A surgical model of permanent and transient middle cerebral artery stroke in the sheep

Background

Animal models are essential to study the pathophysiological changes associated with focal occlusive stroke and to investigate novel therapies. Currently used rodent models have yielded little clinical success, however large animal models may provide a more suitable alternative to improve clinical translation. We sought to develop a model of acute proximal middle cerebral artery (MCA) ischemic stroke in sheep, including both permanent occlusion and transient occlusion with reperfusion.

Materials and Methods

18 adult male and female Merino sheep were randomly allocated to one of three groups (n = 6/gp): 1) sham surgery; 2) permanent proximal MCA occlusion (MCAO); or 3) temporary MCAO with aneurysm clip. All animals had invasive arterial blood pressure, intracranial pressure and brain tissue oxygen monitoring. At 4 h following vessel occlusion or sham surgery animals were killed by perfusion fixation. Brains were processed for histopathological examination and infarct area determination. 6 further animals were randomized to either permanent (n = 3) or temporary MCAO (n = 3) and then had magnetic resonance imaging (MRI) at 4 h after MCAO.

Results

Evidence of ischemic injury in an MCA distribution was seen in all stroke animals. The ischemic lesion area was significantly larger after permanent (28.8%) compared with temporary MCAO (14.6%). Sham animals demonstrated no evidence of ischemic injury. There was a significant reduction in brain tissue oxygen partial pressure after permanent vessel occlusion between 30 and 210 mins after MCAO. MRI at 4 h demonstrated complete proximal MCA occlusion in the permanent MCAO animals with a diffusion deficit involving the whole right MCA territory, whereas temporary MCAO animals demonstrated MRA evidence of flow within the right MCA and smaller predominantly cortical diffusion deficits.

Conclusions

Proximal MCAO can be achieved in an ovine model of stroke via a surgical approach. Permanent occlusion creates larger infarct volumes, however aneurysm clip application allows for reperfusion.     

In Vivo MR Imaging of Intraarterially Delivered Magnetically Labeled Mesenchymal Stem Cells in a Canine Stroke Model

Background

This study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model.

Methodology

MSCs harvested from beagles’ bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×10⁶ labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks.

Principal Findings

Home-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining.

Conclusion

It is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.     

Spatial and Temporal Gene Expression Differences in Core and Periinfarct Areas in Experimental Stroke: A Microarray Analysis

Background

A large number of genes are regulated to promote brain repair following stroke. The thorough analysis of this process can help identify new markers and develop therapeutic strategies. This study analyzes gene expression following experimental stroke.

Methodology/Principal Findings

A microarray study of gene expression in the core, periinfarct and contralateral cortex was performed in adult Sprague-Dawley rats (n = 60) after 24 hours (acute phase) or 3 days (delayed stage) of permanent middle cerebral artery (MCA) occlusion. Independent qRT-PCR validation (n = 12) was performed for 22 of the genes. Functional data were evaluated by Ingenuity Pathway Analysis. The number of genes differentially expressed was 2,612 (24 h) and 5,717 (3 d) in the core; and 3,505 (24 h) and 1,686 (3 d) in the periinfarct area (logFC>|1|; adjP<0.05). Expression of many neurovascular unit development genes was altered at 24 h and 3 d including HES2, OLIG2, LINGO1 and NOGO-A; chemokines like CXCL1 and CXCL12, stress-response genes like HIF-1A, and trophic factors like BDNF or BMP4. Nearly half of the detected genes (43%) had not been associated with stroke previously.

Conclusions

This comprehensive study of gene regulation in the core and periinfarct areas at different times following permanent MCA occlusion provides new data that can be helpful in translational research.     

Dual-Phase CT Collateral Score: A Predictor of Clinical Outcome in Patients with Acute Ischemic Stroke

Background and Purpose

The presence of good collaterals on CT angiography (CTA) is a well-known predictor for favorable outcome in acute ischemic stroke. Recently, multiphase CT has been introduced as a more accurate method in assessing collaterals. The aim of this study was to assess the ability of dual-phase CT to evaluate collateral status and predict clinical outcome.

Methods

Forty-three patients who underwent both dual-phase CT and transfemoral cerebral angiography (TFCA) for occluded intracranial internal carotid artery (ICA) and/or middle cerebral artery (M1 segment) were recruited from a prospectively collected database. The collateral status on dual-phase CT was graded by using a 4-point scale: grade 0 = no collaterals; 1 = some collaterals with persistence of some defects; 2 = slow but complete collaterals; and 3 = fast and complete collaterals. Univariate and multivariate analysis were performed to define the independent predictors for favorable outcome at 3 months.

Results

Dual-phase CT collateral status (ρ = 0.744) showed higher correlation with TFCA collateral status than CTA collateral status (ρ = 0.596) and substantial interobserver agreement (weighted κ = 0.776). In the univariate analysis, age, history of hypertension, collateral scores on CTA, dual-phase CT, and TFCA, occlusion in intracranial ICA, final infarct volume, and symptomatic hemorrhage were significantly associated with outcome. Among them, only the dual-phase CT collateral score was an independent predictor for favorable outcome (OR = 26.342 (2.788–248.864); P = 0.004) in the multivariate analysis.

Conclusions

The collateral status on dual-phase CT can be a useful predictor for clinical outcome in acute stroke patients, especially when advanced CT techniques are not available in emergent situations.     

Hemodynamic Factors May Play a Critical Role in Neurological Deterioration Occurring within 72 hrs after Lacunar Stroke

Background

Whether a perfusion defect exists in lacunar infarct and whether it is related to early neurological deterioration (END) is still under debate. The aim of this study was to evaluate whether END in lacunar infarct is related to a perfusion defect using diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI) and perfusion MR imaging.

Methods

One hundred and forty-one consecutive patients had an MRI scan within 30 hours after onset of symptoms and 43 patients with acute lacunar infarct and classic lacunar syndrome were recruited. The MRI sequences included DWI, DTI and cerebral blood flow (CBF) maps to respectively represent the topographic locations of acute infarcts, the corticospinal tract and perfusion defects. The END was defined in reference to the National Institute of Health Stroke Scale (NIHSS) as an increase ≧2 within 72 hours. Cohen''s Kappa coefficient was used to examine the reliability between the 2 image readers. A multivariate logistic regression model was constructed adjusting for baseline variables.

Results

Ten out of the 43 patients had END. Patients having END was significantly associated with lower chances of favorable and good outcomes at 3 months (p = 0.01 and p = 0.002, respectively). END was predicted when the non-core hypoperfused area overlapped on the corticospinal tract, which is defined as the expected END profile. Cohen''s Kappa coefficient between the 2 image readers to define images of expected END profiles was 0.74. In 15 patients with expected END profile, 9 had END clinically, whereas 28 patients had no expected END profile, and only 1 patient had END (p<0.0001). After adjusting for sex, the expected END profile was still associated with END (odds ratio, 42.2; p = 0.002).

Conclusion

Our study demonstrated that the END in acute lacunar stroke is likely related to the transformation of non-core hypoperfused area into infarction in the anatomy of corticospinal tracts.     

Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

Background

Contribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.

Methods

There were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.

Results

After adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.

Conclusions

The NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.     

Long-Term Risk of Cardiovascular Disease among Type 2 Diabetic Patients with Asymptomatic Intracranial Atherosclerosis: A Prospective Cohort Study

Objective

To investigate whether asymptomatic middle cerebral artery (MCA) stenosis is associated with risk of cardiovascular disease (CVD) in Chinese with type 2 diabetes.

Methods

In this prospective cohort study, 2,144 Hong Kong Chinese with type 2 diabetes and without history of stroke or atrial fibrillation were recruited in 1994–1996 and followed up for a median of 14.51 years. Participants were assessed at baseline for MCA stenosis using transcranial Doppler. We performed survival analysis to assess the association between asymptomatic MCA stenosis and first CVD event, defined as ischemic stroke, acute coronary syndrome (ACS) or cardiovascular death.

Results

Of the 2,144 subjects, MCA stenosis at baseline was detected in 264 (12.3%). Rates of stroke, ACS and cardiovascular death per 100 were, respectively, 2.24, 2.92 and 1.11 among participants with stenosis, higher than among those without stenosis. Ten-year cumulative occurrence of stroke, ACS and cardiovascular death in subjects with MCA stenosis was 20%, 24% and 10%, respectively, higher than the corresponding values for subjects without stenosis(all P<0.001). After adjusting for covariates, MCA stenosis was found to be an independent predictor of stroke [hazard ratio (HR) 1.40, 95%CI 1.05–1.86; P = 0.02], ACS (HR 1.35, 95%CI 1.04–1.75; P = 0.02) and cardiovascular death(HR 1.56, 95%CI 1.04–2.33; P = 0.03).

Conclusions

Asymptomatic MCA stenosis is a risk factor for CVD in Chinese with type 2 diabetes, and detection of asymptomatic MCA stenosis by transcranial Doppler can identify diabetic individuals at high risk of future CVD. This finding is particularly important for diabetic individuals in Asia, where intracranial atherosclerosis is common.     

Incidence,Risk Factors,Treatment and Prognosis of Popliteal Artery Embolization in the Superficial Femoral Artery Interventions

Objective

Percutaneous transluminal angioplasty and stenting (PTA + stent) has gained acceptance as a primary treatment modality for the superficial femoral artery (SFA) diseases. Popliteal artery embolization (PAE) is a severe complication in SFA interventions. The purpose of this study was to evaluate the incidence, risk factors, treatment and prognosis of PAE in primary SFA PTA + stent.

Methods

Chronic SFA arteriosclerosis cases that underwent primary PTA + stent were reviewed from a retrospectively maintained database. Runoff vessels were evaluated in all cases before and after the interventions for PAE detection. The primary patency, secondary patency and limb salvage rates were calculated using Kaplan-Meier analysis and compared using log-rank analysis. Cox multivariate regression was performed to evaluate predictors of patency and limb salvage rates.

Results

There were 436 lesions treated in 388 patients with 10 PAE events (2.3%) in total. PAE rate was significantly higher in Transatlantic Inter-Society Consensus (TASC) C/D group compared with TASC A/B group (OR = 8.91, P = .002), in chronic total occlusion (CTO) lesions compared with stenotic lesions (P<.0001), and in group with history of cerebral ischemic stroke (OR = 6.11, P = .007). PAE rates were not significantly affected by age, sex, smoking, hypertension, diabetes, hyperlipidemia and runoff status. The binary logistic regression showed that only the TASC C/D was an independent predictor of PAE (P = .031). The 12-month and 24-month primary patency, secondary patency and limb salvage rates in PAE group showed no significant differences comparing with non-PAE group.

Conclusions

PAE is a rare event in primary SFA PTA + stent. TASC C/D lesion, CTO and cerebral ischemic stroke history are risk factors for PAE. PAE is typically reversible by comprehensive techniques. If the popliteal flow is restored in time, PAE has no significant effect on long-term patency and limb salvage rates.     

Traumatic Intracranial Hemorrhage Correlates with Preinjury Brain Atrophy,but Not with Antithrombotic Agent Use: A Retrospective Study

Background

The impact of antithrombotic agents (warfarin, clopidogrel, ASA) on traumatic brain injury outcomes is highly controversial. Although cerebral atrophy is speculated as a risk for acute intracranial hemorrhage, there is no objective literature evidence.

Materials and Methods

This is a retrospective, consecutive investigation of patients with signs of external head trauma and age ≥60 years. Outcomes were correlated with antithrombotic-agent status, coagulation test results, admission neurologic function, and CT-based cerebral atrophy dimensions.

Results

Of 198 consecutive patients, 36% were antithrombotic-negative and 64% antithrombotic-positive. ASA patients had higher arachidonic acid inhibition (p = 0.04) and warfarin patients had higher INR (p<0.001), compared to antithrombotic-negative patients. Antithrombotic-positive intracranial hemorrhage rate (38.9%) was similar to the antithrombotic-negative rate (31.9%; p = 0.3285). Coagulopathy was not present on the ten standard coagulation, thromboelastography, and platelet mapping tests with intracranial hemorrhage and results were similar to those without hemorrhage (p≥0.1354). Hemorrhagic-neurologic complication (intracranial hemorrhage progression, need for craniotomy, neurologic deterioration, or death) rates were similar for antithrombotic-negative (6.9%) and antithrombotic-positive (8.7%; p = 0.6574) patients. The hemorrhagic-neurologic complication rate was increased when admission major neurologic dysfunction was present (63.2% versus 2.2%; RR = 28.3; p<0.001). Age correlated inversely with brain parenchymal width (p<0.001) and positively with lateral ventricular width (p = 0.047) and cortical atrophy (p<0.001). Intracranial hemorrhage correlated with cortical atrophy (p<0.001) and ventricular width (p<0.001).

Conclusions

Intracranial hemorrhage is not associated with antithrombotic agent use. Intracranial hemorrhage patients have no demonstrable coagulopathy. The association of preinjury brain atrophy with acute intracranial hemorrhage is a novel finding. Contrary to antithrombotic agent status, admission neurologic abnormality is a predictor of adverse post-admission outcomes. Study findings indicate that effective hemostasis is maintained with antithrombotic therapy.     

Genetic Polymorphism in PDE4D Gene and Risk of Ischemic Stroke in Chinese Population: A Meta-Analysis

Background

Stroke is the second most common cause of death and major cause of disability worldwide. The SNP 83 in PDE4D gene has been suggested as a risk factor in ischemic stroke, but direct evidence from genetic association studies remains inconclusive even in Chinese population.

Methods

Meta-analysis of case-control studies on the relationship between SNP 83 in PDE4D gene and susceptibility to ischemic stroke in Chinese population published domestically and abroad from January 2003 to September 2012.

Results

9 case-control studies were selected. Meta-analysis results showed that the significant association between SNP 83 and ischemic stroke was found under the dominant model (OR = 1.34, 95% CI: 1.20–1.49) and recessive model (OR = 1.45, 95% CI: 1.19–1.76) in Chinese population. In subgroup meta-analysis, SNP 83 and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the dominant model (OR = 1.69, 95% CI: 1.41–2.01) and recessive model (OR = 1.47, 95% CI: 1.04–2.06).

Conclusions

The results suggest that SNP 83 in PDE4D gene is significantly associated with susceptibility to ischemic stroke in Chinese population.     

Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model

Introduction

Malignant middle cerebral artery (MCA) stroke has a disproportionately high mortality due to the rapid development of refractory space-occupying cerebral edema. Animal models are essential in developing successful anti-edema therapies; however to date poor clinical translation has been associated with the predominately used rodent models. As such, large animal gyrencephalic models of stroke are urgently needed. The aim of the study was to characterize the intracranial pressure (ICP) response to MCA occlusion in our recently developed ovine stroke model.

Materials and Methods

30 adult female Merino sheep (n = 8–12/gp) were randomized to sham surgery, temporary or permanent proximal MCA occlusion. ICP and brain tissue oxygen were monitored for 24 hours under general anesthesia. MRI, infarct volume with triphenyltetrazolium chloride (TTC) staining and histology were performed.

Results

No increase in ICP, radiological evidence of ischemia within the MCA territory but without space-occupying edema, and TTC infarct volumes of 7.9+/-5.1% were seen with temporary MCAO. Permanent MCAO resulted in significantly elevated ICP, accompanied by 30% mortality, radiological evidence of space-occupying cerebral edema and TTC infarct volumes of 27.4+/-6.4%.

Conclusions

Permanent proximal MCAO in the sheep results in space-occupying cerebral edema, raised ICP and mortality similar to human malignant MCA stroke. This animal model may prove useful for pre-clinical testing of anti-edema therapies that have shown promise in rodent studies.     

Association between Irrigation Fluids,Washout Volumes and Risk of Local Recurrence of Anterior Resection for Rectal Cancer: A Meta-Analysis of 427 Cases and 492 Controls

Background

Rectal washout can prevent local recurrence after anterior resection of rectal cancer. Few studies have focused particularly on the association between irrigation fluids volume or agents and the risk of local recurrence after anterior resection of rectal cancer.

Objective

To estimate the association between irrigation fluids types, volumes of rectal washout and risk of local recurrence after anterior resection for cancer.

Data Sources

Relevant studies were identified by a search of Medline, Embase, Wiley Online Library, China National Knowledge Infrastructure, Cochrane Oral Health Group Specialized Register, Wanfang databases and Google Website from their inception until October 18,2013.

Study Selection

Studies reporting the association between rectal washout types and volumes and risk of local recurrence after anterior resection for cancer were included.

Interventions

Eligible studies used rectal washout. Control groups were defined as no washout.

Study Appraisal and Synthesis Methods

Random-effects model were used to obtain summary estimates of RR and 95% CI, with Stata version 11 and RevMan 5.2.5 softwares used. The quality of report was appraised in reference to the MINORS item.

Results

Of the 919 rectal cancer patients in 8 included studies, a total of 61(6.64%) cases of local recurrence were reported, with a pooled RR 0.51 (95%CI = 0.28–0.92, P = 0.03). The RRs 0.37 and 0.39 in normal saline and washout volume (≥1500 ml normal saline) subgroup, respectively, indicated that rectal washout with normal saline, or ≥1500 ml in volume could significantly reduce local recurrence (LR) rate (95% CI = 0.17–0.79, P = 0.01; 95% CI = 0.18–0.87, P = 0.02) after anterior resection for cancer.

Limitation

The included studies were non-randomized observational studies, with diversity of study designs.

Conclusion

Rectal washout with normal saline alone can reduce the risk of local recurrence in patients with resectable rectal cancer, and 1.5 liters rectal washout in volume is recommended.     

Pro-Inflammatory Mediators and Apoptosis Correlate to rt-PA Response in a Novel Mouse Model of Thromboembolic Stroke

Background

A recent study suggests that patients with persistent occlusion of the middle cerebral artery (MCA) following treatment with recombinant tissue plasminogen activator (rt-PA) have better outcomes than patients with MCA occlusion not receiving rt-PA. We performed a study to elucidate possible mechanisms of this finding in a new model of thromboembolic stroke closely mimicking human pathophysiology.

Methods

Thromboembolic stroke was induced by local injection of thrombin directly into the right MCA of C57 black/6J mice. Rt-PA was administered 20 and 40 min after clot formation. The efficiency of rt-PA to induce thrombolysis was measured by laser Doppler. After 24 h, all animals were euthanized and interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP)-9, Caspase-3, hsp 32 and hsp 70 protein levels were investigated by immunofluorescence. Presence of hemorrhage was verified and infarct volume was measured using histology.

Results

Thrombin injection resulted in clot formation giving rise to cortical brain infarction. Early rt-PA treatment starting at 20 min after the clot formation resulted in 100% recanalization. However, rt-PA-induced thrombolysis dissolved the clot in only 38% of the animals when administered 40 min after clot formation. Protein levels of IL-6, TNF-α, MMP-9, Caspase-3, hsp 32 and hsp 70 were increased after MCAO, whereas treatment with rt-PA attenuated the expressions of inflammatory markers in those animals where the thrombolysis was successful. In addition, the infarct size was significantly reduced with rt-PA treatment compared to non-treated MCAO, regardless of whether MCA thrombolysis was successful.

Conclusions

The present study demonstrates a clear correlation of the protein expression of inflammatory mediators, apoptosis and stress genes with the recanalization data after rt-PA treatment. In this model rt-PA treatment decreases the infarct size regardless of whether vessel recanalization is successful.     

Salt-Restriction-Spoon Improved the Salt Intake among Residents in China

Objective

To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).

Design

A community intervention study.

Setting

Two villages in Beijing.

Participants

403 local adult residents being responsible for home cooking.

Intervention

Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.

Main Outcome Measures

The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.

Analysis

Covariance analyses, Chi-square tests, Student’s t tests, and repeated measures analyses of variance.

Results

After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870).

Conclusions

The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.     

Relationship between Watershed Infarcts and Recent Intra Plaque Haemorrhage in Carotid Atherosclerotic Plaque

Objective

Watershed infarcts (WSI) are thought to result from hemodynamic mechanism, but studies have suggested that microemboli from unstable carotid plaques may distribute preferentially in watershed areas, i.e., between two cerebral arterial territories. Intraplaque haemorrhage (IPH) is an emerging marker of plaque instability and microembolic activity. We assessed the association between WSI and IPH in patients with recently symptomatic moderate carotid stenosis.

Methods and Results

We selected 65 patients with symptomatic moderate (median NASCET degree of stenosis = 31%) carotid stenosis and brain infarct on Diffusion-Weighted Imaging (DWI) on Magnetic Resonance Imaging (MRI) from a multicentre prospective study. Fourteen (22%) had WSI (cortical, n = 8; internal, n = 4; cortical and internal, n = 2). Patients with WSI were more likely to have IPH than those without WSI although the difference was not significant (50% vs. 31%, OR = 2.19; 95% CI, 0.66–7.29; P = 0.20). After adjustment for degree of stenosis, age and gender, the results remained unchanged.

Conclusion

About one in fifth of brain infarcts occurring in patients with moderate carotid stenosis were distributed in watershed areas. Albeit not significant, an association between IPH - more generally plaque component - and WSI, still remains possible.     

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.     

Early PTSD Symptom Trajectories: Persistence,Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS)

Context

Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder''s pathogenesis and prophylaxis.

Objectives

To describe discrete symptom trajectories and examine their relevance for preventive interventions.

Design

Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data.

Setting

Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity.

Participants

Adult survivors of potentially traumatic events consecutively admitted to the hospital''s emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months.

Approach

We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8±5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8±42.4 days. CBT effectively reduced PTSD symptoms in the entire sample.

Main Outcome Measure

Latent trajectories of PTSD symptoms; effects of CBT on these trajectories.

Results

Three trajectories were identified: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes.

Conclusions

The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.     

Frequency and Risk Factors for Under- and Over-Treatment in Stroke Prevention for Patients with Non-Valvular Atrial Fibrillation in General Practice

Objective

To determine adequacy of antithrombotic treatment in patients with non-valvular atrial fibrillation. To determine risk factors for under- and over-treatment.

Design

Retrospective, cross-sectional study of electronic health records from 36 general practitioners in 2008.

Setting

General practice in the Netherlands.

Subjects

Primary care physicians (n = 36) and patients (n = 981) aged 65 years and over.

Main Outcome Measures

Rates of adequate, under and over-treatment, risk factors for under and over-treatment.

Results

Of the 981 included patients with a mean of age 78, 18% received no antithrombotic treatment (under-treatment), 13% received antiplatelet drugs and 69% received oral anticoagulation (OAC). Further, 43% of the included patients were treated adequately, 26% were under-treated, and 31% were over-treated. Patients with a previous ischaemic stroke were at high risk for under-treatment (OR 2.4, CI 1.6–3.5), whereas those with contraindications for OAC were at high risk for over-treatment (OR 37.0, CI 18.1–79.9). Age over 75 (OR 0.2, CI: 0.1–0.3]), diabetes (OR 0.1, CI: 0.1–0.3), heart failure (OR 0.2, CI: 0.1–0.3), hypertension (OR 0.1, CI: 0.1–0.2) and previous ischaemic stroke (OR 0.04, CI: 0.02–0.11) protected against over-treatment.

Conclusions

In general practice, CHADS₂-criteria are being used, but the antithrombotic treatment of patients with atrial fibrillation frequently deviates from guidelines on this topic. Patients with previous stroke are at high risk of not being prescribed OAC. Contraindications for OAC, however, seem to be frequently overlooked.