Evaluation of partial resheathing of EmboTrap III using the microcatheter (PREMIER) technique for fibrin-rich hard clots in an in vitro vessel model.

Background and purpose: Despite the ongoing advancements in mechanical thrombectomy for large vessel occlusions causing acute ischemic stroke, successful recanalization is not achieved in all patients. One contributing factor is the presence of fibrin-rich hard clots. We proposed a new technique called the PREMIER technique, which aims to retrieve fibrin-rich clots. This study evaluated the efficacy of the PREMIER technique on fibrin-rich and erythrocyte-rich clots by comparing it with the simple use of EmboTrap III in an in vitro vessel model. Methods: The PREMIER technique involves partially resheathing a fully deployed EmboTrap III (CERENOVUS, Johnson & Johnson Medical Devices, Irvine, California, USA) using a microcatheter to capture and retrieve a hard clot between the inner channel and outer cages of EmboTrap III. We compared recanalization rate of the PREMIER technique with the simple use of EmboTrap III in an in vitro vessel model, occluding the M1 segment with fibrin-rich hard clots (0% erythrocyte composition) and erythrocyte-rich clots (50% erythrocyte composition). Results: Among the 40 procedures (10 each for the PREMIER technique and the simple use of EmboTrap III for two different clots) for fibrin-rich clots, the PREMIER technique achieved successful recanalization in all 10 cases, with a significantly higher recanalization rate than the EmboTrap III (100% vs. 50%, p = 0.03). For erythrocyte-rich clots, the recanalization rate was not significantly different in the PREMIER technique compared with the simple use of EmboTrap III (80% vs. 70%, p = 1.00). Conclusion: The PREMIER technique is a novel technique for acute large-vessel occlusions caused by fibrin-rich hard clots that hinders successful recanalization during mechanical thrombectomy.

Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study.

OBJECTIVE: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. METHODS: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. RESULTS: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1-3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26-13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99-43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08-2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13-10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02-6.35) significantly increased in SVD score 4 compared to score 0. INTERPRETATION: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774-787.

Detection of Atrial Fibrillation Using Insertable Cardiac Monitors in Patients With Cryptogenic Stroke in Japan (the LOOK Study): Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. OBJECTIVE: In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. METHODS: This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. RESULTS: Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. CONCLUSIONS: The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39307.

Hypoperfusion intensity ratio and CBV index as predictive parameters to identify underlying intracranial atherosclerotic stenosis in endovascular thrombectomy.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion (LVO) is difficult to diagnose before endovascular thrombectomy (EVT) in an emergency. We hypothesized that hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index reflect collateral flow and would be useful parameters to predict underlying ICAS. MATERIALS AND METHODS: Clinical and perfusion imaging parameters of patients receiving EVT for LVO were reviewed retrospectively. Patients were divided into ICAS and embolism groups with angiographical findings. The association between prespecified parameters and underlying ICAS were assessed using multivariable logistic regression analyses. Discriminative ability was assessed using receiver operating characteristic analysis. RESULTS: Among 238 consecutive patients, 47 satisfied the inclusion criteria, including 10 with ICAS-related LVO. In ROC analyses, HIR showed good discrimination with a cutoff value of 0.22 (area under the curve, 0.85; 95%CI, 0.75-0.96; sensitivity, 0.84; specificity, 0.80) for underlying ICAS. CBV index showed excellent discrimination with a cutoff value of 0.90 (area under the curve, 0.92; 95%CI, 0.81-0.98; sensitivity, 0.92; specificity, 0.79). Multivariable logistic regression analysis revealed that HIR ≤ 0.22 (OR, 22.5; 95%CI, 2.9-177.0; P = 0.003) and CBV index ≥ 0.9 (OR, 75.7; 95%CI, 5.8-994.0; P < 0.001) were significantly associated with underlying ICAS. CONCLUSION: HIR ≤ 0.22 and CBV index ≥ 0.9 were associated with underlying ICAS and may predict underlying ICAS before EVT.

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.

Preceding direct oral anticoagulant administration reduces the severity of stroke in patients with atrial fibrillation - K-PLUS registry.

BACKGROUND: Stroke severity can be mitigated by preceding anticoagulant administration in acute ischemic stroke patients with atrial fibrillation (AF). We investigated if such mitigative effects are different between warfarin and direct oral anticoagulants (DOACs). MATERIAL AND METHODS: We collected data from a regional multicenter stroke registry. Ischemic stroke or transient ischemic attack patients with AF were included. Background characteristics, National Institutes of Health Stroke Scale (NIHSS) score on admission, lesion characteristics, and in-hospital death were analyzed according to preceding antithrombotic agents at onset. RESULTS: A total of 2173 patients had AF; 628 were prescribed warfarin, 272 DOACs, 429 antiplatelets alone, and 844 no antithrombotics. The NIHSS score on admission was lowest in the DOACs group compared to the other groups. In neuroimaging analysis, small ischemic lesions were observed more frequently in the DOACs group, while large ischemic lesions were less frequent in this group. When the no antithrombotics group was used as a reference, the adjusted odds ratio for moderate to severe stroke was 0.56 (95% confidence interval, 0.40-0.78) in the DOACs group, while it was 0.98 (0.77-1.24) in the warfarin group and 0.94 (0.72-1.22) in the antiplatelets group. In-hospital mortality was lowest in the DOACs group compared to the other groups. CONCLUSION: Preceding DOAC administration might mitigate the severity of stroke in AF patients more strongly than other antithrombotics, possibly leading to a better outcome in patients with stroke.

Microbleeds and clinical outcome in acute mild stroke patients treated with antiplatelet therapy: ADS post-hoc analysis.

BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.

Clinical characteristics of patients with ischemic stroke after the 2016 Kumamoto earthquake, a multi-center study.

OBJECTIVE: To investigate the clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake. METHODS: We retrospectively studied patients with ischemic stroke admitted to 5 stroke centers for 1 year after the earthquake. We compared clinical characteristics in these patients (the post-earthquake group) to those in the patients with ischemic stroke admitted during the same period from the previous 3 years (the pre-earthquake group). Additionally, we analyzed the trend of the incidence rate of stroke before and after the earthquake. RESULTS: A total of 1979 patients were admitted after the earthquake; 5670 (1,890/year on average) patients were admitted before the earthquake. A first-ever ischemic stroke (71 vs. 75%) and premorbid modified Rankin Scale > 1 (26 vs. 29%) were found significantly more frequently in patients after the earthquake. National Institutes of Health Stroke Scale score ≤ 2 at discharge (60 vs. 65%) was found more frequently in patients after the earthquake, although non-discharge to home (65 vs. 70%) was more frequent in patients after the earthquake. Trend analysis revealed a decrease of small vessel occlusion and large artery atherosclerosis in the month after the earthquake. CONCLUSIONS: The 2016 Kumamoto earthquake may have affected the characteristics of stroke during the early phase of the earthquake and increased the difficulty in returning home.

Pre-hospital Diagnosis of Large Vessel Occlusion in Patients Being Transported by Helicopter.

BACKGROUND: During the helicopter transportation of patients suspected of large vessel occlusion (LVO), an accurate and rapid decision-making process is required. AIMS: We attempted to create an algorithm for the pre-hospital diagnosis of the presence of LVO in patients suspected of stroke using data from patients transported urgently by helicopter. METHODS: One hundred and sixty-five patients transported by helicopter were divided into two subgroups: a training dataset and a validation dataset. We extracted clinical information obtained on site, the unadjusted score of the National Institutes of Health Stroke Scale, and previously reported pre-hospital scales as an LVO screen. On the basis of the analyses of these factors, an algorithm was devised to predict the presence of LVO and its predictive accuracy was evaluated using the validation dataset. RESULTS: Ischemic stroke with LVO was diagnosed in 36 out of 121 cases (29.8%) in the training dataset and in 10 out of 44 cases (22.7%) in the validation dataset. Combining five factors (conjugate deviation, upper limb paresis, atrial fibrillation, Japan Coma Scale ≥ 200, and systolic blood pressure ≥ 180), an algorithm was created to classify cases into six groups with different likelihoods of LVO presence. The algorithm predicted correctly 6 out of 10 cases in the validation dataset. Furthermore, it definitively ruled out 17 out of 34 cases in the validation dataset. CONCLUSIONS: Using the newly created algorithm, emergency staff could easily and accurately distinguish patients suitable for urgent endovascular thrombectomy from patients with non-LVO or stroke mimics.

Cilostazol Addition to Aspirin could not Reduce the Neurological Deterioration in TOAST Subtypes: ADS Post-Hoc Analysis.

BACKGROUND: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. METHODS: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). RESULTS: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030). CONCLUSIONS: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. RESULTS: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00). CONCLUSION: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Pre-Hospital Delay in Patients with Acute Ischemic Stroke in a Multicenter Stroke Registry: K-PLUS.

PURPOSE: There is scant data related to prehospital delay in cases of acute ischemic stroke from multicenter studies conducted after change of the therapeutic window of intravenous tissue plasminogen activator (iv-tPA) administration to within 4.5 h of onset. We investigated factors causing prehospital delay and their associations with clinical outcomes using data from a regional multicenter stroke registry. METHODS: Data from the multicenter regional stroke registry were analyzed. Patients admitted within 24 h of the last known well time were categorized according to whether their admission was early (≤ 4 h; n = 2350) or delayed (> 4 h; n = 2752). We then compared patients' backgrounds and outcomes between the two groups. RESULTS: Five-thousand, one-hundred two patients presented at hospitals within 24 h of onset. On multivariate analysis, atrial fibrillation, higher NIHSS score on admission, anterior circulation stroke, detection of symptoms immediately after onset, and emergency system use were positively associated with early admission, whereas modified Rankin Scale (mRS) score before onset, onset at home, diabetes, current smoking, dementia and symptom detection between 00:00 and 06:00 h were negatively associated. Early admission was associated with mRS scores of 0-2 at discharge independent of backgrounds, stroke severity, and thrombolytic therapy (odds ratio, 1.56; 95% confidence interval, 1.32-1.84). CONCLUSIONS: Certain patient factors relating to prehospital delay, such as lack of awareness of onset or non-cardioembolic etiology, are crucial but often inevitable. However, earlier admission was associated mRS scores of 0-2 independent of other factors. This study may help to plan educational activities to general population or public awareness campaigns.

Trousseau syndrome with intrahepatic cholangiocarcinoma that could be removed radically after endovascular treatment: Report of a case.

BACKGROUND: Trousseau syndrome is a poor prognosis. We report a case of Trousseau syndrome treated by radical resection after endovascular treatment. CASE: A 59-year-old woman presented to our department reporting spontaneous dizziness and pain of the upper abdomen. Magnetic resolution imaging (MRI) showed shower embolization of Brain. Contrast-enhanced computer tomography (CT) showed renal infarction and splenic infarction, and a tumor was observed in the retrohepatic area. On day 9, sudden right side joint prejudice, neglect of left half space, and left hemiplegia were observed. MRI revealed obstruction of the right middle cerebral artery (MCA) perfusion zone. On the same day, endovascular treatment was performed and reperfusion was obtained. We decided on a radical surgery policy because there were a primary lesion and a high risk of new embolism, and no metastasis was seen. DISCUSSION: Trousseau syndrome generally has a poor prognosis, but active treatment should be considered as an option when we can expect the recovery of function.

Cilostazol uncovers covert atrial fibrillation in non-cardioembolic stroke.

BACKGROUND: We hypothesized that administration of cilostazol may clarify the occult atrial fibrillation (AF) during hospitalization in mild stroke patients, who has no history of AF. METHODS: From our prospective non-cardioembolic stroke study, randomized to dual antiplatelet therapy using cilostazol and aspirin or aspirin alone trial (ADS), data on the presence or absence of AF were retrospectively analyzed. In the ADS, during hospitalization, as a routine examination, presence of AF was investigated using electrocardiogram (ECG), ECG monitoring and Holter ECG. Multivariate regression analysis was conducted to evaluate the independent parameters related to the AF. Clinical outcome at 3 months was evaluated using modified Rankin Scale (mRS) score. RESULTS: Data on 1194 patients (793 [66%] men; median age [interquartile range] of 69 [61-77] years, National Institutes of Health Stroke Scale score 2 [1-4], onset-to-admission 10.8 [4.7-20.5] hours) were retrospectively analyzed. AF was newly detected in 41 (3%) patients (3 by ECG, 21 by the ECG monitoring and 17 by the Holter ECG) during hospitalization. Patients treated with combined cilostazol and aspirin therapy frequently had the AF than those took aspirin alone (5% vs. 2%, p = .007). Multivariate regression analysis showed that cilostazol administration was one of the independent factors for new-AF (odds ratio 2.672, 95%CI: 1.205-5.927, p = .016). The frequency of mRS 0-1 was 68% in the new-AF group and 67% in the non-AF group (p = 1.000). CONCLUSION: Cilostazol therapy may increase the detectability of AF in acute non-cardioembolic stroke, though the new-AF was not related to clinical outcome at 3 months.

Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation.

Background and Purpose- We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods- From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results- DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2-7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68-81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69-82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47-1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42-4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28-1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions- Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation-associated ischemic stroke or transient ischemic attack. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01581502.

The bleeding with antithrombotic therapy study 2: Rationale, design, and baseline characteristics of the participants.

AIMS: The bleeding risk of current antithrombotic strategies in clinical settings, including recently developed agents, needs to be clarified. METHODS AND DESIGN: In an investigator-initiated, prospective, multicentre, observational study, patients with cerebrovascular or cardiovascular diseases who were taking oral antiplatelet or anticoagulant agents were enrolled. Compulsory multimodal magnetic resonance images were acquired at baseline to assess cerebral small vessel disease. Six-month follow-up will be performed for two years. The primary outcome is major bleeding as defined by the International Society on Thrombosis and Hemostasis. RESULTS: Between October 2016 and March 2019, 5306 patients (71.7 ± 11.2 years old, 1762 women) were enrolled. Previous intracranial haemorrhage was documented in 181 patients (3.4%), cerebrovascular disease (including asymptomatic) requiring antithrombotic therapy in 5006 patients (94.3%), and atrial fibrillation in 1061 patients (20.0%). At entry, 3726 patients (70.2%) were taking antiplatelet agents alone, including 551 (10.4%) using dual antiplatelet agents, 1317 (24.8%) taking anticoagulants alone, and the remaining 263 (5.0%) taking both. The leading antiplatelet agent was clopidogrel (2014 patients), and the leading combination of dual antiplatelet medication was clopidogrel plus aspirin (362). Use of direct oral anticoagulants (1029 patients, 19.4%) exceeded warfarin use (554, 10.4%). The number of pivotal bleeding events exceeded 200 in April 2020. CONCLUSIONS: This study is expected to provide the incidence of bleeding complications of recent oral antithrombotics in clinical practice and identify their associations with underlying small vessel disease and other biomarkers. Novel risk stratification models for bleeding risk will be able to be created based on the study results.

Percutaneous Transluminal Angioplasty as Potentially Effective Treatment for Persistent Cognitive Decline due to Intracranial Carotid Artery Stenosis.

Objective: We describe a male patient with covert sustained cognitive impairment who underwent endovascular treatment for severe stenosis in the left intracranial internal carotid artery (ICA). Case Presentation: A 64-year-old man presented with transient dysarthria and dysphagia. Although he was alert, a cognitive evaluation revealed significant dysgraphia and a remarkable reduction in cognitive function. Diffusion-weighted imaging (DWI) revealed scattered high-intensity regions in the watershed area of the left cerebral hemisphere and severe stenosis in the C2 portion of the left ICA. Percutaneous transluminal angioplasty (PTA) was performed; a detailed examination revealed significantly improved cognitive function. One year later, the patient demonstrated further cognitive improvement, without any recurrent stroke. Conclusions: We consider that patients with severe intracranial stenosis, who have covert cognitive decline without apparent sustained symptoms, might be promising candidates for revascularization. Higher brain function in patients with severe intracranial arterial stenosis should be carefully screened because cognitive decline might not be evident at the time of initial presentation.

Stent Retriever-Assisted Continuous Aspiration for Distal Intracranial Vessel Embolectomy: The Distal Combined Technique.

OBJECTIVE: We investigated the efficacy of a combined approach with stent retriever-assisted aspiration catheter for distal intracranial vessel occlusion (distal combined technique [DCT]). METHODS: We evaluated consecutive patients with acute ischemic stroke with distal occlusion in anterior circulation, including occlusions of the M2/M3 or A2/A3 segments, who received endovascular therapy (EVT) in a single center. Modified Thrombolysis in Cerebral Infraction (mTICI) score including TICI 2C category, processing time from puncture to reperfusion, proportion of a favorable clinical outcome at discharge (modified Rankin Scale [mRS] score ≤2), and incidence of symptomatic intracranial hemorrhage (sICH) were compared between the DCT and single device approach technique (non-DCT) groups. RESULTS: Of 65 patients, 28 were treated with EVT using the DCT and 37 were treated with EVT with a single device approach (non-DCT). In the DCT group, a higher reperfusion rate at the first pass (mTICI score ≥2B, 92% vs. 54%; P = 0.0008; mTICI score ≥2C, 71% vs. 16%; P < 0.0001; mTICI score 3, 57% vs. 14%; P = 0.0004) and shorter time from puncture to successful reperfusion (median, 31 vs. 43 minutes; P = 0.0006) were achieved, respectively. The final successful reperfusion rate was also higher in the DCT group than in the non-DCT group (mTICI score ≥2C, 85% vs. 51%; P = 0.004; mTICI score 3, 75% vs. 43%; P = 0.012), respectively. sICH occurred in 2 patients in the non-DCT group. Patients with mRS score ≤2 at discharge were more prevalent in the DCT than in the non-DCT group (57% vs. 27%, respectively; P = 0.021). CONCLUSIONS: This retrospective analysis indicated that the DCT is a useful and safe strategy for patients with distal anterior intracranial vessel occlusion.

Acute Aspirin Plus Cilostazol Dual Therapy for Noncardioembolic Stroke Patients Within 48 Hours of Symptom Onset.

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non-Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator-initiated, prospective, multicenter (34 hospitals in Japan), randomized, open-label, and aspirin-controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61-77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1-4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short-term neurological worsening. Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.