Effect of Hospital Arrival Time on Functional Prognosis of Stroke Patients: Japan Stroke Data Bank Over 20 Years.

AIMS: The impact of weekend/holiday and nighttime hospitalization on functional outcomes and long-term trends in stroke patients is unclear. We examined functional and life outcomes and changes over time. METHODS: We analyzed the clinical data of 203,176patients for hospital arrival day of week and 76,442patients for arrival times using Japan Stroke Data Bank. The endpoints were favorable outcome (Modified Rankin Scale[mRS]0-2), unfavorable outcome(mRS 5-6), and in-hospital mortality. We calculated odds ratios(OR) and 95% confidence interval(CI) of weekends/holidays and off-hours versus weekdays and on-hours for 2000-2009 and 2010-2020 using a mixed-effect multivariate model adjusted for confounding factors and evaluated interactions. Thereafter, we performed to check for year trends. RESULTS: All endpoints were worse in weekend/holiday admissions for all stroke and in off-hours hospitalization for total stroke(TS), ischemic stroke(IS), and intracerebral hemorrhage(ICH). The adjusted ORs for favorable outcomes of weekend/holiday admissions were TS, 0.90(0.87-0.93); IS, 0.89(0.86-0.93); ICH, 0.91(0.84-0.98) and unfavorable outcome TS, 1.04(1.002-1.08) IS, 1.06(1.01-1.11). Off-hour hospitalization had adjusted ORs for favorable outcome(TS, 0.86 [95% CI: 0.82-0.91]; IS, 0.90 [0.84-0.95]; ICH, 0.85 [0.75-0.96]), unfavorable outcome(TS, 1.14 [1.07-1.22]; IS, 1.13 [1.04-1.23]; ICH, 1.15 [1.01-1.31]), and mortality (TS, 1.15 [1.05-1.26]; IS, 1.17 [1.04-1.32]). For IS, the incidence of unfavorable outcomes during off-hours was significantly lower in 2010-2020 than in 2000-2009; after adjusting for reperfusion therapy, it was no longer significant. CONCLUSION: Stroke patients admitted on weekends/holidays and off-hours had worse functional and life outcomes. Functional outcomes for off-hour admission for IS improved at 10-year intervals, possibly due to improvements in stroke care systems.

Favorable prognosis in posterior circulation ischemic stroke: Insights from a nationwide stroke databank.

INTRODUCTION: Clinical trials have historically underrepresented patients with posterior circulation ischemic stroke (PCIS). This study aimed to comprehensively assess the clinical characteristics and outcomes of PCIS patients compared to those with anterior circulation ischemic stroke (ACIS). METHODS: A retrospective analysis was conducted using data from the Japan Stroke Data Bank, encompassing 20 years across 130 stroke centers. The study focused on patients diagnosed with PCIS or ACIS. RESULTS: Among 37,069 patients reviewed, 7425 had PCIS, whereas 29,644 had ACIS. PCIS patients were younger and had a lower female representation than ACIS patients. Notably, PCIS patients had more favorable outcomes: 71% achieved a modified Rankin Scale of 0-2 or showed no deterioration at discharge (17 days at the median after admission), compared to 60% for ACIS patients (p < 0.001). Factors associated with an unfavorable outcome in the PCIS subgroup were older age, female sex (assigned at birth), history of hypertension, and higher National Institute of Health Stroke Scale (NIHSS) scores at admission. In both sexes, older age and higher NIHSS scores were negatively associated with favorable outcomes. CONCLUSIONS: PCIS patients demonstrated a more favorable prognosis than ACIS patients. Factors like older age, female sex, and higher NIHSS scores at admission were identified as independent predictors of unfavorable outcomes in PCIS patients. Older age and higher NIHSS scores at admission were common independent negative factors for a favorable outcome regardless of sex.

Clinical impact of body mass index on outcomes of ischemic and hemorrhagic strokes.

BACKGROUND AND AIM: To investigate the prognostic implication of body mass index (BMI) on clinical outcomes after acute ischemic and hemorrhagic stroke. METHODS: The subjects of the study included adult patients with available baseline body weight and height data who had suffered an acute stroke and were registered in the Japan Stroke Data Bank-a hospital-based, multicenter stroke registration database-between January 2006 and December 2020. The outcome measures included unfavorable outcomes defined as a modified Rankin Scale (mRS) score of 5-6 and favorable outcomes (mRS 0-2) at discharge, and in-hospital mortality. Mixed effects logistic regression analysis was conducted to determine the relationship between BMI categories (underweight, normal weight, overweight, class I obesity, class II obesity; <18.5, 18.5-23.0, 23.0-25.0, 25-30, ⩾30 kg/m2) and the outcomes, after adjustment for covariates. RESULTS: A total of 56,230 patients were assigned to one of the following groups: ischemic stroke (IS, n = 43,668), intracerebral hemorrhage (ICH, n = 9741), and subarachnoid hemorrhage (SAH, n = 2821). In the IS group, being underweight was associated with an increased likelihood of unfavorable outcomes (odds ratio, 1.47 (95% confidence interval (CI):1.31-1.65)) and in-hospital mortality (1.55 (1.31-1.83)) compared to outcomes in those with normal weight. Being overweight was associated with an increased likelihood of favorable outcomes (1.09 (1.01-1.18)). Similar associations were observed between underweight and these outcomes in specific IS subtypes (cardioembolic stroke, large artery stroke, and small-vessel occlusion). Patients with a BMI ⩾30.0 kg/m2 was associated with an increased likelihood of unfavorable outcomes (1.44 (1.01-2.17)) and in-hospital mortality (2.42 (1.26-4.65)) in large artery stroke. In patients with ICH, but not those with SAH, being underweight was associated with an increased likelihood of unfavorable outcomes (1.41 (1.01-1.99)). CONCLUSIONS: BMI substantially impacts functional outcomes following IS and ICH. Lower BMI consistently affected post-stroke disability and mortality, while higher BMI values similarly affected these outcomes after large artery stroke.

Improvement of Functional Outcomes in Patients with Stroke who Received Alteplase for Over 15 Years: Japan Stroke Data Bank.

AIM: The nationwide verification of intravenous thrombolysis (IVT) was rarely performed after the extension of the therapeutic time window of alteplase or after the expansion of mechanical thrombectomy (MT). We aimed to examine the long-term change in accurate real-world outcomes of IVT in patients with acute ischemic stroke (AIS) using the Japan Stroke Databank, a representative Japan-wide stroke database. METHODS: We extracted all patients with AIS who received IVT with alteplase between October 11, 2005, the approval date for alteplase use for AIS in Japan, and December 31, 2020. Patients were categorized into three groups using two critical dates in Japan as cutoffs: the official extension date of the therapeutic time window for IVT to within 4.5 h of symptom onset and the publication date of the revised guideline, where the evidence level of MT was heightened. We assessed the yearly trend of IVT implementation rates and the secular changes and three-group changes in clinical outcomes at discharge. RESULTS: Of 124,382 patients with AIS, 9,569 (7.7%) received IVT (females, 41%; median age, 75 years). The IVT implementation rate has generally increased over time and plateaued in recent years. The proportion of favorable outcomes (modified Rankin Scale score of 0-2) increased yearly over 15 years. The results of the changes in the outcomes of the three groups were similar to those of the annual changes. CONCLUSIONS: We revealed that IVT implementation rates in patients with AIS increased, and the functional outcome in these patients improved over 15 years. Therefore, the Japanese IVT dissemination strategy is considered appropriate and effective.

Effects of Obesity, Blood Pressure, and Blood Metabolic Biomarkers on Grey Matter Brain Healthcare Quotient: A Large Cohort Study of a Magnetic Resonance Imaging Brain Screening System in Japan.

This study investigated the relationship between grey matter (GM) volume and blood biomarkers, blood pressure, and obesity. We aimed to elucidate lifestyle factors that promote GM volume loss. A total of 1799 participants underwent the brain dock as a medical checkup. Data regarding blood pressure, obesity measurements, and standard blood biomarkers were obtained. Further, brain magnetic resonance imaging (MRI), including high-resolution T1-weighted imaging, was performed. We calculated the grey matter brain healthcare quotient (GM-BHQ), which represents GM volume as a deviation value. After adjusting for confounding variables, multiple regression analysis revealed that body mass index (BMI) (b = −0.28, p < 0.001), gamma-glutamyltransferase (γ-GTP) (b = −0.01, p = 0.16), and fasting blood glucose (b = −0.02, p = 0.049) were significantly correlated with GM-BHQ. Although the current cross-sectional study cannot determine a cause-and-effect relationship, elevated BMI, γ-GTP, and fasting blood glucose could promote GM volume loss.

Relationship between Alcohol Intake and Stroke Severity in Japanese Patients: a Sex- and Subtype-Stratified Analysis.

OBJECTIVES: This study aims to clarify the association between alcohol intake and stroke severity at admission and discharge according to sex and stroke subtype in Japanese patients with acute stroke. MATERIALS AND METHODS: We analyzed the data of 199,599 patients registered in the Japan Stroke Data Bank from 1999 to 2018, including sex, age, stroke subtypes (cardioembolic ischemic, noncardioembolic ischemic, hypertensive hemorrhagic, nonhypertensive hemorrhagic, and subarachnoid hemorrhagic), dates of onset and admission, National Institutes of Health Stroke Scale score at admission, modified Rankin Scale score at discharge, and alcohol intake. Multivariable logistic regression analysis adjusted for stroke-related factors was performed to estimate the odds ratios of alcohol intake for stroke severity. RESULTS: In cardioembolic ischemic stroke, a significant protective effect of moderate intake on severity at admission was observed in both sexes. In noncardioembolic ischemic stroke, a significant protective effect on stroke severity at admission was found for each sex. At discharge, the results also showed a significant protective effect for each sex with moderate intake. For both subtypes of ischemic stroke, a J-shaped relationship between alcohol intake and stroke severity at admission and discharge was observed in women and men. In hypertensive hemorrhagic stroke, a significant protective effect was found in men at both admission and discharge. In women, heavy drinking had a significant harmful effect on stroke severity at admission. CONCLUSIONS: Habitual alcohol intake is associated with stroke severity at admission and discharge regardless of sex.

Etiology and Outcome of Ischemic Stroke in Patients With Renal Impairment Including Chronic Kidney Disease: Japan Stroke Data Bank.

BACKGROUND AND OBJECTIVES: Chronic kidney disease is a worldwide public health problem that is recognized as an established risk factor for stroke. It remains unclear whether its distribution and clinical impact are consistent across ischemic stroke subtypes in patients with renal impairment. We examined whether renal impairment was associated with the proportion of each stroke subtype vs ischemic stroke overall and with functional outcomes after each stroke subtype. METHODS: Study participants were 10,392 adult patients with an acute stroke from the register of the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between October 2016 and December 2019, whose baseline serum creatinine levels or a dipstick proteinuria result were available. All ischemic strokes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Unfavorable functional outcome was defined as modified Rankin Scale (mRS) score 3-6 at discharge. Mixed effect logistic regression was used to determine the relationship between the outcomes and the estimated glomerular filtration rate (eGFR), eGFR strata (<45, 45-59, ≥60 mL/min/1.73 m2), or dipstick proteinuria ≥1 adjusted for covariates. RESULTS: Overall, 2,419 (23%) patients had eGFR 45-59 mL/min/1.73 m2 and 1,976 (19%) had eGFR <45 mL/min/1.73 m2, including 185 patients (1.8%) receiving hemodialysis. Both eGFR 45-59 and eGFR <45 mL/min/1.73 m2 were associated with a higher proportion of cardioembolic stroke (odds ratio [OR], 1.21 [95% CI, 1.05-1.39] and 1.55 [1.34-1.79], respectively) and a lower proportion of small vessel occlusion (0.79 [0.69-0.90] and 0.68 [0.59-0.79], respectively). A similar association with the proportion of these 2 subtypes was proven in the analyses using decreased eGFR as continuous values. Both eGFR <45 mL/min/1.73 m2 and proteinuria were associated with unfavorable functional outcomes in patients with cardioembolic stroke (OR, 1.30 [95% CI, 1.01-1.69] and 3.18 [2.03-4.98], respectively) and small vessel occlusion (OR, 1.44 [1.01-2.07] and 2.08 [1.08-3.98], respectively). DISCUSSION: Renal impairment contributes to the different distributions and clinical effects across specific stroke subtypes, particularly evident in cardioembolic stroke and small vessel occlusion. This possibly indicates shared mechanisms of susceptibility and potentially enhancing pathways.

Twenty-Year Change in Severity and Outcome of Ischemic and Hemorrhagic Strokes.

Importance: Whether recent changes in demographic characteristics and therapeutic technologies have altered stroke outcomes remains unknown. Objective: To determine secular changes in initial neurological severity and short-term functional outcomes of patients with acute stroke by sex using a large population. Design, Setting, and Participants: This nationwide, hospital-based, multicenter, prospective registry cohort study used the Japan Stroke Data Bank and included patients who developed acute stroke from January 2000 through December 2019. Patients with stroke, including ischemic and hemorrhagic strokes, who registered within 7 days after symptom onset were studied. Modified Rankin Scale scores were assessed at hospital discharge for all patients. Exposure: Time. Main Outcomes and Measures: Initial severity was assessed by the National Institutes of Health Stroke Scale for ischemic stroke and intracerebral hemorrhage and by the World Federation of Neurological Surgeons grading for subarachnoid hemorrhage. Outcomes were judged as favorable if the modified Rankin Scale score was 0 to 2 and unfavorable if 5 to 6. Results: Of 183 080 patients, 135 266 (53 800 women [39.8%]; median [IQR] age, 74 [66-82] years) developed ischemic stroke, 36 014 (15 365 women [42.7%]; median [IQR] age, 70 [59-79] years) developed intracerebral hemorrhage, and 11 800 (7924 women [67.2%]; median [IQR] age, 64 [53-75] years) developed subarachnoid hemorrhage. In all 3 stroke types, median ages at onset increased, and the National Institutes of Health Stroke Scale and World Federation of Neurological Surgeons scores decreased throughout the 20-year period on multivariable analysis. In ischemic stroke, the proportion of favorable outcomes showed an increase over time after age adjustment (odds ratio [OR], 1.020; 95% CI, 1.015-1.024 for women vs OR, 1.015; 95% CI, 1.011-1.018 for men) but then stagnated, or even decreased in men, on multivariate adjustment including reperfusion therapy (OR, 0.997; 95% CI, 0.991-1.003 for women vs OR, 0.990; 95% CI, 0.985-0.994 for men). Unfavorable outcomes and in-hospital deaths decreased in both sexes. In intracerebral hemorrhage, favorable outcomes decreased in both sexes, and unfavorable outcomes and deaths decreased only in women. In subarachnoid hemorrhage, the proportion of favorable outcomes was unchanged, and that of unfavorable outcomes and deaths decreased in both sexes. Conclusions and Relevance: In this study, functional outcomes improved in patients with ischemic stroke during the past 20 years in both sexes presumably partly owing to the development of acute reperfusion therapy. The outcomes of patients with hemorrhagic stroke did not clearly improve in the same period.

Grey-matter brain healthcare quotient and cognitive function: A large cohort study of an MRI brain screening system in Japan.

There is sometimes a divergence between brain atrophy and impairments in cognitive function. The present study aimed to assess the relationship between cognitive function and the grey-matter brain healthcare quotient (GM-BHQ), which represents brain volume as a deviation value. In addition, we aimed to investigate lifestyle factors that can help maintain cognitive function despite brain atrophy. A total of 1,757 adults included in a Japanese MRI brain screening cohort underwent MRI. We classified the participants into two age groups: under 65 years old (young adult/middle age group) and over 64 years old (elder group). The GM-BHQ was more strongly correlated with cognitive function in the young adult/middle age group than in the elder group (p < .01). Regression analysis revealed that years of education was associated with the maintenance of cognitive function despite brain atrophy (p < .05). In conclusion, our findings suggest that the relationship between brain volume and cognitive function becomes more obscure with age.

Visualisation of the non-linear correlation between age and poor outcome in patients with aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To visualise the non-linear correlation between age and poor outcome at discharge in patients with aneurysmal subarachnoid haemorrhage (SAH) while adjusting for covariates, and to address the heterogeneity of this correlation depending on disease severity by a registry-based design. METHODS: We extracted data from the Japanese Stroke Databank registry for patients with SAH treated via surgical clipping or endovascular coiling within 3 days of SAH onset between 2000 and 2017. Poor outcome was defined as a modified Rankin Scale Score ≥3 at discharge. Variable importance was calculated using machine learning (random forest) model. Correlations between age and poor outcome while adjusting for covariates were determined using generalised additive models in which spline-transformed age was fit to each neurological grade of World Federation of Neurological Societies (WFNS) and treatment. RESULTS: In total, 4149 patients were included in the analysis. WFNS grade and age had the largest and second largest variable importance in predicting the outcome. The non-linear correlation between age and poor outcome was visualised after adjusting for other covariates. For grades I-III, the risk slope for unit age was relatively smaller at younger ages and larger at older ages; for grade IV, the slope was steep even in younger ages; while for grade V, it was relatively smooth, but with high risk even at younger ages. CONCLUSIONS: The clear visualisation of the non-linear correlation between age and poor outcome in this study can aid clinical decision making and help inform patients with aneurysmal SAH and their families better.

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank.

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II-V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III-V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model's scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.

[Use AI for Dementia Diagnosis].

Using AI for dementia diagnosis is still in research stage, however some of the work points to the development of new medical devices. One is a voxel-based morphometry analysis of brain atrophy, and a brain network analysis using a resting state functional MRI and diffusion tensor imaging. The other is an application to detect dementia in daily life using "IoT" technology. As it has been determined that elderly people's dementia is closely related to lifestyle, the use of AI in the diagnosis is to predict the possibility of dementia in the preclinical stage and to link it to prevention, rather than to provide a definitive diagnosis.

Effect of Edaravone on Neurological Symptoms in Real-World Patients With Acute Ischemic Stroke.

Background and Purpose- In Japan, nearly half of ischemic stroke patients receive edaravone for acute treatment. The purpose of this study was to assess the effect of edaravone on neurological symptoms in patients with ischemic stroke stratified by stroke subtype. Methods- Study subjects were 61 048 patients aged 18 years or older who were hospitalized ≤14 days after onset of an acute ischemic stroke and were registered in the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between June 2001 and July 2013. Patients were stratified according to ischemic stroke subtype (large-artery atherosclerosis, cardioembolism, small-vessel occlusion, and cryptogenic/undetermined) and then divided into 2 groups (edaravone-treated and no edaravone). Neurological symptoms were evaluated using the National Institutes of Health Stroke Scale (NIHSS). The primary outcome was changed in neurological symptoms during the hospital stay (ΔNIHSS=NIHSS score at discharge-NIHSS score at admission). Data were analyzed using multivariate linear regression with inverse probability of treatment weighting after adjusting for the following confounding factors: age, gender, and systolic and diastolic blood pressure at the start of treatment, NIHSS score at admission, time from stroke onset to hospital admission, infarct size, comorbidities, concomitant medication, clinical department, history of smoking, alcohol consumption, and history of stroke. Results- After adjusting for potential confounders, the improvement in NIHSS score from admission to discharge was greater in the edaravone-treated group than in the no edaravone group for all ischemic stroke subtypes (mean [95% CI] difference in ΔNIHSS: -0.46 [-0.75 to -0.16] for large-artery atherosclerosis, -0.64 [-1.09 to -0.2] for cardioembolism, and -0.25 [-0.4 to -0.09] for small-vessel occlusion). Conclusions- For any ischemic stroke subtype, edaravone use (compared with no use) was associated with a greater improvement in neurological symptoms, although the difference was small (<1 point NIHSS) and of limited clinical significance.

Relationships between Alcohol Intake and Ischemic Stroke Severity in Sex Stratified Analysis for Japanese Acute Stroke Patients.

BACKGROUND: The aim of this study is to evaluate in the relationships between alcohol intake and ischemic stroke severity in Japanese stroke patients. METHODS: Of a total of 101,165 registered cases of stroke in Japan, patient data of total strokes (n = 60,836), cardiogenic strokes (n = 11,894), and noncardiogenic strokes (n = 29,129) were extracted. The National Institutes of Health Stroke Scale (NIHSS) score at admission and the modified Rankin Scale (mRS) score at discharge were used. Significant alcohol consumption in regard to stroke severity at admission and discharge was identified by multivariate adjusted logistic regression analysis. RESULTS: Among all subject and males, nondrinkers had significantly poorer NIHSS scores of cardiogenic strokes as did those consuming greater than or equal to 60 g/day, whereas there was a significant difference in past heavy drinkers with noncardiogenic strokes. Among females, nondrinkers had a significance of cardiogenic stroke and non-cardiogenic strokes. Among all subjects and males, 20-39 g/day and 40-59 g/day were significantly associated with protective effects on mRS severity of cardiogenic strokes, whereas 40-59 g/day also had significant protective effects for noncardiogenic strokes. Among females, greater than or equal to 60 g/day had a significant protective effect for cardiogenic strokes. CONCLUSIONS: For males, alcohol intake of less than 60 g/day played a protective role in functional prognosis at discharge and showed a J-shape relationship. For females, although there was a limitation that the number of female drinkers was small, negative effects were shown at admission with less consumption than males.

Transplantation of a bone marrow mesenchymal stem cell line increases neuronal progenitor cell migration in a cerebral ischemia animal model.

Mesenchymal stem cell (MSC) transplantation is demonstrated to improve functional and pathological recovery in cerebral ischemia. To understand the underlying mechanism, we transplanted a MSC line (B10) in a rat middle cerebral artery occlusion (MCAO) model and checked the proliferation and migration of neuronal progenitor cells (NPCs). B10 transplantation increased NPCs in the subventricular zone and their migration towards the lesion area at an earlier time. Fourteen days after MCAO, some NPCs were differentiated to neurons and astrocytes. Although B10 transplantation increased total number of both astrocytes and neurons, it only increased the differentiation of NPC to astrocyte. The mRNA of polysialylation enzyme ST8SiaIV and a chemokine SDF-1 were persistently increased in B10-transplanted groups. SDF-1-positive cell number was increased in the core and penumbra area, which was expressed in macrophage/microglia and transplanted B10 cells at 3 days after MCAO. Furthermore, SDF-1 mRNA expression in cell culture was high in B10 compared to a microglia (HMO) or a neuronal (A1) cell line. B10 culture supernatant increased in vitro A1 cell migration, which was significantly inhibited by siRNA-mediated SDF-1 silencing in B10. Thus, our results suggested that MSC transplantation increased endogenous NPC migration in cerebral ischemic condition by increasing chemokine and polysialylation enzyme expression, which could be helpful for the restorative management of cerebral ischemia.

Effect of actual age on outcome at discharge in patients by surgical clipping and endovascular coiling for ruptured cerebral aneurysm in Japan.

The Japanese population features the highest rate of elderly individuals worldwide. However, the difference of actual age indication for surgical clipping (SC) and endovascular coiling (EC) has never reported. We clarified the effect of actual age on poor outcome at discharge in patients by each treatment for ruptured cerebral aneurysm according to the Japanese Stroke Data Bank. A total of 3593 patients with ruptured saccular cerebral aneurysm were treated by SC and/or EC between 2000 and 2013. The effect of actual age on poor outcome (modified Rankin scale [mRS] score > 2) at discharge was evaluated by the cutoff age using receiver operating characteristic analysis for each treatment. There were 2666 cases in the SC group and 881 cases in the EC group. The cutoff age for poor outcome was 3 to 9 years older for EC than for SC. The gap of cutoff age between two treatments was 3 years shorter in mild subarachnoid hemorrhage than severe cases. The gap of cutoff age between two treatments was 7 years in elderly patients over 65 years old. The cutoff age was 78 years old for both SC and EC in elderly female patients. In conclusion, the cutoff age for poor mRS score > 2 was 3 to 9 years older for EC than for SC. Actual age was one of the indications for elderly patients to achieve the optimum outcome; however, the treatment indication should be carefully considered based on the condition in each country.

Analysis of outcome at discharge after aneurysmal subarachnoid hemorrhage in Japan according to the Japanese stroke databank.

The outcomes at discharge for ruptured cerebral aneurysms after subarachnoid hemorrhage (SAH) were investigated using data from the Japanese stroke databank. Among 101,165 patients with acute stroke registered between 2000 and 2013, 4693 patients had SAH caused by ruptured saccular aneurysm. Of these, 3593 patients (1140 men and 2453 women; mean age 61.3 ± 13.7 years) were treated by surgical clipping (SC) and/or endovascular coiling (EC). The outcomes of modified Rankin scale (mRS) at discharge were compared between the SC and EC groups. There were 2666 cases in the SC group, 881 cases in the EC group, and 46 cases in the SC and EC group. The rates of poor outcome of mRS > 2 were 33.0 and 45.5% in the SC and EC groups (p < 0.05), respectively. Cases were selected using two types of criteria compatible with both treatments. Under the first compatible criteria, the rates of poor outcome of mRS > 2 were 18.9 and 24.8% in the SC and EC groups (p < 0.05), respectively. Under the second compatible criteria, the rates of poor outcome of mRS > 2 were 16.0 and 14.8% in the SC and EC groups (p = 0.22), respectively. No significant differences were found in clinical characteristics or outcomes between the two groups. Multivariate analysis of aneurysmal SAH revealed no significant risk for poor outcome associated with the treatment method. The present study was not a randomized controlled study, but no significant differences in mRS at discharge were found between SC and EC in the Japanese stroke databank.

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).

Greater Severity of Neurological Defects in Women Admitted With Atrial Fibrillation-Related Stroke.

BACKGROUND: The magnitude of the CHA2DS2-VASc score is associated with not only stroke incidence but also long-term outcomes. The association between sex and initial stroke severity in AF-related cardioembolic stroke patients has not been clarified. The present study aimed to elucidate the risk factors for initial stroke severity among patients with cardioembolic stroke enrolled in a multicenter registry. METHODS AND RESULTS: We selected 12,701 patients (age, 77±10 years; 5,653 women) with AF-related cardioembolic stroke from the Japan Standard Stroke Registry Study between January 2000 and July 2013. Indicators of National Institutes of Health Stroke Scale (NIHSS) scores at admission were identified using a multiple linear regression. Increased NIHSS scores positively correlated with CHA2DS2-VASc score (ρ=0.197; P<0.001). The initial neurological deficits were more severe in women than in men (NIHSS scores, median [interquartile range] 14 [5-22] vs. 8 [3-18]; P<0.001). Multiple regression analysis revealed that higher age (standardized partial regression coefficient [ß] 0.162; P<0.001), female sex (ß 0.120; P<0.001), diabetes mellitus (ß 0.020; P=0.019), dyslipidemia (ß -0.076; P<0.001), congestive heart failure (ß 0.039; P<0.001), vascular disease (ß 0.030; P=0.001), prior stroke/TIA (ß 0.085; P<0.001) and prior anticoagulant use (ß -0.020; P=0.028) were associated with the NIHSS score at admission. CONCLUSIONS: Female sex was independently associated with the initial neurological severity among AF-related cardioembolic stroke patients.

A human neural stem cell line provides neuroprotection and improves neurological performance by early intervention of neuroinflammatory system.

A human neural stem cell line, HB1.F3, demonstrated neuroprotective properties in cerebral ischemia animal models. In this study, we have investigated about the mechanisms of such neuroprotection, mainly focusing on the neuroinflammatory system at an earlier time point of the pathology. Cerebral ischemia model was generated by middle cerebral artery occlusion (MCAO) in adult male Wister rats. HB1.F3 cells were transplanted through jugular vein 6h after MCAO. Forty eight hours after MCAO, transplanted rats showed better neurological performance and decreased TUNEL positive apoptotic cell number in the penumbra. However, haematoxylin and eosin staining and immunostaining showed that, HB1.F3 cells did not affect the necrotic cell death. Twenty four hours after MCAO (18h after HB1.F3 transplantation), infiltrated granulocytes and macrophage/microglia number in the core regions were decreased compared to PBS-treated controls. Immunohistochemical analysis further demonstrated that the transplantation decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressing cell number in the core and penumbra, respectively. Double immunofluorescence results revealed that iNOS was mainly expressed in granulocytes and macrophage/microglia in the core region, and COX-2 mainly expressed in neurons, endothelial cells and granulocytes in penumbra. Further analysis showed that although the percentage of iNOS expressing granulocytes and macrophage/microglia was not decreased, COX-2 expressing neurons and vessel number was decreased by the transplantation. In vitro mRNA analysis showed that brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (ßFGF) and bone morphogenic protein (BMP)-4 expression was high in cultured HB1.F3 cells. Thus, our results demonstrated that HB1.F3 cell transplantation provide neuroprotection possibly through the regulation of early inflammatory events in the cerebral ischemia condition.