Prognosis Of Ischemic Stroke Patients Research Articles

Abnormal glucose regulation, hypoglycemic treatment during hospitalization and prognosis of acute ischemic stroke

BackgroundTo examine the effect of abnormal glucose regulation on prognosis and whether hypoglycemic treatment during hospitalization improves prognosis in acute ischemic stroke patients. MethodsA total of 3882 acute ischemic stroke patients with an elevated systolic blood pressure between 140mmHg and 220mmHg were included in the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score≥3) at 3months after stroke. Secondary outcomes included death, major disability, and vascular events. ResultsCompared with normal fasting plasma glucose, odds ratios (95% confidence interval) associated with impaired fasting glucose (IFG) and diabetes mellitus (DM) were 1.25 (0.92–1.68) and 1.38 (1.13–1.67) for composite outcome of death or major disability, respectively, and there was a significant trend for death or major disability (Ptrend=0.001). A linear association between fasting plasma glucose and the risk of combined outcome of death and major disability was observed among the patients without hypoglycemic treatment during hospitalization (P for linearity=0.005). We found protective effect of hypoglycemic treatment for risk of death (odds ratio, 0.47; 95% confidence interval, 0.24–0.92) among ischemic stroke patients with DM. ConclusionsAbnormal glucose regulation, especially DM, increased risks of 3-month poor outcomes after an acute ischemic stroke and hypoglycemic treatment during hospitalization might improve prognosis in ischemic stroke patients with DM.

Serum 25-hydroxyvitamin D deficiency predicts long-term poor prognosis among ischemic stroke patients without hyperglycaemia

BackgroundIt is unclear whether 25-hydroxyvitamin D [25(OH)D] has a protective effect on long-term prognosis of ischemic stroke and whether it is affected by blood glucose levels. We aim to examine the effect of serum vitamin D especially its deficiency on 1-year poor outcome of ischemic stroke patients in total patients and by blood glucose subgroups. MethodsA total of 3041 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included. The serum concentrations of 25(OH)D were measured at baseline. All subjects were followed up for death and vascular events at 1year after acute ischemic stroke. ResultsAmong total ischemic stroke patients and those with hyperglycemia, 25(OH)D deficiency was not associated with the risk of vascular events and death. In the normoglycemic subgroup, 25(OH)D deficiency subjects had a significantly higher risk of poor prognosis compared with those with 25(OH)D≥20ng/ml. The hazard ratio (95% confidence interval) was 1.58(1.04–2.41) in the multivariable adjusted model (P for linear trend=0.02). ConclusionSerum 25(OH)D deficiency may be merely an independent risk factor of 1-year poor prognosis in ischemic stroke patients without hyperglycemia. Future studies about improving long-term prognosis of ischemic stroke by vitamin D supplementation could be first applied to these patients.

Long noncoding RNA Malat1 is a potent autophagy inducer protecting brain microvascular endothelial cells against oxygen-glucose deprivation/reoxygenation-induced injury by sponging miR-26b and upregulating ULK2 expression

Brain microvascular endothelial cell (BMEC) injury induced by ischemia–reperfusion (I/R) is the initial stage of blood–brain barrier (BBB) disruption, which results in a poor prognosis in ischemic stroke patients. Autophagy has been shown to have protective effects on BMECs against cerebral ischemic insults. However, molecular mechanism of BMEC autophagy during I/R is unclear. Long noncoding RNAs (lncRNAs) are emerging as new factors involved in cell autophagy. LncRNA Malat1 is one of the most highly upregulated I/R or OGD/R-responsive endothelial lncRNA and plays a protective role in BMECs against cerebral ischemic insults. Oxygen-glucose deprivation/reoxygenation (OGD/R) is used to mimic I/R injury in vitro. Based on these findings, we hypothesized that Malat1 might play a protective role by enhancing BMEC autophagy. We performed GFP-LC3 puncta formation, LC3 conversion, p62 expression, and cell death assays, and the results were consistent with our hypothesis that Malat1 promoted BMEC autophagy and survival under OGD/R condition. We further explored the molecular mechanisms by which Malat1 exerted regulatory effects, and found that Malat1 served as an endogenous sponge to downregulate miR-26b expression by binding directly to miR-26b. Furthermore, Malat1 overturned the inhibitory effect of miR-26b on BMEC autophagy and survival, which involved in promoting the expression of miR-26b target ULK2. Collectively, our study illuminated a new Malat1-miR-26b-ULK2 regulatory axis in which Malat1 served as a competing endogenous RNA by sponging miR-26b and upregulating ULK2 expression, thereby promoting BMEC autophagy and survival under OGD/R condition.

Combination of five clinical data as prognostic factors of mortality after ischemic stroke

<p>Background <br />The mortality rate after ischemic stoke is influenced by various factors. Prognosis after ischemic stroke can be predicted using a scoring system to help the doctor to evaluate patient’s condition, neurologic deficits, and possible prognosis as well as make appropriate management decisions. The objective of this study was to identify the factors which determine mortality rates in patients after ischemic stroke and to determine the prognosis of ischemic stroke patients using the predictive mortality score.</p><p>Methods<br />This was a nested case control study using data from the stroke registry and medical records of patients at the Neurology Clinic of Bethesda Hospital Yogyakarta between 2011-2015. Data was analysed using simple and multiple logistic regression analysis. The scoring was analyzed using receiver-operating characteristic (ROC) curve and the cut-off point using area under the curve (AUC).</p><p>Results<br />Multiple logistic regression analysis showed a significant association between mortality of ischemic stroke patients and age (OR: 4.539, 95% CI: 1.974-10.439, p<0.001), random blood glucose (OR: 2.692, 95% CI: 1.580-4.588, p<0.001), non-dyslipidemia (OR: 2.313, 95% CI: 1.395-3.833, p=0.001), complications (OR: 1.609, 95% CI: 1.019-2.540, p=0.041), risk of metabolic encephalopathy (OR: 2.499, 95% CI: 1.244-5.021, p=0.010) and use of ventilators (OR: 17.278, 95% CI: 2.015-148.195, p=0.009).</p><p>Conclusions<br />Age, high random blood glucose level, complications, metabolic encephalopathy risk and the use of ventilators are associated with mortality after ischemic stroke. The predictive mortality score can be used to assess the prognosis of patients with ischemic stroke.</p>

Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic Interactions in a Chinese Population

Background/Aims: To investigate the roles of the oxidative stress related-genes ALOX5, ALOX5AP and MPO in ischemic stroke susceptibility in the Han Chinese population. Methods: A total of 351 ischemic stroke patients and 417 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 gene polymorphisms were genotyped. Results: We identified that rs2107545 of MPO gene was significantly associated with ischemic stroke susceptibility after adjusting for covariates. Furthermore, we also considered the likely complexity of oxidative stress and inflammatory process in stroke by assessing the combined effects of multiple genes. Generalized multifactor dimensionality reduction (GMDR) analysis revealed that the combination of ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 was significantly associated with increased risk of ischemic stroke (P=0.0040, OR (95% CI) =1.991 (1.241 to 3.195)). Additionally, the MPO rs2107545 genotype was significantly associated with clinical outcomes at 6 months after discharge from the hospital. Conclusion: Our study revealed that epistatic interaction among the ALOX5, ALOX5AP and MPO genes played a significant role in vulnerability to ischemic stroke. Furthermore, these results also suggest that the rs2107545 of MPO gene can be used as a biomarker for the susceptibility and prognosis of ischemic stroke patients.

The Relationship between Ischemic Stroke Patients with and without Retroflex Tongue: A Retrospective Study.

Background. Patients suffering from stroke exhibit different levels of capability in retroflex tongues, in our clinical observation. This study aims to derive the association of tongue retroflexibility with the degree of severity for stroke patients. Methods. All ischemic stroke patients were collected from August 2010 to July 2013 in the Stroke Center, Changhua Christian Hospital, Taiwan. All participants underwent medical history collection and clinical examination, including tongue images captured by ATDS. Statistical analysis was performed to compare the differences of ischemic stroke patients with and without retroflex tongue. Result. Among the total of 308 cases collected, 123 patients cannot retroflex their tongues, that is, the non-RT group. The length of stay in the non-RT group, 32.0 ± 21.5, was longer than those of the RT counterparts, 25.9 ± 14.4 (p value: 0.007). The NIHSS on admission, 14.1 ± 7.8 versus 8.9 ± 5.2, was higher and the Barthel Index upon admission, 18.6 ± 20.7 and 35.0 ± 24.2, was lower for the non-RT patients than that of the RT counterparts. Also, the non-RT patients account for 60.2% and 75.6% for Barthel Index ≤ 17 and NIHSS ≥ 9, respectively. Conclusion. The stroke patients in non-RT group showed significantly poor prognosis and were more serious in the degree of severity and level of autonomy than RT group, indicating that the ability to maneuver tongue retroflex can serve as a simple, reliable, and noninvasive means for the prognosis of ischemic stroke patients.

Long-Term Prognosis in Ischemic Stroke Patients Treated with Intravenous Thrombolytic Therapy

It remains unclear if intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator has an impact on the survival and maintenance of a favorable effect on functional recovery over a long follow-up period. The aim of this study was to assess whether or not IVT treatment has a favorable effect on functional recovery and survival less than 1 year after a stroke. This matched cohort study included 259 patients with acute ischemic stroke (IS) who were treated with IVT and standard care and 259 patients treated with standard care alone in the stroke unit between February 2006 and January 2013. After a median follow-up period of 3 years (range, 1-7 years), survival did not differ significantly between the groups; specifically, 56 patients (21.6%) in the thrombolysed group died versus 62 patients (23.94%) in the nonthrombolysed group (log-rank, .240, P = .624). Based on a multivariate Cox proportional hazards regression model, older age (>70 years), stroke severity (National Institutes of Health Stroke Scale score ≥ 15), diabetes mellitus, and a history of atrial fibrillation were independent predictors of long-term mortality after stroke. After the follow-up period, 144 patients (55.6%) in the IVT-treated group versus 112 patients (43.2%) in the control group had an excellent outcome, with a modified Rankin Scale score of 0-1 (hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.16-2.32). Based on a multivariate Cox proportional hazards regression model, an excellent 3-month functional recovery was a strong predictor of favorable outcome (HR = 11.27, 95% CI = 6.45-19.63). The results suggest that IVT for acute IS has a favorable effect on functional recovery more than 1 year after stroke.

Redox Imbalance and Stroke.

Redox status is correlated with mitochondrial function, lipid raft turnover, and cellular cross talk in the neurovascular coupling. Redox imbalance is a hallmark event in the pathophysiology and prognosis of stroke. Excessive reactive oxygen species (ROS) can cause oxidative damage to various biological macromolecules including DNA, lipids, and proteins, thereby altering several signaling pathways that ultimately promote cellular damage and death. It is critical to address the relationship between redox status and stroke and to translate the accumulated mechanistic knowledge from animal models to clinical settings. This special issue is devoted to highlighting novel findings on the role of redox imbalance in stroke and possibilities of the antioxidant supplementation for stroke treatment. In this issue there are two investigations focused on the contribution of systemic inflammatory status to pathophysiology and prognosis of ischemic stroke patients. In a cross-sectional study, lower serum level of caveolin-1, which has been reported to maintain blood-brain barrier integrity and counteract oxidative stress, was found to be significantly related to cerebral microbleeds in patients with acute ischemic stroke. However, no relationship was observed between caveolin-1 and the presence of silent lacunar infarcts and white matter hyperintensities, two other types of cerebral small vessel disease. Though the relatively small sample size (~156 patients) may cripple the power of the evaluation, this study strongly supports caveolin-1 as a biomarker for predicting cerebral microbleeds in acute ischemic stroke. Maintaining caveolin-1 level appeared to be a potential strategy in treating cerebral small vessel diseases. X. Zhang et al. carried out a prospective study on the predictive effects of the presence of metabolic syndrome (MetS) on early neurological deterioration following acute ischemic stroke. Interestingly, systemic markers of inflammation, fibrinogen and high-sensitivity C-reactive protein, were not the mediators of the relation between MetS and early neurological deterioration. The authors addressed that local oxidative or inflammatory response markers may be more appropriate when involved in studies of stroke and other potential correlated factors. Two investigations focused on how comorbidity affects stroke outcome and therapeutic approaches. Stroke patients with diabetes mellitus have worsened mortality and neurological recovery. Bradykinin receptors have been demonstrated to play important roles in cerebral ischemia/reperfusion injury in the context of diabetes. R. Shi et al. carried out a study to elucidate the differential roles of bradykinin B1 receptor and B2 receptor underlying the effect of tissue kallikrein on the stroke outcome in diabetic rats. The results revealed that tissue kallikrein protects against inflammatory reactions by suppression of microglial activation and neutrophil infiltration through bradykinin B2 receptor, rather than B1 receptor. The bradykinin B2 receptor-dependent protection requires the activation of ERK/CREB/Bcl-2 signaling pathway to counteract apoptosis and neuroinflammation. Another potent antioxidant agent, minocycline, was investigated by E. A. Fontes-Junior et al. in cortical ischemic injury combined with chronic alcohol intoxication. The results showed that chronic alcohol intoxication increased nitrite and lipid peroxidation levels and neuronal loss caused by ischemia. Minocycline was effective in preventing histological and neurological damage caused by stroke alone. Nevertheless, the protection of minocycline was abolished when stroke was preceded by chronic alcohol intoxication. This study suggests that ischemic stroke combined with chronic alcohol intoxication is more severe and may require different therapeutic strategies. J. Qu et al. provided a comprehensive review to summarize the role of ROS in the intracerebral hemorrhage. ROS is mainly released from neurons exposed to hemoglobin metabolic products after intracerebral hemorrhage, which is strikingly different from the pathophysiology in ischemic stroke. This ROS is harmful to the central nervous system through cell death and structural damage, especially the disruption of the blood-brain barrier. The review continues to discuss how endogenous antioxidant system interacts with the oxidant agents and why previous antioxidant therapy failed to confer practical neuroprotection in clinical trials. The authors suggest more attention be paid to the local and systemic influences of ROS in intracerebral hemorrhage and the longitudinal profile of ROS burst after intracerebral hemorrhage. In another review article, J. Bu et al. discussed the effects of a natural product, omega-3 polyunsaturated fatty acids (n-3 PUFAs), the major component of fish oil, on the redox imbalance after stroke. Due to their antioxidation, anti-inflammation, and interaction with pathways such as Nrf2/HO-1 signaling, n-3 PUFAs are neuroprotective in reducing infarction volume and improving neurogenesis and revascularization. The authors also expressed that further studies were warranted to establish the specific treatment strategy of n-3 PUFAs in stroke. In conclusion, the goal of this special issue is to drive a better understanding of how redox imbalance modulates pathophysiology and prognosis of stroke and how this can be harnessed as a therapeutic target in the stroke treatment. The original and review articles in this issue contributed by the experts in the fields of redox and stroke will nurture and expand knowledge of the mechanisms behind oxidative damage. Ruidong Ye Ming Shi Qian Liu Jieli Chen

Prediction of the prognosis of ischemic stroke patients after intravenous thrombolysis using artificial neural networks.

In general, around 80% of all strokes are ischemic. Take caring of the patients who have suffered an ischemic stroke is both expensive and time consuming. It is known that thrombolysis in patients with ischemic stroke can reduce the disability and increase the survival rate, however some patients still have poor outcomes. Therefore, to be able to predict the outcome of ischemic stroke patients after intravenous thrombolysis would be useful while making clinical decisions. In this study, we collected retrospective data of 82 ischemic stroke patients who received intravenous thrombolysis from July 2005 to June 2012 in Tri-service General Hospital. Of these patients, 10 died within 3 months, and only 36 patients made a good recovery. We used STATISTICA 10 software to select the best artificial neural network. The parameters of model 1 were age, blood sugar, onset to treatment time, National Institute of Health Stroke Scale (NIHSS) score, dense cerebral artery sign, and old stroke to predict 3-month outcomes. The parameters of model 2 were age, onset to treatment time, NIHSS score, hypertension, heart disease, diabetes and old stroke to predict the 3-month prognosis. The sensitivity, specificity and accuracy for model 1 were 77.78%, 80.43% and 79.27%, respectively, and 94.44%, 95.65% and 95.12%, respectively, for model 2. Artificial neural networks are used to establish prediction models with good performance to predict thrombolysis outcomes. These models may be able to help physicians to discuss and explain the likely outcomes to patients and their families before thrombolysis treatment.

Abstract T MP42: Mitral Ratio of Peak Early to Late Diastolic Filling Velocity as a Predictor of Mortality in Acute Ischemic Stroke

Background: Diastolic dysfunction has a significant impact on symptoms, functional outcomes, and prognosis in ischemic stroke patients. The ratio of peak early to late diastolic filling velocity (E/A) is the simplest and most commonly used index to assess diastolic dysfunction. Methods: One thousand seven hundred seven patients with acute ischemic stroke who had a transthoracic echocardiogram during admission were identified. We classified patients into 3 groups by E/A ratios based on the previous literature search. We conducted binary logistic regression analysis for death, vascular death, and stroke death. Results: Among a total of 1707 patients, 261 (15.3%) had E/A <0.6 and 124 (7.3%) had E/A>1.5. All cause death was higher with E/A <0.6 or E/A >1.5 compared to E/A 0.6-1.5 (25.7% and 16.9% versus 15.1%), as was vascular death (10.2% and 8.5% versus 5.8%). After adjusting for age, gender, previous stroke history, hypertension, diabetes, smoking, dyslipidemia, atrial fibrillation, stroke subtype, left ventricular end-diastolic diameter, LA/Ao ratio, mitral E deceleration time, relative wall motion abnormality, and initial stroke severities, the relative risk of all-cause death with E/A >1.5 was 2.24 (95% CI, 1.14-4.33; p= 0.02); the relative risk of vascular death with E/A>1.5 was 3.50 (95% CI, 1.39-8.80; p<0.01 ); the relative risk of stroke death with E/A >1.5 was 3.42 (95% CI, 1.21-9.69; p=0.02 ). Conclusion: The E/A>1.5 is associated with 2-fold increased all-cause mortality and 3-fold vascular and stroke mortalities independent of covariates in ischemic stroke patients.

Abstract T P170: Carotid Artery Intima-Media Thickness and Ankle-Brachial Index are Strong Predictors of Complicated Aortic Arch Plaque in Acute Cerebral Embolism Patients

Background: Complicated aortic arch plaque (CAP) detected by transesophageal echocardiography (TEE) provides prognostic information regarding cerebrovascular disease risk. Coexistence of peripheral atherosclerotic disease worsens the prognosis in ischemic stroke patients. Methods: We examined TEE, carotid artery intima-media thickness (CIMT, calculated from carotid echograms), and ankle-brachial index (ABI, calculated from ankle/brachial blood pressure ratios) in 100 consecutive cerebral embolism patients within 2 weeks of onset of symptoms. CAP was defined as atherosclerotic plaque (≥4mm) or presence of ulcerated plaque assessed by TEE. Patients were classified into those with CAP (n=36, Group A) or without CAP (n=64, Group B). Results: Comparing patients in the two groups, significantly higher values were seen in Group A for age (69±8 vs. 63±11 years, p<0.01), prevalence of hypertension (75% vs. 50%, p<0.05) and ischemic heart disease (19% vs. 3%, p<0.01), and CIMT (1.9±0.8 vs. 1.2±0.5 mm, p<0.0001). Significantly lower values were seen in Group B for ABI (0.93±0.22 vs. 1.11±0.11, p<0.0001). Defining arteriosclerosis obliterans (ASO) as ABI <0.9 and CIMT thickening as CIMT ≥1.1mm, CAP was predicted by ASO with 39% sensitivity and 97% specificity, and by CIMT thickening with 78% sensitivity and 48% specificity. Combined ASO and CIMT thickening predicted CAP with 83% sensitivity and 81% positive predictive value, and with 97% specificity and 83% negative predictive value in all of the subjects. Furthermore, aortic arch intima-media thickness was significantly correlated with CIMT and ABI (r=0.441, p<0.0001 and r=-0.384, p<0.0001, respectively). Conclusions: For non-invasive evaluation of patients with acute cerebral embolism, the combination of both ABI and CIMT predicts CAP more strongly than either ABI or CIMT considered alone, with higher figures for sensitivity, specificity, and positive and negative predictive value.

Evaluation of the protective potential of brain microvascular endothelial cell autophagy on blood-brain barrier integrity during experimental cerebral ischemia-reperfusion injury.

Brain microvascular endothelial cell (BMVEC) injury induced by ischemia-reperfusion (I/R) is the initial phase of blood-brain barrier (BBB) disruption, which results in a poor prognosis for ischemic stroke patients. Autophagy occurs in ischemic brain and has been shown to exhibit protective effects on endothelial cell against stress. However, the potential effects of BMVEC autophagy on BBB permeability during I/R and the mechanisms underlying these effects have yet to be elucidated. In the current study, we answered these questions by using chemical modulators of autophagy, including rapamycin and lithium carbonate acting, respectively, as mammalian target of rapamycin (mTOR)-dependent and mTOR-independent autophagy inducers and 3-methyladenine (3-MA) as an autophagy inhibitor. To mimic I/R injury, BMVECs were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), and a rat transient middle cerebral artery occlusion/reperfusion (MCAO/R) model was performed. All the drugs were given at 0.5h before OGD/R or MCAO/R. First, enhancement of autophagy by rapamycin and lithium carbonate attenuated, whereas suppression of autophagy by 3-MA intensified BMVEC apoptosis and the high level of ROS induced by OGD/R. In addition, rapamycin and lithium carbonate pretreatments significantly reversed the decreased level of tight junction protein zonula occludens-1 (ZO-1) induced by OGD/R and promoted the distribution of ZO-1 on cell membranes. Finally, pretreatments with rapamycin and lithium carbonate reduced evans blue extravasation and brain water content in the ischemic hemisphere of the rat. In contrast, 3-MA pretreatment exerted opposite effects both in vitro and in vivo. These results may indicate a beneficial effect of BMVEC autophagy on BBB integrity during I/R injury.

Alterations in the time course of expression of the Nox family in the brain in a rat experimental cerebral ischemia and reperfusion model: effects of melatonin.

Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS), which results in a poor prognosis for ischemic stroke patients. This study was designed to evaluate the time course of expression of the Nox family, a major source of ROS, and whether melatonin, a potent scavenger of ROS, influences these parameters in a rat model of cerebral I/R caused by middle cerebral artery occlusion (MCAO). After 2-hr occlusion, the filament was withdrawn to allow reperfusion. At 0, 3, 6, 12, 24, and 48hr after reperfusion, brain tissue samples were obtained for assays. Among the Nox family, the mRNA and protein levels of Nox2 and Nox4 were increased both in the ischemic hemisphere and contralateral counterpart in the experimental I/R rats at 0hr after reperfusion, peaked at 3hr, and then returned to the basal level at 24hr. Double-immunofluorescence staining further confirmed the expressions of Nox2 and Nox4 in three major types of brain cells, including neurons, astrocytes, and endothelial cells. In addition, melatonin (5mg/kg) or its vehicle was injected intraperitoneally at 0.5hr before MCAO. Compared with I/R + vehicle group, melatonin pretreatment diminished the increased expression of Nox2 and Nox4, reduced ROS levels, and inhibited cell apoptosis. Our findings suggested that the inhibition of Nox2 and Nox4 expressions by melatonin may essentially contribute to its antioxidant and anti-apoptotic effects during brain I/R.

The effects of lipoprotein(a) and homocysteine on prognosis and risk factors in acute ischemic stroke

The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and homocysteine (Hcy) and lipoprotein(a) Lp(a) were found to have roles during the process. This study aims to investigate the relationship between acute ischemic stroke and Lp(a) and Hcy levels and to determine the prognosis and functional disability. Forty-one patients with acute ischemic stroke and 33 controls were included in the study. Lp(a) and Hcy levels were examined in both groups. The modified Rankin scale (MRS) scores at discharge and in the first and third months were determined to establish the functional disability and prognosis of stroke patients. In patients with acute ischemic stroke, Hcy levels were significantly higher than the controls (p = 0.003). There was no significant difference between Lp(a) levels in patients with acute ischemic stroke and controls (p = 0.150). Because there was a significant difference in terms of Hcy levels between the groups, it will be suitable to routinely monitor the Hcy levels of individuals who are known to have risk factors for stroke. Neither Lp(a) nor Hcy levels had any correlations with functional disability; therefore, it can be concluded that the Lp(a) and Hcy levels are inexpressive in predicting the functional disability and prognosis for ischemic stroke patients.

OPN Gene Polymorphism and the Serum OPN Levels Confer the Susceptibility and Prognosis of Ischemic Stroke in Chinese Patients

Aim: To investigate the association of Osteopontin (OPN) gene polymorphism and serum thrombin-cleaved OPN level with the susceptibility to ischemic stroke (IS) and its prognosis. Methods: A total of 377 patients with IS and 551 healthy individuals were recruited. The OPN gene polymorphisms at -156 G>GG, -443 C>T and -66 T>G were genotyped. Serum full-length and the thrombin-cleaved OPN were determined. Results: We found that only the -443 C>T polymorphism was significantly associated with the susceptibility to IS. The -443 CC represented a near 2 time higher risk for IS incidence than TT carriers. Also, the -443 CC genotype had significantly poorer outcome and they significantly had higher occurrence for bad recovery as determined by modified Rankin Scale (mRS) (OR=2.18, p=0.043) and Barthel Index (BI) (OR=2.12, p=0.05). The mean serum thrombin-cleaved OPN level in IS group were significantly higher than that in control group. ROC analysis showed that the thrombin-cleaved OPN level (cut-off value, 166.8 ng/ml) can discriminate IS patients from controls with a specificity of 86.3% and a sensitivity of 57.7%. The serum thrombin-cleaved OPN was significantly associated with the clinical outcome at 12 months after discharge from hospital. Conclusion: These results suggest that the -443 C>T polymorphism of OPN gene and serum thrombin-cleaved OPN can be used as a biomarker for the susceptibility and prognosis of IS patients.

Use of Magnetic Resonance Angiography to Predict Long-Term Outcomes of Ischemic Stroke Patients with Concurrent Stenoses in Hong Kong

Purpose: To determine the long-term outcome of ischemic stroke patients with concurrent intracranial and extracranial atherosclerosis using magnetic resonance angiography. Methods: A prospective cohort of patients in Hong Kong with acute ischemic stroke was studied with magnetic resonance angiography of the brain and carotid duplex. All patients were followed up regularly for the development of recurrent stroke, cardiac events, or death. Results: Totally 343 patients with acute ischemic stroke were included, of whom 104 (30%) had concurrent intracranial and extracranial lesions. The follow-up period was up to 76 months (mean 44.5 months). Overall, 55 patients (15.5%) died of any cause and 91 patients (26.5%) suffered a further nonfatal vascular event. The overall 5-year cumulative rates of mortality, restroke and poor outcomes (combined death and further vascular events) were 18, 27 and 37%, respectively. In patients with concurrent lesions, these rates were 31, 41 and 51%, respectively. The corresponding rates were 13, 22 and 31% in patients without concurrent lesions. The risks were highest in the first year after stroke. More deaths (log rank, 16.3; p = 0.0001), restrokes (log rank, 9.71; p = 0.002) and poor outcomes (log rank, 13.87; p = 0.0001) were found among patients with concurrent lesions. The presence of concurrent vascular lesions, advanced age, smoking, hyperlipidemia and previous history of stroke were independent predictors of poor outcomes. Conclusions: The long-term prognosis of ischemic stroke patients with concurrent atherosclerosis of intracranial and extracranial vessels is poor. They are at high risk of further vascular events or death.

Hyperglycemia after Acute Ischemic Stroke: Prediction, Significance and Immediate Control with Insulin-Potassium-Saline-Magnesium Infusions

Introduction: It is well known that in the first 24 h after stroke onset, plasma glucose concentrations are elevated in 20–43% of patients, of whom more than half are not known to have diabetes mellitus. Glucose levels >8 mmol/l have been found to be predictive of a poor prognosis in ischemic stroke patients. It is thought that the clinical use of insulin infusions has a beneficial effect on hyperglycemia. Indeed, insulin therapy in critically ill patients, including acute stroke patients, is safe and results in lower mortality and complication rates. Unfortunately, the impact of intensive insulin therapy in non-critically ill patients with hyperglycemia is poorly understood. Objectives: It was the aim of this study to determine the clinical efficacy and safety of early-onset therapy with human recombinant insulin: glycemic control measured by reduction in plasma glucose concentrations, vital activity measured by the Barthel index (no significant disability was defined as ≤50, moderate disability was defined as 51–75, and severe disability was defined as ≧75), and neurological deficit measured by the National Institutes of Health Stroke Scale (NIHSS; values ranging from 0 = normal to 42 = worst case) in non-critically ill ischemic stroke diabetic and non-diabetic patients. Design: We used a randomized prospec- tive open trial of insulin-potassium-saline-magnesium (IPSM) infusions in patients after acute ischemic stroke presenting with mild to moderate hyperglycemia. Acute (<24 h) ischemic stroke patients (n = 128) with hyperglycemia on admission between 7.0 and 16 mmol/l with and without type 2 diabetes mellitus (T2DM) were randomly divided into four groups: (1) hyperglycemia associated with T2DM and treated with IPSM (n = 36), (2) hyperglycemia associated with T2DM without IPSM administration (n = 40), (3) hyperglycemia without confirmed T2DM and treated with IPSM (n = 25), and (4) hyperglycemia without confirmed T2DM and without IPSM administration (n = 27). Results: Treatment with the IPSM regimen permitted to normalize blood glucose levels. The neurological deficit according to the NIHSS in stroke patients with hyperglycemia treated with insulin did not worsen in the first 3 days. Results were expressed as means ± SD of NIHSS scores at admission and at day 30. At the same time, the clinical status of patients not treated with insulin worsened. Three weeks after admission, the neurological deficit improved in treated stroke patients (13.5 ± 1.5 and 8.6 ± 1.1, respectively; p < 0.05) and untreated patients with T2DM (13.2 ± 1.7 and 8.9 ± 1.3; p < 0.05). However, the neurological deficit in stroke patients without T2DM, but with hyperglycemia not treated with insulin did not improve significantly (14.4 ± 1.5 and 10.1 ± 1.0, respectively; p > 0.05). Administration of IPSM led to a significant improvement in the neurological status (14.6 ± 1.5 and 8.9 ± 1.3; p < 0.05). Conclusions: Insulin therapy (IPSM infusion) is a safe and effective approach to normalize blood glucose levels after ischemic stroke. Administration of insulin to patients with hyperglycemia improves functional recovery and vital activity of stroke patients. However, other clinical benefits of the insulin therapy remain to be determined.

Inflammation, Statins, and Outcome After Ischemic Stroke

To the Editor: In the recently article by Jonsson and Asplund,1 the authors demonstrate that statins have a moderate effect in improving the prognosis of ischemic stroke patients, underlying the possible complex role of statins in determining prognosis after ischemic stroke. Their data are in agreement with our preliminary results on the concurrent use of statins in patients with first-ever ischemic stroke.2 Previously, we found that the use of statins reduces the levels of C-reactive protein (CRP) after ischemic stroke, the initial neurological deficit, and improves the prognosis of stroke patients with a significant reduction of the 1-year risk of death or new vascular events.2 Recently, we have extended these observations in the same ischemic stroke cohort that had concluded the 2-year follow-up. All patients (n=193) were recruited in the period between March 1, 1998, and March 31, 1999. Design, methods, and baseline characteristics of our stroke data bank have been previously reported.3,4 We measured levels of CRP after stroke (within 24 hours), at 3 months, and at the end of the 2-year follow-up, together with total cholesterol, HDL and LDL subfractions, and triglycerides. Differences in proportions were evaluated by χ2 test. Continuous variables are described as mean±SD or median values with 25th and 75th percentiles, and comparisons between groups were evaluated with the Student t test or Mann-Whitney U test, when appropriate. The Kaplan-Meier technique (log-rank test) was applied in survival analysis. Log-normalized values of CRP were used to evaluate correlations over time. At the entry, mean total cholesterol concentrations were 4.62±1.25 mmol/L in men and 5.31±1.06 mmol/L …