Journal: J Stroke

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Abstract

Initiation of Guideline-Matched Oral Anticoagulant in Atrial Fibrillation-Related Stroke.

Eun MY, Kim JY, Hwang YH, Park MS, ... Kim GM, Seo WK
Background:
and purpose
To evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF).
Methods
Patients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered.
Results
Among 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups.
Conclusions
ESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.



J Stroke: 30 Dec 2020; 23:113-123
Eun MY, Kim JY, Hwang YH, Park MS, ... Kim GM, Seo WK
J Stroke: 30 Dec 2020; 23:113-123 | PMID: 33600708
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Abstract

General Anesthesia versus Conscious Sedation in Mechanical Thrombectomy.

Feil K, Herzberg M, Dorn F, Tiedt S, ... Kellert L, GSR Investigators
Background:
and purpose
Anesthesia regimen in patients undergoing mechanical thrombectomy (MT) is still an unresolved issue.
Methods
We compared the effect of anesthesia regimen using data from the German Stroke Registry-Endovascular Treatment (GSR-ET) between June 2015 and December 2019. Degree of disability was rated by the modified Rankin Scale (mRS), and good outcome was defined as mRS 0-2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction scale was 2b-3.
Results
Out of 6,635 patients, 67.1% (n=4,453) patients underwent general anesthesia (GA), 24.9% (n=1,650) conscious sedation (CS), and 3.3% (n=219) conversion from CS to GA. Rate of successful reperfusion was similar across all three groups (83.0% vs. 84.2% vs. 82.6%, P=0.149). Compared to the CA-group, the GA-group had a delay from admission to groin (71.0 minutes vs. 61.0 minutes, P<0.001), but a comparable interval from groin to flow restoration (41.0 minutes vs. 39.0 minutes). The CS-group had the lowest rate of periprocedural complications (15.0% vs. 21.0% vs. 28.3%, P<0.001). The CS-group was more likely to have a good outcome at follow-up (42.1% vs. 34.2% vs. 33.5%, P<0.001) and a lower mortality rate (23.4% vs. 34.2% vs. 26.0%, P<0.001). In multivariable analysis, GA was associated with reduced achievement of good functional outcome (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71 to 0.94; P=0.004) and increased mortality (OR, 1.42; 95% CI, 1.23 to 1.64; P<0.001). Subgroup analysis for anterior circulation strokes (n=5,808) showed comparable results.
Conclusions
We provide further evidence that CS during MT has advantages over GA in terms of complications, time intervals, and functional outcome.



J Stroke: 30 Dec 2020; 23:103-112
Feil K, Herzberg M, Dorn F, Tiedt S, ... Kellert L, GSR Investigators
J Stroke: 30 Dec 2020; 23:103-112 | PMID: 33600707
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Abstract

Safety and Angiographic Efficacy of Intra-Arterial Fibrinolytics as Adjunct to Mechanical Thrombectomy: Results from the INFINITY Registry.

Kaesmacher J, Abdullayev N, Maamari B, Dobrocky T, ... Gralla J, Fischer U
Background:
and purpose
Data on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse.
Methods
INtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months.
Results
Of 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9).
Conclusions
Administration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.



J Stroke: 30 Dec 2020; 23:91-102
Kaesmacher J, Abdullayev N, Maamari B, Dobrocky T, ... Gralla J, Fischer U
J Stroke: 30 Dec 2020; 23:91-102 | PMID: 33600706
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Abstract

Dual-Energy CT Angiography Improves Accuracy of Spot Sign for Predicting Hematoma Expansion in Intracerebral Hemorrhage.

Peeters MTJ, Kort KJD, Houben R, Henneman WJP, ... Staals J, Postma AA
Background:
and purpose
Spot sign (SS) on computed tomography angiography (CTA) is associated with hematoma expansion (HE) and poor outcome after intracerebral hemorrhage (ICH). However, its predictive performance varies across studies, possibly because differentiating hyperdense hemorrhage from contrast media is difficult. We investigated whether dual-energy-CTA (DE-CTA), which can separate hemorrhage from iodinated contrast, improves the diagnostic accuracy of SS for predicting HE.
Methods
Primary ICH patients undergoing DE-CTA (both arterial as well as delayed venous phase) and follow-up computed tomography were prospectively included between 2014 and 2019. SS was assessed on both arterial and delayed phase images of the different DE-CTA datasets, i.e., conventional-like mixed images, iodine images, and fusion images. Diagnostic accuracy of SS for prediction of HE was determined on all datasets. The association between SS and HE, and between SS and poor outcome (modified Rankin Scale at 3 months ≥3) was assessed with multivariable logistic regression, using the dataset with highest diagnostic accuracy.
Results
Of 139 included patients, 47 showed HE (33.8%). Sensitivity of SS for HE was 32% (accuracy 0.72) on conventional-like mixed arterial images which increased to 76% (accuracy 0.80) on delayed fusion images. Presence of SS on delayed fusion images was independently associated with HE (odds ratio [OR], 17.5; 95% confidence interval [CI], 6.14 to 49.82) and poor outcome (OR, 3.84; 95% CI, 1.16 to 12.73).
Conclusions
Presence of SS on DE-CTA, in particular on delayed phase fusion images, demonstrates higher diagnostic performance in predicting HE compared to conventional-like mixed imaging, and it is associated with poor outcome.



J Stroke: 30 Dec 2020; 23:82-90
Peeters MTJ, Kort KJD, Houben R, Henneman WJP, ... Staals J, Postma AA
J Stroke: 30 Dec 2020; 23:82-90 | PMID: 33600705
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Abstract

Delayed Lesions on Diffusion-Weighted Imaging in Initially Lesion-Negative Stroke Patients.

Kim K, Kim BJ, Huh J, Yang SK, ... Kim JH, Bae HJ
Background:
and purpose
Lesions on diffusion-weighted imaging (DWI) occasionally appear on follow-up magnetic resonance imaging (MRI) among initially DWI-negative but clinically suspicious stroke patients. We established the prevalence of positive conversion in DWI-negative stroke and determined the clinical factors associated with it.
Methods
This retrospective, observational, single-center study included 5,271 patients hospitalized due to stroke/transient ischemic attack (TIA) in a single university hospital during 2010 to 2017. Patients without initial DWI lesions underwent follow-up DWI imaging as a routine practice. Adjusted hazard ratios (aHRs) for recurrent stroke risk according to positive conversion were determined using Cox proportional hazard regression. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for positive conversion among initially DWI-negative patients were estimated.
Results
In total, 694 (13.2%) patients (mean±standard deviation age, 62.9±13.7 years; male, 404 [58.2%]) were initially DWI-negative. Among them, 22.5% had positive-conversion on follow-up DWI. Positive conversion was associated with a higher risk of recurrent stroke (aHR, 3.12; 95% CI, 1.56 to 6.26). Early neurologic deterioration (aOR, 15.1; 95% CI, 5.71 to 47.66), atrial fibrillation (aOR, 6.17; 95% CI, 3.23 to 12.01), smoking (aOR, 3.76; 95% CI, 2.19 to 6.63), pre-stroke dependency (aOR, 1.62; 95% CI, 1.15 to 2.27), objective hemiparesis (aOR, 4.39; 95% CI, 1.90 to 10.32), longer symptom duration (aOR, 2.17; 95% CI, 1.57 to 3.08), high cholesterol (aOR, 4.70; 95% CI, 1.78 to 12.77), National Institutes of Health Stroke Scale score (aOR, 1.44; 95% CI, 1.08 to 1.91), and high systolic blood pressure (aOR, 1.01; 95% CI, 1.00 to 1.02) were associated with a higher incidence of lesions with delayed appearance. Regarding the location of lesions on follow-up DWI, 34.6% and 21.2% were in the cortex and brainstem, respectively.
Conclusions
In DWI-negative stroke/TIA, positive conversion is associated with a higher risk of recurrent stroke. DWI-negative stroke with factors related to positive conversion may require follow-up MRI for a definitive diagnosis.



J Stroke: 30 Dec 2020; 23:69-81
Kim K, Kim BJ, Huh J, Yang SK, ... Kim JH, Bae HJ
J Stroke: 30 Dec 2020; 23:69-81 | PMID: 33600704
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Abstract

Perfusion and Diffusion Variables Predict Early Neurological Deterioration in Minor Stroke and Large Vessel Occlusion.

Gwak DS, Kwon JA, Shim DH, Kim YW, Hwang YH
Background:
and purpose
Patients with acute large vessel occlusion (LVO) presenting with mild stroke symptoms are at risk of early neurological deterioration (END). This study aimed to identify the optimal imaging variables for predicting END in this population.
Methods
We retrospectively analyzed 94 patients from the prospectively maintained institutional stroke registry admitted between January 2011 and May 2019, presenting within 24 hours after onset, with a baseline National Institutes of Health Stroke Scale score ≤5 and anterior circulation LVO. Patients who underwent endovascular therapy before END were excluded. Volumes of Tmax delay (at >2, >4, >6, >8, and >10 seconds), mismatch (Tmax >4 seconds - diffusion-weighted imaging [DWI] and Tmax >6 seconds - DWI), and mild hypoperfusion lesions (Tmax 2-6 and 4-6 seconds) were measured. The association of each variable with END was examined using receiver operating characteristic curves. The variables with best predictive performance were dichotomized at the cutoff point maximizing Youden\'s index and subsequently analyzed using multivariable logistic regression.
Results
END occurred in 39.4% of the participants. The optimal variables were identified as Tmax >6 seconds, Tmax >6 seconds - DWI, and Tmax 4-6 seconds with cut-off points of 53.73, 32.77, and 55.20 mL, respectively. These variables were independently associated with END (adjusted odds ratio [aOR], 12.78 [95% confidence interval (CI), 3.36 to 48.65]; aOR, 5.73 [95% CI, 2.04 to 16.08]; and aOR, 9.13 [95% CI, 2.76 to 30.17], respectively).
Conclusions
Tmax >6 seconds, Tmax >6 seconds - DWI, and Tmax 4-6 seconds could identify patients at high risk of END following minor stroke due to LVO.



J Stroke: 30 Dec 2020; 23:61-68
Gwak DS, Kwon JA, Shim DH, Kim YW, Hwang YH
J Stroke: 30 Dec 2020; 23:61-68 | PMID: 33600703
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Abstract

Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention.

Pan Y, Li Z, Li J, Jin A, ... Wang Y, Wang Y
Background:
and purpose
Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk.
Methods
Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months.
Results
Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk.
Conclusions
There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.



J Stroke: 30 Dec 2020; 23:51-60
Pan Y, Li Z, Li J, Jin A, ... Wang Y, Wang Y
J Stroke: 30 Dec 2020; 23:51-60 | PMID: 33600702
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Abstract

Tobacco Use: A Major Risk Factor of Intracerebral Hemorrhage.

Cho S, Rehni AK, Dave KR
Spontaneous intracerebral hemorrhage (sICH) is one of the deadliest subtypes of stroke, and no treatment is currently available. One of the major risk factors is tobacco use. In this article, we review literature on how tobacco use affects the risk of sICH and also summarize the known effects of tobacco use on outcomes following sICH. Several studies demonstrate that the risk of sICH is higher in current cigarette smokers compared to non-smokers. The literature also establishes that cigarette smoking not only increases the risk of sICH but also increases hematoma growth, results in worse outcomes, and increases the risk of death from sICH. This review also discusses potential mechanisms activated by tobacco use which result in an increase in risk and severity of sICH. Exploring the underlying mechanisms may help alleviate the risk of sICH in tobacco users as well as may help better manage tobacco user sICH patients.



J Stroke: 30 Dec 2020; 23:37-50
Cho S, Rehni AK, Dave KR
J Stroke: 30 Dec 2020; 23:37-50 | PMID: 33600701
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Abstract

Development and Testing of Thrombolytics in Stroke.

Nikitin D, Choi S, Mican J, Toul M, ... Mikulik R, Kim DE
Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies in vitro and in vivo.



J Stroke: 30 Dec 2020; 23:12-36
Nikitin D, Choi S, Mican J, Toul M, ... Mikulik R, Kim DE
J Stroke: 30 Dec 2020; 23:12-36 | PMID: 33600700
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Abstract

Role of Blood Pressure Management in Stroke Prevention: A Systematic Review and Network Meta-Analysis of 93 Randomized Controlled Trials.

Zhong XL, Dong Y, Xu W, Huang YY, ... Dong Q, Yu JT
Background:
and purpose
The present study aimed to compare the efficacy and tolerability of different blood pressure (BP)-lowering strategies.
Methods
Randomized controlled trials that compared various antihypertensive treatments and stroke outcomes were included. Eligible trials were categorized into three scenarios: single or combination antihypertensive agents against placebos; single or combination agents against other agents; and different BP-lowering targets. The primary efficacy outcome was the risk reduction pertaining to strokes. The tolerability outcome was the withdrawal of drugs, owing to drug-related side effects (PROSPERO registration number CRD42018118454 [20/12/2018]).
Results
The present study included 93 trials (average follow-up duration, 3.3 years). In the pairwise analysis, angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) were inferior to calcium channel blockers (CCBs) (odds ratio [OR], 1.123; 95% confidence interval [CI], 1.008 to 1.252) (OR, 1.261; 95% CI, 1.116 to 1.425) for stroke prevention, BB was inferior to angiotensin II receptor blockers (ARB) (OR, 1.361; 95% CI, 1.142 to 1.622), and diuretics were superior to ACEi (OR, 0.871; 95% CI, 0.771 to 0.984). The combination of ACEi+CCB was superior to ACEi+diuretic (OR, 0.892; 95% CI, 0.823 to 0.966). The network meta-analysis confirmed that diuretics were superior to BB (OR, 1.34; 95% CI, 1.11 to 1.58), ACEi+diuretic (OR, 1.47; 95% CI, 1.02 to 2.08), BB+CCB (OR, 2.05; 95% CI, 1.05 to 3.79), and renin inhibitors (OR, 1.87; 95% CI, 1.25 to 2.75) for stroke prevention. Regarding the tolerability profile, the pairwise analysis revealed that ACEi was inferior to CCB and less tolerable, compared to the other treatments.
Conclusions
Monotherapy using diuretics, CCB, or ARB, and their combinations could be employed as first-line treatments for stroke prevention in terms of efficacy and tolerability.



J Stroke: 30 Dec 2020; 23:1-11
Zhong XL, Dong Y, Xu W, Huang YY, ... Dong Q, Yu JT
J Stroke: 30 Dec 2020; 23:1-11 | PMID: 33600699
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Impact:

This program is still in alpha version.