours after measurements. The combination of the biomarkers WBC, CRP and copeptin (AUC: 0.92) and WBC, CRP and PCT (AUC: 0.90) showed a better predictive accuracy concerning the development of pneumonia during hospitalization compared to each marker by itself (p-Wald <0.0001). Conclusion Among ischemic stroke patients, copeptin, PCT, WBC and CRP measured on admission were predictors of infection in general, and specifically for pneumonia and UTI within 5 days after stroke. The combination of these biomarkers improved the prediction of patients who developed an infection.
Detection of copeptin in peripheral blood of patients with aneurysmal subarachnoid hemorrhage
Xiang-Dong Zhu, Jing-Sen Chen, Feng Zhou, Qi-Chang Liu, Gao Chen, Jian-Min Zhang
Critical Care , 2011, DOI: 10.1186/cc10575
Abstract: In this retrospective study, 303 consecutive patients were included. Upon admission, plasma copeptin levels were measured by enzyme-linked immunosorbent assay. The end points were mortality after 1 year, in-hospital mortality, cerebrovasospasm and poor functional outcome (Glasgow Outcome Scale score of 1-3) after 1 year.Upon admission, plasma copeptin level in patients was statistically significantly higher than that in healthy controls. A multivariate analysis showed that plasma copeptin level was an independent predictor of poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm. A receiver operating characteristic curve showed that plasma copeptin level on admission predicted poor functional outcome and mortality after 1 year, in-hospital mortality and cerebrovasospasm of patients statistically significantly. The area under curve of the copeptin concentration was similar to those of World Federation of Neurological Surgeons (WFNS) score and modified Fisher score for the prediction of poor functional outcome and mortality after 1 year, and in-hospital mortality, but not for the prediction of cerebrovasospasm. In a combined logistic-regression model, copeptin improved the area under curve of WFNS score and modified Fisher score for the prediction of poor functional outcome after 1 year, but not for the prediction of mortality after 1 year, in-hospital mortality, and cerebrovasospasm.Copeptin level is a useful, complementary tool to predict functional outcome and mortality after aneurysmal subarachnoid hemorrhage.Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is associated with the severity and outcome of critical illness, and therefore, has been proposed as a prognostic marker in acute illness [1-11]. Recently, it has been reported that plasma copeptin levels were also elevated in the patients with traumatic brain injury [11,12] and intracerebral hemorrhage [10,13] and ischemic stroke [8,9]; in th
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
Copeptin is associated with mortality and outcome in patients with acute intracerebral hemorrhage
Christian Zweifel, Mira Katan, Philipp Schuetz, Martin Siegemund, Nils G Morgenthaler, Adrian Merlo, Beat Mueller, Mirjam Christ-Crain
BMC Neurology , 2010, DOI: 10.1186/1471-2377-10-34
Abstract: In 40 consecutive patients who were admitted to the hospital within 72 hours after a spontaneous ICH, the plasma copeptin level was measured with a sandwich immunoassay upon admission. The prognostic value of copeptin to predict 30 day mortality and functional outcome after 90 days was assessed. A favorable outcome was defined as a Barthel score above 85 and a score below 3 on the Modified Rankin Scale.Copeptin correlated positively with hematoma volume (r = 0.32, p < 0.05) and negatively with the Glasgow Coma Scale (GCS) on admission (r = -0.35, p < 0.05). Copeptin levels were higher in patients who died within 30 days than in 30-day survivors (179.0 pmol/l (IQR 33.7- 566.0) vs. 12.9 pmol/l (IQR 5.2 - 42.8), p = 0.003). Copeptin levels were also higher in patients with an unfavorable functional outcome at 90 days compared to patients with a favorable outcome (32.4 pmol/l (IQR 9.5-97.8) vs. 11.9 pmol/l (IQR 3.2-19.8), p = 0.04). For the prediction of death, receiver-operating-characteristics analysis revealed an area under the curve (AUC) for copeptin of 0.88 (95%CI 0.75-1.00). The predictive value of the copeptin concentration was thus similar to that of GCS (AUC 0.82 (95%CI 0.59-1.00) p = 0.53), of the ICH Score (AUC 0.89, (95%CI 0.76-1.00), p = 0.94) and the ICH Grading Scale (AUC 0.86 (95%CI 0.69-1.00), p = 0.81).Copeptin is a new prognostic marker in patients with an ICH. If this finding can be confirmed in larger studies, copeptin might be an additional valuable tool for risk stratification and decision-making in the acute phase of ICH.(Clinical Trial Registration: ISCTRN00390962)Intracerebral hemorrhage (ICH) is more fatal and disabling than ischemic stroke and ranges from 10 to 20 cases per 100,000 population reflecting 10 to 15 percent of all stroke patients [1]. Early prognostication of the risk of death or of a poor long-term outcome would enable optimized care and improved allocation of health-care resources. Several scales of outcome prediction after pr
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).
Cortisol as a Prognostic Marker of Short-Term Outcome in Chinese Patients with Acute Ischemic Stroke  [PDF]
Wen-Jie Zi, Jie Shuai
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072758
Abstract: Background Early prediction of outcome is important for allocation of therapeutic strategies. Endocrine alterations of the hypothalamus–pituitary–axis are one of the first stress-induced alterations after cerebral ischemia. We therefore evaluated the prognostic value of serum cortisol in Chinese patients with an acute ischemic stroke. Methods In a prospective observational study, serum cortisol was measured using a solid-phase, competitive chemiluminescent enzyme immunoassay on admission in serum of 226 consecutive Chinese patients with an acute ischemic stroke. The prognostic value of serum cortisol to predict the functional outcome, mortality within 90 days, was compared with clinical variables (e.g., advanced age and the National Institutes of Health Stroke Scale [NHISS] score) and with other known predictors. Results Patients with a poor outcome and nonsurvivors had significantly increased serum cortisol levels on admission (P<0.0001, P<0.0001). There was a positive correlation between levels of cortisol and the NIHSS (r = 0.298, P<0.0001), glucose levels (r = 0.324, P<0.0001) and infarct volume (r = 0.328, P<0.0001). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio 3.44 (2.58–6.23) and 4.21 (1.89–9.24), respectively, P<0.0001 for both, adjusted for age, the NIHSS and other predictors] in patients with ischemic stroke. In receiver operating characteristic curve analysis, cortisol could improve the NIHSS score in predicting short-term functional outcome (Area under the curve [AUC] of the combined model, 0.87; 95% CI, 0.82–0.92; P = 0.01) and mortality (AUC of the combined model, 0.90; 95% CI, 0.84–0.95; P = 0.01). Conclusion Cortisol can be seen as an independent short-term prognostic marker of functional outcome and death in Chinese patients with acute ischemic stroke even after correcting confounding factors. Combined model can add significant additional predictive information to the clinical score of the NIHSS.
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
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.
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