MYEF2: an immune infiltration-related prognostic factor in IDH-wild-type glioblastoma.

Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze RNA binding protein (RBP) expression data from The Cancer Genome Atlas (TCGA) for the IDH-wild type GBM cohort. The CIBERSORT algorithm quantified the cellular composition of immune cells and was used to identify key modules associated with CD8+ T cell infiltration. Coexpression networks analysis and protein-protein interaction (PPI) network analysis was used to filter out central RBP genes. Eleven RBP genes, including MYEF2, MAPT, NOVA1, MAP2, TUBB2B, CDH10, TTYH1, PTPRZ1, SOX2, NOVA2 and SCG3, were identified as candidate CD8+ T cell infiltration-associated central genes. A Cox proportional hazards regression model and Kaplan-Meier analysis were applied to identify candidate biomarkers. MYEF2 was selected as a prognostic biomarker based on the results of prognostic analysis. Flow Cytometric Analysis indicated that MYEF2 expression was negatively correlated with dysfunctional CD8+ T cell markers. Kaplan-Meier survival analysis (based on IHC staining) revealed that GBM patients with elevated MYEF2 expression have a better prognosis. Knockdown of MYEF2 in GBM cells via in vitro assays was observed to promote cell proliferation and migration. Our study suggests that MYEF2 expression negatively correlates with T cell exhaustion and tumor progression, rendering it a potentially valuable prognostic biomarker for GBM.

Is STA really a low-flow graft? A quantitative ultrasonographic study of the flow of STA for cerebral revascularization in MMD patients.

OBJECTIVE: Direct revascularization remains an important tool in the treatment of patients with Moyamoya disease (MMD). The superficial temporal artery (STA) is the most commonly used donor vessel for direct bypass, and an STA graft has traditionally been considered a low-flow graft for flow augmentation. This study aimed to quantitatively evaluate the blood flow of the STA after direct revascularization. METHODS: All direct revascularization procedures performed between 2018 and 2021 by one experienced neurosurgeon were screened. Quantitative ultrasound was used to measure the flow data of the patient's bilateral parietal branch of the STA(STA-PB), the bilateral frontal branch of the STA(STA-FB), and the left radial artery. Data on the patients' basic information, Suzuki grade, Matsushima type, anastomosis type, and blood biochemical parameters were collected and analyzed using univariate and multivariate models. An MBC Scale scoring system was proposed to evaluate the recipient artery network of the middle cerebral artery (MCA) tree. The relationship between MBC Scale score and STA graft flow was statistically analyzed. RESULTS: In total, 81 patients (43 males and 38 females) successfully underwent STA-MCA bypass and were included in this study. The mean flow rates in the STA-PB graft on 1 day preoperatively, 1 day postoperatively, 7 days postoperatively, and >6 months postoperatively (long-term) were 10.81, 116.74, 118.44, and 56.20 mL/min respectively. Intraoperative graft patency was confirmed in all patients. Comparing the preoperative and all postoperative time points, the STA-PB flow rates were statistically significant (p < 0.001). The MCA-C score was significantly associated with postoperative flow rate on day 1 (p = 0.007). CONCLUSION: The STA is a useful donor artery for direct revascularization inpatients with MMD and can provide sufficient blood supply to the ischemic cerebral territory.

Ultrasonic hemodynamic changes of superficial temporal artery graft in different angiogenesis outcomes of Moyamoya disease patients treated with combined revascularization surgery.

Objective: Combined bypass is commonly used in adult Moyamoya disease (MMD) for revascularization purposes. The blood flow from the external carotid artery system supplied by the superficial temporal artery (STA), middle meningeal artery (MMA), and deep temporal artery (DTA) can restore the impaired hemodynamics of the ischemic brain. In this study we attempted to evaluate the hemodynamic changes of the STA graft and predict the angiogenesis outcomes in MMD patients after combined bypass surgery by using quantitative ultrasonography. Methods: We retrospectively studied Moyamoya patients who were treated by combined bypass between September 2017 and June 2021 in our hospital. We quantitatively measured the STA with ultrasound and recorded the blood flow, diameter, pulsatility index (PI) and resistance index (RI) to assess graft development preoperatively and at 1 day, 7 days, 3 months, and 6 months after surgery. All patients received both pre- and post- operative angiography evaluation. Patients were divided into either well- or poorly-angiogenesis groups according to the transdural collateral formation status on angiography at 6 months after surgery (W group or P group). Patients with matshushima grade A or B were divided into W group. Patients with matshushima grade C were divided into P group, indicating a poor angiogenesis development. Results: A total of 52 patients with 54 operated hemispheres were enrolled, including 25 men and 27 women with an average age of 39 ± 14.3 years. Compared to preoperative values, the average blood flow of an STA graft at day 1 postoperation increased from 16.06 ± 12.47 to 117.47± 73.77 (mL/min), diameter increased from 1.14 ± 0.33 to 1.81 ± 0.30 (mm), PI dropped from 1.77 ± 0.42 to 0.76 ± 0.37, and RI dropped from 1.77 ± 0.42 to 0.50 ± 0.12. According to the Matsushima grade at 6 months after surgery, 30 hemispheres qualified as W group and 24 hemispheres as P group. Statistically significant differences were found between the two groups in diameter (p = 0.010) as well as flow (p = 0.017) at 3 months post-surgery. Flow also remained significantly different at 6 months after surgery (p = 0.014). Based on GEE logistic regression evaluation, the patients with higher levels of flow post-operation were more likely to have poorly-compensated collateral. ROC analysis showed that increased flow of ≥69.5 ml/min (p = 0.003; AUC = 0.74) or a 604% (p = 0.012; AUC = 0.70) increase at 3 months post-surgery compared with the pre-operative value is the cut-off point which had the highest Youden's index for predicting P group. Furthermore, a diameter at 3 months post-surgery that is ≥0.75 mm (p = 0.008; AUC = 0.71) or 52% (p =0.021; AUC = 0.68) wider than pre-operation also indicates a high risk of poor indirect collateral formation. Conclusions: The hemodynamic of the STA graft changed significantly after combined bypass surgery. An increased flow of more than 69.5 ml/min at 3 months was a good predictive factor for poor neoangiogenesis in MMD patients treated with combined bypass surgery.

A Preliminary Report of One-Session Treatment with Cranioplasty and Superficial Temporal Artery-Middle Cerebral Artery Bypass for Hemorrhagic Moyamoya Disease Patients with Skull Defect.

OBJECTIVE: The objective of this study was to conduct a retrospective analysis of the safety and efficacy of one-session treatment with cranioplasty and superficial temporal artery-middle cerebral artery (STA-MCA) bypass after decompressive craniectomy in hemorrhagic moyamoya disease (MMD). METHODS: From March 2019 to August 2021, 5 patients with hemorrhagic MMD after DC were admitted in Nanfang Hospital. All patients underwent digital subtraction angiography to exclude any spontaneous revascularization between the cortex and temporal muscle and the preservation of STA. Then one-stage treatment with STA-MCA bypass and cranioplasty were performed. If no suitable recipient artery was available, an encephalo-myo-synangiosis procedure was used as a salvage plan. RESULTS: Four patients underwent direct STA-MCA bypass, while one underwent encephalo-myo-synangiosis due to absence of a suitable recipient artery. All patients had no hemorrhage on postoperative computed tomography, and no new infarcts were detected on magnetic resonance imaging. There were no new recurrent symptoms at clinical follow-up 8 to 24 months after surgery. Three patients had improved Glasgow Outcome Scale scores, and 2 patients had stable Glasgow Outcome Scale scores. Perfusion computed tomography showed improvement in cerebral hemodynamics. Four follow-up digital subtraction angiographies were performed, suggesting graft patency. CONCLUSIONS: One-session treatment with extracranial to intracranial bypass and cranioplasty are safe and effective in patients with MMD who have undergone previous decompressive craniectomy due to hemorrhagic attack.

Use of a panel of four microRNAs in CSF as a predicted biomarker for postoperative neoangiogenesis in moyamoya disease.

INTRODUCTION AND AIMS: At present, the treatment for moyamoya disease (MMD) primarily consists of combined direct and indirect bypass surgery. Nevertheless, more than half of indirect bypass surgeries fail to develop good collaterals from the dura and temporal muscle. This study aimed to investigate whether microRNAs (miRNAs) in cerebrospinal fluid (CSF) could serve as biomarkers for the prediction of postoperative collateral formation. METHODS: Moyamoya disease patients with indirect bypass surgery were divided into angiogenesis and non-angiogenesis groups, CSF was obtained, and miRNA sequencing was performed using the CSF. Candidate miRNAs were filtered and subsequently verified through qRT-PCR. The diagnostic utility of these differential miRNAs was investigated by using receiver operating characteristic (ROC) curve analysis. Finally, the potential biological processes and signaling pathways associated with candidate miRNAs were analyzed using R software. RESULTS: The expression levels of four miRNAs (miR-92a-3p, miR-486-3p, miR-25-3p, and miR-155-5p) were significantly increased in the angiogenesis group. By combining these four miRNAs (area under the curve [AUC] =0.970), we established an accurate predictive model of collateral circulation after indirect bypass surgery in MMD patients. GO and KEGG analyses demonstrated a high correlation with biological processes and signaling pathways related to angiogenesis. CONCLUSION: The 4-miRNA signature is a good model to predict angiogenesis after indirect bypass surgery and help the surgeon to select a appreciate bypass strategy.

A Panel of Exosome-Derived miRNAs of Cerebrospinal Fluid for the Diagnosis of Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is an important cause of stroke in children and young adults in Asia. To date, diagnosis remains challenging due to varying clinical manifestations and unknown pathogenesis. The study aims to identify cerebrospinal fluid (CSF) exosomal microRNAs (exomiRs) that can serve as a novel diagnostic biomarker for diagnosis and assess its clinical applications. METHODS: CSF samples were taken from 31 MMD patients and 31 healthy controls. Initial screening of miRNA expression was performed on samples pooled from MMD patients and controls using microarray and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic accuracy of the potential exosomal miRNAs was evaluated using receiver operating characteristic curve analyses in an independent patient cohort. The potential pathways regulated by the miRNAs was also determined using bioinformatics analysis. RESULTS: The microarray results demonstrated that six exomiRs were dysregulated in the MMD patients compared to the controls. Using qRT-PCR, we validated four of the miRNAs (miR-3679-5p, miR-6165, miR-6760-5p, and miR-574-5p) as a biomarker for MMD diagnosis. The four exomiRs showed enhanced sensitivity (75%) and specificity (93.75%) in terms of differentiating MMD patients from healthy subjects [area under the curve (AUC) = 0.9453]. Pathway enrichment analysis for potential targets of six exomiRs identified proteins involved in cell adhesion and junction formation in the brain. CONCLUSIONS: We identified a novel and highly sensitive exomiRs signature for MMD detection and explored its potential targets using bioinformatics analysis.

Flow evaluation of STA-MCA bypass using quantitative ultrasonography: An alternative to standard angiography for follow up of bypass graft.

PURPOSE: To date, digital subtraction angiography (DSA) has been considered as the gold imaging modality for assessing graft patency after extracranial-intracranial bypass. The utility of a noninvasive and quantitative method of assessing graft flow postoperatively was evaluated by using quantitative ultrasonography. METHOD: All STA-MCA bypass surgery performed over a 5-year period at a single institution were reviewed. Measured by duplex ultrasonography, pre-operative (day1) and post-operative (day1, day7, 3month and 6 month) graft blood flow rates were recorded and analyzed. Results were correlated to Matsushima grade determined by DSA performed within 24 h when ultrasonography was conducted to confirm the graft function. RESULTS: 100 patients with 131 operated hemispheres were included in this study. The mean flow rates in the STA graft on pre-operative day1, post-operative day 1 and 7, at 3- and 6-month postoperatively were 24.1, 106.7, 112.6, 97.4 and 79.7 ml/min respectively. The mean post-operative flow in the STA graft graded as A/B/C were significantly different (168.0 ± 34.8 ml/min, 91.0 ± 15.5, 42.1 ± 17.2 ml/min, respectively, p = 0.000). 124.5 ml/min and 65.5 ml/min are good cut-off value for predicting post-operative graft Matsushima grade. The analysis also showed excellent agreement between ultrasonography and DSA for assessing bypass function (κ = 0.78). CONCLUSIONS: The patency of the STA grafts can be assessed noninvasively by quantitative ultrasonography, which results are comparable to those of conventional DSA. This, therefore, suggest that quantitative ultrasonography may be an alternative method to standard DSA for serial follow up of STA grafts.

Membrane Retraction Technique in Bypass Surgery for the Treatment of Adult Moyamoya Disease with Deep-Seated Recipient Artery.

OBJECTIVE: To introduce a membrane retraction technique that can provide good exposure of deep-seated recipient arteries in cortical sulci and simplify the anastomosis procedure. METHODS: Only those adult patients with moyamoya disease who underwent superficial temporal artery to middle cerebral artery bypass surgery during which the suitable recipient arteries were located deep in cortical sulci were included in this retrospective study. By placing 10-0 prolene sutures to the arachnoid membrane of the 2 banks of sulcus, arachnoid retraction was applied to pull the sulcus apart and then the deep-seated recipient arteries were exposed. Standard end-to-side anastomosis was completed. The mean occlusion time and successful rate were recorded and compared with those of the normal procedure. RESULTS: From June to November 2019, 124 superficial temporal artery to middle cerebral artery bypass surgeries for the treatment of moyamoya disease were performed in Nanfang Hospital. The membrane retraction technique was used in 5 patients (5/110, 4.5%) and the success rates were 100%. The mean temporary occlusion time was 27.2 minutes. No procedure-related complications were observed. All patients recovered uneventfully. The postoperative angiograms confirmed good patency of bypass grafts in all 5 cases. CONCLUSIONS: The membrane retraction technique is an effective and safe method for the treatment of adult patients with moyamoya disease with deep-seated recipient arteries within the sulci.

A Hybrid Strategy for Patients With Complex Cerebral Aneurysm: STA-MCA Bypass in Combination With Endovascular Embolization.

Objective: This work aims to present our experience of patients with complex cerebral aneurysm treated with a hybrid approach: superficial temporal artery-middle cerebral artery (STA-MCA) bypass in combination with endovascular exclusion of the aneurysm. Method: Patients with aneurysms deemed unclippable and uncoilable were included. All patients were treated with a hybrid approach. After STA-MCA bypass, the parent artery was temporarily occluded. If the intraoperative motor evoked potential (MEP) and somatosensory evoked potential (SEP) waveforms remain normal and last for 30 min, the aneurysm and te parent artery will be embolized permanently with detachable balloons or coils. Results: A total of 20 patients with 22 aneurysms were included in this study. There were 13 women and 7 men, with an average age of 42.5 years. Intraoperative angiography showed the good patency of all the STA grafts, and neither SEP nor MEP abnormalities were detected. After the parent artery and the aneurysm were occluded, the intraoperative angiography showed an immediately successful exclusion of the aneurysm in 20 aneurysms and immediate contrast stasis in two. All patients recovered uneventfully without ischemic or hemorrhagic complication. Angiography at 6-month follow-up showed the total obliteration in 20 aneurysms. Two aneurysms showed residuals and were recoiled. All STA grafts showed a good patency, and the mean graft flow was 124.2 ml/min. Conclusion: STA-MCA bypass in combination with endovascular exclusion is an appropriate option for patients with complex cerebral aneurysms that are not amenable to direct surgical clipping or endovascular embolization.

[Characteristics of collateral circulation in adult moyamoya disease based on modified Suzuki staging].

OBJECTIVE: To investigate the characteristics of collateral circulation in adult moyamoya disease (MMD). METHODS: The clinical data were collected from all adult patients with MMD undergoing digital subtractive angiography (DSA) in our department from 2006 to 2016. Based on the imaging findings, the patients were divided into ischemia group and bleeding group. A double-blind analysis was conducted of the CT or magnetic resonance imaging findings and the severity of the disease was graded using the modified Suzuki score (mSS). We classified the anastomotic networks in MMD into the superficial meningeal type and deep parenchymal type. The superficial meningeal type was further classified into the leptomeningeal and the durocortical networks, and the deep parenchymal networks into subependymal networks and the inner striatal and inner thalamic networks. RESULTS: No significant difference was found in the distribution of mSS scores between the hemorrhage group and the ischemic group (Χ2=5.812, v=5, P=0.325), but the posterior communicating artery and internal carotid artery diameter ratio (Pcom/ICA ratio) was significantly greater in the hemorrhage group (t=2.119, v=108, P=0.036). The Pcom/ICA ratio differed significantly among the groups with different mSS scores (f=8.924, P=0.00), higher in groups with mSS scores of 3, 4 and 5. The incidence of anterior choroidal artery dilation differed significantly between hemorrhage and ischemic groups (Χ2=11.79, P=0.001). The incidences of durocortical networks (Χ2=0.327, P=0.567) and subependymal networks (Χ2=0.011, P=0.917) were comparable between hemorrhage group and ischemic groups, but the incidence of leptomeningeal networks (P=0.018) and inner striatal and inner thalamic networks (Χ2=7.551, P=0.006) differed significantly between the two groups. CONCLUSION: The collateral circulation vascular system is an important component of cerebral blood flow in MMD patients and varies from patient to patient. Patients with MMD exhibit increased Pcom/ICA ratio with abnormal expansion of the anterior choroidal artery, and the leptomeningeal networks and the inner striatal and inner thalamic networks are independent risk factors for cerebral hemorrhage.