The association of hyperglycemia with cerebral edema in stroke

A retrospective review of stroke patients admitted to our hospital revealed 39 patients diagnosed as suffering an acute completed ischemic stroke who also had had fasting (AC) serum glucose determinations and sequential computer tomography (CT) studies. The patients were divided into three groups on the basis of mean AC serum glucose: Group 1 (n = 12) mean serum AC glucose greater than 150 mg/dl; Group 2 (n = 13) mean serum AC glucose 100-150 mg/dl; and Group 3 (n = 14) mean serum AC glucose less than 100 mg/dl. CT scans performed on each patient were studied for the presence of midline shift and/or ventricular compression, which were interpreted as evidence of cerebral edema. The three groups were comparable with respect to mean age, average mean arterial blood pressure and initial infarct size. Our results show that in Group 1, 42% of the patients died within the first week following their CVA with clinical evidence of transtentorial herniation confirmed by CT or autopsy. In contrast, none of the Group 3 patients died and only one showed radiological evidence for cerebral edema. Group 2 patients showed intermediate mortality and evidence of cerebral edema. These trends were statistically significant at p less than 0.005. In addition, the combined hyperglycemic group (1 and 2) had a significantly higher rate of development of hypodensity on CT (p less than 0.05) than the normoglycemic group. Our findings suggest that patients with hyperglycemia in association with their CVA develop more pronounced cerebral edema and have a worse clinical outcome. Possible pathophysiological mechanisms that may underlie this observation are discussed.     

Hemorrhage after an acute ischemic stroke.MAST-I Collaborative Group

BACKGROUND AND PURPOSE: Hemorrhagic transformation is frequently seen on CT scans obtained in the subacute phase of ischemic stroke. Its prognostic value is controversial. METHODS: We analyzed 554 patients with acute ischemic stroke enrolled in the Multicenter Acute Stroke Trial-Italy (MAST-I) study in whom a second CT scan was performed on day 5. Presence of 1) intraparenchymal hemorrhages (hematoma or hemorrhagic infarction), 2) extraparenchymal bleeding (intraventricular or subarachnoid) and 3) cerebral edema (shift of midline structure, sulcal effacement or ventricular compression) alone or in association were evaluated. Death or disability at 6 months were considered as "unfavorable outcome." RESULTS: Patients who developed intraparenchymal hemorrhages, extraparenchymal bleeding, or cerebral edema had unfavorable outcome (83%, 100%, and 80%, respectively), but multivariate analysis demonstrated that only extraparenchymal bleeding (collinearity) and cerebral edema (OR=6.8; 95% CI, 4.5 to 10.4) were significant independent prognostic findings. Unfavorable outcome correlated with size of intraparenchymal hemorrhage (chi2 for trend=30.5, P<0.0001). Nevertheless, when a large hematoma was present the negative effect was mostly due to concomitant extraparenchymal bleeding (chi2=51.6, P<0.0001), and when hemorrhagic infarction was detected the negative effect was mostly explained by the association with cerebral edema (chi2=36.6, P<0.0001). CONCLUSIONS: Extraparenchymal bleeding and cerebral edema are the main prognostic CT scan findings in the subacute phase of ischemic stroke. Stroke patients with a high risk for developing these 2 types of brain damage should be identified. Measures to prevent and adequately treat their development should be implemented.     

Blutzucker und Schlaganfall

There is strong evidence that severe hypoglycemia can worsen the prognosis in acute stroke. In contrast, the influence of acute hyperglycemia on cerebral ischemia remains controversial. The conflicting results of clinical and experimental studies can partly be explained if different stroke subtypes are regarded separately and the time course of the blood-glucose level during the acute insult is taken into account. Hyperglycemia seems to worsen the neuronal injury during the subacute period of cerebral ischemia if there is insufficient collateral blood supply. Furthermore, it increases the risk of hemorrhagic transformation in this time interval. In contrast, acute hyperglycemia may protect neuronal tissue from structural damage by improving the substrate supply if there is only a moderate decrease in cerebral blood flow. This situation is observed in the penumbra and if good collateral blood supply is provided. We therefore hypothesize that both negative and positive effects of acute hyperglycemia depend on the local cerebral blood flow.     

Hyperglycemia as a Predictor of Poor Outcome at Discharge in Patients with Acute Spontaneous Cerebellar Hemorrhage

Acute stroke patients commonly suffer from hyperglycemia. However, the relationship between hyperglycemia and poor outcome after discharge of patients with acute cerebellar hemorrhage (CH) had not been hitherto investigated.Sixty-two patients with acute spontaneous CH were retrospectively analyzed. The consciousness level, blood glucose/sugar (BS) on arrival and maximum diameter of hematoma, etc., were obtained. Patient prognosis was scored by the Glasgow Outcome Scale (GOS) at discharge and we divided them into good outcome (GOS score of 4 or 5) and poor outcome (GOS score of 1 or 2 or 3) groups. The association between early outcome and clinical characteristics were investigated by multivariate logistic regression. There were 33 (53.4%) patients in the poor outcome group and 29(46.6%) in the good outcome group. The initial BS was significantly higher in the poor outcome group (186.4±57 mg/dl) compared with good outcome group (136.6±31.1 mg/dl)(p<0.001). BS≥140 mg/dl (OR=25.217, p=0.008) and maximum diameter of hematoma ≥3 cm (OR=216.422, p<0.001) were independently correlated with poor outcome. We report the first study that hyperglycemia (BS≥140 mg/dl) on arrival and maximum diameter of hematoma ≥3 cm were found to be strong predictive factors of poor outcome at discharge in patients with acute spontaneous CH.     

Associations between multiple sclerosis and in-hospital outcomes of patients with hemorrhagic stroke

ObjectiveTo determine the influence of multiple sclerosis (MS) on in-hospital outcomes of patients with hemorrhagic strokes using a large, nationally representative database.Materials and methodsThis population-based, retrospective study extracted data of adults with hemorrhagic stroke from the US Nationwide Inpatient Sample (NIS) database from 2016 to 2018. Patients with/without MS were then compared. Hemorrhagic stroke and MS were identified by the International Classification of Diseases, Tenth editions (ICD-10) codes. In-hospital outcomes (i.e., in-hospital mortality, discharge destination, length of stay [LOS], total hospital cost, and major complications) were compared between subjects with and without MS using logistic regression analysis.ResultsAmong 107,573 patients with hemorrhagic stroke, 0.3% (n=337) had MS. After 1:10 propensity-score (PS) matching, 3,707 patients remained in the analytic sample. Multivariable analysis revealed that patients with MS had significantly shorter LOS (adjusted β=-1.34 days; 95% CI: -2.41 to -0.26, p=0.015), and lower total hospital costs (adjusted β=-28.82; 95% CI: -43.57 to -14.06, p<0.001) than those without MS. No significant different risks of any major complications, in-hospital mortality, or transfer to nursing homes/long-term care facilities were observed. For major complications, patients with MS had a significantly lower risk of cerebral edema than those without MS (adjusted odds ratio [aOR] = 0.66, 95%CI: 0.51 to 0.86, p =0.002)ConclusionsIn hospitalized patients with hemorrhagic stroke, those with MS have shorter LOS, lower costs, and a lower risk of cerebral edema compared to no MS. More relevant experiments and studies are needed to confirm results of this study.     

Inpatient Hyperglycemia Following Aneurysmal Subarachnoid Hemorrhage: Relation to Cerebral Metabolism and Outcome

Introduction  Despite its clear association with impaired prognosis, it remains controversial whether hyperglycemia after aneurysmal subarachnoid hemorrhage (SAH) actively contributes to neuronal damage. This study aimed to identify a threshold for blood glucose predicting unfavorable outcome, and to evaluate differences in cerebral metabolism in normo and hyperglycemic SAH patients. Methods  Prospectively, blood glucose and cerebral metabolism, measured by cerebral microdialysis, were evaluated in 178 patients (WFNS grade I–V; age 51.6 ± 12.4 years) during days 1–7 after SAH. Patients were classified into groups with mean blood glucose levels ≤/> 6.1 mmol/l (110 mg/dl) and 7.8 mmol/l (140 mg/dl). Glasgow Outcome Score was assessed after 12 months. Results  Higher inpatient blood glucose was associated with impaired prognosis, with a threshold of 7.5 mmol/l (135 mg/dl) distinguishing best between favorable and unfavorable outcome. Inpatient glucose levels >6.1 mmol/l (110 mg/dl) were associated with higher cerebral lactate and lactate/pyruvate ratio (P < 0.05). Cerebral glucose was elevated only at blood levels >7.8 mmol/l (140 mg/dl). Inpatient glucose levels above 7.8 mmol/l (140 mg/dl) were independent predictors of unfavorable outcome and mortality. Conclusion  Blood glucose levels >7.8 mmol/l (140 mg/dl), but not levels >6.1 mmol/l (110 mg/dl), independently predicted unfavorable outcome. While blood glucose levels >6.1 mmol/l (110 mg/dl) were already associated with slight metabolic derangements, cerebral glucose increased only at blood levels >7.8 mmol/l (140 mg/dl). Considering the risks associated with tight glycemic control, a moderate regimen accepting blood glucose levels up to 7.8 mmol/l (140 mg/dl) might be more reasonable after SAH.     

Glibenclamide in Cerebral Ischemia and Stroke

The sulfonylurea receptor 1 (Sur1)–transient receptor potential 4 (Trpm4) channel is an important molecular element in focal cerebral ischemia. The channel is upregulated in all cells of the neurovascular unit following ischemia, and is linked to microvascular dysfunction that manifests as edema formation and secondary hemorrhage, which cause brain swelling. Activation of the channel is a major molecular mechanism of cytotoxic edema and “accidental necrotic cell death.” Blockade of Sur1 using glibenclamide has been studied in different types of rat models of stroke: (i) in conventional non-lethal models (thromboembolic, 1–2 h temporary, or permanent middle cerebral artery occlusion), glibenclamide reduces brain swelling and infarct volume and improves neurological function; (ii) in lethal models of malignant cerebral edema, glibenclamide reduces edema, brain swelling, and mortality; (iii) in models with rtPA, glibenclamide reduces swelling, hemorrhagic transformation, and death. Retrospective studies of diabetic patients who present with stroke have shown that those whose diabetes is managed with a sulfonylurea drug and who are maintained on the sulfonylurea drug during hospitalization for stroke have better outcomes at discharge and are less likely to suffer hemorrhagic transformation. Here, we provide a comprehensive review of the basic science, preclinical experiments, and retrospective clinical studies on glibenclamide in focal cerebral ischemia and stroke. We also compare the preclinical work in stroke models to the updated recommendations of the Stroke Therapy Academic Industry Roundtable (STAIR). The findings reviewed here provide a strong foundation for a translational research program to study glibenclamide in patients with ischemic stroke.     

Hypoxia-inducible factor-1α contributes to brain edema after stroke by regulating aquaporins and glycerol distribution in brain

Brain edema following stroke is a critical clinical problem due to its association with increased morbidity and mortality. Despite its significance, present treatment for brain edema simply provides symptomatic relief due to the fact that molecular mechanisms underlying brain edema remain poorly understood. The present study investigated the role of hypoxia-inducible factor-1α (HIF-1α) and aquaporins (AQP-4 and -9) in regulating cerebral glycerol accumulation and inducing brain edema in a rodent model of stroke. Two-hours of middle cerebral artery occlusion (MCAO) followed by reperfusion was performed in male Sprague-Dawley rats (250-280 g). Anti-AQP-4 antibody, anti-AQP-9 antibody, or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) was given at the time of MCAO. The rats were sacrificed at 1 and 24 hours after reperfusion and their brains were examined. Extracellular and intracellular glycerol concentration of brain tissue was calculated with an enzymatic glycerol assay. The protein expressions of HIF-1α, AQP-4 and AQP-9 were determined by Western blotting. Brain edema was measured by brain water content. Compared to control, edema (p < 0.01), increased glycerol (p < 0.05), and enhanced expressions of HIF-1α, AQP-4, and AQP-9 (p < 0.05) were observed after stroke. With inhibition of AQP-4, AQP-9 or HIF-1α, edema and extracellular glycerol were significantly (p < 0.01) decreased while intracellular glycerol was increased (p < 0.01) 1 hour after stroke. Inhibition of HIF-1α with 2ME2 suppressed (p < 0.01) the expression of AQP-4 and AQP-9. These findings suggest that HIF-1α serves as an upstream regulator of cerebral glycerol concentrations and brain edema via a molecular pathway involving AQP-4 and AQP-9. Pharmacological blockade of this pathway in stroke patients may provide novel therapeutic strategies.     

Crotalus atrox disintegrin reduces hemorrhagic transformation by attenuating matrix metalloproteinase-9 activity after middle cerebral artery occlusion in hyperglycemic male rats

Hemorrhagic transformation after ischemic stroke is an independent predictor for poor outcome and is characterized by blood vessel rupture leading to brain edema. To date, no therapies for preventing hemorrhagic transformation exist. Disintegrins from the venom of Crotalus atrox have targets within the coagulation cascade, including receptors on platelets. We hypothesized that disintegrins from C. atrox venom can attenuate hemorrhagic transformation by preventing activation of matrix metalloproteinase after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. We subjected 48 male Sprague-Dawley rats weighing 240–260 g to MCAO and hyperglycemia to induce hemorrhagic transformation of the infarction. At reperfusion, we administered either saline (vehicle), whole C. atrox venom (two doses were used), or fractionated C. atrox venom (HPLC Fraction 2). Rats were euthanized 24 hr post-ictus for measurement of infarction and hemoglobin volume. Reversed-phase HPLC was performed to fractionate the whole venom and peaks were combined to form Fraction 2, which contained the disintegrin Crotatroxin. Fraction 2 protected against hemorrhagic transformation after MCAO, and attenuated activation of matrix metalloproteinase-9. Administering matrix metalloproteinase antagonists prevented the protection by Fraction 2. The results of this study indicate that disintegrins found in C. atrox venom may have therapeutic potential for reducing hemorrhagic transformation after ischemic stroke. Moreover, the RP-HPLC fractions retained sufficient protein activity to suggest that gentler and less efficient orthogonal chromatographic methods may be unnecessary to isolate proteins and explore their function.     

Trends in risk factors, patterns and causes in hospitalized strokes over 25 years: The Lausanne Stroke Registry

BACKGROUND AND OBJECTIVE: The Lausanne Stroke Registry includes, from 1979, all patients admitted to the department of Neurology of the Lausanne University Hospital with the diagnosis of first clinical stroke. Using the Lausanne Stroke Registry, we aimed to determine trends in risk factors, causes, localization and inhospital mortality over 25 years in hospitalized stroke patients. METHODS: We assessed temporal trends in stroke patients characteristics through the following consecutive periods: 1979-1987, 1988-1995 and 1996-2003. Age-adjusted cardiovascular risk factors, etiologies, stroke localizations and mortality were compared between the three periods. RESULTS: Overall, 5,759 patients were included. Age was significantly different among the analyzed periods (p < 0.001), showing an increment in older patients throughout time. After adjustment for age, hypercholesterolemia increased (p < 0.001), as opposed to cigarette smoking (p < 0.001), hypertension (p < 0.001) and diabetes and hyperglycemia (p < 0.001). In patients with ischemic strokes, there were significant changes in the distribution of causes with an increase in cardioembolic strokes (p < 0.001), and in the localization of strokes with an increase in entire middle cerebral artery (MCA) and posterior circulation strokes together with a decrease in superficial middle cerebral artery stroke (p < 0.001). In patients with hemorrhagic strokes, the thalamic localizations increased, whereas the proportion of striatocapsular hemorrhage decreased (p = 0.022). Except in the older patient group, the mortality rate decreased. CONCLUSIONS: This study shows major trends in the characteristics of stroke patients admitted to a department of neurology over a 25-year time span, which may result from referral biases, development of acute stroke management and possibly from the evolution of cerebrovascular risk factors.     

The role of hyperglycemia in acute stroke

BACKGROUND: Ischemic stroke is a leading cause of death and long-term disability, and hyperglycemia is believed to aggravate cerebral ischemia. OBJECTIVES: To review animal and human studies on the relationship between hyperglycemia and brain ischemia that elucidate some of the mechanisms for the deleterious effect of hyperglycemia. To discuss present and future clinical recommendations for glucose control. METHODS: Computerized data sources and published indexes and articles from 1976 through 2000 were searched for human studies that evaluated the association between stroke and hyperglycemia, and studies focused on experimental models of hyperglycemic animals with focal and global brain ischemia. RESULTS: Most human studies have shown that in acute stroke, admission hyperglycemia in patients with or without diabetes is associated with a worse clinical outcome than in patients without hyperglycemia. This association is more consistent in the nonlacunar type of stroke. Animal studies support these findings by showing both in global and in focal postischemic models that hyperglycemia exaggerates the following damaging processes: intracellular acidosis, accumulation of extracellular glutamate, brain edema formation, blood-brain barrier disruption, and tendency for hemorrhagic transformation. Insulin treatment of hyperglycemic animals was found to have a beneficial effect in focal and global brain ischemia, which may be mediated by the glucose-reduction effect or by a direct neuroprotection. CONCLUSIONS: Most studies show the deleterious effect of early hyperglycemia, especially in patients with nonlacunar focal or global ischemia. Clinical trials of intensive insulin treatment are needed. Meanwhile simple measures to avoid excessive hyperglycemia are recommended.     

Immunohematologic characteristics of infection-associated cerebral infarction.

We evaluated 50 consecutive patients with acute ischemic stroke to assess the prevalence of systemic infection preceding the neurological event. We analyzed the immunohematologic characteristics of patients with and without signs and/or symptoms of a preceding infectious process. Patients were examined less than or equal to 7 days after cerebral infarction and evaluated for fibrinogen, anticardiolipin antibodies, fibrin D-dimer (a fragment of cross-linked fibrin), plasminogen activator inhibitor-1, and protein S. Of the 50 patients, 17 had symptoms of infection beginning less than or equal to 1 month before the stroke (11 had upper respiratory tract infections, three urinary tract infections, two subacute bacterial endocarditis, and one pneumonia). Compared with patients without infection, patients with infection had significant increases in fibrin D-dimer concentration (5.3 +/- 1.1 versus 4.7 +/- 0.9 log-transformed ng/ml, p less than 0.05) and cardiolipin immunoreactivity, IgG isotype (1.8 +/- 1.3 versus 1.1 +/- 0.9 log-transformed phospholipid units, p less than 0.04), and, when studied less than or equal to 2 days after the stroke, increased fibrinogen levels (459 +/- 126 versus 360 +/- 94 mg/dl, p less than 0.05). In conclusion, infection-associated cerebral infarction is common and is associated with substantial immunohematologic abnormalities.     

急性脑梗死后出血转化的危险因素分析

目的 探讨急性脑梗死后出血转化的相关危险因素。方法 选取2016年12月-2017年12月入住本院的140例急性脑梗死患者,其中急性脑梗死后出现出血转化者70例,其余为无出血转化者70例,分析2组患者在入院时首次空腹血糖、总胆固醇、同型半胱氨酸、尿酸水平、高血压病病史、糖尿病病史、房颤病史、饮酒史及既往脑卒中病史的差异,先进行单因素分析,对差异有统计学意义的指标进一步行多因素Logistic回归分析。结果 急性脑梗死后出血转化组患者在入院时首次空腹血糖水平、心房颤动病史、高血压病史的例数均高于非出血转化组(P<0.05),而非出血转化组中总胆固醇水平高于出血转化组(P<0.05),2组同型半胱氨酸、尿酸水平、糖尿病病史、饮酒史、既往脑卒中病史无统计学差异(P>0.05)。结论 急性脑梗死患者入院时高空腹血糖水平(>6.1 mmol/l)、房颤病史、高血压病史是急性脑梗死发生出血转化的独立危险因素,而总胆固醇(TC)是防止出血转化的一个保护因素。     

BDNF -270 C>T polymorphisms might be associated with stroke type and BDNF -196 G>A corresponds to early neurological deficit in hemorrhagic stroke

Genetic factors might be involved in stroke prognosis, however the role of brain-derived neurotrophic factor (BDNF) in stroke recovery is unknown. We have studied BDNF -196 G>A and -270 C>T polymorphisms in ischemic and hemorrhagic stroke and their impact on stroke prognosis. There was higher occurrence of BDNF -270 CC genotype in patients with hemorrhagic than ischemic stroke (96% versus 86%, p=0.0495). In hemorrhagic stroke BDNF -196 GG carriers scored better in NIHSS at admission (14.23 versus 21.00, p=0.0192) and after 7days (8.60 versus 15.00, p=0.0408) of onsets. None of the determined polymorphisms had any impact on 30-day early outcome in ischemic and hemorrhagic stroke.     

Brain hypothermia treatment for the management of severe pediatric brain injury

In the management of severe pediatric brain injury, attention has previously been paid to brain edema, ICP elevation and low cerebral perfusion pressure (CPP). However, in the acute stage within 3-6 hours after trauma, brain hypoxia and hyperglycemia associated with diffuse brain injury are often observed. We have pointed out brain thermo-pooling (elevation of brain tissue temperature) and brain hypoxia caused by defective release of oxygen from hemoglobin (due to decrease in red blood cell enzyme (DPG)) as a new mechanism of brain injury. To treat these pathologic changes, we have developed a brain hypothermia treatment, the major purpose of which is to prevent brain hypoxia, brain thermo-pooling, neurohormonal changes causing cytokine encephalopathy, and a selective, radical-mediated damage of the dopamine A10 nervous system. The brain tissue temperature is initially adjusted to 35 degrees C with adequate cerebral oxygenation, followed by brain hypothermia at 34 degrees C for 1 weeks to prevent brain hypoxia, free radical reactions, brain edema and ICP elevation. What is most difficult in the pediatric brain hypothermia treatment is to maintain metabolic balance in the injured brain tissue and pulmonary infections associated with an immune crisis. When a rapid elevation of serum glucose is noted it is critical to lower the value because glucose quickly penetrates the blood-brain barrier and increases pyruvate and lactate by inhibiting the TCA cycle metabolism. Thus, hyperglycemia during brain hypothermia treatment is one of the major target of management. Another problem is immune crisis associated with secondary pulmonary infections. To prevent them, early enteral nutrition and replacement of L-arginine were most useful, as well as preconditioning for rewarming as follows: serum albumin > 3.0 g/dl; lymphocyte > 1500/mm3; T-H (CD4) lymphocytes > 55%; serum glucose, 120-140 mg/dl; vitamin A > 50 mg/dl; Hb > 12 g/dl and 2,3 DPG, 10-15 mumol/gHb; O2 ER, 23-25% and AT-III, > 100%. The clinical benefit of this therapy is still controversial.     

Vascular protection in brain ischemia

Vascular damage occurring after cerebral ischemia may lead to a worse outcome in patients with ischemic stroke, as it facilitates edema formation and hemorrhagic transformation. There are several phases in the development of vascular injury (acute, subacute and chronic) and different mediators act in each one. Therapeutic options to avoid vascular injury must be focused on acting in each phase. However, even though experimental studies have demonstrated the benefit of therapeutic interventions both in the acute and chronic phases of cerebral ischemia, only the chronic phase offers a therapeutic window sufficiently wide enough to provide vascular protection in clinical practice. Several drugs including erythropoietin and HMG-CoA reductase inhibitors (statins), antihypertensive (angiotensin modulators), antibiotics (minocycline) and antihyperglycemic drugs (thiazolidinediones) have been proved to provide vascular protection in patients with ischemic stroke. Anti-inflammatory, antioxidant, and antiapoptotic actions are responsible for the vascular protective effect related to these drugs.     

Systemic White Blood Cell Count as a Biomarker for Malignant Cerebral Edema in Large Vessel Ischemic MCA Stroke

ObjectivesLarge middle cerebral artery (MCA) strokes remain a major cause for mortality and morbidity all over the world, and therefore early identification of patients with the highest risk for malignant cerebral edema is crucial for early intervention. Neutrophils to lymphocytes ratio (NLR) and peripheral total white blood cell (WBC) count are inflammatory markers done routinely for all patients, and this study evaluated the use of NLR and elevated white blood cell count within the first 24 h of MCA ischemic stroke onset, with the absence of significant hemorrhagic transformation, to predict malignant cerebral edema.Materials and methodsA total of 156 patients with large MCA strokes were included. We collected demographic, clinical, radiological data, and NLR and WBCs within the first 24 h from admission.We excluded patients who had any underlying infections diagnosed 7 days before or within 72 h after admission. We used a body temp of 38 C or more, abnormal CXR or abnormal urine analysis within the first 72 h to exclude patients with possible infections.We excluded immune-compromised patients and patients on steroid therapy. We compared the NLR and WBC count in patients who developed malignant cerebral edema versus the patients who did not. NLR > 3.5 and < 3.5 was used for comparison. We then conducted multivariate logistic regression models to explore the relationship between cerebral edema, WBCs and NLR count simultaneously.ResultsNLR, WBC, radiological involvement of more than 50% of MCA territory infarction on presentation, hyperdense MCA sign, and NIH stroke scale were all significantly higher in patients with malignant cerebral edema within the first 24 h. Using univariate logistic regression, NLR performs better than WBC when predicting the occurrence of malignant cerebral edema (AUC = 0.74 vs. 0.62). However, NIH stroke scale scores, and radiological involvement of more than 50% of MCA territory infarction on the first 24 h of presentation on CT scan both showed better discriminative performance for malignant cerebral edema than NLR (AUC = 0.84 and 0.76, respectively). When combined, NLR > 3.5 paired with the NIH stroke scale score had the best predictive performance (AUC = 0.87).ConclusionNLR > 3.5 can be used for early prognostication in patients with large vessel MCA ischemic strokes with no significant hemorrhagic transformation within the first 24 h regardless if they had reperfusion therapy or not. Combining NLR of > 3.5 in addition to high NIHSS provided the best predictive model in our study. Further studies are needed to further develop the best predictive model in diverse populations.     

Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model

Increasing evidence indicates that physical activity reduces brain damage after stroke. The purpose of this study was to determine whether exercise-induced neuroprotection is associated with improved brain integrity in stroke.Adult male Sprague-Dawley rats (3 months old, n=38) exercised on a treadmill, which required repetitive locomotor movement, for 30 minutes each day for 3 weeks. Then, using an intraluminal filament, stroke was induced by either 2 hours middle cerebral artery (MCA) occlusion followed by 24 or 48 hours of reperfusion. Brain damage was determined by evaluating brain infarction and brain edema, as well as ultrastructural alteration in endothelial-matrix-astrocyte interfaces.Pre-ischemic motor exercise significantly (p<0.01) reduced infarct volume in the frontoparietal cortex and the dorsolateral striatum by 79%. By comparing the percentage difference in brain volume between the right (stroke site) and left hemispheres, we demonstrated a significant (p<0.01) reduction in brain edema associated with reduced infarct volume in a 3 week exercise group (Group 1, n=10) and a 3 week exercise plus 3 week rest group (Group 2, n=10). Edema in cortex and striatum was 19 +/- 4% without exercise pre-conditioning (n=10), in contrast to 5 +/- 3% (Group 1) or 6 +/- 4% (Group 2). The thickness of the basal lamina was enhanced by exercise. In ischemic rats without pre-exercise, alterations in microvessel ultrastructure with decreased luminal area, parenchymal edema and swollen astrocyte end-feet, as well as an abnormally thin basal lamina were observed. In contrast, exercise pre-conditioning significantly reduced the ischemic alterations, decreasing brain edema and increasing basal lamina thickness.This study suggests that exercise pre-conditioning reduces brain injury by decreasing cerebral permeability and enhancing brain integrity after stroke. This exercise-induced endogenous neuroprotection could be an effective strategy to ameliorate ischemic brain injury from stroke.     

高血糖对急性缺血性卒中早期预后影响的初步研究

目的 探讨高血糖对急性缺血性卒中早期预后的影响。方法 采用前瞻性研究设计,连续纳入发病72h内入院的急性缺血性卒中患者143例。急诊入院时检测入院随机静脉血清血糖,高血糖定义为入院随机静脉血清血糖≥7.2mmol/L。入院时评定美国国立卫生研究院卒中量表（NIH Stroke Scale,NIHSS）评分,根据病史及辅助检查确定缺血性卒中类型（TOAST分型）。发病30d时进行改良Rankin’s评分（mRS）,作为评估早期预后的指标。结果 （1）本研究入选的143例急性缺血性卒中患者中,85例（59.4%）出现高血糖,单因素分析显示,年龄、糖尿病史、NIHSS评分是急性缺血性卒中合并高血糖的危险因素（P＜0.05）,logistic回归分析显示,糖尿病史、NIHSS评分是急性缺血性卒中合并高血糖的独立危险因素（P＜0.05）。（2）单因素分析显示,年龄、感染、高血糖、NIHSS评分和TOAST分型对mRS评分的影响有统计学差异（P＜0.05）,logistic回归分析显示,高血糖、NIHSS评分是预后不良的独立危险因素（P＜0.05）。结论 高血糖在急性缺血性卒中患者中的发生率较高,其出现与卒中的严重程度密切相关,可以作为反映急性缺血性卒中发病时病情较重的指标之一,高血糖是急性缺血性卒中早期预后不良的独立危险因素。     

Quantification of brain edema and hemorrhage by MRI after experimental traumatic brain injury in rabbits predicts subsequent functional outcome

We use multiple MRI modalities to measure cerebral edema and intracerebral hemorrhage quantitatively after TBI in rabbits and to acquire the early prognostic MRI information. Multiple MRI modalities (DCE-MRI, DWI and SWI) were used to assess cerebral edema and intracerebral hemorrhage quantitatively at different time points within a month after TBI in 15 rabbits. The functional outcomes were evaluated at 1 and 30 days after TBI. The relationships between the quantitative MRI information at different time points and functional outcome at 30 days were analyzed. The volume transfer coefficient (K (trans)) in the focal lesion area and the perifocal lesion area at the acute phase correlated with the functional outcome at 30 days (p < 0.05). The apparent diffusion coefficient (ADC) value at 7 days in the focal lesion area correlated with the functional outcome at 30 days (p < 0.01) and had a trend to correlate at 3 days (p = 0.08). In the perifocal lesion area, the ADC values at both acute and subacute phase correlated with the functional outcome at 30 days (p < 0.05). The volume of hemorrhage correlated with functional outcome at 30 days (p < 0.05). The cerebral edema assessed by DCE-MRI (K (trans)) and DWI (ADC) and intracerebral hemorrhage assessed by SWI may have predictive values.