Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).

Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke.

OBJECTIVES: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS: Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS: Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS: The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.

Multidelay Arterial Spin Labeling Versus Computed Tomography Perfusion in Penumbra Volume of Acute Ischemic Stroke.

BACKGROUND: Multidelay arterial spin labeling (ASL) is a novel perfusion method of ASL, with arterial transit time (ATT) calculated by multiple postlabeling delays to correct cerebral blood flow (CBF). We verify the accuracy of multidelay ASL in evaluating the ischemic penumbra and perfusion levels in patients with acute ischemic stroke, compared with computed tomography perfusion (CTP). METHODS: Patients with acute ischemic stroke with anterior circulation large vessel occlusion received baseline CTP, multidelay ASL, and diffusion-weighted imaging (DWI) in succession. Multidelay ASL image was processed to reconstruct ATT, CBF without ATT correction, and CBF corrected by ATT. The consistency of hypoperfusion and ischemic penumbra volume calculated by CTP and multidelay ASL were quantified by intraclass correlation coefficient (ICC) in 2-way mixed effects, absolute agreement, and single measure. Wilcoxon signed-rank test was used to compare the difference in penumbra volume between CTP, corrected ASL, and uncorrected ASL. RESULTS: Thirty patients were included. Hypoperfusion volume based on multidelay ASL with different thresholds were 117.95 (87.77-151.49) mL for corrected relative CBF<40%, 130.29 (85.99-249.37) mL for CBF corrected by ATT<20 mL·100g-1·min-1, no statistical difference (P>0.05) compared with the volume of CTP, and consistency was almost excellent (ICC, 0.91) and substantial consistent (ICC, 0.727). The volumes of ischemic penumbra were 91.00 (42.68-125.27) mL for corrected relative CBF<40%-DWI, 108.94 (62.03-150.86) mL for CBF corrected by ATT<20 mL·100 g-1·min-1-DWI, which showed no statistical difference compared with the penumbra volume of CTP (P>0.05). The consistency was excellent (ICC, 0.822) and moderate (ICC, 0.501), respectively. The volume of uncorrected relative CBF <40%-DWI was 209.57 (123.21-292.45) mL, statistically larger than corrected relative CBF <40%-DWI (P<0.001) and CTP (P<0.001). The volume of uncorrected CBF<20 mL·100g-1·min-1-DWI was 186.23 (86.56-298.22) mL, statistically larger than CBF corrected by ATT<20 mL·100g-1·min-1-DWI (P<0.001) and CTP(P<0.001). CONCLUSIONS: The volume of ischemic penumbra determined by CBF/DWI mismatch based on multidelay ASL is consistent with CTP. The penumbra volume calculated by CBF adjusted by ATT is more accurate.

Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study.

BACKGROUND: Neutrophil serine proteinases (NSPs), released by activated neutrophils, are key proteins involved in the pathophysiologic processes of stroke. NSPs are also implicated in the process and response of thrombolysis. This study aimed to analyze three NSPs (neutrophil elastase, cathepsin G, and proteinase 3) in relation to acute ischemic stroke (AIS) outcomes and in relation to the outcomes of patients treated with intravenous recombinant tissue plasminogen activator (IV-rtPA). METHODS: Among 736 patients prospectively recruited at the stroke center from 2018 to 2019, 342 patients diagnosed with confirmed AIS were included. Plasma neutrophil elastase (NE), cathepsin G (CTSG), and proteinase 3 (PR3) concentrations were measured on admission. The primary endpoint was unfavorable outcome defined as modified Rankin Scale score 3-6 at 3 months, and the secondary endpoints were symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality within 3 months. In the subgroup of patients who received IV-rtPA, post-thrombolysis early neurological improvement (ENI) (defined as National Institutes of Health Stroke Scale score = 0 or decrease of ≥ 4 within 24 h after thrombolysis) was also included as the secondary endpoint. Univariate and multivariate logistic regression analyses were performed to evaluate the association between NSPs levels and AIS outcomes. RESULTS: Higher NE and PR3 plasma levels were associated with the 3-month mortality and 3-month unfavorable outcome. Higher NE plasma levels were also associated with the risk of sICH after AIS. After adjusting for potential confounders, plasma NE level > 229.56 ng/mL (odds ratio [OR] = 4.478 [2.344-8.554]) and PR3 > 388.77 ng/mL (OR = 2.805 [1.504-5.231]) independently predicted the 3-month unfavorable outcome. Regarding rtPA treatment, patients with NE plasma concentration > 177.22 ng/mL (OR = 8.931 [2.330-34.238]) or PR3 > 388.77 ng/mL (OR = 4.275 [1.045-17.491]) were over 4 times more likely to suffer unfavorable outcomes after rtPA treatment. The addition of NE and PR3 to clinical predictors of unfavorable functional outcome after AIS and the outcome after rtPA treatment improved discrimination as well as reclassification (integrated discrimination improvement = 8.2% and 18.1%, continuous net reclassification improvement = 100.0% and 91.8%, respectively). CONCLUSIONS: Plasma NE and PR3 are novel and independent predictors of 3-month functional outcomes after AIS. Plasma NE and PR3 also possess predictive value to identify patients with unfavorable outcomes after rtPA treatment. NE is probably an important mediator of the effects of neutrophils on stroke outcomes, which worth further investigation.

LC-MS/MS metabolomic profiling of the protective butylphthalide effect in cerebral ischemia/reperfusion mice.

OBJECTIVES: This study was designed to investigate metabolic biomarker changes and related metabolic pathways of Butylphthalide (NBP) on cerebral ischemia/reperfusion. METHODS: In this study, a mouse cerebral ischemia/reperfusion (I/R) model was prepared using the middle cerebral artery occlusion method, and neurobehavioral score and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining experiments were used to confirm the obvious NBP anti-cerebral ischemia effect. The protective effect of NBP in the mouse cerebral I/R model and its metabolic pathway and mechanism were investigated using mouse blood samples. RESULTS: The metabolic profiles of mice in the I/R+NBP, I/R, and sham groups were significantly different. Under the condition that I/R vs. sham was downregulated and I/R + NBP vs. I/R was upregulated, 88 differential metabolites, including estradiol, ubiquinone-2, 2-oxoarginine, and L-histidine trimethylbetaine, were screened and identified. The related metabolic pathways involved arginine and proline metabolism, oxidative phosphorylation, ubiquitin and other terpenoid-quinone biosynthesis, and estrogen signaling. CONCLUSIONS: Metabolomics was used to elucidate the NBP mechanism in cerebral ischemia treatment in mice, revealing synergistic NBP pharmacological characteristics with multiple targets.

Intravenous antagomiR-494 lessens brain-infiltrating neutrophils by increasing HDAC2-mediated repression of multiple MMPs in experimental stroke.

Neutrophil infiltration and phenotypic transformation are believed to contribute to neuronal damage in ischemic stroke. Emerging evidence suggests that histone deacetylase 2 (HDAC2) is an epigenetic regulator of inflammatory cells. Here, we aimed to investigate whether microRNA-494 (miR-494) affects HDAC2-mediated neutrophil infiltration and phenotypic shift. MiR-494 levels in neutrophils from acute ischemic stroke (AIS) patients were detected by real-time PCR. Chromatin Immunoprecipitation (ChIP)-Seq was performed to clarify which genes are the binding targets of HDAC2. Endothelial cells and cortical neurons were subjected to oxygen-glucose deprivation (OGD), transwell assay was conducted to examine neutrophil migration through endothelial cells, and neuronal injury was examined after stimulating with supernatant from antagomiR-494-treated neutrophils. C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO) and antagomiR-494 was injected through tail vein immediately after reperfusion, and neutrophil infiltration and phenotypic shift was examined. We found that the expression of miR-494 in neutrophils was significantly increased in AIS patients. HDAC2 targeted multiple matrix metalloproteinases (MMPs) and Fc-gamma receptor III (CD16) genes in neutrophils of AIS patients. Furthermore, antagomiR-494 repressed expression of multiple MMPs genes, including MMP7, MMP10, MMP13, and MMP16, which reduced the number of brain-infiltrating neutrophils by regulating HDAC2. AntagomiR-494 could also exert its neuroprotective role through inhibiting the shift of neutrophils toward pro-inflammatory N1 phenotype in vivo and in vitro. Taken together, miR-494 may serve as an alternative predictive biomarker of the outcome of AIS patients, and antagomiR-494 treatment decreases the expression of multiple MMPs and the infiltration of neutrophils and inhibits the shift of neutrophils into N1 phenotype partly by targeting HDAC2.

Influence of first-pass effect on recanalization outcomes in the era of mechanical thrombectomy: a systemic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis summarized the current literature to compare the safety and efficacy between first-pass effect (FPE) and multiple-pass effect (MPE) for thrombectomy in treatment of acute ischemic stroke (AIS). METHODS: Major databases were searched for studies which reported clinical outcomes regarding successful or complete recanalization after first pass of mechanical thrombectomy in AIS. The assessment of bias was performed using different scales. I2 statistic was used to evaluate heterogeneity between reviewers. Subgroup, meta-regression, and sensitivity analyses were conducted to explore the source of heterogeneity. Visualization of funnel plots was used to evaluate publication bias. RESULTS: A total of 9 studies were eligible for final analysis. For successful recanalization (mTICI 2b-3), favorable outcomes were seen in 49.7% (95% confidence interval (CI): 40.5-58.9%) and 34.7% (95% CI: 26.8-42.7%) of FPE and MPE patients, respectively. Mortality at 3 months was 13.8% (95% CI: 10.8-16.9%) and 26.0% (95% CI: 17.7-34.2%), respectively. For complete recanalization (mTICI 2c-3), proportion of favorable outcomes were 62.7% (95% CI: 51.2-74.2%) and 47.7% (95% CI: 37.4-58.0%) in FPE and MPE; mortality was seen in 11.5% (95% CI: 4.9-18.2%) and 17.0% (95% CI: 5.2-28.7%), respectively. For AIS with successful recanalization, FPE had more favorable outcome (odds ratio (OR): 1.85, 95% CI: 1.48-2.30; p < 0.01; I2 = 0%) and lower mortality than MPE (OR: 0.58, 95% CI: 0.42-0.79; p = 0.001; I2 = 61.9%). Similar results were seen in a subgroup analysis of patients with complete recanalization, with FPE having better outcome (OR: 1.79, 95% CI: 1.40-2.28; p < 0.01; I2 = 0%) and lower mortality risk (OR: 0.61, 95% CI: 0.44-0.86; p = 0.005; I2 = 0%) compared to MPE. CONCLUSION: FPE is associated with better outcomes than MPE after achieving successful or complete recanalization.

The prognostic value of general laboratory testing in patients with COVID-19.

BACKGROUND: Lymphocyte count (LYM) of peripheral blood and some indices of general biochemical analysis had diagnostic and prognostic value for coronavirus disease 2019 (COVID-19), and the value of other remaining indices is rare. METHODS: A total of 94 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 49, severe 35, and critical 10), and 40 healthy cases were enrolled in the same period as healthy controls. The diagnostic and prognostic value of indices in peripheral blood cell count and general biochemical analysis was analyzed. RESULTS: Compared with healthy cases, the value differences in peripheral blood analysis in patients with COVID-19 were statistically significant (p < 0.01), the differences in LYM, neutrophil count (Neu), platelet count (PLT), and white blood cell count (WBC) were statistically significant among different severity of COVID-19 (p < 0.05). Compared with healthy cases, the differences in general biochemical results in patients with COVID-19 were statistically significant (p < 0.01), the value differences in direct bilirubin (DBIL), low-density lipoprotein cholesterol (LDL-Ch), and nitrogen (urea) were statistically significant among different severity of COVID-19 (p < 0.05). Neutrophil/lymphocyte ratio (NLR) had higher sensitivity and specificity for COVID-19 diagnosis. CONCLUSIONS: Some indices of peripheral blood cell count and general biochemical analysis were valuable in discriminating COVID-19 and predicting severity and adverse outcome of patients with COVID-19. For clinician, it is better to use more economical and easy-to-get indices to diagnose and predict the prognosis of COVID-19.

Longitudinal Changes of Sensorimotor Resting-State Functional Connectivity Differentiate between Patients with Thalamic Infarction and Pontine Infarction.

Purpose. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine infarction. Methods. Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. Results. At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. Conclusions. The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.

Prognostic significance of plasma IL-2 and sIL-2Rα in patients with first-ever ischaemic stroke.

BACKGROUND: An imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear. METHODS: A total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses. RESULTS: Patients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p < 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p < 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%, p = 0.003; integrated discrimination improvement 5.78%, p = 0.0003). CONCLUSIONS: sIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.

Major vault protein plays important roles in viral infection.

Viral replication and related protein expression inside the host cells, and host antiviral immune responses can lead to the occurrence of diverse diseases. With the outbreak of viral infection, a large number of newly diagnosed and died patients infected with various viruses are still reported every year. Viral infection has already been one of the major global public health issues and lead to huge economic and social burdens. Studying of viral pathogenesis is a very important way to find methods for prevention, diagnosis, and cure of viral infection; more evidence has confirmed that major vault protein (MVP) is closely associated with viral infection and pathogenesis, and this review is intended to provide a broad relationship between viruses and MVP to stimulate the interest of related researchers.

The value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2019.

Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.

Glycosylated Hemoglobin A1c Predicts Intracerebral Hemorrhage with Acute Ischemic Stroke Post-Mechanical Thrombectomy.

BACKGROUND: Intracerebral hemorrhage, including symptomatic intracerebral hemorrhage, is a serious post-mechanical thrombectomy complication in patients with acute ischemic stroke. We aimed to determine whether glycosylated hemoglobin A1c parameters could predict intracerebral hemorrhage in this patient population. METHODS: We enrolled patients with acute occlusion of the internal carotid artery or proximal middle cerebral artery and who had undergone mechanical thrombectomy. According to the glycosylated hemoglobin A1c level (%) assessed during the hospital stay, the patients were divided into two groups: > 6.5% and ≤ 6.5%. Intracerebral hemorrhage was evaluated and classified based on cranial computed tomography scans obtained within 24-48 h or when neurological conditions worsened. We assessed the outcome at the end of 90 days using the modified Rankin Scale scores. RESULTS: Among 202 patients, 86 (42.6%) suffered intracerebral hemorrhage, while 25 (12.4%) had symptomatic intracerebral hemorrhage; 35.6% of the patients had a favorable outcome (modified Rankin Scale scores 0-2). Multivariable analysis demonstrated an association of glycosylated hemoglobin A1c > 6.5% with intracerebral hemorrhage. Furthermore, glycosylated hemoglobin A1c > 6.5% was independently associated with symptomatic intracerebral hemorrhage (OR, 2.136; 95% CI, 1.279-3.567; P = 0.004). In addition, glycosylated hemoglobin A1c > 6.5% was significantly associated with increased mortality (OR, 1.511; 95% CI, 1.042-2.191; P = 0.029) and negatively associated with favorable outcome (OR, 0.480; 95% CI, 0.296-0.781; P = 0.003) at 90 days. CONCLUSIONS: Glycosylated hemoglobin A1c is an independent predictor of intracerebral hemorrhage (specifically, symptomatic intracerebral hemorrhage) in patients with acute ischemic stroke treated with mechanical thrombectomy. Further studies are needed to validate these findings.

Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis.

Background and Purpose- Early use of antiplatelet drugs within 24 hours after intravenous thrombolysis (IVT) has always been a confusing clinical problem. The purpose of this study was to assess the safety and efficacy of early low-dose tirofiban treatment in patients with early neurological deterioration (END) within the first 24 hours after IVT. Methods- This was a retrospective analysis of prospectively collected data of 1764 consecutive patients with acute ischemic stroke treated with IVT between January 2017 and September 2018. Patients with early neurological deterioration within the first 24 hours after IVT were treated with or without tirofiban. The safety outcomes included symptomatic intracranial hemorrhage, any ICH, severe systemic bleeding, and mortality. Efficacy outcomes included excellent (modified Rankin scale scores 0-1) and favorable (modified Rankin scale scores 0-2) 3-month functional outcomes. Results- Early neurological deterioration occurred in 278 (15.8%) patients. Of the 187 eligible patients, 121 (64.7%) were treated with tirofiban within the first 24 hours after IVT. Adjusted multivariate analysis showed that early tirofiban use was not associated with symptomatic intracranial hemorrhage (adjusted odds ratio [aOR], 1.05; 95% CI, 0.088-11.02; P=1.000), ICH (aOR, 1.13; 95% CI, 0.45-4.25; P=0.512), and mortality (aOR, 0.77; 95% CI, 0.19-2.27; P=0.875) but was significantly associated with excellent (aOR, 2.24; 95% CI, 1.16-3.94; P=0.027) and favorable (aOR, 2.31; 95% CI, 1.48-3.99; P=0.011) functional outcomes. Subgroup analyses suggested that early tirofiban-use efficacy is time dependent, being more effective in patients receiving tirofiban treatment earlier. Conclusions- Low-dose tirofiban use in patients with early neurological deterioration within the first 24 hours after IVT did not increase the risk of symptomatic intracranial hemorrhage, ICH, and mortality, it seems associated with neurological improvement at 3 months. Future randomized clinical trials will be needed to validate these results.

The stability of Magoh and Y14 depends on their heterodimer formation and nuclear localization.

Reduced expression of the Y14 gene is a cause of Thrombocytopenia-absent radius (TAR) syndrome. This gene contains a conserved RNA recognition motif (RRM) in the central region and nuclear localization/export sequences (NLS/NES) in the N-terminal. Y14 and Magoh proteins form tight heterodimers and are the core of exon junction complexes (EJCs), which mediate various processes of mRNA metabolism after transcription. In this report, we found that protein expression levels of exogenously expressed Magoh L136R and Y14 L118R (leucine-to-arginine substitution at amino acid residue 136 and 118 respectively, that results in the formation of the complex being lost) are lower than their wild-types. This reduction is likely caused by protein levels, as no difference in mRNA levels was detected. Meanwhile, a cycloheximide chase assay determined that the degradation rates of Magoh L136R and Y14 L118R were faster than their wild-types. Both Y14 L118R and Magoh L136R lost the ability to form heterodimers with corresponding wild-type proteins. However, Y14 L118R is able to still localize in the nucleus which causes the stability of Y14 L118R to be higher than Magoh L136R. These results reveal that the stability of Magoh and Y14 is not only dependent on the heterodimer structure, but also dependent on nuclear localization.

Disrupted functional connectivity and activity in the white matter of the sensorimotor system in patients with pontine strokes.

BACKGROUND: White matter (WM) blood oxygenation level-dependent (BOLD) signals are reported to be related to neural activity. However, sensitivity of WM BOLD signals to disease remains unclear. PURPOSE: To investigate WM BOLD signal changes, directional variations of resting-state correlations in sensorimotor system in patients with pontine strokes, and to determine the relationship between WM BOLD signals and motor deficits. STUDY TYPE: Prospective. SUBJECTS: Ethical approval was obtained from the local Ethics Committee and each participant gave written informed consent. Sixteen patients with focal pontine lesions and 16 age-matched control subjects were included. FIELD STRENGTH/SEQUENCE: 3.0T T1 -weighted anatomic images using a 3D magnetization-prepared rapid gradient-echo sequence. Resting-state fMRI images using gradient-echo echo-planar imaging sequence. Diffusion-weighted images using single-shot spin-echo diffusion echo-planar imaging. ASSESSMENT: Relevant WM tracts in the sensorimotor system by region of interest-wise analysis were identified. Power spectra of BOLD signals and anisotropy of resting-state correlations were measured in sensorimotor system and compared between two groups. Their relationships with clinical scores were analyzed. STATISTICAL TESTS: Two-sample t-test; partial correlation analysis. RESULTS: Power spectra of BOLD signals in nerve tracts on the ipsilesional side were significantly decreased (P < 0.05). Compared with that in healthy subjects, the anisotropy of resting-state correlations along identified WM tracts was decreased in the thalamus-dorsolateral prefrontal cortex bundle on the contralesional side, and all nerve tracts on the ipsilesional side. Partial least squares regression analysis showed the predicted outcome scores correlated significantly with actual Fugl-Meyer scores (R2 = 0.944, P = 0.013). DATA CONCLUSION: Our findings suggest that disrupted activity and functional connectivity in WM areas of the sensorimotor system can be detected in pontine strokes, and may serve as a biomarker for motor function prediction. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:478-486.

Hyperintense Plaque on Intracranial Vessel Wall Magnetic Resonance Imaging as a Predictor of Artery-to-Artery Embolic Infarction.

BACKGROUND AND PURPOSE: The aim of the present study was to investigate atherosclerotic plaque characteristics in patients with artery-to-artery (A-to-A) embolic infarction by whole-brain high-resolution magnetic resonance imaging. METHODS: Seventy-four patients (mean age, 54.7±12.1 years; 59 men) with recent stroke in the territory of middle cerebral artery because of intracranial atherosclerotic disease were prospectively enrolled. Whole-brain high-resolution magnetic resonance imaging was performed in all the patients both precontrast and postcontrast administration by using a 3-dimensional T1-weighted vessel wall magnetic resonance imaging technique known as inversion-recovery prepared sampling perfection with application-optimized contrast using different flip angle evolutions. Patients were divided into A-to-A embolic infarction and non-A-to-A embolic infarction groups based on diffusion-weighted imaging findings. The characteristics of the intracranial atherosclerotic plaques were compared between groups. RESULTS: A total of 74 intracranial atherosclerotic plaques were analyzed (36 in A-to-A embolism group and 38 in non-A-to-A embolism group). Hyperintense plaques (HIPs) were more frequently observed in A-to-A embolism group (75.0% versus 21.1%; P<0.001). Eighteen of the 27 HIPs (66.7%) demonstrated hyperintense spots or areas located adjacent to the lumen versus 9 HIPs (33.3%) located within the plaque in A-to-A embolism group. Furthermore, a higher prevalence of plaque surface irregularity was also observed in A-to-A embolism group (41.7% versus 18.4%; P=0.029). Logistic regression analysis showed that HIP was the most powerful independent predictor of A-to-A embolic infarction (P<0.001), with the odds ratio of 11.2 (95% confidence interval, 3.5-36.2). CONCLUSIONS: A-to-A embolic infarction has distinct vulnerable plaque characteristics compared with non-A-to-A embolic infarction. HIP and plaque surface irregularity may predict A-to-A embolic infarction.

Outcome of endovascular treatment for acute basilar artery occlusion in the modern era: a single institution experience.

PURPOSE: The beneficial effect of endovascular treatment (EVT) for patients with acute basilar artery occlusion (ABAO) remains uncertain. The purpose of the present study was to evaluate clinical outcome of EVT for patients with ABAO and analyze prognostic factors of good outcome. METHODS: From our prospectively established database, we reviewed all patients with ABAO receiving EVT during January 2014 to December 2016. Baseline characteristics and outcomes were evaluated. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 3 assessed at 3-month follow-up. The association between clinical and procedural characteristics and functional outcome was assessed. RESULTS: Of the 68 patients included, 50 patients (73.5%) received mechanical thrombectomy with stent retriever device. Successful reperfusion (thrombolysis in cerebral infarction grades 2b-3) was achieved in 61 patients (89.7%). Overall favorable functional outcome was reached by 31 patients (45.6%). In univariate analysis, Glasgow Coma Scale sum score, baseline National Institutes of Health stroke scale score (NIHSS), and baseline glycemia level were identified predicting good clinical outcome. Multivariate analysis showed that lower NIHSS was the only independent risk factor of favorable functional outcome (OR 0.832; 95% CI, 0.715-0.968; p = 0.018). No difference of favorable outcomes was observed between the subgroups of time to EVT < 6 h and ≽ 6 h. CONCLUSIONS: Data in the present study suggests that EVT for ABAO patients should be reasonable within 24 h of symptom onset. The most important factor determining clinical outcome is initial stroke severity.

L-3-n-Butylphthalide reduces ischemic stroke injury and increases M2 microglial polarization.

Overwhelming evidence suggests that microglia play an important role in ischemic injury and they polarize into two different phenotypes with distinct functions after ischemic stroke. We performed the present study to investigate whether L-3-n butylphthalide (NBP) has an effect on microglial polarization. Mice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min, and then immediately after reperfusion were treated with NBP or vehicle via the caudal vein for 7 consecutive days. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that NBP treatment resulted in a tendency to decrease cerebral infarct volume at 1 day after MCAO, and significant decreased infarct volume at 3 days after MCAO. Sensorimotor function was evaluated by the adhesive removal test and balance beam test, which were superior in NBP-treated mice compared with vehicle-treated mice at 1 and 3 days after MCAO. Immunofluorescent staining further indicated that NBP treatment significantly increased the number of CD206+/Iba1+ M2 microglia/macrophages and reduced the number of CD16+/Iba1+ M1 cells at 3 and 7 days after MCAO reperfusion. Western blot also showed an elevation of M2 marker (arginase-1) in NBP-treated brains at 7 days after MCAO. In conclusion, our results clearly show that NBP treatment significantly mitigates ischemic brain damage and promotes recovery of neurological function in early phase after ischemic stroke, probably by skewing M1 microglia/macrophages polarization towards M2 phenotype. Thus, our study provides new evidence that NBP might be a promising candidate for ameliorating injury caused by ischemic stroke.