Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke.

BACKGROUND: Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM). METHODS: We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS2 score. RESULTS: Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5-76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397-827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend P<0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24-3.58) and 3.23 (95% CI, 2.07-5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14-5.74) and 4.25 (2.14-8.47), respectively. CONCLUSIONS: The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke.

One-year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after acute large vessel occlusion stroke.

Although low-dose direct oral anticoagulants (DOACs) are recommended for patients at high risk of bleeding complications, it remains unclear whether the dose reduction in real-world setting is also appropriate in patients after large-vessel occlusion (LVO) stroke. This study hypothesized that patients with atrial fibrillation (AF) and LVO receiving low-dose DOACs have an increased risk of ischemic and hemorrhagic events. The study aimed to assess 1 year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after LVO stroke. A post hoc analysis was performed using the acute LVO registry data, which enrolled patients with AF and LVO who received apixaban within 14 days of stroke onset. The incidences of ischemic events (ischemic stroke, acute coronary syndrome, acute myocardial infarction, and systemic embolism), major bleeding events, and death from any cause were compared between patients receiving standard- and low-dose apixaban. Of 643 patients diagnosed with LVO, 307 (47.7%) received low-dose apixaban. After adjustment for clinically relevant variables, no significant differences were observed in the incidence of ischemic events (adjusted hazard ratio [aHR]: 2.12, 95% confidence interval [CI] 0.75-6.02), major bleeding events (aHR: 1.17, 95% CI 0.50-2.73), and death from any cause (aHR: 1.95, 95% CI 0.78-4.89) between patients receiving standard- and low-dose apixaban. No significant differences were observed in the incidence of ischemic events, major bleeding events, or death from any cause between patients with AF and LVO receiving standard- and low-dose apixaban.

P-wave terminal force in lead V1 and atrial fibrillation burden in cryptogenic stroke with implantable loop recorders.

Implantable loop recorders (ILRs) are useful for the detection of atrial fibrillation (AF) in patients with cryptogenic stroke (CS). P-wave terminal force in lead V1 (PTFV1) is associated with AF detection; however, data on the association between PTFV1 and AF detection using ILRs in patients with CS are limited. Consecutive patients with CS with implanted ILRs from September 2016 to September 2020 at eight hospitals in Japan were studied. PTFV1 was calculated by 12-lead ECG before ILRs implantation. An abnormal PTFV1 was defined as ≥ 4.0 mV × ms. The AF burden was calculated as a proportion based on the duration of AF to the total monitoring period. The outcomes included AF detection and large AF burden, which was defined as ≥ 0.5% of the overall AF burden. Of 321 patients (median age, 71 years; male, 62%), AF was detected in 106 patients (33%) during the median follow-up period of 636 days (interquartile range [IQR], 436-860 days). The median time from ILRs implantation to AF detection was 73 days (IQR, 14-299 days). An abnormal PTFV1 was independently associated with AF detection (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.00-2.90). An abnormal PTFV1 was also independently associated with a large AF burden (adjusted odds ratio, 4.70; 95% CI, 2.50-8.80). In patients with CS with implanted ILRs, an abnormal PTFV1 is associated with both AF detection and a large AF burden.Clinical Trial Registration Information: UMIN Clinical Trials Registry 000044366.

Characterization of Moyamoya and Middle Cerebral Artery Diseases by Carotid Canal Diameter and RNF213 p.R4810K Genotype.

OBJECTIVES: It is sometimes difficult to differentiate middle cerebral artery disease from moyamoya disease because the two can present similarly yet have different treatment strategies. We investigated whether the presence of a narrow carotid canal and the RNF213 mutation can help differentiate between the two phenotypes. POPULATION AND METHODS: We analyzed 78 patients with moyamoya disease, 27 patients with middle cerebral artery disease, and 79 controls from 2 facilities. The carotid canal diameter was measured using computed tomography. The p.R4810K mutation was genotyped by TaqMan assay. A receiver operating characteristics analysis was performed to assess the significance of the carotid canal diameter for the accurate diagnosis of moyamoya disease. RESULTS: The carotid canal diameter was significantly narrower in patients with moyamoya disease than in controls. The optimal cutoff values were 5.0 mm for adult males and 4.5 mm for adult females and children (sensitivity: 0.82; specificity: 0.92). Among the patients with middle cerebral artery disease, 18.5% and 25.0% of the affected hemispheres had the p.R4810K mutation and narrow canal (i.e., below the cutoff), respectively, whereas only 3.1% of those had both. Contrastingly, 68.8% of the affected hemispheres in patients with moyamoya disease had both these characteristics. Among the patients with moyamoya disease, those with the p.R4810K mutation tended to have narrower carotid canals. CONCLUSIONS: Although the presence of a narrow carotid canal or the p.R4810K mutation alone could not be used to distinguish those with moyamoya disease from those with middle cerebral artery disease, the combination of these factors could better characterize the two phenotypes.

CREB Coactivator CRTC2 Plays a Crucial Role in Endothelial Function.

The cAMP pathway is known to stabilize endothelial barrier function and maintain vascular physiology. The family of cAMP-response element binding (CREB)-regulated transcription coactivators (CRTC)1-3 activate transcription by targeting the basic leucine zipper domain of CREB. CRTC2 is a master regulator of glucose metabolism in liver and adipose tissue. However, the role of CRTC2 in endothelium remains unknown. The aim of this study was to evaluate the effect of CRTC2 on endothelial function. We focused the effect of CRTC2 in endothelial cells and its relationship with p190RhoGAP-A. We examined the effect of CRTC2 on endothelial function using a mouse aorta ring assay ex vivo and with photothrombotic stroke in endothelial cell-specific CRTC2-knock-out male mice in vivo CRTC2 was highly expressed in endothelial cells and related to angiogenesis. Among CRTC1-3, only CRTC2 was activated under ischemic conditions at endothelial cells, and CRTC2 maintained endothelial barrier function through p190RhoGAP-A expression. Ser171 was a pivotal regulatory site for CRTC2 intracellular localization, and Ser307 functioned as a crucial phosphorylation site. Endothelial cell-specific CRTC2-knock-out mice showed reduced angiogenesis ex vivo, exacerbated stroke via endothelial dysfunction, and impaired neurologic recovery via reduced vascular beds in vivo These findings suggest that CRTC2 plays a crucial protective role in vascular integrity of the endothelium via p190RhoGAP-A under ischemic conditions.SIGNIFICANCE STATEMENT Previously, the role of CRTC2 in endothelial cells was unknown. In this study, we firstly clarified that CRTC2 was expressed in endothelial cells and among CRTC1-3, only CRTC2 was related to endothelial function. Most importantly, only CRTC2 was activated under ischemic conditions at endothelial cells and maintained endothelial barrier function through p190RhoGAP-A expression. Ser307 in CRTC2 functioned as a crucial phosphorylation site. Endothelial cell-specific CRTC2-knock-out mice showed reduced angiogenesis ex vivo, exacerbated stroke via endothelial dysfunction, and impaired neurologic recovery via reduced vascular beds in vivo These results suggested that CRTC2 maybe a potential therapeutic target for reducing blood-brain barrier (BBB) damage and improving recovery.

Improvement of the diagnostic accuracy for intracranial haemorrhage using deep learning-based computer-assisted detection.

PURPOSE: To elucidate the effect of deep learning-based computer-assisted detection (CAD) on the performance of different-level physicians in detecting intracranial haemorrhage using CT. METHODS: A total of 40 head CT datasets (normal, 16; haemorrhagic, 24) were evaluated by 15 physicians (5 board-certificated radiologists, 5 radiology residents, and 5 medical interns). The physicians attended 2 reading sessions without and with CAD. All physicians annotated the haemorrhagic regions with a degree of confidence, and the reading time was recorded in each case. Our CAD system was developed using 433 patients' head CT images (normal, 203; haemorrhagic, 230), and haemorrhage rates were displayed as corresponding probability heat maps using U-Net and a machine learning-based false-positive removal method. Sensitivity, specificity, accuracy, and figure of merit (FOM) were calculated based on the annotations and confidence levels. RESULTS: In patient-based evaluation, the mean accuracy of all physicians significantly increased from 83.7 to 89.7% (p < 0.001) after using CAD. Additionally, accuracies of board-certificated radiologists, radiology residents, and interns were 92.5, 82.5, and 76.0% without CAD and 97.5, 90.5, and 81.0% with CAD, respectively. The mean FOM of all physicians increased from 0.78 to 0.82 (p = 0.004) after using CAD. The reading time was significantly lower when CAD (43 s) was used than when it was not (68 s, p < 0.001) for all physicians. CONCLUSION: The CAD system developed using deep learning significantly improved the diagnostic performance and reduced the reading time among all physicians in detecting intracranial haemorrhage.

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.

Frequent Premature Atrial Contractions in Cryptogenic Stroke Predict Atrial Fibrillation Detection with Insertable Cardiac Monitoring.

OBJECTIVE: To determine whether frequent premature atrial contractions (PAC) predict atrial fibrillation (AF) in cryptogenic stroke patients, we analyzed the association between frequent PACs in 24-h Holter electrocardiogram recording and AF detected by insertable cardiac monitoring (ICM). METHODS: We retrospectively analyzed a database of 66 consecutive patients with cryptogenic stroke who received ICM implantation between October 2016 and March 2018 at 5 stroke centers. We included the follow-up data until June 2018 in this analysis. We defined frequent PACs as the upper quartile of the 66 patients. We analyzed the association of frequent PACs with AF detected by ICM. RESULTS: Frequent PACs were defined as >222 PACs per a 24-h period. The proportion of patients with newly detected AF by ICM was higher in patients with frequent PACs than those without (50% [8/16] vs. 22% [11/50], p < 0.05). Frequent PACs were associated with AF detection and time to the first AF after adjustment for CHADS2 score after index stroke, high plasma -B-type natriuretic peptide (BNP; >100 pg/mL) or serum -N-terminal pro-BNP levels (>300 pg/mL), and large left atrial diameter (≥45 mm). CONCLUSION: High frequency of PACs in cryptogenic stroke may be a strong predictor of AF detected by ICM.

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.

Hematological Abnormalities and Malnutrition Mediate Pathway between Cancer and Outcomes in Ischemic Stroke Patients.

BACKGROUND: The present study aimed to examine whether variables including D-dimer, high-sensitivity C-reactive protein (hsCRP), hemoglobin, platelet count, and nutritional status mediate the pathway between cancer and ischemic stroke outcomes. METHODS: We reviewed data from consecutive patients with ischemic stroke admitted to Osaka University Hospital between January 1, 2006, and December 31, 2016. Patients with ischemic stroke were grouped according to the presence of cancer. Nutritional status was assessed using Controlling Nutritional Status (CONUT) scores. Mediation analyses were utilized to address the study aims. RESULTS: Among 1,570 patients with ischemic stroke, 185 (12%) had active cancer. Relative to patients with ischemic stroke in the non-cancer group, those in the cancer group exhibited higher National Institutes of Health Stroke Scale scores on admission, higher D-dimer and hsCRP levels, lower hemoglobin levels and platelet counts, higher CONUT scores, and poorer modified Rankin Scale scores at discharge. Mediation analysis revealed that D-dimer, hsCRP, hemoglobin, platelet count, and CONUT scores acted as mediators of poor prognosis in the cancer group. The association between the exposure and outcome variables was no longer significant in the models containing D-dimer and CONUT scores as mediator variables, suggesting that they were strong mediators. Regarding the association between the mediator and outcome variables, hemoglobin, platelet count, and CONUT exhibited non-linearity (p for non-linearity < 0.001). CONCLUSIONS: D-dimer, hsCRP, hemoglobin, platelet count, and CONUT score act as mediators of poor prognosis in patients with ischemic stroke with comorbid cancer. Such abnormalities can help to predict ischemic stroke outcomes.

Total small vessel disease score and functional outcomes following acute intracerebral hemorrhage.

BACKGROUND: Individual cerebral small vessel disease (SVD) markers are independent predictors for poor prognosis following intracerebral hemorrhage (ICH), however, the impact of the cumulative SVD burden on outcomes remains unclear. We aimed to investigate the association between the global SVD burden and functional outcomes following ICH. METHODS: We retrospectively evaluated a consecutive cohort of patients with ICH who underwent brain magnetic resonance imaging and magnetic resonance angiography, from a prospective registry. We identified the presence and severity of the SVD markers (cerebral microbleeds, lacunar infarctions, periventricular hyperintensities, and deep white matter hyperintensities) and summed them to obtain the modified total SVD score (0-4). Poor functional outcomes were defined as a modified Rankin Scale score at discharge ≥ 3. A multivariate logistic regression model was used to assess the association between patient outcomes and the SVD score. RESULTS: A total of 144 patients were included (65.0 ± 12.2 years, 67.4% male). The modified total SVD score was potentially associated with poor functional outcomes (odds ratio [OR] 1.72, 95% confidence interval [CI] 0.97-3.03) after adjustment for age, sex, history of stroke, chronic kidney disease, prior use of antithrombotic agents, the National Institutes of Health Stroke Scale score on admission, the non-lobar location of ICH, and hematoma volume on admission. Moreover, among older patients (≥ 65 years), the SVD score was associated with poor outcomes (OR 3.11, 95% CI 1.01-9.55). Among those with supratentorial ICH, the score remained significant (OR 2.06, 95% CI 1.11-3.83). CONCLUSIONS: The modified total SVD score may have predictive value for poor functional outcomes following ICH.

Cortical Cerebral Microinfarcts on 3T Magnetic Resonance Imaging in Patients With Carotid Artery Stenosis.

Background and Purpose- Carotid artery stenosis is common in the elderly and contributes to cognitive impairment and dementia. Cortical cerebral microinfarcts (CMIs) play an important role in vascular cognitive impairment and dementia. We aimed to investigate the association between CMIs on 3T magnetic resonance imaging and clinical and radiological features, including plaque morphology, and cognitive function in patients with carotid stenosis. Methods- Eighty-nine patients with >30% carotid stenosis on ultrasound were prospectively enrolled, and underwent brain and carotid artery magnetic resonance imaging. CMIs were rated according to predetermined criteria based on 3D-double inversion recovery and fluid-attenuated inversion recovery images. Results- CMIs were identified in 26 patients (29%; median number 0, range 0-9). Poisson regression models adjusted for age and sex revealed that CMIs were associated with intraplaque hemorrhage (rate ratio, 1.95; 95% CI, 1.26-3.18), lacunar infarcts (rate ratio, 1.54; 95% CI, 1.00-2.44), and cortical infarcts (rate ratio, 3.22; 95% CI, 2.20-5.00). These associations were also observed in asymptomatic patients (n=64). Of 81 patients with unilateral carotid stenosis, the prevalence and number of CMIs were significantly higher in the hemisphere ipsilateral to the carotid stenosis than in the contralateral hemisphere ( P=0.005 and P<0.001, respectively). The presence of CMIs was associated with poor cognitive function. Conclusions- Our results indicate that vulnerable carotid plaque increases the risk of CMIs and subsequent cognitive impairment. Carotid atherosclerosis could be a potential therapeutic target for cognitive impairment.

Successful Reperfusion with Endovascular Therapy Has Beneficial Effects on Long-Term Outcome Beyond 90 Days.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. METHODS: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. RESULTS: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score. CONCLUSIONS: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.

High Detection Rate of Atrial Fibrillation With Insertable Cardiac Monitor Implantation in Patients With Cryptogenic Stroke Diagnosed by Magnetic Resonance Imaging.

BACKGROUND: Detection and treatment of atrial fibrillation (AF) is a major goal in preventing secondary stroke. Insertable cardiac monitors (ICMs) are available for diagnosis of arrhythmia monitoring in patients with cryptogenic stroke. Magnetic resonance imaging (MRI)-based diagnostic evaluation for acute ischemic stroke subtype classification is common in Japan and can be useful for specific diagnosis of cryptogenic stroke. PURPOSE: We aimed to investigate the detection rate of AF with an ICM in patients with cryptogenic stroke who were diagnosed by MRI. METHODS: We performed a retrospective, multicenter, observational study. AF monitoring data of an ICM (Reveal LINQ) in patients with cryptogenic stroke were registered from 5 stroke centers in Japan between October 2016 and March 2018. ICM candidates in cryptogenic stroke were diagnosed by MRI-based evaluation and selected according to the criteria proposed by the Japan Stroke Society. Detection of AF was defined as AF for longer than 120 seconds. RESULTS: Eighty-four consecutive patients (64 men; aged 38-90 years) underwent ICM implantation after diagnosis of cryptogenic stroke. AF was detected in 22 of 84 (26.2%) patients with an ICM during a median follow-up of 221.5 days (range: 93-365 days). The detection rate of AF within 3 months after ICM implantation was 21.4%. CONCLUSIONS: The AF detection rate with an ICM is approximately one fifth within 3 months in patients with cryptogenic stroke as diagnosed by MRI. Our data suggest that the Japanese criteria based on MRI may be useful for selecting adequate candidates for ICM implantation.

Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org.

BACKGROUND: TIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.5 We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients. METHODS: The patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke. RESULTS: Current smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption. CONCLUSIONS: The two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.

Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Isolated cortical vasogenic edema and hyperintense vessel signs may be early features of reversible cerebral vasoconstriction syndrome: Case reports.

Background The temporal and anatomical features of vasoconstriction in patients with reversible cerebral vasoconstriction syndrome within hours after symptom onset, in the hyperacute phase, are unclear. Case result Herein we report the cases of two patients with acute severe headache who were diagnosed with reversible cerebral vasoconstriction syndrome. Magnetic resonance imaging within hours after symptom onset revealed multiple areas of isolated cortical vasogenic edema and hyperintense vessel signs of the distal cerebral arteries. Follow-up imaging performed four days later in both cases showed diffuse segmental arterial vasoconstriction in the proximal regions of the cerebral arteries. Both patients received antivasoconstrictive therapy shortly after admission, and neither had neurological sequelae at discharge. The magnetic resonance imaging findings improved gradually within three months after symptom onset. Conclusion Isolated cortical vasogenic edema and hyperintense vessel signs, when observed within hours from sudden severe headache onset, may be useful early markers of reversible cerebral vasoconstriction syndrome.

Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor Assessment and Improvement-Intracerebral Hemorrhage Study.

BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.

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.