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Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

BackgroundWe aimed to identify the large ischemic core (LIC) volume ranges in acute ischemic stroke patients that can benefit from mechanical thrombectomy (MT).MethodsConsecutive patients within 24 hours of onset of anterior circulation ischemic stroke with large vessel occlusion and ischemic core volumes of 70–300 mL were included from our single-center prospective database from March 2014 to December 2019. Subjects were divided into three groups by baseline ischemic core volume (A: 70–100 mL; B: 101–130 mL; C: >130 mL). We compared modified Rankin Scale (mRS) score 0–2 at 3 months and parenchymal hematoma between patients receiving MT and standard medical treatment (SMT), and determined clinically treatable core volume ranges for MT.ResultsOf 157 patients (86 women; median age, 81 years; median ischemic core volume, 123 mL), 49 patients underwent MT. In Group A (n=52), MT patients (n=31) showed a higher proportion of mRS 0–2 at 3 months (52% vs 5%, PConclusionsIschemic core volumes between 70 and 100 mL may benefit from MT. The treatable upper core limit is approximately 120 mL in selected patients with LIC of 70–300 mL.

Background: Thyroid diseases and elevated thyroid autoantibodies are associated with moyamoya disease (MMD). MMD susceptibility variant RNF213 p.R4810K is known to increase the risk of ischemic stroke (IS), but whether thyroid diseases and thyroid autoantibody levels are altered in IS patients carrying the RNF213 p.R4810K variant remains elusive. Methods: Of the consecutive adult IS patients from 2011 to 2020 admitted in our institute, patients who signed a consent form for RNF213 genotyping were included, while definitive MMD patients were excluded. We compared the patient background, history of thyroid disease (hyperthyroidism or hypothyroidism), and levels of serum triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), antithyroperoxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb) between the variant carrier and non-carrier. Each thyroid autoantibody was measured by the electro-chemiluminescent immunoassay method. Results: Of the 1570 patients (525 women; 72 years of median age) analyzed, 74 (4.7%) patients had the RNF213 p.R4810K variant. The variant carriers were more likely to be female (52.7% vs. 35.3%, P P P =0.01), middle cerebral artery M1 stenosis (29.7% vs. 6.0%, P =0.01), and large-artery atherosclerosis (47.3% vs. 25.0%, P P P Conclusions: Hypothyroidism and elevated TPOAb levels were frequently observed in IS patients with the RNF213 p.R4810K variant, which may be associated with immune aberrancies relevant to or underlying thyroid autoimmunity, contributing to the different features of IS.

Introduction: Cervico-cephalic dissections (extracranial artery dissection [EAD] and intracranial artery dissection [IAD]) are defined by a mural hematoma in the wall of a cervical or intracranial artery and represent an important cause of stroke in young adults. It is relatively uncommon in the general population and likely to represent the ethnic difference with higher frequency of IAD in Asian than European populations. A few studies examining the genetic contributions for these phenotypes were reported. In EAD, the PHACTR1 genes which had previously been identified as common genetic risk variants of hypertension and migraine was associated with EAD using genome-wide association study (GWAS) approaches. RNF213 , an important susceptibility gene for Moyamoya disease was associated with IAD in one small study (n=24) using a candidate-SNP analysis but no GWAS of IAD have been reported so far. We performed GWAS to identify common variants associated with IAD. Methods: A total of 100 Japanese patients with IAD based on imaging diagnostic criteria from multidisciplinary expert consensus were prospectively enrolled in National Cerebral and Cardiovascular Center from March 2011 to August 2018. Results: We performed GWAS in 100 IAD cases (61 men, 50 years of median age[IQR, 45-61]) and 8380 controls from the Tohoku Medical Megabank Project which is a publicly available healthy cohort. No variant reached to genome-wide significant but 14 variants (7 regions) showed nominal significant association with IAD (p < 10 -5 ). Among 14 variants, rs73828631 on RBMS3 gene showed highest association with IAD (odds ratio = 2.16, 95% confidence interval = 1.59-2.92; P = 3.08 х 10 -7 ). RBMS3 was previously identified as genetic loci associated with brain aneurysm. According to the Genotype-Tissue Expression (GTEx) project database, RBMS3 is highly expressed in artery. Conclusions: We identified potential 14 variants associated with IAD. We need to increase the number of IAD cases for further confirmation.

Introduction: Spontaneous intracranial artery dissection (IAD) can be diagnosed with the detection of intramural hematoma (IMH). We previously reported that high-resolution 3-dimensional T1-weighted magnetic resonance imaging (HR-3D-T1WI) is useful to detect IMH. Limited evidence is available regarding sequential detection rates of IMH and appropriate timing of the detection. Methods: We retrieved data on consecutive patients from our prospective cohort databases from March 2011 to August 2018 who had definite, probable, or possible IAD based on the multidisciplinary expert consensus criteria. We detected IMH on initial and follow-up HR-3D-T1WI. We explored the association between detection of IMH and days from symptom onset to initial or follow-up HR-3D-T1WI. Results: A total of 104 patients (mean age 51 ± 13; 30 female; 68 patients, definite IAD; 31 patients; probable IAD, 5 patients; possible IAD) with at least initial HR-3D-T1WI data were included in the analysis. Clinical diagnoses included ischemic stroke (46%), subarachnoid hemorrhage (6%), transient ischemic attack (2%), and head or neck pain alone (46%). Age, Sex, vascular risk factors and modified Rankin Scale at 3 months were comparable between patients with IMH and without. Among them, follow-up HR-3D-T1WI was performed in 54 patients (52%). IMH was observed in 61 patients, 59% of all and 90% of definite IAD. The median days from symptom onset to initial or follow-up HR-3D-T1WI were 11 (interquartile range[IQR] 8–15) and 29 (IQR 19–57) days, respectively. The median days from symptom onset to first IMH detection were 12 (IQR range 8–17). The detection rate of IMH on initial HR-3D-T1WI was 55% overall, reaching 20% on day 3, 40% on day 7, and 50% on day 8–12 ( Figure ). Of the 23 patients who did not have an IMH on the initial HR-3D-T1WI, 4 (17%) had an IMH detected on the follow-up imaging. Conclusion: The detection rate of IMH on HR-3D-T1WI was approximately 60%, which reached the maximum in 1-2 weeks.

Background: Poststroke dementia (PSD) is a serious problem for stroke survivors. However, there is still limited data on the real-world state and clinical management of PSD worldwide, and several countries already have a super-aged society. Objective: We conducted a nationwide questionnaire survey to examine the real-world state and management of PSD in Japan. Methods: A survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated between July 2018 and August 2019. Thirteen questions regarding PSD were mailed to doctors responsible for stroke management. Results: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The median numbers of patients admitted annually with stroke in the departments of neurology and neurosurgery in the hospitals were 281.0 (interquartile range [IQR], 231.8–385.3) and 253.5 (IQR, 210.0–335.3), respectively, and most hospitals were acute care hospitals. Executive dysfunction was the most common cognitive dysfunction (10.9%), followed by amnesia (9.5%) and apathy (4.1%). Surprisingly, many stroke survivors lived alone at home (23.7%). Montreal Cognitive Assessment was significantly uncommon compared to Mini-Mental State Examination (p

Introduction: There has been increasing evidence that higher systolic blood pressure variability (SBPV) is related to unfavorable outcomes in patients with stroke. We explored the relation between SBPV and clinical outcomes after reperfusion therapy; intravenous thrombolysis (IVT) and endovascular therapy (EVT). Methods: We retrieved data of consecutive patients with acute ischemic stroke (AIS) treated with reperfusion therapy from our prospective stroke registry between October 2005 and December 2018. We calculated the following five SBPV during 24 hours after IVT or EVT; mean, standard deviation (SD), coefficient of variation (CV), successive variation (SV), and average real variability (ARV). Clinical outcomes included unfavorable outcomes as modified Rankin Scale (mRS) score 3-6 at 3 months and symptomatic intracranial hemorrhage (sICH) as any hemorrhage with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale (NIHSS). Successful reperfusion was indicated with early neurological improvements of 4 points of more on the NIHSS after IVT alone or Thrombolysis in Cerebral Infarction scores of 2b or 3 after EVT alone or EVT combined with IVT. Results: Among 933 patients with premorbid mRS scores of 0-1 (72±12 years; 316 women), 426 patients with unfavorable outcomes and 35 patients with sICH were observed. In adjusted analyses, all measures of SBPV but CV were related to unfavorable outcomes, while all measures of SBPV but mean SBP were related to sICH. In 566 patients with successful reperfusion, 228 patients with unfavorable outcomes and 10 patients with sICH were observed. In adjusted analyses, all measures of SBPV but mean SBP were positively related to unfavorable outcomes, while no measures of SBPV were independently related to sICH (table). Conclusion: High SBPV after successful reperfusion therapy contributed to unfavorable outcomes, suggesting high SBPV after reperfusion therapy might need more attention.

Dysgeusia is rare in Guillain-Barre syndrome, particularly as the initial symptom. We herein report the case of a 59-year-old woman who presented with only dysgeusia as the initial symptom of Guillain-Barre syndrome, followed by gradually worsening muscle weakness and bilateral sensory disturbances in the extremities. Her dysgeusia was so unpleasant that she could not eat anything, so she received nasogastric tube feeding without dysphasia. We speculate that the dysgeusia in our patient was mainly caused by inflammation of the chorda tympani nerves. Guillain-Barre syndrome should be considered a possible cause of acute dysgeusia.

Non-doped Mg x Zn 1 − x O films (Mg x Zn 1 − x O films) and nitrogen-doped Mg x Zn 1 − x O films (Mg x Zn 1 − x O:N films) were grown epitaxially on Zn faces of ZnO single crystal substrates by the plasma-assisted reactive evaporation (PARE) method using ZnMg alloys. Optical parameters, refractive index n , extinction coefficient k , and absorption coefficient α of these films and ZnO substrate were easily estimated by variable angle spectroscopic ellipsometry. The k values of these films abruptly increased with increase in photon energy near the absorption edge region. Dispersions of n of these films were sharper with larger peak values than that of a ZnO substrate. Mg x Zn 1 − x O films and Mg x Zn 1 − x O:N films grown on a ZnO substrate by the PARE method are of high quality with less defects than those of a ZnO substrate. Maximum value of α of these films calculated from k was about 2 × 10 5 cm − 1 . The values of intercepts on photon energy hν axis of ( αhν ) 2 ‐ hν plots for these films and the ZnO substrate agree with peak energy of PL spectra, the origin of which is free excitons. These results indicate that absorption in those materials is dominated by exciton absorption.