The Paradoxical Protective Effect of Liver Steatosis on Severity and Functional Outcome of Ischemic Stroke

Background: There is very limited information on the relationship between non-alcoholic fatty liver disease (NAFLD) and the severity or functional outcomes of ischemic stroke or transient ischemic stroke (TIA). We investigated the correlation between NAFLD and stroke outcomes.Methods: NAFLD was assessed in 321 patients with first-ever acute ischemic stroke or TIA, who underwent transient elastography from January 2014 to December 2014. The association of liver steatosis with stroke severity, assessed using the National Institute of Health Stroke Scale (NIHSS), was investigated using robust regression analysis. We also compared the functional outcome at 90 days according to the presence or burden of liver steatosis.Results: NAFLD was observed in 206 (64.2%) patients. Patients with NAFLD had less severe stroke (median NIHSS score 2 vs. 3, P = 0.012) and more favorable functional outcome at 90 days (85.3 vs. 70.5, P = 0.004). Patients with NAFLD were likely to have a 23.3% lower [95% confidence interval (CI), −39.2 to −3.2%, P = 0.026] NIHSS score and a 2.5-fold higher (95% CI, 1.08–5.67, P = 0.033) possibility of favorable functional outcome in multivariate analysis.Conclusions: Our study shows that a higher burden of liver steatosis seems to be associated with less severe stroke and better functional outcome after ischemic stroke or TIA

Stochastic Particle Flow for Nonlinear High-Dimensional Filtering Problems

A series of novel filters for probabilistic inference that propose an alternative way of performing Bayesian updates, called particle flow filters, have been attracting recent interest. These filters provide approximate solutions to nonlinear filtering problems. They do so by defining a continuum of densities between the prior probability density and the posterior, i.e. the filtering density. Building on these methods' successes, we propose a novel filter. The new filter aims to address the shortcomings of sequential Monte Carlo methods when applied to important nonlinear high-dimensional filtering problems. The novel filter uses equally weighted samples, each of which is associated with a local solution of the Fokker-Planck equation. This hybrid of Monte Carlo and local parametric approximation gives rise to a global approximation of the filtering density of interest. We show that, when compared with state-of-the-art methods, the Gaussian-mixture implementation of the new filtering technique, which we call Stochastic Particle Flow, has utility in the context of benchmark nonlinear high-dimensional filtering problems. In addition, we extend the original particle flow filters for tackling multi-target multi-sensor tracking problems to enable a comparison with the new filter

AKAP12 Mediates Barrier Functions of Fibrotic Scars during CNS Repair

The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process

Endovascular and Clinical Outcomes of Vertebrobasilar Intracranial Atherosclerosis-Related Large Vessel Occlusion

Background and Purpose: Endovascular treatment (EVT) for acute vertebrobasilar intracranial atherosclerosis-related large vessel occlusion (ICAS-LVO) and its outcomes are not well known. We aimed to evaluate endovascular and clinical outcomes of vertebrobasilar ICAS-LVO patients who underwent EVT.Methods: Consecutive acute stroke patients who underwent EVT for vertebrobasilar LVO were retrospectively reviewed. Patients were assigned to the ICAS (+) or the ICAS (–) group based on angiographical findings. Procedural details and clinical outcomes were compared between the ICAS (+) and ICAS (–) groups.Results: This study included 77 patients with acute vertebrobasilar LVO who underwent EVT. Among the study subjects, 24 (31.2%) had an ICAS-LVO. Recanalization was achieved in 19 patients in the ICAS (+) group (79.2%), which was comparable with the ICAS (–) group (84.9%; p = 0.529). However, recanalization using conventional endovascular modalities (stent retriever thrombectomy, contact aspiration thrombectomy, or intra-arterial urokinase infusion) was less successful in the ICAS (+) group (36.8%) than the ICAS (–) group (100.0%; p < 0.001). All the remaining patients in the ICAS (+) group required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, or intra-arterial glycoprotein IIb/IIIa inhibitor infusion to obtain a successful recanalization. Procedural time was not significantly longer in the ICAS (+) group. The rates of favorable outcomes (37.5% vs. 41.5%; p = 0.740), death, and symptomatic intracerebral hemorrhage were not significantly different between the groups.Conclusion: ICAS-LVO was common in patients who underwent EVT for acute vertebrobasilar LVO. Although conventional modalities were often ineffective for vertebrobasilar ICAS-LVO, a comparable recanalization rate could be obtained with ICAS-specific modalities. Recanalization rate and procedural time were comparable, and clinical outcomes did not differ between patients with or without ICAS-LVO

Intracranial Stenting After Failed Thrombectomy in Patients With Moderately Severe Stroke: A Multicenter Cohort Study

Background and Purpose: Recently, acute intracranial stenting (ICS) has gained more interest as a potential bailout strategy for large vessel occlusions (LVO) that are refractory to thrombectomy. However, there are currently no reports on ICS in patients with moderately severe stroke discussing the question if implementing a permanent stent is feasible and leads to improved recanalization after failed thrombectomy. Methods: We analyzed a large multicenter database of patients receiving ICS for anterior circulation LVO after failed thrombectomy. Inclusion criteria were defined as: Moderately severe stroke (National Institute Health Stroke Scale (NIHSS) ≤9 on admission), anterior circulation LVO, acute ICS after failed stent retriever MT. Primary endpoint was the rate of improved successful recanalization after ICS defined as a modified Thrombolysis In cerebral Infarction (mTICI) score≥2b. Favorable neurological outcome was defined as an early neurological improvement (ENI) of 4 points or reaching 0 with respect to baseline NIHSS. Results: Forty-one patients met the inclusion criteria. A median of 2 retrievals were performed (IQR 1–4) prior decision-making for ICS. ICS led in 90.2% (37/41) of cases to a final mTICI≥2b with significant improvement (p < 0.001) after the last retrieval attempt. The median NIHSS decreased (p = 0.178) from 7 (IQR 3.5–8) on admission to 2.5 (IQR 0–8.25) at discharge. ENI was observed in 47.4% (18/38). sICH occurred in 4.8% (2/41). Conclusion: ICS after failed thrombectomy appears to effectively improve recanalization rates in patients with moderately severe strokes. Thus, ICS should be considered also for patients with baseline NIHSS ≤9 if thrombectomy fails

Impact of Non-vitamin K Antagonist Oral Anticoagulant Withdrawal on Stroke Outcomes

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF).Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groupsResults: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1–17)], followed by the warfarin withdrawal group [11, IQR (1–14, 18)], the no antithrombotic group [5, IQR (1–13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1–10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384–8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group.Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes

Stroke awareness decreases prehospital delay after acute ischemic stroke in korea

BACKGROUND: Delayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea. METHODS: A prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay. RESULTS: Among the 500 patients (median 67 years, 62% men), the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313). Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS) score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381), knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633) and use of ambulance (OR 1.961, 95% CI 1.176-3.270) were significantly associated with early arrival. CONCLUSIONS: In Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.ope

Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH