Factors Associated with Thrombolysis Outcome in Ischemic Stroke Patients with Atrial Fibrillation

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P < 0.001) and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were: heart failure (P = 0.045); high systolic pressure (P = 0.039); high blood glucose (P = 0.030); and a high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001). Moreover, high systolic pressure at admission (P = 0.007), high blood glucose (P = 0.027), and a high NIHSS score (P < 0.001) were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score (P = 0.006) and warfarin taken within 48 h before stroke onset (P = 0.032) were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke.     

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.

     

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.

     

Serum levels of homocysteine at admission are associated with post-stroke depression in acute ischemic stroke

The primary purpose of this study was to assess the serum levels of homocysteine (HCY) at admission to the presence of post-stroke depression (PSD). From September 2014 to December 2015, first-ever acute ischemic stroke patients within the first 24 h after stroke onset were consecutively recruited and followed-up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression. By the time of 3 month after stroke, 238 had finished the follow-up and included in our study. Totally, 65 out of the 238 patients were diagnosed as depression (27.3%; 95% CI 19.6–35.4%). The results showed significantly higher HCY levels in patients with depression [21.4 (IQR 16.5–23.4) mmol/L vs. 14.1 (IQR 11.2–18.5) mmol/L, P < 0.0001) at admission than patients without depression. In multivariate logistic regression analysis, HCY was an independent predictor of PSD with an adjusted OR of 1.07 (95% CI 1.01–1.22; P = 0.013). Based on the ROC curve, the optimal cut-off value of serum HCY levels as an indicator for prediction of PSD was projected to be 16.5 mmol/L, which yielded a sensitivity of 82.5% and a specificity of 63.6%, with the area under the curve at 0.745 (95% CI 0.672–0.818; P < 0.0001). An increased risk of PSD was associated with serum HCY levels ≥16.5 mmol/L (adjusted OR 6.13, 95% CI 3.32–14.16; P < 0.001) after adjusting for above-recorded confounders. Elevated serum levels of HCY at admission were associated with depression 3-month after stroke, suggesting that these alterations might participate in the pathophysiology of depression symptoms in stroke patients.     

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.

     

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.     

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).     

Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials

This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30–50 ml Cerebrolysin once daily for 10–21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P?<?0.0001, N?=?1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P?=?0.0118, N?=?314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke.     

Susceptibility-weighted imaging predicts infarct size and early-stage clinical prognosis in acute ischemic stroke

Susceptibility-weighted imaging (SWI) is a non-invasive technique that can reveal venous structures and iron in the brain. This retrospective study evaluated SWI, relative to other imaging techniques, for determining cerebral infarct size and early-stage clinical prognosis in patients with acute ischemic stroke. Within 3 days after onset, 22 patients with acute ischemic stroke underwent SWI, diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), fluid-attenuated inversion recovery (FLAIR), and magnetic resonance angiography (MRA). At least 7 days after onset, the patients also underwent cranial FLAIR or computed tomography (CT). The severity of neurological damage was adjudged with NIHSS (National Institutes of Health Stroke Scale) scores. The imaged cranial lesions were evaluated according to ASPECTS (Alberta Stroke Program Early CT Score). The SWI-ASPECTS significantly correlated with mean transit time (MTT)-ASPECTS (Spearman’s test, r?=?0.662, P?=?0.001) in evaluating ischemic penumbra and significantly correlated with the FLAIR and CT-ASPECTS (Spearman’s test, r?=?0.765, P?<?0.001) in predicting infarct size. SWI is feasible for the early evaluation of cerebral infarct size and clinical prognosis of patients with acute cerebral infarction. SWI is a useful predictor of early infarct growth and early-stage outcome.     

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.     

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.     

Serum neuron specific enolase may be a marker to predict the severity and outcome of cerebral venous thrombosis

The objective is to explore the effective of baseline serum neuron specific enolase (NSE) on predicting the severity and outcome in patients with cerebral venous thrombosis (CVT). A total of 156 patients confirmed as CVT in Xuanwu Hospital were enrolled in this retrospective study from March 2011 through September 2016. The severity was evaluated with the National Institutes of Health Stroke Score (NIHSS), intracranial pressure (ICP), and CVT-related complications; the outcome was evaluated by modified Rankin Scale (mRS); the relationship between baseline serum NSE and mRS was analyzed with receiver operating characteristic curve (ROC), logistic regression analysis, and Kaplan–Meier curves. Baseline level of serum NSE was positively associated with baseline NIHSS (r = 0.322, p < 0.001). Among which, patients with high level of serum NSE were also noticed with cerebral venous infarction (p < 0.001), intracranial hemorrhage (p < 0.001), seizure (p = 0.035). Meanwhile, patients in NSE ≥ 15.05 ng/mL group vs. NSE < 15.05 ng/mL group had large mRS scores (≥ 3) at discharge (adjusted OR: 5.40, 95% CI 1.27–22.91; p = 0.022) and higher percentage of mRS scores ≥ 3 during 40 months of outpatient follow-up (log-rank p < 0.001). Baseline level of serum NSE is positively associated with the severity of CVT. Presumably NSE may be a potential predictor for the clinical outcome of CVT.     

Circulating miR-126 and miR-130a levels correlate with lower disease risk,disease severity,and reduced inflammatory cytokine levels in acute ischemic stroke patients

To investigate the correlations of five angiogenesis-related miRNA (miR-126, miR-130a, miR-222, miR-218, and miR-185) expression levels with risk, severity, and inflammatory cytokines levels in acute ischemic stroke (AIS) patients. A total of 148 AIS patients and 148 age- and gender-matched controls were consecutively enrolled. Blood samples were collected from AIS patients and controls, and plasma was separated for miRNAs and cytokine level detection. Plasma levels of miRNAs were evaluated by real-time qPCR method, and inflammatory cytokine levels were detected using an enzyme-linked immunosorbent assay (ELISA). Plasma miR-126 and miR-130a expression levels in AIS patients were lower than those of controls, while the levels of miR-222, miR-218, and miR-185 were elevated in AIS patients compared with controls. After pooling the five miRNA expression levels together, the area under the curve (AUC) for predicting AIS risk was 0.840 (95% CI 0.795–0.885) with a sensitivity of 83.8% and a specificity of 69.6% at the best cut-off point. Plasma miR-126 (r?=???0.402, P?<?0.001) and miR-130a (r?=???0.161, P?=?0.050) levels were negatively correlated with NIHSS scores, while plasma miR-218 level was positively correlated with NIHSS scores (r?=?0.471, P?<?0.001). Most importantly, plasma miR-126 expression was negatively correlated with TNF-α (r?=???0.168, P?=?0.041), IL-1β (r?=???0.246, P?=?0.003), and IL-6 (r?=???0.147, P?=?0.035) levels, while miR-130a expression was negatively correlated with TNF-α (r?=???0.287, P?<?0.001), IL-1β (r?=???0.168, P?=?0.041), and IL-6 (r?=???0.239, P?=?0.003) expression levels and positively associated with IL-10 level (r?=?0.261, P?=?0.001). Circulating miR-126 and miR-130a levels correlate with lower disease risk, decreased disease severity, and reduced inflammatory cytokine levels in AIS patients.     

Quality of Life and Hormonal,Biochemical, and Anthropometric Profile Between Olanzapine and Risperidone Users

This cross-sectional study compared quality of life and side effects in 108 users of olanzapine or risperidone suffering schizophrenia and being attended at psychiatric ambulatory services in Rio Grande do Norte, Brazil. Economic, socio-demographic, anthropometric, biochemical, and hormonal variables were compared. The EuroQoL Five-Dimension Scale (EQ-5D) was used to evaluate quality of life, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson–Angus Scale. Data were analysed using the χ² test and Student’s t test, with a significance level of 5 %.The household incomes of approximately 80 % of patients were <2.0 minimum wages ($678). Anthropometric variables (waist circumference, hip circumference, weight, waist-to-hip ratio) and systolic and diastolic blood pressure were noted among male olanzapine users (all p < 0.05). EQ-5D scores showed that olanzapine use significantly impacted self-help ability (p < 0.001). Risperidone users had a mean quality-adjusted life year value of 1. Mean total Simpson–Angus Scale scores was 0.38 for olanzapine users and 0.11 for risperidone users (p < 0.02). Significant differences in UKU were observed for the following items: asthenia/lassitude/fatigue (higher among olanzapine users, p = 0.02), dystonia (higher among olanzapine users, p = 0.01), tremors (higher among olanzapine users, p = 0.03), gynecomastia (higher among risperidone users, p < 0.02), and ejaculatory dysfunction (higher among risperidone users, p < 0.02). Olanzapine users had impaired quality of life, which can be explained in part by adverse motor, biochemical, and hormonal effects characteristic of metabolic syndrome.     

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.     

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.     

Comparative analysis of background EEG activity in childhood absence epilepsy during valproate treatment: a standardized,low-resolution,brain electromagnetic tomography (sLORETA) study

Valproate (VPA) is an antiepileptic drug (AED) used for initial monotherapy in treating childhood absence epilepsy (CAE). EEG might be an alternative approach to explore the effects of AEDs on the central nervous system. We performed a comparative analysis of background EEG activity during VPA treatment by using standardized, low-resolution, brain electromagnetic tomography (sLORETA) to explore the effect of VPA in patients with CAE. In 17 children with CAE, non-parametric statistical analyses using sLORETA were performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the untreated and treated condition. Maximum differences in current density were found in the left inferior frontal gyrus for the delta frequency band (log-F-ratio = ?1.390, P > 0.05), the left medial frontal gyrus for the theta frequency band (log-F-ratio = ?0.940, P > 0.05), the left inferior frontal gyrus for the alpha frequency band (log-F-ratio = ?0.590, P > 0.05), and the left anterior cingulate for the beta frequency band (log-F-ratio = ?1.318, P > 0.05). However, none of these differences were significant (threshold log-F-ratio = ±1.888, P < 0.01; threshold log-F-ratio = ±1.722, P < 0.05). Because EEG background is accepted as normal in CAE, VPA would not be expected to significantly change abnormal thalamocortical oscillations on a normal EEG background. Therefore, our results agree with currently accepted concepts but are not consistent with findings in some previous studies.     

The BRAIN test: a keyboard-tapping test to assess disability and clinical features of multiple sclerosis

Background

The BRadykinesia Akinesia INcordination (BRAIN) test is an online keyboard-tapping test previously validated as a sensitive tool for detecting signs of Parkinson’s disease.

Objectives

To determine whether the BRAIN test can measure disability in MS and identify the presence of pyramidal or cerebellar dysfunction.

Methods

Kinesia scores (KS, number of key taps in 30 s), akinesia times (AT, mean dwell time on each key) and incoordination scores (IS, variance of travelling time between keys) were calculated in 39 MS patients. These were correlated against the Expanded Disability Status Scale (EDSS) scores, pyramidal and cerebellar functional system scores and 9-hole peg test scores.

Results

EDSS correlated with KS (r = ? 0.594, p < 0.001), AT (r = 0.464, p = 0.003) and IS (r = 0.423, p = 0.007). 9-HPT scores strongly correlated with KS (r = 0.926, p < 0.001). Pyramidal scores correlated with KS (r = ? 0.517, p < 0.001). Cerebellar scores correlated with KS (r = ? 0.665, p < 0.001), AT (r = 0.567, p < 0.001) and IS (r = 0.546, p = 0.007). Receiver operating characteristic curves demonstrate that KS can distinguish between the presence or absence of pyramidal and cerebellar dysfunction with area under curve 0.840 (p < 0.001) and 0.829 (p < 0.001), respectively.

Conclusions

The BRAIN test can remotely measure disability in MS. Specific scores differ according to the presence and severity of pyramidal or extrapyramidal dysfunction. It demonstrates huge potential in monitoring disease progression in clinical trials.

     

Serum Coenzyme Q10 Is Associated with Clinical Neurological Outcomes in Acute Stroke Patients

Disruption of prooxidant-antioxidant balance may lead to oxidative stress which is known as a mechanism contributing to ischemic stroke. Coenzyme Q10 (CoQ10) is an endogenous antioxidant that could be effective in preventing oxidative stress. However, the contribution of serum levels of CoQ10 in clinical neurological outcomes following ischemic stroke has not been clearly established. This study aims at measuring serum concentration of CoQ10 along with major indicators of antioxidant and oxidant among patients within 24 h after onset of the stroke symptoms, and investigating their relation with the clinical status of patients. Serum levels of CoQ10, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured in 76 patients and 34 healthy individuals. Severity of the neurological deficit, functional disability, and cognitive status in ischemic subjects were respectively studied with the National Institutes of Health stroke scale (NIHSS), modified Rankin Scale (MRS), and Mini-Mental State Examination (MMSE). Stroke patients had significantly lower serum level of CoQ10 and SOD as compared to controls (27.34?±?35.40 ng/ml, 18.58?±?0.76 μ/ml, respectively; p?<?0.05), whereas the serum MDA level was significantly higher (38.02?±?2.61 μm, p?<?0.05). A significant negative correlation was detected between the serum CoQ10 level and scores of NIHSS and MRS. A similar association was discerned between the SOD level and the neurological deficit score. The serum MDA level was also found to be strongly correlated with all three neurological scales. These findings suggest that the serum level of CoQ10 like other antioxidant and oxidant markers can significantly change early after ischemic stroke and they are substantially associated with clinical neurological outcomes.     

Circulating insulin-like growth factor 1 and insulin-like growth factor binding protein-3 level in Alzheimer’s disease: a meta-analysis

It has been reported that the associations between circulating insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) and Alzheimer’s disease (AD) are controversial. Thus, present meta-analysis was carried out to confirm the probable associations. We searched “PubMed”, “Springer” and “Medline” databases using the term (“insulin-like growth factor-1” or “IGF-1” or “insulin-like growth factor binding protein-3” or “IGFBP-3”) and (“Alzheimer’s disease”) until April 2016. Furthermore, standard mean differences (SMDs) were calculated. A total of seven reports involving 1342 percipients were pooled. SMDs were ?0.25 (P = 0.22) and ?0.33 (P = 0.08) for IGF-1 and IGFBP-3, respectively. Furthermore, the circulating IGF-1 levels in AD patients were lower than controls when studies with the difference of mean age ≤1 year (SMD ?0.57, P = 0.007) or 2 years (SMD ?0.58, P = 0.02) or difference of mean MMSE scores ≤10 scores (SMD ?0.94, P < 0.00001), or studies from Europe (SMD ?0.89, P < 0.00001) were excluded. In addition, the circulating IGFBP-3 levels in AD patients were lower than controls when studies with the difference of mean age ≤2 years (SMD ?0.62, P = 0.006) or difference of mean MMSE scores ≤6 scores (SMD ?0.48, P = 0.0004), 7 scores (SMD ?0.58, P = 0.02), or 8 scores (SMD ?0.80, P = 0.03) were excluded. Even though no significant difference of circulating IGF-1 and IGFBP-3 levels in AD patients comparing with controls was found in present meta-analysis, the current study provided the evidence that the circulating IGF-1 and IGFBP-3 level in AD patients were influenced by the difference of mean age as well as MMSE scores. Furthermore, circulating IGFBP-3 levels in AD patients may be decreased earlier than IGF-1.