Infarction Distribution Pattern in Acute Stroke May Predict the Extent of Leptomeningeal Collaterals

Objective

The aim of this study was to evaluate whether the distribution pattern of early ischemic changes in the initial MRI allows a practical method for estimating leptomeningeal collateralization in acute ischemic stroke (AIS).

Methods

Seventy-four patients with AIS underwent MRI followed by conventional angiogram and mechanical thrombectomy. Diffusion restriction in Diffusion weighted imaging (DWI) and correlated T2-hyperintensity of the infarct were retrospectively analyzed and subdivided in accordance with Alberta Stroke Program Early CT score (ASPECTS). Patients were angiographically graded in collateralization groups according to the method of Higashida, and dichotomized in 2 groups: 29 subjects with collateralization grade 3 or 4 (well-collateralized group) and 45 subjects with grade 1 or 2 (poorly-collateralized group). Individual ASPECTS areas were compared among the groups.

Results

Means for overall DWI-ASPECTS were 6.34 vs. 4.51 (well vs. poorly collateralized groups respectively), and for T2-ASPECTS 9.34 vs 8.96. A significant difference between groups was found for DWI-ASPECTS (p<0.001), but not for T2-ASPECTS (p = 0.088). Regarding the individual areas, only insula, M1-M4 and M6 showed significantly fewer infarctions in the well-collateralized group (p-values <0.001 to 0.015). 89% of patients in the well-collateralized group showed 0–2 infarctions in these six areas (44.8% with 0 infarctions), while 59.9% patients of the poor-collateralized group showed 3–6 infarctions.

Conclusion

Patients with poor leptomeningeal collateralization show more infarcts on the initial MRI, particularly in the ASPECTS areas M1 to M4, M6 and insula. Therefore DWI abnormalities in these areas may be a surrogate marker for poor leptomeningeal collaterals and may be useful for estimation of the collateral status in routine clinical evaluation.     

Relationship between Blood Pressure and Outcomes in Acute Ischemic Stroke Patients Administered Lytic Medication in the TIMS-China Study

Objective

Increased blood pressure (BP) management following acute ischemic stroke (AIS) remains controversial. This study aimed to identify the association between BP and clinical outcomes in AIS patients administered lytic medication in the TIMS-China (thrombolysis implementation and monitor of acute ischemic stroke in China) database.

Methods

The sample comprised 1128 patients hospitalized within 4.5 hours (h) of AIS for intravenous recombinant tissue plasminogen activator (i.v. rt-PA) thrombolysis. Systolic BP (SBP) and diastolic BP (DBP) at baseline, 2 h and 24 h after treatment, and changes from baseline were analyzed. The study outcomes comprised a favorable outcome (modified Rankin Scale 0–1 at 90 days) and symptomatic intracerebral hemorrhage (SICH), analyzed using logistic regression, with low BP as the reference group.

Results

Lower BP (baseline, 2 h, and 24 h) was beneficial in AIS patients and significantly related to a favorable outcome (P<0.05). A substantial BP decrease at 24 h after rt-PA thrombolysis was significantly associated with a favorable outcome compared with a moderate BP decrease (P = 0.0298). A SBP >160 mmHg 2 h after rt-PA thrombolysis was significantly associated with SICH compared with a SBP <140 mmHg (P = 0.0238). An increase or no change (>25 mmHg) in SBP was significantly associated with SICH (P = 0.002) compared with a small SBP decrease (1–9 mmHg).

Conclusions

This study provides novel evidence that lower BP within the first 24 h is associated with a more favorable outcome and less frequent SICH in AIS patients administered lytic medication. Routine BP-lowering treatment should be considered in AIS patients following lytic medication.     

Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

Background

CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.

Materials and Methods

This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.

Results

Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.

Conclusion

For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly differed between ischemic lesion agreement and misclassified CTP ischemic core, suggesting that CTP analysis may benefit from revisions.     

Fate of Diffusion Restricted Lesions in Acute Intracerebral Hemorrhage

Background

Diffusion-restricted lesions on diffusion-weighted imaging (DWI) are detected in patients with intracerebral hemorrhage (ICH). In this study, we aimed to determine the fate of DWI lesions in ICH patients and whether the presence of DWI lesions is associated with functional outcome in patients with ICH.

Methods

This prospective study enrolled 153 patients with acute ICH. Baseline MRI scans were performed within 2 weeks after ICH to detect DWI lesions and imaging markers for small vessel disease (SVD). Follow-up MRI scans were performed at 3 months after ICH to assess the fate of the DWI lesions. We analyzed the associations between the characteristics of DWI lesions with clinical features and functional outcome.

Results

Seventeen of the 153 patients (11.1%) had a total of 25 DWI lesions. Factors associated with DWI lesions were high initial systolic and mean arterial blood pressure (MAP) at the emergency room, additional lowering of MAP within 24 hours, and the presence of white matter hyperintensity and cerebral microbleeds. Thirteen of the 25 DWI lesions (52%) were not visible on follow-up T2-weighted or fluid-attenuated inversion recovery images and were associated with high apparent diffusion coefficient value and a sharper decease in MAP. The regression of DWI lesions was associated with good functional outcome.

Conclusions

More than half of the DWI lesions in the ICH patients did not transition to visible, long-term infarction. Only if the DWI lesion finally transitioned to final infarction was a poor functional outcome predicted. A DWI lesion may be regarded as an ischemic change of SVD and does not always indicate certain cerebral infarction or permanent tissue injury.     

Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Importance

Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke.

Objective

To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke.

Data Sources

MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015.

Study Selection

Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected.

Data Extraction and Synthesis

Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes.

Main Outcomes and Measures

The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage.

Results

Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration.

Conclusions and Relevance

This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment.     

Case-Control Study of Platelet Glycoprotein Receptor Ib and IIb/IIIa Expression in Patients with Acute and Chronic Cerebrovascular Disease

Background

Animal models have been instrumental in defining thrombus formation, including the role of platelet surface glycoprotein (GP) receptors, in acute ischemic stroke (AIS). However, the involvement of GP receptors in human ischemic stroke pathophysiology and their utility as biomarkers for ischemic stroke risk and severity requires elucidation.

Aims

To determine whether platelet GPIb and GPIIb/IIIa receptors are differentially expressed in patients with AIS and chronic cerebrovascular disease (CCD) compared with healthy volunteers (HV) and to identify predictors of GPIb and GPIIb/IIIa expression.

Methods

This was a case—control study of 116 patients with AIS or transient ischemic attack (TIA), 117 patients with CCD, and 104 HV who were enrolled at our University hospital from 2010 to 2013. Blood sampling was performed once in the CCD and HV groups, and at several time points in patients with AIS or TIA. Linear regression and analysis of variance were used to analyze correlations between platelet GPIb and GPIIb/IIIa receptor numbers and demographic and clinical parameters.

Results

GPIb and GPIIb/IIIa receptor numbers did not significantly differ between the AIS, CCD, and HV groups. GPIb receptor expression level correlated significantly with the magnitude of GPIIb/IIIa receptor expression and the neutrophil count. In contrast, GPIIb/IIIa receptor numbers were not associated with peripheral immune-cell sub-population counts. C-reactive protein was an independent predictor of GPIIb/IIIa (not GPIb) receptor numbers.

Conclusions

Platelet GPIb and GPIIb/IIIa receptor numbers did not distinguish between patient or control groups in this study, negating their potential use as a biomarker for predicting stroke risk.     

Drip,Ship, and On-Demand Endovascular Therapy for Acute Ischemic Stroke

Background

The “drip and ship” approach can facilitate an early initiation of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) at community hospitals. New endovascular treatment modalities, such as stent retrieval, have further improved the rate of safe and successful recanalization. We assessed the clinical outcomes of on-demand endovascular therapy in patients with AIS who were transported to a comprehensive stroke center under the “drip and ship” paradigm.

Methods

This retrospective study evaluated prospectively registered patients with acute large vessel occlusions in the anterior circulation who underwent endovascular recanalization after IVT at our regional comprehensive stroke center between January 2011 and April 2014. Clinical outcomes and neuroradiological findings were compared between patients who received IVT at the center (direct visit, DV) and at a community hospital (drip and ship, DS).

Results

Baseline characteristics such as age, initial National Institutes of Health Stroke Scale (NIHSS) score, and risk factors for stroke were similar, and most patients underwent endovascular therapy with a Solitaire stent (81.9% vs. 89.3% for DV and DS, respectively, P = 0.55). The average initial NIHSS score was 12.15±4.1 (12.06 vs. 12.39 for DV and DS, respectively, P = 0.719). The proportions of long-term favorable outcomes (modified Rankin Scale score ≤2 at 90 days) and successful recanalization (Thrombolysis in Cerebral Ischemia score ≥2b) were not significantly different (P = 0.828 and 0.158, respectively). The mortality rates and occurrences of symptomatic intracerebral hemorrhage were not significantly different (P = 0.999 and 0.267, respectively).

Conclusions

The “drip and ship” approach with subsequent endovascular therapy is a feasible treatment concept for patients with acute large vessel occlusion in the anterior circulation that could help improve clinical outcomes in patients with AIS.     

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective,Combined Semi-Quantitative and Quantitative Assessment

Introduction

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned.

Methods

62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded.

Results

Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome.

Conclusions

Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.     

Ischemic Stroke in Critically Ill Patients with Malignancy

Background

Cerebrovascular diseases are a frequent cause of neurological symptoms in patients with cancer. The clinical characteristics of ischemic stroke (IS) in patients with cancer have been reported in several studies; however, limited data are available regarding critically ill patients with cancer who develop IS during their stay in the intensive care unit (ICU).

Methods

All consecutive patients who underwent brain magnetic resonance imaging (MRI) for suspicion of IS with acute abnormal neurologic symptoms or who developed signs of IS while in the ICU were retrospectively evaluated. We compared the clinical characteristics and diffusion-weighted imaging (DWI) lesion patterns between patients finally diagnosed as having or not having IS.

Results

Over the study period, a total of 88 patients underwent brain MRI for suspicion of IS, with altered mental status in 55 (63%), hemiparesis in 28 (32%), and seizure in 20 (23%). A total of 43 (49%) patients were ultimately diagnosed with IS. Multiple DWI lesions (41%) were more common than single lesions (8%). The etiologies of IS were not determined in the majority of patients (n = 27, 63%). In the remaining 16 (37%) patients, the most common aetiology of IS was cardioembolism (n = 8), followed by large-vessel atherosclerosis (n = 3) and small-vessel occlusion (n = 2). However, brain metastases were newly diagnosed in only 7 (8%) patients. Univariate comparison of the baseline characteristics between patients with or without IS did not reveal any significant differences in sex, malignancy type, recent chemotherapy, vascular risk factors, or serum D-dimer levels at the time of suspicion of IS. Thrombotic events were more common in the IS group than in the non-IS group (P = 0.028). However, patients who were ultimately diagnosed with IS had more hemiparesis symptoms at the time of suspicion of IS (P = 0.001). This association was significant even after adjusting for potentially confounding factors (adjusted odds ratio 5.339; 95% confidence interval, 1.521–19.163).

Conclusions

IS developed during ICU stays in critically ill patients with cancer have particular features that may be associated with cancer-related mechanism.     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.     

New Cerebral Lesions at Magnetic Resonance Imaging after Carotid Artery Stenting Versus Endarterectomy: An Updated Meta-Analysis

Background

Carotid endarterectomy (CEA) or stenting (CAS) are associated with a relatively low rate of clinical events, but diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions. Therefore, we conducted an updated meta-analysis on the occurrence of post-procedural new DWI lesions after CAS versus CEA.

Methods and Results

MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched and 20 studies (2 randomized and 18 non-randomized) with a total of 2104 procedures (CAS = 989; CEA = 1115) were included. The incidence of new DWI cerebral lesions was significantly greater after CAS than CEA (40.3% vs 12.2%; 20 studies; 2104 patients; odds ratio [OR] 5.17; 95% confidence interval [CI], 3.31-8.06; p<0.00001). Also peri-procedural stroke (17 studies; 1833 patients; OR 2.01; 95% CI, 1.14-3.55; p=0.02) and stroke or TIA (17 studies; 1833 patients; OR 2.40; 95% CI, 1.42-4.08; p=0.001) were significantly increased after CAS. This latter clinical advantage in the CEA group over CAS was tempered when CEA procedures were performed with shunting in all instead of selective shunting or when CAS was performed with only closed cell stents instead of both closed and open cell stents, however, no significant differences between subgroups emerged.

Conclusions

CAS is associated with an increased incidence of post-procedural brain DWI lesions. This greater amount of ischemic burden may also reflect a higher rate of cerebral events after CAS. However, whether recent technical advances mainly for CAS could potentially reduce these ischemic events still remains to be evaluated.     

Evaluation of Off-Hour Emergency Care in Acute Ischemic Stroke: Results from the China National Stroke Registry

Background and Purpose

The quality of after-hour emergency care of patients with acute ischemic stroke is debatable. We therefore, sought to analyze the performance measures, quality of care and clinical outcomes in these patients admitted during off-hours.

Methods

Our study included 4493 patients from a selected cohort of patients admitted to the hospitals with ischemic stroke in the China National Stroke Registry (CNSR) from September 2007 to August 2008. On-hour presentation was defined as arrival at the emergency department from the scene between 8AM and 5PM from Monday through Friday. Off-hours included the remainder of the on-hours and statutory holidays. The association between off-hour presentation and outcome was analyzed using multivariate logistic-regression models.

Results

Off-hour presentation was identified in 2672 (59.5%) patients with ischemic stroke. Comparison of patients admitted during off-hours with those admitted during on-hours revealed an unadjusted odds ratio of in-hospital mortality of 1.38 (95% confidence interval, 1.04–1.85), which declined to 1.34 (95% confidence interval, 0.93–1.93) after adjusting for patient characteristics (especially, pre-hospital delay). No difference in 30-day mortality, total death or dependence at three, six and 12 months between two groups was observed. No association between off-hour admission and quality of care was found.

Conclusions

In the CNSR database, compared with on-hour patients, off-hour patients with acute ischemic stroke admitted to the emergency departments from scene manifested a higher incidence of in-hospital mortality. However, the difference in incidence and quality of care between the groups disappeared after adjusting for pre-hospital delay and other variables.     

Reliability of Two Diameters Method in Determining Acute Infarct Size. Validation as New Imaging Biomarker

Background

In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI) has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml.

Methods

Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od-values) the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians.

Results

For 108 included patients (53 female, mean age 71.36 years) with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951). Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50) od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method.

Conclusion

The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to identify large infarctions with volume larger than 100 ml. Further studies can analyze the therapeutic utility of this new method.

Trail Registration

ClinicalTrials.org NCT00715533     

Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting

Background and Purpose

Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.

Methods

Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.

Results

A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03–2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10–3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12–3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.

Conclusions

PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events.     

Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

Background

Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial.

Methods

Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism.

Results

Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI₉₅ 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI₉₅ 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%).

Conclusions

ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke.

Trial Registration

ClincalTrials.gov NCT00235495     

Effect of X-Ray Attenuation of Arterial Obstructions on Intravenous Thrombolysis and Outcome after Ischemic Stroke

Objective

To assess whether the x-ray attenuation of intra-arterial obstruction measured on non-contrast CT in ischemic stroke can predict response to thrombolysis and subsequent functional outcome.

Methods

The Third International Stroke Trial (IST-3) was a multicenter randomized-controlled trial of intravenous thrombolysis (rt-PA) given within six hours of ischemic stroke. Ethical approval and informed consent were obtained. In a subgroup of 109 IST-3 patients (38 men, median age 82 years), a single reader, masked to all clinical and other imaging data, manually measured x-ray attenuation (Hounsfield Units, HU) on non-contrast CT at the location of angiographically-proven intra-arterial obstructions, pre-randomization and at 24–48 hour follow-up. We calculated change in attenuation between scans. We assessed the impact of pre-randomization arterial obstruction attenuation on six-month functional outcome.

Results

Most arterial obstructions (64/109, 59%) were hyperattenuating (mean 51.0 HU). Compared with control, treatment with rt-PA was associated with a greater, but non-significant, reduction in obstruction attenuation at follow-up (-8.0 HU versus -1.4 HU in patients allocated control, p = 0.117). In multivariable ordinal regression analysis controlled for patient age, stroke severity, location and extent of obstruction, time from stroke onset to baseline scan and rt-PA treatment allocation, the attenuation of pre-randomization arterial obstruction was not independently associated with six-month outcome (odds ratio = 0.99, 95% confidence interval = 0.94–1.03, p = 0.516).

Conclusions

In ischemic stroke, the x-ray attenuation of the arterial obstruction may decline more rapidly from baseline to 24–48 hours following treatment with thrombolysis but we found no evidence that baseline arterial obstruction attenuation predicts six-month outcome.     

Acute Endovascular Reperfusion Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Randomized controlled trials (RCTs) of endovascular therapy for acute ischemic stroke have had inconsistent results. We evaluated the efficacy and safety of endovascular therapy in published RCTs.

Methods

We performed a systematic review of RCTs of endovascular therapy with thrombolytic or mechanical reperfusion compared with interventions without endovascular therapy. Primary outcome was the frequency of good functional outcome (modified Rankin scale (mRS) of 0-2 at 90 days) and secondary outcomes were mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Random-effects meta-analysis was performed and the Cochrane risk of bias assessment was used to evaluate quality of evidence.

Results

Ten studies involving 1,612 subjects were included. Endovascular therapy was not significantly associated with good functional outcome (Relative Risk [RR] =1.17; 95% CI, 0.97 to 1.42; p=0.10 and Absolute Risk Difference [ARD] =7%; 95%CI -0.1% to 14%; p=0.05); heterogeneity was moderate among studies (I²=30%). Mortality was unchanged with endovascular therapy (RR=0.92; 95 % CI, 0.75 to 1.13; p=0.45) and there was no difference in sICH (RR=1.20; 95 % CI, 0.79 to 1.82; p=0.39). The quality of evidence was low for all outcomes and the recommendation is weak for the use of endovascular therapy as per GRADE methodology.

Conclusions

Intra-arterial therapy did not show significant increase in good outcomes and no changes in either mortality or sICH in patients with acute ischemic stroke. We need further RCTs with better design and quality to evaluate the true efficacy of endovascular therapy.     

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke

Background

Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever.

Methods

We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months.

Results

Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months.

Conclusion

Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.     

Impact of Temporary Opening Using a Stent Retriever on Clinical Outcome in Acute Ischemic Stroke

Background

Stent retriever has a distinct ability to restore blood flow temporarily before achieving final reperfusion. There has been a limited report regarding the clinical impact of it. We investigated if temporary opening of occluded vessels using a stent retriever before final reperfusion might improve clinical outcome in acute ischemic stroke patients who received the endovascular reperfusion treatment.

Methods

We enrolled consecutive ischemic stroke patients who had an initial occlusive lesion in the anterior circulation and achieved final reperfusion (Thrombolysis In Cerebral Infarction [TICI] ≥2) by endovascular treatment. Temporary opening was defined as the presence of ante grade flow (TICI≥2) during deployment of a stent retriever. Favorable outcome was defined as a modified Rankin scale score≤2 at 90 day.

Results

A total of 98 patients were included in the study and temporary opening was achieved in 49 (50%). Temporary opening was associated with favorable outcome (odds ratio, 7.825; 95% confidence interval, 1.592–38.461; p = 0.011) in the multivariate analysis. The probability of having a favorable outcome tended to decrease as time from onset to final reperfusion increased in patients without temporary opening. However, this trend was not evident in the patient with temporary opening. The beneficial effect of temporary opening on clinical outcome seemed to be present in patients with good collaterals but not in patients with poor collaterals.

Conclusions

Temporary opening of occluded vessel using a stent retriever may be beneficial for improving clinical outcome in acute ischemic stroke patients.     

Accuracy of Non-Enhanced CT in Detecting Early Ischemic Edema Using Frequency Selective Non-Linear Blending

Purpose

Ischemic brain edema is subtle and hard to detect by computed tomography within the first hours of stroke onset. We hypothesize that non-enhanced CT (NECT) post-processing with frequency-selective non-linear blending (“best contrast”/BC) increases its accuracy in detecting edema and irreversible tissue damage (infarction).

Methods

We retrospectively analyzed the NECT scans of 76 consecutive patients with ischemic stroke (exclusively middle cerebral artery territory—MCA) before and after post-processing with BC both at baseline before reperfusion therapy and at follow-up (5.73±12.74 days after stroke onset) using the Alberta Stroke Program Early CT Score (ASPECTS). We assessed the differences in ASPECTS between unprocessed and post-processed images and calculated sensitivity, specificity, and predictive values of baseline NECT using follow-up CT serving as reference standard for brain infarction.

Results

NECT detected brain tissue hypoattenuation in 35 of 76 patients (46.1%). This number increased to 71 patients (93.4%) after post-processing with BC. Follow-up NECT confirmed brain infarctions in 65 patients (85.5%; p = 0.012). Post-processing increased the sensitivity of NECT for brain infarction from 35/65 (54%) to 65/65 (100%), decreased its specificity from 11/11 (100%) to 7/11 (64%), its positive predictive value (PPV) from 35/35 (100%) to 65/69 (94%) and increased its accuracy 46/76 (61%) to 72/76 (95%).

Conclusions

This post-hoc analysis suggests that post-processing of NECT with BC may increase its sensitivity for ischemic brain damage significantly.