The efficacy and safety of alteplase treatment in patients with acute ischemic stroke with unknown time of onset: -Real world data.

INTRODUCTION: Treatment with alteplase for acute ischemic stroke patients with an unknown time of onset is safe and effective. However, clinical trials have some selection bias. The purpose of this study was to clarify the efficacy and safety of alteplase treatment in patients with unknown time of onset in a real-world clinical setting. METHODS: We included consecutive patients with acute ischemic stroke visited within 4.5 h of onset or symptom recognition. We divided patients into two groups: onset clear group (C-group) and unknown time of onset group (U-group). We treated patients with an unknown time of onset if the DWI-FLAIR mismatch was positive. We calculated the prevalence of alteplase treatment in each group and compared prognosis between the two groups. RESULTS: Six hundred thirty-two patients arrived within 4.5 h of onset or symptom recognition. Of these, 446 patients (71 %) were in the C-group and 186 (29 %) in the U group. Alteplase treatment was performed in 35 % of patients in the C group and in 18 % in the U group (p < 0.001). Favorable outcomes at 90 days in patients treated with alteplase were comparable between the C group (52 %) and the U group (53 %) (p = 0.887). All hemorrhagic complications, including non-symptomatic hemorrhagic transformation, occurred in 11 of 157 patients (7 %) in the C-group and one of 34 patients (3 %) in the U-group (p = 0.696). CONCLUSION: In a real-world clinical setting, alteplase treatment was performed safe in 18% of patients with an unknown time of stroke onset based on patient selection using the DWI-FLAIR mismatch.

Diffusion-Weighted Imaging Hyperintensities in Acute and Subacute-Phase Intracerebral Hemorrhage.

OBJECTIVE: Diffusion-weighted imaging hyperintensities are observed in intracerebral hemorrhage patients at times and might be associated with unfavorable functional outcomes. However, the suitable time to evaluate diffusion-weighted imaging hyperintensities to influence stroke outcome remains unclear. This study investigated the associations between acute and sub-acute diffusion-weighted imaging hyperintensities and functional outcomes among patients with acute intracerebral hemorrhage. METHODS: Diffusion-weighted imaging hyperintensities were evaluated within 24 h (acute phase) and at 14 ± 5 days (sub-acute phase). An unfavorable functional outcome was a score of 5-6 on the modified Rankin Scale at 3 months. RESULTS: Among 268 intracerebral hemorrhage patients, diffusion-weighted imaging hyperintensities in the acute phase were observed in 32 (11.9%). Among 227 patients who underwent a second magnetic resonance imaging in the sub-acute phase, diffusion-weighted imaging hyperintensities were observed in 57 (25.1%). Multivariable analysis revealed that the baseline intracerebral hemorrhage volume, history of stroke, and severe white matter lesions were associated with sub-acute diffusion-weighted imaging hyperintensities. The patients with unfavorable outcomes (n = 37) had a higher frequency of sub-acute diffusion-weighted imaging hyperintensities than those without (n = 190) (51.4% vs. 20.0%, P < 0.001); the frequencies of acute diffusion-weighted imaging hyperintensities were not significantly different between the groups (13.5% vs. 10.0%, P = 0.559). Sub-acute diffusion-weighted imaging hyperintensities were independently associated with unfavorable outcomes after adjusting for confounding factors (Odds Ratio, 3.35, 95% CI 1.20-9.35, P = 0.021). CONCLUSION: The rate of sub-acute diffusion-weighted imaging hyperintensities was higher than acute diffusion-weighted imaging hyperintensities among acute intracerebral hemorrhage patients and likely to be associated with unfavorable outcomes.

Various effects of nutritional status on clinical outcomes after intracerebral hemorrhage.

Although the assessment of nutrition is essential for stroke patients, detailed associations between nutritional status at admission, subsequent complications, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH) are unclear. We aimed to elucidate these associations using the Controlling Nutritional Status (CONUT) score. Consecutive patients with acute ICH were investigated. Nutritional status was evaluated using the CONUT score, calculated from the serum albumin level, lymphocyte count, and total cholesterol level. Subsequent complications, such as hemorrhage expansion (HE) during the acute stage and aspiration pneumonia during hospitalization, were evaluated. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. Of the 721 patients, 49 had HE, 111 had aspiration pneumonia, and 409 had poor outcomes. Patients with HE had significantly lower total cholesterol levels than those without HE. Patients with aspiration pneumonia had significantly lower albumin levels, lower lymphocyte counts, and higher CONUT scores than those without aspiration pneumonia. Patients with poor outcomes had significantly lower albumin levels, lower lymphocyte counts, lower total cholesterol levels, and higher CONUT scores than those with good outcomes. Multivariable logistic analysis showed that higher CONUT scores were independently associated with poor outcome (odds ratio, 1.28; 95% confidence interval, 1.09-1.49; P = 0.002) after adjusting for baseline characteristics, HE, and aspiration pneumonia. Each component of CONUT was a useful predictor of subsequent complications. Malnutrition, determined using the CONUT score, was independently associated with poor outcomes in patients with ICH after adjusting for these complications.

Temporal Validation of an Assessment Tool that Predicts a Possibility of Home Discharge for Patients with Acute Stroke.

OBJECTIVES: Several prediction models have been developed to assess discharge destinations for patients with acute stroke; however, few studies have performed external validation. We aimed to perform a temporal external validation of a prediction tool to identify stroke patients with a high possibility of discharge to home. MATERIALS AND METHODS: From December 2017 to July 2019, consecutive patients with acute stroke were included. Clinical nurses and physical therapists applied the prediction model to assess the patients' possibility of home discharge. Whether or not the patient was discharged their own home was the outcome measured. We calculated the sensitivity and specificity of the model and evaluated the discrimination and calibration based on the area under the curve (AUC) and the calibration plot. RESULTS: Of the 1214 patients assessed, 618 (51%) were discharged home. Using the same cutoff values recommended in the study that first described the tool, we determined the sensitivity and specificity of 91% and 59%, respectively. The AUC to assess the model discrimination was 0.80 (95% confidence interval, 0.77-0.82) and the calibration plot showed acceptable agreement between the predicted and observed outcomes. CONCLUSIONS: The tool showed a high sensitivity, as expected, in the present study, which examined external validity during the different study periods.

cnm-Positive Streptococcus mutans and diffusion-weighted imaging hyperintensities in acute intracerebral hemorrhage.

BACKGROUND: Strains of Streptococcus mutans expressing the cell surface collagen-binding protein, Cnm, encoded by cnm (cnm-positive S. mutans), are associated with hypertensive intracerebral hemorrhage (ICH) and the occurrence of cerebral microbleeds (CMBs). Small diffusion-weighted imaging (DWI) hyperintensities in patients with acute ICH are also associated with CMBs. However, the association between cnm-positive S. mutans and DWI hyperintensities is unclear. Hence, this study aimed to investigate the association between cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH. METHODS: Patients with acute ICH were prospectively registered at three hospitals. Dental plaque specimens were collected within 4 days after admission, and cnm-positive S. mutans was detected using the polymerase chain reaction. Magnetic resonance imaging at 14 ± 5 days after admission was used to evaluate DWI hyperintensities and CMBs. RESULTS: A total of 197 patients were enrolled in this study. cnm-positive S. mutans was detected in 30 patients (15.2%), and DWI hyperintensities were observed in 56 patients (28.4%). Patients with cnm-positive S. mutans had a higher frequency of DWI hyperintensities (50.0% vs 24.6%; p = 0.008) and a higher number of CMBs (5.5 vs 1.5; p < 0.001) than those without cnm-positive S. mutans. Multivariable logistic analysis revealed that the presence of cnm-positive S. mutans was independently associated with DWI hyperintensities (OR 2.38; 95% CI 1.01-5.61; p = 0.047) after adjusting for several confounding factors. CONCLUSION: This study found an association between the presence of cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.

Warm Front Passage on the Previous Day Increased Ischemic Stroke Events.

BACKGROUND AND PURPOSE: The influence of a weather front passage is rarely evaluated on stroke events. We hypothesized that a weather front passage on the stroke onset day or during the previous days may play an important role in the incidence of stroke. METHODS: A multicenter retrospective study was conducted to evaluate the frequency of stroke events and their interaction with weather front passages. Consecutive acute stroke patients (n = 3935, 73.5 ± 12.4 years, 1610 females) who were admitted to 7 stroke hospitals in 3 cities from January 2012 to December 2013 were enrolled in this study. Multivariate Poisson regression models involving time lag variables were used to compare the daily rates of stroke events with the day of a weather front passage and the previous 6 days, adjusting for considerable influences of ambient temperature and atmospheric pressure. RESULTS: There were a total of 33 cold fronts and 13 warm fronts that passed over the 3 cities during the study period. The frequency of ischemic stroke significantly increased when a warm front passed on the previous day (risk ratio 1.34, 95% confidence interval 1.07-1.69, P= .016). CONCLUSIONS: This study indicated that a weather front passage on the previous days may be associated with the occurrence of stroke.

Off-Site Indoor Localization Competitions Based on Measured Data in a Warehouse.

The performance of indoor localization methods is highly dependent on the situations in which they are used. Various competitions on indoor localization have been held for fairly comparing the existing indoor localization methods in shared and controlled testing environments. However, it is difficult to evaluate the practical performance in industrial scenarios through the existing competitions. This paper introduces two indoor localization competitions, which are named the "PDR Challenge in Warehouse Picking 2017" and "xDR Challenge for Warehouse Operations 2018" for tracking workers and vehicles in a warehouse scenario. For the PDR Challenge in Warehouse Picking 2017, we conducted a unique competition based on the data measured during the actual picking operation in an actual warehouse. We term the dead-reckoning of a vehicle as vehicle dead-reckoning (VDR), and the term "xDR" is derived from pedestrian dead-reckoning (PDR) plus VDR. As a sequel competition of the PDR Challenge in Warehouse Picking 2017, the xDR Challenge for Warehouse Operations 2018 was conducted as the world's first competition that deals with tracking forklifts by VDR with smartphones. In the paper, first, we briefly summarize the existing competitions, and clarify the characteristics of our competitions by comparing them with other competitions. Our competitions have the unique capability of evaluating the practical performance in a warehouse by using the actual measured data as the test data and applying multi-faceted evaluation metrics. As a result, we successfully organize the competitions due to the many participants from many countries. As a conclusion of the paper, we summarize the findings of the competitions.

Screening for Fabry Disease in Japanese Patients with Young-Onset Stroke by Measuring α-Galactosidase A and Globotriaosylsphingosine.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in GLA, which encodes the enzyme α-galactosidase A (α-Gal A). Although the prevalence of Fabry disease in patients with stroke has been reported to range from 0% to 4%, few cohort studies have examined Japanese stroke patients. We aimed to clarify the prevalence of Fabry disease and the frequency of GLA mutations among patients with young-onset stroke in Japan. METHODS: From April 2015 to December 2016, we enrolled patients with young-onset (≤60 years old) ischemic stroke or intracerebral hemorrhage. We measured α-Gal A activity and the concentration of globotriaosylsphingosine in plasma. Genetic evaluations were performed in patients with low α-Gal A activity or high concentrations of globotriaosylsphingosine. RESULTS: Overall, 516 patients (median age of onset, 52 years old; 120 women) were consecutively enrolled in this study. Five patients (4 men and 1 woman) had low α-Gal A activity, and no patients were detected with the screen for plasma globotriaosylsphingosine levels. The genetic analysis did not identify a causative mutation responsible for classic Fabry disease in any of the patients, but 2 patients (.4%) carried the p.E66Q in GLA. CONCLUSIONS: No patient with Fabry disease was detected in our young-onset stroke cohort.

Controlling nutritional status score for predicting 3-mo functional outcome in acute ischemic stroke.

BACKGROUND: Malnutrition is an independent risk factor for poor outcomes in patients with acute ischemic stroke. However, the indicator of malnutrition has not yet been established. We investigated the relationship between the Controlling Nutritional Status score, a useful prognostic measure of malnutrition in patients with cardiovascular diseases and malignant tumors, and functional outcomes in patients with acute ischemic stroke. METHODS: Patients with acute ischemic stroke (n = 264, 71 ± 12 y old) were consecutively evaluated within 7 d of stroke onset. The Controlling Nutritional Status score was calculated from the serum albumin, total peripheral lymphocyte count, and total cholesterol; a Controlling Nutritional Status score of 5 to 12 was defined as malnutrition. Poor functional outcome was defined as a modified Rankin Scale score of 3 to 6 at 3 mo. RESULTS: Of the total cohort, 230 patients (87.1%) were assessed. The patients with poor functional outcome (n = 85) were older; had a lower body mass index; had a higher frequency of atrial fibrillation, chronic heart failure, and anemia; and had a lower frequency of dyslipidemia and a current smoking status. In addition, the Controlling Nutritional Status score and National Institutes of Health Stroke Scale score at admission were significantly higher for the patients with poor functional outcome. After multivariate analysis, adjusted for baseline characteristics, a Controlling Nutritional Status score of 5 to 12 was found to be independently associated with poor outcome (odds ratio: 4.15, 95% confidence interval: 1.52-11.67, P = 0.005). CONCLUSIONS: The Controlling Nutritional Status score at admission could be a useful prognostic marker of 3-mo functional outcomes in patients with acute ischemic stroke.

Alpha-2-macroglobulin as a Promising Biological Marker of Endothelial Function.

AIMS: Alpha-2-macroglobulin (α2MG) is thought to be associated with inflammatory reactions and procoagulant properties that might cause ischemic stroke. Endothelial dysfunction plays an important role in atherosclerosis development and in the occurrence of cardiovascular events. In this study, we investigated whether serum α2MG levels, endothelial function, and endothelial progenitor cell (EPC) number were associated in patients with chronic stroke or cardiovascular risk factors. METHODS: Patients with a history of stroke or any established cardiovascular risk factors were enrolled in this study (n=102; 69 men, 70.1±9.2 years). Endothelial function was assessed by flow-mediated dilation (FMD). EPC numbers (CD34＋/CD133＋) were measured using flow cytometry (n=91). Serum α2MG levels were measured by nephelometry. RESULTS: Patients in the highest tertile of serum α2MG levels were older (P=0.019) and more frequently exhibited dyslipidemia (P=0.021). Univariate-regression analysis revealed that increased α2MG levels were negatively associated with FMD values (r=-0.25; P=0.010), whereas increased EPC numbers were positively associated (r=0.21; P=0.044). Multivariate-regression analysis adjusted for male gender, hypertension, and severe white-matter lesions showed that serum α2MG levels were independently associated with FMD values (standardized partial regression coefficient [ß] -0.185; P=0.033), although not significantly associated with EPC numbers. CONCLUSION: Serum α2MG levels might reflect endothelial dysfunction evaluated by FMD in patients with chronic stroke or cardiovascular risk factors.

Binding of 11C-Pittsburgh compound-B correlated with white matter injury in hypertensive small vessel disease.

OBJECTIVE: 11C-Pittsburgh compound-B (11C-PIB) positron emission tomography (PET) is used to visualize and quantify amyloid deposition in the brain cortex in pathological conditions such as Alzheimer's disease (AD). Intense 11C-PIB retention is also observed in the white matter (WM) of both healthy individuals and AD patients. However, the clinical implications of this retention in brain WM have not been clarified. We investigated the relationship between the extent of white matter lesions (WMLs) and the binding potential of 11C-PIB (BPND) in the WM in patients with hypertensive small vessel disease. We further examined the relationship between the extent of WMLs and BPND in WML and in normal-appearing white matter (NAWM). METHODS: Twenty-one hypertensive vasculopathy patients, without AD and major cerebral arterial stenosis and/or occlusion, were enrolled (9 women, 68 ± 7 years). Regions of WML and NAWM were extracted using magnetization-prepared rapid gradient-echo and fluid-attenuated inversion recovery of magnetic resonance images. Volumes of interest (VOIs) were set in the cortex-subcortex, basal ganglia, and centrum semiovale (CS). BPND in the cortex-subcortex, basal ganglia, CS, WML, and NAWM were estimated on 11C-PIB PET using Logan graphical analysis with cerebellar regions as references. The relationships between WML volume and BPND in each region were examined by linear regression analysis. RESULTS: BPND was higher in the CS and basal ganglia than in the cortex-subcortex regions. WML volume had a significant inverse correlation with BPND in the CS (Slope = -0.0042, R 2 = 0.44, P < 0.01). For intra WM comparison, BPND in NAWM was significantly higher than that in WML. In addition, although there were no correlations between WML volume and BPND in WML, WML volume was significantly correlated inversely with BPND in NAWM (Slope = -0.0017, R 2 = 0.26, P = 0.02). CONCLUSIONS: 11C-PIB could be a marker of not only cortical amyloid-ß deposition but also WM injury accompanying the development of WMLs in hypertensive small vessel disease.

Temporal Trends in Stroke Severity and Prior Antithrombotic Use Among Acute Ischemic Stroke Patients in Japan.

BACKGROUND: Few existing stroke registries allow for evaluation of stroke severity, stroke subtype and antithrombotic usage prior to stroke onset over a given time period. The present study aimed to elucidate temporal trends in initial presenting stroke severity, stroke subtype and prior antithrombotic use over a 12-year period in a Japanese multicenter stroke registry. METHODS AND RESULTS: We included 71,017 acute ischemic stroke patients (72±12 years old; 27,445 women) from the Japan Standard Stroke Registry Study (JSSRS) who were admitted to 94 hospitals between 2001 and 2012. The mean age of stroke onset increased gradually over time (P<0.001). Cardioembolic stroke patients (n=19,247) exhibited more severe NIHSS scores when compared with those with non-cardioembolic stroke (n=50,427). The proportion of cardioembolic stroke patients tended to increase over time, rising from 25.9% in 2001-2002 to 30.2% in 2011-2012 (P<0.001). Among the cardioembolic stroke patients, the frequency of prior anticoagulant use significantly increased from 15.6% in 2001-2002 to 24.8% in 2011-2012 (P<0.001). The frequency of prior antiplatelet use increased from 2001-2002 to 2007-2008 but decreased after 2007-2008. Among both cardioembolic and non-cardioembolic stroke patients, initial stroke severity at admission decreased over time, particularly after 2008. CONCLUSIONS: In this Japanese study, the mean age of ischemic stroke onset increased, while the initial neurological severity at presentation decreased, over a 12-year period. (Circ J 2016; 80: 2033-2036).

Cerebral blood flow and metabolism associated with cerebral microbleeds in small vessel disease.

OBJECTIVE: Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease. METHODS: We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and (15)O-labeled gases. The functional values in the cortex-subcortex, basal ganglia, and centrum semiovale were compared between the two groups. RESULTS: Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1-91.5 mL vs. median: 11.3; range: 4.2-73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO2 between the two groups. CONCLUSIONS: Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.