Angiography-based hemodynamic features predict recurrent ischemic events after angioplasty and stenting of intracranial vertebrobasilar atherosclerotic stenosis.

OBJECTIVES: To assess the predictive value of hemodynamic features for stroke relapse in patients with intracranial vertebrobasilar atherosclerotic stenosis treated with percutaneous transluminal angioplasty and stenting (PTAS) using quantitative digital subtraction angiography (q-DSA). METHODS: In this retrospective longitudinal study, patients with intracranial vertebrobasilar atherosclerotic stenosis and who underwent PTAS treatment between January 2012 and May 2020 were enrolled. The q-DSA assessment was performed before and after PTAS. ROIs 1-4 were placed along the vertebral artery, proximal and distal basilar artery, and posterior cerebral artery; ROIs 5-8 were in 5 mm and 10 mm proximal and distal to the lesion, respectively. Relative time to peak (rTTP) was defined as the difference in TTP between ROIs. Cox regression analyses were performed to determine risk factors for recurrent stroke. RESULTS: A total of 137 patients (mean age, 62 years ± 10 [standard deviation], 83.2% males) were included, and 26 (19.0%) patients had stroke relapse during follow-up (median time of 42.6 months [interquartile range, 19.7-60.7]). Preprocedural rTTP4-1 (adjusted hazard ratio (HR) = 2.270; 95% CI 1.371-3.758; p = 0.001) and preprocedural rTTP8-5 (adjusted HR = 0.240; 95% CI 0.088-0.658; p = 0.006) were independently associated with the recurrent stroke. These hemodynamic parameters provided an incremental prognostic value for stroke relapse (AUC, 0.817 [0.704-0.931]; the net reclassification index, 0.431 [0.057-0.625]; and the integrated discrimination index, 0.140 [0.035-0.292]). CONCLUSIONS: In patients with intracranial vertebrobasilar atherosclerosis treated with PTAS, preprocedural prolonged TTP of the target vessel and shortened trans-stenotic TTP difference were associated with stroke relapse. Q-DSA-defined hemodynamic parameters provided incremental predictive value over conventional parameters for stroke recurrence. CLINICAL RELEVANCE STATEMENT: Quantitative DSA analysis enables intuitive observation and semi-quantitative evaluation of peri-therapeutic cerebral blood flow. More importantly, quantitative DSA-defined hemodynamic parameters have the potential for risk stratification of patients with intracranial atherosclerotic stenosis. KEY POINTS: Semi-quantitative angiography-based parameters can reflect pre- and postprocedural subtle changes in blood flow in patients with intracranial atherosclerotic stenosis. Although angioplasty procedures can significantly improve blood flow status, patients with more restricted baseline blood flow still show a higher risk of stroke recurrence. Angiography-based hemodynamic features possess prognostic value and can serve as clinical markers to assess stroke risk of patients with intracranial atherosclerotic stenosis.

Distinguishing Intracranial Diabetes-Related Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging-Based Radiomics Study.

INTRODUCTION: Diabetes markedly affects the formation and development of intracranial atherosclerosis. The study was aimed at evaluating whether radiomics features can help distinguish plaques primarily associated with diabetes. MATERIALS AND METHODS: We retrospectively analyzed patients who were admitted to our center because of acute ischemic stroke due to intracranial atherosclerosis between 2016 and 2022. Clinical data, blood biomarkers, conventional plaque features, and plaque radiomics features were collected for all patients. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined from logistic regression models. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to describe diagnostic performance. The DeLong test was used to compare differences between models. RESULTS: Overall, 157 patients (115 men; mean age, 58.7 ± 10.7 years) were enrolled. Multivariate logistic regression analysis showed that plaque length (OR: 1.17; 95% CI: 1.07-1.28) and area (OR: 1.13; 95% CI: 1.02-1.24) were independently associated with diabetes. On combining plaque length and area as a conventional model, the AUCs of the training and validation cohorts for identifying diabetes patients were 0.789 and 0.720, respectively. On combining radiomics features on T1WI and contrast-enhanced T1WI sequences, a better diagnostic value was obtained in the training and validation cohorts (AUC: 0.889 and 0.861). The DeLong test showed the model combining radiomics and conventional plaque features performed better than the conventional model in both cohorts (p < 0.05). CONCLUSIONS: The use of radiomics features of intracranial plaques on high-resolution magnetic resonance imaging can effectively distinguish culprit plaques with diabetes as the primary pathological cause, which will provide new avenues of research into plaque formation and precise treatment.

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury.

BACKGROUND: Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. METHODS: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen-glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. RESULTS: LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2-/-) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2-/- mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. CONCLUSION: LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.

Rescuers from the Other Shore: Intercellular Mitochondrial Transfer and Its Implications in Central Nervous System Injury and Diseases.

As the powerhouse and core of cellular metabolism and survival, mitochondria are the essential organelle in mammalian cells and maintain cellular homeostasis by changing their content and morphology to meet demands through mitochondrial quality control. It has been observed that mitochondria can move between cells under physiological and pathophysiological conditions, which provides a novel strategy for preserving mitochondrial homeostasis and also a therapeutic target for applications in clinical settings. Therefore, in this review, we will summarize currently known mechanisms of intercellular mitochondrial transfer, including modes, triggers, and functions. Due to the highly demanded energy and indispensable intercellular linkages of the central nervous system (CNS), we highlight the mitochondrial transfer in CNS. We also discuss future application possibilities and difficulties that need to be addressed in the treatment of CNS injury and diseases. This clarification should shed light on its potential clinical applications as a promising therapeutic target in neurological diseases. Intercellular mitochondrial transfer maintains the homeostasis of central nervous system (CNS), and its alteration is related to several neurological diseases. Supplementing exogenous mitochondrial donor cells and mitochondria, or utilizing some medications to regulate the process of transfer might mitigate the disease and injury.

Review of net water uptake in the management of acute ischemic stroke.

CT densitometry-based methods to directly quantify net water uptake in ischemic brain tissue have been increasingly applied recently. There is potential for net water uptake to be used as an imaging biomarker for the pathophysiology of infarcted lesions. This review is aimed at summarizing the potential and current status of the application of net water uptake as a biomarker in the management of ischemic stroke and future directions in this context. Specifically, we provide a brief overview of the principle and different methods of net water uptake measurement, followed by a discussion of the role of net water uptake in predicting malignant brain edema and hemorrhagic transformation, evaluating lesion age, and predicting the efficacy of reperfusion therapy and long-term clinical prognosis. Artificial intelligence will help address the lack of automation and standardization in the measurement of net water absorption. Further validation of net water uptake in a prospective multicenter setting is necessary. KEY POINTS: • NWU can be used as a quantitative imaging biomarker for developing malignant brain edema in anterior and posterior circulation strokes. • The difference in NWU in edema arrest or reversibility suggests that rapid and successful revascularization can influence the progression of ischemic edema. • NWU can be used to predict the age of a lesion, with predictive power comparable to that of DWI/FLAIR mismatch.

Automated quantitative lesion water uptake in acute stroke is a predictor of malignant cerebral edema.

OBJECTIVES: Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE). METHODS: One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared. RESULTS: CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p < 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p < 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p < 0.001). CONCLUSIONS: This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. KEY POINTS: • The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

The MRI enhancement ratio and plaque steepness may be more accurate for predicting recurrent ischemic cerebrovascular events in patients with intracranial atherosclerosis.

OBJECTIVES: To assess the complementary value of high-resolution multi-contrast MRI (hrMRI) in identifying symptomatic patients with intracranial atherosclerosis (ICAS) who are likely to experience recurrent ischemic cerebrovascular events. METHODS: In this retrospective cohort study, eighty patients with acute ischemic events attributed to ICAS who underwent hrMRI examination between January 2015 and January 2019 were included. Median follow-up for all patients was 30 months (range: 1 to 52 months) and recurrent ischemic cerebrovascular events were recorded. Cox regression analysis and time-dependent ROC were performed to quantify the association between the plaque characteristics and recurrent events. RESULTS: During the follow-up, 14 patients experienced recurrent ischemic cerebrovascular events. Young males and those with diabetes and poor medication persistence were more likely to experience recurrent events. ICAS in patients with recurrence had significantly higher enhancement ratio and steepness which is defined as the ratio between the plaque height and length than those without (p < 0.001 and p = 0.015, respectively). After adjustment of clinical factors, enhancement ratio (HR, 13.13 [95% CI, 3.58-48.20], p < 0.001) and plaque steepness (HR, 110.27 [95% CI, 4.75-2560.91], p = 0.003) were independent imaging biomarkers associated with recurrent events. Time-dependent ROC indicated that integrated high enhancement ratio and steepness into clinical risk factors improved discrimination power with the ROC increased from 0.79 to 0.94 (p = 0.008). CONCLUSIONS: The enhancement ratio and plaque steepness improved the accuracy over traditional clinical risk factors in predicting recurrent ischemic cerebrovascular events for patients with ICAS. KEY POINTS: • High-resolution magnetic resonance imaging helps clinicians to evaluate high-risk Intracranial plaque. • The higher enhancement ratio and plaque steepness (= height/length) were the primary biomarkers associated with future ischemic cerebrovascular events. • High-resolution magnetic resonance imaging combined with clinical characteristics showed a higher accuracy for the prediction of recurrent events in patients with intracranial atherosclerosis.

ASPECTS-Based Attenuation Changes on CT Angiography as an Imaging Biomarker to Predict Hemorrhagic Transformation in Acute Ischemic Stroke.

INTRODUCTION: Imaging-based early warning indicators and feasible stratification of acute ischemic stroke (AIS) patients with hemorrhagic transformation (HT), especially high-risk patients with parenchymal hematoma (PH), are crucial in determining subsequent treatment strategies. This study combined automated ASPECTS software with noncontrast CT (NCCT) and CTA source image (CTASI) attenuation changes using Hounsfield unit (HU) values to predict HT and PH in patients with AIS. MATERIALS AND METHODS: We retrospectively enrolled 172 consecutive patients with anterior circulation large-vessel occlusion between 2016 and 2020. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) analyses were used to investigate the relationship between NCCT and CTASI-ASPECTS-HU, as well as other clinical and radiological parameters of HT and PH. Univariate and multivariate logistic regression analyses were performed to explore risk factors for HT or PH, and an ROC curve was used to evaluate their diagnostic values. RESULTS: A multivariate analysis showed that CTASI-ASPECTS-HU and NIHSS score were independent predictors of HT (CTASI-ASPECTS-HU: odds ratio (OR), 2.22; 95% CI, 1.01-4.92; NIHSS: OR, 1.07; 95% CI, 1.02-1.13) and PH (CTASI-ASPECTS-HU: OR, 6.51; 95% CI, 2.29-18.50; NIHSS: OR, 1.07; 95% CI, 1.01-1.13). According to ROC analysis, CTASI-ASPECTS-HU >0.09 identified HT (area under the curve, 0.70; sensitivity, 70.15%; specificity, 61.90%), and CTASI-ASPECTS-HU >0.10 identified PH (area under the curve, 0.79; sensitivity, 76.19%; specificity, 73.33%). The area under the curve for predicting HT or PH increased when CTASI-ASPECTS-HU was combined with NIHSS score (HT: area under the curve, 0.74; sensitivity, 73.13%; specificity, 70.48%; PH: area under the curve, 0.81; sensitivity, 85.71%; specificity, 72.38%). CONCLUSION: CTASI-ASPECTS-HU is a reliable radiological predictor of HT and PH in patients with AIS. Its predictive efficacy is moderately improved when combined with NIHSS score.

Homocysteine is related to enlarged perivascular spaces in the brainstem in patients with isolated pontine infarction.

BACKGROUND: Homocysteine is correlated with several imaging features of cerebral small vessel disease including white matter hyperintensities, lacunes, and enlarged perivascular spaces (EPVS) in the basal ganglia. However, little is known about EPVS in the brainstem. This study aimed to investigate the correlation between serum total homocysteine (tHcy) and EPVS in the brainstem in patients with acute isolated pontine infarction. METHODS: Consecutive patients with isolated pontine infarction were retrospectively enrolled. Clinical characteristics and laboratory tests including tHcy were recorded. Imaging markers of cerebral small vessel disease including EPVS in the basal ganglia (BG-EPVS), EPVS in the centrum semiovale, and EPVS in the midbrain or pons (brainstem-EPVS) were assessed using conventional magnetic resonance imaging. The relation between tHcy and EPVS of different parts in the brain was analyzed using univariate and multivariate regression model. RESULTS: A total of 227 patients were included (mean age 67.10 ± 9.38 years, male sex 58.6%). The frequencies of brainstem-EPVS and moderate to severe BG-EPVS accounted for 40.1% (91/227) and 40.5% (92/227) respectively. After controlling for confounding factors, multivariate logistic regression analyses showed that tHcy was an independent risk factor for both moderate to severe BG-EPVS (P = 0.003, P for trend < 0.001) and the presence of brainstem-EPVS (P < 0.001, P for trend < 0.001) in a dose-dependent manner. Furthermore, multivariate linear regression model indicated that the presence of brainstem-EPVS (ß = 0.264, 95% confidence interval = 0.143-0.402, P < 0.001) and the severity of BG-EPVS (ß = 0.162, 95% confidence interval = 0.024-0.197, P = 0.013) were positively associated with serum tHcy. CONCLUSIONS: Serum tHcy is correlated with brainstem-EPVS and BG-EPVS dose-dependently. This study may support a contributing role for homocysteine in the pathophysiology of EPVS in the brainstem and the basal ganglia.

[Coronary CT angiography derived fractional flow reserve: the consideration and practice of functional evaluation for cerebral arterial diseases].

Cerebrovascular disease is a significant global public health concern, despite the diagnosis and treatment of stroke has made great progress in recent years, however, its mainly guided by anatomical indicators, which still needs to be further improved, and there is an urgent need to explore a more accurate and comprehensive functional imaging assessment method. Rapid development of coronary CT angiography derived fractional flow reserve (CT-FFR) has become an important technique for noninvasive evaluation of coronary artery disease, and these successful application experiences inspiried neurologists to explore the functional evaluation technique of cerebral arteries and demonstrated broad application prospects. In this paper, by analyzing and comparing the coronary CT-FFR technology, the progress, existing problems and possible solutions of the functional evaluation for cerebral arterial stenosis are discussed from the aspects of coronary CT-FFR study, cerebral artery functional evaluation study, and the comparison and consideration of cerebral arterial and coronary CT-FFR.

Early Neurological Deterioration and Hypoperfusion Volume Ratio on Arterial Spin Labeling in Patients with Acute Ischemic Stroke.

BACKGROUND: Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to quantify cerebral blood perfusion by labeling blood water as it flows throughout the brain. Hypoperfusion volume ratio (HVR) can be calculated using proportional hypoperfusion volume on ASL-based cerebral blood flow (CBF). This study aimed to explore the relation between HVR and early neurological deterioration (END) in AIS patients. SUBJECTS AND METHODS: Patients with AIS were recruited consecutively, and ASL and regular MRI scans were performed. HVR was calculated from 1.5 and 2.5s post labeling delay (PLD) ASL-CBF maps. END was defined as ≥2 points increment of NIHSS within 72 hours of stroke onset. Univariate and multivariate analysis were used to evaluate the relation between HVR and END. Receiver operating characteristic (ROC) curves were used to determine the ability of HVR in predicting END. RESULTS: Of the 52 enrolled patients, 18 (34.5%) were determined with END. In patients with END, the median hypoperfusion volume was 20 mL [Inter Quartile Range)IQR, 6-72.5 mL] at 1.5s PLD, and 11.2 mL (IQR, 5.3-26 mL) at 2.5s PLD; Sixteen (88.9%) patients had HVR ≥50%, and 13 (72.2%) patients hypoperfusion volume at 2.5s PLD ASL were greater than diffusion-weighted imaging (DWI) infarct volume. In patients without END, median hypoperfusion volume was 7 mL (IQR, 4-30 mL) at 1.5s PLD, and 4 mL (IQR, 1.5-8.5 mL) at 2.5s; Eleven (32.4%) patients had HVR ≥50%, and 10 (29.4%) patients hypoperfusion volume at 2.5s PLD ASL were greater than DWI infarct volume. The proportion of HVR ≥50% and hypoperfusion volume >DWI infarct volume were more frequent in patients with END than patients without (all P<0.001). After adjusted for age, admission NIHSS, proportion of hypoperfusion volume > DWI infarct and arterial transit artifact (ATA) by logistic regression analysis, HVR ≥50% (OR=13.1, P=0.003) was an independent risk factor for END. ROC analysis demonstrated that the HVR could predict END with an area under the curve of 0.794 (P=0.001). CONCLUSIONS: HVR obtained from the 1.5 and 2.5s PLD ASL may be a useful predictor of END in AIS. The value of HVR may be a marker for hemodynamic impairments.

CD99 mediates neutrophil transmigration through the bEnd.3 monolayer via the induction of oxygen-glucose deprivation.

AIM/BACKGROUND: CD99 participate in neutrophil infiltration after inflammatory events; however, despite the important role of inflammation in ischemic stroke, the role of CD99 in ischemic stroke remains unclear. METHOD: In the present study, we detected the protein expression of CD99, ICAM-1, and CD31 (PECAM-1) in oxygen-glucose deprivation (OGD)-induced bEnd.3 cells and neutrophils and explored the influence of HIF-1α and IL-1ß on their expression. We also explored the role of CD99 in the OGD-induced transmigration of neutrophils. RESULTS: Our results showed that OGD induction upregulated CD99 in bEnd.3 cells and that this effect could be abolished by the preadministration of IL-1ß and was not mediated by HIF-1α. However, the activation of ICAM-1 by OGD remained activated with IL-1ß treatment. No significant influence of IL-1ß on OGD-induced CD31. Finally, we found a significant increase in infiltrated neutrophils after OGD induction compared with the control and OGD + anti-CD99 groups. CONCLUSION: Our results indicated that CD99 mediates neutrophil infiltration and transmigration via OGD induction and thus constitutes a potential therapeutic target for anti-inflammatory treatment after ischemic stroke.

Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury.

BACKGROUND: Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemic stroke. NLRP3 inflammasome, involved in the regulation of inflammatory cascade, can simultaneously lead to GSDMD-executed pyroptosis in cerebral ischemia. Low-density lipoprotein receptor (LDLR), responsible for cholesterol uptake, was noted to exert potential anti-inflammatory bioactivities. Nevertheless, the role of LDLR in neuroinflammation mobilized by cerebral ischemia/reperfusion (I/R) has not been investigated. METHODS: Ischemic stroke mice model was accomplished by middle cerebral artery occlusion. Oxygen-glucose deprivation was employed after primary cortical neuron was extracted and cultured. A pharmacological inhibitor of NLRP3 (CY-09) was administered to suppress NLPR3 activation. Histological and biochemical analysis were performed to assess the neuronal death both in vitro and in vivo. In addition, neurological deficits and behavioral deterioration were evaluated in mice. RESULTS: The expression of LDLR was downregulated following cerebral I/R injury. Genetic knockout of Ldlr enhanced caspase-1-dependent cleavage of GSDMD and resulted in severe neuronal pyroptosis. LDLR deficiency contributed to excessive NLRP3-mediated maturation and release of IL-1ß and IL-18 under in vitro and in vivo ischemic conditions. These influences ultimately led to aggravated neurological deficits and long-term cognitive dysfunction. Blockade of NLRP3 substantially retarded neuronal pyroptosis in Ldlr-/- mice and cultured Ldlr-/- neuron after experimental stroke. CONCLUSIONS: These results demonstrated that LDLR modulates NLRP3-mediated neuronal pyroptosis and neuroinflammation following ischemic stroke. Our findings characterize a novel role for LDLR as a potential therapeutic target in neuroinflammatory responses to acute cerebral ischemic injury.

Feasibility of Thrombectomy in Treating Acute Ischemic Stroke Because of Cervical Artery Dissection.

Background and Purpose- Acute ischemic stroke caused by cervical artery dissection tend to result in unfavorable outcomes even with appropriate medical treatment. This study evaluated the safety and effectiveness of endovascular thrombectomy in treating acute ischemic stroke associated with cervical artery dissection. Methods- Patients with acute ischemic stroke and with large artery occlusion associated with dissection were selected. Propensity score matching was performed to increase the comparability. Patients with a 90-day modified Rankin Scale score of 0 to 2 were defined as with favorable outcome. Results- Eighty patients with and 80 patients without thrombectomy were enrolled. After propensity score matching, 48 patients with and 48 patients without thrombectomy were matched for further analysis. Proportion of favorable outcome (modified Rankin Scale score of 0-2) was higher in patients with thrombectomy than in those without (66.7% versus 39.6%; P=0.008). There were no significance differences about the incidence of symptomatic intracranial hemorrhage (8.3% versus 4.2%; P=0.677) and the 90-day mortality (10.4% versus 6.3%; P=0.714) between matched patients with and without thrombectomy. Conclusions- Endovascular thrombectomy seems to be an effective treatment in selected patients with acute ischemic stroke associated with cervical artery dissection, but the safety of thrombectomy needs further research.

Neutrophil-Lymphocyte Ratio Predicts Functional and Safety Outcomes after Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVE: Endovascular treatment (EVT) is proven to be safe and effective for treating acute large vessel occlusion stroke (LVOS). The neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, which plays an important role in the process of treating ischemic stroke. This study aims to explore the relationship between NLR and the clinical outcomes of LVOS patients undergoing EVT. METHODS: Patients were selected from the EVT for acUte Anterior circuLation (ACTUAL) ischemic stroke registry. The laboratory data (neutrophil count, lymphocyte count) before EVT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3-6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR with functional outcome, symptomatic intracranial hemorrhage (sICH), and mortality. RESULTS: We eventually included 616 patients (median of age, 66 years; 40.3% female). There were 350 (56.7%) patients achieving mRS of 3-6 at 3 months, 98 (15.9%) patients with sICH, and the mortality at 3 months was 24.8% (153/616). Baseline NLR was independently associated with poor functional outcome (OR 1.58; 95% CI 1.02-2.45; p = 0.039) and sICH (OR 1.84; 95% CI 1.09-3.11; p = 0.023) but showed a trend for predicting 3-month mortality (OR 1.57; 95% CI 0.94-2.65; p = 0.088). CONCLUSIONS: NLR independently predicts 3-month functional outcome and sICH but the existence of a trend association with mortality after EVT for acute anterior circulation LVOS patients.

Emergent loading dose of antiplatelets for stenting after IV rt-PA in acute ischemic stroke: a feasibility study.

BACKGROUND: A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear. METHODS: A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients. RESULTS: A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients. CONCLUSION: Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Lack of improvement following endovascular therapy in patients with acute ischemic stroke.

BACKGROUND: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. METHODS: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0-1) or good (grades 2-4). RESULTS: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29-8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66-9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39-21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. CONCLUSION: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.

Correlation study between small vessel disease and early neurological deterioration in patients with mild/moderate acute ischemic stroke.

AIMS: Cerebral small vessel disease (SVD) refers to a group of pathological processes that affect small arteries, arterioles, venules, and capillaries of the brain. We hypothesized that imaging markers of SVD could be associated with neurological deterioration during acute phase of mild/moderate ischemic stroke. METHODS: We performed a prospective cohort with 687 consecutive patients with acute ischemic stroke and also with admission NIHSS score below 12 points. Imaging markers of SVD include silent lacunar infarction, deep cerebral microbleeds (CMBs), brain atrophy, periventricular and semiovale white matter hyperintensities, basal ganglia and semiovale enlarged perivascular spaces as well as SVD burden rating scale, which were evaluated and calculated, respectively. Early neurology deterioration (END) was defined as an increment of NIHSS score ≥2 points in the first 72 h after admission. RESULTS: None of these imaging markers and rating scale of SVD significantly correlated with END after adjusted for major confounders. Post hoc analysis indicated similar negative results in different age, TOAST classification and infarction location subgroups. Only silent infarction (OR 2.42, 95%CI 1.33-5.10) and deep CMBs (OR 2.10, 95%CI 1.08-3.72) seemed to be predictors for END in female patients. However, due to the increased type I error in multiple comparisons, these relationships should not be regarded as statistically significant. CONCLUSION: In patients with mild/moderate acute ischemic stroke, imaging markers of SVD did not correlate with END.

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway.

Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1's prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.

Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complications after thrombolysis. METHODS: A total of 189 ischemic stroke patients were prospectively enrolled. Blood samples for leukocyte, neutrophil, and lymphocyte counts were obtained at admission and at 3-6, 12-18, and 36-48 h after IVT. Head CT was performed on admission and repeated after 36-48 h, and a CT scan was done immediately in case of clinical worsening. Hemorrhagic events were categorized as symptomatic intracranial hemorrhage (sICH) and parenchymal hematomas (PH) according to previously published criteria. RESULTS: An increasing trend in the NLR was observed after stroke, and the NLR was higher in patients who developed PH or sICH at 3-6, 12-18, and 36-48 h after IVT (P < 0.01) than in those without PH or sICH. The optimal cutoff value for the serum NLR as an indicator for auxiliary diagnosis of PH and sICH was 10.59 at 12-18 h. Furthermore, the NLR obtained at 12-18-h post-treatment was independently associated with PH (adjusted odds ratio [OR] 1.14) and sICH (adjusted OR 1.14). In addition, patients with a NLR ≥10.59 had an 8.50-fold greater risk for PH (95 % confidence interval [CI] 2.69-26.89) and a 7.93-fold greater risk for sICH (95 % CI 2.25-27.99) than patients with a NLR <10.59. CONCLUSIONS: NLR is a dynamic variable, and its variation is associated with HT after thrombolysis in stroke patients.