Genetic Variation at the BDNF Locus: Evidence for Association with Long-Term Outcome after Ischemic Stroke

Background and Purpose

Rates and extent of recovery after stroke vary considerably between individuals and genetic factors are thought to contribute to post-stroke outcome. Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair and has been shown to be involved in stroke severity, recovery, and outcome in animal models. Few clinical studies on BDNF genotypes in relation to ischemic stroke have been performed. The aims of the present study are therefore to investigate whether genetic variation at the BDNF locus is associated with initial stroke severity, recovery and/or short-term and long-term functional outcome after ischemic stroke.

Methods

Four BDNF tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS; 600 patients and 600 controls, all aged 18–70 years). Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke recovery was defined as the change in NIHSS over a 3-month period. Short- and long-term functional outcome post-stroke was assessed using the modified Rankin Scale at 3 months and at 2 and 7 years after stroke, respectively.

Results

No SNP was associated with stroke severity or recovery at 3 months and no SNP had an impact on short-term outcome. However, rs11030119 was independently associated with poor functional outcome 7-years after stroke (OR 0.66, 95% CI 0.46–0.92; P =  0.006).

Conclusions

BDNF gene variants were not major contributors to ischemic stroke severity, recovery, or short-term functional outcome. However, this study suggests that variants in the BDNF gene may contribute to poor long-term functional outcome after ischemic stroke.     

Early Vascular Aging in Young and Middle-Aged Ischemic Stroke Patients: The Norwegian Stroke in the Young Study

Background

Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients.

Methods

We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram.

Results

Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p<0.01) in multivariate linear regression analysis (multiple R² = 0.42, p<0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p<0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02–1.06; p<0.01), history of hypertension (OR 3.59; 95% CI 1.52–8.51; p<0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00–9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01–1.06; p<0.01) were associated with high for age PWV.

Conclusions

Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01597453","term_id":"NCT01597453"}}NCT01597453     

Dietary Habits in Patients with Ischemic Stroke: A Case-Control Study

Background and Aims

Diet appears to have some role in stroke development. The objective of our study was to describe the dietary habits in patients admitted with acute ischemic stroke and compare selected dietary components with healthy controls. Adherence to healthy diet behaviors was also assessed.

Methods

A case-control study of consecutive patients with acute ischemic stroke admitted to the Neurology Department of Hospital del Mar from 2007 to 2010. Patients were matched by age and sex with control subjects. A previously validated nutritional survey was administered to patients and controls. Demographic data, vascular risk factors, caloric intake and dietary nutrients were evaluated. Intention to follow a healthy diet was also assessed in both groups.

Results

A total of 300 acute ischemic stroke patients and 300 controls with evaluation of dietary habits. No differences were observed in vascular risk factors, except smoking habit, diabetes and ischemic heart disease. Stroke patients reported a higher caloric intake: 2444.8(1736.8–3244.5) vs 2208.7(1753.1–2860.7) Kcal, p = 0.001. After adjusting for energy intake, patients had higher intake of proteins (p<0.001; OR 1.02), total cholesterol (p = 0.001; OR 1.04), and breaded foods (p = 0.001; OR 1.94) and lower consumption of probiotic yogurt (p = 0.002; OR 0.88). Compared to patients, control participants indicated greater intention to eat vegetables (p = 0.002; OR 1.5) and whole foods (p = 0.000; OR 2.4) and reduce their intake of salt (p = 0.002; OR 1.7), fat (p = 0.000; OR 3.7) and sweets (p = 0.004; OR 1.7) than patients.

Conclusion

We observed different dietary patterns between stroke patients and controls. Stroke patients have a higher caloric intake and are less concerned about maintaining healthy nutritional habits.     

Plasma Midregional Pro-Adrenomedullin Improves Prediction of Functional Outcome in Ischemic Stroke

Background

To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke.

Methods

In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied.

Results

Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3–6) compared to favourable (mRS 0–2) outcomes. MR-proADM levels were entered into a predictive model including the patients'' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p<0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI = 0.175; p = 0.04). Kaplan-Meier survival analysis showed a rising risk of death with increasing MR-proADM quintiles.

Conclusions

Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients'' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients'' functional outcome.     

Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients

Background

The Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment.

Methodology/Principal Findings

In a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (<100 ng/ml) were subject to a considerably decreased risk of an unfavorable outcome three months after ischemic stroke (adjusted odds ratio 0.38, p<0.05) and showed smaller lesion volumes (mean size 0.6 vs. 18.4 ml, p = 0.0025). In contrast, no association of MBL concentration with infarction volume or functional outcome was found in the thrombolysis group. However, the small sample size limits the significance of this observation.

Conclusions

MBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.     

The Predictive Value of the Boston Acute Stroke Imaging Scale (BASIS) in Acute Ischemic Stroke Patients among Chinese Population

Objective

Evaluate the predictive value of Boston Acute Stroke Imaging Scale (BASIS) in acute ischemic stroke in Chinese population.

Methods

This was a retrospective study. 566 patients of acute ischemic stroke were classified as having a major stroke or minor stroke based on BASIS. We compared short-term outcome (death, occurrence of complications, admission to intensive care unit [ICU] or neurological intensive care unit [NICU]), long-term outcome (death, recurrence of stroke, myocardial infarction, modified Rankin scale) and economic index including in-hospital cost and length of hospitalization. Continuous variables were compared by using the Student t test or Kruskal-Wallis test. Categorical variables were tested with the Chisquare test. Cox regression analysis was applied to identify whether BASIS was the independent predictive variable of death.

Results

During hospitalization, 9 patients (4.6%) died in major stroke group while no patients died in minor stroke group (p<0.001), 12 patients in the major stroke group and 5 patients in minor stroke group were admitted to ICU/NICU (p = 0.001). There were more complications (cerebral hernia, pneumonia, urinary tract infection) in major stroke group than minor stroke group (p<0.05). Meanwhile, the average cost of hospitalization in major stroke group was 3,100 US$ and 1,740 US$ in minor stroke group (p<0.001); the average length of stay in major and minor stroke group was 21.3 days and 17.3 days respectively (p<0.001). Results of the follow-up showed that 52 patients (26.7%) died in major stroke group while 56 patients (15.1%) died in minor stroke group (P<0.001). 62.2% of the patients in major stroke group and 80.4% of the patients in minor stroke group were able to live independently (P = 0.002). The survival analysis showed that patients with major stroke had 80% higher of risk of death than patients with minor stroke even after adjusting traditional atherosclerotic factors and NIHSS at baseline (HR = 1.8, 95% CI: 1.1–3.1).

Conclusion

BASIS can predict in-hospital mortality, occurrence of complication, length of stay and hospitalization cost of the acute ischemic stroke patients and can also estimate the long term outcome (death and the dependency). BASIS could and should be used as a dichotomous stroke classification system in the daily practice.     

The Genetics of Primary Haemorrhagic Stroke,Subarachnoid Haemorrhage and Ruptured Intracranial Aneurysms in Adults

Background

The genetic basis of haemorrhagic stroke has proved difficult to unravel, partly hampered by the small numbers of subjects in any single study. A meta-analysis of all candidate gene association studies of haemorrhagic stroke (including ruptured subarachnoid haemorrhage and amyloid angiopathy-related haemorrhage) was performed, allowing more reliable estimates of risk.

Methods

A systematic review and meta-analysis of all genetic studies in haemorrhagic stroke was conducted. Electronic databases were searched until and including March 2007 for any candidate gene in haemorrhagic stroke. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models.

Results

Our meta-analyses included 6,359 cases and 13,805 controls derived from 55 case-control studies, which included 12 genes (13 polymorphisms). Statistically significant associations with haemorrhagic stroke were identified for those homozygous for the ACE/I allele (OR, 1.48; 95% CI, 1.20–1.83; p = 0.0003) and for the 5G allele in the SERPINE1 4G/5G polymorphism (OR, 1.42; 95% CI, 1.03–1.96; p = 0.03). In addition, both &b.epsi;2 and &b.epsi;4 alleles of APOE were significantly associated with lobar haemorrhage (OR, 1.81; 95% CI, 1.26–2.62; p = 0.002 and OR, 1.49; 95% 1.08–2.05; p = 0.01 respectively). Furthermore, a significant protective association against haemorrhagic stroke was found for the factor V Leiden mutation (OR, 0.30; 95% CI, 0.10–0.87; p = 0.03).

Conclusion

Our data suggests a genetic contribution to some types of haemorrhagic stroke, with no overall responsible single gene but rather supporting a polygenic aetiology . However, the evidence base is smaller compared to ischaemic stroke. Importantly, for several alleles previously found to be associated with protection from ischaemic stroke, there was a trend towards an increased risk of haemorrhagic stroke.     

Association between Statin Use and Short-Term Outcome Based on Severity of Ischemic Stroke: A Cohort Study

Background

Statins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity.

Methods

A total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0–5) at 3 months after onset using multivariable logistic regression models.

Results

A total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38–0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81–1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31–0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57–0.92) at 3 months in the non-minor stroke group.

Conclusions

Statin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.     

The Outcome of Patients with Mild Stroke Improves after Treatment with Systemic Thrombolysis

Introduction

In up to one third of patients with mild stroke suitable to receive systemic thrombolysis the treatment is not administered because the treating physicians estimate a good spontaneous recovery. However, it is not settled whether the fate of these patients is equivalent to those who are thrombolysed.

Methods

We analyzed 203 consecutive patients (134 men and 69 women, mean age 69±14 years) without premorbid disability and a NIHSS score ≤5 at admission [median 3 (IQR 2–4)]. Intravenous thrombolysis was administered within 4.5 hours from stroke onset (n = 119), or it was withheld (n = 84) whenever the treating physician predicted a spontaneous recovery. The baseline risk factors, clinical course, infarction volume, bleeding complications, and functional outcome at 3 months were analyzed and declared to a Web-based registry which was accessible to the local Health Authorities.

Results

Expectedly, not thrombolysed patients had the mildest strokes at admission [median 2 (IQR 1–3.75)]. At day 2 to 5, the infarct volume on DWI-MRI was similar in both groups. There were no symptomatic cerebral bleedings in the study. An ordinal regression model adjusted for baseline stroke severity showed that thrombolysis was associated with a greater proportion of patients who shifted down on the modified Rankin Scale score at 3 months (OR 2.66; 95% CI 1.49–4.74, p = 0.001).

Conclusions

Intravenous thrombolysis seems to be safe in patients with mild stroke and may be associated with improved outcome compared with untreated patients. These results support the evaluation of the efficacy of intravenous thrombolysis in mild stroke patients in randomized clinical trials.     

Efficacy of Single and Multiple Injections of Human Umbilical Tissue-Derived Cells following Experimental Stroke in Rats

Introduction

Human umbilical tissue-derived cells (hUTC) are a promising source of cells for regenerative treatment of stroke. In this study, we tested the efficacy of hUTC in experimental stroke and whether multiple injections of hUTC provide additional therapeutic benefits as compared to a single injection.

Methods

Adult male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo), and randomly selected animals were injected (i.v) with 3×10⁶ hUTC or with vehicle control (at day: 1, 1&3 or 1&7 after MCAo, n = 8–9/group). A battery of functional outcome tests was performed at days 1, 7, 14, 21, 28, 35, 42, 49, 56 and 63 after MCAo. Rats were sacrificed at 63 days after MCAo and lesion volumes were measured. To investigate the underlying mechanism of hUTC treatment of stroke, Von Willebrand Factor (vWF), and Synaptophysin immunostaining were performed.

Results

All hUTC treated groups, single or multiple injections, had better functional recovery compared to control (p<0.01). There was no statistically significant difference between a single and multiple injections of hUTC (p = 0.23) or between different multiple injections groups (p>0.07) in functional outcome. All hUTC treatment groups showed significant increases in Synaptophysin, vascular density and perimeter compared to the control group (p<0.05). There was no statistically significant difference between a single and multiple injections of hUTC or between the two groups of multiple injections in all immunohistochemical measurements (p>0.1).

Conclusion

hUTC treatment significantly improves long term functional outcome after stroke and promotes vascular density and synaptic plasticity. At the proscribed doses, multiple injections of hUTC were not superior to single injection therapy in both functional outcome and histological assessments.     

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

Background

Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure.

Methods and Results

MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = −0.609, p<0.001 and r = −0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052–6.210; and HR 1.426, 95% CI 1.013–2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3.

Conclusions

This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation.     

IV t-PA Influences Infarct Volume in Minor Stroke: A Pilot Study

Background

There is an ongoing debate whether stroke patients presenting with minor or moderate symptoms benefit from thrombolysis. Up until now, stroke severity on admission is typically measured with the NIHSS, and subsequently used for treatment decision.

Hypothesis

Acute MRI lesion volume assessment can aid in therapy decision for iv-tPA in minor stroke.

Methods

We analysed 164 patients with NIHSS 0–7 from a prospective stroke MRI registry, the 1000+ study (clinicaltrials.org {"type":"clinical-trial","attrs":{"text":"NCT00715533","term_id":"NCT00715533"}}NCT00715533). Patients were examined in a 3 T MRI scanner and either received (n = 62) or did not receive thrombolysis (n = 102). DWI (diffusion weighted imaging) and PI (perfusion imaging) at admission were evaluated for diffusion - perfusion mismatch. Our primary outcome parameter was final lesion volume, defined by lesion volume on day 6 FLAIR images.

Results

The association between t-PA and FLAIR lesion volume on day 6 was significantly different for patients with smaller DWI volume compared to patients with larger DWI volume (interaction between DWI and t-PA: p = 0.021). Baseline DWI lesion volume was dichotomized at the median (0.7 ml): final lesion volume at day 6 was larger in patients with large baseline DWI volumes without t-PA treatment (median difference 3, IQR −0.4–9.3 ml). Conversely, in patients with larger baseline DWI volumes final lesion volumes were smaller after t-PA treatment (median difference 0, IQR −4.1–5 ml). However, this did not translate into a significant difference in the mRS at day 90 (p = 0.577).

Conclusion

Though this study is only hypothesis generating considering the number of cases, we believe that the size of DWI lesion volume may support therapy decision in patients with minor stroke.

Trial Registration

Clinicaltrials.org {"type":"clinical-trial","attrs":{"text":"NCT00715533","term_id":"NCT00715533"}}NCT00715533     

Cardioembolic and Small Vessel Disease Stroke Show Differences in Associations between Systemic C3 Levels and Outcome

Background

Activation of the complement system has been proposed to play a role in the pathophysiology of stroke. As the specific involvement of the complement proteins may be influenced by stroke etiology, we compared plasma C3 and C3a levels in patients with cardioembolic (CE) and small vessel disease (SVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at three months and two years.

Methodology/Principal Findings

Plasma C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and at three months after stroke, and age- and sex-matched control subjects from The Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assesed with modified Rankin Scale. In the CE group, plasma C3 levels were elevated only in the acute phase, whereas C3a was elevated at both time points. The follow-up phase plasma C3 levels in the upper third were associated with an increased risk of unfavorable outcome at three months (OR 7.12, CI 1.72–29.46, P = 0.007) as well as after two years (OR 8.25, CI 1.61–42.28, P = 0.011) after stroke. These associations withstand adjustment for age and sex. Conversely, three-month follow-up plasma C3a/C3 level ratios in the middle third were associated with favorable outcome after two years both in the univariate analysis (OR 0.19, CI 0.05–0.82, P = 0.026) and after adjustment for age and sex (OR 0.19, CI 0.04–0.88, P = 0.033). In the SVD group, plasma C3 and C3a levels were elevated at both time points but showed no significant associations with outcome.

Conclusions

Plasma C3 and C3a levels are elevated after CE and SVD stroke but show associations with outcome only in CE stroke.     

Increased Risk of Ischemic Stroke in Young Patients with Ankylosing Spondylitis: A Population-Based Longitudinal Follow-Up Study

Background

Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS.

Methods

A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates.

Results

During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20–3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16–3.20; p = 0.0110).

Conclusion

Our study showed an increased risk of developing ischemic stroke in young patients with AS.     

Reversal of Ophthalmic Artery Flow and Stroke Outcomes in Asian Patients with Acute Ischemic Stroke and Unilateral Severe Cervical Carotid Stenosis

Background

The aim of this study was to assess the clinical implications of reversed ophthalmic artery flow (ROAF) for stroke risk and outcomes in subjects with unilateral severe cervical carotid stenosis/occlusion.

Methods

We investigated 128 subjects (101 with acute stroke and 27 without), selected from a large hospital patients base (n  =  14,701), identified with unilateral high-grade cervical carotid stenosis/occlusion by using duplex ultrasonography and brain magnetic resonance imaging. All clinical characteristics were compared for stroke risk between acute stroke and nonstroke groups. Patients with acute stroke were divided into 4 subgroups according to ophthalmic artery flow direction and intracranial stenosis severity, and stroke outcomes were evaluated.

Results

The acute stroke group had significantly higher percentages of ROAF (52.5%, p  =  0.003), carotid occlusion (33.7%, p  =  0.046), and severe intracranial stenosis (74.3%, p<0.001). However, multivariate analysis demonstrated that intracranial stenosis was the only significant risk factor (odds ratio  =  10.38; 95% confidence interval  =  3.64–29.65; p<0.001). Analysis of functional outcomes among the 4 subgroups of patients with stroke showed significant trends (p  =  0.018 to 0.001) for better stroke outcomes from ROAF and mild or no intracranial stenosis. ROAF improved 10–20% stroke outcomes, as compared to forward ophthalmic artery flow, among the patients with stroke and the same degree of severities of intracranial stenosis.

Conclusions

Patients with acute stroke and severe unilateral cervical carotid stenosis/occlusion significantly have high incidence of intracranial stenosis and ROAF. Intracranial stenosis is a major stroke risk indicator as well as a predictor for worse stroke outcomes, and ROAF may provide partial compensation for improving stroke outcomes.     

Variable Lengths of Stay among Ischemic Stroke Subtypes in Chinese General Teaching Hospitals

Background

Length of stay (LOS) is one of the most important quantitative indexes that measures health service utilization within a hospital. Many studies have examined the association of three major stroke categories with LOS. Our aim is to investigate the differences of LOS among ischemic stroke subtypes, results from which are helpful to healthcare providers and government agencies to improve health care delivery efficiency.

Methodology/Principal Findings

Using the Beijing Municipal Health Bureau’s hospitalization summary reports, we performed a retrospective study among first-ever in-hospital patients with ischemic stroke (ICD-10 I63) in three general teaching hospitals in Beijing, China, from 2006 to 2010 with generalized linear model. In our study, 5,559 patients (female, 36.0%; age, 64.4±12.9 years) were included. The estimated mean LOS of ischemic stroke was 17.4±1.8 days. After adjusting for confounders, LOS of lacunar infarction (14.7 days; p<0.001) and LOS of small cerebral infarction (17.0 days; p = 0.393) were shorter than that of single cerebral infarction (17.9 days, p<0.001). LOS of multi-infarct (19.0 days; p = 0.028), brainstem infarction (19.3 days; p = 0.045), basal ganglia infarction (18.5 days; p = 0.452) and other subtypes of ischemic stroke (18.9 days; p = 0.327) were longer than that of single cerebral infarction.

Conclusions

LOS of ischemic stroke patient differes across single cerebral infarction, lacunar infarction, multi-infarct and brainstem infarction patients. The ascending order of LOS was lacunar infarction, small cerebral infarction, single cerebral infarction, basal ganglia infarction, other subtypes of ischemic stroke, multi-infarct and brainstem infarction.     

Plasma D-Dimer Levels Are Associated with Stroke Subtypes and Infarction Volume in Patients with Acute Ischemic Stroke

Background

It has been suggested that modestly elevated circulating D-dimer values may be associated with acute ischemic stroke (AIS). Thus, the purpose of this study was to investigate the association between plasma D -dimer level at admission and AIS in Chinese population.

Methods

In a prospective observational study, plasma D-dimer levels were measured using a particle-enhanced, immunoturbidimetric assay on admission in 240 Chinese patients with AIS. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to D-dimer levels.

Results

Plasma median D-dimer levels were significantly (P = 0.000) higher in AIS patients as compared to healthy controls (0.88; interquartiler range [IQR], 0.28–2.11 mg/L and 0.31; IQR, 0.17–0.74 mg/L). D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score(r = 0.179, p = 0.005) and infarct volume(r = 0.425, p = 0.000). Those positive trends still existed even after correcting for possible confounding factors (P = 0.012, 0.000; respectively). Based on the Receiver operating characteristic (ROC) curve, the optimal cut-off value of plasma D-dimer levels as an indicator for diagnosis of cardioembolic strokes was projected to be 0.91 mg/L, which yielded a sensitivity of 83.7% and a specificity of 81.5%, the area under the curve was 0.862(95% confidence interval [CI], 0.811–0.912).

Conclusion

We had shown that plasma D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score and infarct volume. These associations were independent other possible variables. In addition, cardioembolic strokes can be distinguished from other stroke etiologies by measuring plasma D-dimer levels very early (0–48hours from stroke symptom onset).     

Hospital Acquired Pneumonia Is Linked to Right Hemispheric Peri-Insular Stroke

Purpose

Hospital acquired pneumonia (HAP) is a major complication of stroke. We sought to determine associations between infarction of specific brain regions and HAP.

Methods

215 consecutive acute stroke patients with HAP (2003–2009) were carefully matched with 215 non-pneumonia controls by gender, then NIHSS, then age. Admission imaging and binary masks of infarction were registered to MNI-152 space. Regional atlas and voxel-based log-odds were calculated to assess the relationship between infarct location and the likelihood of HAP. An independently validated penalized conditional logistic regression model was used to identify HAP associated imaging regions.

Results

The HAP and control patients were well matched by gender (100%), age (95% within 5-years), NIHSS (98% within 1-point), infarct size, dysphagia, and six other clinical variables. Right hemispheric infarcts were more frequent in patients with HAP versus controls (43.3% vs. 34.0%, p = 0.054), whereas left hemispheric infarcts were more frequent in controls (56.7% vs. 44.7%, p = 0.012); there was no significant difference between groups in the rate of brainstem strokes (p = 1.0). Of the 10 most infarcted regions, only right insular cortex volume was different in HAP versus controls (20 vs. 12 ml, p = 0.02). In univariate analyses, the highest log-odds regions for pneumonia were right hemisphere, cerebellum, and brainstem. The best performing multivariate model selected 7 brain regions of infarction and 2 infarct volume-based variables independently associated with HAP.

Conclusions

HAP is associated with right hemispheric peri-insular stroke. These associations may be related to autonomic modulation of immune mechanisms, supporting recent hypotheses of stroke mediated immune suppression.     

Prognostic Value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in Acute Coronary Syndrome Patients

Background

Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes.

Methods

The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone.

Results

During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03–0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1–54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05–0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004–0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02–1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56–145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters.

Conclusions

Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.     

Proteinuria Independently Predicts Unfavorable Outcome of Ischemic Stroke Patients Receiving Intravenous Thrombolysis

Background and Purpose

Patients with low estimated glomerular filtration rate (eGFR) and proteinuria may be at increased risk for stroke. This study investigated whether low eGFR and proteinuria are outcome predictors in stroke patients treated with intravenous thrombolysis.

Methods

We studied 432 consecutive stroke patients who received thrombolysis from January 2006 to December 2012, in Taiwan. Unfavorable outcome was defined as modified Rankin scale ≥2 at 3 months after stroke. Proteinuria was classified as negative or trace, mild, and moderate to severe. Using logistic regression analysis, we identified independent factors for unfavorable outcome after thrombolysis.

Results

Of all patients, 32.7% had proteinuria. Patients with proteinuria were older, had higher frequencies of diabetes mellitus, hyperlipidemia, atrial fibrillation, lower eGFR, and greater severity of stroke upon admission than those without proteinuria. Proteinuria, not low eGFR, was an independent predictor for unfavorable outcome for stroke (OR = 2.00 for mild proteinuria, p = 0.035; OR = 2.54 for moderate to severe proteinuria, p = 0.035). However, no clear relationship was found between proteinuria and symptomatic hemorrhage after thrombolysis.

Conclusions

Proteinuria is an independent predictor of unfavorable outcome for acute ischemic stroke in patients treated with intravenous thrombolysis, indicating the crucial role of chronic kidney disease on the effectiveness of thrombolysis.