The Body Mass Index as a Determinant of Acute Ischemic Location in Mild Non-cardioembolic Stroke Patients.

Objective Although the body mass index (BMI) is considered a meaningful parameter for evaluating obesity, the association between the BMI and acute non-cardioembolic stroke remains unclear. We investigated how the BMI was related to patients' background, type of infarction, and infarction location in patients with non-cardioembolic stroke using an acute dual study (ADS) cohort. Methods The ADS trial was conducted between May 2011 and June 2017 in Japan. The BMI classifications were those proposed by the World Health Organization classification: underweight, <18.5 kg/m2; normal weight, 18.5-24.9 kg/m2; overweight, 25-29.9 kg/m2; and obese, ≥30 kg/m2. Results Data from 1136 patients were analyzed. The median BMI was 23.6 kg/m2 (interquartile range: 21.6-25.8 kg/m2), with a BMI ≥30 kg/m2 in 63 patients (6%), 25-29.9 kg/m2 in 321 (28%), 18.5-24.9 kg/m2 in 692 (61%), and <18.5 kg/m2 in 60 (5%). The group with a BMI ≥30 kg/m2 was the youngest, and the group with a BMI <18.5 kg/m2 was the oldest (p<0.001). The proportion of patients with a history of hypertension (p<0.001), diabetes (p<0.001), dyslipidemia (p<0.001), and statin therapy (p=0.005) increased with increasing BMI. Pontine infarcts were frequent in the following order: obese, overweight, normal weight, and underweight (24%, 18%, 14%, and 13%, respectively; p=0.034). In contrast, cortical infarct were frequent in the order of underweight, normal weight, overweight, and obese at 20%, 19%, 14%, and 3%, respectively (p=0.007). Conclusion Acute stroke patients with a high BMI have more atherosclerosis-related factors in their backgrounds than those with lower BMIs. In addition, the BMI may be a determinant of infarct location in patients with acute stroke.

Intima-Media Thickness in the Carotid Bifurcation is Related to Silent Brain Infarction: A Cross-Sectional Study.

AIMS: Carotid intima-media thickness (IMT) measurement is used to assess subclinical atherosclerosis. We aimed to examine the association between the maximum IMT by location and the occurrence of silent brain infarction (SBI). METHODS: Overall, 280 Japanese individuals (92 females, 52.6±5 years old) underwent a medical check-up at our hospital in Tokyo in 2015. Carotid IMT was measured at each site on ultrasound images (common carotid artery [CCA], internal carotid artery, or bifurcation). The risk factors for arterial dysfunction were evaluated. SBI was assessed using magnetic resonance imaging (MRI). The cross-sectional relationship between carotid maximum IMT and SBI was evaluated. RESULTS: Of the 280 individuals, 18 (6.4%) were diagnosed with SBI on MRI. The mean age of the SBI(-) and SBI(+) groups was 51.9±10.6 and 63.6±18.6 years, respectively. The correlation coefficients between the carotid maximum IMT at each location were very weak (correlation coefficient range: 0.180-0.253). The percentage of participants with SBI increased significantly with increasing maximum CCA and bIMT values. After adjusting for confounders, SBI was found to be significantly associated with the maximum bIMT (per 0.1-mm increase) (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI]: 1.03-1.17). When bIMT was categorized according to three groups (＜1.0 mm, 1.0-＜2.0 mm, and ≥ 2.0 mm), a significant SBI risk was also observed with an increase by each category of bIMT (aOR: 3.96, 95% CI: 1.63-9.52, P=0.002). CONCLUSION: The maximum bIMT was found to be the main determinant of SBI. A significant SBI risk was associated with an increase in each category of the maximum bIMT. Therefore, the maximum bIMT might be a useful predictor of future stroke in Japanese stroke-free medical check-up participants.

High brain natriuretic peptide level is associated with severe stroke in patients taking oral anticoagulants: A sub-analysis of the PASTA registry study.

BACKGROUND: Brain natriuretic peptides (BNP) are an important diagnostic and prognostic marker in patients with heart failure. However, the relationship between BNP levels and stroke severity in patients with atrial fibrillation (AF) remains unelucidated. In this study, we aimed to investigate the association between stroke severity at admission and BNP levels. METHODS: In this prospective observational study, we used data from 513 patients with AF and acute ischemic stroke treated with oral anticoagulants (OAC) registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study. The patients were divided into two groups: high-BNP (≥200 pg/mL) and low-BNP level (<200 pg/mL) groups. We compared the clinical characteristics between the two groups and determined the effect of BNP levels on stroke severity on admission. RESULTS: Among the 513 enrolled patients, 248 (females, n = 30; median age, 82 years) and 265 (females, n = 76; median age, 71 years) were assigned to the high- and low-BNP level groups, respectively. The high-BNP level group had a higher proportion of patients with severe stroke (National Institutes of Health Stroke Scale score, ≥10) on admission (49.2% vs. 32.8%, p = 0.002) and major vessel occlusion (57.5% vs. 39.2%, p < 0.0001) than that had by the low-BNP level group. Multivariate analysis showed that high BNP level was independently associated with severe stroke on admission (odds ratio 1.07, 95% confidence interval 1.00-1.15; p = 0.0478). CONCLUSIONS: High BNP level compared with low BNP level was associated with severe stroke and major vessel occlusion, even before OAC treatment.

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis.

Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

Magnetic Resonance Imaging-Guided Intravenous Thrombolysis in Cardioembolic Stroke Patients With Unknown Time of Onset　- Subanalysis of the THAWS Randomized Control Trial.

BACKGROUND: We investigated the clinical effect of intravenous thrombolysis using a magnetic resonance imaging (MRI)-guided approach in cardioembolic stroke (CE) patients with unknown time of onset.Methods and Results: This subanalysis of the THAWS trial assessed the efficacy and safety of alteplase 0.6 mg/kg in CE patients with unknown time of onset and showing diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch. Patients were classified as CE and non-CE using the SSS-TOAST classification system during the acute period. The efficacy outcome was a modified Rankin Scale score of 0-1 at 90 days. In all, 126 patients from the THAWS trial were included in this study, of whom 45 (35.7%) were diagnosed with CE. In the CE group, a favorable outcome was numerically more frequent in the alteplase than control group (52% vs. 35%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 0.50-9.99). However, in the non-CE group, favorable outcomes were comparable between the alteplase and control groups (44% vs. 55%, respectively; aOR 0.39; 95% CI 0.12-1.21). Treatment-by-cohort interaction for a favorable outcome was modestly significant between the CE and non-CE groups (P=0.069). In the CE group, no patients experienced symptomatic intracranial hemorrhage (ICH) or parenchymal hematoma Type II following thrombolysis. CONCLUSIONS: When an MRI-guided approach is used, CE patients with unknown time of onset appear to be suitable candidates for thrombolysis.

Clinical characteristics of stroke in SARS-CoV-2 infected patients in Japan: A prospective nationwide study.

INTRODUCTION: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan. METHODS: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately. RESULTS: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26). CONCLUSION: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log10 D-dimer. REGISTRATION: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

The effect of asymptomatic intracranial hemorrhage after mechanical thrombectomy on clinical outcome.

BACKGROUND AND OBJECTIVE: Whether asymptomatic intracranial hemorrhage (ICH) affects the clinical outcomes in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains unclear. This study aimed to address this uncertainty. METHODS: We retrospectively analyzed patients with acute ischemic stroke and internal carotid or middle cerebral (M1 segment) artery occlusion treated with MT between April 2011 and March 2021 at a single center. All patients had a premorbid modified Rankin scale (mRS) score ≤ 2 and an anterior circulation occlusion and underwent magnetic resonance imaging at admission. Asymptomatic ICH was defined as ICH without symptomatic ICH defined by the SITS-MOST criteria. A favorable outcome was defined as an mRS score ≤ 2 at 90 days after stroke onset. RESULTS: Our study included 349 patients; 62% were men, the median age was 76 [67-83] years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 15 [8-21]. As determined via computed tomography, 103 (30%) patients had ICH (20 symptomatic and 83 asymptomatic). The favorable outcome rate was significantly lower for asymptomatic vs. no ICH (30% vs. 67%, p < 0.01). In a multivariate regression analysis, a high NIHSS score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p < 0.01) and low Alberta Stroke Program Early CT Score (OR, 0.78; 95% CI, 0.65-0.92; p < 0.01) were independent risk factors for ICH. CONCLUSIONS: Asymptomatic ICH is associated with poor clinical outcome at 90 days after stroke onset.

Hyperglycemia and Outcomes in Patients with Successful Reperfusion by Mechanical Thrombectomy.

Background This study examined whether or not hyperglycemia on admission is associated with poor outcomes in patients with successful reperfusion by mechanical thrombectomy (MT). Methods Consecutive patients with acute anterior circulation stroke and large-vessel occlusion treated with MT were evaluated. Hyperglycemia was defined as a blood glucose level of >140 mg/dL on admission. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction of grade 2b or 3. A poor clinical outcome 90 days after the onset was defined as a modified Rankin Scale score of 4-6. We compared characteristics, including outcomes, between the normoglycemic (≤140 mg/dL) and hyperglycemic groups. In addition, the association between hyperglycemia and outcomes was evaluated in patients with successful reperfusion using MT. Results The participants comprised 407 patients (median age, 76.5 years old; 58.0% men; median NIHSS (National Institutes of Health Stroke Scale) score, 17). The site of occlusion was the ICA (Internal Carotid Artery) in 119 patients (29.2%) and the M1 in 178 patients (43.7%). Normoglycemia, hyperglycemia, successful reperfusion, and poor outcomes were found in 138 (33.9%), 269 (66.1%), 320 (78.6%), and 141 (34.4%) patients, respectively. Poor outcomes were more frequent in hyperglycemic patients (61.6%) than in normoglycemic patients (43.9%, P=0.001). Among patients with successful reperfusion, poor outcomes were more frequent in hyperglycemic patients (57.8%) than in normoglycemic patients (37.9%; P<0.001). In patients with successful reperfusion, a multivariate regression analysis identified hyperglycemia as a factor associated with poor outcomes (odds ratio, 2.151; confidence interval, 1.166-3.970; P=0.014). Conclusions Among all patients, hyperglycemia on admission was associated with a poor outcome in those treated with MT. Regarding the presence of successful reperfusion by MT, patients with successful reperfusion had such effects.

Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Cilostazol addition to aspirin may worsen the short-term outcome in patients with large artery disease: ADS subanalysis.

BACKGROUND: Our previous acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of neurological deterioration in non-cardioembolic stroke patients. In this post-hoc analysis, we investigated whether the impact of dual antiplatelet therapy (DAPT) may depend on neurological severity, as represented by large artery disease. METHODS: Neurological deterioration was defined as neurological progression with an increment of the National Institutes of Health Stroke Scale (NIHSS) score of ≥2. NIHSS score subgroups were divided into that of 0-1, 2-4, 5-10, and >10. RESULTS: Among 1014 patients, 203 (20%) had the large artery disease, and 811 (80%) did not. In the total cohort, the rate of neurological deterioration was 10.8% in the DAPT group and 8.3% in the aspirin group (P = 0.197). When we focused on the large artery disease group, DAPT group had a higher rate of neurological deterioration as 18.3% compared to 8.2% in the aspirin group (P = 0.036). Among patients with NIHSS score of 0-1 and 2-4, the rates of neurological deterioration were not different between the two group (both, P = 1.000). However, when NIHSS score elevated to 5-10, 45% in the DAPT group and 9.1% in the aspirin group deteriorated (P = 0.013). Among the patients with NIHSS score of >10, 60% in the DAPT group and none (0%) in the aspirin group had the neurological deterioration (P = 0.045). CONCLUSION: DAPT with aspirin and cilostazol was associated with higher rate of neurological deterioration when patients have large artery disease and not mild neurological deficits.

High pre-stroke CHADS2 score predicts unfavorable functional outcome in acute cardioembolic stroke patients prescribed oral anticoagulant therapy: A sub-analysis of the PASTA registry study.

BACKGROUND AND PURPOSE: The impact of CHADS2 score on outcome in patients with stroke taking an oral anticoagulant (OAC) has not yet been fully elucidated. We investigated the association between pre-stroke CHADS2 score and outcome at discharge in patients with acute cardioembolic (CE) stroke due to atrial fibrillation (AF) who were prescribed OAC. METHODS: The data of 548 OAC-treated patients with AF and CE stroke who were registered in the multicenter Prospective Analysis of Stroke patients Taking oral Anticoagulants (PASTA) study were analyzed. High CHADS2 score was defined as a pre-stroke CHADS2 score ≥2. Unfavorable outcome was defined as a modified Rankin scale (mRS) of 3-6. The impacts of pre-stroke CHADS2 score on outcome at discharge were evaluated using multiple logistic regression analysis. RESULT: A high CHADS2 score was found in 472/548 patients and unfavorable outcome was found in 330/548 patients. In patients with unfavorable outcome, age, male sex, pre-stroke CHADS2 score, initial National Institute Health Stroke Scale (NIHSS) score, and glucose level on admission were significantly higher, whereas creatinine clearance and body weight were significantly lower, than those with favorable outcome (each p < 0.001). Multivariate logistic regression analysis indicated that high CHADS2 score (OR 2.18, 95 %CI 1.08-4.42, p = 0.031), pre-stroke mRS (OR 2.21, 95 %CI 1.69-2.67, p < 0.001), and initial NIHSS score (OR 1.19, 95 %CI 1.17-1.24, p < 0.001) were independently associated with unfavorable outcome. CONCLUSION: Pre-stroke CHADS2 score was associated with poor outcome in patients with cardioembolic stroke due to AF, even in those taking OAC.

Prevalence and outcome of pre-onset frailty in patients with acute stroke.

BACKGROUND: Frailty in older individuals is an underappreciated condition that affects the incidence and/or prognosis of stroke. OBJECTIVES: We evaluated the prevalence of pre-onset frailty in patients with acute first-onset and recurrent strokes and association between pre-onset frailty and functional disability at hospital discharge. METHODS: This prospective cohort study included 210 acute stroke patients admitted to the Stroke Unit of Nippon Medical School Hospital during November 2021-June 2022. The mean participant age was 79.2 ± 7.4 years. Age, sex, pre-onset frailty, body mass index (BMI), stroke type, medical history, and National Institutes of Health Stroke Scale (NIHSS) score at admission were evaluated. Frailty was defined as a clinical frailty scale (CFS) score ≥ 5. Frailty prevalence was calculated for all patients, and scores of functional disabilities at discharge were evaluated using modified Rankin scale. RESULTS: Overall frailty prevalence was 31% in all stroke patients, with 24% and 47% of first-onset and recurrent strokes, respectively. Pre-onset frailty, NIHSS score at admission, age, stroke type, previous stroke, sex, BMI, dyslipidemia, and atrial fibrillation were significantly associated with functional disability at discharge. Logistic regression analysis revealed that CFS score, NIHSS score at admission, and previous stroke were independent predictors of functional disability at discharge. CONCLUSIONS: Approximately one-fourth of patients with first-onset stroke had pre-onset frailty; the rate doubled in recurrent stroke; these rates appear to be much larger than rate in healthy individuals. Pre-onset frailty, a negative independent factor affecting functional disability at discharge, is important for pre-onset frailty evaluation and rehabilitation intervention in acute stroke patients.

IL-27 produced during acute malaria infection regulates Plasmodium-specific memory CD4+ T cells.

Malaria infection elicits both protective and pathogenic immune responses, and IL-27 is a critical cytokine that regulate effector responses during infection. Here, we identified a critical window of CD4+ T cell responses that is targeted by IL-27. Neutralization of IL-27 during acute infection with Plasmodium chabaudi expanded specific CD4+ T cells, which were maintained at high levels thereafter. In the chronic phase, Plasmodium-specific CD4+ T cells in IL-27-neutralized mice consisted mainly of CD127+ KLRG1- and CD127- KLRG1+ subpopulations that displayed distinct cytokine production, proliferative capacity, and are maintained in a manner independent of active infection. Single-cell RNA-seq analysis revealed that these CD4+ T cell subsets formed independent clusters that express unique Th1-type genes. These IL-27-neutralized mice exhibited enhanced cellular and humoral immune responses and protection. These findings demonstrate that IL-27, which is produced during the acute phase of malaria infection, inhibits the development of unique Th1 memory precursor CD4+ T cells, suggesting potential implications for the development of vaccines and other strategic interventions.

Intravenous alteplase before endovascular therapy for acute large vessel occlusion with large ischemic core: subanalysis of a randomized clinical trial.

BACKGROUND: The efficacy of endovascular therapy (EVT) in patients with large ischemic core has been reported, but it remains unclear whether IV alteplase (IVT) has beneficial effects in addition to EVT in such patients. We evaluated the efficacy and safety of EVT with or without IVT. METHODS: The RESCUE-Japan LIMIT was an open-label, prospective, multicenter, randomized clinical trial to evaluate the efficacy and safety of EVT in stroke patients with large ischemic core, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5. This subanalysis evaluated the differences in the effects of EVT with medical care (EVT group) compared with medical care alone (No-EVT group) between those who received IVT (IVT stratum) and those who did not (No-IVT stratum) before EVT. RESULTS: Among 202 enrolled patients, 147 (73%) did not receive IVT. In the No-IVT stratum, the modified Rankin Scale (mRS) score of 0-3 at 90 days was significantly higher in the EVT group than in the No-EVT group (31.1% vs 12.3%, OR 3.21 (95% CI 1.37 to 7.53)). In the IVT stratum, the mRS score of 0-3 was 30.8% in the EVT group and 13.8% in the No-EVT group (OR 2.78 (95% CI 0.72 to 10.7)) (interaction p=0.77). The incidence of symptomatic intracranial hemorrhage was not different between the two groups in the No-IVT stratum (OR 1.20 (95% CI 0.35 to 4.12)), but it was significantly higher in the EVT group than in the No-EVT group in the IVT stratum (11.5% vs 0%, p=0.03). CONCLUSIONS: There was no difference in efficacy of EVT with or without IVT, while IVT before EVT might increase symptomatic intracranial hemorrhage in patients with large ischemic core. TRIAL REGISTRATION INFORMATION: NCT03702413.

Mode of Imaging Study and Endovascular Therapy for a Large Ischemic Core: Insights From the RESCUE-Japan LIMIT.

BACKGROUND AND PURPOSE: Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core. METHODS: The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan-Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3-5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum. RESULTS: Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65-2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46-16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008). CONCLUSION: Patients with ASPECTS of 3-5 on MRI benefitted more from EVT than those with ASPECTS of 3-5 on CT.

Resumption of oral anticoagulation in patients with non-valvular atrial fibrillation after intracerebral hemorrhage: A sub-analysis of the PASTA registry study.

PURPOSE: To investigate the rate and timing of oral anticoagulant (OAC) resumption and its safety in patients after intracerebral hemorrhage (ICH) in current clinical practice in Japan. METHODS: We conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1043 patients with stroke receiving OACs in Japan, by including patients with ICH on OAC treatment for non-valvular atrial fibrillation (NVAF). The clinical characteristics of the patients in the resumption and non-resumption groups, rate and timing of OAC resumption, its safety, and switching of OACs after ICH were investigated. RESULTS: Of the 160 patients (women, n = 52; median age, 77 years) included, OACs were resumed in 108 (68%) at a median of 7 days (interquartile range, 4-11) after acute ICH onset. The non-resumption group had higher rates of hematoma expansion (21.2% vs. 7.4%; P = 0.0118) and modified Rankin Scale (mRS) scores at discharge (4 (Suda et al., 2019; Steiner et al., 2014 [3, 4]) vs. 4 (Suda et al., 2019; Steiner et al., 2014; Pasquini et al., 2014 [3-5]); P = 0.0302}. The resumption rate in the mRS 0-4 group was higher than that in the mRS 5 group (75.2% vs. 46.5%; P = 0.00006). The number of days to resumption after ICH onset was longer in the mRS 5 than that in the mRS 0-4 group (median 12 days vs. 7 days, P = 0.0065). There were no significant differences in new-onset ICH, symptomatic hematoma expansion, or gastrointestinal bleeding between groups (P > 0.05). CONCLUSIONS: Early resumption of OAC for NVAF in patients after ICH appeared to be safe. Expected functional outcomes at discharge were associated with OAC resumption and with the timing of resumption. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Regular pulse checks for patients with non-cardioembolic stroke in rehabilitation hospitals to improve recognition and detection of atrial fibrillation (the ESCORT study): protocol for a prospective multicenter observational study.

Background: Cryptogenic stroke (CS) are heterogeneous in origin; however, most CS are embolic mechanism. Paroxysmal atrial fibrillation (AF) is suspected to be a major type of CS that leads to severe cerebral infarction without anticoagulant use. Therefore, the identification of AF is vital in patients with CS. However, patients are often unaware of AF because they have no symptoms, and AF may not be detected on an electrocardiogram (ECG) or Holter ECG on admission. After patients with stroke are treated in the acute phase, they are promptly transferred to a rehabilitation hospital for functional recovery. Once the patient is transferred to a hospital, a few attempts are made to detect AF. In addition, rehabilitation therapists are considered to have insufficient awareness of the possibility of undiagnosed AF. Objective: This study aimed to increase the understanding of the importance of AF detection in patients with ischemic stroke among therapists in rehabilitation hospitals and to investigate whether regular pulse screening can aid in the detection of AF. If AF was detected, we determined the rate and timing of AF detection and identified the patient characteristics. Methods: This multicenter prospective observational study aimed to detect AF in patients with non-cardiac stroke at rehabilitation hospitals. Therapists performed pulse checks before, during, and after rehabilitation. If arrhythmia or tachycardia was detected, an ECG was performed, and the physician checked for AF. If the patient complained of chest symptoms, electrocardiography (ECG) was performed to check for AF. We investigated the characteristics, laboratory data, cognitive status, complications, such as stroke recurrence, and functional outcomes of patients with AF. Results: The study is in the enrollment phase. Recruitment began in September 2022 and will end in August 2023. Patients have provided written informed consent. The main results have been submitted for publication in your journal. Conclusion: The findings of this study will help identify patients with AF in rehabilitation hospitals and improve awareness among therapists.

The impact of SAH finding on CT to the clinical outcome after mechanical thrombectomy for large vessel occlusion.

BACKGROUND AND PURPOSE: Whether subarachnoid haemorrhage (SAH) after mechanical thrombectomy affects the clinical outcomes of patients with acute large-vessel occlusion remains unclear. This study aimed to investigate the clinical impact of SAH on computed tomography (CT) after mechanical thrombectomy. METHODS: The SKIP study was an investigator-initiated, multicentre, randomised, open-label clinical trial. This study was performed in 23 hospital networks in Japan from January 1, 2017, to July 31, 2019. Among the 204 patients, seven were excluded because they did not undergo mechanical thrombectomy (MT) and had a modified Rankin scale (mRS) score > 2. The main outcome was the association between SAH within 36 h after mechanical thrombectomy and the clinical outcome at 90 days. RESULTS: Among 197 patients, the median age was 74 (67-79) years, 62.9% were male. Moreover, 26 (13.2%) patients had SAH (seven isolated SAH) on CT within 36 h. The SAH rate did not differ according to IV rt-PA administration (p = 0.4). The rate of favourable clinical outcomes tended to be lower in patients with SAH rather than patients without SAH (11 [42%] vs. 106 [62%], p = 0.08). Among the seven patients with isolated SAH, 6 showed favourable outcomes at 90 days. In the multivariate regression analysis, the presence of SAH within 36 h from onset was not associated with clinical outcome (Odd ratio, 0.59; 95% confidence interval, 0.18-1.95; p = 0.38). CONCLUSIONS: Among patients with acute stroke treated with MT, SAH, especially isolated SAH findings on CT, were not associated with poor clinical outcomes after 90 days. TRIAL REGISTRATION NUMBER: UMIN000021488.

Ultra-early rt-PA administration should improve patient outcome on mechanical thrombectomy: Post hoc analysis of SKIP.

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.