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Aim: The constellation of cardiovascular disease (CVD) risk factors greatly impacts the lifetime risk (LTR) of incident CVD, but the LTR has not been thoroughly evaluated in the Japanese population., Methods: We conducted a prospective study involving a total of 25,896 individuals 40-69 years old without a history of CVD in 1995 (Cohort I) and 1993-1994 (Cohort II) in Japan. CVD risk factors (blood pressure, non-high-density lipoprotein [HDL] cholesterol levels, smoking status, and glucose concentrations) were used to stratify them by risk. The sex-specific LTR of incident coronary heart disease, stroke, atherosclerotic CVD, and total CVD were estimated for participants 45 years old in the 4 risk categories with the cumulative incidence rate, adjusting for the competing risk of death., Results: We found apparent differences in the LTR of total CVD according to the risk stratification. Individuals with ≥ 2 of the risk factors of blood pressure ≥ 140/90 mmHg or treated, non-HDL cholesterol level ≥ 170 mg/dL or treated, current smoker, and diabetes had substantially higher adjusted LTRs of CVD than those in other groups, with a LTR of 26.5% (95% confidence interval, 24.0%-29.0%) for men and 15.3% (13.1%-17.5%) for women at 45 years. The LTR of incident stroke was the highest among CVDs, and the presence of hypertension and diabetes mellitus strongly influenced the LTR of total CVD., Conclusion: The impact of risk accumulation on LTR of CVD was greater in men, and 1 in 4 men with ≥ 2 major risk factors at 45 years of age developed CVD in their lifetime.

Background: How the weight-bearing asymmetry pattern and related maximum lateral weight-bearing capacity, physical functions, balance, and mobility involved in weight-bearing asymmetry and lesions are related to weight-bearing asymmetry in patients with early-onset stroke remains unclear., Objective: To investigate the difference between weight-bearing in the early phase after stroke categorized as symmetrical or nonsymmetrical regarding impairments, balance, walking, and independence, and any lesion location difference., Methods: This cross-sectional study included 46 persons with hemiparetic stroke within 3 weeks from onset undergoing inpatient rehabilitation and classified into symmetrical, paretic, and non-paretic groups. We performed posturographic, functional, mobility, and lesion location assessments on participants once the evaluation was possible., Results: The symmetrical, paretic, and non-paretic groups included 14, 11, and 21 patients, respectively. The non-paretic group had lesser mean % body weight in maximum lateral weight-bearing to the paretic direction (79% versus 55%, p < .001), motor function of the hip lower limb (64 versus 58, p = .003) per the Stroke Impairment Assessment Set, Trunk Impairment Scale (18 versus 15, p = .020), and Berg Balance Scale (42 versus 32, p = .047) than the paretic group with more lesions in the insula (55% versus 0%, p < .001) and parietal cortex (36% versus 0%, p = .009) than the non-paretic group., Conclusion: The non-paretic group had low dynamic balance, severe motor paresis, and trunk dysfunction. The paretic group had lesions in the insula or parietal cortex.

Background: Associations of major risk factors for stroke with total and each type of stroke, as well as subtypes of ischemic stroke, and their population attributable fractions had not been examined comprehensively., Methods: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n = 14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥25 kg/m 2 ), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (<40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fractions (PAFs) were estimated using the hazard ratios and the prevalence of risk factors among cases., Results: Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage, while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic, and large-artery occlusive strokes were 36.7%, 44.5%, and 61.5%, respectively., Conclusion: Although there are differences according to subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.

Background: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups., Methods: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis., Results: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect ( P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively ( P =0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively ( P =0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control., Conclusions: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903., Competing Interests: Disclosures Dr Ma has consulted for Independent Sector. Dr Ringleb has consulted for Boehringer Ingelheim and Daiichi Sankyo Company and reports personal fees from Bayer Healthcare and Bristol-Myers Squibb. Dr Wu reports grants from National Institutes of Health. Dr Schwamm serves as a scientific consultant regarding trial design and conduct to Genentech (late-window thrombolysis) and as a member of steering committee (TIMELESS [A Phase III, Prospective, Double-Blind, Randomized, Placebo-Controlled Trial of Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase] NCT03785678); stroke systems of care consultant to the Massachusetts Dept of Public Health; member of a Data Safety Monitoring Boards (DSMB) for Penumbra (MIND NCT03342664) and for Diffusion Pharma PHAST-TSC (Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Efficacy and Safety of Trans Sodium Crocetinate [TSC] Administered Onboard Emergency Vehicles for Treatment of Suspected Stroke; NCT03763929); and delivering continuing medical education lectures for Boehringer Ingelheim and Prime Education: stroke systems of care and improving time to thrombolysis. Dr Warach has consulted for Genentech. Dr Davis reports personal fees from Boehringer Ingelheim. Dr Donnan has consulted for Amgen. Dr Gerloff has consulted for Abbott Canada, Allergan, Amgen, Astra-Zeneca, Bayer Healthcare, and Boehringer Ingelheim and reports grants from Deutsche Forschungsgemeinschaft, Deutsches Zentrum für Luft- und Raumfahrt, European Union, Gemeinnützige Hertie-Stiftung, Merz Farmaceutica Comercial LTDA, and Schilling-Stiftung. Dr Thomalla has consulted for Acandis, Bayer, PORTOLA PHARMACEUTICALS, LLC, and Stryker and reports personal fees from Alexion Pharmaceuticals Inc, Amarin Pharma Inc, Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo Europe GmbH. Dr Kitazono reports grant from Daiichi Sankyo Company LTD. Dr Toyoda has consulted for Otsuka Pharmaceutical and reports personal fees from Abbott Japan, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, and Novartis. Dr Koga has consulted for Janssen Pharmaceuticals, reports personal fees from Daiichi Sankyo Company, Bayer, Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation and Pfizer, and reports grants from Daiichi Sankyo Company LTD, Nippon Boehringer Ingelheim Co Ltd. The other authors report no conflicts.

Background: We investigated the clinical effect of intravenous thrombolysis using a magnetic resonance imaging (MRI)-guided approach in cardioembolic stroke (CE) patients with unknown time of onset., Methods and results: This subanalysis of the THAWS trial assessed the efficacy and safety of alteplase 0.6 mg/kg in CE patients with unknown time of onset and showing diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch. Patients were classified as CE and non-CE using the SSS-TOAST classification system during the acute period. The efficacy outcome was a modified Rankin Scale score of 0-1 at 90 days. In all, 126 patients from the THAWS trial were included in this study, of whom 45 (35.7%) were diagnosed with CE. In the CE group, a favorable outcome was numerically more frequent in the alteplase than control group (52% vs. 35%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 0.50-9.99). However, in the non-CE group, favorable outcomes were comparable between the alteplase and control groups (44% vs. 55%, respectively; aOR 0.39; 95% CI 0.12-1.21). Treatment-by-cohort interaction for a favorable outcome was modestly significant between the CE and non-CE groups (P=0.069). In the CE group, no patients experienced symptomatic intracranial hemorrhage (ICH) or parenchymal hematoma Type II following thrombolysis., Conclusions: When an MRI-guided approach is used, CE patients with unknown time of onset appear to be suitable candidates for thrombolysis.

Objective: The associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk., Materials and Methods: We followed 88,754 participants, aged 40-69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m 2 . Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40-59 and ≥60 years) and the age of the individuals was updated., Results: During the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05)., Conclusion: BMI and stroke associations did not vary significantly with age, although the association may differ according to subtype., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 &gt;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., (© 2023 S. Karger AG, Basel.)

Background: The association between hobby engagement and risk of dementia reported from a short-term follow-up study for individuals aged ≥65 years may be susceptible to reverse causation. We examined the association between hobby engagement in age of 40-69 years and risk of dementia in a long-term follow-up study among Japanese, including individuals in mid-life, when the majority of individuals have normal cognitive function., Methods: A total of 22,377 individuals aged 40-69 years completed a self-administered questionnaire in 1993-1994. The participants answered whether they had hobbies according to the three following responses: having no hobbies, having a hobby, and having many hobbies. Follow-up for incident disabling dementia was conducted with long-term care insurance data from 2006 to 2016., Results: During a median of 11.0 years of follow-up, 3,095 participants developed disabling dementia. Adjusting for the demographic, behavioral, and psychosocial factors, the multivariable hazard ratios of incident disabling dementia compared with "having no hobbies" were 0.82 (95% confidence interval [CI], 0.75-0.89) for "having a hobby" and 0.78 (95% CI, 0.67-0.91) for "having many hobbies". The inverse association was similarly observed in both middle (40-64 years) and older ages (65-69 years). For disabling dementia subtypes, hobby engagement was inversely associated with the risk of dementia without a history of stroke (probably non-vascular type dementia), but not with that of post-stroke dementia (probably vascular type dementia)., Conclusion: Hobby engagement in both mid-life and late life was associated with a lower risk of disabling dementia without a history of stroke.

Background: The increased risk of intracranial hemorrhage with multiple passes in endovascular therapy (EVT) for large vessel occlusion with a large ischemic core is a concern. We explored the effect of the number of EVT passes on patients in a randomized clinical trial., Methods: This post hoc study was the secondary analysis of RESCUE-Japan LIMIT, which was a randomized clinical trial comparing EVT and medical treatment alone for large vessel occlusion with large ischemic core. We grouped patients according to the number of passes with successful reperfusion (modified Thrombolysis in Cerebral Infarction score, ≥2b) in 1, 2, and 3 to 7 passes and failed reperfusion (modified Thrombolysis in Cerebral Infarction score, 0-2a) after any pass in the EVT group, and these groups were compared with medical treatment group. The primary outcome was modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were improvement in National Institutes of Health Stroke Scale score of ≥8 at 48 hours, mortality at 90 days, symptomatic intracranial hemorrhage, and any intracranial hemorrhage within 48 hours., Results: The number of patients who received EVT with successful reperfusion after 1, 2, and 3 to 7 passes and failed reperfusion were 44, 23, 19, and 14, respectively, and 102 received medical treatment alone. The adjusted odds ratios (95% CIs) for the primary outcome relative to medical treatment were 5.52 (2.23-14.28) after 1 pass, 6.45 (2.22-19.30) after 2 passes, 1.03 (0.15-4.48) after 3 to 7 passes, and 1.17 (0.16-5.37) if reperfusion failed. The adjusted odds ratios (95% CIs) for any intracranial hemorrhage within 48 hours relative to medical treatment were 1.88 (0.90-3.93) after 1 pass, 5.14 (1.97-14.72) after 2 passes, 3.00 (1.09-8.58) after 3 to 7 passes, and 6.16 (1.87-24.27) if reperfusion failed., Conclusions: The successful reperfusion within 2 passes was associated with better clinical outcomes., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03702413., Competing Interests: Disclosures Dr Uchida reports lecturer fees from Daiichi Sankyo, Bristol Myers Squibb, Stryker, and Medtronic. Dr Shindo reports lecturer fees from Medtronic, Kaneka, Stryker, Daiichi Sankyo, Asahi Intec, Ezai, Bayer, Abbot Medical, Medico’s Hirata, and Johnson and Johnson. Dr Yoshimura reports research grants from Asahi Intec, Asahi Kasei Medical, Bayer, Biomedical Solution, Bristol Myers Squibb, Chugai Pharmaceutical, CSL Behring, Daiichi Sankyo, Eisai, Healios, Kowa, Medico’s Hirata, Medtronic, Miyano Medical Instrument, Otsuka, Sanofi, Siemens, Stryker, Takeda, Teijin, Terumo, and Unimedic and lecturer fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Kaneka, Medtronic, Stryker, and Termo. Dr Sakai reports a research grant from Biomedical Solutions, Medtronic, and Terumo; lecturer fees from Asahi Intec, Biomedical Solutions, Medtronic, and Terumo; and membership on the advisory boards for Johnson & Johnson, Medtronic, and Terumo outside the submitted work. Dr Yamagami discloses research grants from Bristol Myers Squibb; lecturer fees from Stryker, Medtronic, Terumo, Johnson & Johnson, Biomedical Solutions, and Medico’s Hirata; and membership of the advisory boards for Daiichi Sankyo. Dr Toyoda reports lecture fees from Otsuka, Novartis, Bayer, Daiichi Sankyo, Bristol Myers Squibb, and Abbott Medical. Dr Matsumaru reports lecturer fees from Medtronic, Stryker, Terumo, Johnson & Johnson, Kaneka, and Jimro. Dr Matsumoto reports lecturer fees from Kaneka, Medico’s Hirata, Fuji Systems, GE Healthcare, Otsuka, Takeda, Century Medical, Terumo, Medtronic, and Stryker. Dr Kimura reports research grants from CSL Behring, EP-CRSU, Amgen Astellas BioPharma, Alexion, Eisai, Kyowa Kirin, Daiichi Sankyo, Teijin, Medtronic, Bristol Myers Squibb, Bayer, Boehringer Ingelheim, and Helios; and lecturer’s fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol Myers Squibb, Bayer, Takeda, Medtronic, Otsuka, FP pharmaceutical corporation, Alexion, Nippon, Chugai, Kyowa Kirin, Abbott, Shire PLC, Sanofi, CSL Behring, Novartis, Toa Eiyo, Medico’s Hirata, and Helios. Dr Beppu reports manuscript fees from Medicus Shuppan. Dr Inoue reports lecturer fees from Bayer, Bristol Myers Squibb, and Medico’s Hirata and manuscript fees from Gakken and Hokuryukan. Dr Sakakibara reports manuscript fees from Medicus Shuppan. Dr Shirakawa reports lecturer’s fees from Stryker, Terumo, Johnson & Johnson, and Medtronic. Dr Ueda reports grants, personal fees, and nonfinancial support from Pfizer and Alnylam Pharmaceuticals outside the submitted work. Dr Morimoto reports lecturers’ fees from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, and Tsumura; manuscript fees from Bristol Myers Squibb and Kowa; and advisory board for Novartis and Teijin. The other authors report no conflicts.

Background We aimed to clarify which time-to-maximum of the tissue residue function (Tmax) mismatch ratio is useful in predicting anterior intracranial atherosclerotic stenosis (ICAS)-related large-vessel occlusion (LVO) before endovascular therapy. Methods and Results Patients with ischemic stroke who underwent perfusion-weighted imaging before endovascular therapy for anterior intracranial LVO were divided into those with ICAS-related LVO and those with embolic LVO. Tmax ratios of >10 s/>8 s, >10 s/>6 s, >10 s/>4 s, >8 s/>6 s, >8 s/>4 s, and >6 s/>4 s were considered Tmax mismatch ratios. Binominal logistic regression was used to identify ICAS-related LVO, and the adjusted odds ratio (aOR) and 95% CI for each Tmax mismatch ratio increase of 0.1 were calculated. A similar analysis was performed for ICAS-related LVO with and without embolic sources, using embolic LVO as the reference. Of 213 patients (90 women [42.0%]; median age, 79 years), 39 (18.3%) had ICAS-related LVO. The aOR (95% CI) per 0.1 increase in Tmax mismatch ratio in ICAS-related LVO with embolic LVO as reference was lowest with Tmax mismatch ratio >10 s/>6 s (0.56 [0.43-0.73]). Multinomial logistic regression analysis also showed the lowest aOR (95% CI) per 0.1 increase in Tmax mismatch ratio with Tmax >10 s/>6 s (ICAS-related LVO without embolic source: 0.60 [0.42-0.85]; ICAS-related LVO with embolic source: 0.55 [0.38-0.79]). Conclusions A Tmax mismatch ratio of >10 s/>6 s was the optimal predictor of ICAS-related LVO compared with other Tmax profiles, with or without an embolic source before endovascular therapy. Registration clinicaltrials.gov. Identifier NCT02251665.

Background: Effects of therapeutic interventions backward disequilibrium following stroke are scarcely reported., Objective: To clarify the effects of standing and sit-to-stand/stand-to-sit training aimed at postural deviation in the anterior direction for backward disequilibrium and posterior deviation of subjective postural vertical., Case Description: The participant presented with backward disequilibrium and pontine hemorrhage-associated sensory impairment of the extremities. Physical therapy included standing and sit-to-stand/stand-to-sit training, expected to bias the center of gravity in the anterior direction. We measured subjective postural vertical on the sagittal plane to assess vertical perception. Backward disequilibrium was evaluated using the Backward Disequilibrium Scale. Walking ability was assessed using the functional ambulation category. These outcomes were assessed before and at 3 days post-intervention., Outcomes: Neurological findings were unchanged between pre- and post-intervention. Post-intervention, in subjective postural vertical, tilt direction modulated from -6.1° to 1.3°, variability changed from 5.9° to 3.3°, and Backward Disequilibrium Scale score improved from 7 to 1 point. Functional ambulation category changed from 2 to 3., Conclusion: Standing and sit-to-stand/stand-to-sit training aimed at shifting center of gravity and subjective postural vertical in the anterior direction appeared to improve backward disequilibrium and correct tilt to the anterior direction for this participant. Long-term effects of the training for this participant were not determined.

Background: Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk., Methods: Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation., Results: Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death., Conclusion: Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background & Aims: A balanced diet integrating several foods and nutrients may promote the maintenance of brain function. Previous studies have substantiated the above hypothesis in the regional population in Japan. This study aimed to investigate the potential effect of dietary diversity on the risk of disabling dementia in a nationwide large-scale cohort of the Japanese population., Methods: A total of 38,797 participants (17,708 men and 21,089 women) aged 45-74 years were followed up for a median of 11.0 years. The daily frequencies of the consumption of each of the 133 food and beverage items listed on a food frequency questionnaire (excluding five alcoholic beverages) were measured. The dietary diversity score was calculated as the number of food items consumed per day. Multivariable adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of the dietary diversity score quintile groups., Results: We documented 4302 participants with disabling dementia (11.1%) during the follow-up period. Among women, the dietary diversity score was inversely associated with disabling dementia (highest quintile HR [with the lowest quintile as the reference]: 0.67; 95% CI: 0.56-0.78; Q1-Q5 p for trend <0.001), but this was not true among men (highest quintile HR: 1.06; 95% CI: 0.87-1.29; Q1-Q5 p for trend = 0.415). These results did not change substantially when using disabling dementia with stroke as the outcome; the association remained significant among women but was absent among men., Conclusions: Our findings indicate that eating a variety of foods may prevent disabling dementia only among women. Thus, the habit of consuming a variety of food items has important public health implications for women., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p < 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (r s  = 0.09, p = 0.348), they were higher in HAIS with CDM (n = 34; 0.81 vs. 0.61 nmol/L, p < 0.001) or MDM (n = 26; 0.83 vs. 0.62 nmol/L, p = 0.002). These differences remained significant after adjusting baseline factors (adjusted odds ratio, 4.06 [95% CI, 1.31-12.55], p = 0.015 and 4.65 [1.35-16.11], p = 0.015, respectively). Plasma MR-proADM is elevated in HAIS, especially in those with a substantial penumbra, suggesting potential as a blood biomarker in this region., (© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Introduction: Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes., Methods and Analysis: We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results., Ethics and Dissemination: The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals., Trial Registration Number: UMIN000047023., Competing Interests: Competing interests: The following authors have potential conflicts of interest: YO received research funding from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Pfizer and Boston Scientific Japan, and accepted remuneration from Bayer Healthcare, Daiichi-Sankyo and Bristol-Meyers Squibb. KNas accepted remuneration from Johnson & Johnson K.K. TK received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Bayer Healthcare, Boston Scientific and Medtronic Japan. HF accepted remuneration from Daiichi-Sankyo, Bayer Yakuhin, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Abbott Medical Japan, Medtronic Japan and Japan Lifeline. SN received speaker honoraria from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb and Medtronic Japan. WS received grants from Daiichi Sankyo Co., Ltd, and Nippon Boehringer Ingelheim; and remuneration for lectures, presentations, speakers bureaus, manuscript writing or educational events from Daiichi Sankyo, Nippon Boehringer Ingelheim, Bristol-Meyers Squibb, K.K., Bayer Yakuhin, Pfizer, Ono Pharmaceutical and Medtronic Japan. YM received lecture fees from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Japan Lifeline K.K, Medtronic Japan, Pfizer and Boston Scientific Japan. SSu received research funding from Daiichi Sankyo and remuneration from Bristol-Myers Squibb and Daiichi Sankyo. MHar received research funding from BIOTRONIK Japan, Medtronic Japan, Abbott Japan, Japan Lifeline, Nihon Kohden and Boston Scientific Japan, and accepted remuneration from Nippon Boehringer Ingelheim, Daiichi-Sankyo, Bristol-Meyers Squibb, Medtronic Japan, Japan Life Line and Abbott Japan. TY received speaker honoraria from Medtronic Japan and Abbott Medical Japan. MTo received research funding from Japan Lifeline and consulting fee from Medtronic Japan. MTa belongs to the Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine. This section supported by an endowment from Abbott Japan, Medtronic Japan and Boston Scientific Japan. MS is affiliated with an endowed division supported by BIOTRONIK Japan, Boston Scientific Japan K.K., Medtronic Japan and Abbott Medical Japan. AO taught courses endowed by BIOTRONIK, Abbott, Medtronic, Boston Scientific Japan and Japan Lifeline. KSa accepted remuneration from Abbott Japan, Medtronic Japan and Japan Lifeline. HKi accepted remuneration from Otsuka Pharmaceutical., AstraZeneca, Bristol-Meyers Squibb, Ono Pharmaceutical, Pfizer and Novo Nordisk. KMu received honoraria for Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, MSD, Kyowa Kirin, Yakult Pharmaceutical and Boehringer Ingelheim. KKus received speaker honoraria from Daiichi-Sankyo, Nippon Boehringer Ingelheim, Bayer Yakuhin, Pfizer and Medtronic Japan, and research grants from Medtronic Japan and JSR. KoM received speaker honoraria from Medtronic Japan and Abbott Japan, and research funding from Bristol-Meyers Squibb, Pfizer, Medtronic Japan, Japan Lifeline and Boston Scientific Japan., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke., Methods: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication., Results: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication., Conclusion: Alteplase appears more beneficial in patients with prior antithrombotic medication.

Background: The single-device simplicity for mechanical thrombectomy (MT) is now challenged by the complementary efficacy of dual-device first-line with a stent retriever and an aspiration catheter., Objective: To compare the outcomes after MT initiated with a single device vs dual devices in acute anterior circulation large vessel occlusion., Methods: Patients who underwent MT for acute internal carotid artery (ICA) or M1 occlusion between 2015 and 2020 were retrospectively analyzed. We divided patients into 2 groups: single-device first-line, defined as patients who underwent first-device pass with either a stent retriever or aspiration catheter, and dual-device first-line, defined as first-device pass with both devices., Results: One hundred forty-one patients were in the single-device group, and 119 were in the dual-device group. In the dual-device group, coiling or kinking of the extracranial ICA was more frequent ( P = .07) and the guide catheters were less frequently navigated to the ICA ( P < .001). 37% of the single-device group was converted to dual-device use. The proportions of mTICI ≥ 2c after the first pass were similar (33% vs 32%. adjusted odds ratio 0.91, 95% CI 0.51-1.62). An mRS score of 0 to 2 at 3 months was achieved similarly (53% vs 48%, P = .46). The total cost for thrombectomy devices was lower in the single-device group ( P < .001)., Conclusion: The proportions of first-pass mTICI ≥ 2c were not different between the 2 groups with similar functional outcomes, although the dual-device group more likely to have unfavorable vascular conditions., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objectives This study clarified the usefulness of carotid duplex ultrasound (CDU) in evaluating large vessel occlusion (LVO) in patients with acute stroke planned to be treated with mechanical thrombectomy (MT). Methods This study was single-center, prospective, observational trial. If the ratio of end-diastolic velocity in the common carotid arteries was ≥1.4, or diastolic flow in the affected internal carotid artery (ICA) was absent on CDU, patients were immediately transferred to the angio-suite without additional cerebrovascular imaging. Clinical parameters, including time metrics and outcomes, were evaluated in participants. Patients We enrolled stroke patients with a National Institutes of Health Stroke Scale score ≥6 and Alberta Stroke Program Early CT score ≥6 in whom MT could be initiated within 6 hours of the stroke onset. Results Among 140 patients screened during the study period, 48 were ultimately enrolled. Twenty-seven patients were diagnosed with LVO by CDU alone. CDU offered 83% sensitivity and 82% specificity for identifying the occlusion of the ICA or M1 segment of the middle cerebral artery. Among the 29 total patients treated with MT, 20 (67%) showed a modified Rankin Scale score ≤2 at 90 days. The door-to-puncture time was significantly shorter in patients evaluated by CDU alone (34 minutes) than in those evaluated by magnetic resonance angiography after CDU (47.5 minutes, p<0.001). Conclusion CDU might reduce the time metrics for early initiation of MT with good sensitivity and specificity in identifying LVO.

Importance: Endovascular therapy (EVT) has been found to reduce functional disability in patients with acute stroke due to large-vessel occlusion. However, the extent of the ischemic region, measured using Alberta Stroke Program Early Computed Tomography Scores, may limit the efficacy of EVT., Objective: To compare the efficacy and safety of EVT according to ASPECTS 3 or less vs 4 to 5., Design, Setting, and Participants: The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial (RESCUE-Japan LIMIT) was an open-label randomized clinical trial conducted from November 2018 to December 2021 at 45 stroke centers across Japan. The trial enrolled adult patients with acute ischemic stroke with a large ischemic region, defined as ASPECTS 3 to 5 primarily determined by magnetic resonance imaging, with occlusion site at the internal carotid artery or middle cerebral artery segment 1. Among 203 enrolled patients, 1 withdrew consent and 202 were included in the original trial and secondary analysis. This secondary analysis was conducted in April 2022., Interventions: Patients were randomly assigned to EVT with medical therapy or medical therapy alone., Main Outcomes and Measures: Modified Rankin Scale (mRS) score at 90 days and symptomatic and any intracranial hemorrhage within 48 hours., Results: Among 202 patients, 106 (52%) had ASPECTS 3 or less (mean [SD] age, 76.7 [9.6] years; 54 female individuals [50.9%]) and 96 had ASPECTS 4 to 5 (mean [SD] age, 75.6 [10.6] years; 36 female individuals [37.5%]). Of patients with ASPECTS 3 or less, 12 (21.4%) in the EVT group and 9 (18.0%) in the no EVT group had an mRS score of 0 to 3 (odds ratio [OR], 1.24; 95% CI, 0.47-3.26). Of patients with ASPECTS 4 to 5, 19 patients (43.2%) in the EVT group and 4 (7.7%) in the no EVT group had an mRS score of 0 to 3 at 90 days (OR, 9.12; 95% CI, 2.80-29.70; interaction P = .01). The ordinal shift across the range of mRS scores toward a better outcome was not significant in those with ASPECTS or 3 or less (common OR, 1.56; 95% CI, 0.79-3.10) but was significant in those with ASPECTS 4 to 5 (common OR, 4.48; 95% CI, 2.07-9.71; interaction P = .046). The risk of intracranial hemorrhage was significantly increased in patients with ASPECTS 3 or less when EVT was conducted (OR, 4.14; 95% CI, 1.84-9.32) and nonsignificantly increased in those with ASPECTS 4 to 5 (OR, 2.05; 95% CI, 0.89-4.73; interaction P = .24)., Conclusions and Relevance: In this study, EVT was associated with improved 90-day functional outcomes in patients with acute large vessel occlusive stroke and ASPECTS was 4 to 5 but not in those with ASPECTS 3 or less., Trial Registration: ClinicalTrials.gov Identifier: NCT03702413.

Background: The effects of task-specific and voluntary exercise in upright positions for pusher behavior remain unclear. In this report, we aimed to describe the effects of dynamic supported standing training using a modified standing frame to correct the alignment in a patient with severe pusher behavior., Case Description: A 76-year-old man with cardioembolic ischemic stroke demonstrated pusher behavior. The patient underwent 3 days of dynamic supported standing training using a modified standing frame. The Scale for Contraversive Pushing, the Burke Lateropulsion Scale, and the Trunk Control Test were used to assess changes., Outcomes: Immediate improvements in sitting balance were observed after the intervention, and the effects persisted to 8 days later., Conclusion: Dynamic supported standing training using a modified standing frame may improve pusher behavior with short-term training. The collapsed posture of the patient in the present case was corrected using the modified standing frame. This neutral standing position could have a positive effect on motor learning with respect to holding one's posture.

Background: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD., Methods: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of <60 ml/min/1.73m 2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality., Results: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect ( P interaction =0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55-2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls ( P =0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls ( P =0.539)., Conclusions: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

Background: Mechanical thrombectomy (MT) is effective in acute ischemic stroke patients ≥80 years old with large vessel occlusion (LVO). However, data for patients ≥90 years old remain very limited, and factors influencing functional outcomes are unclear. This study aimed to investigate factors influencing functional outcomes in patients ≥90 years old treated with MT for acute LVO., Methods: This retrospective observational study used prospectively collected data from the Tokyo/tama-REgistry of Acute endovascular Thrombectomy (TREAT) study. Inclusion criteria were as follows: 1) patients ≥90 years old treated with MT for LVO and 2) prestroke modified Rankin Scale (mRS) score, 0-3. The functional outcome was defined based on the mRS score at 90 days after the procedure: good functional outcome, mRS score 0-3 and poor functional outcome, mRS score 4-6., Results: Data were analyzed for 104 patients ≥90 years old. The good functional outcome was observed in 25 patients (24.0%), and the poor functional outcome was observed in the remaining 79 patients. Significant differences were identified in initial National Institutes of Health Stroke Scale (NIHSS) score, modified Thrombolysis in Cerebral Infarction grade 2b-3, modified Thrombolysis in Cerebral Infarction grade 3, and any intracranial hemorrhage and hemorrhagic infarction in univariate analyses. Multivariable analysis confirmed the initial NIHSS score (odds ratio, 1.08; 95% confidence interval, 1.01-1.17; P = 0.045) and any intracranial hemorrhage (odds ratio, 11.6; 95% confidence interval, 1.43-95.0; P = 0.022) as independent factors for the functional outcome., Conclusions: An initial high NIHSS score and any intracranial hemorrhage are independent factors for the poor functional outcome in acute ischemic stroke patients ≥90 years old treated with MT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay between each phase of the with-COVID-19 period., Methods: Patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis and/or mechanical thrombectomy were selected from our single-center prospective registry. The time to perform reperfusion therapy were compared between patients admitted from March 2019 to February 2020 (pre-COVID-19 group) and those from March 2020 to February 2021 (with-COVID-19 group). Patients in the with-COVID-19 group were further divided into three 4-month-long subgroups (first-phase: March to June 2020; second-phase: July to October 2020; third-phase: November 2020 to February 2021), and the time delay of reperfusion therapy were compared between these subgroups., Results: Of 1,260 patients with AIS hospitalized in the study period, 265 patients were examined. Compared with the pre-COVID-19 group (133 patients; median age, 79 years), the with-COVID-19 group (132 patients; median age, 79 years) had a longer median door-to-imaging time (25 min vs. 27 min, P=0.04), and a longer door-to-groin puncture time (65 min vs. 72 min, P=0.02). In the three 4-month-long subgroups, the median door-to-needle time (49 min, 43 min, and 38 min, respectively; P=0.04) and door-to-groin puncture time (83 min, 70 min, and 61 min, P＜0.01, respectively) decreased significantly during the with-COVID-19 period., Conclusions: The delay in reperfusion therapy increased during the with-COVID-19 period compared with the pre-COVID-19 period. However, the door-to-needle time and door-to-groin puncture time decreased as time elapsed during the with-COVID-19 period., Clinicaltrials: gov Identifier: NCT02251665.

Background and Aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke., Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days., Results: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( p  = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group ( p interaction = 0.042)., Conclusion: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

Objectives: The management of acute type A aortic dissection with malperfusion syndrome remains challenging. To evaluate preoperative condition, symptoms might be subjective and objective evaluation of cerebral artery has not yet been established. For quantitative evaluation, this study focused on brain computed tomography perfusion (CTP), which has been recommended by several guidelines of acute ischaemic stroke., Methods: In the last 2 years, 147 patients hospitalized due to acute type A aortic dissection were retrospectively reviewed. Among the 23 (16%) patients with cerebral malperfusion, 14 who underwent brain CTP (6 preoperative and 8 postoperative) were enrolled. CTP parameters, including regional blood flow and time to maximum, were automatically computed using RApid processing of Perfusion and Diffusion software. The median duration from the onset to hospital arrival was 129 (31-659) min., Results: Among the 6 patients who underwent preoperative CTP, 4 with salvageable ischaemic lesion (penumbra: 8-735 ml) without massive irreversible ischaemic lesion (ischaemic core: 0-31 ml) achieved acceptable neurological outcomes after emergency aortic replacement regardless of preoperative neurological severity. In contrast, 2 patients with an ischaemic core of >50 ml (73, 51 ml) fell into a vegetative state or neurological death due to intracranial haemorrhage. CTP parameters guided postoperative blood pressure augmentation without additional supra-aortic vessel intervention in the 8 patients who underwent postoperative CTP, among whom 6 achieved normal neurological function regardless of common carotid true lumen stenosis severity., Conclusions: CTP was able to detect irreversible ischaemic core, guide critical decisions in preoperative patients and aid in determining the blood pressure augmentation for postoperative management focusing on residual brain ischaemia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background and Aims: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined., Methods: A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4-6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography., Summary of Review: Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00-1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02-1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00-1.05 per hour)., Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

Background: Outcome prediction for dysphagia recovery is essential for rehabilitation treatment planning. Several studies have reported various predictors for resuming oral feeding after post-stroke dysphagia. However, evidence on oral health and function, a crucial part of feeding, has rarely been reported. Therefore, the goal of this study was to identify the oral status-related factors that could predict oral intake resumption in acute stroke patients., Methods: 80 acute stroke patients with dysphagia were included. Clinical data, including the changes of general condition, oral and swallowing functions, were collected once a week until discharge. Patients were divided into two groups based on the outcome of the food intake level scale at discharge, and data were compared between the groups., Results: 60 patients had regained complete oral intake before discharge. Multiple logistic regression showed that posterior tongue pressure could significantly predict complete oral intake recovery. Tongue pressure and modified water swallowing test score also significantly influenced diet forms. In addition, Spearman correlation analysis showed that improvement of other oral status-related factors, such as oral moisture and dentition status, also indicated the improvement of diet forms and swallowing function during the hospital stay., Conclusion: Tongue pressure measurement could be a useful oral status-related indicator for predicting complete oral intake and adjusting diet forms for acute stroke patients during hospitalization. Acute stroke patients should receive proper oral status evaluation and implementation to enhance functional recovery., Competing Interests: Disclosures None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Endovascular therapy is strongly recommended for acute cerebral large vessel occlusion (LVO) with an Alberta stroke program early computed tomography score (ASPECTS) ≥6 due to occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. However, the effect of endovascular therapy for patients with a large ischemic core with an ASPECTS ≤5 (0-5) was not established. A multicenter, randomized, open-label, parallel-group trial was conducted to investigate the superiority of endovascular therapy over medical therapy without endovascular therapy for a large ischemic core with ASPECTS (3-5). Patients were randomly assigned to receive endovascular therapy or without endovascular therapy at a ratio of 1:1. The primary outcome was a moderate functional outcome, defined as a modified Rankin scale (mRS; scores ranging from 0 [no symptoms] to 6 [death]) ≤3 after 90 days. The secondary outcomes were defined as ordinal mRS, good functional outcome (mRS ≤2), excellent functional outcome (mRS ≤1), mRS shift analysis after 90 days, and early improvement of neurological findings at 48 hours. A total sample size of 200 was estimated to provide a power of 0.9 with a two-sided alpha of 0.05, for the primary outcome, considering a 15% dropout rate. This randomized clinical trial reported the applicability of endovascular therapy in patients with acute cerebral LVO with a large ischemic core.

Purpose: To investigate the effect of alteplase, either combined with stent-retriever thrombectomy or a direct aspiration first pass technique (ADAPT), in patients with large-vessel occlusion stroke., Methods: This was a retrospective post hoc analysis of data from The Direct Mechanical Thrombectomy in Acute LVO Stroke (SKIP) study. Patients were divided into two groups according to the first-line thrombectomy technique: stent-retriever and ADAPT. Each group was further divided into two subgroups, namely MT and MT + alteplase. The procedural outcomes, such as first pass effect (FPE) ratio and number of passes, were evaluated. The clinical outcomes included mRS score at 3 months., Results: A total of 180 patients were included (116 in the stent-retriever group and 64 in the ADAPT group). No interaction was detected between the first-line technique and alteplase administration. In the stent-retriever group, after adjusting for factors associated with FPE, the adjusted odds ratio (95% confidence interval) of FPE of the MT + alteplase subgroup versus the MT subgroup was 3.57 (1.5-8.48) and in the ADAPT group it was 1.35 (0.37-4.91). With alteplase, the number of passes decreased with adjusted odds ratios of 0.59 (0.37-0.93) in the stent-retriever group but not in the ADAPT group. In both first-line technique groups, clinical outcomes did not differ between subgroups., Conclusion: In the SKIP study, alteplase administration was associated with increased FPE when combined with stent-retriever thrombectomy, but not with ADAPT. We found no differences in the clinical outcomes., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation., Methods and results: We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences., Conclusions: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years., Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk., Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR ≥85y  = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR <85y  = 0.79, 95%-CI [0.66, 0.95]) in simple (p interaction  = 0.129), adjusted (p interaction  = 0.094) or weighted (p interaction  = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1)., Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78-88., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background We retrospectively compared early- (<6 hours) versus late- (6-24 hours) presenting patients using perfusion-weighted imaging selection and evaluated clinical/radiographic outcomes. Methods and Results Large vessel occlusion patients treated with mechanical thrombectomy from August 2017 to July 2020 within 24 hours of onset were retrieved from a single-center database. Perfusion-weighted imaging was analyzed by automated software and final infarct volume was measured semi-automatically within 14 days. The primary end point was good outcome (modified Rankin Scale 0-2 at 90 days). Secondary end points were excellent outcome (modified Rankin Scale 0-1 at 90 days), symptomatic intracranial hemorrhage, and death. Clinical characteristics/radiological values including hypoperfusion volume and infarct growth velocity (baseline volume/onset-to-image time) were compared between the groups. Of 1294 patients, 118 patients were included. The median age was 74 years, baseline National Institutes of Health Stroke Scale score was 14, and core volume was 13 mL. The late-presenting group had more female patients (67% versus 31%, respectively; P =0.001). No statistically significant differences were seen in good outcome (42% versus 53%, respectively; P =0.30), excellent outcome (26% versus 32%, respectively; P =0.51), symptomatic intracranial hemorrhage (6.5% versus 4.6%, respectively; P =0.74), and death (3.2% versus 5.7%, respectively; P =0.58) between the groups. The late-presenting group had more atherothrombotic cerebral infarction (19% versus 6%, respectively; P =0.03), smaller hypoperfusion volume (median: 77 versus 133 mL, respectively; P =0.04), and slower infarct growth velocity (median: 0.6 versus 5.1 mL/h, respectively; P =0.03). Conclusions Patients with early- and late-time windows treated with mechanical thrombectomy by automated perfusion-weighted imaging selection have similar outcomes, comparable with those in randomized trials, but different in infarct growth velocities. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02251665.

Background: We aimed to identify the large ischemic core (LIC) volume ranges in acute ischemic stroke patients that can benefit from mechanical thrombectomy (MT)., Methods: Consecutive 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., Results: Of 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%, P<0.05) versus SMT, respectively. Group B (n=36) MT patients (n=14) also had a higher proportion of mRS 0-2 at 3 months (29% vs 9%, P=0.13) versus SMT, respectively. In Group C (n=69), only four patients received MT. The 95% confidence intervals for the probability of mRS 0-2 at 3 months in patients with MT (n=49) versus SMT (n=108) intersected at 120-130 mL., Conclusions: Ischemic 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : For patients with severe post-stroke pusher behavior (PB), acquiring a vertical posture involves correcting paretic-sided body tilt to the non-paretic side. Active lateral sitting training may facilitate improvement in postural orientation for patients with PB. However, its effect on patients with severe PB remains unclear. Objective : To determine the effect of performing a lateral-reaching exercise in patients with severe PB seated on a tilted surface Methods : Three patients with severe PB due to right hemispheric stroke participated in our study. Using a single-case design, the intervention's effect was verified using the applied behavior analysis method. Conventional physical therapy was performed for 1 h at baseline and at follow-up. During the intervention, lateral sitting training on a tilted surface was performed 40 times per session (total, 2 sessions). PB was assessed using the Scale for Contraversive Pushing and the Burke Lateropulsion Scale, and patient-reported fear of falling. The Function in Sitting Test (FIST) and the Trunk Control Test (TCT) were administered. Results : PB improved in all patients post-intervention and persisted at follow-up. Fear of falling during the passive sitting task while moving toward the non-paretic side disappeared post-intervention and at follow-up. FIST and TCT scores improved in 2 patients. Conclusion : The lateral sitting exercise reduced severe PB in all patients; however, sitting balance and trunk performance did not improve in 1 patient. Future studies to examine the adaptability of this task and long-term effects are needed.

Objectives: An association has been reported between delays in the onset-to-door (O2D) time for mechanical thrombectomy (MT) and outbreaks of coronavirus disease 2019 (COVID-19). However, the association between other MT time courses or functional outcomes and COVID-19 outbreaks remains unclear. We compared the time courses of stroke pathways or functional outcomes in 2020 (the COVID-19 era) with those in 2019 (the pre-COVID-19 era) in Tokyo, Japan., Materials and Methods: This retrospective observational study used data from the Tokyo-tama-REgistry of Acute endovascular Thrombectomy (TREAT), a multicenter registry of MT for acute large vessel occlusion in the Tokyo Metropolitan Area. Patients who had undergone acute MT from January 2019 to December 2020 were included. Patients were classified by the year they had undergone MT (2019 or 2020)., Results: In total, 477 patients were analyzed. O2D time was significantly longer in 2020 (146.0 min) than in 2019 (105.0 min; p = 0.034). No significant difference in door-to-puncture time (D2P) time or modified Rankin Scale (mRS) score 0-2 at 90 days was seen between 2019 and 2020. In the subgroup analysis, O2D time was significantly longer in the first half of 2020 compared with 2019. Multivariable logistic regression analysis revealed that the year 2020 was a independent predictor of longer O2D time, but not for mRS score 0-2 at 90 days., Conclusions: Although O2D time was significantly longer in the COVID-19 compared with the pre-COVID-19 era, D2P may not be significantly delayed and functional outcomes may not be different, despite the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest Yoshiaki Shiokawa has received research grants from AbbVie GK and ONO Pharmaceitocal CO., LTD. Teruyuki Hirano has received honoraria from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Otsuka Pharma, Pfizer, and Sanofi. All the other authors have nothing to disclosure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To investigate the intensity and effectiveness of rehabilitation in acute stroke patients according to the severity of functional impairments in them., Materials and Methods: This retrospective cohort study included 294 patients with acute hemispheric stroke admitted to three acute-care hospitals who subsequently underwent an inpatient rehabilitation program. Stroke severity was classified according to neurological deficits and trunk dysfunction. The following data were obtained from medical records: age, sex, stroke type, lesion side, hospitalization duration, initial functional status determined using the National Institutes of Health Stroke Scale, rehabilitation start date, first day out of bed after admission, total treatment duration, total number of treatment sessions, rehabilitation implementation rate between start of rehabilitation and discharge, trunk control test and Barthel Index score on the first day out of bed after admission and discharge, and post-discharge outcomes. Hierarchical cluster analysis was performed with clusters categorized using the National Institutes of Health Stroke Scale and trunk control test scores. Variables were compared using the Kruskal-Wallis test, and Dunn's nonparametric comparison test was performed for post-hoc analysis to determine differences between clusters., Results: The National Institutes of Health Stroke Scale and trunk control test showed a significant correlation (r = -0.816, p < 0.01) using which cluster analysis identified three clusters. Rehabilitation showed a ceiling effect in patients with mild stroke and a floor effect in patients with severe stroke., Conclusion: These results may guide the determination of rehabilitation intensity with reference to the severity of neurological deficits and trunk dysfunction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Imaging diagnosis is essential to perform appropriate reperfusion therapy for acute ischemic stroke. To equally perform reperfusion therapy all over in Japan, it is important to properly facilitate acute imaging evaluation for stroke suspected patients by medical staff not only in stroke-specialized hospitals but also in non-stroke-specialized hospitals. It is unique that CT and MRI are available in most of Japanese hospitals. Even in non-stroke-specialized hospitals, inpatients may suffer from in-hospital stroke. We review statements and recommendation items for a diagnostic imaging to appropriately perform reperfusion therapy based on major clinical trials, stroke guidelines and the current status of acute stroke imaging in Japan.

Purpose: To clarify the effects of diagonally aligned sitting training using a tilted surface on sitting balance for patients with low sitting performance in the early phase after stroke., Materials and Methods: This was an assessor-blinded randomised controlled trial. The experimental group used a surface tilted 10° backward and down toward the most affected side; the control group trained on a horizontal surface. Both groups were asked to move their trunk diagonally forward toward the least affected side. Participants performed the activity 40 times/session for seven sessions over 8 days. Sitting performances were assessed using the function in sitting test (FIST), subjective postural vertical (SPV) on the diagonal plane, and trunk impairment scale (TIS)., Results: Thirty-three stroke patients were randomly allocated into two groups. Treatment effects differed significantly: mean differences between groups for FIST (total score, static, dynamic, scooting, and reactive) were 8.96, 2.35, 3.01, 1.27, and 1.72 points, for the mean SPV value was 1.82°, and for the TIS (total score and static) were 1.87 and 1.58 points, respectively. These results were more favourable in the experimental group., Conclusions: Diagonally aligned sitting training on a tilted surface improves sitting balance and modulates the SPV compared with a horizontal surface.

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8 months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71-1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49-0.94) and had a CHA 2 DS 2 -VASc score  < 3 (HR 0.66 [vs. CHA 2 DS 2 -VASc score ≥ 3], 95% CI 0.43-0.98]). The 2-year risk reduction achieved by ablation may be small among Japanese patients, but AF ablation may benefit those with paroxysmal AF and a CHA 2 DS 2 -VASc score < 3.

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.

Objectives: Sitting ability during the acute phase after stroke is a useful indicator of functional outcomes; however, factors that affect this ability have not been evaluated. Therefore, this study aimed to identify and evaluate factors that affect sitting ability in the acute phase after stroke., Materials and Methods: This multicenter prospective cohort study included hemispheric stroke patients who underwent an inpatient rehabilitation program after acute stroke from five acute care hospitals. The effect of age, sex, lesion side, etiology, consciousness disorder, stroke and dementia history, stroke-related complications, National Institutes of Health Stroke Scale score, hemiparalysis, turn-over movement from the supine position and sit-up movement, and Scale for Contraversive Pushing on the "remain sitting" item in the revised version of the Ability of Basic Movement Scale at the time of acute hospital discharge were investigated. Factors affecting sitting ability were identified using binomial logistic regression analysis., Results: We included 293 stroke patients. Age (odds ratio: 0.943, 95% confidence interval: 0.910-0.977, p=0.001), National Institutes of Health Stroke Scale score (odds ratio: 0.862, 95% confidence interval: 0.811-0.916, p<0.001), and Scale for Contraversive Pushing score (odds ratio: 0.543, 95% confidence interval: 0.419-0.705, p<0.001) were identified as independent predictors of sitting ability at the time of hospital discharge (median; 23.0 days)., Conclusions: Older patients and those with high Scale for Contraversive Pushing and National Institutes of Health Stroke Scale scores experienced difficulties in regaining sitting ability. These results may guide physical therapy for patients with impaired sitting ability due to hemispheric stroke., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We examined the association between meat intake and mortality due to all-cause and major causes of death using a population-based cohort study in Japan., Methods: 87,507 Japanese aged between 45 and 74 years old at 5-year follow-up study were followed for 14.0 years on average. Associations between meat intake and mortality risk were assessed using a Cox proportional hazards model., Results: A heavy intake of total meat was associated with a higher risk of all-cause mortality relative to the lowest quartile intake in men (Q4: HR,1.18; 95%CIs, 1.06-1.31). A higher intake of total meat was associated with a lower risk of stroke mortality in women (Q2: HR, 0.70; 95%CIs, 0.51-0.94, Q3: HR, 0.68; 95%CIs, 0.50-0.95, Q4: HR, 0.66; 95%CIs, 0.44-0.99). A heavy intake of red meat was also associated with all-cause mortality (Q4: HR, 1.13; 95%CIs, 1.02-1.26) and heart disease mortality (Q4: HR, 1.51; 95%CIs, 1.11-2.06) in men but not in women. Heavy intake of chicken was inversely associated with cancer mortality in men., Conclusions: Heavy intakes of total and red meat were associated with an increase in all-cause and heart disease mortality in men, while total meat intake was associated with a lower risk of stroke mortality in women., Competing Interests: The authors have declared that no competing interests exist.

Background: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran., Methods: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model., Results: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001)., Conclusion: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA 2 DS 2 -VASc scores differed significantly between DOAC dosing regimens, with patients given an appropriate standard-dose being significantly younger (63.3 ± 9.4 versus 64.8 ± 9.5 versus 73.2 ± 6.8 years, P < 0.0001) and lower (2.1 ± 1.5 versus 2.4 ± 1.6 versus 3.4 ± 1.4, P < 0.0001) than those given an off-label under-dose or an appropriate low-dose. During the median 19.0-month follow-up period, the AF recurrence rate was similar between the appropriate standard-dose and off-label under-dose groups but relatively low in the appropriate low-dose group (42.5% versus 41.2% versus 35.4%, P = 0.08). Annualized rates of thromboembolic events, major bleeding, and death from any cause were 0.47%, 0.70%, and 0.23% in the off-label under-dose group, while those rates were 0.74%, 0.73%, and 0.65% in the appropriate standard-dose, and 1.58%, 2.12%, and 1.57% in the appropriate low-dose groups.In conclusion, the clinical adverse event rates for patients on an off-label under-dose DOAC regimen after ablation, predicated on careful patient evaluations, was not high as seen with that of patients on a standard DOAC dosing regimen.

Background and Purpose: We hypothesized that the relationships between treatments and outcomes in acute basilar artery occlusion (BAO) are different, depending on the severity of initial neurological deficits., Methods: Of 2420 ischemic stroke patients with large vessel occlusion in a prospective, multicenter registry in Japan, patients with acute BAO were enrolled. Subjects were divided into two severity groups according to the baseline NIH Stroke Scale score: severe (≥10) and mild (<10) groups. The primary effectiveness outcome was favorable outcome, defined as modified Rankin Scale score 0-3 at 3 months. Safety outcomes included any intracranial hemorrhage (ICH) within 72 h. Outcomes in each group were compared between patients who received endovascular therapy (EVT) and those with standard medical treatment (SMT)., Results: In this study, 167 patients (52 female; median age 75 years) were analyzed. The favorable outcome was seen in 93 patients (56%) overall. In the severe group (n = 128), the proportion of favorable outcome was higher in patients who received EVT (60/111, 54%) than those with SMT (2/17, 12%, P < 0.01). In the mild group (n = 39), the rates of favorable outcome were comparable between the EVT (13/18, 72%) and SMT patients (18/21, 86%, P = 0.43). No significant differences in the rates of any ICH were seen among any groups., Conclusions: In acute BAO stroke with severe neurological deficit, independent ambulation was more frequently seen in patients who received EVT than those with SMT. Patients with mild neurological deficits showed similar rates of independent ambulation between the two treatment selections., (Copyright © 2020. Published by Elsevier Inc.)

During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.

Pusher behavior (PB) is a severe lateral postural disorder that involves a disturbed subjective postural vertical (SPV) in the frontal plane. SPV is measured by determining the mean value and standard deviation of several trials beginning on both the contralesional- and ipsilesional-tilted positions. However, the postural representation, when passively tilted to the contralesional versus ipsilesional position, is different between patients with and without PB. Therefore, we hypothesized that SPV dependence on the starting position will be influenced by PB. For 53 patients with hemispheric stroke enrolled, SPV was measured using a non-motorized vertical board with eyes closed. The mean value (tilt direction) and standard deviation (variability) were calculated in four trials, each from two positions, with the patient tilted to the contralesional position (SPV-CL condition) and then to the ipsilesional position (SPV-IL condition). Patients were categorized into the non-pusher (n = 29) and pusher (n = 24) groups. In the SPV-CL trials, the tilt direction was significantly tilted contralesionally for the pusher group (- 6.3° ± 1.6°) compared with that for the non-pusher group (- 2.2° ± 1.8°; p < 0.001), with no significant difference in variability between the groups. In the SPV-IL trials, the tilt direction was not significantly different between the groups, but the variability was significantly higher in the pusher group (4.8° ± 2.0°) than in the non-pusher group (2.2° ± 1.3°; p < 0.001). The dependence of tilt direction and variability of SPV on the starting position in patients with PB differed from those noted in patients without PB. These results may help explain this abnormal posture and optimize neurological rehabilitation strategies for PB.