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.     

National Institutes of Health Stroke Scale in patients with primary intracerebral hemorrhage

Background

The National Institutes of Health Stroke Scale (NIHSS) is able to predict mortality and functional outcome in patients with ischemic stroke. Its role in primary intracerebral hemorrhage (ICH) is not clear. The objective of our study was to investigate whether NIHSS is a reliable instrument of clinical monitoring and correlates with mortality and functional outcome in ICH.

Methods

One hundred fifty-six consecutive subjects with primary ICH were included. We evaluated NIHSS at admission. The functional state after a 30-day and a 3-month-long follow-up was assessed by the modified Rankin Scale (mRS). Spearman’s rank correlation coefficient analysis was used for statistics. Sensitivity, specificity, positive predictive value, negative predictive value, global accuracy, and ROC curve were computed using the median score 7 as NIHSS cutoff and the score 4 as mRS cutoff.

Results

Median NIHSS score at admission was 7 (16–4); the mean (± SD) was 10.82 (±?8.27). Thirty-two patients (20.5%) died within 30 days and other 22 (14.1%) within 3 months. The median mRS score at 3 months was 4 (6–1); the mean (± SD) was 3.38 (±?2.42). We found a statistically significant correlation between initial NIHSS score and mRS score after 30 days (0.74) and 3 months (0.66, p?<?0.01). Sensitivity was 93.5 and 92.2%, specificity 82.3 and 69.6%, and GA 87.8 and 80.8%, respectively, at 1 and 3 months. The 1- and 3-month ROC curves comparing initial NIHSS and mRS showed a fitted area as 0.914 and 0.833, respectively.

Conclusions

NIHSS is a reliable tool of clinical monitoring and correlates with 30-day and 3-month mortality and functional outcome in subjects with ICH.

     

The SETscore to Predict Tracheostomy Need in Cerebrovascular Neurocritical Care Patients

Background and Purpose

Patients with severe stroke who require mechanical ventilation and neurointensive care unit (NICU) management often require a tracheostomy (TT). The optimal time point for TT remains unclear and a controversy in everyday NICU life. Here, we prospectively evaluated a score for prediction of TT need in NICU patients with cerebrovascular disease.

Methods

Seventy-five consecutively ventilated stroke patients were prospectively included in the study and assessed by the stroke-related early tracheostomy score (SETscore) within the first 24 h of admission. Endpoints were TT need, NICU-length of stay (NICU-LOS), and ventilation time (VT). We examined the correlation of these variables with the SETscore using regression analysis and determined a cut-off by receiver operating characteristic (ROC) analysis.

Results

Twenty-six patients had to be tracheostomized. The mean VT was 8.7 ±8 days and the mean NICU-LOS was 11.6 ± 8 days. The SETscore predicted NICU-LOS with a positive predictive value of 0.748 (p < 0.001) and VT with a positive predictive value of 0.799 (p < 0.001). The ROC analysis demonstrated a SETscore value of 8 to be the optimal cut-off to predict prolonged NICU-LOS, VT, and TT need with a sensitivity of 64 % and a specificity of 86 %.

Conclusions

Based on this monocentric study, the SETscore seems to be a valid tool to indicate prolonged NICU-LOS and VT, as well as TT need in cerebrovascular NICU patients. Confirmation of these results in larger cohorts with various settings may help to develop the SETscore as a decisive tool on primary TT early in time to avoid extubation failure.

     

Efficacy and safety of interferon beta-1b sc in older RRMS patients—a posthoc analysis of the BEYOND study

Evidence of a significant improvement of IFNB-1b in clinical severity in the older population with RRMS has not been established so far. The aim of this exploratory post hoc analysis of the 250 mcg IFNB-1b group of the BEYOND study is to compare the efficacy and safety of older versus younger patients using a cut-off at the age of 50 and at the age of 40, respectively. There was no difference between age groups in adjusted relapse risk (age 50 cut-off: P = 0.482, age 40 cut-off: P = 0.073) nor in adjusted time to confirmed EDSS progression (age 50 cut-off: P = 0.096, age 40 cut-off: P = 0.189). There were no significant differences between patients <50 and ≥50 years in the adjusted annualized relapse rate (P = 0.285), whereas relapse rate was higher in the <40 as compared to the ≥40 group (P = 0.024). The proportion of patients with confirmed disability progression was not significantly different for the 50 cutoff (P = 0.148), whereas significantly fewer <40 than ≥40 patients had disability progression (P = 0.047). Only minor differences in adverse event frequencies between the age groups for the two cut-offs were seen. These results indicate that IFNB-1b is as efficacious and safe in patients ≥50 years as <50 years of age.     

Prediction of Poor Outcome in Cerebellar Infarction by Diffusion MRI

Objective

Identification of patients with posterior fossa infarction at risk for neurological deterioration remains a challenge. MRI-based assessments of MCA infarction can predict poor outcome. Similar quantitative imaging measures after cerebellar stroke have not been studied. We tested the hypothesis that MRI-based volumetric assessment of cerebellar infarcts can provide reliable information for the prediction of poor outcome.

Design

We retrospectively identified 44 consecutive subjects (age 55.2 ± 13) with cerebellar stroke who underwent MRI with diffusion-weighted imaging (DWI) (median 63.7 h). Subjects were divided into poor (n = 13) and good outcomes (n = 31). Poor outcome was defined as having at least one of the following criteria: (1) mortality, (2) decompressive craniectomy, (3) ventriculostomy, and (4) decrease level of consciousness. DWI and cerebellar volume were defined on apparent diffusion coefficient maps. The ratio of the lesion volume to the whole cerebellum volume was calculated (rVolume).

Measurements and Main Results

Logistic regression revealed that lesion volume and rVolume were associated with increased risk of poor outcome, even after adjusting for age and NIHSS (χ ² = 8.2230, p < 0.0042; χ ² = 8.3992, p < 0.0038, respectively). The receiver operating characteristic curve with age, NIHSS, and volume or rVolume achieved an AUC of 0.816 (95 % CI 0.678–0.955) and 0.831 (95 % CI 0.6989–0.9636), respectively.

Conclusions

Quantitative volumetric measurement predicts poor outcome of cerebellar stroke patients, even when controlling for age and NIHSS. Quantitative analysis of diffusion MRI may assist in identification of patients with cerebellar stroke at highest risk of neurological deterioration. Prospective validation is warranted.     

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.     

A simple risk score for early ischemic stroke mortality derived from National Institutes of Health Stroke Scale: A discriminant analysis

Objectives

The aim of the current study was to design a new simpler form of National Institutes of Health Stroke Scale (NIHSS) for use in emergency settings, and compare its predictive ability with original NIHSS score for mortality.

Methods

A total of 152 consecutive patients with first ever ischemic stroke admitted to a university affiliated hospital were recruited. NIHSS score on admission was estimated and the predictive ability of NIHSS items for mortality at 28 days was evaluated by logistic regression. Stepwise discriminant analysis was performed on NIHSS items to obtain a discriminant function with the best discriminative ability for mortality. Further, receiver operating characteristics (ROC) curves were depicted to compare the new determined discriminant function with the original NIHSS score.

Results

Cumulative rate of mortality was 11.8% for 28-day follow-up period. Among NIHSS items, scores of visual field, limb ataxia and extinction neglect were not associated with mortality (P > 0.05). On the contrary, level of consciousness-commands, language and gaze were determined as independent indicators of mortality (P < 0.05), and their coefficients on discriminant function were equal to 0.65, 0.44 and 0.30, respectively. In addition, area under the ROC curve of the calculated discriminant function was not statistically different from NIHSS score (P > 0.05).

Conclusions

The suggested discriminant function, comprising NIHSS items of level of consciousness-commands, language and gaze, can predict 28-day mortality after ischemic stroke in a similar way to the original NIHSS score and can provide a baseline for stroke severity in emergency settings.     

The Effect of Clot Volume and Permeability on Response to Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke

Background and AimsThe characteristics of clot causing acute ischemic stroke, such as size, content, and location, are among the main determinants of response to intravenous tissue plasminogen activator [IV tPA]. Clot heterogeneity and permeability are under-recognized features that might provide additional information in predicting the efficacy of IV tPA.Methods and PatientsPatients with proximal middle cerebral artery occlusion treated with “IV tPA alone” were included. The mean Hounsfield's unit (HU) value, as objective measure of clot attenuation, and its standard deviation (SD), as proposed measure of clot heterogeneity, were obtained. The difference in HU values between CT Angiography and CT was defined as “clot permeability”, or “perviousness’. The size (length and volume-mm3) of pre-clot pouch and occluding clot along with ASPECT score and Maas’ silvian and leptomeningeal collateral score were measured.ResultsThe study included 84 cases (44 women, age: 68 ± 14 years, pretPA NIHSS: 16 ± 5). Patients with excellent response to tPA (31%) had lower thrombus volume (37.54 ± 32.37 versus 63.49 ± 37.36, P = .009) and heterogeneity (4.05 ± 1.49 versus 5.35 ± 2.34, P = .011), along with higher clot permeability (48 ± 35.48 to 31.32 ± 18.62, P = .006). However, significance of permeability did not survived in the regression analysis with adjustment for NIHSS (β:−.296, P = .003); clot volume (β:−.240, P = .014) and collateral status (β:.346, P < .001). In patients with good prognosis, clot volume was significantly lower (37.76 ± 30.08 versus 67.57 ± 37.83, P < .001), whereas permeability was significantly higher (43.97 ± 32.33 versus 31.13 ± 19.01, P = .026). However, this effect did not persist in the regression analysis after adjustment for NIHSS (β:−.399, P < .001), collateral status (β: .343, P < .001) and clot volume (β:−.297, P = .001). Clot permeability was significantly higher (45.78 ± 36.34 versus 33 ± 20.2, P = .045) and heterogeneity was lower (4.1 ± 1.55 to 5.27 ± 2.32, P = .028) in patients with dramatic response to tPA (27%). In patients responding positively to IV tPA (48%), clot permeability was numerically higher (39.85 ± 31.79 to 33.47 ± 19.28, P = .268), while clot volume (48.15 ± 34.5 to 62.07 ± 39.62, P = .093) was lower. Clot volume, permeability and heterogeneity did not show a significant difference in any (38.1%) or symptomatic (8.3%) bleeders after IV tPA. The chance of IV tPA to be beneficial increased in patients with clot volume lower than 45 mm³, with an increased likelihood of this benefit to be observed within the first day after IV tPA. Our detailed explorative ROC analysis was not able to detect a volume threshold above which the positive effect of IV tPA disappeared.ConclusionClot volume is critical for the effectiveness of IV tPA in acute ischemic stroke. Clot permeability and heterogeneity may modify its effect. CT technologies, which are readily available when evaluating a stroke patient in an emergency setting, provide us with useful parameters regarding the size, permeability and heterogeneity of the clot.     

Clinical Impact of Early Hyperglycemia During Acute Phase of Traumatic Brain Injury

Introduction

While tight glucose control has been widely adopted in the critical care setting, the optimal target glucose level following acute traumatic brain injury (TBI) remains debatable. This observational study was conducted to delineate the relationship between glucose levels and clinical outcomes during acute phase (first 5 days) of TBI.

Methods

We retrospectively identified 429 TBI patients admitted to the intensive care unit (ICU) from January 2005 to December 2006. Of those, 380 patients were retained for final analysis. Collected data included demographics, admission Glasgow Coma Scale (GCS), and APACHE II, glucose on admission and during the first 5 days of admission, and insulin use. Clinical outcomes included mortality, ICU, and hospital length of stay.

Results

The overall hospital mortality was 13.2% (n = 50). Demographics were similar between survivor and nonsurvivor groups; however, nonsurvivors were older and had worse disease severity on admission. Nonsurvivors also had significantly higher glucose levels at admission and during the first 24 h of admission (P < 0.001). Based on the receiver operating characteristic (ROC) curve, admission and day-1 peak glucose were better predictors for mortality compared to hospital days 2–5 glucose levels, with day-1 peak glucose being the best predictor of mortality (AUC = 0.820). A Kaplan–Meier survival analysis also showed that patients with glucose <160 mg/dl during the first day of ICU admission had a significantly better survival rate compared to those with glucose ≥160 mg/dl (P < 0.001). Two glucose bands, <60 and ≥160 mg/dl, were identified to be associated with increased mortality irrespective of injury severity (OR = 1.130; 95% CI 1.034–1.235; P = 0.007; OR = 1.034; 95% CI 1.021–1.047, P < 0.001; respectively).

Conclusions

Findings from our study suggest a glucose level ≥160 mg/dl within the first 24 h of admission following TBI is associated with poor outcomes irrespective of severity of injury, and this presents a timeframe for which active therapeutic interventions may improve clinical outcomes. Prospective efficacy trials are needed to corroborate these findings.     

Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatase 1: A Meaningful and Independent Marker to Predict Stroke in the Chinese Population

Label-free liquid chromatography-mass spectrometry (LC-MS) quantification methods have been described to determine serum proteins biomarkers in many diseases. Thus, the purpose of this study was to investigate the serum proteins biomarkers in the Chinese patients with acute ischemic stroke (AIS). In the study period, sera from 40 AIS patients and 40 normal cases were selected for screening study. Immunoaffinity subtraction was used to deplete the top most abundant serum proteins; the remaining serum proteins were subjected to trypsin digestion and analyzed in triplicate by label-free LC-MS/MS. The selected protein associations with disease risk were further evaluated by enzyme-linked immunosorbent assay (ELISA) testing of the remaining stroke cases and controls. Its value for biomarkers diagnosis was appreciated through receiver operating curve (ROC). Patients versus control levels differences were suggested for 19 proteins (nominal P?<?0.05) for stroke, with three proteins having a false discovery rate <0.05. The association of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (SHIP-1) with stroke (P?<?0.001) was confirmed using ELISA in replication studies. Based on the ROC curve, the optimal cut-off value of serum SHIP-1 levels for diagnosis of stroke was projected to be 1,550 pg/ml, which yielded a sensitivity of 77.5 % and a specificity of 88.3 %. In multivariate analysis, there was an increased risk of AIS associated with SHIP-1 levels ≥1,550 pg/ml (OR 4.28, 95 % CI: 1.97–8.96) after adjusting for possible confounders. Conclusion: The discovery and replication studies presented here show SHIP-1 to be a risk marker for AIS in the Chinese population, which appears to be a novel finding.     

Plasma copeptin levels in Chinese patients with acute ischemic stroke: a preliminary study

Copeptin is a stable by-product of arginine-vasopressin synthesis and reflects its secretion. The objective of the study was to evaluate the predictive value of copeptine on functional outcome at 90-day follow-up from stroke onset. We conducted a prospective, observational cohort study in the emergency department of two hospitals and enrolled 125 patients with acute ischemic stroke. Plasma copeptin concentrations, determined by a CT-proAVP-luminescence-immunoassay, were measured. There was a good correlation between levels of plasma copeptin and NIHSS score (r = 0.733, P < 0.01). In the 41 patients (32.8 %) with a poor functional outcome, copeptin levels were higher compared with those in patients with a favorable outcome (27.3; IQR, 14.9–34.8 pmol/L vs. 12.9; IQR, 9.4–21.6 pmol/L; P < 0.0001). Copeptin levels in 18 patients who died were more than two times greater as compared to patients who survived (32.4; IQR, 18.7–38.5 pmol/L vs. 15.1; IQR, 12.4–24.6 pmol/L; P < 0.0001). After adjusting for all other significant outcome predictors, copeptin level remained an independent predictor for poor functional outcome and mortality with an odds ratio of 3.12 (95 % CI 1.54–6.46), 3.16 (95 % CI 0.92–6.15), respectively. Our study suggests that copeptin levels are a useful tool to predict outcome and mortality 3 months after acute ischemic stroke and have a potential to assist clinicians     

Early Systemic Procalcitonin Levels in Patients with Aneurysmal Subarachnoid Hemorrhage

Background

Early (≤24 h) systemic procalcitonin (PCT) levels are predictive for unfavorable neurological outcome in patients after out-of-hospital cardiac arrest (OHCA). Subarachnoid hemorrhage (SAH) due to aneurysm rupture might lead to a cerebral perfusion stop similar to OHCA. The current study analyzed the association of early PCT levels and outcome in patients after SAH.

Methods

Data from 109 consecutive patients, admitted within 24 h after SAH, were analyzed. PCT levels were measured within 24 h after ictus. Clinical severity was determined using the World Federation of Neurological Societies (WFNS) scale and dichotomized into severe (grade 4–5) and non-severe (1–3). Neurological outcome after 3 months was assessed by the Glasgow outcome scale and dichotomized into unfavorable (1–3) and favorable (4–5). The predictive value was assessed using receiver operating curve (ROC) analysis.

Results

Systemic PCT levels were significantly higher in patients with severe SAH compared to those with non-severe SAH: 0.06 ± 0.04 versus 0.11 ± 0.11 μg/l (median ± interquartile range; p < 0.01). Patients with unfavorable outcome had significantly higher PCT levels compared to those with favorable outcome 0.09 ± 0.13 versus 0.07 ± 0.15 ng/ml (p < 0.01). ROC analysis showed an area under the curve of 0.66 (p < 0.01) for PCT, which was significantly lower than that of WFNS with 0.83 (p < 0.01).

Conclusions

Early PCT levels in patients with SAH might reflect the severity of the overall initial stress response. However, the predictive value is poor, especially compared to the reported predictive values in patients with OHCA. Early PCT levels might be of little use in predicting neurological outcome after SAH.     

Factors predicting the Montreal cognitive assessment (MoCA) applicability and performances in a stroke unit

The evaluation of cognitive status is not routine in the acute stroke setting. We aimed to investigate feasibility, applicability, and performances of the Montreal cognitive assessment (MoCA) in acute stroke patients. Consecutive stroke patients (ischemic or hemorrhagic) admitted to one stroke unit were evaluated 5–9 days after stroke with MoCA (score range: 0–30; higher scores indicate better cognitive performance). Pre-morbid functional and cognitive status was assessed by a structured interview to caregivers. Neuroimaging data regarding index stroke and pre-existing lesions were collected. From December 2009 to December 2010, out of 207 patients with stroke, 137 (66 %) were enrolled [mean age 69.2 ± 14.8 years; males 62 %; mean National Institute of Health and Stroke Scale (NIHSS) score 5.9 ± 7.9]. The most common reason for non-enrolment was unfitting the time window inclusion criteria. MoCA was entirely applicable to 113/137 (82.5 %) patients and the mean score was 17.8 ± 7.1. Multivariate analyses showed that non-applicability was associated with higher NIHSS scores [OR (95 % CI) = 1.4 (1.2–1.7) for each point], left sided lesions [OR (95 % CI) = 18.8 (2.3–155.2)], and worse pre-morbid functional status [OR (95 % CI) = 0.7 (0.6–0.9) for each point of the instrumental activity of daily living scale]. Factors influencing MoCA performance were low education (β = 0.264, p < 0.01), higher NIHSS scores (β = ?0.277, p < 0.01) and worse pre-morbid functional status (β = 0.504, p < 0.001). MoCA administration is feasible in acute patients with mild-to-moderate stroke, with lesion location, stroke severity, and pre-morbid functional status as major determinants of its applicability and performance. MoCA seems to reveal some degree of cognitive deficit even in patients with mild stroke.     

Chronic Pretreatment with Acetyl-l-Carnitine and ±DL-α-Lipoic Acid Protects Against Acute Glutamate-Induced Neurotoxicity in Rat Brain by Altering Mitochondrial Function

Cellular oxidative stress and energy failure were shown to be involved in Glutamate (l-Glu) neurotoxicity, whereas, acetyl-l-carnitine (ALCAR) and ±DL-α-lipoic acid (LA) are known to be key players in the mitochondrial energy production. To evaluate the effects of the above antioxidants, adult rats were pretreated with ALCAR (100 mg/kg i.p for 21 days) and both ALCAR and LA (100 mg/kg i.p + 50 mg/kg i.p for 21 days), before stereotactically administering l-Glu bolus (1μmole/1 μl) in the cerebral cortex. Results showed that acute l-Glu increased ROS (P < 0.001), LPO (P < 0.001), Ca²⁺ (P < 0.001), TNF-α (P < 0.001), IFN-γ (P < 0.001), NO (P < 0.001) levels and mRNA expression of Caspase-3, Casapase-9, iNOS, and nNOS genes with respect to saline-injected control group. Key antioxidant parameters such as SOD, CAT, GSH, GR along with mitochondrial transmembrane potential (Ψ?m) were decreased (P < 0.05), while ALCAR pretreatment prevented these effects by significantly inhibiting ROS (P < 0.001), LPO (P < 0.001), Ca²⁺ (P < 0.05), TNF-α (P < 0.05), IFN-γ (P < 0.001), NO (P < 0.01) levels and expression of the above genes. This chronic pretreatment of ALCAR also increased SOD, CAT, GSH, GR, and Ψ?m (P < 0.0.01, P < 0.0.01, P < 0.05, P < 0.05, and P < 0.001, respectively) with respect to l-Glu group. The addition of LA to ALCAR resulted in further increases in CAT (P < 0.05), GSH (P < 0.01), GR (P < 0.05), Ψ?m (P < 0.05) and additional decreases in ROS (P < 0.001), LPO (P < 0.05), Ca²⁺ (P < 0.05), TNF-α (P < 0.05) and mRNA expression of iNOS and nNOS genes with respect to ALCAR group. Hence, this “one-two punch” of ALCAR + LA may help in ameliorating the deleterious cellular events that occur after l-Glu.     

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.

     

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.     

Neutrophil-to-Lymphocyte Ratio and Response to Intravenous Thrombolysis in Patients with Acute Ischemic Stroke

Background and Aims: The Neutrophil-to-Lymphocyte Ratio (NLR) is suggested as a readily available and inexpensive biomarker to predict prognosis of acute stroke. Experience with intravenous (IV) tissue plasminogen activator (tPA) treatment is limited. Methods: Total 142 (80 female, age: 69 ± 13 yearr) consecutive acute stroke patients treated with IV tPA were evaluated. Admission and 24th hour lymphocyte, neutrophil, and monocyte counts were measured and the NLR was calculated. Results: Average NLR elevated (by 3.47 ± 6.75) significantly from admission to 24th hour (P< .001). Total 52% of patients exerted good response to IV tPA (NIHSS ≤1 or decrease in NIHSS ≥4 at end of 24 hour), while 27% showed dramatic response (decrease in NIHSS ≥8 at end of 24 hour). The patients with “thrombolysis resistance” had significantly higher 24 hour Neutrophil-to-Lymphocyte Ratio (24h NLR) (P= .001). At the end of 3rd month, 46.5% of patients had favorable (modified Rankin's score, mRS 0-2) and 32.4% had excellent (mRS 0-1) outcome. Patients without favorable/excellent outcome had significantly higher 24h NLRs. Regression analysis indicated that post-tPA, but not admission NLR, was an independent negative predictor of excellent (β =?.216, P= .006) and favorable (β = ?.179, P= .034) outcome after adjustment for age, hypertension, and admission NIHSS. Nine patients who developed symptomatic intracerebral hemorrhage had elevated pre-tPA (7.6 ± 7.39 versus 3.33 ± 3.07, P< .001) and 24h NLR (26.2 ± 18.6 versus 5.78 ± 4.47, P< .001). Of note, receiver operating characteristics analysis failed to detect any reliable NLR threshold for absence of tPA effectiveness/dramatic response, 3rd month good/excellent outcome or any type tPA-induced hemorrhage. Conclusions: As a marker of stroke-associated acute stress response, the NLR, which increases during the first 24 hours, is an epiphenomenon of poor prognosis. However, pretreatment NLR values have no importance in predicting IV tPA response.     

Fifteen-Year Experience in Treating Blepharospasm with Botox or Dysport: Same Toxin, Two Drugs

Objectives To compare the clinical characteristics and the long-term outcome of a large series of patients with blepharospasm (BS) treated with the two most used brands of BoNT-A over the last 15 years. Methods We have reviewed the clinical charts of 128 patients with BS who received botulinum neurotoxin (BoNT) in 1341 treatments (Botox in 1009, Dysport in 332) over the last 15 years. Results Mean dose per session was 34U ± 15 for Botox and 152U ± 54 for Dysport. Mean latency of clinical effect was 4.5 ± 4.6 days for Botox and 5.0 ± 5.7 days for Dysport (P > 0.05). Mean duration of clinical improvement was higher for Dysport than Botox: 80.1 ± 36.3 and 66.2 ± 39.8 days, respectively (P < 0.01). In a six-point scale (0: no efficacy, 6: remission of BS), the mean efficacy of both treatments was 3.60 ± 1.3; 3.51 ± 1.4 (Botox) and 3.85 ± 1.2 (Dysport), P < 0.01. The doses of Botox (β = 0.40) and Dysport (β = 0.16) were significantly increased over time. Side effects occurred in 325 out of 1341 treatments (24.2%): 21.8% of the patients who had received Botox, and in 31.6% of those who had received Dysport (P < 0.01). Conclusions Both brands are effective and safe in treating blepharospasm; efficacy is long lasting. The differences in outcome and side effects suggest that, albeit the active drug is the same, Botox and Dysport should be considered as two different drugs.     

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.

     

Motor outcomes in patients with advanced Parkinson’s disease treated with levodopa/carbidopa intestinal gel in Italy: an interim analysis from the GREENFIELD observational study

Several levodopa/carbidopa intestinal gel (LCIG) studies showed a significant reduction of OFF time and a significant increase of ON time, as well as a reduction of dyskinesia, and improvement of non-motor symptoms and quality of life. However, few studies have been conducted in a large population for more than 3 years. Interim outcomes from GREENFIELD observational study on a large Italian cohort of advanced PD patients who started LCIG in routine care between 2007 and 2014, still on treatment at the enrollment, are presented. Comparison between baseline (before LCIG start) and visit 1 (at enrollment) is reported. Primary endpoint was Unified Parkinson’s Disease Rating Scale (UPDRS) IV Item 39; secondary endpoints were UPDRS I and II, as outcome of quality of life. Overall, 145 of 148 enrolled patients from 14 Movement Disorder Centers in Italy were evaluable with a mean LCIG treatment period of 1.38 ± 1.66 years at enrollment. Compared with baseline, the mean score regarding daily time spent in OFF (UPDRS IV Item 39) at visit 1 significantly decreased from 2.1 ± 0.8 to 0.9 ± 0.7 (57 % reduction vs baseline, P < 0.0001); UPDRS IV improved by 39 % (P < 0.0001); scores for dyskinesia duration and disability were reduced by 28 % (1.8 ± 1.0–1.3 ± 0.9; P < 0.0001) and 33 % (1.5 ± 1.1 to 1.0 ± 1.0; P < 0.0001), respectively; and the scores for painful dyskinesia and early morning dystonia were reduced by 56 % (0.9 ± 1.0–0.4 ± 0.7; P < 0.0001) and 25 % (0.4 ± 0.5–0.3 ± 0.5; P < 0.001), respectively. The preliminary results of this interim analysis support the efficacy of LCIG on motor complications and activities of daily living.