Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial.

We determined the associations of follow-up blood pressure (BP) after stroke as a time-dependent covariate with the risk of subsequent ischemic stroke, as well as those of BP levels with the difference in the impact of long-term clopidogrel or aspirin monotherapy versus additional cilostazol medication on secondary stroke prevention. In a sub-analysis of a randomized controlled trial (CSPS.com), patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone, or a combination of cilostazol with aspirin or clopidogrel. The percent changes, differences, and raw values of follow-up BP were examined. The primary efficacy outcome was the first recurrence of ischemic stroke. In a total of 1657 patients (69.5 ± 9.3 years, female 29.1%) with median 1.5-year follow-up, ischemic stroke recurred in 74 patients. The adjusted hazard ratio for ischemic stroke of a 10% systolic BP (SBP) increase from baseline was 1.19 (95% CI 1.03-1.36), that of a 10 mmHg SBP increase was 1.14 (1.03-1.28), and that of SBP as the raw value with the baseline SBP as a fixed (time-independent) covariate was 1.14 (1.00-1.31). Such significant associations were not observed in diastolic BP-derived variables. The estimated adjusted hazard ratio curves for the outcome showed the benefit of dual therapy over a wide SBP range between ≈120 and ≈165 mmHg uniformly. Lower long-term SBP levels after ischemic stroke were associated with a lower risk of subsequent ischemic events. The efficacy of dual antiplatelet therapy including cilostazol for secondary stroke prevention was evident over a wide SBP range.

The cutoff values of functional independence measure scores for predicting discharge destination in the early stroke phase.

This study aimed to determine cutoff values of functional independence measure (FIM) scores to predict the discharge destinations of patients with acute stroke. The sample included 318 patients with acute stroke (mean age, 72.0 years; women, 39%). The discharge destination was categorized into three groups: home, postacute rehabilitation (hospital with convalescent rehabilitation wards), and postacute care (institution without convalescent rehabilitation wards). We assessed FIM after lifting bed restriction. Multinomial logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of the FIM scores for predicting discharge destinations, with postacute rehabilitation as a reference. Cutoff values of motor and cognitive FIM scores for distinguishing home from postacute rehabilitation and postacute care from postacute rehabilitation were determined using receiver operating characteristic curves. The proportion of home, postacute rehabilitation, and postacute care were 34.6%, 41.8%, and 23.6%, respectively. After adjustments for clinical variables, the ORs (95% CIs) for motor and cognitive FIM scores for home versus postacute rehabilitation were 1.08 (1.04-1.11) and 1.05 (0.98-1.12). Furthermore, those for postacute care versus postacute rehabilitation were 1.01 (0.98-1.04) and 0.92 (0.87-0.98). The cutoff values of the motor and cognitive FIM scores for distinguishing home from postacute rehabilitation were 37.5 (sensitivity: 0.92; specificity: 0.64) and 23.5 (sensitivity: 0.78; specificity: 0.67). Furthermore, those for distinguishing postacute care from postacute rehabilitation were 15.5 (sensitivity, 0.81; specificity, 0.51) and 12.5 (sensitivity, 0.74; specificity, 0.64). The identified cutoff values may serve as early indicators for predicting discharge destinations from acute stroke care.

Safety of Antithrombotic Therapy within 24 Hours after Recombinant Tissue-Plasminogen Activator Treatment for Large-Artery Atherosclerosis Stroke: Insights from Emergent PTA/CAS Cases.

BACKGROUND: Antithrombotic therapy (AT) should generally be avoided within 24 hours after recombinant tissue-plasminogen activator (rt-PA) treatment but should be considered in patients with large-artery atherosclerosis (LAA) who undergo concomitant emergent endovascular treatment (EVT). The aim of the present study was to assess the safety of AT within 24 hours after rt-PA treatment in patients with hyperacute ischemic stroke due to LAA who received concomitant EVT. METHODS: From January 2013 through July 2019, consecutive patients with acute ischemic cerebrovascular disease due to LAA who were admitted within 6 hours from symptom onset were recruited. The patients were classified into six groups based on the reperfusion treatment and early (within 24 hours) AT from rt-PA treatment. Safety outcomes were compared among the groups. RESULTS: A total of 155 patients (35 women [23%], median age 74 [IQR 66-79] years; NIHSS score 3 [1-10]) were included in the present study. Of these, 73 (47%) received no reperfusion therapy, 24 (15%) received rt-PA treatment and early AT, seven (6%) received rt-PA without early AT, 26 (17%) received EVT only, six (4%) received both rt-PA and EVT without early AT, and 19 (12%) received rt-PA and EVT with early AT. AT was administered a median of 3.9 (1.6-8.0) hours after rt-PA in patients with rt-PA+EVT with early AT. AT within 24 hours after rt-PA and EVT treatment did not increase hemorrhagic complications (p > 0.05 for all). CONCLUSION: In this retrospective analyses, early AT administration for patients with hyperacute stroke due to LAA treated with rt-PA plus EVT did not increase hemorrhagic events.

Pathological Findings of Embolus Retrieved by Mechanical Thrombectomy in Cerebral Embolism with Libman-Sacks Endocarditis: A Report of Two Cases.

Libman-Sacks endocarditis is an important cause of embolic stroke in systemic lupus erythematosus, although the detailed pathogenesis of stroke remains unclear. We herein report two cases of stroke with Libman-Sacks endocarditis in which the emboli were retrieved by mechanical thrombectomy. The embolus consisted of eosinophilic homogeneous acellular structures, whereas fibrin-platelet thrombi were hardly observed in the embolus. Immunohistochemistry showed immunoglobulin deposits in the embolus, suggesting that immunological mechanisms were involved in the growth of the embolus. A pathological analysis of the embolus retrieved by mechanical thrombectomy provided useful information on the etiology, leading to optimal treatment.

The extracellular-to-total body water ratio reflects improvement in the activities of daily living in patients who experienced acute stroke.

OBJECTIVES: To determine the relationship between bioelectrical impedance analysis (BIA) parameters, including the extracellular water-to-total body water ratio (ECW/TBW), and the activities of daily living (ADL) improvement, in patients who experienced acute stroke. MATERIALS AND METHODS: This retrospective cohort study included 307 patients (mean age, 72 years; 39 % female) who experienced acute stroke and were admitted to the stroke unit of the Nippon Medical School Hospital (Bunkyo-ku, Tokyo, Japan) between April 2021 and March 2022. The Functional Independence Measure (FIM) was assessed at initial rehabilitation and discharge, and FIM effectiveness was calculated as ADL improvement in the participating acute care hospitals. BIA markers included the skeletal muscle mass index (SMI), phase angle (PhA), and ECW/TBW. Multiple linear regression models were used to estimate the relationship between the FIM effectiveness and each BIA marker. RESULTS: The mean (±SD) FIM effectiveness was 0.45 ± 0.36. The proportions of low SMI (male, <7.0 kg/m2; female, <5.7 kg/m2) and low PhA (male <5.36 degrees, female <3.85 degrees), were 48.9 % and 43.3 %, respectively. In addition, the proportions of of low (<0.36), normal (0.36-0.40), and high (>0.4) ECW/TBW ratios were 1.3 %, 78.5 %, and 20.2 %, respectively. After adjustments for demographic and clinical variables, low PhA, low ECW/TBW, and high ECW/TBW were all significantly associated with FIM effectiveness (P < 0.05), with ß coefficients of -0.126, -0.089, and -0.117, respectively. CONCLUSIONS: Low and High ECW/TBW and low PhA levels were negatively correlated with improvements in ADL. The ECW/TBW ratio may be an additional indicator of rehabilitation trainability in patients who experience acute stroke.

The randomized study of enteral nutrition with rapid versus conventional administration in acute stroke patients; the protocol of rapid EN trial.

Rationale: Enteral nutrition is beneficial for stroke patients with oral intake difficulties. However, it is time consuming and may interfere with routine medical care. Therefore, there is a clinical benefit if enteral nutrition can be safely administered in a short time. Although our retrospective study showed the safety of rapid administration, it remains unclear whether rapid administration of enteral nutrition is as safe as conventional administration. Aim: The randomized study of Enteral Nutrition with Rapid versus conventional administration in acute stroke patients (Rapid EN trial) aims to clarify the safety of rapid feeding of enteral nutrition compared with conventional feeding. Methods and design: This is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligible criteria include acute stroke patients who have difficulty with oral intake defined as severe altered consciousness (Japan Coma Scale 10-300) or modified water swallowing test <4. The target enrollment is 700 patients, with 350 patients receiving rapid enteral nutrition at a rate of 100 mL in 5 min (Rapid EN group) and 350 patients receiving conventional enteral nutrition at a rate of 100 mL in 30 min (Conventional EN group). Study outcome: The primary outcome is the incidence of one or more complications of vomiting or diarrhea or pneumonia within 7 days would be non-inferior in the rapid EN group compared to the conventional EN group. Secondary outcomes were total time spent on enteral nutrition within 7 days from enteral nutrition, the incidence of vomiting, diarrhea and pneumonia within 3 or 7 days, and the rate of favorable clinical outcome. Discussion: Since no previous reports have focused on the speed of administration, we felt it was necessary to prove the safety of rapid administration. If this study shows positive results, it will not only benefit patients, but also reduce the burden of medical care. We believe this study is novel and will be useful in clinical practice. Clinical trial registration: https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046610 Identifier UMIN000046610.

Migraine-like headache with aura induced by a small infarct in the parieto-occipital cortex: A case report.

A 56-year-old right-handed man was referred to our hospital for evaluation of sudden-onset transient quadrantanopia, which was followed by throbbing headache consistent with migraine with aura (MA). Magnetic resonance imaging (MRI) of the right parieto-occipital cortex on admission showed a hyperintense region on diffusion-weighted imaging, which disappeared 7 days later. A small cortical infarct in the parieto-occipital cortex can cause MA-like headache, and the present infarct lesion was only detectable on MRI during the acute phase. Performing MRI for patients with suspected acute MA might help identify the cause of MA-like headache and ensure appropriate management of patients.

Expanding the Treatable Imaging Profile in Patients With Large Ischemic Stroke: Subanalysis From a Randomized Clinical Trial.

BACKGROUND: We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes. METHODS: This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0-3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed. RESULTS: Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65-160) mL in patients with EVT and 115 (71-141) mL in the medical management group (P=0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80-223] mL versus 211 [123-289] mL in the medical management group; P<0.001). CONCLUSIONS: In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413.

Clinical significance of intracranial hemorrhage after thrombectomy detected solely by magnetic resonance imaging and not by computed tomography.

BACKGROUND AND OBJECTIVE: Whether intracranial hemorrhage (ICH) detected using magnetic resonance imaging (MRI) affects the clinical outcomes of patients with large-vessel occlusion (LVO) treated with mechanical thrombectomy (MT) remains unclear. This study investigated the clinical features of ICH after MT detected solely by MRI. METHODS: This was a retrospective analysis of patients with acute ischemic stroke and occlusion of the internal carotid artery or middle cerebral artery treated with MT between April 2011 and March 2021. Among 632 patients, patients diagnosed with no ICH using CT, with a pre-morbid modified Rankin Scale (mRS) score ≤ 2, and those who underwent MRI including T2* and computed tomography (CT) within 72 h from MT were enrolled. The main outcomes were the association between ICH detected solely by MRI and clinical outcomes at 90 days. Poor clinical outcomes were defined as mRS score > 2 at 90 days after onset. RESULTS: Of the 246 patients, 29 (12%) had ICH on MRI (MRI-ICH(+)), and 217 (88%) were MRI-ICH(-). There was no significant difference between number of patients with MRI-ICH(+) experiencing poor (10 [12%]) and favorable (19 [12%]) outcomes. The mRS score at 90 days between patients with MRI-ICH (+) and MRI-ICH(-) was not significantly different (2 [1-4] vs. 2 [1-4], respectively). Higher age and lower ASPECTS were independent risk factors for poor outcomes, as shown by multivariate regression analysis. MRI-ICH(+) status was not associated with poor outcomes. CONCLUSIONS: ICH detected by MRI alone did not influence clinical outcomes in patients with LVO treated with MT.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials.

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

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.