Publications by authors named "Masatoshi Koga"

183 Publications

Twenty-Year Change in Severity and Outcome of Ischemic and Hemorrhagic Strokes.

JAMA Neurol 2021 Dec 6. Epub 2021 Dec 6.

Shimane University School of Medicine, Izumo, Shimane, Japan.

Importance: Whether recent changes in demographic characteristics and therapeutic technologies have altered stroke outcomes remains unknown.

Objective: To determine secular changes in initial neurological severity and short-term functional outcomes of patients with acute stroke by sex using a large population.

Design, Setting, And Participants: This nationwide, hospital-based, multicenter, prospective registry cohort study used the Japan Stroke Data Bank and included patients who developed acute stroke from January 2000 through December 2019. Patients with stroke, including ischemic and hemorrhagic strokes, who registered within 7 days after symptom onset were studied. Modified Rankin Scale scores were assessed at hospital discharge for all patients.

Exposure: Time.

Main Outcomes And Measures: Initial severity was assessed by the National Institutes of Health Stroke Scale for ischemic stroke and intracerebral hemorrhage and by the World Federation of Neurological Surgeons grading for subarachnoid hemorrhage. Outcomes were judged as favorable if the modified Rankin Scale score was 0 to 2 and unfavorable if 5 to 6.

Results: Of 183 080 patients, 135 266 (53 800 women [39.8%]; median [IQR] age, 74 [66-82] years) developed ischemic stroke, 36 014 (15 365 women [42.7%]; median [IQR] age, 70 [59-79] years) developed intracerebral hemorrhage, and 11 800 (7924 women [67.2%]; median [IQR] age, 64 [53-75] years) developed subarachnoid hemorrhage. In all 3 stroke types, median ages at onset increased, and the National Institutes of Health Stroke Scale and World Federation of Neurological Surgeons scores decreased throughout the 20-year period on multivariable analysis. In ischemic stroke, the proportion of favorable outcomes showed an increase over time after age adjustment (odds ratio [OR], 1.020; 95% CI, 1.015-1.024 for women vs OR, 1.015; 95% CI, 1.011-1.018 for men) but then stagnated, or even decreased in men, on multivariate adjustment including reperfusion therapy (OR, 0.997; 95% CI, 0.991-1.003 for women vs OR, 0.990; 95% CI, 0.985-0.994 for men). Unfavorable outcomes and in-hospital deaths decreased in both sexes. In intracerebral hemorrhage, favorable outcomes decreased in both sexes, and unfavorable outcomes and deaths decreased only in women. In subarachnoid hemorrhage, the proportion of favorable outcomes was unchanged, and that of unfavorable outcomes and deaths decreased in both sexes.

Conclusions And Relevance: In this study, functional outcomes improved in patients with ischemic stroke during the past 20 years in both sexes presumably partly owing to the development of acute reperfusion therapy. The outcomes of patients with hemorrhagic stroke did not clearly improve in the same period.
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http://dx.doi.org/10.1001/jamaneurol.2021.4346DOI Listing
December 2021

Developing a Stroke Risk Prediction Model Using Cardiovascular Risk Factors: The Suita Study.

Cerebrovasc Dis 2021 Nov 29:1-8. Epub 2021 Nov 29.

Division of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Introduction: Stroke remains a major cause of death and disability in Japan and worldwide. Detecting individuals at high risk for stroke to apply preventive approaches is recommended. This study aimed to develop a stroke risk prediction model among urban Japanese using cardiovascular risk factors.

Methods: We followed 6,641 participants aged 30-79 years with neither a history of stroke nor coronary heart disease. The Cox proportional hazard model estimated the risk of stroke incidence adjusted for potential confounders at the baseline survey. The model's performance was assessed using the receiver operating characteristic curve and the Hosmer-Lemeshow statistics. The internal validity of the risk model was tested using derivation and validation samples. Regression coefficients were used for score calculation.

Results: During a median follow-up duration of 17.1 years, 372 participants developed stroke. A risk model including older age, current smoking, increased blood pressure, impaired fasting blood glucose and diabetes, chronic kidney disease, and atrial fibrillation predicted stroke incidence with an area under the curve = 0.76 and p value of the goodness of fit = 0.21. This risk model was shown to be internally valid (p value of the goodness of fit in the validation sample = 0.64). On a risk score from 0 to 26, the incidence of stroke for the categories 0-5, 6-7, 8-9, 10-11, 12-13, 14-15, and 16-26 was 1.1%, 2.1%, 5.4%, 8.2%, 9.0%, 13.5%, and 18.6%, respectively.

Conclusion: We developed a new stroke risk model for the urban general population in Japan. Further research to determine the clinical practicality of this model is required.
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http://dx.doi.org/10.1159/000520100DOI Listing
November 2021

Weight Change Since Age 20 and the Risk of Cardiovascular Disease Mortality: A Prospective Cohort Study.

J Atheroscler Thromb 2021 Nov 20. Epub 2021 Nov 20.

Division of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

Aim: Weight change could have many health outcomes. This study aimed to investigate the association between weight change and mortality risk due to total cardiovascular disease (CVD), ischemic heart disease (IHD), and stroke among Japanese.

Methods: We used Suita Study data from 4,746 people aged 30-79 years in this prospective cohort study. Weight change was defined as the difference between baseline weight and weight at age 20. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total CVD, IHD, and stroke mortality for 1) participants with a weight change (>10, 5 to 10, -5 to -10, and <-10 kg) compared to those with stable weight (-4.9 to 4.9 kg) and 2) participants who moved from one body mass index category (underweight, normal weight, or overweight) to another compared to those with normal weight at age 20 and baseline.

Results: Within a median follow-up period of 19.9 years, the numbers of total CVD, IHD, and stroke mortality were 268, 132, and 79, respectively. Weight loss of >10 kg was associated with the increased risk of total CVD mortality 2.07 (1.29, 3.32) and stroke mortality 3.02 (1.40, 6.52). Moving from normal weight at age 20 to underweight at baseline was associated with the increased risk of total CVD, IHD, and stroke mortality: 1.76 (1.12, 2.77), 2.10 (1.13, 3.92), and 2.25 (1.05, 4.83), respectively.

Conclusion: Weight loss, especially when moving from normal to underweight, was associated with the increased risk of CVD mortality.
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http://dx.doi.org/10.5551/jat.63191DOI Listing
November 2021

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation.

Ann Neurol 2021 Nov 8. Epub 2021 Nov 8.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.

Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.

Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR  = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR  = 0.79, 95%-CI [0.66, 0.95]) in simple (p  = 0.129), adjusted (p  = 0.094) or weighted (p  = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1).

Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021.
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http://dx.doi.org/10.1002/ana.26267DOI Listing
November 2021

ESO guideline for the management of extracranial and intracranial artery dissection.

Eur Stroke J 2021 Sep 13;6(3):XXXIX-LXXXVIII. Epub 2021 Oct 13.

Department of Neurology, University of Utah, Salt Lake City, UT, USA.

The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of extracranial artery dissection (EAD) and intracranial artery dissection (IAD). EAD and IAD represent leading causes of stroke in the young, but are uncommon in the general population, thus making it challenging to conduct clinical trials and large observational studies. The guidelines were prepared following the Standard Operational Procedure for European Stroke Organisation guidelines and according to GRADE methodology. Our four recommendations result from a thorough analysis of the literature comprising two randomized controlled trials (RCTs) comparing anticoagulants to antiplatelets in the acute phase of ischemic stroke and twenty-six comparative observational studies. In EAD patients with acute ischemic stroke, we recommend using intravenous thrombolysis (IVT) with alteplase within 4.5 hours of onset if standard inclusion/exclusion criteria are met, and mechanical thrombectomy in patients with large vessel occlusion of the anterior circulation. We further recommend early endovascular or surgical intervention for IAD patients with subarachnoid hemorrhage (SAH). Based on evidence from two phase 2 RCTs that have shown no difference between the benefits and risks of anticoagulants versus antiplatelets in the acute phase of symptomatic EAD, we strongly recommend that clinicians can prescribe either option. In post-acute EAD patients with residual stenosis or dissecting aneurysms and in symptomatic IAD patients with an intracranial dissecting aneurysm and isolated headache, there is insufficient data to provide a recommendation on the benefits and risks of endovascular/surgical treatment. Finally, nine expert consensus statements, adopted by 8 to 11 of the 11 experts involved, propose guidance for clinicians when the quality of evidence was too low to provide recommendations. Some of these pertain to the management of IAD (use of IVT, endovascular treatment, and antiplatelets versus anticoagulation in IAD with ischemic stroke and use of endovascular or surgical interventions for IAD with headache only). Other expert consensus statements address the use of direct anticoagulants and dual antiplatelet therapy in EAD-related cerebral ischemia, endovascular treatment of the EAD/IAD lesion, and multidisciplinary assessment of the best therapeutic approaches in specific situations.
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http://dx.doi.org/10.1177/23969873211046475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564160PMC
September 2021

Transesophageal Echocardiography in Ischemic Stroke With Atrial Fibrillation.

J Am Heart Assoc 2021 Nov 6;10(22):e022242. Epub 2021 Nov 6.

Department of Cerebrovascular Medicine National Cerebral and Cardiovascular Center Suita Japan.

Background To clarify differences in clinical significance of intracardiac thrombi in nonvalvular atrial fibrillation-associated stroke as identified by transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). Methods and Results Using patient data on nonvalvular atrial fibrillation-associated ischemic stroke between 2011 and 2014 from 15 South Korean stroke centers (n=4841) and 18 Japanese centers (n=1192), implementation rates of TEE/TTE, and detection rates of intracardiac thrombi at each center were correlated. The primary outcome was recurrent ischemic stroke at 1 year after the onset. A total of 5648 patients (median age, 75 years; 2650 women) were analyzed. Intracardiac thrombi were detected in 75 patients (1.3%) overall. Thrombi were detected in 7.8% of patients with TEE (either TEE alone or TEE+TTE: n=679) and in 0.6% of those with TTE alone (n=3572). Thrombus detection rates varied between 0% and 14.3% among centers. As TEE implementation rates at each center increased from 0% to 56.7%, thrombus detection rates increased linearly (detection rate [%]=0.11×TEE rate [%]+1.09 [linear regression], <0.01). TTE implementation rates (32.3%-100%) were not associated with thrombus detection rates (=0.53). Intracardiac thrombi were associated with risk of recurrent ischemic stroke overall (adjusted hazard ratio [aHR] 2.35, 95% CI, 1.07-5.16). Thrombus-associated ischemic stroke risk was high in patients with TEE (aHR, 3.13; 95% CI, 1.17-8.35), but not in those with TTE alone (aHR, 0.89; 95% CI, 0.12-6.51). Conclusions Our data suggest clinical relevance of TEE for accurate detection and risk stratification of intracardiac thrombi in nonvalvular atrial fibrillation-associated stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502.
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http://dx.doi.org/10.1161/JAHA.121.022242DOI Listing
November 2021

Distinction in Prevalence of Atherosclerotic Embolic Sources in Cryptogenic Stroke With Cancer Status.

J Am Heart Assoc 2021 11 23;10(21):e021375. Epub 2021 Oct 23.

Department of Neurology Juntendo University Urayasu Hospital Chiba Japan.

Background Cerebrovascular diseases are common comorbidities in patients with cancer. Although active cancer causes ischemic stroke by multiple pathological conditions, including thromboembolism attributable to Trousseau syndrome, the relationship between stroke and inactive cancer is poorly known. The aim of this study was to elucidate the different underlying pathogeneses of cryptogenic stroke in active and inactive patients with cancer, with detailed investigation by transesophageal echocardiography. Methods and Results CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke) registry is a multicenter registry including data of patients initially diagnosed as having cryptogenic stroke and undergoing transesophageal echocardiography. Patients were divided into active cancer, inactive cancer, and noncancer groups, and their clinical features were compared. Of the total 667 enrolled patients (age, 68.7±12.8 years; 455 men), 41 (6.1%) had active cancer, and 51 (7.5%) had a history of inactive cancer. On multinomial logistic regression analysis, infarctions in multiple vascular territories (odds ratio [OR], 2.73; 95% CI, 1.39-5.40) and CRP (C-reactive protein) (OR, 1.10; 95% CI, 1.01-1.19) were independently associated with active cancer, whereas age (OR, 1.05; 95% CI, 1.01-1.08), contralateral carotid stenosis from the index stroke lesion (OR, 4.05; 95% CI, 1.60-10.27), calcification of the aortic valve (OR, 2.10; 95% CI, 1.09-4.05), and complicated lesion of the aortic arch (OR, 2.13; 95% CI, 1.11-4.10) were significantly associated with inactive cancer. Conclusions Patients with cancer were not rare in cryptogenic stroke. Although patients with active cancer had more multiple infarctions, patients with inactive cancer had more atherosclerotic embolic sources potentially causing arteriogenic strokes. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000032957.
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http://dx.doi.org/10.1161/JAHA.120.021375DOI Listing
November 2021

Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: an observational study and individual patient data pooled analysis.

J Neurol Neurosurg Psychiatry 2021 Oct 11. Epub 2021 Oct 11.

Stroke Research Center, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.

Objective: The optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start.

Methods: This is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH.

Results: A total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke.

Conclusions: Our results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.
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http://dx.doi.org/10.1136/jnnp-2021-327236DOI Listing
October 2021

Prediction of recurrent stroke among ischemic stroke patients with atrial fibrillation: Development and validation of a risk score model.

PLoS One 2021 8;16(10):e0258377. Epub 2021 Oct 8.

Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Republic of Korea.

Background: There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF.

Methods: AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine-Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset.

Results: The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA).

Conclusions: Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258377PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500448PMC
November 2021

Intensive blood pressure lowering with nicardipine and outcomes after intracerebral hemorrhage: An individual participant data systematic review.

Int J Stroke 2021 Sep 20:17474930211044635. Epub 2021 Sep 20.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Aims: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined.

Methods: A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4-6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography.

Summary Of Review: Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00-1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02-1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00-1.05 per hour).

Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.
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http://dx.doi.org/10.1177/17474930211044635DOI Listing
September 2021

Antiseizure medications for post-stroke epilepsy: A real-world prospective cohort study.

Brain Behav 2021 09 22;11(9):e2330. Epub 2021 Aug 22.

Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.

Background And Purpose: The management of post-stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older-generation and newer-generation ASM for PSE.

Methods: This prospective multicenter cohort study (PROgnosis of Post-Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non-interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older-generation and newer-generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens.

Results: Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64-81] years; 139 women [37.4%]), 36 were treated with older-generation, 286 with newer-generation, and 50 with mixed-generation ASM. In older- and newer-generation ASM groups (n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow-up (371 [347-420] days). Seizure recurrence was lower in newer-generation, compared with the older-generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27-0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer-generation ASM (HR, 0.34, 95% CI 0.21-0.56, p < .0001).

Conclusions: Newer-generation ASM possess advantages over older-generation ASM for secondary prophylaxis of post-stroke seizures in clinical practice.
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http://dx.doi.org/10.1002/brb3.2330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442594PMC
September 2021

Evaluation of Workflow Delays in Stroke Reperfusion Therapy: A Comparison between the Year-Long Pre-COVID-19 Period and the with-COVID-19 Period.

J Atheroscler Thromb 2021 Aug 13. Epub 2021 Aug 13.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

Aim: We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay between each phase of the with-COVID-19 period.

Methods: Patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis and/or mechanical thrombectomy were selected from our single-center prospective registry. The time to perform reperfusion therapy were compared between patients admitted from March 2019 to February 2020 (pre-COVID-19 group) and those from March 2020 to February 2021 (with-COVID-19 group). Patients in the with-COVID-19 group were further divided into three 4-month-long subgroups (first-phase: March to June 2020; second-phase: July to October 2020; third-phase: November 2020 to February 2021), and the time delay of reperfusion therapy were compared between these subgroups.

Results: Of 1,260 patients with AIS hospitalized in the study period, 265 patients were examined. Compared with the pre-COVID-19 group (133 patients; median age, 79 years), the with-COVID-19 group (132 patients; median age, 79 years) had a longer median door-to-imaging time (25 min vs. 27 min, P=0.04), and a longer door-to-groin puncture time (65 min vs. 72 min, P=0.02). In the three 4-month-long subgroups, the median door-to-needle time (49 min, 43 min, and 38 min, respectively; P=0.04) and door-to-groin puncture time (83 min, 70 min, and 61 min, P<0.01, respectively) decreased significantly during the with-COVID-19 period.

Conclusions: The delay in reperfusion therapy increased during the with-COVID-19 period compared with the pre-COVID-19 period. However, the door-to-needle time and door-to-groin puncture time decreased as time elapsed during the with-COVID-19 period.ClinicalTrials.gov Identifier: NCT02251665.
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http://dx.doi.org/10.5551/jat.63090DOI Listing
August 2021

Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH-2.

J Am Heart Assoc 2021 08 13;10(16):e020364. Epub 2021 Aug 13.

Department of Cerebrovascular Medicine National Cerebral and Cardiovascular Center Suita Japan.

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH-2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post-randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH-2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14-1.50) but not with hematoma expansion, while HR-ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01-1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01-1.3). Every 10-bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR-ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR-ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR-ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01176565.
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http://dx.doi.org/10.1161/JAHA.120.020364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475052PMC
August 2021

p.R4810K (c.14429G > A) Variant Determines Anatomical Variations of the Circle of Willis in Cerebrovascular Disease.

Front Aging Neurosci 2021 15;13:681743. Epub 2021 Jul 15.

Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan.

Introduction: Dysregulation of the RING finger protein 213 gene impairs vascular formation in experimental animal models. In addition, vascular abnormalities in the circle of Willis are associated with cerebrovascular disease. Here, we evaluated the relationship between the East Asian founder variant p.R4810K and consequent anatomical variations in the circle of Willis in cerebrovascular disease.

Patients And Methods: The present study is an observational cross-sectional study. It included patients with acute anterior circulation non-cardioembolic stroke admitted to our institution within 7 days of symptom onset or last-known-well from 2011 to 2019, and those who participated in the National Cerebral and Cardiovascular Center Biobank. We compared anatomical variations of the vessels constituting the circle of Willis between p.R4810K (c.14429G > A) variant carriers and non-carriers using magnetic resonance angiography and assessed the association between the variants and the presence of the vessels constituting the circle of Willis. Patients with moyamoya disease were excluded.

Results: Four hundred eighty-one patients [146 women (30%); median age 70 years; median baseline National Institutes of Health Stroke Scale score 5] were analyzed. The p.R4810K variant carriers ( = 25) were more likely to have both posterior communicating arteries (PComAs) than the variant non-carriers ( = 456) (56% vs. 13%, < 0.01). Furthermore, variant carriers were less likely to have an anterior communicating artery (AComA) than non-carriers (68% vs. 84%, = 0.04). In a multivariate logistic regression analysis, the association of p.R4810K variant carriers with the presence of both PComAs and the absence of AComA remained significant.

Conclusion: Our findings suggest that the p.R4810K variant is an important factor in determining anatomical variations in the circle of Willis.
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http://dx.doi.org/10.3389/fnagi.2021.681743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322682PMC
July 2021

Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others.

Stroke 2021 Nov 27;52(11):3472-3481. Epub 2021 Jul 27.

Department of Neurology and Stroke Center (L.M., A.A.P., F.S., V.L.A., C.T., S.T., B.W., J.F., A.Z., T.D., U.F., N.P., G.M.D.M., H.G., L.H.B., P.A.L., S.T.E.), University Hospital Basel and University of Basel, Switzerland.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.033862DOI Listing
November 2021

Left Ventricular Abnormality and Covert Atrial Fibrillation in Embolic Stroke of Undetermined Source.

J Atheroscler Thromb 2021 Jul 22. Epub 2021 Jul 22.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

Aims: The relationship between left ventricular (LV) function and AF detection in embolic stroke of undetermined source (ESUS) patients with insertable cardiac monitors (ICMs) remains unclear. We investigated the association between LV function and AF detection in patients with ESUS after ICMs implantation.

Methods: We enrolled patients with ESUS who underwent ICMs implantation from September 2016 to September 2020 using a single-center, prospective registry. LV systolic and diastolic functions were assessed on precordial echocardiography by LV fractional shortening (LVFS) and average E/e', respectively. Associations between characteristics of LV function and detection of AF by ICMs were analyzed.

Results: Participants comprised 101 patients (median age, 74 years; male, 62%). During a median follow-up period of 442 days (interquartile range (IQR), 202-770 days), AF was detected in 24 patients (24%). Median duration from ICMs implantation to AF detection was 71 days (IQR, 13-150 days). When LVFS and E/e' were dichotomized by cutoff value, each of low LVFS (<35.5%; adjusted hazard ratio (HR), 4.77; 95% confidence interval (CI), 1.77-12.9) and high E/e' (≥ 8.65; adjusted HR, 4.56; 95%CI, 1.17-17.7) were independently associated with AF detection after adjusting for age and sex. When patients were divided into four groups according to dichotomized LVFS and E/e', the combination of low LVFS and high E/e' was independently associated with AF.

Conclusions: In patients with ESUS after ICMs implantation, the LV characteristics of low LVFS and high E/e' were associated with AF detection.
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http://dx.doi.org/10.5551/jat.62994DOI Listing
July 2021

Cerebral microbleeds development after stroke thrombolysis: A secondary analysis of the THAWS randomized clinical trial.

Int J Stroke 2021 Aug 3:17474930211035023. Epub 2021 Aug 3.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke.

Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days.

Results: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group ( interaction = 0.042).

Conclusion: New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.
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http://dx.doi.org/10.1177/17474930211035023DOI Listing
August 2021

[Cerebrovascular imaging to facilitate stroke reperfusion therapy in Japan].

Rinsho Shinkeigaku 2021 Aug 17;61(8):517-521. Epub 2021 Jul 17.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

Imaging diagnosis is essential to perform appropriate reperfusion therapy for acute ischemic stroke. To equally perform reperfusion therapy all over in Japan, it is important to properly facilitate acute imaging evaluation for stroke suspected patients by medical staff not only in stroke-specialized hospitals but also in non-stroke-specialized hospitals. It is unique that CT and MRI are available in most of Japanese hospitals. Even in non-stroke-specialized hospitals, inpatients may suffer from in-hospital stroke. We review statements and recommendation items for a diagnostic imaging to appropriately perform reperfusion therapy based on major clinical trials, stroke guidelines and the current status of acute stroke imaging in Japan.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001603DOI Listing
August 2021

Impact of Renal Impairment on Intensive Blood-Pressure-Lowering Therapy and Outcomes in Intracerebral Hemorrhage: Results From ATACH-2.

Neurology 2021 08 1;97(9):e913-e921. Epub 2021 Jul 1.

From the Departments of Cerebrovascular Medicine (M.F.-D., M.K., S.Y., K.M., A.I., M.S., K.T.), Data Science (M.F.-D., H.Y., K.O.), and Neurology (M.I.), National Cerebral and Cardiovascular Center; Department of Nephrology (Y.D.), Osaka University Graduate School of Medicine, Suita, Japan; Zeenat Qureshi Stroke Institute (A.I.Q.), St. Cloud, MN; and Department of Neurology (A.I.Q.), University of Missouri, Columbia.

Background And Objective: The clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH.

Methods: We conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis.

Results: Among the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m, respectively. Compared with normal eGFR (≥90 mL/min/1.73 m), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m, respectively ( for interaction = 0.02).

Discussion: Decreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment.

Trial Registration Information: Clinicaltrials.gov identifier: NCT01176565.

Classification Of Evidence: This study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control.
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http://dx.doi.org/10.1212/WNL.0000000000012442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408509PMC
August 2021

Echocardiographic predictors of cardioembolic stroke due to underlying atrial fibrillation: Reliable left atrial remodeling signs in acute stroke.

J Neurol Sci 2021 08 1;427:117514. Epub 2021 Jun 1.

Department of Neurology, National Cerebral and Cardiovascular Center, Japan.

Introduction: Atrial remodeling due to high-burden atrial fibrillation (AF) is associated with cardioembolic stroke (CES). As not all CESs is caused by AF, we analyzed the diagnostic values of each echocardiographic parameter to distinguish likely AF-related CES in acute stroke patients while in non-AF rhythm.

Methods: The data of consecutive patients with acute ischemic stroke in sinus rhythm between 2012 and 2015 were obtained. The echocardiographic parameters of patients with CES due to underlying AF (n = 61) and control patients (n = 319) with either large artery atherosclerosis or small-vessel occlusion were compared using receiver operating characteristic curves and logistic regression analyses. Each parameter was reassessed in acute stroke patients through a validation study using the same database with different periods of generalization.

Results: CES patients with underlying AF showed a significantly larger left atrial volume index (LAVi), higher mitral inflow E wave (E), and lower A wave (A) than the controls. The area under the curve (AUC) (95% confidence interval) for diagnosing CES due to underlying AF was significantly higher for LAVi/A than for LAVi (0.785 versus 0.696, P < 0.01). Among patients aged >60 years, the E/A ratio had the highest AUC (0.857) of the parameters. The cut-off values were ≥ 0.70 (sensitivity, 55.7%; specificity, 90.9%) and ≥ 0.82 (sensitivity, 71.4%; specificity, 84.1%) for LAVi/A and the E/A ratio, respectively, in patients >60 years. The cut-off values of all parameters showed similar trends in a validation study.

Conclusion: LAVi/A is a useful indicator for distinguishing CES patients with underlying AF regardless of age, and the E/A ratio is reliable among patients aged >60 years in evaluation during acute stroke admission.
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http://dx.doi.org/10.1016/j.jns.2021.117514DOI Listing
August 2021

Atherosclerotic Components in Thrombi Retrieved by Thrombectomy for Internal Carotid Artery Occlusion Due to Large Artery Atherosclerosis: A Case Report.

Front Neurol 2021 28;12:670610. Epub 2021 May 28.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

The correlation between the composition of thrombi retrieved by mechanical thrombectomy (MT) and stroke etiology is inconclusive. We describe a case with atherosclerotic components in thrombi retrieved by MT for acute internal carotid artery (ICA) occlusion. A 69-year-old man with acute onset of global aphasia and right hemiplegia was transferred to our institute. His baseline National Institutes of Health Stroke Scale score was 24. Magnetic resonance imaging demonstrated acute ischemic stroke in the left parietal lobe. Magnetic resonance angiography revealed occlusion of the left ICA. MT was attempted for acute left ICA occlusion. The initial angiography showed occlusion of the proximal ICA, while intraprocedural angiography revealed a large thrombus that extended from the cervical ICA to the intracranial ICA. Successful reperfusion was achieved by five passes using stent retrievers and an aspiration catheter. A large volume of red thrombus was retrieved by each pass. The final angiogram showed successful reperfusion with modified Thrombolysis in Cerebral Ischemia grade 2b and severe stenosis in the proximal ICA. Neck magnetic resonance imaging showed severe left ICA stenosis with a vulnerable plaque. Hence, his stroke etiology was determined as large artery atherosclerosis. Histopathological examination of the retrieved thrombi revealed atheromatous components, including cholesterol clefts, foam cells, and a necrotic core. Atherosclerotic components in retrieved thrombi might provide useful clues for diagnosing stroke pathogenesis. Further studies are warranted to clarify the utility of assessing atheromatous components in retrieved thrombi in diagnosing stroke etiology.
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http://dx.doi.org/10.3389/fneur.2021.670610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194065PMC
May 2021

Cardiac and Echocardiographic Markers in Cryptogenic Stroke with Incidental Patent Foramen Ovale.

J Stroke Cerebrovasc Dis 2021 Aug 6;30(8):105892. Epub 2021 Jun 6.

Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan. Electronic address:

Objective: Some cardiac abnormalities could be a substrate for potential embolic source in cryptogenic stroke (CS). We evaluated whether cardiac and echocardiographic markers were associated with CS in patients with incidental patent foramen ovale (PFO) as defined using the Risk of Paradoxical Embolism (RoPE) score.

Materials And Methods: Among 677 patients enrolled in a multicenter observational CS registry, 300 patients (44%) had PFOs detected by transesophageal echocardiography. They were classified into probable PFO-related stroke (RoPE score>6, n = 32) and stroke with incidental PFO (RoPE score≤6, n = 268) groups, and clinical characteristics, laboratory findings, cardiac and echocardiographic markers (i.e. brain natriuretic peptide, left atrial [LA] diameter, ejection fraction, early transmitral flow velocity/early diastolic tissue Doppler imaging velocity [E/e'], LA appendage flow velocity, spontaneous echo contrast, atrial septal aneurysm, substantial PFO, and aortic arch plaques), stroke recurrence, and excellent outcome (modified Rankin scale score <2) at discharge were compared. Risk factors for low RoPE scores were determined using multiple logistic regression analysis.

Results: Higher brain natriuretic peptide levels (p = 0.032), LA enlargement (p < 0.001), higher E/e' (p = 0.001), lower LA appendage flow velocity (p < 0.001), non-substantial PFO (p = 0.021), and aortic arch plaques (p = 0.002) were associated with the low RoPE score group. Patients with high RoPE scores had excellent outcomes (58% versus 78%, p = 0.035). LA enlargement (age- and sex-adjusted odds ratio, 1.15; 95 % confidence interval, 1.00-1.32; p = 0.039) was an independent predictor of low RoPE scores.

Conclusions: Abnormal cardiac substrate could be associated with CS occurrence in a subset of patients with PFO. Patients with CS who had incidental PFO may be at risk of cardioembolism.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105892DOI Listing
August 2021

Blind Exchange With Mini-Pinning Technique Using the Tron Stent Retriever for Middle Cerebral Artery M2 Occlusion Thrombectomy in Acute Ischemic Stroke.

Front Neurol 2021 19;12:667835. Epub 2021 May 19.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

The usefulness of the blind exchange with mini-pinning (BEMP) technique has recently been reported for mechanical thrombectomy in patients with stroke owing to medium vessel occlusion (MeVO). The Tron stent retriever can be delivered and deployed through a 0.0165-inch microcatheter. This retriever has potential as an effective and safe treatment for acute ischemic stroke (AIS) due to occlusion of the M2 segment of the middle cerebral artery (MCA). Here, we report the outcomes of the BEMP technique using Tron stent retrievers for M2 occlusion thrombectomy. Consecutive patients with AIS owing to M2 occlusion who underwent the BEMP technique using 2 × 15-mm or 4 × 20-mm Tron stent retrievers were included. The technique involves deploying a Tron stent retriever through a 0.0165-inch microcatheter, followed by microcatheter removal and blind navigation of a 3MAX or 4MAX aspiration catheter over the bare Tron delivery wire until the aspiration catheter reaches the clot. A Tron stent retriever is inserted into the aspiration catheter like a cork and subsequently pulled as a unit. We assessed procedural outcomes [first-pass expanded thrombolysis in cerebral infarction (eTICI) score 2c/3 and 2b/2c/3], safety outcomes [symptomatic intracranial hemorrhage (sICH)], and clinical outcomes (good outcome rate defined as modified Rankin Scale score 0-2 at 90 days and mortality at 90 days). Eighteen M2 vessels were treated in 15 patients (six female, median age: 80 years, and median National Institutes of Health Stroke Scale score: 18). The BEMP technique was performed successfully in all cases. Whether to use a 3MAX or 4MAX catheter was determined by considering one of the following target vessels: dominant, non-dominant, or co-dominant M2 (3MAX, = 9; 4MAX, = 9). The first-pass eTICI 2c/3 and 2b/2c/3 rates were 47 (7/15) and 60% (9/15), respectively; sICH was not observed. Seven patients (47%) achieved good outcomes, and one patient (7%) died within 90 days. The Tron stent retriever was safely and effectively used in the BEMP technique for acute MCA M2 occlusion and can be combined with a 0.0165-inch microcatheter, which may be useful for treating MeVO, in general.
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http://dx.doi.org/10.3389/fneur.2021.667835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172139PMC
May 2021

Histopathological analysis of retrieved thrombi from patients with acute ischemic stroke with malignant tumors.

J Neurointerv Surg 2021 May 28. Epub 2021 May 28.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Background: The procoagulant state in cancer increases the thrombotic risk, and underlying cancer could affect treatment strategies and outcomes in patients with ischemic stroke. However, the histopathological characteristics of retrieved thrombi in patients with cancer have not been well studied. This study aimed to assess the histopathological difference between thrombi in patients with and without cancer.

Methods: We studied consecutive patients with acute major cerebral artery occlusion who were treated with endovascular therapy between October 2010 and December 2016 in our single-center registry. The retrieved thrombi were histopathologically investigated with hematoxylin and eosin and Masson's trichrome staining. The organization and proportions of erythrocyte and fibrin/platelet components were studied using a lattice composed of 10×10 squares.

Results: Of the 180 patients studied, 17 (8 women, age 76.5±11.5 years) had cancer and 163 (69 women, age 74.1±11.2 years) did not. Those with cancer had a higher proportion of fibrin/platelets (56.6±27.4% vs 40.1±23.9%, p=0.008), a smaller proportion of erythrocytes (42.1±28.3% vs 57.5±25.1%, p=0.019), and higher serum D-dimer levels (5.9±8.2 vs 2.4±4.3 mg/dL, p=0.005) compared with the non-cancer cases. Receiver operating characteristic curve analysis showed the cut-off ratio of fibrin/platelet components related to cancer was 55.7% with a sensitivity of 74.8%, specificity 58.8% and area under the curve (AUC) value of 0.67 (95% CI 0.53 to 0.81), and the cut-off ratio of erythrocyte components was 44.7% with a sensitivity of 71.2%, specificity 58.9% and AUC value of 0.66 (95% CI 0.51 to 0.80).

Conclusions: Thromboemboli of major cerebral arteries in patients with cancer were mainly composed of fibrin/platelet-rich components.
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http://dx.doi.org/10.1136/neurintsurg-2020-017195DOI Listing
May 2021

[A case of lower urinary tract dysfunction due to acute hemorrhage in the lateral medulla oblongata].

Rinsho Shinkeigaku 2021 Jun 20;61(6):392-397. Epub 2021 May 20.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

A 67-year-old woman was transported to our hospital with abnormal sensation in the left temporal region and unstable gait. She had a history of increased urinary frequency without medication. Head CT showed intracerebral hemorrhage in the left dorsal medulla oblongata. On the day of admission, she became aware of difficulty in urination and the volume of residual urine was 100 ml. Cystometry revealed normal voiding sensation and relatively lower intravesical pressure during voiding effort. The maximum cystometric capacity was also mildly decreased. The lower urinary tract dysfunction in this patient was diagnosed as detrusor underactivity. An α1-adrenoreceptor antagonist, urapidil, was started and her residual urine was decreased. Urapidil was terminated on the 14th day of onset, but her lower urinary tract symptoms did not recur thereafter. The brain MR imaging with magnetization-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) clearly demonstrated a small hematoma in the dorsolateral medulla with surrounding edema. The perihematomal edema initially spread to involve the left lateral tegmentum of the medulla, but it almost disappeared in the follow-up MP2RAGE imaging on the 21st day. At the medulla level, the descending tract from the pontine micturition center is assumed to lie lateral tegmentum. The lower urinary tract dysfunction in this case was presumed to be caused by damage to the descending tract from the pontine micturition center, and the disappearance of perihematomal edema and the compensation by the contralateral tract would have contributed to the early improvement of symptoms.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001580DOI Listing
June 2021

Different aspects of early and late development of atrial fibrillation during hospitalization in cryptogenic stroke.

Sci Rep 2021 03 29;11(1):7127. Epub 2021 Mar 29.

Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.

The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been studied. CHALLENGE ESUS/CS is a multicenter registry of cryptogenic stroke patients undergoing transesophageal echocardiography. Twelve-lead electrocardiogram, continuous cardiac monitoring, and 24-h Holter electrocardiogram were all used for the detection of AF. Early and late detection of AF was determined with an allocation ratio of 1:1 among patients with AF. A total of 677 patients (68.7 ± 12.8 years; 455 men) were enrolled, and 64 patients developed AF during hospitalization. Four days after admission was identified as the approximate median day to classify early and late phases to detect AF: ≤ 4 days, 37 patients; > 4 days, 27 patients. Multiple logistic regression analysis showed that spontaneous echo contrast (SEC) (OR 5.91; 95% CI 2.19-15.97; p < 0.001) was associated with AF ≤ 4 days, whereas a large infarction > 3 cm in diameter (OR 3.28; 95% CI 1.35-7.97; p = 0.009) was associated with AF > 4 days. SEC and large infarctions were important predictors of in-hospital AF detection, particularly in the early and late stages, respectively; thus, they could serve as indications for recommending ICM.
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http://dx.doi.org/10.1038/s41598-021-86620-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007744PMC
March 2021

Stroke Care during the COVID-19 Pandemic: International Expert Panel Review.

Cerebrovasc Dis 2021 23;50(3):245-261. Epub 2021 Mar 23.

Department of Diagnostic and Interventional Neuroradiology, Klinikum Bremen-Mitte, Germany.

Background: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions.

Summary: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.
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http://dx.doi.org/10.1159/000514155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089455PMC
June 2021

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Lancet Neurol 2021 04 17;20(4):294-303. Epub 2021 Mar 17.

Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk.

Methods: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602.

Findings: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models.

Interpretation: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted.

Funding: British Heart Foundation and Stroke Association.
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http://dx.doi.org/10.1016/S1474-4422(21)00024-7DOI Listing
April 2021

Macrosquare-wave Jerks Subsiding after Hydrocephalus Treatment in a Thalamic Hemorrhage Patient.

Intern Med 2021 Aug 1;60(15):2487-2490. Epub 2021 Mar 1.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Japan.

A 54-year-old man suddenly developed impaired consciousness and left hemiplegia due to a right thalamic hematoma. Emergent ventricular drainage for acute hydrocephalus improved the level of consciousness, but macrosquare-wave jerks (MSWJ) consisting of a right-ward intrusive saccade and corrective saccade appeared. The MSWJ disappeared on day 2 when follow-up CT revealed improvement of hydrocephalus. However, on day 36, after ventricular drainage was clamped, the MSWJ reappeared. After ventriculoperitoneal shunt, MSWJ again subsided. In this patient, hydrocephalus may have stretched the superior colliculus, thereby decreasing activity of the fixation neurons and then omnipause neurons, and eventually resulting in the reversible MSWJ.
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http://dx.doi.org/10.2169/internalmedicine.6293-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381181PMC
August 2021
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