Albumin-Induced Neuroprotection in Focal Cerebral Ischemia in the ALIAS Trial: Does Severity,Mechanism, and Time of Infusion Matter?

Objective

To determine whether there is any differential benefit of albumin administration within 2 h of onset of ischemia and in settings (severe ischemia with reperfusion in cardioembolic strokes with National Institutes of Health Stroke Scale [NIHSS] ≥15), most representative of experimental models of cerebral ischemia in which albumin was effective in reducing neurological injury.

Background

High-dose intravenous (IV) albumin treatment for acute ischemic stroke (ALIAS) trial did not show overall clinical benefit in ischemic stroke patients in contrast to preclinical studies; however, models of preclinical studies were not completely followed.

Methods

A total of 1275 patients combined from ALIAS trials I and II were included in our analysis. We analyzed preclinical studies and selected patients with large ischemic stroke (NIHSS ≥15) related to cardioembolic etiology (n = 189). Outcomes were then studied including time from onset to IV albumin administration.

Results

The odds of excellent outcome (mRS 0–1) at 3 months was not different with high-dose IV albumin infusion (n = 100) compared with placebo (n = 89) ((odds ratio [OR]) 1.632 [0.719–3.708], p value 0.2419). When we further classified these subjects according to time of IV albumin administration, we observed significantly higher odds of excellent outcome at 3 months when patients received IV albumin within 2 h, OR 9.369 (CI 1.040–84.405), p value 0.0461, after adjusting for age, gender, baseline NIHSS score, and any therapeutic procedure.

Conclusion

A trend for benefit is noted in ischemic stroke patients with large cardioembolic stroke (NIHSS ≥15) when high-dose albumin was initiated within 2 h, suggesting that certain ischemic stroke subgroups of patients most representative of preclinical settings may benefit from such a treatment. Additional clinical trials maybe needed to stratify subjects and treatment assignments according to NIHSS severity and timely randomization to evaluate this concept further.

     

TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis

Background and Purpose

Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema.

Methods

We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC).

Results

Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63–0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61–0.73).

Conclusions

Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.

     

Association of post stroke depression with social factors,insomnia, and neurological status in Chinese elderly population

The purpose of this study was to investigate the association of post stroke depression (PSD) with social factors, insomnia, and neurological status among elderly Chinese patients with ischemic stroke. Six hundred and eight patients over 60 years of age, who had suffered from a first episode of ischemic stroke within 7 days, were enrolled into the study. They were divided into PSD and non-PSD groups according to the Self-rating Depression Scale (SDS) scores. The association of PSD with social factors, insomnia, and neurological status was analyzed using multivariable logistic regression analysis. Compared with the patients who did not develop PSD, those with PSD reported adverse life events more frequently, and more subjects with PSD lived alone, had left carotid artery infarction and cortical infarction (P < 0.05), history of insomnia, and high National Institute of Health Stroke Scale (NIHSS) scores and low Barthel Index (BI) scores (P < 0.01). The multivariable logistic regression analysis showed that the occurrence of PSD was associated with a history of insomnia (HR = 1.59, 95 % CI 1.12–2.36, P < 0.01), NIHSS scores (HR = 2.45, 95 % CI 1.42–3.91, P < 0.01) and BI scores (HR = 2.56, 95 % CI 1.39–4.25, P < 0.01). Insomnia and the degree of neurological deficit were associated with PSD in an elderly population of Chinese people.     

Lymphocyte-to-monocyte ratio on day 7 is associated with outcomes in acute ischemic stroke

The main features of stroke-induced immunosuppression are lymphopenia and deactivation of monocytes in peripheral blood. We hypothesized that lymphocyte-to-monocyte ratio (LMR) in peripheral blood may represent the degree of stroke-induced immunosuppression. To prove this hypothesis, we evaluated whether LMR is associated with risk of post-stroke infection and clinical outcome at 3 months in patients with acute ischemic stroke. We selected patients with stroke in anterior circulation within 24 h from onset. Peripheral blood sampling for differential blood count was performed on days 1 and 7. The LMRs on days 1 and 7 were analyzed to determine associations with excellent outcomes (modified Rankin Scale of score 0–1 at 3 months). One hundred and two patients were included. The initial National Institutes of Health Stroke Scale score (adjusted odd ratio [OR] 0.89; 95% confidence interval [CI], 0.83–0.95; P = 0.001) and LMR on day 7 (adjusted OR 1.49; 95% CI, 1.09–2.02; P = 0.011) were associated with excellent outcomes. LMRs on day 1 were significantly lower in stroke patients with pneumonia (P = 0.007) and pneumonia or urinary tract infection (P = 0.012) than those without infections. LMRs on day 7 were also significantly lower in stroke patients with infection (P = 0.005 in pneumonia, P = 0.003 in urinary tract infection, and P < 0.001 in pneumonia or urinary tract infection) than those without infections. Lower LMRs on day 7 are associated with worse outcomes at 3 months after stroke onset. LMR may be a useful marker for assessing the stroke-induced immunosuppression.     

Impact of D-dimer levels for short-term or long-term outcomes in cryptogenic stroke patients

Background

D-dimer levels are used in several clinical settings, such as in predicting venous thrombosis, cardioembolic stroke and cancer status. In the present study, we investigated the associations between plasma D-dimer levels at admission, clinical characteristics and mortality at discharge in cryptogenic stroke patients. We also investigated whether D-dimer levels can predict long-term outcomes in those patients, including those with and without right-to-left shunt (RLS).

Methods

Acute cryptogenic stroke patients (n = 295, 72 ± 13 years old) were consecutively enrolled and retrospectively analyzed. We defined the cryptogenic stroke as an undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Plasma D-dimer levels at admission were evaluated. Assessments for RLS were performed using saline contrast-transcranial Doppler ultrasonography or contrast-transesophageal echography. Survivors (at discharge) underwent follow-up for up to 3 years after stroke onset.

Results

Of the total enrolled cohort, 17 patients died at discharge. D-dimer levels correlated with initial National Institutes of Health Stroke Scale (NIHSS) score (r = 0.391, P < 0.001) and were associated with mortality at discharge [odds ratio 1.04; 95% confidence interval (CI) 1.00–1.08, P = 0.049] after adjusting for age, sex and initial NIHSS score. Of the 278 survivors at discharge, 266 patients were evaluated to assess RLS during hospitalization, and 62 patients (23.3%) exhibited RLS. According to the median plasma D-dimer levels at admission (0.7 µg/ml), the patients were divided into a low D-dimer group (n = 136, < median) and a high D-dimer group (n = 130, ≥ median). Patients in the high D-dimer group were older, more frequently female, had a lower BMI, had a higher prevalence of cancer and had greater initial neurological severity compared to the patients in the low D-dimer group. During the follow-up period (median, 1093 days), 31 patients developed recurrent stroke and 33 patients died. High D-dimer levels at admission were independently associated with recurrent stroke and all-cause mortality [hazard ratio (HR) 3.76; 95% CI 1.21–14.1, P = 0.021) in patients with RLS, but not in those without RLS (HR 1.35; 95% CI 0.74–2.50, P = 0.335).

Conclusions

Increased D-dimer levels at admission were associated with mortality at discharge in cryptogenic stroke patients. In addition, high D-dimer levels were also associated with long-term outcomes in cryptogenic stroke patients with RLS.

     

Relation between lipoprotein-associated phospholipase A<Subscript>2</Subscript> mass and incident ischemic stroke severity

Background

Manifestations of ischemic stroke vary widely, and serum biomarkers may be useful for stratification of risk of severe stroke. This study evaluated the association of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) mass and initial severity.

Methods

We employed a retrospective analysis on our hospital-based registry and recruited 488 first-onset ischemic stroke patients admitted within 24 h after onset and with Lp-PLA₂ mass measured. Stroke severities evaluated by National Institutes of Health Stroke Scale (NIHSS) were compared between Lp-PLA₂ categories dichotomized by median. Multivariate logistic regression was used to detect the independent risk factors of severe stroke (NIHSS ≥?7) and receiver operator curve (ROC) was constructed to detect the value of addition of Lp-PLA₂ to the model of other risk factors for predicting severe stroke.

Results

Of the overall patients, the median admission NIHSS scores was 3 and 28.1% had severe manifestation. Admission NIHSS scores were different between patients of Lp-PLA₂ above and under the median (median NIHSS 4 vs. 3, P?<?0.001). Lp-PLA₂ levels was correlated with admission NIHSS (r?=?0.268, P?<?0.001). Logistic regression showed Lp-PLA₂ category (OR 2.37, 95%CI 1.44–3.90, P?<?0.001) and levels per 100 ng/ml (OR 1.69, 95%CI 1.35–2.11, P?<?0.001) were both independently associated with severe stroke. Addition of Lp-PLA₂ category and levels to other independent risk factors both increased the area under curves (from 0.676 to 0.718 with category and 0.734 with levels).

Conclusion

Lp-PLA2 was independently related to admission severity in ischemic stroke patients, implying a potential predictive value of Lp-PLA2 for severe stroke in prevention.

     

Role of <Emphasis Type="Italic">TLR4</Emphasis> (C1196T) and <Emphasis Type="Italic">CD14</Emphasis> (C-260T) Polymorphisms in Development of Ischemic Stroke,Its Subtypes and Hemorrhagic Stroke

In the present study, we evaluated the association of TLR4 and CD14 polymorphisms, i.e. C1196T and C-260T, respectively, with ischemic stroke (n = 700), its subtypes and hemorrhagic stroke (n = 300) in a South Indian population from Telangana. The genotypes were determined using PCR–RFLP, and the strength of association between genotypes and stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. The results revealed a lack of association for TLR4 variant with ischemic stroke and hemorrhagic stroke, although a significant association was observed with the subtypes extracranial large artery (p = 0.008), other determined aetiology (p = 0.03) and undetermined aetiology (p = 0.01). Investigations on the variant of CD14 gene revealed negative association among ischemic stroke patients; however, a significant association was observed for hemorrhagic stroke following dominant and recessive genotypic model (p = 0.05, p = 0.02). Among ischemic stroke subtype, a significant association was observed with intracranial large artery, extracranial large artery, other determined aetiology and undetermined aetiology form of stroke (p < 0.01). Further, analysis of the CD14 variant between the two major stroke types revealed a significant difference in genotype distribution following the co-dominant genotypic model (p = 0.01).     

The importance of atrial fibrillation and selected echocardiographic parameters for the effectiveness and safety of thrombolytic therapy in patients with stroke

Background

The efficacy and safety of thrombolytic therapy in stroke depend on multiple factors. The aim of this study was to evaluate the significance of atrial fibrillation the prognosis in terms of the functional status in patients with stroke treated with intravenous thrombolysis. An additional aim was also to assess the potential significance of reduced ejection fraction (EF) and enlarged left atrium (LA) of the heart for the prognosis in patients with stroke who underwent thrombolytic therapy.

Safety outcomes of Alteplase among acute ischemic stroke patients with special characteristics

Background

Although tissue plasminogen activator (tPA) has been approved for use in acute ischemic stroke, concerns linger regarding its safety. We analyzed whether patients in special subgroups (i.e., age >70 years, baseline National Institute of Health Stroke Scale (NIHSS) score >20, diabetes, congestive heart failure (CHF), and of Hispanic origin) have a higher risk of symptomatic intracerebral hemorrhage (SICH) than patients without these characteristics.

Methods

Four prospective observational studies of acute ischemic stroke patients treated within 3 h with Alteplase were identified and individual patient data were pooled for this analysis. These included the Standard Treatment with Alteplase to Reverse Stroke Study [STARS, N = 389], Epidemiology Study of Ischemic Stroke [ESIS, N = 236], University Of Texas Houston Stroke Study [UT, N = 241], and Canadian Activase For Stroke Effectiveness Study [CASES, N = 1100]. The risk of SICH was calculated for all patients and for each of five subgroups.

Results

A total of 1966 patients were studied. Overall the risk of symptomatic ICH was 4.7% (95%CI, 3.8–5.8%) and the risk was similar among patients with and without each of the five characteristics. Patients with advanced age, baseline NIHSS score >20, CHF or diabetes had increased mortality and significantly lower rate of functional recovery.

Conclusions

The present study suggests that these specified subgroups of patients are not at increased risk of SICH after stroke thrombolysis compared to those without these characteristics.     

Endovascular vs. medical therapy in symptomatic vertebral artery stenosis: a meta-analysis

This meta-analysis aims to compare percutaneous transluminal angioplasty (PTA) to medical treatment (MT) for symptomatic vertebral artery stenosis (SVAS) treatment. We searched PubMed, Springer, Google Scholar, Clinical Trials, Cochrane Central, Chinese National Knowledge Infrastructure, and China Biological Medicine databases. All relevant comparative trials were included. All summary estimates were calculated by random-effect models. Ten comparative trials involving 672 patients were identified. Within 30-day follow-up, there was no significant difference between PTA plus MT and MT alone in vascular death, any stroke, posterior circulation TIA, posterior circulation infarction, and ischemic stroke (all P > 0.05). With a follow-up of more than 1 year, no significant difference was found between PTA plus MT and MT alone in all-cause death (3 vs. 7 %, P = 0.24), vascular death (4 vs. 7 %, P = 0.34), posterior circulation stroke (5 vs. 8 %, P = 0.48), posterior circulation ischemic events (8 vs. 25 %, P = 0.23), posterior circulation TIA (10 vs. 38 %, P = 0.11), posterior circulation infarction (6 vs. 12 %, P = 0.51), vertebral artery occlusion (6 vs. 12 %, P = 0.58), and in secondary long-term events, including any stroke, anterior circulation stroke, hemorrhagic stroke, and myocardial infarction (all P > 0.05), although PTA plus MT could largely reduce the vertebral artery stenosis rate [MD 63.05 %, 95 % CI (32.77–93.34 %), P < 0.01]. Hence, PTA plus MT may be not superior to MT alone for SVAS treatment. Larger randomized trials are needed to verify the optimum therapy for SVAS.     

Metabolic syndrome is associated with increased risk of short-term post-procedural complications after carotid artery stenting

The risk factors for post-procedural events after carotid artery stenting (CAS) have not been well established. The aim of this study was to investigate the association between metabolic syndrome (MetS) and the risk of post-CAS complications. A total of 358 consecutive patients who underwent CAS were enrolled in this prospective study. Patients’ demographic data, clinical characteristics, and complications after CAS within 30 days were recorded. Logistic regression analysis was performed to identify possible risk factors for post-procedural complications after CAS. The incidence of complications after CAS within 30 days was 7.0%. Logistic regression analysis identified the following as independent risk factors for 30-day transient ischemic attacks, stroke, myocardial infarction, and death after CAS: metabolic syndrome (OR = 2.31, 95% CI 1.91–3.01, P = 0.004), diabetes (OR = 2.24, 95% CI 1.74–2.76, P = 0.026), symptomatic patient (OR = 1.73, 95% CI 1.23–3.05, P = 0.011), and age (OR = 1.87, 95% CI 1.35–2.57, P = 0.042). Among the components of MetS, central obesity (OR = 2.21, 95% CI 1.24–2.63, P = 0.006), low high-density lipoprotein cholesterol (HDL-C) (OR = 1.66, 95% CI 1.34–2.27, P = 0.022), and high fasting plasma glucose (OR = 2.32, 95% CI 1.85–2.74, P = 0.003) were associated with increased risk of 30-day complications after CAS. This present study suggests that patients with metabolic syndrome have significantly increased risk of complications after CAS within 30 days. Moreover, MetS patients with central obesity, high fasting plasma glucose, or low HDL-C have significantly increased risk of complications after CAS within 30 days.     

Risk of Venous Thromboembolism in Patients with Large Hemispheric Infarction Undergoing Decompressive Hemicraniectomy

Background

Deep-venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute ischemic stroke. This study is the first to examine the risk of venous thromboembolism in patients with large hemispheric infarction undergoing decompressive hemicraniectomy.

Methods

The study population included 95 consecutive patients with a large hemispheric infarction who underwent decompressive hemicraniectomy between 2006 and 2014 at our institution. All patients received prophylactic unfractionated heparin and intermittent compression devices (SCD). Patients were systematically screened for DVT at 5-day interval using Duplex ultrasound. PE was diagnosed on chest CT angiography.

Results

Mean age was 57 ± 12 years; mean BMI was 28.3 ± 7.4 kg/m². 30.5 % of patients had infarction in the dominant hemisphere and 69.5 % in the non-dominant hemisphere. The mean NIHSS score was 16.0 ± 5 at admission. The mean length of stay was 22 ± 17 days. 35 % of patients developed a DVT including 27 % who developed above-knee DVT and required placement of an inferior vena cava filter. In multivariable analysis, predictors of DVT were an NIHSS ≥ 17 (p = 0.007), seizures (p = 0.003), hypertension (p = 0.03), and increasing length of stay (p = 0.01). The proportion of patients who developed PE was 13 %. In multivariate analysis, BMI ≥ 30 predicted PE (p = 0.05).

Conclusions

The rate of DVT and PE is remarkably high in patients with large hemispheric infarction undergoing decompressive hemicraniectomy despite prophylactic measures. We recommend routine screening for DVT in this population. Interventions beyond the standard prophylactic measures may be necessary in this high-risk group.

     

Impact of TLR5 rs5744174 on stroke risk,gene expression and on inflammatory cytokines,and lipid levels in stroke patients

Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case–control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real-time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFα were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: β = ? 0.14, 95 % CI: ?0.24 to ?0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population.     

Leukoaraiosis is a predictor of futile recanalization in acute ischemic stroke

Futile recanalization occurs when successful recanalization fails to improve clinical outcome in acute ischemic stroke patients. Predictors of futile recanalization are still debated and may help in selecting patients for reperfusion strategies. We aim to determine whether leukoaraiosis may be useful in predicting futile recanalization in acute ischemic stroke patients treated by endovascular mechanical thrombectomy. We included in the analysis patients with acute ischemic stroke due to anterior circulation large vessel occlusion undergoing endovascular mechanical thrombectomy obtaining complete vessel recanalization. Demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale score, time from symptoms onset to recanalization, Alberta Stroke Program Early CT Score, and leukoaraiosis graded on a 4-point van Swieten scale were collected. We dichotomized patients into those with moderate–severe leukoaraiosis (2–4) versus those with absent-slight leukoaraiosis (0, 1). Outcome measures were symptomatic intracranial hemorrhage, and modified Rankin scale score at 90 days. The relationships among radiological parameters and clinical data with outcome measures were studied with univariate and multivariable analyses. Sixty-eight patients were identified. Recanalization was futile in 32.4% of cases. On multivariable logistic regression analysis, the presence of moderate–severe LA was independent predictors of FR (P = 0.01). Furthermore, higher NIHSS score at baseline (P < 0.01) end endovascular mechanical thrombectomy alone treatment (P < 0.01) resulted associated with futile recanalization. Our results showed that the presence of moderate–severe leukoaraiosis is associated with poor outcome in recanalized patients.     

The Role of FEIBA in Reversing Novel Oral Anticoagulants in Intracerebral Hemorrhage

Background

Activated prothrombin complex concentrates factor eight inhibitor bypassing activity (FEIBA) has been recommended for reversing novel oral anticoagulants (NOAC) in the context of intracerebral hemorrhage (ICH), though few clinical studies report its use.

Methods

A prospective study of patients with spontaneous ICH was conducted from May 2013 to May 2015. Hospital complications including hemorrhage (gastrointestinal bleeding, anemia requiring transfusion, and surgical site bleeding) and thrombosis (pulmonary embolus, deep vein thrombosis, ischemic stroke, and myocardial infarction) were recorded. All ICH patients underwent baseline head CT and a follow-up stability scan in 6 h. NOAC taken within 48 h of presentation was reversed with FEIBA (50 u/kg) per protocol. Three-month outcomes were assessed using the modified rankin score (mRS).

Results

Of 127 ICH patients enrolled, 6 (5 %) had NOAC-related ICH including: oral factor XA inhibitor N = 5 (4 %; N = 4 rivaroxaban, N = 1 apixaban] and direct thrombin inhibitor N = 1 (0.8 %; dabigatran). The indication for NOAC was atrial fibrillation in all patients and the median CHADS2–VASC score was 4 (range 2–5). The median admission NIHSS was 2 (range 0–14) and the median ICH volume was 8 mL (range 1–20). Five patients (3 rivaroxaban, 1 apixaban, 1 dabigatran) presented within 48 h and received FEIBA within a median of 13 h (range 10–29 h) from their last NOAC dose and 8 h (range 4.5–20) from the time last known well. None of the patients had ICH expansion, hemorrhagic, or thrombotic complications. Three-month median mRS was 1 (range 0–6).

Conclusion

In this small case series, reversal of NOAC with FEIBA was not associated with ICH expansion or any thrombotic or hemorrhagic complications.

     

The initial glycemic variability is associated with early neurological deterioration in diabetic patients with acute ischemic stroke

The association between glycemic variability and early neurological deterioration (END) in acute ischemic stroke remains unclear. This study attempted to explore whether initial glycemic variability increases END in diabetic patients with acute ischemic stroke. We enrolled type 2 diabetic patients undergoing acute ischemic stroke from November 2015 to November 2016. A total of 336 patients within 72 h from stroke onset were included. The serum glucose levels were checked four times per day during the initial 3 hospital days. The standard deviation of blood glucose (SDBG) values and the mean amplitude of glycemic excursions (MAGE) were calculated for glycemic variability. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥?2 points between hospital days 0 and 5. The frequencies of END and HbA1c were significantly different in subjects grouped according to tertiles of MAGE (9.09, 12.07 and 50.00%, p?<?0.001 for END; 7.36?±?1.91, 7.83?±?1.93 and 8.56?±?1.79, p?<?0.001 for HbA1c). Compared to patients without END, patients with END had significantly higher HbA1c levels (8.30?±?1.92 vs 7.80?±?1.93, p?=?0.043), increased SDBG (3.42?±?1.14 vs 2.60?±?0.96, p?<?0.001), and increased MAGE (6.46?±?2.09 vs 4.59?±?1.91, p?<?0.001). In a multivariable logistic regression, stroke etiology (OR 0.675; 95% CI 0.485–0.940, p?=?0.020), baseline NIHSS (OR 1.086; 95% CI 1.004–1.175, p?=?0.040), and MAGE (OR 1.479; 95% CI 1.162–1.882, p?=?0.001) were significantly associated with END. Initial glycemic variability is associated with END in diabetic patients with acute ischemic stroke.     

Safety and efficacy of Cerebrolysin in motor function recovery after stroke: a meta-analysis of the CARS trials

This meta-analysis combines the results of two identical stroke studies (CARS-1 and CARS-2) assessing efficacy of Cerebrolysin on motor recovery during early rehabilitation. Cerebrolysin is a parenterally administered neuropeptide preparation approved for the treatment of stroke. Both studies had a prospective, randomized, double-blind, placebo-controlled design. Treatment with 30 ml Cerebrolysin once daily for 3 weeks was started 24–72 h after stroke onset. In addition, patients participated in a standardized rehabilitation program for 21 days that was initiated within 72 h after stroke onset. For both studies, the original analysis data were used for meta-analysis (individual patient data analysis). The combination of these two studies by meta-analytic procedures was pre-planned, and the methods were pre-defined under blinded conditions. The nonparametric Mann-Whitney (MW) effect size of the two studies on the ARAT score on day 90 indicated superiority of Cerebrolysin compared with placebo (MW 0.62, P < 0.0001, Wei-Lachin pooling procedure, day 90, last observation carried forward; N = 442). Also, analysis of early benefit at day 14 and day 21 by means of the National Institutes of Health Stroke Scale, which is regarded as most sensitive to early improvements, showed statistical significance (MW 0.59, P < 0.002). The corresponding number-needed-to-treat (NNT) for clinically relevant changes in early NIHSS was 7.1 (95% CI: 4 to 22). Cerebrolysin had a beneficial effect on motor function and neurological status in early rehabilitation patients after acute ischemic stroke. Safety aspects were comparable to placebo, showing a favourable benefit/risk ratio.     

Role of infarct location and pre-existing depression on cardiac baroreceptor sensitivity in subacute ischemic stroke

Reduced cardiac baroreceptor sensitivity (BRS) after acute stroke is associated with worse outcome. The underlying mechanisms of reduced BRS are unclear. We evaluated cross correlation BRS (xBRS) in 184 patients with suspected acute ischemic stroke within 72 h of symptom onset. Among these patients, 22 had a transient ischemic attack (TIA) and 27 had a stroke mimic. Sixty-four age- and sex-matched ambulant control subjects without stroke were included. Compared with controls, xBRS was significantly lower in patients with ischemic stroke, TIA, and stroke mimics (4.6, 4.7, and 4.4, respectively, vs 6.6, p < 0.01). There was no difference in xBRS between right and left hemispheric infarctions (4.3 vs 4.9, p = 0.144), right and left insular infarctions (4.5 vs 5.3, p = 0.286), and insular infarction vs non-insular infarctions (4.7 vs 4.5, p = 0.996). Stroke patients with pre-existing depression/use of antidepressant medication had lower xBRS values than stroke patients with normal mental health (2.9 vs 4.8, p < 0.05). Control patients with depression also had lower xBRS compared to controls without depression (3.4 vs 5.9, p < 0.01). Our results suggest that decreased xBRS in the subacute phase after stroke is not associated with infarct localization. We found preliminary evidence for an association between pre-existing depression and use of antidepressant medication, and decreased BRS.     

Intravenous thrombolysis for ischemic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry

As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset (“golden hour”), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(?)] the “golden hour” by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24 h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24 h, respectively. A relative reduction in NIHSS-score of ≥40% at 2 h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0–1 at 3 months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(?) patients, with no differences in baseline characteristics (p > 0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p < 0.001) and 24 h (41 vs. 27%; p = 0.010), CREC at 2 h (39 vs. 21%; p < 0.001) and FFO (46.5 vs. 34.0%; p = 0.028) at 3 months. The rates of sICH and 3-month mortality did not differ (p > 0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53–11.03) and CREC (OR: 2.38; 95% CI 1.38–4.09), 24-h CR (OR: 1.88; 95% CI 1.08–3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15–3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement.     

CSF Volumetric Analysis for Quantification of Cerebral Edema After Hemispheric Infarction

Background

Malignant cerebral edema (CED) complicates at least 20 % of large hemispheric infarcts (LHI) and may result in neurological deterioration or death. Midline shift (MLS) is a standard but crude measure of edema severity. We propose that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time provides a reliable means of quantifying the spectrum of edema severity after LHI.

Methods

We identified 38 patients from 2008 to 2014 with NIHSS ≥8, baseline CT <6 h after stroke onset, at least 1 follow-up (FU) CT, and no parenchymal hematoma. The volumes of CSF (sulci, ventricles, and cisterns) ipsilateral (IL) and contralateral (CL) to infarct on baseline and FU CTs were quantified by manually assisted outlining with MIPAV image analysis software, as was infarct volume and MLS on FU CTs. Percentage change in CSF volumes (?CSF) from baseline to FU scans was correlated with MLS and compared in those with vs. without malignant edema (defined as hemicraniectomy, osmotic therapy, or death/neurological deterioration with MLS ≥5 mm).

Results

11 of 38 subjects (29 %) developed malignant edema. Neither baseline NIHSS nor CSF volume differed between those with and without edema (median NIHSS 18 vs. 13, p = 0.12, CSF volume 102 vs. 124 ml, p = 0.16). Inter-rater reliability for CSF measurements was excellent (intraclass correlation coefficient 0.97). ?CSF correlated strongly with MLS at peak edema (r = ?0.75), even adjusting for infarct volume (p = 0.009). ?CSF was also greater in those with malignant edema [?55 % (IQR ?49 to ?62) vs. ?36 % (?27 to ?45), p = 0.004]. ?CSF was the greatest within IL sulci [?97 % (?86 to ?99) vs. ?71 % (?41 to ?79), p = 0.002] but also significantly greater within CL sulci in those with malignant edema [?50 % (?29 to ?65) vs. ?25 % (0 to ?31), p = 0.014]. More than half this CSF volume reduction occurred by the time of first FU CT around 24 h after stroke, while MLS rose later.

Conclusions

Volumetric CSF analysis reliably quantifies CED and distinguishes those with malignant edema and MLS from those with a more benign course after LHI. ?CSF may provide an earlier and more sensitive indicator of edema severity across a broader dynamic range than MLS.