The role of radiosurgery in preventing haemorrhage in brainstem cavernous malformations remains a subject of debate. This study aimed to evaluate whether radiosurgery provides a protective benefit against haemorrhage in these patients. This multicentre, prospective observational study was conducted in 17 centres and enrolled eligible patients with brainstem cavernous malformations consecutively. Data collected included clinical baseline information, radiosurgery planning details, periodic follow-up evaluations and any adverse radiation effects. The primary outcome of the study was the incidence of first prospective haemorrhage, and the secondary outcome was the development of new or worsening neurological dysfunctions. The impact of radiosurgery was assessed using multivariate Cox regression analysis. From March 2016 to August 2018, the study enrolled 377 patients: 280 in the observation group receiving standard care alone and 97 in the radiosurgery group receiving both radiosurgery and standard care. The overall cohort consisted of 173 females (45.9%) with a mean age of 40.5 years (range, 18-68 years), and there were no significant differences in baseline characteristics between the two groups. After a median follow-up period of 70 months, haemorrhage occurred in 25.0% (n = 70) of patients in the observation group and 10.3% (n = 10) of patients in the radiosurgery group. Multivariate Cox regression analysis identified radiosurgery as an independent protective factor against haemorrhage (hazard ratio 0.379, 95% confidence interval 0.195-0.738, P = 0.004). Following 1:2 propensity score matching, the incidence of prospective haemorrhage was 24.9% (45/181) in the observation group compared with 10.3% (10/97) in the radiosurgery group (hazard ratio 0.379, 95% confidence interval 0.190-0.755, P = 0.006). Adverse radiation effects were observed in 12 patients (12.4%), with none being permanent. Additionally, new or worsening neurological dysfunctions were significantly more common in the observation group (28.9%) compared with the radiosurgery group (16.5%) (P = 0.016). These results suggest that radiosurgery is associated with a low rate of haemorrhage in patients with brainstem cavernous malformations and could provide a benefit in selected patients. However, further research is required to confirm these findings. In a prospective cohort study, Li et al. found that patients with brainstem cavernous malformations who received radiosurgery plus standard medical care had lower rates of haemorrhage, and of new or worsening neurological dysfunction, than patients who received standard medical care alone.

OBJECTIVE: Based on anatomical magnetic resonance imaging (MRI) sequences, we developed a radiomic signature for brainstem cavernous malformation patients (BSCMs) using radiomic analysis and explore its effectiveness as a prognostic biomarker. METHODS:One hundred and fourteen BSCMs with clinical, and radiomic information were collected and randomly divided into training (n = 68) and validation set (n = 46). Clinical and radiomic nomogram were constructed for the prognosis. Radiomic features were screened with three algorithms (univariate analysis, Pearson analysis, and elastic net algorithm). Cox regression model was used to build the radiomics nomogram. Finally, concordance index (C-index), time-independent receiver operating characteristic (ROC) analysis, and Decision curve analysis (DCA) were utilized to evaluate the clinical application of the radiomics nomogram. RESULTS: The radiomic signature score was calculated with 11 hemorrhage-free survival (HFS) related radiomic features from the training cohort. The patients were divided into high-risk group and low-risk group with the help of radiomic signature and the low-risk group has a better HFS than the high-risk group. In addition, three clinical characteristics including the number of hemorrhages, size, mRS, and radiomics score (Rad-score) were used to develop the radiomics nomogram. The calibration plots showed that the nomogram has good agreement between the predicted and actual survival probabilities. And, the C-index was 0.784 and 0.787 in the training cohort and validation cohort in predicting HFS; the area under curve (AUC) was 72.51 and 76.41 in the training cohort and validation cohort in 3-year survival and 67.62 and 72.57 in 5-year survival. Lastly, the DCA curve showed that the radiomics nomogram has a better clinical application than the clinical model. CONCLUSIONS: Radiomics nomogram integrating radiomics signature and clinical information showed great performance and high sensitiveness in prediction HFS in BSCMs than the clinical model.

目的 探讨开颅减压手术治疗出血性颅内静脉窦血栓并发脑疝的疗效.方法 回顾性分析2019年10月至2022年8月首都医科大学附属北京天坛医院神经外科学中心(5例)和拉萨市人民医院神经外科(2例)行开颅减压手术治疗的7例出血性颅内静脉窦血栓并发脑疝患者的临床资料.术前患者格拉斯哥昏迷评分(GCS)中位数为6分(3～11分).所有患者术前影像学检查均显示颅内静脉窦血栓出血伴脑疝征象,且患者意识障碍进行性加重.患者均行去骨瓣减压手术,5例患者同时行血肿清除术.以术后1周GCS及术后3～6个月改良Rankin量表评分(mRS)评价疗效及预后.结果 7例患者手术均顺利完成.术后1周GCS为3～15分.2例于术后1 d死亡,1例于术后31d死亡.4例生存患者的随访时间为3～36个月.术后患者口服抗凝药物治疗3～12个月.3～6个月复查头颅CT静脉血管成像或磁共振静脉成像未见颅内新发静脉窦血栓形成及出血.至末次随访,预后较好(mRS 1～2分)2例,预后较差(mRS 3分)2例.结论 对于出血性颅内静脉窦血栓并发脑疝的患者,开颅减压手术可在一定程度上改善患者预后,但该病总体预后较差.

OBJECTIVE:Rosai-Dorfman disease (RDD) is a rare, idiopathic, and non-neoplastic histio-proliferative disease that is uncommon in the central nervous system. Hence, reports of management of RDD in the skull base are scarce and only a few studies on skull base RDD are available. The objective of this study was to analyze the diagnosis, treatment, and prognosis of RDD in the skull base and explore an appropriate treatment strategy thereof. METHODS:Nine patients with clinical characteristics and follow-up data from our department between 2017 and 2022 were included in this study. From this information, the clinical profiles, imaging, treatment, and prognosis data were collected. RESULTS:There were 6 male and 3 female patients with skull base RDD. These patients ranged in age from 13 to 61 years, with a median age of 41 years. The locations included 1 anterior skull base orbital apex, 1 parasellar region, 2 sellar regions, 1 petroclivus, and 4 foramen magnum regions. Six patients underwent total resection and 3 underwent subtotal resection. Patient follow-up lasted 11-65 months, with a median duration of 24 months. One patient died, 2 experienced recurrence, and the other patients' lesions were stable. The symptoms worsened and new complications occurred in 5 patients. CONCLUSIONS:Skull base RDDs are intractable diseases with a high rate of complications. Some patients are at risk of recurrence and death. Surgery may be the basic treatment for this disease, and combined therapy including targeted therapy or radiation therapy may also be a valuable therapeutic strategy.

Abstract Background Skull base chordoma is a rare and aggressive tumour of the bone that has a high likelihood of recurrence. The fundamental differences in single cells between primary and recurrent lesions remain poorly understood, impeding development of effective treatment approaches. Methods To obtain an understanding of the differences in single cells between primary and recurrent chordomas, we performed single‐cell RNA sequencing and T‐cell/B‐cell receptor (BCR) sequencing. This allowed us to delineate the differences between the two types of tumour cells, tumour‐infiltrating lymphocytes, myeloid cells, fibroblasts and B cells. Copy number variants (CNVs) were detected and compared between the tumour types to assess heterogeneity. Selected samples were subjected to immunohistochemistry to validate protein expression. Fluorescence in situ hybridisation experiments, Transwell assays and xenograft mouse models helped verify the role of fibronectin 1 (FN1) in chordoma. Results Promoting natural killer (NK) cell and CD8_GZMK T‐cell function or inhibiting the transformation of CD8_GZMK T cells to CD8_ZNF683 T cells and promoting the transformation of natural killer T (NKT) cells to NK cells are promising strategies for preventing chordoma recurrence. Additionally, inhibiting the M2‐like activity of tumour‐associated macrophages (TAMs) could be an effective approach. Antigen‐presenting cancer‐associated fibroblasts (apCAFs) and dendritic cells (DCs) with high enrichment of the antigen‐presenting signature were enriched in primary chordomas. There were fewer plasma cells and BCR clonotypes in recurrent chordomas. Remarkably, FN1 was upregulated, had more CNVs, and was more highly secreted by tumours, macrophages, CD4 T cells, CD8 T cells and fibroblasts in recurrent chordoma than in primary chordoma. Finally, FN1 enhanced the invasion and proliferation of chordomas in vivo and in vitro. Conclusion Our comprehensive picture of the microenvironment of primary and recurrent chordomas provides deep insights into the mechanisms of chordoma recurrence. FN1 is an important target for chordoma therapy.

BACKGROUND:The function and regulation of miRNAs in progression of chordoma were unclear.METHODS:Five miRNAs were identified by the machine learning method from the miRNA expression array. CCk-8 assay, EDU assay, wound healing migration assay, and trans-well assay were used to reveal the effect of the miRNAs in chordoma cell lines. Moreover, bioinformation analysis and the mRNA expression array between the primary chordomas and recurrent chordomas were used to find the target protein genes of miRNAs. Furthermore, qRT-PCR and luciferase reporter assay were used to verify the result.RESULTS:miR-186-5p, miR-30c-5p, miR-151b, and miR-125b-5p could inhibit proliferation, migration, and invasion of chordoma while miR-1260a enhances proliferation, migration, and invasion of chordoma. Recurrent chordoma has a worse disease-free outcome than the primary chordoma patients. AMOT, NPTX1, RYR3, and P2RX5 were the target protein mRNAs of miR-186-5p; NPTX1 was the target protein mRNAs of miR-125b-5p; and AMOT and TNFSF14 were the target protein mRNAs of miR-1260a.CONCLUSIONS:miR-186-5p, miR-125b-5p, miR-1260a, and their target protein mRNAs including AMOT, NPTX1, RYR3, P2RX5, TNFSF14 may be the basement of chordoma research.

BACKGROUND Extra-axial cavernous malformations involving the foramen magnum are rare, and preoperative diagnosis becomes difficult when they mimic meningiomas. OBSERVATIONS The authors present 2 cases of extra-axial cavernous malformations involving the foramen magnum. Surgical removal of the lesions was performed via far lateral craniotomy. The authors investigate the disease and elaborate the differential diagnosis. LESSONS The authors recommend that extra-axial cavernous malformations should be considered in the differential diagnosis of lesions in the foramen magnum region. Intraoperative frozen sections are helpful to the diagnosis, and resection warranted a favorable long-term outcome.

INTRODUCTION:This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs). METHODS:A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses. RESULTS:The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042). CONCLUSION:The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.

Background Skull-base chordomas are rare malignant bone cancers originating from the remnant of the notochord. Survival is variable, and clinical or molecular factors cannot reliably predict their outcomes. This study therefore identified epigenetic subtypes that defined new chordoma epigenetic profiles and their corresponding characteristics. Methods Methylation profiles of 46 chordoma-resected neoplasms between 2008 and 2014, along with clinical information, were collected. K-means consensus clustering and principal component analysis were used to identify and validate the clusters. Single-sample gene set enrichment analysis, methylCIBERSORT algorithm, and copy number analysis were used to identify the characteristics of the clusters. Results Unsupervised clustering analysis confirmed two clusters with a progression-free survival difference. Gene set enrichment analysis indicated that the early and late estrogen response pathways and the hypoxia pathway were activated whereas the inflammatory and interferon gamma responses were suppressed. Forty-six potential therapeutic targets corresponding to differentially methylated sites were identified from chordoma patients. Subgroups with a worse outcome were characterized by low immune cell infiltration, higher tumor purity, and higher stemness indices. Moreover, copy number amplifications mostly occurred in cluster 1 tumors and the high-risk group. Additionally, the presence of a CCNE1 deletion was exclusively found in the group of chordoma patients with better outcome, whereas RB1 and CDKN2A/2B deletions were mainly found in the group of chordoma patients with worse outcome. Conclusions Chordoma prognostic epigenetic subtypes were identified, and their corresponding characteristics were found to be variable.

目的 探讨突变型p53在颅底脊索瘤中的表达与患者预后及临床特点的关联,并在细胞层面验证突变型p53在颅底脊索瘤中的功能.方法 纳入2005年1月-2014年12月在首都医科大学附属北京天坛医院接受手术治疗的颅底脊索瘤患者49例,应用石蜡切片进行免疫组织化学染色,分析突变型p53表达与颅底脊索瘤患者预后及临床特点的关系.应用siRNA敲降脊索瘤细胞系UCH-1中的p53基因,分析敲降前后细胞功能的变化.结果 在蛋白水平,突变型p53表达水平是肿瘤术后进展的风险因素,随突变型p53表达水平升高,肿瘤进展风险增加(OR:1.040,95％CI:1.007～1.073,P=0.016);另外,骨质浸润型肿瘤较非浸润型中突变型p53表达升高(t=3.319,P=0.002),质地硬的较质地软的肿瘤突变型p53表达升高(t=-3.503,P=0.001),血供丰富型较不丰富型肿瘤突变型p53表达升高(t=2.081,P=0.043).细胞水平,与对照组相比,p53敲降组的细胞活力在不同时间点间有差异(F=305.715,P=0.000);p53敲降组细胞凋亡率低于对照组(t=-3.961,P=0.017);与对照组相比,p53敲降组在第6(t=-5.232,P=0.014)、12(t=4.778,P=0.017)及24(t=-9.303,P=0.003)小时穿透至下室的肿瘤细胞均增多.结论 颅底脊索瘤中突变型p53表达升高可导致术后肿瘤进展风险增加,其表达与肿瘤质地、侵袭性和血供情况相关;突变型p53表达受抑制后脊索瘤细胞增殖和侵袭能力提高,凋亡减少.