Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarct in China.

BACKGROUND: Endovascular therapy administered within 24 hours has been shown to improve outcomes for patients with acute ischemic stroke with large infarction, but the data on its cost-effectiveness are limited. OBJECTIVE: To evaluate the cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarction in China, the largest low- and middle-income country. METHODS: A short-term decision tree model and a long-term Markov model were used to analyze the cost-effectiveness of endovascular therapy for patients with acute ischemic stroke with large infarction. Outcomes, transition probability, and cost data were obtained from a recent clinical trial and published literature. The benefit of endovascular therapy was assessed by the cost per quality-adjusted life-years (QALYs) gained in the short and long term. Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: Compared with medical management alone, endovascular therapy for acute ischemic stroke with large infarction was found to be cost-effective from the fourth year onward and during a lifetime. In the long term, endovascular therapy yielded a lifetime gain of 1.33 QALYs at an additional cost of ¥73 900 (US$ 11 400), resulting in an incremental cost of ¥55 500 (US$ 8530) per QALY gained. Probabilistic sensitivity analysis showed that endovascular therapy was cost-effective in 99.5% of the simulation runs at a willingness-to-pay threshold of ¥243 000 (3 × gross domestic product per capita of China in 2021) per QALY gained. CONCLUSIONS: Endovascular therapy for acute ischemic stroke with large infarction could be cost-effective in China.

First pass effect of mechanical thrombectomy for acute vertebrobasilar artery occlusion: data from the ANGEL-ACT registry.

BACKGROUND: To explore the incidence, predictors, and association of first pass effect (FPE) on clinical outcomes of mechanical thrombectomy (MT) for acute vertebrobasilar artery occlusion (VBAO) in the Asian population. METHODS: We selected patients from the ANGEL-ACT registry. We defined FPE as complete recanalization after one MT attempt without rescue treatment, multiple pass effect (MPE) as complete recanalization after >1 MT attempt or after one MT attempt with rescue treatment, and incomplete recanalization (ICR) as a modified Thrombolysis in Cerebral Ischemia score of 2b, independent of the number of MT attempts. We conducted multivariable logistic analyses to identify the independent predictors of FPE and to compare the outcomes, including favorable outcome, mortality within 90 days, and intracranial hemorrhage (ICH) among the FPE, MPE, and ICR groups. RESULTS: Two hundred and seventy-nine patients, 68 with FPE (24.4%), 114 with MPE (40.9%), and 83 with ICR (29.7%), were included. Underlying intracranial atherosclerosis disease (ICAD) (adjusted OR (aOR) 0.16, 95% CI 0.08 to 0.34, P<0.001) was independently associated with a low chance of FPE. Furthermore, FPE was associated with a favorable outcome compared with MPE and ICR (MPE vs FPE, aOR 0.49, 95% CI 0.25 to 0.97, P=0.040; ICR vs FPE, aOR 0.38, 95% CI 0.18 to 0.81, P=0.012), and decreased mortality (MPE vs FPE, aOR 2.57, 95% CI 1.04 to 6.36, P=0.041) compared with MPE but similar mortality to ICR (P=0.374). No difference was found for ICH among the three groups (P>0.05). CONCLUSIONS: FPE occurred in 24.4% of patients with VBAO in our cohort, which was associated with improved clinical outcomes compared with MPE and ICR. VBAO with underlying ICAD was less likely to achieve FPE. TRIAL REGISTRATION NUMBER: NCT03370939.

Futile reperfusion of endovascular treatment for acute anterior circulation large vessel occlusion in the ANGEL-ACT registry.

BACKGROUND: Some patients with large vessel occlusion (LVO) still cannot achieve functional independence despite successful reperfusion after endovascular treatment (EVT), named futile reperfusion. We aimed to explore the incidence and predictors of futile reperfusion of EVT for anterior circulation LVO in the Chinese population based on a nationwide prospective multicenter registry. METHODS: We selected patients from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) registry. Successful reperfusion was defined as modified Treatment In Cerebral Ischemia (mTICI) 2b-3 after EVT, and functional independence was defined as 90-day modified Rankin Scale (mRS) 0-2. A multivariable regression model was performed to identify the independent predictors of futile reperfusion in anterior circulation LVO patients. RESULTS: A total of 1158 anterior circulation LVO patients were included in our study. 600 of the 1158 patients (51.8%) suffered futile reperfusion. Age ≥69 (adjusted OR (aOR) 1.69, 95% CI 1.21 to 2.35, P=0.002), baseline National Institutes of Health Stroke Scale (NIHSS) ≥14 (aOR 2.36, 95% CI 1.71 to 3.27, P<0.001), baseline serum glucose ≥6.5 mmol/L (aOR 1.73, 95% CI 1.27 to 2.36, P=0.001), drip and ship (aOR 1.56, 95% CI 1.11 to 2.18, P=0.011), and general anesthesia (aOR 2.28, 95% CI 1.66 to 3.14, P<0.001) were associated with a high risk of futile reperfusion in the anterior LVO patients after EVT, whereas baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥8 (aOR 0.65, 95% CI 0.47 to 0.91, P=0.011) and complete reperfusion (aOR 0.62, 95% CI 0.43 to 0.89, P=0.010) were associated with a low risk of futile reperfusion in the anterior LVO patients after EVT. CONCLUSIONS: In the ANGEL-ACT registry, 51.8% of anterior circulation LVO patients suffered futile reperfusion after EVT. Age ≥69 years, baseline NIHSS ≥14, baseline serum glucose ≥6.5 mmol/L, drip and ship, general anesthesia, baseline ASPECTS <8, and incomplete reperfusion were the independent predictors of futile reperfusion.

Predicting the Rapid Improvement of Papilledema After Stenting in Idiopathic Intracranial Hypertension.

PURPOSE: This study aimed to identify predictors of rapid improvement of papilledema after stenting and develop a simple preintervention scale. METHODS: A prospective cohort of idiopathic intracranial hypertension (IIH) with venous sinus stenosis (VSS) treated with stenting in a tertiary hospital from January 2014 to December 2019 was reviewed. We categorized papilledema improvement into favorable (grades 0-1) and unfavorable (grades 2-5). We employed logistic regression analysis to find the predictive factors and develop the predictive scale. We then estimated the performance of the scale using the ROC curve and Hosmer-Lemeshow test. RESULTS: There were 110 patients who underwent venous sinus stenting, with a mean age of 37.1 years and a predominance of females (77.3%). A total of 85 patients had a favorable outcome following stenting, while 25 patients had an unfavorable outcome. The results of the multivariate analysis indicate that lower preoperative pressure gradients (odds ratio, OR: 4.01; 95% confidence interval, CI: 1.27-12.68), stenosis rates (OR: 4.16; 95% CI: 1.11-15.56), and preoperative papilledema grades (OR: 2.92; 95% CI: 1.44-5.91) were independently associated with rapid improvement of papilledema following stenting treatment. The 3­item scale exhibited good discrimination with an area under the curve (AOC) of 0.81 (95% CI 0.72-0.89, p < 0.001), as well as acceptable calibration determined by the Hosmer-Lemeshow test (P = 0.42). The optimal cut-off value of the scale (range 0-6 points) was ≥ 4 points, with a sensitivity of 72%, specificity of 73%, and accuracy of 78%. CONCLUSION: The presence of lower preoperative pressure gradients, stenosis severity, and preoperative status of papilledema were identified as positive predictors of rapid improvement of the papilledema following stenting in IIH patients. The 3­item scale provides a promising preintervention predictive model for predicting rapid response following stenting treatment in IIH patients with VSS.

Stenting versus medical treatment for idiopathic intracranial hypertension: a matched-control study.

BACKGROUND: This prospective cohort study compared the outcomes of stenting and medical treatment for patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis (VSS). METHODS: In this single-center cohort study, patients with IIH and VSS were evaluated between January 2014 and December 2019 with follow-up periods of 1, 3, and 6 months. The patients received either stenting or medical treatment. The two groups underwent 1:1 matching using propensity score analysis, and the clinical outcomes were compared. RESULTS: Following 1:1 matching, 36 patients who underwent stenting and 36 who underwent medical treatment were matched. The median improvements in the papilledema Frisén grade were greater in the stenting group at 1 month (-2 vs 0), 3 months (-3 vs -1), and 6 months (-3 vs -1) than in the medical treatment group. Patients who received stenting treatment had a significantly higher prevalence of complete resolution of their respective symptoms (headache, tinnitus, or visual disturbances) at 3 months (58.3% vs 13.9%, OR 8.68, 95% CI 2.74 to 27.52) and 6 months (80.6% vs 22.2%, OR 14.50, 95% CI 4.64 to 45.32) than those receiving medical treatment. CONCLUSIONS: This matched-control study shows that stenting has a greater efficacy rate and rapid resolution of papilledema and its respective symptoms compared with medical treatment.

Predictors of parenchymal hemorrhage after endovascular treatment in acute ischemic stroke: data from ANGEL-ACT Registry.

BACKGROUND: Parenchymal hemorrhage (PH) is a troublesome complication after endovascular treatment (EVT). OBJECTIVE: To investigate the incidence, independent predictors, and clinical impact of PH after EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). METHODS: Subjects were selected from the ANGEL-ACT Registry. PH was diagnosed according to the European Collaborative Acute Stroke Study classification. Logistic regression analyses were performed to determine the independent predictors of PH, as well as the association between PH and 90-day functional outcome assessed by modified Rankin Scale (mRS) score. RESULTS: Of the 1227 enrolled patients, 147 (12.0%) were diagnosed with PH within 12-36 hours after EVT. On multivariable analysis, low admission Alberta Stroke Program Early CT score (ASPECTS)(adjusted OR (aOR)=1.13, 95% CI 1.02 to 1.26, p=0.020), serum glucose >7 mmol/L (aOR=1.82, 95% CI 1.16 to 2.84, p=0.009), and neutrophil-to-lymphocyte ratio (NLR; aOR=1.05, 95% CI 1.02 to 1.09, p=0.005) were associated with a high risk of PH, while underlying intracranial atherosclerotic stenosis (ICAS; aOR=0.42, 95% CI 0.22 to 0.81, p=0.009) and intracranial angioplasty/stenting (aOR=0.37, 95% CI 0.15 to 0.93, p=0.035) were associated with a low risk of PH. Furthermore, patients with PH were associated with a shift towards to worse functional outcome (mRS score 4 vs 3, adjusted common OR (acOR)=2.27, 95% CI 1.53 to 3.38, p<0.001). CONCLUSIONS: In Chinese patients with AIS caused by anterior circulation LVO, the risk of PH was positively associated with low admission ASPECTS, serum glucose >7 mmol/L, and NLR, but negatively related to underlying ICAS and intracranial angioplasty/stenting. TRIAL REGISTRATION NUMBER: NCT03370939.

Unexplained early neurological deterioration after endovascular treatment for acute large vessel occlusion: incidence, predictors, and clinical impact: Data from ANGEL-ACT registry.

BACKGROUND: Early neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (ENDunexplained), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of ENDunexplained after EVT in patients with acute LVO. METHODS: Subjects were selected from the ANGEL-ACT registry. ENDunexplained was defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of ENDunexplained, as well as the association between ENDunexplained and 90-day outcomes assessed by modified Rankin Scale (mRS) score. RESULTS: Among the 1557 enrolled patients, the incidence of ENDunexplained was 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p<0.001), general anesthesia (OR=3.15, 95% CI 1.81 to 5.48, p<0.001), admission neutrophil to lymphocyte ratio >5 (OR=2.82, 95% CI 1.61 to 4.94, p<0.001), and number of EVT attempts >3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of ENDunexplained. Furthermore, patients with ENDunexplained were associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, p<0.001). CONCLUSIONS: ENDunexplained associated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of ENDunexplained were identified in this study, which should be considered in daily practice to improve acute LVO management. CLINICAL TRIAL REGISTRATION: http://wwwclinicaltrialsgov NCT03370939.

Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry.

BACKGROUD: The goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT). METHODS: This is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0-1, 0-2, and 0-3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days. RESULTS: A total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes. CONCLUSIONS: In patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

Quantitative analysis of unruptured intracranial aneurysm wall thickness and enhancement using 7T high resolution, black blood magnetic resonance imaging.

BACKGROUND: This study was performed to quantify intracranial aneurysm wall thickness (AWT) and enhancement using 7T MRI, and their relationship with aneurysm size and type. METHODS: 27 patients with 29 intracranial aneurysms were included. Three-dimensional T1 weighted pre- and post-contrast fast spin echo with 0.4 mm isotropic resolution was used. AWT was defined as the full width at half maximum on profiles of signal intensity across the aneurysm wall on pre-contrast images. Enhancement ratio (ER) was defined as the signal intensity of the aneurysm wall over that of the brain parenchyma. The relationships between AWT, ER, and aneurysm size and type were investigated. RESULTS: 7T MRI revealed large variations in AWT (range 0.11-1.24 mm). Large aneurysms (>7 mm) had thicker walls than small aneurysms (≤7 mm) (0.49±0.05 vs 0.41±0.05 mm, p<0.001). AWT was similar between saccular and fusiform aneurysms (p=0.546). Within each aneurysm, a thicker aneurysm wall was associated with increased enhancement in 28 of 29 aneurysms (average r=0.65, p<0.05). Thicker walls were observed in enhanced segments (ER >1) than in non-enhanced segments (0.53±0.09 vs 0.38±0.07 mm, p<0.001). CONCLUSION: Improved image quality at 7T allowed quantification of intracranial AWT and enhancement. A thicker aneurysm wall was observed in larger aneurysms and was associated with stronger enhancement.

Factors influencing early neurological improvement after mechanical thrombectomy among patients with acute basilar artery occlusion: a single center prospective observational cohort study.

The predictive value of and the influencing factors associated with early neurological improvement (ENI) among patients with acute basilar artery occlusion (BAO) have not been well studied. The present study aimed to evaluate whether ENI predicted a better functional outcome and to identify the influencing factors of ENI. We performed a prospective observational analysis among 187 patients with acute BAO who underwent endovascular treatment (EVT) in Beijing Tiantan Hospital from January 2012 to July 2018. ENI was defined as having a drop on the National Institutes of Health Stroke Scale (NIHSS) by 8 or more scores or having a NIHSS of 0-1 within 24 h after EVT. A multivariate logistic regression model with backward selection was used to identify the influencing factors associated with ENI. ENI had a sensitivity of 0.69 and a specificity of 0.68 to predict a favorable outcome at 90 days after EVT. In addition, patients with ENIs had lower modified Rankin Scale score (mRS) (median: 2.0 vs. 5.0, p < 0.001) and were more likely to survive (95.2% vs. 72.0%, p < 0.001) and achieve functional independence (74.2% vs. 36.8%, p < 0.001). NIHSS before EVT, complete recanalization, white blood cell counts and general anesthetics were significant factors associated with ENI. A one-unit higher NIHSS and complete recanalization were associated with 1.04 (95% CI 1.01-1.08) and 2.71 (95% CI 1.14-6.45) times higher odds of achieving ENI, respectively. In conclusion, in patients with acute BAO, ENI within 24 hours after EVT can predict favorable outcomes at 90 day. Patients with higher NIHSS, lower white blood cell counts before surgery, without general anesthetics and patients with complete recanalization were more likely to achieve ENIs.

Silencing of Long Non-coding RNA GAS5 Suppresses Neuron Cell Apoptosis and Nerve Injury in Ischemic Stroke Through Inhibiting DNMT3B-Dependent MAP4K4 Methylation.

Ischemic stroke is associated with various physiological and pathological processes including neuronal apoptosis. Growth-arrest-specific transcript 5 (GAS5), a long non-coding RNA (lncRNA), has been recently reported to affect ischemic stroke-induced neuron apoptosis, while its mechanisms remain largely undefined. Through in silico analysis, GAS5 was predicted to interact with the promoter of MAP4K4. The aim of the present study was therefore to investigate the possible role of GAS5 in the progression of ischemic stroke via regulation of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) methylation. The expression of MAP4K4 was found to be lowly expressed in the clinical samples collected from 55 patients. MAP4K4 was suggested to be methylated in an in vitro model of oxygen-glucose deprivation (OGD)-treated mouse primary cortical neurons, while its overexpression could inhibit OGD-induced neuronal apoptosis. A series of dual-luciferase reporter, RIP, RNA pull-down, ChIP MSP, and BSP assays confirmed that GAS5 significantly induced MAP4K4 methylation and downregulated MAP4K4 expression through the recruitment of DNA methyltransferase 3B (DNMT3B). An in vivo ischemic stroke model was developed using middle cerebral artery occlusion (MCAO). Upregulation of GAS5 promoted OGD-induced neuronal apoptosis in the in vitro model and increased cerebral infarction size and neurological score in the in vivo model by reducing MAP4K4 expression. Collectively, the present study highlights that silencing GAS5 may inhibit neuronal apoptosis and improve neurological function in ischemic stroke by suppressing DNMT3B-mediated MAP4K4 methylation, which contributes to better understanding of the pathologies of ischemic stroke and development of novel therapeutic options for this disease.

Exosomes derived from microRNA-138-5p-overexpressing bone marrow-derived mesenchymal stem cells confer neuroprotection to astrocytes following ischemic stroke via inhibition of LCN2.

BACKGROUND: MicroRNAs (miRNAs) are implicated in the progression of ischemic stroke (IS) and bone marrow-derived mesenchymal stem cells (BMSCs)-derived exosomes play a role in IS therapy. Herein we hypothesized that the BMSCs-derived exosomes containing overexpressed miR-138-5p could protect the astrocytes following IS involved with lipocalin 2 (LCN2). METHODS: The differentially expressed gene related to IS was initially identified by bioinformatics analysis. miR-138-5p was predicted to regulate LCN2. The expression of miR-138-5p and LCN2 was altered in the oxygen-glucose deprivation (OGD)-induced astrocytes. Furthermore, the cell behaviors and inflammatory responses were evaluated both in astrocytes alone and astrocytes co-cultured with exosomes derived from BMSCs overexpressing miR-138-5p to explore the involvement of miR-138-5p and LCN2 in IS. Besides, middle cerebral artery occlusion (MCAO) mouse model was established to explore the effect of BMSCs-derived exosomal miR-138-5p in IS in vivo. RESULTS: LCN2 was highly expressed in IS. Besides, LCN2 was a target gene of miR-138-5p. BMSCs-derived exosomes could be endocytosed by astrocytes via co-culture. Overexpression of miR-138-5p promoted the proliferation and inhibited apoptosis of astrocytes injured by OGD, accompanied by the reduced expression of inflammatory factors, which was achieved by down-regulating LCN2. More importantly, BMSCs delivered miR-138-5p to the astrocytes via exosomes and BMSCs-derived exosomal miR-138-5p alleviated neuron injury in IS mice. CONCLUSION: BMSCs-derived exosomal miR-138-5p reduces neurological impairment by promoting proliferation and inhibiting inflammatory responses of astrocytes following IS by targeting LCN2, which may provide a novel target for IS treatment.

Cerebral Fat Embolism as Complication of Facial Fat Graft: Retrospective Analysis of Clinical Characteristics, Treatment, and Prognosis.

BACKGROUND: Cerebral fat embolism (CFE) is a rare complication that usually occurs after trauma injury. The incidence of CFE due to aesthetic surgery is extremely rare and can lead to fatal outcome. Due to the rarity of this complication, there is still lack of knowledge and standardization of the treatment. CASE DESCRIPTION: Herein, we reported 6 cases of CFE that occurred in patients who underwent cosmetic surgery. Among 5 patients who had large artery occlusion, 3 patients survived and 2 patients died due to progression of the disease. One patient had the ophthalmic artery occlusion. In addition, embolectomy was performed in 5 patients and 3 patients had decompressive craniectomy following endovascular treatment due to severe brain edema. CONCLUSIONS: CFE is associated with high morbidity and mortality, and early surgical intervention can improve the prognosis.

Mechanical thrombectomy and rescue therapy for intracranial large artery occlusion with underlying atherosclerosis.

OBJECTIVE: To investigate the safety and efficacy of mechanical thrombectomy plus rescue therapy for intracranial large artery occlusion (ILAO) with underlying intracranial atherosclerosis (ICAS). METHODS: Patients enrolled in the intervention group of EAST (Endovascular Therapy for Acute ischemic Stroke Trial) were analyzed. For underlying ICAS identified during the stent retrieval procedure, rescue treatment was required for those with (1) a degree of arterial stenosis >70% or (2) any degree of arterial with blood flow impairment or (3) evidence of re-occlusion. Outcomes were compared between the ICAS group and the embolic group. Multivariate logistic regression was performed to determine independent predictors of functional independence at 90 days. RESULTS: Among the 140 patients included in the analysis, underlying ICAS was identified in 47 (34%), and 30 patients (21.4%) were considered to be eligible to receive rescue treatment. Of the 30 patients, 27 (90%) actually received rescue therapy. Recanalization rate (95.7% vs 96.8%, P=0.757) and functional independence at 90 days (63.8% vs 51.6%, P=0.169) were comparable between the ICAS group and the embolic group. No significant difference in symptomatic hemorrhage (4.3% vs 4.3%, P=1.000) or death (12.8% vs 12.9%, P=0.982) was found between the two groups. National Institutes of Health Stroke Scale score at presentation (OR=0.865, 95% CI 0.795 to 0.941; P=0.001) and modified Thrombolysis in Cerebral Infarction after the procedure (OR=2.864, 95% CI 1.018 to 8.061; P=0.046) were independently associated with functional independence at 90 days. CONCLUSIONS: Mechanical thrombectomy is safe in patients with ILAO with underlying ICAS. By employing a standard rescue therapy, favorable outcomes could be achieved in such patients. CLINICAL TRIAL REGISTRATION: NCT02350283 (Post-results).

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial.

INTRODUCTION: Brain arteriovenous malformations (BAVMs) are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. METHODS: This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety), and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy). Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula), volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS). DISCUSSION: The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs.

Gamma Knife surgical treatment for partially embolized cerebral arteriovenous malformations.

OBJECTIVE: A combination of embolization and radiosurgery is used as a common strategy for the treatment of large and complex cerebral arteriovenous malformations (AVMs). This study presents the experiences of partially embolized cerebral AVMs followed by Gamma Knife surgery (GKS) and assesses predictive factors for AVM obliteration and hemorrhage. METHODS: The interventional neuroradiology database that was reviewed included 404 patients who underwent AVM embolization. Using this database, the authors retrospectively analyzed all partially embolized AVM cases followed by GKS for a residual nidus. Except for cases of complete AVM obliteration, the authors excluded all patients with radiological follow-up of less than 2 years. Logistic regression analysis was used to analyze the predictive factors related to AVM obliteration and hemorrhage following GKS. Kaplan-Meier analysis was used to evaluate the obliteration with a cutoff AVM nidus volume of 3 cm(3) and 10 cm(3). RESULTS: One hundred sixty-two patients qualified for the study. The median patient age was 26 years and 48.8% were female. Hemorrhage presented as the most common symptom (48.1%). The median preembolization volume of an AVM was 14.3 cm(3). The median volume and margin dose for GKS were 10.92 cm(3) and 16.0 Gy, respectively. The median radiological and clinical follow-up intervals were 47 and 79 months, respectively. The annual hemorrhage rate was 1.71% and total obliteration rate was 56.8%. Noneloquent area (p = 0.004), superficial location (p < 0.001), decreased volume (p < 0.001), lower Spetzler-Martin grade (p < 0.001), lower Virginia Radiosurgery AVM Scale (RAS; p < 0.001), lower Pollock-Flickinger score (p < 0.001), lower modified Pollock-Flickinger score (p < 0.001), increased maximum dose (p < 0.001), and increased margin dose (p < 0.001) were found to be statistically significant in predicting the probability of AVM obliteration in the univariate analysis. In the multivariate analysis, only volume (p = 0.016) was found to be an independent prognostic factor for AVM obliteration. The log-rank (Mantel-Cox) test of the Kaplan-Meier analysis (chi-square = 54.402, p < 0.001) showed a significantly decreased obliteration rate of different cutoff AVM volume groups of less than 3 cm(3), 3-10 cm(3), and more than 10 cm(3). No independent prognostic factor was found for AVM hemorrhage in multivariate analysis. CONCLUSIONS: Partially embolized AVMs are amenable to successful treatment with GKS. The volume of the nidus significantly influences the outcome of radiosurgical treatment. The Virginia RAS and Pollock-Flickinger score were found to be reliable scoring systems for selection of patient candidates and prediction of partially embolized AVM closure and complications for GKS.

Inhibition of ocular neovascularization by co-inhibition of VEGF-A and PLGF.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. METHODS: Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. RESULTS: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. CONCLUSIONS: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF as novel targets for CNV therapy.