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.

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.

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.

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.

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.

Associations between Pre-Admission Risk Scores and Two-Year Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. METHODS: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. RESULTS: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. CONCLUSIONS: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.

Two-Year Outcomes of Anticoagulation for Acute Ischemic Stroke With Nonvalvular Atrial Fibrillation　- SAMURAI-NVAF Study.

BACKGROUND: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS2and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users. CONCLUSIONS: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Calcified Cerebral Embolism Due to a Calcified Amorphous Tumor.

A 59-year-old man developed brain embolism in the frontal and parietal cortex. Brain CT showed a high-density spot in the upper branch of the left middle cerebral artery, indicating calcified cerebral embolism. Calcified amorphous tumor attached to the mitral valve was identified as the cause of embolism. After surgical resection, anticoagulation was started and recurrent stroke did not occur.

Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Than Those With Paroxysmal Atrial Fibrillation.

BACKGROUND AND PURPOSE: The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. METHODS: Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. RESULTS: The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08). CONCLUSIONS: Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502.

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.

Hyperacute-phase computed tomography-diffusion-weighted imaging discrepancy and response to thrombolysis.

This study investigated the incidence and clinical features of reversed discrepancy (RD) in patients with hyperacute ischemic stroke. Sixty-two patients with anterior circulation ischemic stroke were enrolled. All patients underwent computed tomography (CT) and magnetic resonance imaging within 3 hours and received therapy with intravenous tissue plasminogen activator. The relationships between the Alberta Stroke Programme Early CT Score on CT and diffusion-weighted imaging (DWI); deep white matter lesion on DWI (DWI-W), CT, or magnetic resonance imaging after 24 hours; dramatic improvement (defined as a change in National Institutes of Health Stroke Scale score of ≥ 10 points or a total National Institutes of Health Stroke Scale score of 0 or 1 after 24 hours); and thrombolysis-related hemorrhage were assessed. Two investigators identified RD when the early ischemic change was detected on CT but no obvious hyperintensity was noted on DWI. RD was found in 10 patients (16.1%), located in the basal ganglia in 5 patients (50%), in the basal ganglia plus the cortical area in 3 patients (30%), and in the cortical area in 2 patients (20%). Four of these 10 patients had an infarction of the basal ganglia and a DWI-W lesion. All 4 patients with both RD in the basal ganglia (bRD) and DWI-W (the bRD+W+ group) had an infarction of the basal ganglia within 24 hours. In contrast, all 4 patients with bRD but without DWI-W (the bRD+W- group) had no basal ganglia infarction. Dramatic improvement after intravenous tissue plasminogen activator therapy was significantly less common in the bRD+W+ group (0 of 4 patients) than in the bRD+W- group (3 of 4 patients; P = .0285). Our findings suggest that the presence of both bRD and a DWI-W lesion can be used to predict whether dramatic improvement will occur and whether the basal ganglia will progress to infarction.

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.

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.

Presence of deep white matter lesions on diffusion-weighted imaging is a negative predictor of early dramatic improvement after intravenous tissue plasminogen activator thrombolysis.

BACKGROUND: The impact of deep white matter lesions observed at the corona radiata on diffusion-weighted MRI (DWI-W lesions) on the clinical recovery of patients after tissue plasminogen activator (tPA) therapy is unclear. Our goal was to elucidate whether DWI findings before tPA could predict clinical recovery. METHODS: A total of 83 consecutive patients with hyperacute anterior circulation ischemic stroke were enrolled. All patients underwent MRI within 3 h and received intravenous tPA. The relationships among the Alberta Stroke Program Early CT Score (ASPECTS) on DWI (DWI-ASPECTS), DWI-W lesions, early dramatic improvement (> or =10-point reduction in the total National Institutes of Health Stroke Scale, NIHSS, score or a total NIHSS score of 0-2 after 24 h), early improvement (> or =4-point reduction in the total NIHSS score after 24 h) and worsening (> or =4-point increase in the total NIHSS score after 24 h) were assessed. RESULTS: The median of the baseline DWI-ASPECTS value was 9 (range: 5-10), and DWI-W lesions were found in 36 patients (43%). Patients with early dramatic improvement had a shorter time from onset to tPA (116.1 +/- 34.9 vs. 133.2 +/- 33.1 min; p = 0.0281) and higher DWI-ASPECTS (medians: 9 vs. 9; p = 0.0568). DWI-W lesions were seen less frequently in patients with than without early dramatic improvement (26 vs. 54%; p = 0.0213). Multivariate logistic regression analysis demonstrated that absence of DWI-W lesions (OR: 1.80; 95% CI: 1.08-3.13; p = 0.0279), higher ASPECTS (OR: 1.56; 95% CI: 1.06-2.46; p = 0.0346) and shorter time from onset to tPA (OR: 0.98; 95% CI: 0.97-0.99; p = 0.0429) were independent predictors of early dramatic improvement. CONCLUSIONS: DWI-ASPECTS and DWI-W lesions appear to be useful tools for predicting early dramatic improvement.

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.