Wendan Tao

Characteristics, Treatment and Outcome of Ischemic Stroke with Atrial Fibrillation in a Chinese Hospital-Based Stroke Study

Background: There is scant information on characteristics, treatment, functional outcome and case fatality of ischemic stroke with atrial fibrillation (AF) in China. Methods: For this study, first-ever ischemic stroke patients who were admitted within 1 month of stroke onset during the period of March 2002 through December 2008 were included. Data on ischemic stroke patients were collected which included: demographics, risk factors, treatment administered, stroke-related complications and 3-month, 6-month and 1-year death and disability. Multivariate regression models were used to analyze predictors for death and disability. Results: Of the 2,683 patients included in this study, 366 (13.6%) had AF. In this group, valvular AF was observed in 153 (41.8%) patients. Compared to patients without AF, patients with AF were older (66.1 vs. 63.6, p = 0.001) and had a higher NIHSS score on admission (median 10 vs. 4, p < 0.001) and more frequently suffered from hemorrhagic transformation (7.3 vs. 2.8%, p < 0.001), pulmonary infection (27 vs. 10.6%, p < 0.001), urinary tract infection (8.5 vs. 3.0%, p < 0.001), acute gastrointestinal tract hemorrhage (4.1 vs. 1.9%, p = 0.008), electrolyte disturbance (5.2 vs. 1.8%, p < 0.001), acute renal failure (1.1 vs. 0.5%, p = 0.005) and urinary incontinence (3.8 vs. 0.6%, p < 0.001) during hospitalization. The percentages of patients with AF who received oral anticoagulants were 3.3% before stroke onset and 14.2% at discharge. Moreover, patients with AF had a higher proportion of disability (determined as modified Rankin Scale score 3–5) in 3-month, 6-month and 1-year follow-ups (46.6, 41.9 and 37.6 vs. 29.1, 24.0 and 19.3%, respectively, p < 0.001) and higher case fatality in hospitalization, 3-month, 6-month and 1-year follow-ups (10.1, 25.5, 29.1 and 34.0 vs. 2.0, 7.4, 8.8 and 11.6%, respectively, p < 0.001). Multivariate logistic regression determined that AF, age and NIHSS score were the independent predictors for the 3-month, 6-month and 1-year death. Conclusions: Ischemic stroke patients with AF have a poorer outcome, a higher frequency of stroke-related complications and a higher case fatality than patients without AF. Oral anticoagulants were underused in AF patients.

Predictors of one-year disability and death in Chinese hospitalized women after ischemic stroke.

Background and Purpose: Women have a worse functional outcome after stroke, but the specific factors associated with a poor outcome in women are rarely reported. This study was designed to investigate the clinical predictors of 1-year disability and death in women after ischemic stroke. Methods: Patients with ischemic stroke consecutively registered from March 2002 to July 2007 were followed prospectively for 1 year. Multivariate regression models were employed to analyze predictors of disability (defined as modified Rankin scale score, mRS, 3–5 ) and death. Results: A total of 2,774 ischemic stroke patients were included with 1,119 (40.3%) females (mean age 65 ± 13.5 years). Among female patients, disability (mRS 3–5) is 1.68-fold higher and case fatality is 1.23-fold higher than in men at the 1-year follow-up. Diabetes is an independent predictor of 1-year disability among women (odds ratio, 1.56; 95% confidence interval, CI, 1.01–2.39). In-hospital acute renal failure (hazard ratio, HR, 7.26; 95% CI, 3.47–5.19), suboptimal antiplatelets (HR, 0.55; 95% CI, 0.37–0.83) and antihypertensive therapy (HR, 0.61; 95% CI, 0.42–0.90) are associated with death at 1 year after stroke among women. Conclusions: The present study indicates that diabetes, in-hospital acute renal failure, suboptimal antiplatelets and antihypertensive therapy are the possible explanations for the poor 1-year outcome of women hospitalized with ischemic stroke.

Association between cerebral microbleeds and cognitive function: a systematic review

Background Cerebral microbleeds (MBs), defined as haemorrhagic microvascular lesions or microangiopathy in the brain, have traditionally been considered clinically silent. Recent studies, however, suggest that MBs are associated with a decline in cognitive function. Objective To determine whether an association between MBs and cognitive function exists, we conducted a systematic review of the literature using the Cochrane Library, MEDLINE, EMBASE and the China National Knowledge Infrastructure database. We also searched the reference lists of relevant studies and review articles. Results A total of seven studies were included. Qualitative meta-analysis of two studies suggested that the presence of MBs was significantly associated with cognitive impairment, while quantitative meta-analysis revealed an association between MBs and cognitive dysfunction in two studies (OR 3.06, 95% CI1.59 to 5.89) and implicated MBs as important in cognitive function decline in three other studies (standardised mean difference −1.06, 95% CI −2.10 to −0.02). MBs in the frontal or temporal region and the basal ganglia might also be related to cognitive dysfunction. Conclusions These results suggest that rather than being clinically silent, cerebral MBs might be a factor inducing cognitive function decline.

Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke.

ABSTRACT Background and Purpose: FTY720 (fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist, which has been used in clinical trials for treating multiple sclerosis, renal transplantation, and decreasing reperfusion injury in heart, liver, and kidney. Most of these clinical trials have showed a positive effect. Especially, the trials of MS showed a reduction of relapse rate in FTY720-treated patients. Now, some animal experiments indicated that FTY720 could be a new compound available treatment for stroke patients by exerting neuroprotection via S1P1 mediated antiapoptotic mechanisms. Whether it could be effective in animals is unclear, so we conducted a systematic review to make it clear. Methods: We conducted a systematic review and meta-analysis of the efficacy of FTY720 in animal models of focal cerebral ischemia by electronic and manual searches of the literature. Data on study quality, FTY720 dose, time of administration, and outcome measured as infarct volume or functional deficit were extracted. Data from all studies were analyzed by means of a standardized mean difference meta-analysis. Results: Of the 19 identified studies, 9 were included. Among all the included studies, 178 animals were calculated for infarct size and 194 animals were assessed of neurological deficits. The methodological quality of the studies ranged from 2 to 10 according to a published 11-item quality scale. Of the nine studies selected, only one reported a negative result of FTY720. The result indicated that FTY720 reduced the infarct volume (SMD = −1.31, 95% CI −1.99 to −0.63) and improve the functional outcome (SMD = −1.61,95% CI −2.17 to −1.05). Conclusions: The data we included supporting FTY720 was a candidate drug for stroke, but it should be considered with caution. More good quality experimental studies should be performed to evaluate the safety of FTY720 in the future. Whether FTY720 is effective in aged animals that mimicked human with comorbidities like diabetes and hypertension should also be deliberated.

Association between Renal Function and Clinical Outcome in Patients with Acute Stroke

Background and Purpose: Data on the association between renal dysfunction and outcome in patients with stroke are controversial and scarce. We investigated the predictors of renal dysfunction upon admission and the association between renal dysfunction and clinical outcome in patients with acute stroke in a hospitalized Chinese population. Methods: 1,758 acute stroke patients were consecutively enrolled into the study. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease equation. Reduced estimate of the glomerular filtration rate was defined as eGFR <60 ml/min/1.73 m2. Multivariate logistical regression was used to evaluate the predictors of renal dysfunction upon admission and to examine the association between renal dysfunction and outcomes. The main outcome measures were death and death/disability (disability defined as modified Rankin Scale score >2) at 12 months after stroke. Results: Of the included 1,758 cases (ischemic stroke: n = 1,192; hemorrhagic stroke: n = 566), 463 cases had reduced eGFR, which accounted for 26.3% of the total number. The distribution of eGFR upon admission was normal and the mean was 75.87 ± 38.31 ml/min/1.73 m2 (ischemic stroke: 75.07 ± 29.89 ml/min/1.73 m2; hemorrhagic stroke: 77.57 ± 51.73 ml/min/1.73 m2). There was no significant difference between the two groups (p = 0.285). The independent predictors of eGFR upon admission were age (OR = 1.039, 95% CI = 1.028–1.050), male gender (OR = 0.658, 95% CI = 0.504–0.859), hematocrit on admission (OR = 1.008, 95% CI = 1.003–1.013), history of hypertension (OR = 1.307, 95% CI = 1.034–1.653), history of diabetes (OR = 1.411, 95% CI = 1.012–1.967) and NIHSS scores upon admission (OR = 1.497, 95% CI = 1.286–1.743). After adjustment for confounders, the patients with renal dysfunction had a significantly higher risk of death/disability (OR = 1.864, 95% CI = 1.170–2.970) compared with patients whose eGFR was more than 90 ml/min/1.73 m2 at the end of the 12th month. Further analysis on type of stroke showed that reduced eGFR was an independent predictor of death/disability at the end of the 12th month in patients with hemorrhagic stroke (OR = 2.353, 95% CI = 1.063–5.209), but not for ischemic stroke (OR = 1.625, 95% CI = 0.881–2.999). Conclusions: Our study indicated that more than 1/4 of all patients with acute stroke presented with renal dysfunction. Reduced eGFR on admission is a strong predictor of poor outcome for hemorrhagic stroke but not for ischemic stroke.

Posterior Versus Anterior Circulation Infarction How Different Are the Neurological Deficits

Background and Purpose— Distinguishing between symptoms of posterior circulation infarction (PCI) and anterior circulation infarction (ACI) can be challenging. This study evaluated the frequency of symptoms/signs in the 2 vascular territories to determine the diagnostic value of particular symptoms/signs for PCI. Methods— Neurological deficits were reviewed and compared from 1174 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. The diagnostic value of specific symptoms/signs for PCI was determined by measuring their sensitivity, specificity, positive predictive value (PPV), and the OR. Results— Homolateral hemiplegia (PCI, 53.6% versus ACI, 74.9%; P<0.001), central facial/lingual palsy (PCI, 40.7% versus ACI, 62.2%; P<0.001), and hemisensory deficits (PCI, 36.4% versus ACI, 34.2%; P=0.479) were the 3 most common symptoms/signs in PCI and ACI. The signs with the highest predictive values favoring a diagnosis of PCI were Horners syndrome (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), crossed sensory deficits (3.0% versus 0%; P<0.001; PPV=100.0%; OR=3.98), quadrantanopia (1.3% versus 0%; P<0.001; PPV=100.0%; OR=3.93), oculomotor nerve palsy (4.0% versus 0%; P<0.001; PPV=100.0%; OR=4.00), and crossed motor deficits (4.0% versus 0.1%; P<0.001; PPV=92.3%; OR=36.04); however, all had a very low sensitivity, ranging from 1.3% to 4.0%. Conclusions— This study indicates that the symptoms/signs considered typical of PCI occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate PCI from ACI. Neuroimaging is vital to ensure accurate localization of cerebral infarction.

A cohort study of patients with anemia on admission and fatality after acute ischemic stroke

Reduced blood hemoglobin levels may impair oxygen delivery to the brain and hinder neurological improvement. We prospectively registered consecutively hospitalized Chinese patients with acute ischemic stroke within 24 hours of symptom onset to investigate whether anemia on admission influences case fatality and functional outcome of acute ischemic stroke at 12 months. Anemia was defined as a blood hemoglobin level of < 120 g/L for women, and < 130 g/L for men. We also performed a meta-analysis of the current cohort and previously published studies. We included 1176 patients, of whom 351 patients (29.8%) had anemia. Age (odds ratio [OR]=1.02, 95% confidence interval [CI]: 1.01-1.03), history of hemorrhagic stroke (OR=3.34, 95% CI: 1.17-9.56), alcohol consumption (OR=0.59, 95% CI: 0.38-0.92), and estimated glomerular filtration rate < 60 mL/minute per 1.73 m(2) (OR=1.34, 95% CI: 1.00-1.80) were the independent predictors of anemia. After adjustment for potential confounders, anemia on admission was shown to be an independent predictor of death at discharge and at 12 months (OR=1.66, 95% CI, 1.08-2.56; OR=1.56, 95% CI, 1.05-2.31). A meta-analysis of six included studies involving 3810 participants confirmed that anemia on admission was an independent predictor of death at the end of follow-up (OR=1.67, 95% CI, 1.25-2.08). Further studies are required to confirm these findings.

High-mobility group box1 protein promotes neuroinflammation after intracerebral hemorrhage in rats.

High-mobility group box1 (HMGB1) protein is massively released into the cytoplasm and induces inflammation following various insults such as sepsis, acute cerebral ischemia, and pancreatitis. However, whether HMGB1 can act as an early proinflammatory cytokine to promote inflammation after intracerebral hemorrhage (ICH) is unclear. We explored this question using a rat model of collagenase-induced ICH. We found that HMGB1 was released into the cytoplasm soon after ICH. Administration of ethyl pyruvate decreased the level of HMGB1 and microglia around the hematoma. Ethyl pyruvate also ameliorated ICH-induced neuronal apoptosis, cerebral edema, and neurological impairment. These findings suggest that HMGB1 may act as an early proinflammatory cytokine within the neurovascular unit to mediate inflammation during the acute phase of ICH.

Acute ischemic stroke in the very elderly Chinese: Risk factors, hospital management and one-year outcome

BACKGROUND Little information is available on Asian patients over 80 years with stroke. We aimed to investigate characteristics of the very elderly ischemic stroke hospitalized patients in China. METHODS We prospectively enrolled consecutive patients with acute ischemic stroke from March, 2002 to October, 2008 into the analysis. Patients were divided into two groups: <80 years versus ≥80 years and risk factors, hospital management and one-year outcome were compared. RESULTS Of the 2619 cases included, 302 (11.5%) patients were 80 years or older. Compared with patients <80 years, patients over 80 years old had higher rates of hypertension (66.2% versus 56.1%, p=0.001), atrial fibrillation (23.5% versus 14.5%, p=0.000), and coronary heart disease (13.6% versus 5.7%, p=0.000). In addition, they were less likely to have received transthoracic echocardiography (45.4% versus 55.4%, p=0.001), color Doppler of extracranial vessels (54.0% versus 61.2%, p=0.015), antiplatelet agents (80.8% versus 86.8%, p=0.004), or anticoagulants (4.0% versus 9.0%, p=0.003). After adjusting for sex and stroke severity on admission, the very elderly patients had higher case-fatality and disability rates at one year (33.8% versus 13.2%, p=0.000; 37.8% versus 20.9%, p=0.000; respectively). CONCLUSIONS In China, the proportion of the very elderly in hospitalized stroke population is lower than that in western countries whereas the most common risk factors seem similar. The hospital management for these patients is relatively insufficient and the long-term outcome is generally unfavorable compared with patients under 80 years old.

Effects of high-mobility group box1 on cerebral angiogenesis and neurogenesis after intracerebral hemorrhage.

Neural stem cells, which reside mainly in the subventricular and subgranular zones of the hippocampus, can regenerate new neuroblasts after various brain insults. Aided by vascular remodeling, these new neuroblasts migrate long distances to injured brain regions. Studies have suggested that high-mobility group box1 (HMGB1), a nonhistone nuclear DNA-binding protein, may stimulate such remodeling in the late phase of some types of brain injury, but it is unclear whether this is true for intracerebral hemorrhage (ICH). Here we used a rat model of collagenase-induced ICH to determine whether HMGB1 can promote neurogenesis and angiogenesis in the late phase of injury. Daily administration of ethyl pyruvate, which inhibited HMGB1 expression, reduced the recovery of neurological function, decreased vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) levels in the ipsilateral striatum, and decreased the numbers of 5-bromo-2-deoxyuridine (BrdU)- and doublecortin (DCX)-positive cells around the hematoma. These findings suggest that HMGB1 may promote angiogenesis and neurogenesis in the late phase of ICH.