The brain nebula: minimally invasive brain-computer interface by endovascular neural recording and stimulation.

A brain-computer interface (BCI) serves as a direct communication channel between brain activity and external devices, typically a computer or robotic limb. Advances in technology have led to the increasing use of intracranial electrical recording or stimulation in the treatment of conditions such as epilepsy, depression, and movement disorders. This indicates that BCIs can offer clinical neurological rehabilitation for patients with disabilities and functional impairments. They also provide a means to restore consciousness and functionality for patients with sequelae from major brain diseases. Whether invasive or non-invasive, the collected cortical or deep signals can be decoded and translated for communication. This review aims to provide an overview of the advantages of endovascular BCIs compared with conventional BCIs, along with insights into the specific anatomical regions under study. Given the rapid progress, we also provide updates on ongoing clinical trials and the prospects for current research involving endovascular electrodes.

Zabramski classification in predicting the occurrence of symptomatic intracerebral hemorrhage in sporadic cerebral cavernous malformations.

OBJECTIVE: The authors aimed to investigate the evolutionary characteristics of the Zabramski classification of cerebral cavernous malformations (CCMs) and the value of the Zabramski classification in predicting clinical outcome in patients with sporadic CCM. METHODS: This retrospective study consecutively included cases of sporadic CCM that had been untreated from January 2001 through December 2021. Baseline and follow-up patient information was recorded. The evolution of the Zabramski classification of a sporadic CCM was defined as the initial lesion type changing into another type for the first time on MRI follow-up. The primary outcome was the occurrence of a hemorrhage event, which was defined as a symptomatic event with radiological evidence of overt intracerebral hemorrhage. RESULTS: Among the 255 included cases, 55 (21.6%) were classified as type I CCM, 129 (50.6%) as type II CCM, and 71 (27.8%) as type III CCM, based on initial MRI. During a mean follow-up of 58.8 ± 33.6 months, 51 (20.0%) patients had lesion classification transformation, whereas 204 (80.0%) patients maintained their initial type. Among the 51 transformed lesions, 29 (56.9%) were type I, 11 (21.6%) were type II, and 11 (21.6%) were type III. Based on all follow-up imaging, of the initial 55 type I lesions, 26 (47.3%) remained type I and 27 (49.1%) regressed to type III because of hematoma absorption; 91.5% of type II and 84.5% of type III lesions maintained their initial type during MRI follow-up. The classification change rate of type I lesions was statistically significantly higher than those of type II and III lesions. After a total follow-up of 1157.7 patient-years, new clinical hemorrhage events occurred in 40 (15.7%) patients. The annual cumulative incidence rate for symptomatic hemorrhage in all patients was 3.4 (95% CI 2.5-4.7) per 100 person-years. Kaplan-Meier survival analysis showed that the annual cumulative incidence rate for symptomatic hemorrhage of type I CCM (15.3 per 100 patient-years) was significantly higher than those of type II (0.6 per 100 patient-years) and type III (2.3 per 100 patient-years). CONCLUSIONS: This study suggests that the Zabramski classification is helpful in estimating clinical outcome and can assist with surgical decision-making in patients with sporadic CCM.

Effectiveness of indirect revascularization for adult hemorrhagic moyamoya disease: a 10-year follow-up study.

OBJECTIVE: The optimal surgical approach for hemorrhagic moyamoya disease (hMMD) continues to be a topic of debate. The authors' prior research demonstrated that both combined and indirect revascularization were efficacious. However, questions remain regarding the long-term prognosis consistency between these two treatments. Therefore, the objective of this study was to evaluate and compare the enduring effects of these surgical modalities on adult hMMD, extending the findings of the authors' previous studies. METHODS: The authors recruited patients diagnosed with hMMD between 2010 and 2015. The patients were categorized into two groups: those who underwent combined revascularization (superficial temporal artery-middle cerebral artery bypass alongside dural reverse application) and those who underwent indirect revascularization (encephaloduroarteriosynangiosis [EDAS]). The primary and secondary endpoints of this study were instances of rebleeding, confirmed with CT scan, and death resulting from rebleeding, respectively. The authors estimated rebleeding-free and death-free survival rates by utilizing the Kaplan-Meier survival method. They used Cox regression to adjust for confounders and to evaluate the effects of the varying surgical modalities on the endpoints. RESULTS: After an average follow-up period of 114 months, 35 patients (28.6%) experienced 40 rebleeding events, yielding an average annual incidence of 3.5%. Of the 79 patients who received combined revascularization, 17 (21.5%) experienced rebleeding events. Similarly, of 43 patients who underwent EDAS, 18 (41.9%) experienced rebleeding events (p = 0.018). Most rebleeding instances occurred 61-120 months after surgery (21 patients [60%]), followed by 12-60 months (11 patients [31.4%]). Multivariate survival analysis highlighted significant differences in surgical outcomes (HR 0.33, 95% CI 0.15-0.74, p = 0.007). The authors observed that 8 patients (10.1%) died of rebleeding events in the combined group, as well as 10 patients (23.3%) in the EDAS group. Despite the lack of a statistically significant difference in mortality (p = 0.051), multivariable survival analysis found a significant difference (HR 0.31, 95% CI 0.10-0.97, p = 0.044). CONCLUSIONS: High rebleeding rates persist in adult hMMD patients, even after revascularization. Combined revascularization proved superior to EDAS in preventing long-term rebleeding. In contrast, EDAS alone did not display a clear effect on reducing long-term rebleeding rates.

Hybrid surgery can improve neurocognitive function in patients with internal carotid artery occlusion.

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.

Identification of heterogeneous subtypes and a prognostic model for gliomas based on mitochondrial dysfunction and oxidative stress-related genes.

Objective: Mitochondrial 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. Methods: A 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. Results: We identified two OMRG-related clusters and cluster 1 was significantly associated with poor outcomes (P<0.001). The mutant frequencies of IDH were significantly lower in cluster 1 (P<0.05). We found that the OMRG-related risk scores were significantly correlated to the levels of immune infiltration and immune checkpoint expression. High-risk samples were more sensitive to most chemotherapeutic agents. We identified the prognostic role of OMRG-related risk score in LGG patients (HR=2.665, 95%CI=1.626-4.369, P<0.001) and observed that patients with high-risk scores were significantly associated with poor prognosis (P<0.001). We validated our findings in three external datasets. The results of qRT-PCR and IHC staining verified the expression levels of the selected genes. The functional experiments showed a significant decrease in the migration of glioma after knockdown of SCNN1B. Conclusion: We identified two molecular subtypes and constructed a prognostic model, which provided a novel insight into the potential biological function and prognostic significance of mitochondrial dysfunction and oxidative stress in LGG. Our study might help in the development of more precise treatments for gliomas.

High ECM2 Expression Predicts Poor Clinical Outcome and Promotes the Proliferation, Migration, and Invasiveness of Glioma.

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.

Heterogenous profiles between primary lung cancers and paired brain metastases reveal tumor evolution.

Background: Brain 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. Methods: To 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. Results: In 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. Conclusion: Our 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.

Somatic GJA4 mutation in intracranial extra-axial cavernous hemangiomas.

OBJECTIVE: Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown. METHODS: Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model. RESULTS: We detected somatic GJA4 mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that the GJA4 mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing the GJA4 mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683. CONCLUSIONS: We identified a somatic GJA4 mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to GJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.

The language-related cerebro-cerebellar pathway in humans: a diffusion imaging-based tractographic study.

Background: The cerebellum and cerebral cortex form the most important cortico-cerebellar system in the brain. However, diffusion magnetic resonance imaging (MRI)-based tractography of the connecting white matter between the cerebellum and cerebral cortex, which support language function, has not been extensively reported on. This work aims to serve as a guideline for facilitating the analysis of white matter tracts along the language-related cerebro-cerebellar pathway (LRCCP), which includes the corticopontine, pontocerebellar, corticorubral, rubroolivary, olivocerebellar, and dentatorubrothalamic tracts. Methods: The LRCCP templates were developed via processing the high-resolution, population-averaged atlas available in the Human Connectome Project (HCP)-1065 dataset (2017 Q4, 1,200-subject release) in DSI Studio. The deterministic tracking was performed with the manually selected regions of interest (ROIs) on this atlas according to prior anatomic knowledge. Templates were then applied to the MRI datasets of 30 health participants acquired from a single hospital to verify the practicability of the tracking. The diffusion tensor and shape analysis metrics were calculated for all LRCCP tracts. Differences in the tracking metrics between the left and right hemispheres were compared, and the related white matter asymmetry was discussed. Results: The LRCCP templates were successfully created and applied to healthy participants for quantitative analysis. Significantly higher mean fractional anisotropy (FA) values were discovered on the left (L) corticorubral tract [L, 0.43±0.02 vs. right (R), 0.41±0.02; P<0.01] and left dentatorubrothalamic tract (L, 0.47±0.02 vs. R, 0.46±0.02; P<0.01). Significant differences in tract volume and streamline number were observed between the corticopontine, corticorubral, and dentatorubrothalamic tracts. The size of the right corticopontine and corticorubral tracts were smaller, and both had smaller streamline numbers and innervation areas when compared with the contralateral sides. The R dentatorubrothalamic tract showed a larger volume (R, 23,582.47±4,160.71 mm3 vs. L, 19,821.27±2,983.91 mm3; P<0.01) and innervation area (R, 2,117.37±433.98 mm2 vs. L, 1,610.00±356.19 mm2; P<0.01) than did the L side. No significant differences were observed in the rubroolivary tracts. Conclusions: This work suggests the feasibility of applying tractography templates of the LRCCP to quantitatively evaluate white matter properties associated with language function. Lateralized diffusion metrics were observed in preliminary experiments. LRCCP tractography-based research may provide a potential quantitative method to better understanding neuroplasticity.

Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: Relationship with delayed cerebral ischemia and poor prognosis.

AIMS: To assess differences in the clinical prognosis between different treatment timings in poor-grade (Hunt and Hess grade 4-5) aneurysmal subarachnoid hemorrhage patients. METHODS: The treated 127 poor-grade aneurysmal subarachnoid hemorrhage patients were divided into three groups: early treatment within 2 days, treatment on days 3 to 10, and treatment for more than 10 days after the hemorrhage. Odd ratios with a 95% confidence interval were calculated in logistic regression for different timing strategies regarding delayed cerebral ischemia and poor prognosis at 3 months. Subgroup analyses were conducted to determine whether the different timing strategies affect the prognosis. RESULTS: Patients who received the treatment on days 3 to 10 were prone to develop delayed cerebral ischemia and poor prognosis at 3 months. Postponing treatment in patients older than 55 years or diagnosed with an intraventricular hematoma on the initial computed tomography scan may lead to poor prognosis, with the early intervention group as a reference. CONCLUSIONS: Early intervention in poor-grade aneurysmal subarachnoid hemorrhage is suggested to be implemented. The treatment on 3 to 10 days harbored the highest risk of poor prognosis; patients might benefit more from early intervention, especially for ones older than 55 years or diagnosed with an intraventricular hematoma.

Exosomal miR-3131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous malformations.

AIMS: To explore the underlying mechanism by which low-frequency KRAS mutations result in extensive EndMT occurrence. METHODS: Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRASG12D , KRASWT , or KRASNC lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR-3131 and detection of its downstream target, and miR-3131 inhibitor in reversing the EndMT process induced by KRASG12D -transfected HUVECs and bAVM endothelial cells (ECs) were explored. RESULTS: Exosomes derived from KRASG12D bAVM ECs and KRASG12D -transfected HUVECs promoted EndMT in HUVECs. MiR-3131 levels were highest in the exosomes of KRASG12D -transfected HUVECs, and HUVECs transfected with the miR-3131 mimic acquired mesenchymal phenotypes. RNA-seq and dual-luciferase reporter assays revealed that PICK1 is the direct downstream target of miR-3131. Exosomal miR-3131 was highly expressed in KRASG12D bAVMexos compared with non-KRAS-mutant bAVMexos or HUVECexos . Finally, a miR-3131 inhibitor reversed EndMT in HUVECs treated with exosomes or the supernatant of KRASG12D -transfected HUVECs and KRASG12D bAVM ECs. CONCLUSION: Exosomal miR-3131 promotes EndMT in KRAS-mutant bAVMs, and miR-3131 might be a potential biomarker and therapeutic target in KRASG12D -mutant bAVMs.

Endothelial hyperactivation of mutant MAP3K3 induces cerebral cavernous malformation enhanced by PIK3CA GOF mutation.

Cerebral cavernous malformations (CCMs) refer to a common vascular abnormality that affects up to 0.5% of the population. A somatic gain-of-function mutation in MAP3K3 (p.I441M) was recently reported in sporadic CCMs, frequently accompanied by somatic activating PIK3CA mutations in diseased endothelium. However, the molecular mechanisms of these driver genes remain elusive. In this study, we performed whole-exome sequencing and droplet digital polymerase chain reaction to analyze CCM lesions and the matched blood from sporadic patients. 44 of 94 cases harbored mutations in KRIT1/CCM2 or MAP3K3, of which 75% were accompanied by PIK3CA mutations (P = 0.006). AAV-BR1-mediated brain endothelial-specific MAP3K3I441M overexpression induced CCM-like lesions throughout the brain and spinal cord in adolescent mice. Interestingly, over half of lesions disappeared at adulthood. Single-cell RNA sequencing found significant enrichment of the apoptosis pathway in a subset of brain endothelial cells in MAP3K3I441M mice compared to controls. We then demonstrated that MAP3K3I441M overexpression activated p38 signaling that is associated with the apoptosis of endothelial cells in vitro and in vivo. In contrast, the mice simultaneously overexpressing PIK3CA and MAP3K3 mutations had an increased number of CCM-like lesions and maintained these lesions for a longer time compared to those with only MAP3K3I441M. Further in vitro and in vivo experiments showed that activating PI3K signaling increased proliferation and alleviated apoptosis of endothelial cells. By using AAV-BR1, we found that MAP3K3I441M mutation can provoke CCM-like lesions in mice and the activation of PI3K signaling significantly enhances and maintains these lesions, providing a preclinical model for the further mechanistic and therapeutic study of CCMs.

Preoperative nomogram predicting ventriculoperitoneal shunt longevity after initial shunt failure.

Background and objectives: Initial 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. Methods: From 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. Results: At 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. Conclusion: A preoperative nomogram may be an effective tool for assessing VP shunt longevity after initial VP shunt placement.

Establishment and validation of a novel prognostic model for lower-grade glioma based on senescence-related genes.

Objective: Increasing 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. Methods: The 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. Results: The 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<0.001). The high SnG-risk score indicated a worse outcome in LGG (P<0.001). Immune analysis showed a positive correlation between the SnG-risk score and immune infiltration level, and the expression of immune checkpoints. The CGGA datasets confirmed the prognostic role of the SnG-risk score. And Kaplan-Meier analyses in the additional datasets (CGGA, REMBRANDT, and GSE16011) validated the prognostic role of the SnG-signature (P<0.001 for all). Conclusion: The SnG-related prognostic model could predict the survival of LGG accurately. This study proposed a novel indicator for predicting the prognosis of LGG and provided potential therapeutic targets.

Association of RNF213 Variants With Periventricular Anastomosis in Moyamoya Disease.

BACKGROUND: The pathogenic mechanisms of periventricular anastomosis (PA) in moyamoya disease remain unknown. Here, we aimed to describe the angiographic profiles of PA and their relationships with really interesting new gene (RING) finger protein 213 (RNF213) genotypes. METHODS: We conducted a retrospective cohort study of moyamoya disease patients consecutively recruited between June 2019 and January 2021 in Beijing Tiantan Hospital, Capital Medical University, China. C-terminal region of RNF213 was sequenced. Angiographic characteristics of PA vessels (lenticulostriate artery, thalamotuberal artery, thalamoperforating artery, anterior choroidal artery, and posterior choroidal artery) were compared between different groups of RNF213 genotypes. The dilatation and extension of PA vessels were measured by using PA score (positive, score 1-5; negative, score 0). Multivariate regression analysis was conducted to assess variables associated with PA score. In addition, gene expression of RNF213 in human brain regions was evaluated from the Allen Human Brain Atlas. RESULTS: Among 260 patients (484 hemispheres), 71.2% carried no RNF213 rare and novel variants, 20.0% carried p.R4810K heterozygotes, and 8.8% carried other rare and novel variants. PA scores in patients with p.R4810K and other rare and novel variants were significantly higher than in wild-type patients (P<0.001). Age (odds ratio [OR], 0.958 [95% CI, 0.942-0.974]; P<0.001), platelet count (OR, 0.996 [95% CI, 0.992-0.999]; P=0.027), p.R4810K variant (OR, 2.653 [95% CI, 1.514-4.649]; P=0.001), other rare and novel variants (OR, 3.197 [95% CI, 1.012-10.094]; P=0.048), Suzuki stage ≥4 (OR, 1.941 [95% CI, 1.138-3.309]; P=0.015), and posterior cerebral artery involvement (OR, 1.827 [95% CI, 1.020-3.271]; P=0.043) were significantly correlated with PA score. High expression of RNF213 was detected in the periventricular area. CONCLUSIONS: RNF213 variants were confirmed to be associated with PA in moyamoya disease. Individuals with RNF213 p.R4810K heterozygotes and other C-terminal region rare variants exhibited different angiographic phenotypes, compared with wild-type patients.

Infarction Patterns and Recurrent Adverse Cerebrovascular Events in Moyamoya Disease.

For moyamoya disease (MMD) patients who suffered an acute ischemic attack, the infarction patterns on DWI and its association with recurrent adverse cerebrovascular events (ACEs) after bypass surgery remain unknown. 327 patients who suffered an acute ischemic attack and received following revascularization surgery were retrospectively reviewed and were divided into three patterns according to the lesion number and distribution on DWI that obtained within 7 days of onset: no acute infarction (NAI), single acute infarction (SAI), and multiple acute infarctions (MAIs). We used Cox proportional hazard models to estimate hazard ratios (HR) for associations of infarction patterns and the risk of recurrent ACEs and strokes. Over a median follow-up of 41 months (IQR 26-60), there were 61 ACEs and 27 strokes. Compared to the NAI cohort, patients with SAI (HR, 2.92; 95% CI, 1.41-6.05; p = 0.004) and MAIs (HR, 4.44; 95% CI, 2.10-9.41; p < 0.001) were associated with higher risk of ACEs recurrences. In analysis adjusted for age and surgery modalities, the corresponding HR was 2.90 (95% CI: 1.41-5.98) for SAI and 4.10 (95% CI: 1.95-8.63) for MAIs, and this effect remained persistent on further adjustment for several potential confounders. Similar but less precise association was found in separate analysis that only takes into account stroke recurrences. Thus, different infarction patterns on DWI imply different risks of recurrent ACEs, and more attention should be paid to prevent ACEs in MMD patients with MAIs.

Prognostic biomarker SGSM1 and its correlation with immune infiltration in gliomas.

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.

Tumor Necrosis Factor-α: The Next Marker of Stroke.

Although there is no shortage of research on the markers for stroke, to our knowledge, there are no clear markers that can meet the needs of clinical prediction and treatment. The inflammatory cascade is a critical process that persists and functions throughout the stroke process, ultimately worsening stroke outcomes and increasing mortality. Numerous inflammatory factors, including tumor necrosis factor (TNF), are involved in this process. These inflammatory factors play a dual role during stroke, and their mechanisms are complex. As one of the representatives, TNF is the primary regulator of the immune system and plays an essential role in the spread of inflammation. In researches done over the last few years, tumor necrosis factor-alpha (TNF-α) has emerged as a potential marker for stroke because of its essential role in stroke. This review summarizes the latest research on TNF-α in stroke and explores its potential as a therapeutic target.

Three-dimensional printing-assisted precision microcatheter shaping in intracranial aneurysm coiling.

Optimal microcatheter shaping is essential for successful endovascular coiling procedures which is sometimes challenging. Our aim was not only to introduce a new shaping method using three-dimensional (3D) printed vessel models but also to prove its feasibility, efficiency and superiority. This was a retrospective cohort study. From September 2019 to March 2021, 32 paraclinoid aneurysms managed with endovascular coiling were retrospectively included and identified. Sixteen aneurysms were coiled using 3D microcatheter shaping method (3D shaping group), and traditional manual shaping method using shaping mandrels was adopted for another 16 patients (control group). The cost and angiographical and clinical outcomes between the two groups were compared, and the feasibility and effectiveness of the new 3D shaping method were evaluated and described in detail. With technical success achieved in 93.75%, most of the 16 shaped microcatheters using new shaping method could be automatically navigated into the target aneurysms without the assistance of microguidewires and could be assessed with favorable accessibility, positioning and stability. Twenty-seven out of 32 aneurysms (84.38%) were completely occluded with the rate of perioperative complications being 12.50%. Although there was no significant difference between the occlusion rates and complication rates of the two groups, the new shaping method could dramatically decrease the number of coils deployed and reduce the overall procedure time. Patient specific shaping of microcatheters using 3D printing may facilitate easier and safer procedures in coil embolization of intracranial aneurysms with shorter surgery time and less coils deployed.