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Background: Little is known about endovascular therapy (EVT) for patients with medium vessel occlusion (MeVO) and more work is needed to establish its efficacy and to understand hemorrhagic complications., Methods: We analyzed the Japan Trevo Registry, which enrolled patients with acute stroke who underwent EVT using Trevo Retriever alone or in combination with an aspiration catheter. The primary outcome was effective reperfusion, and the secondary outcome was modified Rankin scale 0-2 at 90 days. Safety outcomes, including intracranial hemorrhage (ICH), were evaluated using a subgroup analyses focused on any ICH., Results: Among 1041 registered patients, 1025 patients were analyzed. 253 patients had MeVOs, and the majority (89.3%) had middle cerebral artery segment 2 (M2). The median National Institutes of Health Stroke Scale scores at admission were 15 and 19 for the MeVO and LVO groups (p < 0.0001). The primary outcome was 88.9% in MeVO vs. 91.8% in LVO group: adjusted odds ratio (aOR) [95% confidence interval (CI)] 0.60 [0.35-1.03], p = 0.07, and the secondary outcome was 43.2% vs. 42.2%, and the aOR [95%CI] was 0.70 [0.48-1.002], p = 0.051. However, the incidence of any ICH was more prominent in MeVO than in LVO group (35.7% vs. 28.8%, aOR [95%CI] 1.54 [1.10-2.15], p = 0.01). In subgroup analyses, the incidences of any ICH in MeVO group were generally higher than those in LVO group., Conclusions: The effective reperfusion rate did not differ significantly between MeVO and LVO groups. Future development of devices and treatments for MeVO with fewer hemorrhagic complications is desirable., Competing Interests: Declaration of competing interest Dr. Kuwahara has no conflicts of interest to report. Dr. Uchida reports lecturer's fees from Daiichi Sankyo, Bristol-Myers Squibb, Stryker, and Medtronic. Dr. Sakai reports a research grant from Biomedical Solutions, Medtronic, Terumo and TG Medical; lecturer's fees from Asahi-Intec, Biomedical Solutions, Kaneka, Medtronic, and Terumo; membership on the advisory boards for Johnson&Johnson, Medtronic and Terumo. Dr. Yamagami discloses research grants from Bristol-Myers Squibb; lecturer's fees from Stryker, Medtronic, Terumo, Johnson & Johnson, and Medico's Hirata. Dr. Imamura reports lecturer's fees from Medtronic, Daiichi Sankyo, Johnson and Johnson, Stryker, Terumo, Asahi Intecc. Dr. Takeuchi reports lecturer's fees from Stryker, Daiichi-Sankyo, Johnson & Johnson. Dr. Shirakawa reports lecturer's fees from Stryker, Terumo, Johnson & Johnson and Medtronic. Dr. Sakakibara reports a manuscript fee from Medicus Shuppan. Dr. Haraguchi reports lecturer's fees from Stryker, Medtronic, Kaneka, Asahi intec, Cerenovus, Daiichi Sankyo. Dr. Kimura reports lecturer's fees from Stryker, Terumo, Medtronic, Kaneka, Asahi intec, Cerenovus, Daiichi Sankyo, Nipro, Siemens, Bayer, Nestle Japan, Lifeline and Pfizer, Dr. Shindo reports lecturer fees from Medtronic, Kaneka, Stryker, Daiichi Sankyo, Asahi-Intec, Ezai, Bayer, Abbot medical, Medicos Hirata and Johnson and Johnson.(.) Dr. Suzuki has no conflicts of interest to report. Dr. Yoshimura reports research grants from Medico's Hirata, Medtronic, and Terumo; and lecturer fees from Medtronic, Kaneka, Stryker, Daiichi Sankyo, Bristol-Meyers Squibb, and Johnson & Johnson., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: We investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan., Methods: This prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately., Results: The mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5-6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01-1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51-111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18-51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03-1.17), LVO (aOR: 14.88, 95%CI: 2.33-94.97), and log 10 D-dimer (aOR: 3.38, 95%CI: 1.01-11.26)., Conclusion: Upon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log 10 D-dimer., Registration: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226., (Copyright © 2023. Published by Elsevier B.V.)

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: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots., Methods: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot., Results: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts., Conclusion: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Endovascular therapy (EVT) for real-world patients after extended time frames is associated with concerns about its efficacy and safety. We conducted a prospective registry at 77 centers between November 2019 and October 2020. The registry criteria included patients treated with Trevo Retriever alone or in combined therapy with an aspiration catheter. The primary outcome was effective reperfusion (thrombolysis in cerebral infarction grade ≥ 2b), the secondary outcome was a modified Rankin scale 0-2 at 90 days, and the safety outcomes were worsening of neurologic symptoms within 24 h postoperatively, intracranial hemorrhage (ICH) within 24 h after EVT and mortality. We also exlpored the difference between patients whose last known well time (LKWT) to a puncture was less than 6 h (0-6 h) and those whose LKWT was 6 h or more but less than 24 h (6-24 h). Among the 1041 patients registered, 1025 patients were analyzed. The mean age was 76.9 years, and 53.6% of the participants were males. The 6-24 h group was 206/998 (20.6%), the median National Institute of Health Stroke Scale (NIHSS) score at admission was 18, and the median Alberta Stroke Program Early CT score was 8. Combined technique as the first pass was used on 817 (79.7%) patients. The primary outcome was 934 (91.1%). The secondary outcome was 433/1021 (42.4%). Symptomatic ICH, any ICH, and mortality were 10/1019 (1.0%), 311/1019 (30.5%), and 75 (7.3%). In the subanalysis, the 6-24 h group was lower in NIHSS (median;18 vs 16), and the secondary outcome was not significantly different in the <6 h group. Even after treatment time expansion, this result was comparable to other Trevo-based trials and nationwide registries.

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: Endovascular treatment (EVT) for patients with large vessel occlusion (LVO) and concurrent thrombocytopenia raises concerns about hemorrhagic complications. We examined the association between thrombocytopenia and clinical outcomes after EVT., Methods: This is a sub-analysis of the RESCUE-Japan Registry 2, a nationwide registry that enrolled 2420 consecutive acute LVO patients. We evaluated the clinical outcomes in patients who underwent EVT according to their platelet count on admission (Moderate/Severe, < 100 × 10 9 /L; Mild, 100 to ≤150 × 10 9 /L; Normal, ≥ 150 × 10 9 /L). The outcomes included any and symptomatic intracranial hemorrhage (ICH) after EVT, and modified Rankin Scale (mRS) at 90 days., Results: Of 1268 patients who underwent EVT, the Moderate/Severe and Mild groups consisted of 41 (3.2%), and 193 (15.2%) patients. Any ICH occurred in 37%, 35%, and 24% of Moderate/Severe, Mild, and Normal group patients, respectively, and the adjusted ORs (95% CIs) were 1.50 (0.71-3.18) for Moderate/Severe and 1.87 (1.28-2.73) for Mild, compared to the Normal group (p for trend = 0.004). Symptomatic ICH increased with the severity of thrombocytopenia (9.8% vs 3.6% vs 2.1%), and adjusted ORs were 4.43 (1.16-17.0) in Moderate/Severe and 1.85 (0.71-4.86) in Mild (p for trend = 0.10). Mortality was significantly associated with the severity of thrombocytopenia (p for trend = 0.005), and adjusted ORs were 3.26 (1.29-8.26) in the Moderate/Severe and 2.76 (1.58-4.84) in the Mild groups., Conclusions: Thrombocytopenia in LVO patients was not rare and associated with the incidence and manifestation of ICH after EVT., Competing Interests: Declaration of Competing Interest Dr. Fujiwara: None. Dr. Sakai reports research grants from Biomedical Solutions, NeuroVasc, and Terumo; lecturer's fees from Asahi-Intec, Biomedical Solutions, Medtronic, and Terumo; membership of the advisory boards for Johnson&Johnson, Medtronic, and Terumo not related to this manuscript. Dr. Imamura reports lecturer's fees from Medtronic, Stryker, Johnson & Johnson, Terumo, and Asahi-Intec J-sales. Dr. Tanaka reports lecturer's fees from Johnson & Johnson and Stryker. Dr. Ohara: none. Dr. Yamagami reports a research grant from Bristol-Myers Squibb, lecturer's fees from Bayer, Daiichi-Sankyo, Stryker, Medtronic, Johnson &Johnson, Terumo, and Medicos Hirata; and membership of the advisory board for Daiichi-Sankyo. Dr. Matsumoto reports lecturer's fees from GE Healthcare, Medico's Hirata, Medtronic, Stryker, Century medical, Takeda Pharmaceutical Limited, Otsuka Pharmaceutical Limited, Kaneka Medix and Fuji Systems; reports leadership position/advisory role for GE Health care, Fuji systems, Medicos Hirata, Stryker Corporation; and reports patents and royalties from Sumitomo Bakelite. Dr. Takeuchi reports lecturer's fees from Daiichi Sankyo and Stryker. Dr. Uchida reports lecturer's fees from Daiichi Sankyo. Dr. Yoshimura reports research grants from Medtronic, Medicos Hirata, Termo, Bristol-Myers Squibb, and Otsuka; lecturers' fees from Daiichi Sankyo, Pfizer, Boehringer-Ingelheim, Otsuka, Bayer, Pfizer, Bristol-Myers Squibb, Stryker, Medtronic, and Mitsubishi Tanabe. Dr. Morimoto reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray and Tsumura; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Novartis and Teijin., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Endovascular treatment (EVT) for stroke due to medium vessel occlusion (MeVO) can be technically challenging and specific endovascular tools are needed to safely and effectively recanalize these relatively small and fragile vessels. We aimed to gain insight into availability and desired qualities of endovascular devices used in MeVO stroke and examined barriers to adoption of MeVO EVT in clinical practice on a global scale., Methods: We conducted a case-based international survey among neurointerventionalists. As a part of the survey, participants were asked whether they felt appropriate endovascular tools for MeVO stroke exist and are available to them in their clinical practice. We then examined barriers to adopting MeVO EVT and analyzed them by geographic regions., Results: A total of 263 neurointerventionists participated, of which 178 (67.7%) and 83 (31.6%) provided responses on desired qualities of MeVO EVT tools and on barriers to their adoption in local practice, respectively. The majority 121/178 (68%) felt there was substantial room for improvement regarding existing tools. A large proportion 131/178 (73.6%) felt they had appropriate access to existing tools. The most commonly mentioned barrier for adopting MeVO EVT in North America was "awaiting better tools" (9/28 responses, 32.1%), while "awaiting better evidence" (8/26 responses, 30.8%), and the need for improved "funding" (7/26 responses, 26.9%) were important barriers in Europe., Conclusion: The majority of surveyed neurointerventionalists felt that dedicated MeVO EVT tools can be substantially improved upon. Different regions face various challenges in adoption of MeVO EVT, but overall, physicians are mostly awaiting better MeVO EVT tools., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO., Methods: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days)., Results: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR., Discussion: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management., Classification of Evidence: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function., (© 2022 American Academy of Neurology.)

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.

The efficacy and safety of periprocedural anticoagulant therapy are still controversial. We investigated the effects of periprocedural anticoagulation on patients who underwent endovascular therapy (EVT) for acute ischemic stroke (AIS). The patients were dichotomized into two groups according to the use of intravenous anticoagulant during or within 24 h after EVT (AC or non-AC group). Primary outcome was defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Safety outcomes were defined as any or symptomatic intracerebral hemorrhages (ICH). Among 1278 enrolled patients, 740 patients (57.9%) were in the AC group and the remaining 538 patients (42.1%) were in the non-AC group. The median dose of heparin was 5000 units intraoperatively, and 10,000 units /day postoperatively. In the AC group, hypercholesterolemia, higher pre-stroke modified Rankin Scale score, non-cardiac embolism etiology, higher rate of anticoagulant premedication, non-administration of t-PA (tissue plasminogen activator), later admission, and longer procedure time were observed. The rate of primary outcomes was not significantly different between the AC and non-AC groups (40.1% vs. 43.9%; adjusted odds ratio, 1.29; 95% CI, 0.96-1.73; p = 0.09). The incidence of any (26.2% vs. 25.7%; p = 0.80; adjusted odds ratio, 0.97; 95% CI, 0.72-1.22) and symptomatic (4.3% vs. 5.0%; p = 0.52; adjusted OR, 0.83; 95% CI, 0.46-1.51) intracranial hemorrhage within 72 h were not significantly different between the groups. Periprocedural anticoagulant therapy after acute revascularization did not relate to prognosis and intracranial hemorrhage after EVT., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Anemia is a frequently observed condition, but its clinical impact on large vessel occlusion (LVO) remains unclear. We examined the association between anemic status on admission and clinical outcomes of LVO in a real-world setting., Methods: We conducted a post-hoc analysis of the RESCUE-Japan Registry 2, a nationwide registry which enrolled 2408 consecutive patients with LVO who were admitted within 24 h of onset. The patients were classified into anemia (<11 g/dL) and no-anemia (≥11 g/dL) groups according to their hemoglobin level on admission. The primary outcome was defined as a modified Rankin Scale of 0-2 at day 90., Results: Among the 2373 patients with available baseline hemoglobin data, 307 (13.0%) were classified in the anemia group. Anemia was associated with a lower likelihood of the primary outcome (adjusted odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.47-0.98) and higher mortality within 90 days (adjusted OR: 1.48; 95% CI: 1.01-2.17). Subgroup analyses showed that the likelihood of achieving the primary outcome between the two groups was different between men and women (P for interaction = 0.049), those with Alberta Stroke Program Early CT Score (ASPECTS) <6 and ASPECTS ≥6 (P for interaction = 0.02), and those with National Institute of Health Stroke Scale (NIHSS) ≥16 and NIHSS < 16 (P for interaction = 0.005)., Conclusions: Anemic state on admission was associated with poorer clinical outcomes of LVO in real-world clinical practice. The effects of anemic status were larger in LVO patients with lower NIHSS or higher ASPECTS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic stroke is currently unknown. In stroke due to medium vessel occlusions (MeVO), the occluded vessels are particularly small and more difficult to access, especially in restless or uncooperative patients. In these patients, general anaesthesia (GA) may be preferred by physicians to prevent complications due to patient movement. We investigated physicians' approaches to anaesthesia during EVT for MeVO stroke., Methods: In a worldwide, case-based, online survey, physicians' preferred anaesthesia approach during EVT for MeVO stroke was categorized as "initial GA", "initial GA if necessary" (depending on patient cooperation), "no initial GA, but conversion if necessary" (start with local anaesthesia or conscious sedation), and "no GA". Preferred anaesthesia approaches were reported overall and stratified by physician and patient characteristics., Results: A total of 366 survey participants provided 1464 responses to 4 primary MeVO EVT case-scenarios. One-third of responses (489/1464 [33%]) favoured no initial GA, but conversion if necessary. Both initial GA and initial GA if necessary were preferred in 368/1464 (25%) of responses respectively. No GA was favoured in 244/1464 (17%). Occlusion location, respondent specialization (interventional neuroradiology), higher age, and female respondent sex were significantly associated with GA preference. GA was more often used in Europe than in other parts of the world ( p  < 0.001)., Conclusions: Anaesthesia approaches in MeVO EVT vary across world regions and patient and physician factors. Most physicians in this survey preferred to start with local anaesthesia or conscious sedation and convert to GA if necessary.

Background: The impact of prior antiplatelet therapy (APT) on clinical outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) on clinical outcomes is uncertain. We explored the associations between prior APT and in-hospital and 90-day outcomes in a real-world setting., Methods and Results: The RESCUE-Japan Registry 2 is a physician-initiated registry of 2408 consecutive patients with acute LVO admitted to hospital within 24 h of stroke onset. We compared 1281 patients who received EVT with and without APT before stroke onset (APT group and No-APT group) in terms of intracranial hemorrhage (ICH) within 72 h after the onset, successful recanalization after EVT, and the modified Rankin Scale (mRS) score 0-2 at 90 days were also evaluated. Among the 254 patients (19.8%) in the APT group, 68 (27%) patients presented any ICH and 265 (26%) patients in the No-APT group (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 0.71-1.53). The incidence of symptomatic ICH and successful recanalization were also similar between the APT and No-APT groups. The adjusted ORs of the APT group for mRS of 0-2 and death were 0.93 (95% CI, 0.62-1.41) and 0.59 (95% CI, 0.3-1.19), respectively. In patients with an onset to door time ≥ 180 min, any ICH tended to be more prevalent in the APT group than in their counterparts (P for interaction = 0.008)., Conclusions: The risk of ICH after EVT was not different between patients with and without APT before EVT for acute LVO., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The impact of prehospital notification by emergency medical services (EMS) on outcomes of endovascular therapy (EVT) for large vessel occlusion (LVO) remains unclear. We therefore explored the association between prehospital notification and clinical outcomes after EVT. In this single-center retrospective study from 2016 through 2020, we identified all LVO patients who received EVT. Based on the EMS's usage of a prehospital stroke notification system, we categorized patients into two groups, Hotline and Non-hotline. The primary outcome was good neurological outcome at 90 days; other time metrics were also evaluated. Of all 312 LVO patients, the proportion of good neurological outcomes was 94/218 (43.1%) in the Hotline group and 8/34 (23.5%) in the Non-hotline group (adjusted odds ratio 2.86; 95% confidence interval 1.12 to 7.33). Time from hospital arrival to both tissue plasminogen activator and to groin puncture were shorter in the Hotline group (30 (24 to 38) min vs 48(37 to 65) min, p < 0.001; 40 (32 to 54) min vs 76 (50 to 97) min, p < 0.001), respectively. In conclusion, prehospital notification was associated with a reduction in time from hospital arrival to intervention and improved clinical outcomes in LVO patients treated with EVT., (© 2022. The Author(s).)

Introduction: JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset., Methods and Analysis: This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5-20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×10 8 (cohort 1) to 3 x 10 8 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95., Ethics and Dissemination: The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal., Trial Registration Number: NCT04608838; JapicCTI-194570 and Clinical Trials. gov., Competing Interests: Competing interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Expert Witness from Teijin Pharma Ltd. (SS, CN, KK). Research funding from Teijin Pharma Ltd. (KK). Lecture fee from Teijin Pharma Ltd. (YI). The other authors report no conflicts., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians' decision-making for EVT in primary MeVO stroke., Methods: In an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions ("immediate EVT", "no EVT", or "wait for alteplase effect" [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivariable logistic regression was performed to assess the effect of alteplase on treatment decision., Results: The survey was completed by 366 physicians from 44 countries, resulting in 2196 responses included in this study. In alteplase-treated cases, 641/1098 (58.4%) responses favored immediate EVT, (279/1098 [25.4%]) favored no EVT and 178/1098 (16.2%) opted to wait for alteplase effect. In non-alteplase-treated case scenarios, 846/1098 (78.7%) were in favor of and 252/1098 (21.3%) against EVT. Intravenous alteplase was associated with a lower chance of a decision in favor of immediate EVT (adjusted OR 0.38 [95%CI 0.31 to 0.46])., Conclusions: Intravenous alteplase is an important factor in EVT decision-making for MeVO stroke. However, even in alteplase-treated patients, more than half of the physicians decided to proceed with EVT without waiting for alteplase effect., Competing Interests: Competing interests: Dr. Menon reports editorial board membership at Stroke (Assistant Editor). Dr. Fiehler reports grants and personal fees from Stryker, Acandis, Microvention, Medtronic, personal fees from Codman, Ceronovus, Penumbra, Phenox, other (stock ownership) from Tegus outside the submitted work; and editorial board memberships at Journal of NeuroInterventional Surgery (Associate Editor) and Clinical Neuroradiology (Editor); and executive functions with University Medical Center Hamburg-Eppendorf, Eppdata GmbH. Dr. Chen reports personal fees from Stryker, personal fees from Microvention, Medtronic, Genentech, Ceronovus, Penumbra, outside the submitted work; and editorial board membership at Journal of NeuroInterventional Surgery (Commissioning Editor). Dr. Sakai has nothing to disclose. Dr. Goyal reports personal fees from Stryker, personal fees from Mentice, personal fees from Microvention, personal fees from Medtronic, outside the submitted work; and editorial board membership at Stroke (Consulting Editor); in addition, Dr. Goyal has a patent for systems of acute stroke diagnosis issued and licensed., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: We aimed to explore the preference of stroke physicians to treat patients with primary medium vessel occlusion (MeVO) stroke with immediate endovascular treatment (EVT) in an international cross-sectional survey, as there is no clear guideline recommendation for EVT in these patients., Methods: In the survey MeVO-Finding Rationales and Objectifying New Targets for IntervEntional Revascularization in Stroke (MeVO-FRONTIERS), participants were shown four cases of primary MeVOs (six scenarios per case) and asked whether they would treat those patients with EVT. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to treat. Dominance analysis was performed to assess the influence of factors within the scenarios on decision making., Results: Overall, 366 participants (56 women; 15%) from 44 countries provided 8784 answers to 24 scenarios. Most physicians (59.2%) would treat patients immediately with EVT. Younger patient age (incidence rate ratio (IRR) 1.24, 99% CI 1.19 to 1.30), higher National Institutes of Health Stroke Scale (NIHSS) score (IRR 1.69, 99% CI 1.57 to 1.82), and small core volume (IRR 1.35, 99% CI 1.24 to 1.46) were positively associated with the decision to treat with EVT. Interventionalists (IRR 1.26, 99% CI 1.01 to 1.56) were more likely to treat patients with MeVO immediately with EVT. In the dominance analysis, factors influencing the decision in favor of EVT were (in order of importance): baseline NIHSS, core volume, alteplase use, patients' age, and occlusion site., Conclusions: Most physicians in this survey were interventionalists and would treat patients with MeVO stroke immediately with EVT. This finding supports the need for robust clinical evidence., Competing Interests: Competing interests: AMD reports editorial board membership at International Journal of Stroke (Editor). BKM reports editorial board membership at Stroke (Assistant Editor). MC reports personal fees from Stryker, personal fees from Microvention, Medtronic, Genentech, Cerenovus, Penumbra outside the submitted work; and editorial board membership at Journal of NeuroInterventional Surgery (Commissioning Editor). JF reports grants and personal fees from Stryker, Acandis, Microvention, Medtronic, personal fees from Codman, Ceronovus, Penumbra, Phenox, other (stock ownership) from Tegus outside the submitted work; and editorial board memberships at Journal of NeuroInterventional Surgery (Associate Editor) and Clinical Neuroradiology (Editor); and Executive functions with University Medical Center Hamburg-Eppendorf, Eppdata GmbH. MG reports personal fees from Stryker, personal fees from Mentice, Microvention, and Medtronic outside the submitted work; and editorial board membership at Stroke (Consulting Editor). In addition, NG has a patent for Systems of acute stroke diagnosis issued and licensed. PC, MK, NS, NK, JMO, RM, NS have nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background and Purpose: Patients with acute ischemic stroke due to medium vessel occlusion (MeVO) make up a substantial part of the acute stroke population, though guidelines currently do not recommend endovascular treatment (EVT) for them. A growing body of evidence suggests that EVT is effective in MeVOs, including observational data but no randomized studies. We aimed to explore willingness of physicians worldwide to randomize MeVO stroke patients into a hypothetical trial comparing EVT in addition to best medical management versus best medical management only., Methods: In an international cross-sectional survey among stroke physicians, participants were presented with 4 cases of primary MeVOs (6 scenarios each). Each subsequent scenario changed one key patient characteristic compared to the previous one, and asked survey participants whether they would be willing to randomize the described patient. Overall, physician- and scenario-specific decision rates were calculated. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to randomize., Results: Overall, 366 participants (56 women) from 44 countries provided 8784 answers to 24 MeVO case scenarios. The majority of responses (78.3%) were in favor of randomizing. Most physicians were willing to accept patients transferred for EVT from a primary center (82%) and the majority of these (76.5%) were willing to randomize these patients after transfer. Patient age > 65 years, A3 occlusion, small core volume, and patient intravenous alteplase eligibility significantly influenced the physician's decision to randomize (adjOR 1.24, 95%CI 1.13-1.36; adjOR 1.17, 95%CI 1.01-1.34; adjOR 0.98, 95%CI 0.97-0.99 and adjOR 1.38, 95%CI 1.21-1.57, respectively)., Conclusions: Most physicians in this survey were willing to randomize acute MeVO stroke patients irrespective of patient characteristics into a trial comparing EVT in addition to best medical management versus best medical management only, suggesting there is clinical equipoise., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

To determine whether increasing thrombectomy-capable hospitals with moderate comprehensive stroke center (CSC) capabilities is a valid alternative to centralization of those with high CSC capabilities. This retrospective, nationwide, observational study used data from the J-ASPECT database linked to national emergency medical service (EMS) records, captured during 2013-2016. We compared the influence of mechanical thrombectomy (MT) use, the CSC score, and the total EMS response time on the modified Rankin Scale score at discharge among patients with acute ischemic stroke transported by ambulance, in phases I (2013-2014, 1461 patients) and II (2015-2016, 3259 patients). We used ordinal logistic regression analyses to analyze outcomes. From phase I to II, MTs increased from 2.7 to 5.5%, and full-time endovascular physicians per hospital decreased. The CSC score and EMS response time remained unchanged. In phase I, higher CSC scores were associated with better outcomes (1-point increase, odds ratio [95% confidence interval]: 0.951 [0.915-0.989]) and longer EMS response time was associated with worse outcomes (1-min increase, 1.007 [1.001-1.013]). In phase II, neither influenced the outcomes. During the transitional shortage of thrombectomy-capable hospitals, increasing hospitals with moderate CSC scores may increase nationwide access to MT, improving outcomes., (© 2022. The Author(s).)

Background and Objectives: DS-1040 is a novel inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor that may have therapeutic potential in thromboembolic diseases, such as acute ischemic stroke (AIS) or pulmonary embolism. We undertook a Phase I clinical trial to investigate the safety, pharmacokinetics, and pharmacodynamics of DS-1040 in Japanese patients who were eligible for thrombectomy following AIS., Methods: The trial enrolled patients with AIS due to large vessel occlusion, who were planned for thrombectomy within 8 h of symptom onset. Subjects were randomized to receive a single intravenous infusion of placebo or DS-1040 (0.6, 1.2, 2.4 or 4.8 mg) in a sequential-cohort design. The primary endpoints were the incidence of intracranial hemorrhage (ICH) and major extracranial bleeding within 36 and 96 h, respectively, of treatment initiation. Treatment-emergent adverse events (TEAEs) and pharmacokinetic/pharmacodynamic parameters were also assessed., Results: Nine patients received placebo and 32 patients received DS-1040. There were no cases of symptomatic ICH or major extracranial bleeding with either placebo or DS-1040 after 36 and 96 h. One patient, who received DS-1040 0.6 mg, experienced a subarachnoid hemorrhage that was considered to be drug-related. Three patients died (2 placebo, 1 DS-1040), but no deaths were adjudicated as study drug-related. In vivo exposure to DS-1040 increased in proportion to dosage, but no clear dose-response relationship was seen for D-dimer levels and thrombin-activatable fibrinolysis inhibitor activity., Conclusions: Single doses of DS-1040 0.6-4.8 mg were well tolerated in Japanese patients with AIS undergoing thrombectomy., Clinical Trial Registration Number: NCT03198715; JapicCTI-163164., (© 2022. The Author(s).)

Background and Purpose: A previous report revealed single pass recanalization was associated with better functional outcome for patients with acute ischemic stroke with large vessel occlusion in real-world settings. However, the effect of single pass recanalization in acute large vessel occlusion based on the largest registry in real-world settings in Asian population are not well scrutinized., Materials and Methods: RESCUE-Japan Registry-2 was a physician-initiated prospective multicenter registry that enrolled consecutive patients with acute large vessel occlusion who were admitted within 24 h of onset. We compared patients who underwent endovascular therapy and achieved good recanalization in single or multiple device passes (single-pass group and multiple-passes group, respectively) in terms of the good outcome defined as modified Rankin Scale of 0-2 at 90 days after onset. We estimated the odds ratios, safety and mortality adjusting for confounders., Results: Among 2420 patients registered, 1281 patients treated with endovascular therapy. 829 patients were analyzed (557 patients in single-pass and 272 patients in multiple-passes group). Patient characteristics were almost similar between two groups. The good outcome was more observed of patients in the single groups (51.5% vs 39.3%). The adjusted odds ratio of single pass of good outcome was 1.92 (95% confidence interval, 1.37-2.69). The frequencies of symptomatic intracranial hemorrhage were similar between the two groups., Conclusion: Single pass recanalization was associated with good clinical outcome on real-world settings in Asian population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: There is a paucity of evidence regarding the safety of endovascular treatment for patients with acute ischemic stroke due to primary medium-vessel occlusion. The aim of this study was to examine the willingness among stroke physicians to perform endovascular treatment in patients with mild-yet-disabling deficits due to medium-vessel occlusion., Materials and Methods: In an international cross-sectional survey consisting of 7 primary medium-vessel occlusion case scenarios, participants were asked whether the presence of personally disabling deficits would influence their decision-making for endovascular treatment despite the patients having low NIHSS scores (<6). Decision rates were calculated on the basis of physician characteristics. Univariable logistic regression clustered by respondent and scenario identity was performed., Results: Three hundred sixty-six participants from 44 countries provided 2562 answers to the 7 medium-vessel occlusion scenarios included in this study. In scenarios in which the deficit was relevant to the patient's profession, 56.9% of respondents opted to perform immediate endovascular treatment compared with 41.0% when no information regarding the patient's profession was provided (risk ratio = 1.39, P < .001). The largest effect sizes were seen for female participants (risk ratio = 1.68; 95% CI, 1.35-2.09), participants older than 60 years of age (risk ratio = 1.61; 95% CI, 1.23-2.10), those with more experience in neurointervention (risk ratio = 1.60; 95% CI, 1.24-2.06), and those who personally performed >100 endovascular treatments per year (risk ratio = 1.63; 95% CI, 1.22-2.17)., Conclusions: The presence of a patient-relevant deficit in low-NIHSS acute ischemic stroke due to medium-vessel occlusion is an important factor for endovascular treatment decision-making. This may have relevance for the conduct and interpretation of low-NIHSS endovascular treatment in randomized trials., (© 2021 by American Journal of Neuroradiology.)

Background: In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT)., Methods and results: AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min)., Conclusions: Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.

Background and Purpose- For patients with large vessel occlusion, neuroimaging biomarkers that evaluate the changes in brain tissue are important for determining the indications for mechanical thrombectomy. In this study, we applied deep learning to derive imaging features from pretreatment diffusion-weighted image data and evaluated the ability of these features in predicting clinical outcomes for patients with large vessel occlusion. Methods- This multicenter retrospective study included patients with anterior circulation large vessel occlusion treated with mechanical thrombectomy between 2013 and 2018. We designed a 2-output deep learning model based on convolutional neural networks (the convolutional neural network model). This model employed encoder-decoder architecture for the ischemic lesion segmentation, which automatically extracted high-level feature maps in its middle layers, and used its information to predict the clinical outcome. Its performance was internally validated with 5-fold cross-validation, externally validated, and the results compared with those from the standard neuroimaging biomarkers Alberta Stroke Program Early CT Score and ischemic core volume. The prediction target was a good clinical outcome, defined as a modified Rankin Scale score at 90-day follow-up of 0 to 2. Results- The derivation cohort included 250 patients, and the validation cohort included 74 patients. The convolutional neural network model showed the highest area under the receiver operating characteristic curve: 0.81±0.06 compared with 0.63±0.05 and 0.64±0.05 for the Alberta Stroke Program Early CT Score and ischemic core volume models, respectively. In the external validation, the area under the curve for the convolutional neural network model was significantly superior to those for the other 2 models. Conclusions- Compared with the standard neuroimaging biomarkers, our deep learning model derived a greater amount of prognostic information from pretreatment neuroimaging data. Although a confirmatory prospective evaluation is needed, the high-level imaging features derived by deep learning may offer an effective prognostic imaging biomarker.

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

Introduction: Endovascular treatment (EVT) is effective against acute cerebral large vessel occlusion (LVO). However, it has been associated with a high incidence of intracranial hemorrhage (ICH). Because the incidence of ICH and prognostic impact of ICH were not scrutinized in general patients, we investigated the impact of ICH after EVT on functional outcome at 90 days in patients with acute LVO., Methods: RESCUE-Japan Registry 2 was a multicenter registry that enrolled 2,420 consecutive patients with acute LVO within 24 h of onset. We analyzed 1,281 patients who received EVT and compared the functional outcomes between those with and without ICH (ICH and no-ICH groups, respectively) within 24 h after EVT. We explored the factors associated with ICH and prognostic impact of symptomatic ICH (SICH) among patients with ICH. We estimated the adjusted odds ratios (ORs) for good functional outcome as modified Rankin Scale scores 0-2 and mortality. We also explored the prognostic impact of symptomatic ICH (SICH) among patients with ICH., Results: ICH occurred in 333 patients (26.0%). Several factors such as perioperative edaravone, stent retriever, and baseline glucose were associated with development of ICH within 24 h. A good outcome was observed in 80 (24.0%) and 454 (47.9%) patients in the ICH and no-ICH groups, respectively, and the adjusted OR was 0.3 (95% confidence interval [CI] = 0.2-0.5, p < 0.0001). Incidence of mortality within 90 days was not significantly different between the groups (adjusted OR 1.2; 95% CI: 0.7-1.9, p = 0.5). SICH was observed in 36 (10.8%) of 333 patients with ICH, and the good outcomes were 8.3 and 25.9% in patients with SICH and asymptomatic ICH (AICH), respectively (p = 0.02). Mortality at 90 days was 30.6 and 7.1% in patients with SICH and AICH, respectively (p < 0.0001)., Conclusions: The functional outcomes at 90 days were significantly worse in patients who developed ICH after receiving EVT for acute LVO, but the mortality was generally similar., (© 2020 S. Karger AG, Basel.)

Background and Purpose- Sex differences in the management and outcomes of acute ischemic stroke with large vessel occlusion are unknown in the era of endovascular therapy (EVT). This study investigated these differences in the RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism)-Japan Registry 2 patient database. Methods- RESCUE-Japan Registry 2 registered patients with large vessel occlusion who were admitted within 24 hours of onset were enrolled in this study. We estimated the likelihood to receive EVT according to sex. The primary outcome was good outcome defined as a modified Rankin Scale score of 0 to 2 at 90 days after onset. Secondary outcomes were mortality within 90 days, any or symptomatic intracranial hemorrhage within 72 hours, and recurrence of stroke or transient ischemic attack within 90 days. Results- Among 2399 patients, 1087 patients were female and 1312 were male; 47.9% of females and 57.7% of males received EVT (adjusted odds ratio, 0.71; 95% CI, 0.59-0.86). Good outcome was observed in 27.3% and 44.2% of the females and males, respectively ( P<0.0001). The adjusted odds ratio of a good outcome in females was 0.80 (95% CI, 0.65-0.99). Mortality was 12.3% and 9.9% in females and males, respectively ( P=0.06); the adjusted odds ratio was 0.78 (95% CI, 0.58-1.05). Conclusions- Females with acute ischemic stroke with large vessel occlusion showed poor functional outcome compared to males. Females were less likely to receive EVT; lower utilization of EVT accounted for a portion of the poor outcome.

Background: Although dual antiplatelet therapy with aspirin and clopidogrel reduces early recurrence of ischaemic stroke, with long-term use this type of therapy is no longer effective and the risk of bleeding increases. Given that cilostazol prevents stroke recurrence without increasing the incidence of serious bleeding compared with aspirin, we aimed to establish whether dual antiplatelet therapy involving cilostazol is safe and appropriate for long-term use., Methods: In a multicentre, open-label, randomised controlled trial across 292 hospitals in Japan, patients with high-risk non-cardioembolic ischaemic stroke identified on MRI were randomly assigned to two groups in a 1:1 ratio to receive monotherapy with either oral aspirin (81 or 100 mg, once per day) or clopidogrel (50 or 75 mg, once per day) alone, or a combination of cilostazol (100 mg, twice per day) with aspirin or clopidogrel. Randomisation was done centrally (using block randomisation with a block size of six per each participating hospital) through a web-based registration system and was done by EPS Corporation. The patients were required to have at least 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk factors. Trial medication was continued for half a year or longer, for a maximum of 3·5 years. The primary efficacy outcome was the rate of first recurrence of symptomatic ischaemic stroke. Safety outcomes were severe or life-threatening bleeding; any adverse events; serious adverse events; and any bleeding events. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the as-treated population. This trial was registered with ClinicalTrials.gov (number NCT01995370) and UMIN Clinical Trials Registry (number 000012180)., Findings: Participants were recruited from Dec 13, 2013, to March 31, 2017. 932 patients assigned to the dual therapy group and 947 patients assigned to the monotherapy group were included in the intention-to-treat analysis. The trial was stopped after the enrolment of 1884 patients of an anticipated 4000 patients because of the delay in recruitment. Ischaemic stroke recurred in 29 (3%) of 932 patients (annualised rate 2·2%) on dual therapy including cilostazol and 64 (7%) of 947 patients (annualised rate 4·5%) on monotherapy during a median 1·4 years follow-up (hazard ratio [HR] 0·49, 95% CI 0·31-0·76, p=0·0010). Severe or life-threatening bleeding occurred in eight patients (annualised rate 0·6%) on dual therapy and 13 patients (annualised rate 0·9%) on monotherapy (HR 0·66, 95% CI 0·27-1·60, p=0·35). Occurrence of any type of adverse event was similar between the groups (255 [28%] of 910 patients in the dual therapy group vs 219 [24%] of 921 patients in the monotherapy group); as was occurrence of serious adverse events (87 [10%] vs 142 [15%]) and bleeding events (38 [4%] vs 33 [4%]). Gastrointestinal bleeding, which affected nine (<1%) of 910 patients in the monotherapy group and nine (<1%) of 921 patients in the dual therapy group, was the most common type of bleeding., Interpretation: The combination of cilostazol with aspirin or clopidogrel had a reduced incidence of ischaemic stroke recurrence and a similar risk of severe or life-threatening bleeding compared with treatment with aspirin or clopidogrel alone in patients at high risk for recurrent ischaemic stroke., Funding: Otsuka Pharmaceutical., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To describe our initial experience with the Versi Retriever for mechanical thrombectomy in patients with acute ischemic stroke., Methods: This study is a single-center, single-arm, first-in-man registry under institutional review board control to evaluate the efficacy and safety of the new stent retriever, the Versi Retriever. Patients with acute ischemic stroke were consecutively enrolled between September and November 2017. The clinical and procedural data were retrospectively analyzed. The angiographic result after the procedure was self-graded based on the Thrombolysis in Cerebral Infarction (TICI) scale by each operator., Results: Eleven patients with a mean age of 69.4 years were treated with the Versi Retriever. Median National Institutes of Health Stroke Scale score on admission was 16 (IQR 10-34). The occluded vessel was located in the anterior circulation in 81.8%. Revascularization rates of TICI 2b-3 and TICI 3 at final angiogram were achieved in 100% and 63.6%, respectively. A favorable functional outcome (modified Rankin Scale 0-2) at 90 days was obtained in 72.7%. No symptomatic intracranial hemorrhage occurred and no procedure-related complication was observed., Conclusions: Our initial experience suggests that the Versi Retriever is a safe and effective stent retriever for mechanical thrombectomy in patients with acute ischemic stroke., Clinical Trial Registration: NCT03366818., Competing Interests: Competing interests: NS has been a consultant for Cerenovus, Medtronic, Microvention, Neurovasc, Penumbra and Stryker; NK has been a consultant for Neurovasc; ST holds stock in Neurovasc and has been a consultant for Cerenovus, Medtronic, Neurovasc and Stryker., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy., Methods: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively., Results: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score., Conclusions: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke., (© 2019 S. Karger AG, Basel.)

A middle-aged patient with an internal carotid-posterior communicating artery aneurysm and basilar artery tip aneurysm was treated by stent-assisted coiling. One ischemic infarction and two transient ischemic attacks occurred with the same symptoms (inability to walk unassisted and tendency to fall to the left) during the first 2 years post-treatment. The ischemic infarction was found in the right side of the pons, consistent with the vascular territory of the stent-containing vessel. The cause of the delayed ischemic stroke was investigated on DSA and cone beam CT, which revealed that the proximal end of the stent, one marker band, was just covering a small perforating artery of the basilar artery trunk. The present case suggests that marker band occlusion can induce delayed ischemic stroke. To prevent this complication, it is important to evaluate the perforating vessels preoperatively and carefully deploy a stent for the marker band to avoid occlusion of large perforating vessels. Post-treatment evaluation is also important because dual antiplatelet therapy will be required for a longer period if an artery is occluded by a marker band., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Endovascular therapy has been shown to be effective in patients with acute cerebral large-vessel occlusion, but real-world efficacies are unknown., Methods and Results: We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large-vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score-matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score-matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively ( P= 0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10-1.86, P =0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses., Conclusions: Endovascular therapy decreased disabilities at 90 days in real-world patients with acute cerebral large-vessel occlusion., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02419794., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≥2a. Secondary endpoints were clot migration/embolization; recanalization without symptomatic intracranial hemorrhage (ICH) at 24 h; symptomatic ICH; good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≥10) at day 90; device- or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years; males 46.9%; middle cerebral artery (MCA) occlusion 83.7%; median NIHSS score 17). A post-procedure TICI score ≥2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9-85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4-76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device- or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS.

Background: Clinical outcomes after successful endovascular therapy in patients with acute ischemic stroke are associated with several factors including onset-to-reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS) score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time score, calculated as follows: [NIHSS score] × [onset-to-treatment time (h)] or [NIHSS score] × [ORT (h)], has been reported to predict clinical outcomes after intravenous recombinant tissue plasminogen activator therapy and endovascular therapy for acute stroke. The objective of the current study was to assess whether the combination of the ASPECTS and the ORT can predict the outcomes after endovascular therapy., Methods: The charts of 117 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy were retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as follows: [11 - ASPECTS] × [ORT (h)]., Results: Rates of good outcome for patients with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and 33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that the ASPECTS-time score (per category increase) was an independent predictor for better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P < .05)., Conclusions: A lower ASPECTS-time score may predict better clinical outcomes after endovascular treatment., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Epidemiological studies have suggested a close relationship between cerebral ischemia and Alzheimer's disease (AD). To clarify the pathological association of tau dynamics in both diseases, we performed comprehensive studies on the posttranslational modification of tau in cerebral ischemia and reperfusion (I/R) in rats. The present study suggests that both 4-repeat and 3-repeat tau isoforms are hyperphosphorylated in cerebral I/R, similar to the case in AD. The generation of a 60-kDa Asp 421 -truncated tau in cerebral I/R preceded the emergence of a 17-kDa 3-repeat tau fragment and a 25-kDa 4-repeat tau fragment. The regional redistribution of tau from the neuropil to neuronal perikarya in our stroke model is thought to share similarity with that occurring in AD. In addition, immunofluorescence staining revealed the formation of axonal varicosities in cerebral I/R. Altered tau distribution may influence microtubule stability, disturbances in axonal transport, and the resulting formation of axonal varicosities. The staining profiles of granules in the ischemic cortex that were immunopositive for RD3, RD4, and AT8 in neuronal perikarya and that were argyrophilic on Gallyas-Braak staining were similar to those in AD. These findings suggest that transient cerebral ischemia shares a common pathology with AD, in the modification of tau protein.

Background: Outcomes after successful endovascular therapy in acute ischemic stroke are associated with onset-to-reperfusion time (ORT) and the National Institutes of Health Stroke Scale (NIHSS) score. In intravenous recombinant tissue plasminogen activator therapy, the NIHSS-time score, calculated by multiplying onset-to-treatment time with the NIHSS score, has been shown to predict clinical outcomes. In this study, we assessed whether a similar combination of the ORT and the NIHSS score can be applied to predict the outcomes after endovascular therapy., Methods: We retrospectively reviewed the charts of 128 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy. We analyzed the association of the ORT, the NIHSS score, and the NIHSS-time score with good outcome (modified Rankin Scale score ≤ 2 at 3 months)., Results: Good outcome rates for patients with NIHSS-time scores of 84.7 or lower, scores higher than 84.7 up to 127.5 or lower, and scores higher than 127.5 were 72.1%, 44.2%, and 14.3%, respectively (P < .01). Multivariate logistic regression analysis revealed that the NIHSS-time score was an independent predictor of good outcomes (odds ratio, .372; 95% confidence interval, .175-.789) after adjusting for age, sex, internal carotid artery occlusion, plasma glucose level, ORT, and NIHSS score., Conclusions: The NIHSS-time score can predict good clinical outcomes after endovascular treatment., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Recanalization therapies such as intravenous thrombolysis (IVT) or endovascular treatment (EVT) improve acute ischemic stroke outcomes; however, they carry the risk of intracranial hemorrhage (ICH). The present study assessed the frequency and predictive factor of ICH in Japanese patients with acute large vessel occlusion., Methods: The Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Registry prospectively registered 1442 stroke patients with major vessel occlusion who were admitted to 84 Japanese stroke centers within 24 hours after onset, from July 2010 to June 2011. Among these 1442 patients, 1357 were included to evaluate the incidence rate and predictive factors of ICH within 24 hours after onset., Results: ICH was observed in 284 (20.9%) patients. Among these patients, 46 (3.4%) had symptomatic ICH, and its incidence was higher in the recanalization therapy (IVT and/or EVT) group than in the conservative therapy group (4.5% versus 2.1%, P = .013). On multivariate analyses, symptomatic ICH was related to pretreatment antiplatelet agent use and systemic heparinization, and was related to neither IVT nor EVT., Conclusions: Symptomatic ICH was not affected by recanalization therapy or EVT itself in Japanese patients with acute large vessel occlusion., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The presence or absence of the penumbra area is important when performing reperfusion therapy in patients with acute ischemic stroke. As a predictor of this penumbra area, magnetic resonance angiography (MRA)-diffusion-weighted imaging (DWI) mismatch is attracting attention. The usefulness of MRA-DWI mismatch (MDM) using the DWI-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) in endovascular treatment (EVT) of patients with cerebral large vessel occlusion was evaluated., Methods: Of 1442 patients registered in the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Registry between July 1, 2010 and June 30, 2011 who presented to the hospital within 24 hours of the onset of acute cerebral infarction because of cerebral large vessel occlusion, 188 patients who had internal carotid artery or middle cerebral artery occlusion and achieved recanalization with EVT were included. Of these, 71 patients underwent intracranial EVT because intravenous recombinant tissue plasminogen activator therapy was ineffective. The associations between the presence or absence of MDM (MDM-positive [MDM-P], DWI-ASPECTS≥6; MDM-negative [MDM-N], DWI-ASPECTS<6) and 90-day prognosis (modified Rankin Scale [mRS]) and symptomatic intracranial hemorrhage (sICH) were examined., Results: Of the 188 patients analyzed, the time from symptom onset to admission was within 3 hours in 143 patients, 3-8 hours in 36 patients, and 8 hours or more in 9 patients. The time from the onset was within 3 hours in 118 patients in the MDM-P and 25 patients in the MDM-N cases. Favorable outcomes (mRS score≤2 at 90 days) were seen in 63 patients (53.4%) in the MDM-P group and 7 patients (28.0%) in the MDM-N group, showing a significantly more favorable clinical outcome in the MDM-P group (P=.027). The incidence of sICH was significantly lower in the MDM-P group (MDM-P group 3.4%, MDM-P group 20.0%; P=.009). The time from the onset was 3-8 hours in 29 patients in the MDM-P group and in 7 patients in the MDM-N group. Favorable outcomes were seen in 12 patients (41.4%) in the MDM-P group and 2 patients (28.6%) in the MDM-N group, with no significant difference between the 2 groups. No patients had sICH. The patients admitted 8 hours or more after the onset were all MDM-P. Five patients (55.6%) had a favorable outcome., Conclusions: This study demonstrated the safety and efficacy of EVT in MDM-P patients within 3 hours of symptom onset. Although the ratio of patients who had a favorable outcome was high in the MDM-P patients admitted 3-8 hours after the onset, the difference was not significant., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to clarify the general status and historical transition of endovascular therapy (EVT) of acute stroke with major vessel occlusion before approval of mechanical thrombectomy devices in Japan from January 2005 to December 2009. We extracted 1,409 acute ischemic stroke patients receiving EVT (513 women, 69.8 ± 11.8 years) from two nationwide registry studies, the Japanese Registry of Neuroendovascular Therapy (JR-NET) and JR-NET 2. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 18, and 81.3% of the patients received EVT within 6 hours after symptom onset. The culprit occluded arteries were the internal carotid artery (ICA) in 21.2%, middle cerebral artery (MCA) in 53.0%, and basilar artery (BA) in 20.6%. Intravenous thrombolysis was administered to 6.7% of the patients, and EVT mainly consisted of intra-arterial thrombolysis and percutaneous balloon angioplasty/balloon clot disruption. The final recanalization rate was 82.5%, and the clinical outcome was favorable in 35.8% and fatal in 11.6% at 30 days after onset or at discharge. There was no significant change in neurological severity at baseline throughout the study period, but the onset-to-treatment time became longer and the proportion of ICA or BA occlusion increased annually. Although the final recanalization rate was similar throughout the study period, the incidence of a favorable outcome tended to decreased annually from 41.0% to 29.0%. These results could be considered as baseline data that can be used to validate the beneficial effects of novel EVT devices in Japan.

Surgical and endovascular revascularization for ischemic cerebrovascular diseases (CVD) should be strictly indicated based on medical treatment. In this report, we describe current consensus and controversy in the treatment of ischemic CVD, and perspectives. 1) Local intra-arterial fibrinolytic therapy for acute cerebral embolism; intra-venous t-PA can be beneficial when given within 3 hours of stroke onset (NINDS), but many patients present later after stroke onset and alternative treatments are needed. Despite an increased frequency intracranial hemorrhage, treatment with intra-arterial proUK within 6 hours for MCA occlusion significantly improved clinical outcome at 90 days (mRS 40% >25%, PROACT-II). MELT-Japan are going now and waiting for results. 2) Carotid stenting; Carotid angioplasty and stenting (CAS) has been proposed as an alternative to carotid endarterectomy (CEA) in those considered at high risk for CEA. SAPPHIRE study confirmed CAS is an excellent option for patients with coexisting coronary artery disease, congestive heart failure, and other comorbid conditions that make them poor candidates for CEA. Now, CREST in USA and CSSA in Europe are going for randomized trial compared with CEA and CAS in any risk for CEA patients. 3) Stenting for intracranial arteries; Stroke rates in patients with symptomatic intracranial stenosis may be high on medical therapy. Although there is no clinical evidence and appropriate devices for intracranial vessels, it seems to be a potentially effective in the future.

The present study assessed the safety and efficacy of embolization using Guglielmi detachable coils (GDCs) in 100 asymptomatic cerebral aneurysms classified as sidewall (70) or terminal (30) aneurysms according to the parent artery (68 small aneurysms with a small neck, 21 small aneurysms with a wide neck, and 11 large aneurysms). A balloon-assisted technique was used in 49 aneurysms. Immediate angiography revealed that 71 aneurysms were completely obliterated. Transient deficits occurred in 19 patients, permanent deficits in four patients, and one patient died. Most complications occurred during or immediately after treatment and resolved within a few minutes to a few weeks. None of the surviving patients manifested significant morbidity at 1-year follow up. Follow-up angiographic study was performed in 79 aneurysms. Rates of recanalization and progressive thrombosis (total occlusion of the residual aneurysm at follow up) were 11% and 38%, respectively, in sidewall aneurysms, and 26% and 0%, respectively, in terminal aneurysms. Treatment with GDCs was effective for patients with small aneurysms with small necks, the morbidity was acceptable, and progressive thrombosis occurred during the follow-up period. GDC treatment achieved unsatisfactory results in patients with small terminal aneurysms with wide necks and in large aneurysms, because the obliteration rate was low, and the recanalization and complication rates were high. Multivariate analysis showed that complete occlusion was associated with small-necked aneurysms, and ischemic events tended to occur in terminal aneurysms and in aneurysms treated by the balloon-assisted technique.

We report on the evaluation of cerebral ischemic lesions with perfusion CT. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of 52 patients mostly with ischemic cerebrovascular disease were analysed using the box-modulation transfer function method with 30 ml of contrast medium intravenously injected at 5 ml/sec. CBF, CBV and MTT of the middle cerebral artery (MCA) territory were 43.5 +/- 4.6 ml/100 g/min, 1.9 +/- 0.2 ml/100 g and 2.9 +/- 0.6 seconds at the unaffected side, and 37.7 +/- 7.3 ml/100 g/min, 2.1 +/- 0.3 ml/100 g, 3.7 +/- 0.9 seconds at the lesion side with stenosis or occlusion in the main MCA trunks or internal carotid artery, respectively. A statistically significant difference was shown in CBF and MTT values. Furthermore, there was a close correlation in CBF values of MCA territories between Xe-CT and perfusion CT (r = 0.645, n = 76, p < 0.0001). MTT showed a positive correlation with CBV in those subjects when MTT was below 4.1 seconds (r = 0.526, p < 0.0001, n = 83). MTT also showed a negative correlation with CBF in those patients when MTT indicated more than 4.1 seconds (r = 0.818, p < 0.001, n = 21). These results suggest that the progression of cerebral ischemia may be classified in 4 stages using perfusion CT. The stages are as follows: stage 0; normal CBF without prolonged MTT and increased CBV, stage 1; relatively increased CBV, stage 2; significantly prolonged MTT, and stage 3; significantly decreased CBF with prolonged MTT.

Although cerebral hypoperfusion caused by cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. Recently, a novel therapeutic strategy for ischemic disease using angiogenic growth factors to expedite and/or augment collateral artery development has been proposed. Therapeutic angiogenesis might be useful for the treatment of cerebral occlusive disease. Hepatocyte growth factor (HGF) is a potent angiogenic factor, in addition to vascular endothelial growth factor (VEGF), whereas in the nervous system HGF also acts as neurotrophic factor. Therefore, we hypothesized that gene transfer of these angiogenic growth factors could induce angiogenesis, thus providing an effective therapy for cerebral hypoperfusion or stroke. In this study, we employed a highly efficient gene transfer method, the viral envelop (Hemagglutinating Virus of Japan [HVJ]-liposome) method, because we previously documented that beta-galactosidase gene could be transfected into the brain by the HVJ-liposome method. Indeed, we confirmed wide distribution of transgene expression using beta-galactosidase via injection into the subarachnoid space. Of importance, transfection of HGF or VEGF gene into the subarachnoid space 7 days before occlusion induced angiogenesis on the brain surface as assessed by alkaline phosphatase staining (P<0.01). In addition, significant improvement of cerebral blood flow (CBF) was observed by laser Doppler imaging (LDI) 7 days after occlusion (P<0.01). Unexpectedly, transfection of HGF or VEGF gene into the subarachnoid space immediately after occlusion of the bilateral carotid arteries also induced angiogenesis on the brain surface and had a significant protective effect on the impairment of CBF by carotid occlusion (P<0.01). Interestingly, coinjection of recombinant HGF with HGF gene transfer revealed a further increase in CBF (P<0.01). Here, we demonstrated successful therapeutic angiogenesis using HGF or VEGF gene transfer into the subarachnoid space to improve cerebral hypoperfusion, thus providing a new therapeutic strategy for cerebral ischemic disease.

Three patients with bleeding-type moyamoya disease suffered ischemic complications following their first episode of intracranial bleeding. The patients presented with intraventricular hemorrhage and suffered cerebral infarction on the 14th, 16th, and 11th days after the ictus, respectively. The clinical records revealed no obvious hypotension before progression to infarction and suggested that dehydration accelerated by the administration of hyperosmotic drugs was a contributing factor to the infarction. Two patients underwent superficial temporal artery-middle cerebral artery anastomoses in the chronic stages and have never experienced further ischemic complications. The other patient died despite receiving intensive care. Hemodynamic reserve may be severely impaired in patients with bleeding-type moyamoya disease. Adequate control of hydration is important to prevent cerebral infarction after intracranial bleeding in patients with moyamoya disease.

Background and Purpose: The efficacy of hypothermic intervention for permanent focal ischemia has yet to be clarified. This study investigated the effect of a prolonged moderate or mild hypothermia on permanent focal ischemia in rats., Methods: Two permanent focal ischemia models in male Sprague-Dawley rats were used. Moderate (30 degrees C, in experiment 1) or mild (33 degrees C, in experiment 2) hypothermia was achieved at the time of the induction of focal ischemia and was maintained for 2 hours under general anesthesia. Thereafter, the hypothermic condition was maintained by means of a cold room for a total of 24 hours. The infarct volume and neurological function were analyzed for a maximum of 21 days and compared with that of the normothermia group. Regional cerebral blood flow was monitored for 6 hours in the ischemic core and penumbra region., Results: In experiment 1, the total infarct volume in the normothermic group was 368+/-59 mm(3); in contrast, it was significantly smaller in the hypothermia group: 169+/-33 mm(3) at 48 hours (mean+/-SEM, P:<0.05). In experiment 2, the infarct volume was 211+/-19 mm(3) in the normothermia group and 88+/-15 mm(3) in the hypothermia group at 21 days (P:<0.05). There were significant differences in neurological function from days 2 through 21 between the two groups. Mean regional cerebral blood flow in the penumbra region increased to a level >50% of baseline., Conclusions: Prolonged mild hypothermia suppressed the development of cerebral infarct and neurological deficit chronically after the induction of permanent focal ischemia.

The spin-lattice relaxation time (T1) of water protons and the cross-relaxation time (TIS) between irradiated protein protons and observed water protons were measured in order to study water-macromolecular interactions in ischemic rat brain tissues. Tissues were obtained by bilateral common carotid artery occlusion from stroke-prone spontaneously hypertensive rats. Water, Na, and K contents were measured in ischemic brain tissue at the same time. Water and Na content increased while the TIS value and K content decreased following ischemic insults. The T1 value did not change until 180 min after ischemia had been induced. Changes in the TIS value occurred earlier than changes observed for the T1 value, water, and electrolyte contents. Results indicate that the value of TIS may be useful for detecting cerebral ischemia and that the physical structure of water-macromolecular interaction may be altered soon after ischemic onset in brain tissue.

Spin-lattice relaxation times (T1) of water protons and cross-relaxation times (T(IS)) between irradiated protein protons and observed water protons were measured to study water structure in various rat brain tissue. A tumour-bearing rat model and an incomplete forebrain ischaemia model of stroke prone spontaneously hypertensive rats (SHRSP) were used for the experiments. T(IS) and T1 were measured by the inversion recovery FT method with and without f2-irradiation at 7.13 p.p.m. and gamma H2/2 pi approximately 69 Hz, respectively, using a 360 MHz FT-NMR spectrometer. All of experiments on T1 and T(IS) yielded a single kind of component. In spite of small changes in T1 and water content, T(IS) values in peritumoural oedematous and ischaemic brain tissue were significantly shorter than those of normal brain and far shorter than those of brain tumour, indicating a large amount of hydration of marco-molecules in the oedematous and/or ischaemic rat brain tissue. T(IS) might be sensitive parameter for studying the water structure in various brain tissue.