Journal: J Stroke

Sorted by: date / impact
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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Impact:
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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Impact:
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:
Abstract

Nurse Led Smartphone Electrographic Monitoring for Atrial Fibrillation after Ischemic Stroke: SPOT-AF.

Yan B, Tu H, Lam C, Swift C, ... Liu X, Freedman B
Background:
and purpose
Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate.
Methods
We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection.
Results
One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (P<0.001). Median duration from stroke onset to AF detection for iECG was 3 days (interquartile range [IQR], 2 to 6) compared with 7 days (IQR, 6 to 10) for Holter recordings (P=0.02). Of 25 patients with AF detected by iECG, 11 were commenced on oral anticoagulant, compared to 5/8 for Holter. AF was detected in 8.8% (69/785 patients) who underwent iECG recordings only (P=0.8 vs. those who had both iECG and 24-hour Holter).
Conclusions
Nurse-led in-hospital iECG surveillance after stroke is feasible and effective and detects more PAF earlier and more frequently than routine 24-hour Holter recordings. Screening with iECG could be incorporated into routine post-stroke nursing observations to increase diagnosis of PAF, and facilitate institution of guideline-recommended anticoagulation.



J Stroke: 30 Aug 2020; 22:387-395
Yan B, Tu H, Lam C, Swift C, ... Liu X, Freedman B
J Stroke: 30 Aug 2020; 22:387-395 | PMID: 33053954
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Abstract

Decision-Making Visual Aids for Late, Imaging-Guided Endovascular Thrombectomy for Acute Ischemic Stroke.

Moshayedi P, Liebeskind DS, Jadhav A, Jahan R, ... Nogueira RG, Saver JL
Background:
and purpose
Speedy decision-making is important for optimal outcomes from endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Figural decision aids facilitate rapid review of treatment benefits and harms, but have not yet been developed for late-presenting patients selected for EVT based on multimodal computed tomography or magnetic resonance imaging.
Methods
For combined pooled study-level randomized trial (DAWN and DEFUSE 3) data, as well as each trial singly, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of EVT for patients with AIS and large vessel occlusion using automated (algorithmic) and expert-guided joint outcome table specification.
Results
Among imaging-selected patients 6 to 24 hours from last known well, for the full 7-category modified Rankin Scale (mRS), EVT had number needed to treat to benefit 1.9 (interquartile range [IQR], 1.9 to 2.1) and number needed to harm 40.0 (IQR, 29.2 to 58.3). Visual displays of treatment effects among 100 patients showed that, with EVT: 52 patients have better disability outcome, including 32 more achieving functional independence (mRS 0 to 2); three patients have worse disability outcome, including one more experiencing severe disability or death (mRS 5 to 6), mediated by symptomatic intracranial hemorrhage and infarct in new territory. Similar features were present in person-icon figures based on a 6-level mRS (levels 5 and 6 combined) rather than 7-level mRS, and based on the DAWN trial alone and DEFUSE 3 trial alone.
Conclusions
Personograph visual decision aids are now available to rapidly educate patients, family, and healthcare providers regarding benefits and risks of EVT for late-presenting, imaging-selected AIS patients.



J Stroke: 30 Aug 2020; 22:377-386
Moshayedi P, Liebeskind DS, Jadhav A, Jahan R, ... Nogueira RG, Saver JL
J Stroke: 30 Aug 2020; 22:377-386 | PMID: 33053953
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Impact:
Abstract

Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease.

Peters N, van Leijsen E, Tuladhar AM, Barro C, ... Duering M, de Leeuw FE
Background:
and purpose
Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) cross-sectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally.
Methods
From 503 subjects with SVD, baseline and follow-up magnetic resonance imaging (MRI) was available for 264 participants (follow-up 8.7±0.2 years). Baseline serum-NfL was measured by an ultrasensitive single-molecule-assay. SVD-MRI-markers including white matter hyperintensity (WMH)-volume, mean diffusivity (MD), lacunes, and microbleeds were assessed at both timepoints. Cognitive testing was performed in 336 participants, including SVD-related domains as well as global cognition and memory. Associations with NfL were assessed using linear regression analyses and analysis of covariance (ANCOVA).
Results
Serum-NfL was associated with baseline WMH-volume, MD-values and presence of lacunes and microbleeds. SVD-related MRI- and cognitive measures showed progression during follow-up. NfL-levels were associated with future MRI-markers of SVD, including WMH, MD and lacunes. For the latter, this association was independent of baseline lacunes. Furthermore, NfL was associated with incident lacunes during follow-up (P=0.040). NfL-levels were associated with future SVD-related cognitive impairment (processing speed: β=-0.159; 95% confidence interval [CI], -0.242 to -0.068; P=0.001; executive function β=-0.095; 95% CI, -0.170 to -0.007; P=0.033), adjusted for age, sex, education, and depression. Dementia-risk increased with higher NfL-levels (hazard ratio, 5.0; 95% CI, 2.6 to 9.4; P<0.001), however not after adjusting for age.
Conclusions
Longitudinally, serum-NfL is associated with markers of SVD, especially with incident lacunes, and future cognitive impairment affecting various domains. NfL may potentially serve as an additional marker for disease monitoring and outcome in SVD, potentially capturing both vascular and neurodegenerative processes in the elderly.



J Stroke: 30 Aug 2020; 22:369-376
Peters N, van Leijsen E, Tuladhar AM, Barro C, ... Duering M, de Leeuw FE
J Stroke: 30 Aug 2020; 22:369-376 | PMID: 33053952
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Impact:
Abstract

Liver Enzymes and Risk of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study.

Ruban A, Daya N, Schneider ALC, Gottesman R, ... Lazo M, Koton S
Background:
and purpose
Liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [GGT]) are glutamate-regulatory enzymes, and higher glutamate levels correlated with worse prognosis of patients with neurotrauma. However, less is known about the association between liver enzymes and incidence of stroke. We evaluated the association between serum levels of AST, ALT, and GGT and incidence of stroke in the Atherosclerosis Risk in Communities (ARIC) study cohort from 1990 to 1992 through December 31, 2016.
Methods
We included 12,588 ARIC participants without prevalent stroke and with data on liver enzymes ALT, AST, and GGT at baseline. We used multivariable Cox regression models to examine the associations between liver enzymes levels at baseline and stroke risk (overall, ischemic stroke, and intracerebral hemorrhage [ICH]) through December 31, 2016, adjusting for potential confounders.
Results
During a median follow-up time of 24.2 years, we observed 1,012 incident strokes (922ischemic strokes and 90 ICH). In age, sex, and race-center adjusted models, the hazard ratios (HRs; 95% confidence intervals [CIs]) for the highest compared to lowest GGT quartile were 1.94 (95% CI, 1.64 to 2.30) for all incident stroke and 2.01 (95% CI, 1.68 to 2.41) for ischemic stroke, with the results supporting a dose-response association (P for linear trend <0.001). Levels of AST were associated with increased risk of ICH, but the association was significant only when comparing the third quartile with the lowest quartile (adjusted HR, 1.82; 95% CI, 1.06 to 3.13).
Conclusions
Elevated levels of GGT (within normal levels), independent of liver disease, are associated with higher risk of incident stroke overall and ischemic stroke, but not ICH.



J Stroke: 30 Aug 2020; 22:357-368
Ruban A, Daya N, Schneider ALC, Gottesman R, ... Lazo M, Koton S
J Stroke: 30 Aug 2020; 22:357-368 | PMID: 33053951
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Impact:
Abstract

Geographic Variations of Stroke Incidence in Chinese Communities: An 18-Year Prospective Cohort Study from 1997 to 2015.

Xia F, Yu X, Li Y, Chen Y, ... You C, Hu X
Background:
and purpose
As a leading cause of disability and death in China, stroke as well as its epidemiologic features have gained increasing attention. Prior studies, however, have overgeneralized the north-to-south gradient in China. Whether the differences exist across urban and rural areas remains unexplored. This study therefore aims to investigate the north-to-south gradient in stroke incidence across urban and rural China.
Methods
The present prospective cohort study analyzed data from the China Health and Nutrition Survey 1997 to 2015. By including 16,917 individuals from diverse social contexts, we calculated the age-standardized incidence of stroke across regions and the age-adjusted risk ratio (aRR). Cox proportional hazards models with time-varying covariates were employed to analyze variations in incident stroke.
Results
During the follow-up, age-standardized incidence of stroke ranged from 4.17 per 1,000 person-years (95% confidence interval [CI], 3.38 to 4.96) in the north region to 1.95 (95% CI, 1.60 to 2.30) in the south region (aRR, 2.04; 95% CI, 1.58 to 2.64; P<0.001). The north-to-south gradient of stroke incidence was observed only in rural areas, but not in urban areas. Hierarchical modelling analyses further indicated that the regional differences could be mostly explained by the disparities in the prevalence of hypertension.
Conclusions
The present study extends the current evidence on the north-to-south gradient by demonstrating that the difference varied across urban and rural China. Our findings highlight the importance of hypertension management as the measure for alleviating regional differences in stroke incidence.



J Stroke: 30 Aug 2020; 22:345-356
Xia F, Yu X, Li Y, Chen Y, ... You C, Hu X
J Stroke: 30 Aug 2020; 22:345-356 | PMID: 33053950
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Impact:
Abstract

Long-Term Survival after Stroke in 1.4 Million Japanese Population: Shiga Stroke and Heart Attack Registry.

Takashima N, Arima H, Kita Y, Fujii T, ... Miura K, Nozaki K
Background:
and purpose
Although numerous measures for stroke exist, stroke remains one of the leading causes of death in Japan. In this study, we aimed to determine the long-term survival rate after first-ever stroke using data from a large-scale population-based stroke registry study in Japan.
Methods
Part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based registry study of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in Japan. A total 1,880 patients with non-fatal first-ever stroke (among 29-day survivors after stroke onset) registered in 2011 were followed up until December 2016. Five-year cumulative survival rates were estimated using the Kaplan-Meier method, according to subtype of the index stroke. Cox proportional hazards models were used to assess predictors of subsequent all-cause death.
Results
During an average 4.3-year follow-up period, 677 patients died. The 5-year cumulative survival rate after non-fatal first-ever stroke was 65.9%. Heterogeneity was present in 5-year cumulative survival according to stroke subtype: lacunar infarction, 75.1%; large-artery infarction, 61.5%; cardioembolic infarction, 44.9%; intracerebral hemorrhage, 69.1%; and subarachnoid hemorrhage, 77.9%. Age, male sex, Japan Coma Scale score on admission, and modified Rankin Scale score before stroke onset were associated with increased mortality during the chronic phase of ischemic and hemorrhagic stroke.
Conclusions
In this study conducted in a real-world setting of Japan, the 5-year survival rate after non-fatal first-ever stroke remained low, particularly among patients with cardioembolic infarction and large-artery infarction in the present population-based stroke registry.



J Stroke: 30 Aug 2020; 22:336-344
Takashima N, Arima H, Kita Y, Fujii T, ... Miura K, Nozaki K
J Stroke: 30 Aug 2020; 22:336-344 | PMID: 33053949
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Abstract

Stroke in Coronavirus Disease 2019: A Systematic Review.

Bhatia R, Pedapati R, Komakula S, Srivastava MVP, Vishnubhatla S, Khurana D
Background:
and purpose
Various neurological findings including stroke in patients with coronavirus disease 2019 (COVID-19) have been described, although no clarity exists regarding the nature and pattern of this association. This systematic review aims to report the characteristics of stroke in patients with COVID-19.
Methods
Three authors independently searched Web of Science, Embase, Scopus, and PubMed starting from inception up to May 22, 2020. The data for individual patients was extracted where available from published reports including clinical and laboratory parameters and analysed for any significant associations between variables.
Results
We identified 30 relevant articles involving 115 patients with acute or subacute stroke with COVID-19. The mean±standard deviation age was 62.5±14.5 years. Stroke was ischemic in majority of the patients (101 [87.8%]). Hypertension (42 [42%]), dyslipidaemia (24 [26.1%]), and diabetes (23 [23.2%]) were the major vascular risk factors. Most of the patients (80 [85.1%]) had COVID-19 symptoms at the time of stroke with a median interval of 10 days to stroke from the diagnosis of COVID-19. Three-fourths (86 [74.8%]) of the patients were critically ill which frequently delayed the diagnosis of stroke. High levels of D-dimer, and ferritin were observed in these patients. Patients with COVID-19 and stroke had a high mortality (47.9%). Factors associated with mortality were intensive care unit admission, having two or more vascular risk factors, particularly smoking and high levels of D-dimer, C-reactive protein, and lactate dehydrogenase.
Conclusions
The association between stroke and COVID-19 is probably multifactorial including an amalgamation of traditional vascular risk factors, proinflammatory and a prothrombotic state. Prospectively collected data is required in the future to confirm this hypothesis.



J Stroke: 30 Aug 2020; 22:324-335
Bhatia R, Pedapati R, Komakula S, Srivastava MVP, Vishnubhatla S, Khurana D
J Stroke: 30 Aug 2020; 22:324-335 | PMID: 33053948
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Impact:
Abstract

Mothership versus Drip-and-Ship Model for Mechanical Thrombectomy in Acute Stroke: A Systematic Review and Meta-Analysis for Clinical and Radiological Outcomes.

Romoli M, Paciaroni M, Tsivgoulis G, Agostoni EC, Vidale S
Background:
and purpose
Substantial uncertainty exists on the benefit of organizational paradigms in stroke networks. Here we systematically reviewed and meta-analyzed data from studies comparing functional outcome between the mothership (MS) and the drip and ship (DS) models.
Methods
The meta-analysis protocol was registered international prospective register of systematic reviews (PROSPERO) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, and Cochrane Central databases were searched for randomized-controlled clinical trials (RCTs), retrospective and prospective studies comparing MS versus DS. Primary endpoints were functional independence at 90 days (modified Rankin Scale <3) and successful recanalization (Thrombolysis in Cerebral Infarction Scale [TICI] >2a); secondary endpoints were 3-month mortality and symptomatic intracranial haemorrhage (sICH). Odds ratios for endpoints were pooled using the random effects model and were compared between the two organizational models.
Results
Overall, 18 studies (n=7,017) were included in quantitative synthesis. MS paradigm was superior to DS model for functional independence (odds ratio, 1.34; 95% confidence interval, 1.16 to 1.55; I2=30%). Meta-regression analysis revealed association between onset-to-needle time and good functional outcome, with longer onset-to-needle time being detrimental. Similar rates of recanalization, sICH and mortality at 90 days were documented between MS and DS.
Conclusions
Patients with acute ischemic stroke eligible for reperfusion strategies might benefit more from MS paradigm as compared to DS. RCTs are needed to further refine best management taking into account logistics, facilities and resources.



J Stroke: 30 Aug 2020; 22:317-323
Romoli M, Paciaroni M, Tsivgoulis G, Agostoni EC, Vidale S
J Stroke: 30 Aug 2020; 22:317-323 | PMID: 33053947
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Impact:
Abstract

Anticoagulation in Patients with End-Stage Renal Disease and Atrial Fibrillation: Confusion, Concerns and Consequences.

Goel N, Jain D, Haddad DB, Shanbhogue D
End-stage renal disease (ESRD) patients have a higher prevalence of diabetes mellitus, hypertension, congestive heart failure and advanced age, along with an increased incidence of non-valvular atrial fibrillation (AF), thereby increasing the risk for cerebrovascular accidents. Systemic anticoagulation is therefore recommended in patients with ESRD with AF to reduce the risk and complications from thromboembolism. Paradoxically, these patients are at an increased risk of bleeding due to great degree of platelet dysfunction and impaired interaction between platelet and endothelium. Currently, CHA2DS2-VASc and Hypertension, Abnormal liver/kidney function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol (HAS-BLED) are the recommended models for stroke risk stratification and bleeding risk assessment in patients with AF. There is conflicting data regarding benefits and risks of medications such as antiplatelet agents, warfarin and direct oral anticoagulants in ESRD patients with AF. Moreover, there is no randomized controlled trial data to guide the clinical decision making. Hence, a multi-disciplinary approach with annual re-evaluation of treatment goals and risk-benefit assessment has been recommended. In this article, we review the current recommendations with risks and benefits of anticoagulation in patients with ESRD with AF.



J Stroke: 30 Aug 2020; 22:306-316
Goel N, Jain D, Haddad DB, Shanbhogue D
J Stroke: 30 Aug 2020; 22:306-316 | PMID: 33053946
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Impact:
Abstract

Optimizing Stem Cell Therapy after Ischemic Brain Injury.

Zhang S, Lachance BB, Moiz B, Jia X
Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and in vivo potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.



J Stroke: 30 Aug 2020; 22:286-305
Zhang S, Lachance BB, Moiz B, Jia X
J Stroke: 30 Aug 2020; 22:286-305 | PMID: 33053945
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Impact:
Abstract

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis.

Yoo J, Choi JK, Kim YD, Nam HS, ... Lee HS, Heo JH
Background:
and purpose
Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known.
Methods
We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up.
Results
Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P<0.001). In a multivariate Cox proportional hazard analysis, the presence of NBTE was independently associated with composite outcomes of mortality and stroke events (hazard ratio, 1.941; 95% confidence interval, 1.052 to 3.690).
Conclusions
NBTE should be suspected as a potential cause of stroke in patients with metastatic cancer. Patients with NBTE have a high risk of recurrent stroke and mortality. Future studies are necessary to determine strategies to reduce stroke recurrence in patients with NBTE.



J Stroke: 29 Apr 2020; 22:245-253
Yoo J, Choi JK, Kim YD, Nam HS, ... Lee HS, Heo JH
J Stroke: 29 Apr 2020; 22:245-253 | PMID: 32635688
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Impact:
Abstract

Endovascular Treatment in Patients with Cerebral Artery Occlusion of Three Different Etiologies.

Lee D, Lee DH, Suh DC, Kim BJ, ... Lee JS, Kim JS
Background:
and purpose
The outcome of endovascular treatment (EVT) may differ depending on the etiology of arterial occlusion. This study aimed to assess the differences in EVT outcomes in patients with intracranial arterial steno-occlusion (ICAS-O), artery-to-artery embolism (AT-O), and cardiac embolism (CA-O).
Methods
We retrospectively analyzed 330 patients with ischemic stroke who underwent EVT between January 2012 and August 2017. Patients were classified according to the etiology. The clinical data, EVT-related factors, and clinical outcomes were compared. The modified Rankin Scale (mRS) score at 3 months, determined using ordinal logistic regression (shift analysis), was the primary outcome.
Results
CA-O (n=149) was the most common etiology, followed by ICAS-O (n=63) and AT-O (n=49). Age, initial National Institutes of Health Stroke Scale (NIHSS) score, and rate of hemorrhagic transformation were significantly higher in patients with CA-O compared to AT-O and ICAS-O. The time from onset-to-recanalization was the shortest in the CA-O (356.0 minutes) groups, followed by the AT-O (847.0 minutes) and ICAS-O (944.0 minutes) groups. The rates of successful recanalization, mRS distribution, and favorable outcomes at 3 months (mRS 0-2; CA-O, 36.9%, AT-O, 53.1%; and ICAS-O, 41.3%) did not differ among the three groups. Baseline NIHSS score (odds ratio, 0.87; 95% confidence interval, 0.83 to 0.91) could independently predict a favorable shift in mRS distribution.
Conclusions
The functional outcomes of ICAS-O and AT-O were similar to those of CA-O, despite the delay in symptom onset-to-recanalization, suggesting that the therapeutic time window may be extended in these patients.



J Stroke: 29 Apr 2020; 22:234-244
Lee D, Lee DH, Suh DC, Kim BJ, ... Lee JS, Kim JS
J Stroke: 29 Apr 2020; 22:234-244 | PMID: 32635687
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Impact:
Abstract

Perfusion Imaging to Select Patients with Large Ischemic Core for Mechanical Thrombectomy.

Kerleroux B, Janot K, Dargazanli C, Daly-Eraya D, ... Boulouis G, JENI Research Collaborative
Background:
and purpose
Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.
Methods
This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0-3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).
Results
A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.
Conclusion
s In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted.



J Stroke: 29 Apr 2020; 22:225-233
Kerleroux B, Janot K, Dargazanli C, Daly-Eraya D, ... Boulouis G, JENI Research Collaborative
J Stroke: 29 Apr 2020; 22:225-233 | PMID: 32635686
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Impact:
Abstract

Left Ventricular Hypertrophy and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

Papadopoulos A, Palaiopanos K, Protogerou AP, Paraskevas GP, Tsivgoulis G, Georgakis MK
Background:
and purpose
Left ventricular hypertrophy (LVH) is associated with the risk of stroke and dementia independently of other vascular risk factors, but its association with cerebral small vessel disease (CSVD) remains unknown. Here, we employed a systematic review and meta-analysis to address this gap.
Methods
Following the MOOSE guidelines (PROSPERO protocol: CRD42018110305), we systematically searched the literature for studies exploring the association between LVH or left ventricular (LV) mass, with neuroimaging markers of CSVD (lacunes, white matter hyperintensities [WMHs], cerebral microbleeds [CMBs]). We evaluated risk of bias and pooled association estimates with random-effects meta-analyses.
Results
We identified 31 studies (n=25,562) meeting our eligibility criteria. In meta-analysis, LVH was associated with lacunes and extensive WMHs in studies of the general population (odds ratio [OR]lacunes, 1.49; 95% confidence interval [CI], 1.12 to 2.00) (ORWMH, 1.73; 95% CI, 1.38 to 2.17) and studies in highrisk populations (ORlacunes: 2.39; 95% CI, 1.32 to 4.32) (ORWMH, 2.01; 95% CI, 1.45 to 2.80). The.
Results
remained stable in general population studies adjusting for hypertension and other vascular risk factors, as well as in sub-analyses by LVH assessment method (echocardiography/electrocardiogram), study design (cross-sectional/cohort), and study quality. Across LV morphology patterns, we found gradually increasing ORs for concentric remodelling, eccentric hypertrophy, and concentric hypertrophy, as compared to normal LV geometry. LVH was further associated with CMBs in high-risk population studies.
Conclusion
s LVH is associated with neuroimaging markers of CSVD independently of hypertension and other vascular risk factors. Our findings suggest LVH as a novel risk factor for CSVD and highlight the link between subclinical heart and brain damage.



J Stroke: 29 Apr 2020; 22:206-224
Papadopoulos A, Palaiopanos K, Protogerou AP, Paraskevas GP, Tsivgoulis G, Georgakis MK
J Stroke: 29 Apr 2020; 22:206-224 | PMID: 32635685
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Impact:
Abstract

Unfavorable Vascular Anatomy during Endovascular Treatment of Stroke: Challenges and Bailout Strategies.

Alverne FJAM, Lima FO, Rocha FA, Bandeira DA, ... Lee JS, Nogueira RG
The benefit of mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to large vessel intracranial occlusions is directly related to the technical success of the procedures in achieving fast and complete reperfusion. While a precise definition of refractoriness is lacking in the literature, it may be considered when there is reperfusion failure, long procedural times, or high number of passes with the MT devices. Detailed knowledge about the causes for refractory MT in AIS is limited; however, it is most likely a multifaceted problem including factors related to the vascular anatomy and the underlying nature of the occlusive lesion amongst other factors. We aim to review the impact of several key unfavorable anatomical factors that may be encountered during endovascular AIS treatment and discuss potential bail-out strategies to these challenging situations.



J Stroke: 29 Apr 2020; 22:185-202
Alverne FJAM, Lima FO, Rocha FA, Bandeira DA, ... Lee JS, Nogueira RG
J Stroke: 29 Apr 2020; 22:185-202 | PMID: 32635684
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Impact:
Abstract

Association between Intracranial Arterial Dolichoectasia and Cerebral Small Vessel Disease and Its Underlying Mechanisms.

Zhang DP, Yin S, Zhang HL, Li D, Song B, Liang JX
Intracranial arterial dolichoectasia (IADE), also known as dilatative arteriopathy of the brain vessels, refers to an increase in the length and diameter of at least one intracranial artery, and accounts for approximately 12% of all patients with stroke. However, the association of IADE with stroke is usually unclear. Cerebral small vessel disease (CSVD) is characterized by pathological changes in the small vessels. Clinically, patients with CSVD can be asymptomatic or present with stroke or cognitive decline. In the past 20 years, a series of studies have strongly promoted an understanding of the association between IADE and CSVD from clinical and pathological perspectives. It has been proposed that IADE and CSVD may be attributed to abnormal vascular remodeling driven by an abnormal matrix metalloproteinase/tissue inhibitor of metalloproteinase pathway. Also, IADErelated hemodynamic changes may result in initiation or progression of CSVD. Additionally, genetic factors are implicated in the pathogenesis of IADE and CSVD. Patients with Fabry\'s disease and late-onset Pompe\'s disease are prone to developing concomitant IADE and CSVD, and patients with collagen IV alpha 1 or 2 gene (COL4A1/COL4A2) and forkhead box C1 (FOXC1) variants present with IADE and CSVD. Race, strain, familial status, and vascular risk factors may be involved in the pathogenesis of IADE and CSVD. As well, experiments in mice have pointed to genetic strain as a predisposing factor for IADE and CSVD. However, there have been few direct genetic studies aimed towards determining the association between IADE and CSVD. In the future, more clinical and basic research studies are needed to elucidate the causal relationship between IADE and CSVD and the related molecular and genetic mechanisms.



J Stroke: 29 Apr 2020; 22:173-184
Zhang DP, Yin S, Zhang HL, Li D, Song B, Liang JX
J Stroke: 29 Apr 2020; 22:173-184 | PMID: 32635683
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Impact:
Abstract

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke.

Balch MHH, Nimjee SM, Rink C, Hannawi Y
Stroke research has traditionally focused on the cerebral processes following ischemic brain injury, where oxygen and glucose deprivation incite prolonged activation of excitatory neurotransmitter receptors, intracellular calcium accumulation, inflammation, reactive oxygen species proliferation, and ultimately neuronal death. A recent growing body of evidence, however, points to far-reaching pathophysiological consequences of acute ischemic stroke. Shortly after stroke onset, peripheral immunodepression in conjunction with hyperstimulation of autonomic and neuroendocrine pathways and motor pathway impairment result in dysfunction of the respiratory, urinary, cardiovascular, gastrointestinal, musculoskeletal, and endocrine systems. These end organ abnormalities play a major role in the morbidity and mortality of acute ischemic stroke. Using a pathophysiology-based approach, this current review discusses the pathophysiological mechanisms following ischemic brain insult that result in end organ dysfunction. By characterizing stroke as a systemic disease, future research must consider bidirectional interactions between the brain and peripheral organs to inform treatment paradigms and develop effective, comprehensive therapeutics for acute ischemic stroke.



J Stroke: 29 Apr 2020; 22:159-172
Balch MHH, Nimjee SM, Rink C, Hannawi Y
J Stroke: 29 Apr 2020; 22:159-172 | PMID: 32635682
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Impact:

This program is still in alpha version.