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Abstract To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p

Abstract Background The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. Methods In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRβ, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. Results Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. Conclusion Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.

Abstract Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single‐cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate‐limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti‐inflammatory polymorphonuclear myeloid‐derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research.

BackgroundDisorders of consciousness (DoC) represent a spectrum of neurological conditions that pose significant treatment challenges. Percutaneous short-term spinal cord stimulation (SCS) has emerged as a promising experimental diagnostic treatment to assess and potentially improve consciousness levels. However, the effectiveness of this intervention is frequently compromised by the shift of electrodes, particularly in the cervical region, which can negatively affect therapeutic outcomes.MethodsThis retrospective study aimed to study if electrodes shift in percutaneous short-term SCS in patients with DoC would affect the outcome. We analyzed the relationship between electrode shift length and patient outcome, as well as the correlation with various anatomical parameters, including the actual length of the cervical spine, linear length, spinal canal transverse diameter, spinal canal diameter, and C2 cone height, in a cohort of patients undergoing the procedure.ResultsOur findings revealed that in patients with better outcome, there are significant less patient with electrode shift (p = 0.019). Further, a linear correlation was found between the length of electrode shift and patients’ outcome (Rho = 0.583, p = 0.002), with longer shift lengths associated with poorer outcomes. Contrary to our expectations, there was no significant association between the measured anatomical parameters and the extent of electrode shift. However, a trend was found between the actual length of the cervical spine and the shift of the electrode (p = 0.098). Notably, the shorter spinal canal transverse diameter was found to be significantly associated with better outcome in patients with DoC receiving percutaneous short-term SCS (p = 0.033).ConclusionThese results highlight the clinical importance of electrode stability in the cervical region during SCS treatment for patients with DoC. Ensuring secure placement of electrodes may play a crucial role in enhancing patients’ outcome and minimize postoperative complications. Given the lack of association with expected anatomical parameters, future research should investigate other factors that could impact electrode stability to optimize this therapeutic intervention.

Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Abstract At present, there is limited research on the mechanisms underlying moyamoya disease (MMD). Herein, we aimed to determine the role of glutamine in MMD pathogenesis, and 360 adult patients were prospectively enrolled. Human brain microvascular endothelial cells (HBMECs) were subjected to Integrin Subunit Beta 4 (ITGB4) overexpression or knockdown and atorvastatin. We assessed factors associated with various signaling pathways in the context of the endothelial‐to‐mesenchymal transition (EndMT), and the expression level of related proteins was validated in the superficial temporal arteries of patients. We found glutamine levels were positively associated with a greater risk of stroke (OR = 1.599, p = 0.022). After treatment with glutamine, HBMECs exhibited enhanced proliferation, migration, and EndMT, all reversed by ITGB4 knockdown. In ITGB4‐transfected HBMECs, the MAPK–ERK–TGF–β/BMP pathway was activated, with Smad4 knockdown reversing the EndMT. Furthermore, atorvastatin suppressed the EndMT by inhibiting Smad1/5 phosphorylation and promoting Smad4 ubiquitination in ITGB4‐transfected HBMECs. We also found the protein level of ITGB4 was upregulated in the superficial temporal arteries of patients with MMD. In conclusion, our study suggests that glutamine may be an independent risk factor for hemorrhage or infarction in patients with MMD and targeting ITGB4 could potentially be therapeutic approaches for MMD.

Abstract Background Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive. Methods In this study, we employed a combination of single‐cell RNA sequencing (scRNA‐seq), mass cytometry and RNA‐sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age‐matched healthy controls. Results Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T‐cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA‐DR and p‐STAT3. Conclusions Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T‐cell populations, including a decrease in effector T‐cells and an increase in regulatory T‐cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.

Abstract Internal carotid artery occlusion (ICAO) is a relatively uncommon but important cause of transient ischaemic attack and cerebral infarction. Hybrid surgery (HS) improves cerebral perfusion, but its impact on neurocognitive function has been controversial. Patients with symptomatic chronic ICAO treated by hybrid surgery or medical treatment from 2016 to 2019 were included. We recorded and analysed the clinical characteristics, angiographic data, outcomes and cognitive status. Functional assessments, including the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale–Cognitive Subtest (ADAS-cog), verbal fluency, and Colour Trail test Parts 1 and 2, were administered. Significant improvements in the ADAS (before, 7.5 ± 6.2 versus after, 5.2 ± 5.7; P = 0.022), MMSE (before, 25.5 ± 2.8 versus after, 28.1 ± 2.3; P = 0.013), and Colour Trail test Part 1 (before, 118.3 ± 26.5 versus after, 96.2 ± 23.1; P = 0.016) were observed six months after HS. Moreover, the abovementioned postprocedure scales were ameliorated in the HS group. This study found that in patients with multiple symptomatic ICAO and objective ipsilateral ischaemia, successful HS leads to improvement in the scores of three cognitive tests.

Abstract Background Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain. Methods Single‐cell Cytometry by Time‐of‐Flight (CyTOF) technology was employed to profile the single‐cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression. Results Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up‐regulated in T cells, B cells and monocytes from the controls but down‐regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti‐inflammatory functional molecules (IL‐4 and IL‐10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC = 0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out‐of‐bag errors). Conclusion These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.

Background and objectivesInitial shunt failure following ventriculoperitoneal (VP) shunt surgery has a significant impact on the working time of the shunt. However, there are few studies regarding factors affecting VP shunt longevity. Hence, in this study, we aimed to build a nomogram to predict the longevity of the replacement VP shunt in patients with initial shunt failure.MethodsFrom 2011 to 2021, 142 patients with initial VP failure who underwent VP shunt revision were enrolled and relevant clinical and demographic factors were analyzed. Univariate and multivariate Cox proportional hazard regression models were used to choose predictors, and a nomogram was constructed using nine independent prognostic variables: sex, age, hydrocephalus type, intensive care unit admission, tracheostomy, decompressive craniectomy, craniotomy, lumbar cisterna drainage, and ventricular drainage. The prediction models’ discrimination, accuracy, calibration, and clinical value were evaluated using Harrell’s C-index, a calibration plot, and decision curve analysis.ResultsAt 1 month, 3 months, and 5 years, the nomogram’s C-index was 0.680, 0.708, and 0.694, respectively. The nomogram’s calibration plot provided a good fit for the overall prediction over the course of 1 year. Decision curve analysis predicted that 1–3 months after surgery will yield good net benefits between 30 and 50% probability thresholds.ConclusionA preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement.

Background and purposeWhen it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut microbiome, an environmental variable, and MMD. Consequently, to identify the particular bacteria that cause MMD, we examined the gut microbiome of MMD individuals and healthy controls (HC).MethodsA prospective case-control investigation was performed from June 2021 to May 2022. The fecal samples of patients with MMD and HC were obtained. Typically, 16S rRNA sequencing was employed to examine their gut microbiota. The QIIME and R softwares were used to examine the data. The linear discriminant analysis effect size analysis was used to determine biomarkers. Multivariate analysis by linear models (MaAsLin)2 were used to find associations between microbiome data and clinical variables. Model performance was assessed using the receiver operating characteristic curve and the decision curve analysis.ResultsThis investigation involved a total of 60 MMD patients and 60 HC. The MMD group’s Shannon and Chao 1 indices were substantially lower than those of the HC cohort. β-diversity was significantly different in the weighted UniFrac distances. At the phylum level, the relative abundance of Fusobacteriota/Actinobacteria was significantly higher/lower in the MMD group than that in the HC group. By MaAsLin2 analysis, the relative abundance of the 2 genera, Lachnoclostridium and Fusobacterium, increased in the MMD group, while the relative abundance of the 2 genera, Bifidobacterium and Enterobacter decreased in the MMD group. A predictive model was constructed by using these 4 genera. The area under the receiver operating characteristic curve was 0.921. The decision curve analysis indicated that the model had usefulness in clinical practice.ConclusionsThe gut microbiota was altered in individuals with MMD, and was characterized by increased abundance of Lachnoclostridium and Fusobacterium and decreased abundance of Bifidobacterium and Enterobacter. These 4 genera could be used as biomarkers and predictors in clinical practice.

Abstract Owing to their superior capabilities and advanced achievements, Transformers have gradually attracted attention with regard to understanding complex brain processing mechanisms. This study aims to comprehensively review and discuss the applications of Transformers in brain sciences. First, we present a brief introduction of the critical architecture of Transformers. Then, we overview and analyze their most relevant applications in brain sciences, including brain disease diagnosis, brain age prediction, brain anomaly detection, semantic segmentation, multi‐modal registration, functional Magnetic Resonance Imaging (fMRI) modeling, Electroencephalogram (EEG) processing, and multi‐task collaboration. We organize the model details and open sources for reference and replication. In addition, we discuss the quantitative assessments, model complexity, and optimization of Transformers, which are topics of great concern in the field. Finally, we explore possible future challenges and opportunities, exploiting some concrete and recent cases to provoke discussion and innovation. We hope that this review will stimulate interest in further research on Transformers in the context of brain sciences.

Background and purposeUrea cycle metabolites are expected to be the biomarkers for cerebrovascular diseases. However, the effects of circulating urea cycle metabolites on the risk of MMD and its subcategories remain unclear. The aim of this study was to prospectively investigate the association between plasma urea cycle metabolites and the risk of MMD and its subcategories.MethodsWe measured plasma urea cycle metabolite levels for 360 adult MMD patients and 89 matched healthy controls. Clinical and laboratory characteristics were obtained from the medical record. The study was conducted from July 2020 to December 2021.ResultsAfter multivariate adjustment, the risk of MMD increased with each increment in ornithine level (per natural log [ornithine] increment: OR, 3.893; 95% CI, 1.366–11.090). The risk of MMD decreased with each increment in arginine level (per natural log [arginine] increment: OR, 0.109; 95% CI, 0.028–0.427), urea level (per natural log [urea] increment: OR, 0.261; 95% CI, 0.072–0.940), and global arginine bioavailability ratio (GABR) level (per natural log [GABR] increment: OR, 0.189; 95% CI, 0.074–0.484). The addition of plasma arginine (integrated discrimination improvement: 1.76%, p = 0.021) or GABR (integrated discrimination improvement: 1.76%, p = 0.004) to conventional risk factors significantly improved the risk reclassification for MMD.ConclusionPlasma ornithine levels are positively associated with the risk of MMD. By contrast, the levels of arginine, urea, and GABR are inversely related to the risk of MMD. Plasma urea cycle metabolites might be potential biomarkers for the risk of MMD.

BackgroundBrain metastases (BMs) are the most common central nervous system (CNS) malignant tumors, with rapid disease progression and extremely poor prognosis. The heterogeneity between primary lung cancers and BMs leads to the divergent efficacy of the adjuvant therapy response to primary tumors and BMs. However, the extent of heterogeneity between primary lung cancers and BMs, and the evolutionary process remains little known.MethodsTo deeply insight into the extent of inter-tumor heterogeneity at a single-patient level and the process of these evolutions, we retrospectively analyzed a total of 26 tumor samples from 10 patients with matched primary lung cancers and BMs. One patient underwent four times brain metastatic lesion surgery with diverse locations and one operation for the primary lesion. The genomic and immune heterogeneity between primary lung cancers and BMs were evaluated by utilizing whole-exome sequencing (WESeq) and immunohistochemical analysis.ResultsIn addition to inheriting genomic phenotype and molecular phenotype from the primary lung cancers, massive unique genomic phenotype and molecular phenotype were also observed in BMs, which revealed unimaginable complexity of tumor evolution and extensive heterogeneity among lesions at a single-patient level. By analysis of a multi-metastases case (Case 3) of cancer cells’ subclonal composition, we found similar multiple subclonal clusters in the four spatial and temporal isolated brain metastatic focus, with the characteristics of polyclonal dissemination. Our study also verified that the expression level of immune checkpoints-related molecule Programmed Death-Ligand 1 (PD-L1) (P = 0.0002) and the density of tumor-infiltrating lymphocytes (TILs) (P = 0.0248) in BMs were significantly lower than that in paired primary lung cancers. Additionally, tumor microvascular density (MVD) also differed between primary tumors and paired BMs, indicating that temporal and spatial diversity profoundly contributes to the evolution of BMs heterogeneity.ConclusionOur study revealed the significance of temporal and spatial factors to the evolution of tumor heterogeneity by multi-dimensional analysis of matched primary lung cancers and BMs, which also provided novel insight for formulating individualized treatment strategies for BMs.

ObjectiveMitochondrial dysfunction and oxidative stress are known to involved in tumor occurrence and progression. This study aimed to explore the molecular subtypes of lower-grade gliomas (LGGs) based on oxidative stress-related and mitochondrial-related genes (OMRGs) and construct a prognostic model for predicting prognosis and therapeutic response in LGG patients.MethodsA total of 223 OMRGs were identified by the overlap of oxidative stress-related genes (ORGs) and mitochondrial-related genes (MRGs). Using consensus clustering analysis, we identified molecular subtypes of LGG samples from TCGA database and confirmed the differentially expressed genes (DEGs) between clusters. We constructed a risk score model using LASSO regression and analyzed the immune-related profiles and drug sensitivity of different risk groups. The prognostic role of the risk score was confirmed using Cox regression and Kaplan-Meier curves, and a nomogram model was constructed to predict OS rates. We validated the prognostic role of OMRG-related risk score in three external datasets. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) staining confirmed the expression of selected genes. Furthermore, wound healing and transwell assays were performed to confirm the gene function in glioma.ResultsWe identified two OMRG-related clusters and cluster 1 was significantly associated with poor outcomes (P

Cerebral cavernous malformations (CCMs) are common vascular anomaly diseases in the central nervous system associated with seizures, cerebral microbleeds, or asymptomatic mostly. CCMs can be classified as sporadic or familial, with familial cerebral cavernous malformations (fCCMs) being the autosomal dominant manner with incomplete penetrance. Germline mutations of KRIT1, CCM2, and PDCD10 are associated with the pathogenesis of fCCMs. Till now, little is known about the fCCMs mutation spectrum in the Han Chinese population. In this study, we enrolled a large, aggregated family, 11/26 of the family members were diagnosed with CCMs by pathological or neuroradiological examination, with a high percentage (5/9) of focal spinal cord involvement. Genomic DNA sequencing verified a novel duplication mutation (c.1119dupT, p.L374Sfs*9) in exon 9 of the Krev interaction trapped 1 (KRIT1) gene. The mutation causes a frameshift and is predicted to generate a truncated KRIT1/CCM1 protein of 381 amino acids. All our findings confirm that c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes’ mutational spectrum in the Chinese population and will be beneficial for deep insight into the pathogenesis of Chinese fCCMs. Additionally, with a retrospective study, we analyzed the molecular genetic features of Chinese fCCMs, most of the Chinese fCCMs variants are in the KRIT1 gene, and all these variants result in the functional deletion or insufficiency of the C-terminal FERM domain of the KRIT1 protein.

BackgroundsThis study performed multi-modal hemodynamic analysis including quantitative color-coded digital subtraction angiography (QDSA) and computational fluid dynamics (CFD) to delineate peri-therapeutic hemodynamic changes and explore the risk factors for in-stent restenosis (ISR) and symptomatic ISR (sISR).MethodsForty patients were retrospectively reviewed. Time to peak (TTP), full width at half maximum (FWHM), cerebral circulation time (CCT), angiographic mean transit time (aMTT), arterial stenosis index (ASI), wash-in gradient (WI), wash-out gradient (WO) and stasis index were calculated with QDSA and translesional pressure ratio (PR) and wall shear stress ratio (WSSR) were quantified from CFD analysis. These hemodynamic parameters were compared between before and after stent deployment and multivariate logistic regression model was established to detect predictors for ISR and sISR at follow-up.ResultsIt was found that stenting generally reduced TTP, stasis index, CCT, aMTT and translesional WSSR while significantly increased translesional PR. ASI decreased after stenting, and during the mean follow-up time of 6.48 ± 2.86 months, lower ASI (

ObjectiveMethionine sulfoxide (MetO) has been identified as a risk factor for vascular diseases and was considered as an important indicator of oxidative stress. However, the effects of MetO and its association with moyamoya disease (MMD) remained unclear. Therefore, we performed this study to evaluate the association between serum MetO levels and the risk of MMD and its subtypes.MethodsWe eventually included consecutive 353 MMD patients and 88 healthy controls (HCs) with complete data from September 2020 to December 2021 in our analyzes. Serum levels of MetO were quantified using liquid chromatography-mass spectrometry (LC–MS) analysis. We evaluated the role of MetO in MMD using logistic regression models and confirmed by receiver-operating characteristic (ROC) curves and area under curve (AUC) values.ResultsWe found that the levels of MetO were significantly higher in MMD and its subtypes than in HCs (p

Abstract Objective Glioma was the most common type of intracranial malignant tumor. Even after standard treatment, the recurrence and malignant progression of lower-grade gliomas (LGGs) were almost inevitable. The overall survival (OS) of patients with LGG varied widely, making it critical for prognostic prediction. Small G Protein Signaling Modulator 1 (SGSM1) has hardly been studied in gliomas. Therefore, we aimed to investigate the prognostic role of SGSM1 and its relationship with immune infiltration in LGGs. Methods We obtained RNA sequencing data from The Cancer Genome Atlas (TCGA) to analyze SGSM1 expression. Functional enrichment analyses, immune infiltration analyses, immune checkpoint analyses, and clinicopathology analyses were performed. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. And nomogram model has been developed. Kaplan–Meier survival analysis and log-rank test were used to estimate the relationship between OS and SGSM1 expression. The survival analyses and Cox regression were validated in datasets from the Chinese Glioma Genome Atlas (CGGA). Results SGSM1 was significantly down-regulated in LGGs. Functional enrichment analyses revealed SGSM1 was correlated with immune response. Most immune cells and immune checkpoints were negatively correlated with SGSM1 expression. The Kaplan–Meier analyses showed that low SGSM1 expression was associated with a poor outcome in LGG and its subtypes. The Cox regression showed SGSM1 was an independent prognostic factor in patients with LGG (HR = 0.494, 95%CI = 0.311–0.784, P = 0.003). Conclusion SGSM1 was considered to be a new prognostic biomarker for patients with LGG. And our study provided a potential therapeutic target for LGG treatment.

IntroductionRegardless of the degree of stenosis, vulnerable plaque is an important cause of ischemic stroke and thrombotic complications. The changes of the immune microenvironment within plaques seem to be an important factor affecting the characteristics of the plaque. However, the differences of immune microenvironment between stable and vulnerable plaques were remained unknown.MethodsIn this study, RNA-sequencing was performed on superficial temporal arteries from 5 traumatic patients and plaques from 3 atherosclerotic patients to preliminary identify the key immune response processes in plaques. Mass cytometry (CyTOF) technology was used to explore differences in immune composition between 9 vulnerable plaques and 12 stable plaques. Finally, immunofluorescence technique was used to validate our findings in the previous analysis.ResultsOur results showed that more CD86+CD68+ M1 pro-inflammatory macrophages were found in vulnerable plaques, while CD4+T memory cells were mainly found in stable plaques. In addition, a CD11c+ subset of CD4+T cells with higher IFN-r secretion was found within the vulnerable plaque. In two subsets of B cells, CD19+CD20-B cells in vulnerable plaques secreted more TNF-a and IL-6, while CD19-CD20+B cells expressed more PD-1 molecules.ConclusionIn conclusion, our study suggested that M1-like macrophages are the major cell subset affecting plaque stability, while functional B cells may also contribute to plaque stability.

BackgroundSpinal cord stimulation (SCS) is a promising treatment for patients with disorders of consciousness (DoC); however, the laboratory examinations and different electrodes (permanent #39286 vs. temporary percutaneous #3777, Medtronic, USA) that are associated with postoperative outcomes are unclear. The study aims to study the association between the change in postoperative cerebrospinal fluid (CSF) protein level and improvement in consciousness after SCS in DoC patients and to explore whether different electrodes were associated with elevated CSF protein levels.Materials and methodsA total of 66 DoC patients who received SCS treatment from December 2019 to December 2021 were retrospectively analyzed. Patients were grouped according to their elevated CSF protein level. The clinical characteristics of the patients and SCS stimulation parameters were compared. The preoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior border of the vertebral body to the midpoint of the posterior wall of the spinal canal at the level of the superior border of C3. The postoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior edge of the vertebral body to the anterior edge of the stimulation electrode. Patients with improved postoperative CRS-R scores greater than 3 or who progressed to the MCS + /eMCS were classified as the improved group and otherwise regarded as poor outcome.ResultsWe found that more DoC patients had elevated CSF protein levels among those receiving SCS treatment with permanent electrodes than temporary percutaneous electrodes (P = 0.001), and elevated CSF protein levels were significantly associated with a reduced sagittal diameter (P = 0.044). In DoC patients receiving SCS treatment, we found that elevated CSF protein levels (P = 0.022) and preoperative diagnosis (P = 0.003) were significantly associated with poor outcomes at 3 months. Logistic regression analysis showed that elevated CSF protein levels were significantly associated with poor outcomes (OR 1.008, 95% CI 1.001–1.016, P = 0.032).ConclusionThe results suggest that reducing the effect of electrode pads on anatomical changes may help improve the outcomes of DoC patients receiving SCS treatment. CSF protein levels are associated with poor postoperative outcomes and whether they are potential biomarkers in DoC patients receiving SCS treatment remain further exploration.

ObjectiveIncreasing studies have indicated that senescence was associated with tumorigenesis and progression. Lower-grade glioma (LGG) presented a less invasive nature, however, its treatment efficacy and prognosis prediction remained challenging due to the intrinsic heterogeneity. Therefore, we established a senescence-related signature and investigated its prognostic role in LGGs.MethodsThe gene expression data and clinicopathologic features were from The Cancer Genome Atlas (TCGA) database. The experimentally validated senescence genes (SnGs) from the CellAge database were obtained. Then LASSO regression has been performed to build a prognostic model. Cox regression and Kaplan-Meier survival curves were performed to investigate the prognostic value of the SnG-risk score. A nomogram model has been constructed for outcome prediction. Immunological analyses were further performed. Data from the Chinese Glioma Genome Atlas (CGGA), Repository of Molecular Brain Neoplasia Data (REMBRANDT), and GSE16011 were used for validation.ResultsThe 6-SnG signature has been established. The results showed SnG-risk score could be considered as an independent predictor for LGG patients (HR=2.763, 95%CI=1.660-4.599, P

BackgroundSpinal cord stimulation (SCS) can improve the level of awareness of prolonged disorder of consciousness (pDOC), but its application is restricted due to damage of invasive operation. Short-term spinal cord stimulation (st-SCS) in a minimally invasive manner will better balance the benefits and risks.ObjectivesThis study focuses on the safety and efficacy of st-SCS for pDOC and reveals the modulation characteristics of different frequencies of SCS.Methods31 patients received 2-week st-SCS treatment and 3-months follow-up. All patients were divided into two types of frequency treatment groups of 5 Hz and 70 Hz according to the postoperative electroencephalography (EEG) test. The efficacy was assessed based on the revised coma recovery scale (CRS-R).ResultsThe results showed a significant increase in CRS-R scores after treatment (Z = −3.668, p < 0.001) without significant adverse effects. Univariate analysis showed that the minimally conscious state minus (MCS–) benefits most from treatment. Furthermore, two frequency have a difference in the time-point of the CRS-R score increase. 5 Hz mainly showed a significant increase in CRS-R score at 2 weeks of treatment (p = 0.027), and 70 Hz additionally showed a delayed effect of a continued significant increase at 1 week after treatment (p = 0.004).Conclusionst-SCS was safe and effective in improving patients with pDOC levels of consciousness, and was most effective for MCS–. Both 5 Hz and 70 Hz st-SCS can promote consciousness recovery, with 70 Hz showing a delayed effect in particular.

Abstract Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk‐factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH‐wildtype than in IDH‐mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high‐risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression‐free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta‐analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH‐mutant subtype. Moreover, we found that 1p/19qCodel/TP73low subgroup shared the most favorable OS, 1p/19qNon−codel/TP73high subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73‐related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT‐PCR, which was consistent with the previous analytical result, and TP73 high‐expression subgroup suffered worse PFS than TP73 low‐expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma.

ObjectiveBranched-Chain Amino Acids (BCAAs) has been identified as a risk factor for circulatory disease. Nevertheless, the effects and mechanisms of BCAAs on the risk of moyamoya disease (MMD) remain unrecognized. Hence, we aimed to elucidate the association between circulating BCAAs and the risk of MMD and clinical subtypes.MethodsWe conducted a case-control study of 360 adult MMD patients and 89 matched healthy controls consecutively recruited between September 2020 and December 2021. Serum level of BCAAs was quantified by liquid chromatography-mass spectrometry. The associations between BCAAs and risk of MMD were evaluated.ResultsIncreased level of serum BCAAs was observed in MMD patients (P < 0.001). After adjusting for traditional confounders, the elevated BCAAs level was significantly associated with the risk of MMD (Q4 vs. Q1: odds ratio, 3.10 [95% CI, 1.29–7.50]). The risk of subtypes in MMD also increased with each increment in the quartiles of BCAAs. Furthermore, BCAAs offered substantial improvement in risk reclassification and discrimination for MMD and subtypes.ConclusionHigher level of circulating BCAAs was associated with increased risk of MMD and clinical subtypes. This study will help to elucidate the pathogenesis of MMD, which may provide the support for facilitating the treatments and preventions.

BackgroundCirculating choline pathway nutrients play a critical role in first stroke and recurrent stroke. However, there is limited information available on the effects of choline pathway nutrients on the risk of moyamoya disease (MMD) and its subtypes. We investigated the association between circulating choline and betaine and the incident risk of MMD and its subtypes.MethodsThe case-control study enrolled 385 patients with MMD [i.e., 110 transient ischemic attack (TIA)-type MMD, 157 infarction-type MMD, and 118 hemorrhagic-type MMD] and 89 matched healthy controls.ResultsSerum choline and betaine were inversely related to the risk of MMD and its subtypes. The risk of MMD was decreased with each increment in choline level [per 1 μmol increase: odds ratio (OR), 0.756; 95% CI, 0.678–0.843] and betaine level (per 1 μmol increase: OR, 0.952; 95% CI, 0.932–0.972), respectively. When choline and betaine were assessed as quartiles, compared with the lowest quartile of serum choline and betaine levels, those in the highest quartile had a significantly decreased risk of MMD (choline, Q4 vs. Q1: OR, 0.023; 95% CI, 0.005–0.118; betaine, Q4 vs. Q1: OR, 0.058; 95% CI, 0.018–0.184).ConclusionsSerum choline and betaine were associated with the decreased risk of MMD and its subtypes.

Abstract Background Ischemic events are the most common postoperative complication in bypass surgery for moyamoya disease (MMD), but the risk factors for pediatric MMD remain unclear. The goal of the study was to investigate the risk factors for postoperative ischemic complications in pediatric MMD patients. Methods We retrospectively reviewed a consecutive series of pediatric MMD cases at Beijing Tiantan Hospital, Capital Medical University from June 2010 through June 2019. Preoperative clinical variables and radiographic findings were recorded, and logistic regression analysis was carried out to identify the risk factors for postoperative ischemic events. Results A total of 533 operations in 336 patients were included in this study. Postoperative complications occurred after 51 operations (9.6%), including 40/447 indirect bypass procedures, 9/70 direct bypass procedures, and 2/16 combined bypass procedures. Postoperative ischemic events were the most common complication and occurred in 30 patients after 31 procedures (8.9% per patient; 5.8% per operation), including 26/447 indirect bypass procedures, 4/70 direct bypass procedures, and 1/16 combined bypass procedures, and the incidence of these events did not differ significantly between indirect and non-indirect bypass (5.8% vs 5.8%; p = 0.999). Multivariate logistic regression analyses revealed that older age at operation (OR 1.129, 95% CI 1.011–1.260, p = 0.032) and posterior cerebral artery involvement (OR 2.587, 95% CI 1.030–6.496, p = 0.043) were significantly associated with postoperative ischemic events. Conclusion We speculate that older age at operation and posterior cerebral artery involvement are risk factors for postoperative ischemic events in pediatric MMD patients.

N-acetylneuraminic acid (Neu5Ac) is a functional metabolite and has been demonstrated to be a risk factor for cardiovascular diseases. It is not clear whether Neu5Ac is associated with a higher risk of cerebrovascular disorders, especially moyamoya disease (MMD). We sought to elucidate the association between serum Neu5Ac levels and MMD in a case–control study and to create a clinical risk model. In our study, we included 360 MMD patients and 89 matched healthy controls (HCs). We collected the participants’ clinical characteristics, laboratory results, and serum Neu5Ac levels. Increased level of serum Neu5Ac was observed in the MMD patients (p = 0.001). After adjusting for traditional confounders, the risk of MMD (odds ratio [OR]: 1.395; 95% confidence interval [CI]: 1.141–1.706) increased with each increment in Neu5Ac level (per μmol/L). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves of the basic model plus Neu5Ac binary outcomes, Neu5Ac quartiles, and continuous Neu5Ac are 0.869, 0.863, and 0.873, respectively. Furthermore, including Neu5Ac in the model offers a substantial improvement in the risk reclassification and discrimination of MMD and its subtypes. A higher level of Neu5Ac was found to be associated with an increased risk of MMD and its clinical subtypes.

Objective: Glioma is the most prevalent and fatal intracranial malignant tumor. Extracellular matrix protein 2 (ECM2) has rarely been studied in gliomas. Therefore, we explored the role of ECM2 in lower-grade gliomas (LGGs). Methods: The RNA-seq and clinicopathology data were obtained from the TCGA database. The immunohistochemical (IHC) staining was used to verify the expression of ECM2. Functional enrichment analyses, immune-related analyses, drug sensitivity, and mutation profile analyses were further conducted. Cox regression and Kaplan–Meier curves were utilized for survival analyses, while four external datasets were used to validate the prognostic role of ECM2. Furthermore, qRT-PCR, CCK-8, wound healing, and transwell assays were performed to confirm the function of ECM2 in gliomas. Results: The study found a significant upregulation of ECM2 expression with increasing glioma grades and a significant association between ECM2 expression and tumor immune infiltration. Cox regression verified the prognostic role of ECM2 in LGG patients (HR = 1.656, 95%CI = 1.055–2.600, p = 0.028). High ECM2 expression was significantly associated with poor outcome (p < 0.001). Four external datasets validated its prognostic value. After the knockdown of ECM2, the functional experiments showed a significant decrease in proliferation, migration, and invasion in glioma cell lines. Conclusion: The study suggested the potential of ECM2 as a novel immune-associated prognostic biomarker and therapeutic target for glioma patients.

The comorbidity of aneurysmal subarachnoid hemorrhage (aSAH) with intracranial atherosclerotic stenosis (ICAS) has been suggested to increase the risk of postoperative ischemic stroke. Logistic regression models were established to explore the association between computed tomography perfusion (CTP) parameters and 3-month neurological outcomes and delayed cerebral ischemia (DCI). Prognostic-related perfusion parameters were added to the existing prognostic prediction models to evaluate model performance improvement. Tmax > 4.0 s volume > 0 mL was significantly associated with 3-month unfavorable neurological outcomes after adjusting for potential confounders (OR 3.90, 95% CI 1.11–13.73), whereas the stenosis degree of ICAS was not. Although the cross-validated area under the curve (AUC) was similar after the addition of the Tmax > 4.0 s volume > 0 mL (SAHIT: p = 0.591; TAPS: p = 0.379), the continuous net reclassification index (cNRI) and integrated discrimination index (IDI) showed that the perfusion parameters significantly improved the performance of the two models (p < 0.001 for all comparisons). Patients with coexistent aSAH and ICAS, Tmax > 4.0 s volume > 0 mL is an independent factor of 3-month neurological outcomes. A quantitative assessment of cerebral perfusion may help accurately screen patients with poor outcomes due to the coexistence of aSAH and ICAS.

Background and PurposesThe risk factors of poor postoperative angiogenesis in moyamoya disease (MMD) patients remain unknown. We aimed to investigate the association between hyperhomocysteinemia (HHcy) and postoperative angiogenesis of adult patients with MMD.MethodsA total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 10 patients accepting conservative therapy and 77 individuals without postoperative digital subtraction angiography (DSA), all 51 MMD patients were enrolled, and 28 patients received bilateral operations separately. Patients were grouped according to postoperative angiogenesis and HHcy presentation, respectively. Clinical data and laboratory examinations were compared. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Nomogram was further performed. The biological functions of homocysteine (Hcy) were explored in vitro.ResultsComparing to the normal, patients with poor postoperative angiogenesis were higher in serum Hcy (p = 0.004), HHcy ratio (p = 0.011), creatinine (Cr) (p < 0.001), uric acid (UA) (p = 0.036), Triglyceride (p = 0.001), high-density lipoprotein cholesterol (HDL-C) (p = 0.001), low-density lipoprotein cholesterol (LDL-C) (p = 0.009), ApoA (p = 0.022), apolipoprotein B (ApoB) (p = 0.013). Furthermore, HHcy was more common in men (p = 0.003) than women. Logistic analysis results showed that Hcy (OR = 0.817, 95% CI = 0.707–0.944, p = 0.006) was an independent risk factor. HHcy and Cr were significantly associated with poor postoperative angiogenesis in MMD patients. Further, Hcy could inhibit the proliferation, migration, and tube formation of human brain microvascular endothelial cells (HBMECs), which can be reversed by vascular endothelial growth factor (VEGF).ConclusionThe HHcy was significantly correlated with poor postoperative angiogenesis in adult patients with MMD. Hcy significantly inhibits HBMECs proliferation, migration, and tube formation. Furthermore, VEGF could reverse the inhibition effect induced by Hcy. Lowering the level of Hcy may be beneficial for postoperative MMD patients. Focusing on the pathophysiology and mechanism of HHcy might help to guide postoperative clinical management.

BackgroundIncreasing evidence supports a critical role of chronic inflammation in intracranial aneurysm (IA). Understanding how the immunological alterations in IA provides opportunities for targeted treatment. However, there is a lack of comprehensive and detailed characterization of the changes in circulating immune cells in IA.ObjectiveTo perform a comprehensive and detailed characterization of the changes in circulating immune cells in patients with IA.MethodsPeripheral blood mononuclear cell samples from IA patients (n = 26) and age-and sex-matched healthy controls (HCs, n = 20) were analyzed using high dimensional mass cytometry, and the frequency and phenotype of immune cell subtypes were assessed.ResultsWe identified 28 cell clusters and found that the immune signature of IA consists of cluster changes. IA patients exhibited dysfunction of immunity, with dysregulation of CD4+ T-cell clusters, increased B cells and monocytes, and decreased CD8+ T cells, DNT cells, and DPT cells. Moreover, compared with findings in HC, IA was associated with enhanced lymphocyte and monocyte immune activation, with a higher expression of HLA-DR, CXCR3, and CX3CR1. In addition, the expression of TLR4, p-STAT3, and the exhaustion marker PD1 was increased in T cells, B cells, and NK cells in IA patients.ConclusionsOur data provide an overview of the circulating immune cell landscape of IA patients, and reveal that the dysfunction of circulating immunity may play a potential role in the development of IA.

ObjectiveTo investigate the clinical effects of time window on hyperbaric oxygen treatment (HBOT) in patients with disorders of consciousness (DOC).MethodsAll the clinical research literature regarding HBOT for DOC published between January 2000 and November 2020 were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Standards Database (WFSD) and VIP Database using Chinese key words disorders of consciousness, the vegetable state, minimally conscious state, or hyperbaric oxygen followed by a comprehensive meta-analysis.ResultsThe query gave rise to 348 results, in which 21 articles were eventually selected for meta-analysis. Among the selected 21 articles, 18 articles involved a time window comparison. All the patients were classified into Z = 11.28, P = 0.000, odds ratio = 3.80, 95% CI = 3.02-4.80). Additionally, the adverse reaction rate of the Z = 10.01, P = 0.000, odds ratio = 4.82, 95% CI = 3.54-6.56). The funnel diagram in articles related to curative effect analysis and time window evaluation is inverted and symmetrical, indicating that publication bias was not significant.ConclusionsThe clinical curative effect of the HBOT group is higher compared with that of the control group. However, the conclusions based on meta-analysis are limited because of the methodological problems of some studies. Therefore, the clinical efficacy needs to be further tested using carefully designed large sample trials (multicenter, randomized, controlled, and double-blind).

Abstract Background An epidemic of COVID-19 broke out in Wuhan, China, since December 2019. The ordinary medical services were hindered. However, the emergency cases, including aneurysmal subarachnoid hemorrhage (aSAH), still required timely intervention. Thus, it provoked challenges to the routine management protocol. In this study, we summarized our experience in the emergency management of aSAH (Beijing Tiantan Protocol, BTP) in Beijing, China. Methods Demographic, clinical, and imaging data of consecutive emergency aSAH patients who underwent craniotomy clipping during the COVID-19 epidemic season were reviewed and compared with the retrospective period last year. Subgroup analysis was further performed to assess the outcomes of different screening results and several detailed protocols. Neurological outcomes were evaluated by the modified Rankin Scale (mRS). Results A total of 127 aSAH were referred to our emergency department, and 42 (33.1%) underwent craniotomy clipping between January 20, 2020, and March 25, 2020. The incidence of preoperative hospitalized adverse events and the perioperative outcomes were similar (− 0.1, 95% CI − 1.0 to 0.8, P = 0.779) to the retrospective period last year (January 2019–March 2019). After the propensity score matching (PSM), there were still no statistical differences in prognostic parameters between the two groups. Eight (19.0%) of the 42 individuals were initially screened as preliminary undetermined COVID-19 cases, in which 2 of them underwent craniotomy clipping in the negative pressure operating room (OR). The prognosis of patients with varied COVID-19 screening results was similar (F(2, 39) = 0.393, P = 0.678). Since February 28, 12 cases (28.6%) received COVID-19 nucleic acid testing (NAT) upon admission, and all showed negative. The false-negative rate was 0.0%. The preoperative hospitalized adverse events and postoperative prognosis were still similar between patients with and without COVID-19 NAT (− 0.3, 95% CI − 1.4 to 0.9, P = 0.653). Conclusions Our emergency surgery management protocol (BTP) is reliable for scheduling emergency aneurysm craniotomy clipping in non-major epidemic areas.

Abstract Background Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS). Methods This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models. Results This study included 4274 patients (median age 68 years [interquartile ranges {IQR}: 61–76]; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P

Abstract Background The aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant. Methods Hemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching. Results A total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296–27.737; P = 0.022). Conclusion Lenticulostriate anastomosis might be associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis might not be associted withp.R4810K variant.

Abstract Background The research on postoperative collateral formation for hemorrhagic moyamoya disease (MMD) evaluated by using digital subtraction angiography (DSA) is limited. Our study objective was to investigate the postoperative collateral formation after indirect bypass for hemorrhagic MMD. Methods All consecutive inpatients with hemorrhagic MMD who received indirect bypass at Beijing Tiantan Hospital, Capital Medical University from January 2010 through December 2018 were screened. The site of the hemorrhage was classified as either anterior or posterior. Postoperative collateral formation was evaluated on lateral views using the Matsushima scale. Univariate and multivariate logistic regression analyses were carried out to determine the factors influencing postoperative collateral formation. Results Six-four patients (64 hemispheres) were included in this study. After a median 8.5 months DSA follow-up, 14 (21.9%) hemispheres had grade A collateral circulation, 13 (20.3%) had grade B, and 37 (57.8%) had grade C. Twenty-seven (42.2%) hemispheres had good postoperative collateral formation and 37 (57.8%) had poor postoperative collateral formation. The univariate logistic regression analyses showed that age at operation (OR, 0.954; 95% CI, 0.908–1.003; p = 0.066), hemorrhagic site (OR, 4.694; 95% CI, 1.582–13.923; p = 0.005), and PCA involvement (OR, 3.474; 95% CI, 0.922–13.086; p = 0.066) may effect postoperative collateral formation. The multivariate logistic regression analyses showed that only anterior hemorrhage (OR, 5.222; 95% CI, 1.605–16.987; p = 0.006) was significantly related to good postoperative collateral formation. Conclusion Anterior hemorrhage was significantly related to good postoperative collateral formation after indirect bypass.

ObjectivePaediatric aneurysms are rare and difficult to treat. Studies on the long-term angiographic and clinical outcomes conducted within the past decade are lacking. We aimed to investigate the clinical and radiographic outcomes of paediatric aneurysms treated with different strategies in a contemporary series.MethodsWe performed a retrospective medical record review of paediatric patients examined at our institution between 2011 and 2018. Patient charts were retrospectively reviewed for age, presentation, type and location of the aneurysm, modalities of treatment, complications, and clinical and angiographic outcomes. The rates of aneurysm recurrence and de novo formation were determined.ResultsWe evaluated 61 patients (mean age, 11.6 years; 23 females, 38 males) with 69 intracranial aneurysms. Their presentations included headache, neurological deficits, aneurysmal subarachnoid haemorrhage, incidental aneurysm, and traumatic subarachnoid haemorrhage. Of the aneurysms, 30 (49.2%) were giant. Forty-five (73.8%) patients underwent treatment for their aneurysms, and 16 (26.2%) patients were managed conservatively. The perioperative morbidity rate was 17.8%. There were no deaths. The long-term morbidity rate was 4.6%. The clinical outcomes were favourable in 82.2 and 95.3% at discharge and follow-up, respectively (mean, 41.5 months; range, 1.5–9 years). For treated aneurysms, 2/43 (4.6%) risk of aneurysm recurrence, 1/43 (2.3%) risk of aneurysm bleeding, 1/43 (2.3%) risk of de novo aneurysm formation. The annual bleeding, recurrence, and de novo formation or growth risk were 0.7, 1.4, and 0.7%, respectively.ConclusionsIn neurovascular centres where microsurgical and endovascular options are available, most children with intracranial aneurysms can be successfully treated with low morbidity and mortality. However, they have higher rates of recurrence and a greater risk of de novo formation or growth than their adult counterparts, which mandates lifelong follow-up.

Summary: Background: The national epidemiologic data in mainland China is still absent for moyamoya disease (MMD). Methods: This study was a nationwide hospital-based observational retrospective study to estimate epidemiological characteristics of MMD. The data was based on the Hospital Quality Monitoring System (HQMS), a national database which covers all tertiary hospitals in mainland China. This system consistently collects medical records including demographic characteristics, diagnoses, procedures, and expenses etc. for all inpatients. MMD was identified by ICD-10 code (I67·5) in HQMS. Findings: A total of 47,443 new-onset patients with total 69,680 hospitalization records from 1312 hospitals during 2016 to 2018 were included. The annual incidence rate was 1·14 per 100,000 inhabitants (95% CI, 1·12–1·16) and approximately a 2-fold increase from 2016 to 2018. The incidence in children (0·18 per 100,000 inhabitants per year; 95% CI, 0·17–0·20) was significantly lower than that in adults (1·40 per 100,000; 95% CI, 1·38–1·42) (P

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.

Objectives: To investigate the association between radiomics features and epilepsy in patients with unruptured brain arteriovenous malformations (bAVMs) and to develop a prediction model based on radiomics features and clinical characteristics for bAVM-related epilepsy.Methods: This retrospective study enrolled 176 patients with unruptured bAVMs. After manual lesion segmentation, a total of 858 radiomics features were extracted from time-of-flight magnetic resonance angiography (TOF-MRA). A radiomics model was constructed, and a radiomics score was calculated. Meanwhile, the demographic and angioarchitectural characteristics of patients were assessed to build a clinical model. Incorporating the radiomics score and independent clinical risk factors, a combined model was constructed. The performance of the models was assessed with respect to discrimination, calibration, and clinical usefulness.Results: The clinical model incorporating 3 clinical features had an area under the curve (AUC) of 0.71. Fifteen radiomics features were used to build the radiomics model, which had a higher AUC of 0.78. Incorporating the radiomics score and clinical risk factors, the combined model showed a favorable discrimination ability and calibration, with an AUC of 0.82. Decision curve analysis (DCA) demonstrated that the combined model outperformed the clinical model and radiomics model in terms of clinical usefulness.Conclusions: The radiomics features extracted from TOF-MRA were associated with epilepsy in patients with unruptured bAVMs. The radiomics-clinical nomogram, which was constructed based on the model incorporating the radiomics score and clinical features, showed favorable predictive efficacy for bAVM-related epilepsy.

Aim: It remains a challenge in surgical treatments of brain arteriovenous malformations (AVMs) in Spetzler-Martin Grade (SMG) IV and V to achieve both optimal neurological outcomes and complete obliteration. The authors reported a series of patients with AVMs in SMG IV and V who underwent a surgical paradigm of endovascular embolization and simultaneous microsurgical resection based on the one-staged hybrid operation.Methods: Participants in the multicenter prospective clinical trial (NCT 03774017) between January 2016 and December 2019 were enrolled. Patients who received endovascular embolization plus microsurgical resection (EE+MRS) and those who received intraoperative digital subtraction angiography plus microsurgical resection (iDSA+MRS) were divided into two groups. Information on clinical features, operative details, and clinical outcomes were extracted from the database. Deterioration of neurological deficits (DNDs) was defined as the primary outcome, which represented neurological outcomes. The time of microsurgical operation and blood loss were defined as the secondary outcomes representing microsurgical risks and difficulties. Outcomes and technical details were compared between groups.Results: Thirty-eight cases (male: female = 23:15) were enrolled, with 24 cases in the EE+MRS group and 14 in the iDSA+MRS group. Five cases (13.2%) were in SMG V and 33 cases (86.8%) were in SMG IV. Fourteen cases (36.8%) underwent the paradigm of microsurgical resection plus intraoperative DSA. Twenty-four cases (63.2%, n = 24) underwent the paradigm of endovascular embolization plus simultaneous microsurgical resection. Degradations of SMG were achieved in 15 cases. Of the cases, two cases got the residual nidus detected via intraoperative DSA and resected. Deterioration of neurological deficits occurred in 23.7% of cases (n = 9) when discharged, and in 13.5, 13.5, 8.1% of cases at the follow-ups of 3, 6, and 12 months, respectively, without significant difference between groups (P > 0.05). Intracranial hemorrhagic complications were reported in three cases (7.9%) of the EE+MRS group only. The embolization did not significantly affect the surgical time and intraoperative blood loss. The subtotal embolization or the degradation of size by 2 points resulted in no DNDs.Conclusions: The paradigms based on the one-staged hybrid operation were practical and effective in treating high-grade AVMs. Appropriate intraoperative embolization could help decrease operative risks and difficulties and improve neurological outcomes.

Objective: This study was conducted in order to investigate the association of matrix metalloproteinase (MMP)-9 levels with phenotypes of moyamoya disease (MMD).Methods: This study included plasma samples from 84 MMD patients. The clinical variables of these patients were reviewed from the medical record. The serum concentration of tight junction, adherens junction proteins, and MMPs (MMP-2 and MMP-9) was determined using the ELISA method. Patients with hemorrhagic-onset MMD were compared with those with ischemic-onset MMD.Results: Compared with pediatric patients, the expression of MMP-9 was significantly higher, while the MMP-2 and vascular endothelial-cadherin were lower in adult patients. In adult subgroup analysis, hemorrhagic MMD patients exhibited significantly higher serum concentrations of MMP-9 compared with ischemic MMD patients. The ROC curve identified that a baseline serum MMP-9 level >1,011 ng/ml may be associated with spontaneous hemorrhage in adult MMD patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597–0.864; P = 0.003]. A late Suzuki stage (>4) (OR 4.565, 95% CI 1.028–20.280, P = 0.046) and serum concentrations of MMP-9 >1,011 ng/ml (OR 7.218, 95% CI 1.826–28.533, P = 0.005) are risk predictors of hemorrhages in MMD patients. Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and BBB permeability compared with ischemic-type MMD patients. Adult MMD patients had higher serum levels of MMP-9 and BBB permeability compared with pediatric patients.Conclusions: MMP-9 might serve as a biomarker for hemorrhage prediction in MMD. Serum MMP-9 level >1,011 ng/ml is an independent risk factor of MMD hemorrhagic strokes.

Abstract Background Complex brain arteriovenous malformations (bAVMs) in ≥3 Spetzler-Martin grades have long been challenges among cerebrovascular diseases. None of the traditional methods, such as microsurgical operation, endovascular intervention, or stereotactic radiotherapy, can completely eliminate complex bAVMs without a risk of neural function deterioration. The multistaged hybrid operation solved part of the challenge but remained risky in the installment procedures and intervals. The one-staged hybrid operation was applied in the surgical treatment of cerebrovascular diseases and proved to be a potentially safe and effective method for curing complex bAVMs. However, lacking the support of high-level evidence, its advantages remain unclear. This study was proposed to validate the benefits and risks of one-staged hybrid operation in the treatment of complex bAVMs, as well as its indications, key technologies, and workflows. Methods The study is being conducted from Jan 2016 to Dec 2020 with 20 cooperation centers. It consists of 2 sets. The registry set is designed as a prospective real-world registry. The trial set is designed as a prospective pragmatic clinical trial, specifically for the patients with perforating arterial feeders. The two sets share a common grouping: the traditional operation group and the one-staged hybrid operation group. The assignment is based on the clinical condition in the registry set and is randomized in the trial set. End points will be evaluated at scheduled time points. The safety and efficiency of one-staged hybrid operation in treating complex bAVMs will be validated. Discussion The study is designed for a real-world exploration of benefits and risks of one-staged hybrid operation in the treatment of complex bAVMs. The two-set design reduces the compromise of clinical practice due to the study and improves the statistical power and research quality with a practical sample size. In the study, advantages of the one-staged hybrid operation will be evaluated and compared to those of traditional operation. A spanning development of neurosurgical operation might be facilitated by the study, which means a higher cure rate and lower disability rate in patients with complex bAVMs. Trial registration The study was retrospectively registered in ClinicalTrials.gov (NCT03774017) on 11th Dec, 2018.

Aim: The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas.Methods: An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association.Results: In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III.Conclusions: The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs.

Glioblastoma multiforme (GBM), as one of the most common malignant brain tumors, was limited in its treatment effectiveness with current options. Its invasive and infiltrative features led to tumor recurrence and poor prognosis. Effective treatment and survival improvement have always been a challenge. With the exploration of genetic mutations and molecular pathways in neuro-oncology, gene therapy is becoming a promising therapeutic approach. Therapeutic genes are delivered into target cells with viral vectors to act specific antitumor effects, which can be used in gene delivery, play an oncolysis effect, and induce host immune response. The application of engineering technology makes the virus vector used in genetics a more prospective future. Recent advances in viral gene therapy offer hope for treating brain tumors. In this review, we discuss the types and designs of viruses as well as their study progress and potential applications in the treatment of GBM. Although still under research, viral gene therapy is promising to be a new therapeutic approach for GBM treatment in the future.

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years.Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed.Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p < 0.001, p = 0.001, p < 0.001, and p < 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004).Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes.