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

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

Identifying large vessel occlusion using the hyperdense artery sign in patients treated with mechanical thrombectomy.

OBJECTIVES: The hyperdense artery sign on non-contrast computed tomography-reconstructed images is useful for identifying large vessel occlusion in acute ischemic stroke. This study aimed to assess its efficacy in patients with large vessel occlusion treated with mechanical thrombectomy. MATERIALS AND METHODS: This retrospective and prospective single-centered study from June 2019 to May 2021 evaluated the use of non-contrast computed tomography-reconstructed images for detecting hyperdense artery sign to identify large vessel occlusion from June 2020 to May 2021. We registered consecutive potential candidates for mechanical thrombectomy due to suspected stroke and assessed the accuracy of hyperdense artery sign on non-contrast computed tomography-reconstructed images for large vessel occlusion in the hyperacute setting. Non-contrast computed tomography images were reconstructed into maximum intensity projection images with iterative reconstruction algorithms to detect hyperdense artery signs. We compared the door-to-puncture time and functional outcome at 90 days before and after employing non-contrast computed tomography-reconstructed images in patients with large vessel occlusion treated with mechanical thrombectomy. RESULTS: The cohort included 82 patients, wherein 47 were treated with mechanical thrombectomy. The sensitivity (96%) and specificity (94%) of hyperdense artery sign on non-contrast computed tomography-reconstructed images for large vessel occlusion were performed. The door-to-puncture time was significantly shortened after using non-contrast computed tomography-reconstructed images (49 versus 28 min, p = 0.001), but the functional outcome at 90 days remained unchanged. CONCLUSIONS: Non-contrast computed tomography-reconstructed images, as a vascular imaging tool for mechanical thrombectomy, can reduce workflow time in hospitals by identifying large vessel occlusion with high sensitivity and specificity.

Effect of early mobilization in patients with stroke and severe disturbance of consciousness: Retrospective study.

OBJECTIVES: This study aimed to investigate the effectiveness and safety of early mobilization with a physiatrist and registered therapist Operating rehabilitation (PROr) for patients with stroke and severe disturbance of consciousness (DoC). MATERIALS AND METHODS: We retrospectively screened records from patients with stroke admitted to our hospital from January 2015 to June 2021. Eligible patients with severe DoC were classified into two groups: patients who received standard rehabilitation (control group) and patients who received PROr (PROr group). We studied longitudinal change in the level of consciousness using the Japan Coma Scale (JCS) during hospital stay and compared in-hospital mortality, the incidence of respiratory complication, and modified Rankin Scale of discharge between the two groups. RESULTS: Among the 2191 patients screened for inclusion, 16 patients were included in the PROr group, and 12 patients were included in the control group. Early mobilization was more promoted in the PROr group compared to the control group, but there were no significant differences in in-hospital mortality, the incidence of respiratory complication, or modified Rankin Scale at discharge between the two groups. In patients who survived during their hospital stay, JCS scores 2 weeks after the onset of stroke and JCS scores at discharge significantly improved from the start of rehabilitation in the PROr group, but not in the control group. CONCLUSIONS: Early mobilization provided with the PROr program appears to be a safe treatment and may contribute to the improvement of consciousness level for patients with acute stroke and severe DoC.

Magnetic Resonance Imaging-Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size: THAWS RCT Substudy.

BACKGROUND AND PURPOSE: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. METHODS: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. RESULTS: The median DWI-Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI (P=0.026) and core volume (P=0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33-30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87-43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients. CONCLUSIONS: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr; Unique Identifier: UMIN000011630.

Association of Admission Hyperglycemia with Clinical Outcomes in Japanese Patients with Acute Large Vessel Occlusion Stroke: A post hoc Analysis of the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2.

INTRODUCTION: Admission hyperglycemia is an indicator of poor functional prognosis in acute stroke, but investigations of its prevalence and effects on the outcomes of acute large vessel occlusion in real-world, large-scale studies are limited, especially in Asian population. OBJECTIVE: We aimed to elucidate the relationship between admission hyperglycemia and outcomes in a prospective multicenter registry in Japan. METHODS: We analyzed data from the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism (RESCUE) Japan Registry 2, which was a prospective, multicenter registry that enrolled patients from 46 centers in Japan. Admission hyperglycemia was defined as blood glucose level >140 mg/dL. The relationships between clinical outcomes and admission hyperglycemia were analyzed in all 1,932 assessable patients. A favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at day 90, as well as mortality within 90 days and symptomatic intracranial hemorrhage (SICH) within 72 h, was analyzed. We performed subgroup analyses of the adjusted variables to investigate the association between hyperglycemia and favorable outcome in relation to each variable. RESULTS: Admission hyperglycemia was present in 687 (35.6%) of the assessable patients and in 420 (26.9%) of the 1,561 patients without diabetes. A favorable outcome was significantly less frequent in the hyperglycemia group than in the no-hyperglycemia group (33.2% vs. 47.6%, adjusted odds ratio [OR]: 0.60, 95% confidence interval [CI]: 0.47-0.76). The mortality rates were 12.8% and 6.8% in the hyperglycemia and no-hyperglycemia groups, respectively. The incidence of SICH within 72 h was higher in the hyperglycemia group than in the no-hyperglycemia group (4.4% vs. 1.9%, adjusted OR: 2.54, 95% CI: 1.36-4.82). Hyperglycemia was associated with unfavorable outcomes in almost all subgroups. CONCLUSIONS: Admission hyperglycemia in Japanese patients with large vessel occlusion stroke is associated with an unfavorable functional outcome at 90 days, mortality within 90 days, and the occurrence of SICH within 72 h.

Hypertrophic Pachymeningitis Related Brain Infarction in Synovitis-Acne-Pustulosis-Hyperostosis Osteomyelitis Syndrome.

A 50-year-old woman with a history of synovitis-acne-pustulosis-hyperostosis osteomyelitis (SAPHO) syndrome was admitted for left unilateral neglect, dysarthria, and left hemiparesis. Brain MRI showed multiple infarctions in the territory of the right middle cerebral artery and gadolinium enhancement of the thickened frontotemporal dura mater on the right side. MR angiography showed significant narrowing of the cavernous segment of the right internal carotid artery. The right internal carotid artery stenosis was thought to originate from hypertrophic pachymeningitis associated with SAPHO syndrome. This is the first report of brain infarction due to internal carotid artery stenosis caused by hypertrophic pachymeningitis associated with SAPHO syndrome.

Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA.

OBJECTIVES: The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. RESULTS: In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. CONCLUSIONS: We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

Clinical Outcome of Patients With Large Vessel Occlusion and Low National Institutes of Health Stroke Scale Scores: Subanalysis of the RESCUE-Japan Registry 2.

Background and Purpose- The treatment and prognosis of acute large vessel occlusion with mild symptoms have not been sufficiently studied. The present study aimed to investigate the clinical or radiological predictors of clinical outcome in patients with stroke with mild symptoms due to acute large vessel occlusion. Methods- Of 2420 patients with acute large vessel occlusion in the RESCUE-Japan Registry 2 (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Registry 2), a multicenter prospective registry in Japan, patients with modified Rankin Scale scores of 0 to 2 before onset and initial National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5 were examined in post hoc analysis. We examined the clinical and radiological characteristics associated with a favorable outcome (modified Rankin Scale score, 0-2 at 90 days) using multivariate analysis, as well as the factors associated with a favorable outcome in patients treated with endovascular therapy. Results- We analyzed 272 patients (median age, 73 years; median NIHSS score on admission, 3). Eighty-six (31.6%) patients were treated with intravenous recombinant tissue-type plasminogen activator, 54 (19.9%) underwent endovascular therapy, and 208 (76.5%) showed a favorable outcome. In multivariate analysis, age <75 years (odds ratio [OR], 2.42 [95% CI, 1.30-4.50]), initial NIHSS score 0 to 3 (OR, 3.08 [95% CI, 1.59-5.98]), intravenous recombinant tissue-type plasminogen activator (OR, 2. 86 [95% CI, 1.32-6.21]), and blood glucose level ≤140 mg/dL (OR, 2.37 [95% CI, 1.22-4.60]) were independently associated with a favorable outcome. However, endovascular therapy was not associated with a favorable outcome (OR, 1.65 [95% CI, 0.71-3.88]). Among 54 patients treated with endovascular therapy, good reperfusion status was more common in the favorable outcome group (88.6% versus 60.0%; P<0.05). Conclusions- Younger age, lower initial NIHSS score, intravenous recombinant tissue-type plasminogen activator, and absence of hyperglycemia were independently associated with a favorable outcome in patients with acute large vessel occlusion with low NIHSS scores. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02419794.

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.

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

Clinical Outcomes Depending on Acute Blood Pressure After Cerebral Hemorrhage.

OBJECTIVE: To determine the association between clinical outcomes and acute systolic blood pressure (SBP) levels achieved after intracerebral hemorrhage (ICH). METHODS: Eligible patients who were randomized to the ATACH-2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial (ClinicalTrials.gov: NCT01176565) were divided into 5 groups by 10-mmHg strata of average hourly minimum SBP (<120, 120-130, 130-140, 140-150, and ≥ 150 mmHg) during 2 to 24 hours after randomization. Outcomes included: 90-day modified Rankin Scale (mRS) 4 to 6; hematoma expansion, defined as an increase ≥6 ml from baseline to 24-hour computed tomography; and cardiorenal adverse events within 7 days. RESULTS: Of the 1,000 subjects in ATACH-2, 995 with available SBP data were included in the analyses. The proportion of mRS 4 to 6 was 37.5, 36.0, 42.8, 38.6, and 38.0%, respectively. For the "140 to 150" group relative to the "120 to 130," the odds ratio (OR), adjusting for sex, race, age, onset-to-randomization time, baseline National Institutes of Health Stroke Scale score, hematoma volume, and hematoma location, was 1.62 (95% confidence interval [CI], 1.02-2.58). Hematoma expansion was identified in 16.9, 13.7, 21.4, 18.5, and 26.4%, respectively. The 140 to 150 (OR, 1.80; 95% CI, 1.05-3.09) and "≥150" (1.98; 1.12-3.51) showed a higher frequency of expansion than the 120 to 130 group. Cardiorenal events occurred in 13.6, 16.6, 11.5, 8.1, and 8.2%, respectively. The 140 to 150 (0.43; 0.19-0.88) and ≥ 150 (0.44; 0.18-0.96) showed a lower frequency of the events than the 120 to 130. INTERPRETATION: Beneficial effects of lowering and maintaining SBP at 120 to 130 mmHg during the first 24 hours on clinical outcomes by suppressing hematoma expansion was somewhat offset by cardiorenal complications. ANN NEUROL 2019;85:105-113.

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.

Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.

Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan　­ J-ASPECT Study ­

BACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Proximal Common Carotid Artery Stenosis Induced by Repetitive Mechanical Compression: A Case Report.

OBJECTIVES: Arterial branches and curvatures, such as the common carotid artery (CCA) origin and carotid bifurcation, are usual sites of atherosclerosis, which leads to carotid artery stenosis. Atherosclerosis may occur due to repetitive compression. Stenosis localized to the proximal segment away from the CCA origin and bifurcation is rare. Here, we describe the case of a patient with right proximal CCA stenosis induced by repetitive compression. METHODS: We studied an acute stroke patient who worked for a long time as a geographical surveyor carrying a tripod on his right shoulder. We found severe eccentric stenosis composed of thick plaque in the right proximal CCA, away from the right CCA origin. However, there was no finding of CCA dissection or vasculitis. RESULTS: The patient was diagnosed with ischemic stroke due to artery-to-artery embolization from the right CCA stenosis, which we believed was due to repetitive compression by the tripod. CONCLUSIONS: Repetitive mechanical stimuli can cause stenotic lesions at atypical vascular sites.

Quantitative characterization of carotid plaque components using MR apparent diffusion coefficients and longitudinal relaxation rates at 3T: A comparison with histology.

BACKGROUND: There is limited evidence of parametric MR mapping to characterize carotid plaques associated with cerebral ischemic events. PURPOSE: To explore the apparent diffusion coefficients (ADCs) and longitudinal relaxation rates (R1 ) of carotid plaques, including areas of hemorrhage, lipid-rich/necrotic core (LR/NC) without hemorrhage, and fibrous tissue (Fbr) STUDY TYPE: Prospective. SUBJECTS: Twelve patients who underwent carotid endarterectomy. FIELD STRENGTH/SEQUENCE: R1 was measured using double angle Look-Locker acquisition on 3T systems. Single-shot spin-echo echo-planar imaging with fat suppression and outer-volume suppression (OVS-DWEPI) with b values of 10 and 500 s/mm2 was used for diffusion-weighted imaging. ASSESSMENT: A phantom study using diluted gadolinium solutions and polyvinyl alcohol solutions was used to validate the two protocols. Regions of interest (ROIs) were manually outlined on MR images for areas of LR/NC, hemorrhage, and Fbr based on histological cross-sections. Pixel-based R1 and ADC values in the ROIs were plotted for each component. The probability density function of the plots determined the optimum contours to separate the three components in the ADC-R1 plane. The LR/NC, hemorrhage, and Fbr regions were mapped on MR images based on the above results and compared to histological results. STATISTICAL TESTS: The R1 values of the phantom measurements were tested using Bland-Altman analysis. The accuracies of the MRI classification were calculated. RESULTS: R1 values <8 s-1 calculated using our method agreed with those calculated using an inversion-recovery fast-spin-echo sequence (error, ≤0.1 s-1 ). ADC values obtained using OVS-DWEPI were 4.1% higher than those obtained using standard echo-planar imaging. LR/NC (R1 , 0.4-1.2 s-1 ; ADC, 0-1.5 µm2 /ms), hemorrhage (R1 ≥ 1.5 s-1 ; ADC, 0.5-1.5 µm2 /ms), and Fbr (R1 , 0.2-0.8 s-1 ; ADC, 1.5-2.9 µm2 /ms) were separated on the plots. The accuracies of MRI classification were LR/NC, 0.86; hemorrhage, 0.79; and Fbr, 0.77. CONCLUSION: The combination of ADC and R1 values measured using our method enabled differentiation among LR/NC, hemorrhage, and Fbr. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1657-1667.

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.

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.

A Case of Intrathoracic Carotid Bifurcation Without Klippel-Feil Syndrome.

BACKGROUND: Intrathoracic carotid bifurcation is a rare vascular anomaly, with only 8 cases reported. This vascular anomaly was recently correlated with Klippel-Feil syndrome, a rare congenital disorder involving fusion of the cervical vertebrae. METHODS: A 70-year-old deaf mute man was admitted to our department because of right hemiparesis and right sensory disturbance. He displayed no abnormalities associated with Klippel-Feil syndrome. Diffusion-weighted imaging revealed acute multiple infarcts in bilateral hemispheres. Computed tomography angiography showed that the left common carotid artery bifurcated at the T2 vertebral level. No significant stenosis was seen in the carotid arteries. Transesophageal echocardiography confirmed a complicated atheromatous lesion at the aortic arch. RESULTS: This case was diagnosed with aortogenic brain embolism, incidentally accompanied by left intrathoracic carotid bifurcation without Klippel-Feil syndrome. CONCLUSIONS: Intrathoracic carotid bifurcation can occur in cases without Klippel-Feil syndrome. The knowledge of this anatomic variation is important in evaluating vascular lesions of the carotid arteries in patients with stroke.