Acute Ischemic Stroke Attack Research Articles

Short Term Changes of Serum Lipids in Acute Ischemic Stroke.

Temporal pattern of lipids changes in stroke patients and its prognostic significance has not yet been fully understood. Our aim was to assess the early temporal changes of lipids in acute ischemic stroke patients and its prognostic significance in predicting stroke outcome. Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were measured at admission, 24 hours, 48 hours, 72 hours, and at discharge. Stroke outcome was assessed by infarct volume, neurological deficit at discharge and 90 days stroke mortality. We have included only patients for whom blood and all clinical data were available at all time points during the follow-up period. In our stroke cohort (n = 52) there was a mean decrease of HDL-cholesterol from admission to discharge (0.32 mmol/L, 23%), accompanied with an increase in triglyceride concentration of 0.3 mmol/L (8%). LDL-cholesterol and total cholesterol had an initial rise at 24 hours, followed by the subsequent fall at 48 hours, 72 hours, and at discharge. Decreased HDL-cholesterol at 48 hours after stroke onset and at discharge is associated with poor patient functional outcome. Patients with large infarct volume had significantly higher concentrations of total cholesterol and LDL-cholesterol at 24 hours, 48 hours, and at discharge than patients with small and medium infarct volume. Early after the onset of acute ischemic stroke there is a marked change in the concentration of serum lipids. Reliable assessment of lipid status cannot be done during the early period after the stroke onset.

Early Use of Statin in Patients Treated with Alteplase for Acute Ischemic Stroke.

Studies have reported that statin usage before stroke can increase the incidence of intracerebral hemorrhage after thrombolytic treatment. However, whether the administration of statin at an early stage of ischemic stroke increases hemorrhage occurrence is unknown. The aim of this study was to assess the effect of statin on neurological imaging and functional outcomes after intravenous alteplase treatment, within 24 h of acute ischemic stroke attack. A total of 119 consecutive acute ischemic stroke patients treated by intravenous alteplase were recruited, of which 71 patients (59.7 %) were given statin therapy within 24 h of stroke onset. The physiological parameters, including demography, vascular risk factors, and clinical characteristics were recorded. The occurrence of intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day functional outcomes, and mortality in the patients were further analyzed. There were 24 occurrences of ICH after alteplase treatment (20.2 %) and there was no difference when patients were treated with statin (p = 0.280). Multivariate logistic regression analysis showed no significant correlation between the administration of statin and the occurrence of ICH (p = 0.230) or sICH (p = 0.949). There was a trend toward better neurological function with higher statin dose. The use of statin in the early stage of ischemic stroke is safe and does not increase the risk of intracerebral hemorrhage after alteplase treatment, suggesting that a clinical trial of early statin treatment on a large scale following thrombolysis is needed for further evaluation.

Brachial-ankle pulse wave velocity and ankle-brachial index are complementary tools for transcranial Doppler ultrasonography in early diagnosis of intracranial arterial stenosis/occlusion in patients with acute ischemic stroke

The aim of this study was to explore whether brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are suitable to serve as complementary tools for TCD in early diagnosis of intracranial arterial stenosis/occlusion in patients with acute ischemic stroke (AIS). A total of 52 patients with AIS onset and 52 age-matched healthy controls were included in this study. All participants received TCD detection, and baPWV and ABI were measured. Computed topography (CT)/magnetic resonance imaging (MRI) was applied to confirm diagnosis. TCD data from all participants was collected and reviewed to diagnose stenosis and occlusion of the major intracranial arteries. Receiver operating characteristic (ROC) analysis and logistic regression analysis were used to assess and compare the diagnostic accuracy of the various diagnostic approaches. We found that a combination of TCD with either baPWV or ABI, or a combination of the three provided a significantly higher area under the curve (AUC) in detecting stenosis or occlusion in various intracranial arteries, excluding the anterior cerebral artery (ACA), when compared to TCD alone, thereby demonstrating that these combined approaches provide improved diagnostic accuracy. In conclusion, our findings suggest that both baPWV and ABI are suitable complementary tools for TCD in early diagnosis of intracranial arterial stenosis/occlusion in AIS patients and that these combinations may assist in facilitating the diagnostic process associated with this disease.

Assessment of Blood–Brain Barrier Disruption in Stroke

The disease burden of acute ischemic stroke (AIS) is rising in the United States and Canada. It is estimated that in the United States 795 000 people have a stroke each year, which amounts to $34 billion in medical expenses and lost productivity.1 Recent trials have shown the potential benefit of procedural thrombectomy in the management of AIS.2 However, despite substantial research expenditures over the past 2 decades, there have been no new pharmacological agents for the initial treatment of AIS since the approval of recombinant tissue-type plasminogen activator in 1996.3 Recently, the role of the blood–brain barrier (BBB) in the pathogenesis of AIS has emerged as a focus for new therapeutic strategies. After the onset of AIS, the BBB is rapidly disrupted and this disruption persists for days through the acute and early subacute phases of AIS. The disruption of the BBB can be quantified as an increase in the permeability of the BBB (Figure 1).4 In the setting of AIS, disruption of the BBB is thought to be a precursor to serious clinical consequences such as hemorrhagic transformation (HT),5–7 which refers to the development of a hemorrhage within the ischemic brain tissue. Current research is attempting to elucidate the mechanisms of BBB disruption after AIS and develop therapeutic strategies to mitigate the clinical consequences of BBB disruption. Figure 1. An illustration of the evolution of blood–brain barrier (BBB) disruption after stroke. The extent of BBB disruption is depicted qualitatively and is based on data gathered at our center. The period during which there is greatest disruption of the BBB coincides with the maximum risk of hemorrhagic transformation. Recombinant tissue-type plasminogen activator (r-tPA) can exacerbate BBB disruption. Given these developments, a greater number of preclinical and clinical studies are incorporating assessment of BBB …

Prognosis of Early-Stage Continuous Electrocardiogram Abnormalities on Patients with Acute Ischemic Stroke

To explore the effects of onset time of electrocardiogram (ECG) abnormalities at an early stage of acute ischemic stroke on patient prognosis. Cardiac dysfunction after stroke is a challenge for clinicians. This is a retrospective study of patients in the neurology departments of 23 hospitals in Shanghai and Wuhan, China. The medical records of 351 patients were compared. Chi-square, Kruskal-Wallis, Mann-Whitney U tests, and stratification compared subgroups. Logistic regressions analyzed factors associated with modified Rankin Scale (mRS) score. ECG abnormalities occurred in 70.1% of patients at an early stage (most were within 48 hours of disease onset) at least once, whereas 45.9% of the patients had ECG abnormalities within 48 hours of onset and at 7 days after onset. The incidence of poor prognosis (mRS >1) was significantly higher in the patients with ECG abnormalities for both time points than that in those with normal ECGs (56.3% versus 32%, odds ratio = 2.166). Most patients demonstrated 1 to 2 ECG abnormalities, and very few patients had 3 or more. Increasing number of ECG abnormalities was mirrored by poorer prognosis. ECG abnormalities occurred within 48 hours and at the seventh day after onset of acute ischemic stroke; the abnormalities that appeared within 48 hours and were still found on the seventh day after onset of the disease were independent predictors of poor patient prognosis. The incidence of abnormal ECGs was high in the patients with acute ischemic stroke, and the abnormal ECGs could appear at any stage of the disease.

A Review of Intra-arterial and Intravenous Therapies for Acute Ischemic Stroke: Relevance, Challenges and Developments

Intravenous and intra-arterial thrombolysis (IVT and IAT, respectively) are the two major therapeutic options for management of acute ischemic stroke (AIS). However, the FDA has only approved IVT for management of AIS, when the patient presents within 0-4.5 hours of AIS onset. This recommendation was based on numerous randomized controlled trials (RCT) which, when analyzed together, showed a net benefit towards the use of IVT. But a narrow therapeutic window, which is rarely met by the individual, and the relative inefficacy of IVT in large artery occlusions, leaves a lot to be desired in the management of AIS. Thus, in these situations, the focus has shifted towards the possibility of using IAT, both pharmacologic and mechanical. Numerous studies have been performed comparing IAT and IVT in treating AIS. None of the major trials found any significant benefit of IAT when compared with IVT. In this review, we compare the efficacy and the relative benefits of both IAT and IVT and discuss the significant findings and limitations of major trials studying these therapies. We suggest that IAT appears as a promising alternative to IVT in specific cases. The lack of benefit observed in major RCTs may have been due to inadequate study designs and execution. Further randomized controlled trials are underway to better understand the role of IAT in AIS.

Symptomatic Intracerebral Hemorrhage after Intravenous Thrombolysis in Chinese Patients: Comparison of Prediction Models

To assess the performance of risk scores in predicting symptomatic intracranial hemorrhage (SICH) after intravenous thrombolysis (IVT). A multicenter prospective study was performed in 811 patients who underwent IVT with standard-dose recombinant tissue plasminogen activator within 4.5hours of acute ischemic stroke (AIS) onset in 67 stroke centers involved in the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China program from May 2007 to April 2012. SEDAN (blood sugar, early infarct signs, [hyper]dense cerebral artery sign, age) score, Safe Implementation of Thrombolysis in Stroke (SITS)-SICH score, Glucose Race Age Sex Pressure Stroke Severity (GRASPS) score, Multicenter Stroke Survey (MSS) score, and Stroke Prognostication using Age and National Institutes of Health Stroke Scale (SPAN)-100 index were calculated in selected patients, and their predictive performance for SICH was compared according to the National Institute of Neurological Disorders and Stroke (NINDS), Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), and European Cooperative Acute Stroke Study (ECASS)-II criteria. For predicting the risk of SICH (NINDS definition) after IVT, the area under the receiver operating characteristic (ROC) curve of MSS score was the highest (.71, P<.0001). For predicting the risk of SICH (SITS-MOST definition) after IVT, the area under the ROC curve of GRASPS score was the highest (.73, P=.005). For predicting SICH (ECASS-II definition) after IVT, the area under the ROC curve of MSS score was the highest (.73, P<.0001). SITS-SICH, GRASPS, and MSS scores predicted the risk of SICH after IVT in patients with AIS, but only the latter 2 were better in the Chinese population. MSS score had the best predictive performance for SICH using NINDS and ECASS-II definitions, whereas GRASPS score was the best for SICH using the SITS-MOST definition.

Abstract T P152: N-terminal Pro-brain Natriuretic Peptide Predicts Short-term Functional Outcome In Acute Ischemic Stroke

Introduction: N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts poor outcome in cardiovascular disease. The prognostic value of NT-proBNP in acute ischemic stroke is limited and remains controversial. We sought to determine whether NT-proBNP at admission were associated with short-term functional outcome after acute ischemic stroke. Methods: We measured fasting serum NT-proBNP in consecutive 357 patients (62.2% men, mean age 65.8±13.0 years) within 3 days after the onset of acute ischemic stroke. Outcomes were measured as 3-month modified Rankin Scale (mRS) score. A good functional outcome was defined as a mRS of 0-2 points, whereas a poor outcome was defined as a mRS of &gt;2 points. Multivariate logistic regression was used to assess association between the clinical and serological parameters including NT-proBNP and mRS scores. Results: The frequency of atrial fibrillation, heart failure, hypertension, and diabetes, the NIHSS score at admission, and the level of NT-proBNP, hs-CRP, creatine kinase-MB and D-dimer were each significantly higher in the poor outcome group (p &lt;0.05). The cut-off values of NT-proBNP level and NIHSS score on admission for prediction of the poor outcome were 183 pg/ml (sensitivity 0.758, specificity 0.756) and 3.5 (sensitivity 0.862, specificity 0.787), respectively. In age- and serum creatinine-adjusted analysis, plasma NT-proBNP levels were significantly correlated with CHADS2 scores (partial r = 0.446, p = 0.009) and CHA2DS2-VASc scores (partial r = 0.347, p = 0.048) in stroke with atrial fibrillation and ejection fraction (partial r = -0.358, p = 0.041) and interventricular septal end diastolic dimension (partial r = 0.371, p = 0.033) on echocardiogram. Multivariate logistic regression analysis demonstrated that age of ≥65 (OR, 7.0; 95% CI, 2.48-19.83, p&lt;0.001), presence of diabetes mellitus (OR, 2.5; 95% CI, 1.09-5.78, p = 0.03), NIHSS score of ≥7 (OR, 18.9 95% CI, 7.84-45.46, p&lt;0.001), NT-proBNP of ≥183 pg/ml (OR, 3.0; 95% CI, 1.20-7.39, p = 0.019) were independently associated with poor functional outcome. Conclusion: Serum NT-proBNP is a useful marker for short-term outcome in acute ischemic stroke. NT-ProBNP may have a role in risk stratification for predicting poor outcome.

Intrathecal Autologous Bone Marrow Derived Mesenchymal Stem Cells for Ischemic Stroke: Short Term Safety and Efficacy Study

Background: Preclinical and animal studies provide considerable hope for stem cell therapy in cerebrovascular stroke. This study was designed as a pilot study to explore this provisional data. Autologous bone marrow derived mesenchymal stem cells were chosen due to their proven angiogenic, paracrine and neuroregenerative functions. Subjects and Methods: The present study included 32 patients with ischemic stroke fulfilling the following criteria: Inclusion Criteria: 1. Patients with established stroke in the distribution of the middle cerebral artery territory. 2. Six months at least after the onset of acute ischemic stroke. 3. CT brain at the onset denoting acute ischemic stroke. Exclusion Criteria: 1. Hemorrhagic stroke. 2. Conditions which mimick stroke,e.g., multiple sclerosis, vasculitis, arteriovenous malformations, trauma, tumours. Patients were randomly divided into control group (11 patients) and study group (21 patients) which was further divided according to the time between the onset of the stroke and the beginning of the study into: Group I : onset of the stroke and the beginning of the study :6-12 months( 12 patients: 6 males and 6 females). Group II: onset of stroke and the beginning of the study :13-36 months (9 patients: 5 males and 4 females). Control Group: 11 stroke patients : 6 males and 5 females. Time from onset of stroke to beginning of the study ranged from 6-30 months. Both study and control group were subjected to thorough clinical and laboratory assessment , CT brain, National institutes of Health Stroke Scale (NIHSS) and th Barthel active daily life (ADL) scale at the start of therapy, and at 1,3,6 and 12 months after the start of therapy. Stem Cell Injection: 10 million autologous bone marrow-derived MSCs were injected via lumbar puncture in the study group. Results and Conclusions: Changes in Follow-up Parameters: 1. Changes in NIHSS score: Control group showed non-significant decrease in NIHSS score starting from the 3rd month. On the other hand, study group showed highly significant decrease in NIHSS score starting from 6th month, more in group I. 2. Changes in ADL score: ADL score showed non-significant increase starting from 3rd month in the control group, while it showed a highly significant increase in the study group starting from 6th month, more pronounced in group I. Intrathecal administration of MSCs is safe and enhances regeneration in ischemic stroke patients.

Serum matrix metalloproteinase-9 in acute ischemic stroke and its relation to stroke severity

Background Thrombolytic therapy is currently the only FDA-approved treatment for acute ischemic stroke. Hence, early diagnosis and risk stratification is of great importance in management. Objective The aim of this work was to study serum level of matrix metalloproteinase-9 (MMP-9) within 24 h of acute ischemic stroke onset and its relation with clinical severity. Patients and methods Thirty patients with acute ischemic stroke were subjected to measurement of serum MMP-9 within 24 h of stroke onset and clinical assessment of stroke severity. Thirty healthy volunteers of matched age and sex were included as controls. Results Fifteen male and 15 female patients with a mean age of 61 ± 7.11 years were studied. The mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 11.17 ± 4.76. The mean serum level of MMP-9 in patients was 998.8 ± 154.72 ng/ml, which was significantly higher compared with the serum level of MMP-9 in controls ( P = 0.003). The mean NIHSS of patients with normal serum level of MMP-9 was less than the mean NIHSS in patients with high MMP-9 serum levels ( P = 0.003). There was a significant positive correlation between serum level of MMP-9 and NIHSS score ( r = 0.5; P = 0.005) even after adjustment of other variables )age, sex, diabetes, hypertension, fasting blood sugar, uric acid, serum triglycerides, serum cholesterol, and right and left carotid intima media thickness( ( r = 0.48; P = 0.032). Conclusion Serum MMP-9 level was found to be high in acute ischemic stroke patients and correlated with clinical stroke severity.

Timing of tissue plasminogen activator for acute ischemic stroke: outcomes-based recommendations for practice.

Acute ischemic stroke (AIS) is a major cause of death and disability in the United States. Tissue plasminogen activator (t-PA) is an intravenously administered therapy that can prevent death and disability for patients presenting within early onset of AIS. There has been a debate around the exact time parameters for administration, because very few patients present to the hospital within the initial 0- to 3-hour window of time. Not all of the current national guidelines for timing of AIS in the United States are in agreement with regards to this issue. To the nurse caring for patients with neurologic illnesses, this topic is of utmost importance. Nurse are not only involved in determining the time of stroke symptom onset, but nurses also hold responsibility for a working knowledge of the latest eligibility and exclusion criteria for t-PA administration. This article examines the central body of research related to the timing of t-PA and makes recommendations for eligible candidates based on this literature.

Direct catheter-based thrombectomy in acute ischaemic stroke performed collaboratively by cardiologists, neurologists and radiologists: the single-centre pilot experience (PRAGUE-16 study).

To assess the feasibility of direct catheter-based thrombectomy (d-CBT) performed jointly by cardiologists, neurologists and radiologists. Computed tomography (CT) was completed within <6 hours from onset of acute ischaemic stroke and excluded bleeding or developed ischaemia in 23 patients who fulfilled pre-specified entry criteria. The mean NIHSS was 17 (8-24). Mechanical recanalisation was successful in 19/23 patients (83%). The mean symptom onset – CT time was 81 min, CT – sheath insertion 47 min, sheath – reperfusion 46 min. Three patients died within 30 days, two others within 90 days (overall three-month mortality 22%). The mean mRs at 90 days for the entire group was 3.19, among survivors 2.31 and among survivors treated within <120 minutes 1.17. Favourable functional outcome (mRs ≤2) was achieved in 48% of patients. Five patients (22%) had full (mRs=0) or nearly full (mRs=1) neurologic recovery. Seven patients were able to be discharged from neurology ICU directly home after a short (<7 days) hospital stay. Two patients had symptomatic intracranial haemorrhage. Acute stroke treatment by d-CBT jointly by neurologists, cardiologists and radiologists provided promising results especially in patients reaching the cathlab within <2 hours from stroke onset.

Thrombolysis for Acute Ischaemic Stroke with Alteplase in an Asian Population: Results of the Multicenter, Multinational Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW)

Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe Implementation of Thrombolysis in Stroke-Non-European Union World was required to assess the safety of alteplase in an Asian population by comparison with results from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study and pooled results from randomized controlled trials. To evaluate the efficacy and safety of intravenous alteplase (0·9 mg/kg) as thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an Asian population. The 591 patients included were treated at 48 centers in four countries (South Korea, China, India, and Singapore) between 2006 and 2008. Primary outcomes were symptomatic (deterioration in National Institutes of Health Stroke Scale score ≥4 or death within the first 24 h) intracerebral haemorrhage type 2 22-36 h after the thrombolysis and mortality at three-month follow-up. The secondary outcome was functional independence (modified Rankin Scale score 0-2) at three-months. Results were compared with those from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (n = 6483) and pooled results of patients (n = 415) who received intravenous alteplase (0·9 mg/kg) zero- to three-hours from onset of stroke symptoms in four randomized controlled trials (National Institute of Neurological Disorders and Stroke A and B, Altephase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke, and European Cooperative Acute Stroke Study II). Results are presented as Safe Implementation of Thrombolysis in Stroke-Non-European Union World vs. Safe Implementation of Thrombolysis in Stroke-Monitoring Study vs. pooled randomized controlled trials. Median age was 64 vs. 68 vs. 70 years, National Institutes of Health Stroke Scale score at baseline was 12 vs. 12 vs. 13, time from stroke onset to treatment was 130 vs. 140 vs. 135 mins, and females were 36·4% vs. 39·8% vs. 41·2%. Main outcomes (proportion of patients and 95% confidence intervals) were symptomatic intracerebral haemorrhage: 1·9% (1·1-3·3) vs. 1·7% (1·4-2·0) vs. 3·1% (1·8-5·3); mortality: 10·2% (8·0-12·9) vs. 11·3% (10·5-12·1) vs. 16·4% (13·1-20·3); and functional independence: 62·5% (58·5-66·4) vs. 54·8% (53·5-56·0) vs. 50·1% (45·3-54·9) at three-months. Adjusted odds ratio (95% confidence intervals) between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and Safe Implementation of Thrombolysis in Stroke-Monitoring Study, and between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and the pooled trials were 1·83 (0·89-3·77; P = 0·1156) and 0·63 (0·19-2·07; P = 0·4470) for symptomatic intracerebral haemorrhage, 0·90 (0·64-1·25; P = 0·5092) and 0·93 (0·52-1·64; P = 0·7915) for mortality at three-months, and 1·57 (1·25-1·96; P < 0·0001) and 1·35 (0·91-2·00; P = 0·1325) for functional independence. These data demonstrate the safety and efficacy of the standard dose of intravenous alteplase (0·9 mg/kg) in an Asian population, as previously observed in the European population studied in Safe Implementation of Thrombolysis in Stroke-Monitoring Study and the populations in pooled randomized controlled trials, when used in routine clinical practice within three-hours of stroke onset. The findings should encourage wider use of thrombolytic therapy in Asian countries for suitable patients treated in stroke centers.

Cost-effectiveness of recombinant tissue-type plasminogen activator within 3 hours of acute ischemic stroke: current evidence.

Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA. A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies. Cost data, inflated to 2013 dollars, were based on drug wholesale acquisition cost and the literature. To compare r-tPA to no r-tPA, we calculated incremental total direct costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratios. We performed 1-way and probabilistic sensitivity analyses to evaluate uncertainty in the results. r-tPA resulted in a gain of 0.39 quality-adjusted life years (95% confidence range, 0.16-0.66) on average per patient and a lifetime cost-saving of $25,000 (95% confidence range, -$42,500 to -$11,000) compared with no r-tPA. In probabilistic sensitivity analyses, r-tPA was dominant compared with no r-tPA in ≈100% of simulations. The model was sensitive to inputs for r-tPA efficacy, healthcare costs for disabled patients, mortality rates for disabled and nondisabled patients, and quality of life estimates. Our analysis supports earlier economic evaluations that r-tPA is a cost-effective method to treat stroke. Appropriate use of r-tPA should be prioritized nationally.

Abstract T MP9: Analysis of MR RESCUE Dataset Employing DEFUSE 2 Target Mismatch Criteria for Defining Penumbra

Background: The MR RESCUE trial failed to show a benefit of endovascular therapy over standard medical care for first generation thrombectomy devices within 8 hours of onset of acute ischemic stroke. We now report a subset analysis of patients enrolled with MRI, employing DEFUSE 2 criteria to define favorable penumbral pattern (target mismatch) which differed from MR RESCUE penumbral prediction criteria. Methods: Patients with large vessel, anterior circulation strokes were randomized to mechanical embolectomy (Merci Retriever or Penumbra System) or standard care. Patients were categorized as having a favorable penumbral or non-penumbral pattern employing the DEFUSE 2 criteria for target mismatch ([Tmax &gt; 6s / thresholded ADC &lt; 600 х 10 −6 mm 2 /s] &gt; 1.8, thresholded ADC &lt; 70 cc, and Tmax &gt; 10 s &lt; 100 cc). Results: Among 118 total patients, 94 qualified for this analysis. Mean age was 65.8, mean time to enrollment 5.6 hours, median NIHSS 17, and 47% had target mismatch. Predicted core volume using DEFUSE 2 criteria (thresholded ADC volume &lt; 600 х 10 −6 mm 2 /s) was 18.8 cc (target mismatch) and 64.3 cc (non-target mismatch; p&lt;0.001). Revascularization in the embolectomy group was achieved in 62% (TICI 2a-3), and 21% (TICI 2b-3). Among all patients, mean 90-day mRS scores did not differ between embolectomy and standard care (3.8 vs 3.8; p=0.92). In patients with target mismatch, embolectomy was not superior to standard care (mean mRS 3.5 vs 3.3, p=0.78). Similarly, in patients without target mismatch, embolectomy was not superior (4.1 vs 4.3, p=0.67). Furthermore, there was no interaction between pretreatment penumbral imaging pattern employing DEFUSE 2 target mismatch criteria and treatment assignment in these 90-day mRS scores (p=0.11). Conclusions: In this analysis MR RESCUE patients enrolled with pretreatment MRI, use of the DEFUSE 2 criteria for target mismatch as a definition of penumbral pattern failed to identify a subset of patients with improved outcomes when treated with embolectomy. Further randomized, controlled studies employing new generation thrombectomy devices are needed to validate target mismatch as a selection criterion for acute stroke treatments.

Abstract T MP98: Guideline-directed LDL Management Prior to Onset of Acute Ischemic Stroke in Patients with and Without Pre-existing Cardiovascular Disease: Findings from GWTG-stroke

Context: Limited information is available whether high risk patients had achieved guideline-directed LDL goals prior to presenting with an acute ischemic stroke. Objective: To evaluate differences in the attainment of current LDL guidelines, based on admission LDL testing, in patients with acute ischemic stroke. Methods: Observational study, using data from the AHA-Get With The Guidelines Registry including 913,436 patients with an acute ischemic stroke or transient ischemic attack from April 2003 to September 2012. Participants were classified as high risk if they had prior history of TIA, stroke, and/or coronary artery disease (CAD). We used a previously created algorithm to determine the pre-stroke NCEP ATP-III goal. Results: Of the 913,436 patients admitted with an acute stroke or TIA, 283,162 (31.0%) had prior stroke/TIA, and 148,833 (16.3%) had prior CAD. Overall, only 68% of stroke patients were at their pre-admission NCEP III guideline-recommended LDL target on admission testing; 51.3% had LDL &lt;100 mg/dL and only 19.8% had LDL100 mg/dL. Compared to patients with CAD, patients with prior TIA/Stroke were less likely to have LDL &lt;100 mg/dL or &lt;70 mg/dL (Table 1). In multivariable analysis, older age, male, white race, lack of major vascular risk factors, prior use of cholesterol-lowering therapy, and care provided in larger hospitals or West/Midwest hospitals were associated with meeting NCEP III LDL targets on admission testing. Conclusion: Current management of dyslipidemia in high risk patients with pre-existent CAD or stroke continues to be suboptimal. Only one in four patients with prior TIA/Stroke have LDL levels at the strict target &lt;70 mg/dL.

Abstract T P130: Determinants of White Matter Hyperintensity Burden Differ at the Extremes of Age of Ischemic Stroke Onset

Background: White matter hyperintensity (WMH) detected on MRI scans of patients with acute ischemic stroke (AIS) is associated with greater risk of infarct progression, poor post-stroke outcomes, and recurrent stroke. Age is strongly linked to risk of stroke and WMH. We hypothesized that determinants of WMH severity differ across the lifetime and sought to test it in a prospective cohort of AIS patients with early (&lt;55 years), late (&gt;75 years) versus average age of stroke onset. Methods: Clinical characteristics as well as laboratory and radiographic data were ascertained on admission for AIS in all consecutive patients ≥ 18 years. WMH volume (WMHv) was measured using a previously validated, semi-automated method, normalized for intracranial area, and natural log-transformed for univariate and multivariate linear regression analyses. Results: Of 754 AIS patients, 175 (23.2%) developed early-onset (mean age 46.4 ± 7.5 years) and 237 (31.4%) late-onset (mean age 82.1 ± 5.2 years) stroke. Median WMHv differed between the early-onset AIS (2.4cc, IQR 1.6 - 4.5), late-onset AIS (11cc, IQR 5.8 - 23.2) and average-age-of-onset stroke patients (mean age 65.6 ± 5.8 years, median WMHv 6.4cc, IQR 3.2 - 13.0). In univariate analysis, WMHv burden was associated with age (p = 0.03) and history of tobacco use (p = 6.6E-3) in early-onset AIS, with gender (p = 0.03) in late-onset AIS, versus age (p = 1.8E-8) and hyperlipidemia (p = 0.045) in average-age-of-onset AIS. Although backward stepwise selection confirmed male gender (ß = -0.26, p = 0.04) in late-onset AIS patients as well as age (ß = 0.05, p = 3.9E-8) and hyperlipidemia (ß = -0.26, p = 0.02) in patients with average age of AIS onset as predictors of WMHv, only tobacco use (ß = 0.35, p = 8.8E-3) remained an independent predictor of WMHv severity in early-onset AIS patients. Conclusions: Phenotypic determinants of WMH severity in AIS patients differ at the extremes of age of stroke onset, including a strong link between tobacco use in patients with early-onset stroke and burden of small cerebral vessel disease. While age remains a major risk factor for WMH, modifiable determinants - such as smoking - should be targeted in the future to reduce WMH and mitigate stroke risk in each age group.

Neuronal and glia-related biomarkers in cerebrospinal fluid of patients with acute ischemic stroke.

BACKGROUNDCerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML).METHODSA total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed.RESULTSPatients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test).CONCLUSIONSSeveral CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

Correlative study of serum cystatin C levels with severity of acute ischemic stroke.

Background: The attractiveness of cystatin C as a biomarker for acute ischemic stroke is obvious, in the background of accumulating evidence indicating a link between vascular disease of the kidney and brain. We investigated the association of serum cystatin C levels with first onset acute ischemic stroke and the correlation of serum cystatin C levels with severity of acute ischemic stroke as assessed by NIH stroke scale. Methods: A total of 50 patients with first onset of acute ischemic stroke, aged more than 45 years, presenting within 72 hours after onset, by interview, history, clinical examination, neuroimaging and other investigations. Serum Cystatin C was measured by means of a particle-enhanced immunenephelometric assay (N Latex Cystatin C) with a nephelometer (Siemens BN Prospec). Results: Serum cystatin C levels were significantly raised in 62% (n=31) patients of acute ischemic stroke compared with controls 14% (n=7), with a p < 0.001. Compared with controls, the mean serum cystatin C level was significantly higher in stroke patients (1.33±0.71 versus 0.83±0.24 mg / L, p < 0.001). The diagnostic accuracy of serum cystatin C as a marker of acute ischemic stroke evaluated using Receiver Operating Characteristic (ROC) curve analysis, showed a sensitivity of 66.00 and specificity of 84.00 with an area under curve of 0.80 (and 95 % CI (0.71 - 0.87)). Conclusion: Serum cystatin C was a better marker for acute ischemic stroke and indicator of severe neurological impairment. Key words: Acute ischemic stroke, Cystatin C, NIH Stroke scale.

A Prospective Study of the Incidence and Correlated Factors of Post-Stroke Depression in China

BackgroundPost-stroke depression (PSD) is commonly observed among stroke survivors. However, statistical analysis of such data is scarce in developing countries. The purpose of this study is to examine the incidence of PSD and its relationship with stroke characteristics in China.MethodsThis was a prospective hospital-based study. Stroke patients were assessed within two weeks after acute ischemic stroke onset and then reevaluated at three months. Hamilton Depression Scale (HAMD) was used for screening depression (PSD). Subjects with HAMD score of ≥7 were further assessed with the World Health Organization Composite International Diagnostic Interview. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). Stroke outcome was measured by the modified Rankin Scale (mRS).ResultsOne hundred and two stroke patients were recruited, only ninety-one patients completed del period (men = 53, 63.74%), with mean age 60.0±10.4 years (range, 34–82 years). The incidence of PSD was 27.47% two weeks after stroke. The occurrence of PSD was unrelated with age, stroke type, stroke lesion and the history of disease. In univariate analysis gender, PSD was correlated with female gender. In multivariate logistic regression analysis, poor stroke outcome (mRS≥3) (OR 12.113, CI 1.169 to 125.59, P<0.05) was the important predictors of PSD.ConclusionsThe study indicated that gender, functional dependence and stroke outcome are determinants of PSD occurrence during the first 2 weeks after stroke in China.