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Background and Purpose: The time from onset to reperfusion is associated with clinical outcomes in acute ischemic stroke due to large vessel occlusion (LVO); nevertheless, the time limit of the continuing procedure remains unclear. We analyzed the relationship between procedure time and clinical outcomes in patients with LVO who underwent endovascular treatment (EVT). Methods: We assessed 1,247 patients who underwent EVT for LVO. Data were obtained from our multicenter registry, and patients were included if data on procedure time were available. Multivariate analysis was performed to assess the impact of procedure time on clinical outcomes using the following parameters: favorable outcome (the modified Rankin score of 0–2 at 90 days), mortality within 90 days, symptomatic intracranial hemorrhage within 72 h after stroke onset, and procedure-related complications. Results: The rate of favorable outcomes linearly decreased with increasing procedure time, but there was no linear relationship between procedure time and other outcomes. The adjusted odds ratio for 30-minute delay in procedure time was 0.76 (95% confidence interval, 0.68–0.84) for favorable outcome, 1.15 (0.97–1.36) for mortality, 1.08 (0.87–1.33) for symptomatic intracranial hemorrhage, and 0.92 (0.75–1.16) for complications. Significant interactions in the effect of procedure time on favorable outcome were observed between the subgroups stratified by age (≥75 or Conclusions: Increasing procedure time was associated with less favorable outcomes, but not with the rate of mortality, symptomatic intracerebral hemorrhage, or complications in our cohort.

Introduction: The management and prognosis of acute ischemic stroke due to multiple large-vessel occlusion (LVO) (MLVO) are not well scrutinized. We therefore aimed to elucidate the differences in patient characteristics and prognosis of MLVO and single LVO (SLVO). Methods: The Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) enrolled 2,420 consecutive patients with acute LVO who were admitted within 24 h of onset. We compared patient prognosis between MLVO and SLVO in the favorable outcome, defined as a modified Rankin Scale (mRS) score ≤2, and in mortality at 90 days by adjusting for confounders. Additionally, we stratified MLVO patients into tandem occlusion and different territories, according to the occlusion site information and also examined their characteristics. Results: Among the 2,399 patients registered, 124 (5.2%) had MLVO. Although there was no difference between the 2 groups in terms of hypertension as a risk factor, the mean arterial pressure on admission was significantly higher in MLVO (115 vs. 107 mm Hg, p = 0.004). MLVO in different territories was more likely to be cardioembolic (42.1 vs. 10.4%, p = 0.0002), while MLVO in tandem occlusion was more likely to be atherothrombotic (39.5 vs. 81.3%, p < 0.0001). Among MLVO, tandem occlusion had a significantly longer onset-to-door time than different territories (200 vs. 95 min, p = 0.02); accordingly, the tissue plasminogen activator administration was significantly less in tandem occlusion (22.4 vs. 47.9%, p = 0.003). However, interestingly, the endovascular thrombectomy (EVT) was performed significantly more in tandem occlusion (63.2 vs. 41.7%; adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1–5.0). The type of MLVO was the only and significant factor associated with EVT performance in multivariate analysis. The favorable outcomes were obtained less in MLVO than in SLVO (28.2 vs. 37.1%; aOR, 0.48; 95% CI, 0.30–0.76). The mortality rate was not significantly different between MLVO and SLVO (8.9 vs. 11.1%, p = 0.42). Discussion/Conclusion: The prognosis of MLVO was significantly worse than that of SLVO. In different territories, we might be able to consider more aggressive EVT interventions.

Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) shows limited sensitivity in the acute-phase brainstem infarctions, including lateral medullary infarction (LMI), and the detailed characteristics of acute LMI patients with initially negative DWI-MRI findings have not been reported previously. Therefore, we aimed to investigate the differences in the backgrounds or symptoms of acute LMI patients with initially negative findings in standard axial DWI-MRI and those with positive findings. In this retrospective cohort study, we collected the data for 35 consecutive acute LMI patients who were hospitalized in our hospital from January 2011 to December 2018. Initial standard axial DWI-MRI was assessed, and the patients were divided into positive and negative groups. The characteristics of the two groups were compared, and the usefulness of additional thin-slice coronal DWI-MRI was also investigated. Nine (26%) acute LMI patients were initially negative on standard axial DWI-MRI. The patients were independently associated with smoking history (78% vs. 23%, p = 0.021) and headache (78% vs. 31%, p = 0.046). Thin-slice coronal DWI-MRI showed positive findings in 50% of the patients with negative findings in standard axial DWI-MRI. All four patients with negative findings in both standard axial and thin-slice coronal DWI-MRI had smoking history and headache. Smoking history and headache were associated with initial negative results in standard axial DWI-MRI in acute LMI. Additional thin-slice coronal DWI-MRI was sometimes useful in detecting acute LMI. Follow-up MRI is important for patients showing negative findings in initial DWI-MRI.

This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval [CI], 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.

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.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.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).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.

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. Non-standard Abbreviations and AcronymsEVT, endovascular therapy; t-PA, tissue plasminogen activator; LVO, large vessel occlusion; EMS, emergency medical services; mRS, modified Rankin scale; NIHSS, National Institute of Health Stroke Scale; ASPECTS, Alberta stroke program early computed tomography score; TICI, thrombolysis in cerebral infarction.

Objective Various neurological manifestations have been increasingly reported in coronavirus disease 2019 (COVID-19). We determined the neurological features and long-term sequelae in hospitalized COVID-19 patients. Methods We retrospectively studied 95 consecutive hospitalized patients with COVID-19 between March 1 and May 13, 2020. Acute neurological presentations (within two weeks of the symptom onset of COVID-19) were compared between 60 non-severe and 35 severely infected patients who required high-flow oxygen. In the 12 ventilated patients (the most severe group), we evaluated neurological complications during admission, subacute neurological presentations, and neurological sequelae (51 and 137 days from the onset [median], respectively). Results Of the 95 patients (mean age 53 years old; 40% women), 63% had acute neurological presentations, with an increased prevalence in cases of severe infections (83% vs. 52%, p＜0.001). Impaired consciousness and limb weakness were more frequent in severe patients than in non-severe ones (0% vs. 49%; p＜0.001, and 0% vs. 54%; p＜0.001, respectively). In the most severe group (mean age 72 years old; 42% women), 83% of patients had neurological complications [cerebrovascular disease (17%), encephalopathy (82%), and neuropathy (55%)], and 92% had subacute neurological presentations [impaired consciousness (17%), higher brain dysfunction (82%), limb weakness (75%), and tremor (58%)]. Neurological sequelae were found in 83% of cases, including higher brain dysfunction (73%), limb weakness (50%), and tremor (58%). Conclusions Neurological manifestations are common in COVID-19, with the possibility of long-lasting sequelae.

The ring finger protein 213 gene (RNF213) p.R4810K variant is a major susceptibility gene for intracranial arterial stenosis in East Asia. We hypothesized that if intracranial arterial stenosis is induced by a non-atherosclerotic mechanism similar to moyamoya disease, the patients with RNF213 p.R4810K variant may have a lower cumulative atherosclerotic burden than the non-carriers.A total of 112 participants with intracranial arterial stenosis were enrolled in this multicenter cross-sectional study. We compared the prevalence of atherosclerotic risk factors and three different cardiovascular risk scores (Essen Stroke Risk Score, Framingham Risk Score, and Suita Risk Score) between the RNF213 p.R4810K variant carriers and non-carriers. Patients with moyamoya disease were excluded from the study.The RNF213 p.R4810K variant carriers were younger than the non-carriers (P＜0.001). The prevalence of each atherosclerotic risk factor was not significant, but it tended to be lower in the variant carriers. The Essen Stroke Risk Score (carriers: 2.3±1.5 vs. non-carriers: 2.9±1.5, P=0.047), Framingham Risk Score (10.7±6.4 vs. 15.3±6.2, P=0.001), and Suita Risk Score (35.4±15.8 vs. 48.7±15.2, P＜0.001) were significantly lower in the variant carriers. Among the three risk scores, the Suita score showed the highest predictive accuracy for the variant carriers.RNF213 p.R4810K variant carriers have a lower cumulative atherosclerotic burden than non-carriers among patients with intracranial arterial stenosis. New therapeutic approaches beyond the standard management of atherosclerotic risk factors are required to prevent the development of intracranial arterial stenosis.

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.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).The risk of ICH after EVT was not different between patients with and without APT before EVT for acute LVO.

Objective Various neurological manifestations have been increasingly reported in coronavirus disease 2019 (COVID-19). We determined the neurological features and long-term sequelae in hospitalized COVID-19 patients. Methods We retrospectively studied 95 consecutive hospitalized patients with COVID-19 between March 1 and May 13, 2020. Acute neurological presentations (within two weeks of the symptom onset of COVID-19) were compared between 60 non-severe and 35 severely infected patients who required high-flow oxygen. In the 12 ventilated patients (the most severe group), we evaluated neurological complications during admission, subacute neurological presentations, and neurological sequelae (51 and 137 days from the onset [median], respectively). Results Of the 95 patients (mean age 53 years old; 40% women), 63% had acute neurological presentations, with an increased prevalence in cases of severe infections (83% vs. 52%, p

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

AIM Intensive rehabilitation effectively improves physical functions in patients with acute stroke, but the frequency of intervention and its cost-effectiveness are poorly studied. This study aimed to examine the effect of early high-frequency rehabilitation intervention on inpatient outcomes and medical expenses of patients with stroke. METHODS The study retrospectively included 1759 patients with acute stroke admitted to the Kobe City Medical Center General Hospital between 2013 and 2016. Patients with a transient ischemic attack, subarachnoid hemorrhage, and those who underwent urgent surgery were excluded. Patients were divided into two groups according to the frequency of rehabilitation intervention: the high-frequency intervention group (>2 times/day, n = 1105) and normal-frequency intervention group (

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Background and Purpose: Outcomes in patients ≥90 years of age with stroke due to large vessel occlusion were compared between endovascular therapy (EVT) and medical management. Methods: Of 2420 acute ischemic stroke patients with large vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients aged ≥90 years with occlusion of the internal carotid artery or M1 segment of the middle cerebral artery were included. The primary effectiveness outcome was a favorable outcome at 3 months, defined as achieving a modified Rankin Scale score of 0 to 2 or return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage within 72 hours after onset. Intergroup biases were adjusted by multivariable adjustment with inverse probability of treatment weighting. Results: A total of 150 patients (median age, 92 [interquartile range, 90–94] years; median prestroke modified Rankin Scale score, 2 [interquartile range, 0–4]) were analyzed. EVT was performed in 49 patients (32.7%; mechanical thrombectomy, n=43). The EVT group showed shorter time from onset to hospital arrival ( P =0.03), higher Alberta Stroke Program Early CT Score ( P P P P =0.30). Conclusions: Patients who underwent EVT showed better functional outcomes than those with medical management without increased symptomatic intracranial hemorrhages. Given proper patient selection, withholding EVT solely on the basis of the age of patients may not offer the best chance of good outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.

We retrospectively examined the differences between paramedic triage and final diagnosis in the cases that were transported to our hospital between May 2016 and March 2019. About 30% of the patients with suspected stroke were diagnosed other than stroke. Some of the patients without suspected stroke were diagnosed with large vessel occlusion and were treated with mechanical thrombectomy. The time from arrival at the hospital to treatment was significantly longer in the patients without suspected stroke than with suspected stroke. To achieve a better prehospital care, we need to accept a wide range of stroke mimics, and to continuously feedback the paramedics about the importance of paralysis, cortical symptoms in stroke.

BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.

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

Background Statins have been associated with reduced recurrence and better functional outcomes in patients with acute ischemic stroke. However, the effect of statins in patients with acute large vessel occlusion (LVO) is not well scrutinized. Methods and Results RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism)‐Japan Registry 2, a physician‐initiated registry, enrolled 2420 consecutive patients with acute LVO who were admitted to 46 centers across Japan within 24 hours of onset. We compared patients with and without statin use after acute LVO onset (statin group and nonstatin group, respectively) in terms of the modified Rankin scale at 90 days. We estimated that the odds ratios for the primary outcome was modified Rankin scale and we estimated the odds ratios for a 1‐scale lower modified Rankin scale adjusting for confounders. After excluding 12 patients without LVO and 9 patients without follow‐up, the mean age of 2399 patients was 75.9 years; men accounted for 55% of patients. Statins were administered to 447 (19%) patients after acute LVO onset. Patients in the statin group had more atherothrombotic cerebral infarctions (34.2% versus 12.1%, P P P P =0.02). The mortality at 90 days was lower in the statin group (4.7%) than the nonstatin group (12.5%; P P =0.02). Conclusions Statin administration after acute LVO onset is significantly associated with better functional outcome and mortality at 90 days.

Highlights • COVID-19 epidemic challenged medical systems’ capacity to provide adequate care. • Kobe City stroke facilities operated optimally due to among-facility cooperation. • Stroke incidence decreased but treatment rates increased during the outbreak. • No case of symptomatic stroke in patients with confirmed COVID-19 was recorded., Background The novel coronavirus disease 2019 (COVID-19) outbreak raised concerns over healthcare systems’ ability to provide suitable care to stroke patients. In the present study, we examined the provision of stroke care in Kobe City during the COVID-19 epidemic, where some major stroke centers ceased to provide emergency care. Methods This was a cross-sectional study. The Kobe Stroke Network surveyed the number of stroke patients admitted to all primary stroke centers (PSCs) in the city between March 1 and May 23, 2020, and between March 3 and May 25, 2019. In addition, online meetings between all PSC directors were held regularly to share information. The survey items included emergency response system characteristics, number of patients with stroke hospitalized within 7 days of onset, administered treatment types (IV rt-PA, mechanical thrombectomy, surgery, and endovascular therapy), and stroke patients with confirmed COVID-19. Results During the period of interest in 2020, the number of stroke patients hospitalized across 13 PSCs was 813, which was 15.5% lower than that during the same period of 2019 (p=0.285). The number of patients admitted with cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage decreased by 15.4% (p=0.245), 16.1% (p=0.659), and 14.0% (p=0.715), respectively. However, the rates of mechanical thrombectomy and surgery for intracerebral hemorrhage were slightly increased by 12.1% (p=0.754) and 5.0% (p=0.538), respectively. PSCs that ceased to provide emergency care reported a decrease in the number of stroke cases of 65.7% compared with the same period in 2019, while other PSCs reported an increase of 0.8%. No case of a patient with stroke and confirmed COVID-19 was reported during the study period. Conclusion Kobe City was able to maintain operation of its stroke care systems thanks to close cooperation among all city PSCs and a temporal decrease in the total number of stroke cases.

Background We experienced two cases of ischemic stroke resulting from carotid artery occlusion associated with acute type A aortic dissection (ATAAD), in which carotid artery stenting before the surgery for ATAAD resulted in good clinical outcomes. Case 1 description: A 63-year-old woman was hospitalized for conscious disturbance, right hemiparesis, and total aphasia. Computed tomography of the head showed no abnormal findings. Computed tomography angiography showed ATAAD and bilateral common carotid artery occlusion. Surgery was not indicated for ATAAD because of a poor prognosis of ischemic stroke. However, carotid artery stenting of the left common carotid artery occlusion was successfully performed, and her neurological findings improved. The patient underwent hemiarch replacement for ATAAD on the day after carotid artery stenting. Her final modified Rankin Scale was 1. Case 2 Description: A 57-year-old woman was hospitalized for mild left hemiparesis. Magnetic resonance imaging showed right watershed infarction and right common carotid artery occlusion. Computed tomography angiography showed ATAAD. After hospitalization, conscious disturbance appeared and left hemiparesis worsened. Ischemic stroke indicated a poor prognosis for revascularization by surgery for ATAAD. Thus, carotid artery stenting of the right common carotid artery occlusion was performed. The patient’s neurological findings improved and she underwent hemiarch replacement for ATAAD at 19 days after carotid artery stenting. Her final modified Rankin Scale was 1. Conclusions In the present cases, although ischemic stroke was serious and precluded surgical indication for ATAAD, carotid artery stenting before surgery for ATAAD resulted in good clinical outcomes. Performing carotid artery stenting before surgery for ATAAD is challenging but achievable, and is a valid treatment option depending on the individual cases.

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.

Background and purpose The detection rate of diffusion-weighted (DWI) hyperintense lesions varies widely in patients with transient global amnesia (TGA). The aim was to examine the association of hyperintense lesions on DWI magnetic resonance imaging (MRI) with patient characteristics, precipitating factors, clinical presentation and MRI settings in patients with TGA. Methods In this multicenter retrospective observational study, using the standardized diagnosis entry system of electronic health records of four tertiary medical centers in the Kansai district of Japan, TGA patients (n = 261) who underwent brain MRI within 28 days of onset were examined. When the onset time was unavailable, the discovery time was used. Results Diffusion-weighted hyperintense lesions were observed in 79 patients (30%). There were no significant differences in age, sex, vascular risk factors, precipitating factors or clinical presentation between patients with and without DWI lesions. The detection rate increased linearly 24 h after onset and then reached a plateau of 60%-80% by 84 h. After 84 h, the detection rate decreased rapidly. In a multivariate logistic regression model, MRI examination 24-84 h after onset (odds ratio 7.00, 95% confidence interval 3.50-13.99) and a thin-slice (≤3 mm) DWI sequence (odds ratio 7.59, 95% confidence interval 3.05-18.88) were independent predictors of DWI lesions. Conclusions This study suggests that DWI hyperintense lesions in TGA are not associated with patient characteristics and clinical presentation. Brain MRI examination 24-84 h after onset and thin-slice DWI sequences enhance the detection of DWI lesions in TGA patients.

ObjectiveTo describe our initial experience with the Versi Retriever for mechanical thrombectomy in patients with acute ischemic stroke.MethodsThis 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.ResultsEleven 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.ConclusionsOur 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 registrationNCT03366818

Background and Purpose— Stroke is the most frequent severe clinical event in patients with Fabry disease. We aimed to evaluate the cerebral magnetic resonance imaging findings of patients with Fabry disease and assess their association with future stroke risk after enzyme replacement therapy (ERT) induction. Methods— We retrospectively reviewed the magnetic resonance imaging findings of 25 patients with Fabry disease. Of these, 12 adult patients without prior stroke or ERT were enrolled to evaluate the association between baseline magnetic resonance imaging findings and stroke occurrence after ERT initiation. We assessed white matter hyperintensities, periventricular hyperintensities, and basilar artery diameter as neuroimaging markers. Results— The mean age of participants was 38.8±16.8 years. Fourteen patients (56.0%) were women. White matter hyperintensities and periventricular hyperintensities were observed in 15 and 13 cases, respectively. The mean basilar artery diameter was 3.2±0.55 mm. Two patients demonstrated old infarct lesions. Three of 12 patients in whom ERT was initiated had symptomatic stroke after baseline magnetic resonance imaging. Of these, 2 developed stroke within 6-month post-ERT initiation. The baseline basilar artery diameter was larger in patients who developed stroke than in those who did not (4.0±0.40 versus 2.9±0.49 mm, P =0.02). Conclusions— Basilar artery diameter may be associated with stroke risk after ERT initiation among Japanese patients with Fabry disease.

We report three cases in which carotid ultrasonography was useful for the diagnosis of dural arteriovenous fistula (dAVF). In all cases, dAVFs were fed by branches of the external carotid artery (ECA) and had retrograde leptomeningeal venous drainage. Carotid ultrasonography revealed high end-diastolic ratio (ED ratio) of the common carotid artery (CCA) (1.49-2.16) and low resistance index (RI) of the ECA (0.59-0.66). They were normalized after endovascular treatment (ED ratio of CCA 1.02-1.06, RI of ECA 0.75-0.87). In conclusion, high ED ratio of the CCA and low RI of the ECA might be a useful indicator for both screening and follow-up of dAVF.

A 79-year-old woman was admitted emergently for disturbance of consciousness. Her consciousness level was Japan coma scale 20, and she presented with hypermyotonia. Brain magnetic resonance imaging and cerebrospinal fluid examination showed normal findings. Her blood tests showed an increased ammonia level of 291 μg/dl with normal liver function. We catheterized the bladder for urinary retention. Eight hours after admission, the blood level of ammonia decreased to 57 μg/dl and the patient's consciousness level improved. Corynebacterium pseudodiphtheriticum, which is a bacteria producing urease, was detected from a urine culture. It is important to recognize that obstructive urinary tract infection caused by urease-producing bacteria can cause hyperammonemia.

Background In all of randomized controlled trials of mechanical thrombectomy, the target vessels were proximal. Herein we report a clinical trial of the Tron FX stent retriever, including the smallest size of 2/15 mm for distal intracranial large vessel occlusion (LVO). Objective Eligible patients presented within 8 h of onset with proximal or distal LVOs, and the Tron FX 4/20 mm or 2/15 mm were used as the first-line device. Methods The primary endpoints were rate of modified Thrombolysis in Cerebral Infarction (mTICI) grade 2a–3 immediately after using Tron FX only, and mortality rate 90 d. We compared the outcomes between sizes 4/20 and 2/15 mm. Results The clinical trial was conducted in 50 cases, of which 44% presented with distal LVO and 15 cases were treated using only Tron FX 2/15 mm. The overall rate of mTICI grade 2a–3 was 80.0% (75.8% with Tron FX 4/20 mm, and 86.7% with 2/15 mm), and a 90-day modified Rankin Scale ≤ 2 or improvement of National Institute of Health Stroke Scale after thrombectomy ≥ 10 was achieved in 66.7% of cases (61.3% with Tron FX 4/20 mm, and 80.0% with 2/15 mm). The overall 90-day mortality rate was 8.0%, and symptomatic intracranial hemorrhage within 24 h occurred in 2.0% of cases. Conclusion In this clinical trial using the Tron FX, which included the size of 2/15 mm for distal LVO, its efficacy was similar and its safety was superior compared with previous studies.

We hypothesized that the relationships between treatments and outcomes in acute basilar artery occlusion (BAO) are different, depending on the severity of initial neurological deficits.Of 2420 ischemic stroke patients with large vessel occlusion in a prospective, multicenter registry in Japan, patients with acute BAO were enrolled. Subjects were divided into two severity groups according to the baseline NIH Stroke Scale score: severe (≥10) and mild (10) groups. The primary effectiveness outcome was favorable outcome, defined as modified Rankin Scale score 0-3 at 3 months. Safety outcomes included any intracranial hemorrhage (ICH) within 72 h. Outcomes in each group were compared between patients who received endovascular therapy (EVT) and those with standard medical treatment (SMT).In this study, 167 patients (52 female; median age 75 years) were analyzed. The favorable outcome was seen in 93 patients (56%) overall. In the severe group (n = 128), the proportion of favorable outcome was higher in patients who received EVT (60/111, 54%) than those with SMT (2/17, 12%, P0.01). In the mild group (n = 39), the rates of favorable outcome were comparable between the EVT (13/18, 72%) and SMT patients (18/21, 86%, P = 0.43). No significant differences in the rates of any ICH were seen among any groups.In acute BAO stroke with severe neurological deficit, independent ambulation was more frequently seen in patients who received EVT than those with SMT. Patients with mild neurological deficits showed similar rates of independent ambulation between the two treatment selections.

Detection of paroxysmal atrial fibrillation (PAF) in cryptogenic stroke is critical to selecting an antithrombotic therapy for preventing recurrent stroke. However, the predictor of PAF in patients with acute ischemic stroke is not well elucidated. P-wave terminal force in lead VThe study included 295 consecutive patients who had acute ischemic stroke and were admitted to the hospital between September 2014 and August 2016. Patients with a known history of PAF, persistent atrial fibrillation, or cardiac pacemaker were excluded from the study. The clinical characteristics of patients with or without PAF were compared, and multiple logistic regression analysis was performed to assess the independent contribution of each variable.Among 226 patients eligible for our analysis, 16 (7.1%) were diagnosed with PAF after admission. PTFVPTFV

We describe a case of dural arteriovenous fistulas (DAVFs) involving the superior sagittal sinus (SSS) successfully treated with stent placement for an occluded sinus and transarterial embolization. A 61-year-old man who had been treated with anticoagulation for a known SSS thrombosis presented with a sudden onset of headache. CT scan revealed an intraventricular hemorrhage and cerebral angiography revealed DAVFs involving the SSS which had severe venous congestion and sinus occlusion. We treated this case with a staged endovascular approach which consisted of stent placement for the occluded sinus and transarterial intravenous embolization resulting in complete eradication of DAVFs. Recanalization of an occluded sinus by stent placement can reduce venous congestion and transarterial intravenous embolization can obliterate dural arteriovenous shunts. This staged strategy is feasible and should be considered a first option of treatment, especially for DAVFs which presented with intracranial hemorrhage and aggressive venous hypertension.

Aim: We investigated the influence of preadmission anticoagulation on infarct volume in patients with nonvalvular atrial fibrillation (NVAF). Methods: Data were collected on consecutive ischemic stroke patients with NVAF admitted to Osaka University Hospital between 2004 and 2011. Patients were divided into 3 groups: the no-anticoagulation group, the subtherapeutic anticoagulation group [admission prothrombin time international normalized ratio (PT-INR) 1 before onset. Results: Of the 68 patients, 45 were classified into the no-anticoagulation group, 9 into the subtherapeutic group, and 14 into the therapeutic group. The median value of infarct volume was 60 (interquartile range 9–176), 142 (64–184), and 8 (3–46) ml in each group, respectively. Infarct volume in the therapeutic group was significantly smaller than in the subtherapeutic group (p = 0.010), and tended to be smaller than in the no-anticoagulation group (p = 0.086). National Institute of Health Stroke Scale score at admission, and mRS score at discharge were significantly reduced in the therapeutic group compared with those in the other groups (p = 0.028 and p = 0.017, respectively). Conclusion: Therapeutic anticoagulation reduces infarct volume and improves neurological outcome after ischemic stroke in patients with NVAF.

Influenza-associated encephalopathy (IAE) usually occurs in children aged

Although nonconvulsive status epilepticus (NCSE) is a major neurological emergency, its frequency and clinical course are not well clarified. We investigated the clinical characteristics of status epilepticus focusing on the significance of NCSE. One thousand seven hundred twenty-three patients were admitted as neurological emergency cases in our hospital between October 2003 and September 2006. Of these cases, 94 (5.5%) were diagnosed as status epilepticus of which, 24 (25.5%) were diagnosed with NCSE on admission. Moreover, 8 patients who presented with convulsive status epilepticus on admission had episodes of NCSE during hospitalization. Thus, 32 patients (34.0%) suffered from NCSE during their clinical course. We analyzed the prognostic factors of status epilepticus using the Glasgow Outcome Scale. Poor outcome was significantly correlated with NCSE (p = 0.003) and acute cerebrovascular disease (p = 0.010), independent of age, sex, history of epilepsy, and other etiologies. Our study revealed that NCSE is not a rare condition and results in a poor outcome. Careful EEG evaluation of patients with consciousness disturbance might increase the diagnostic accuracy of NCSE, and aggressive treatment of patients with NCSE should be necessary to improve the prognosis of NCSE.

Background: The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke. Methods: Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE. Results: VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7). Conclusions: In this large well-characterized cohort of patients withrecentlacunarstroke,VBEwaspredictiveof deathbutnotof recurrentstrokeor major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood

A 50-year-old man presented with altered mental status during hospitalization for pneumonia. MRI showed multifocal ring-enhanced lesions, which consisted of multiple cerebral abscesses. We started empirical antibiotic therapy, but the following morning, his condition rapidly deteriorated and a CT scan revealed acute hydrocephalus, which required ventricular drainage. Gram staining of cerebro-spinal fluid from the ventricular drainage showed gram-positive cocci in chains, but culture results were negative. 16S ribosomal RNA sequencing with broad-range PCR of the cerebro-spinal fluid identified Streptococcus intermedius. On the basis of this identification, the antibiotic regimen was changed to ampicillin monotherapy. After 1 year of antibiotic therapy, all the abscesses had disappeared and the patient was discharged without any sequelae. Bacterial 16S rRNA gene analysis with broad-range PCR is a very useful method for facilitating the etiological diagnosis and selection of appropriate treatment for culture-negative infections.

We report a case of internal carotid artery (ICA) occlusion caused by arterial dissection triggered by an elongated styloid process. A 43-year-old man presented with a headache followed by speech disturbance. Magnetic resonance imaging and magnetic resonance angiography scans revealed acute infarction and right ICA occlusion. A T1-weighted magnetic resonance imaging scan revealed a hyperintensity in the occluded ICA, suggesting intramural hematoma. Computed tomographic angiography also revealed ICA occlusion and bilateral elongated styloid processes. We performed transoral carotid ultrasonography, which revealed the absence of flow signal in the double lumen of the dilated extracranial ICA. We diagnosed his condition as arterial dissection and treated him with antithrombotic drugs. Six months later, the occluded ICA recanalized spontaneously, and computed tomographic angiography at that time revealed a close relation between the tip of the styloid process and the recanalized ICA. This finding suggests that an elongated styloid process is involved in arterial dissection. In patients with ICA occlusion of unknown etiology, an evaluation for intramural hematoma and styloid process length are useful for the diagnosis of dissection and its etiology.

Detection of the position of the microcatheter tip is important for safe and effective coil embolization of cerebral aneurysms, but is sometimes difficult, especially in the final stage with a high density of embolized coils. We report a new technique to deduce the position of the microcatheter tip using a novel microguidewire during coil embolization of cerebral aneurysms. The novel microguidewire (ASAHI CHIKAI 10; Asahi Intecc, Nagoya, Aichi), with a radiopaque portion of 30 mm, is advanced into the microcatheter until the distal end of the radiopaque portion reaches the coil mass edge at the neck of the aneurysm. The distance between the second marker of the microcatheter and the proximal end of the radiopaque portion of the microguidewire is checked. The position of the microcatheter tip is deduced from the distance and curve of the microguidewire. Microcatheter tips can be easily detected with this technique without complications. This technique is safe, simple, and useful for deducing the position of the microcatheter tip during coil embolization of cerebral aneurysms.