Tumor-associated monocytes promote mesenchymal transformation through EGFR signaling in glioma.

The role of brain immune compartments in glioma evolution remains elusive. We profile immune cells in glioma microenvironment and the matched peripheral blood from 11 patients. Glioblastoma exhibits specific infiltration of blood-originated monocytes expressing epidermal growth factor receptor (EGFR) ligands EREG and AREG, coined as tumor-associated monocytes (TAMo). TAMo infiltration is mutually exclusive with EGFR alterations (p = 0.019), while co-occurring with mesenchymal subtype (p = 4.7 × 10-7) and marking worse prognosis (p = 0.004 and 0.032 in two cohorts). Evolutionary analysis of initial-recurrent glioma pairs and single-cell study of a multi-centric glioblastoma reveal association between elevated TAMo and glioma mesenchymal transformation. Further analyses identify FOSL2 as a TAMo master regulator and demonstrates that FOSL2-EREG/AREG-EGFR signaling axis promotes glioma invasion in vitro. Collectively, we identify TAMo in tumor microenvironment and reveal its driving role in activating EGFR signaling to shape glioma evolution.

Carotid artery direct access for intracranial stenting of a stroke patient with an aberrant left common carotid artery and right aorta.

A right aortic arch is present in 0.1% of the population and can occur in isolation or be associated with congenital heart disease.1 Moreover, the most common form of right aortic arch in adults is associated with an aberrant left subclavian artery.1 An aberrant left common carotid artery that originated from the ascending aorta with the right aorta is very rare. In this situation, carotid direct access was considered to avoid access challenge due to a large curve from the ascending aorta to the left common carotid artery.2 3 Here we demonstrate carotid artery direct access for intracranial stenting of a stroke patient with aberrant left common carotid artery and right aorta. Manual compression with a long time under general anesthesia to avoid post-procedural puncture site hematoma is recommended (video 1).neurintsurg;jnis-2023-020535v1/V1F1V1Video 1 Carotid artery direct access.

New Diffusion Abnormalities Following Endovascular Treatment for Intracranial Atherosclerosis.

Background There are limited data on new ischemic brain lesions after endovascular treatment for symptomatic intracranial atherosclerotic stenosis (ICAS). Purpose To investigate the (a) characteristics of new ischemic brain lesions at diffusion-weighted MRI (new diffusion abnormalities) after endovascular treatment, (b) characteristics between those treated with balloon angioplasty and stent placement procedures, and (c) predictors of new ischemic brain lesions. Materials and Methods Patients with symptomatic ICAS in whom maximum medical therapy failed were prospectively enrolled between April 2020 and July 2021 from a national stroke center and underwent endovascular treatment. All study participants underwent thin-section diffusion-weighted MRI (voxel size, 1.4 × 1.4 × 2 mm3 with no section gap) before and after treatment. The characteristics of new ischemic brain lesions were recorded. Multivariable logistic regression analysis was performed to determine potential predictors of new ischemic brain lesions. Results A total of 119 study participants (mean age, 59 years ± 11 [SD]; 81 men; 70 treated with balloon angioplasty and 49 with stent placement) were enrolled. Of the 119 participants, 77 (65%) had new ischemic brain lesions. Five of the 119 participants (4%) had symptomatic ischemic stroke. New ischemic brain lesions were located in (61%, 72 of 119) and/or beyond (35%, 41 of 119) the territory of the treated artery. Of the 77 participants with new ischemic brain lesions, 58 (75%) had lesions located in peripheral brain areas. There was no evidence of a difference in the frequency of new ischemic brain lesions between the balloon angioplasty and stent groups (60% vs 71%, P = .20). In adjusted models, cigarette smoking (odds ratio [OR], 3.6; 95% CI: 1.3, 9.7) and more than one operative attempt (OR, 2.9; 95% CI: 1.2, 7.0) were independent predictors of new ischemic brain lesions. Conclusion New ischemic brain lesions on diffusion-weighted MRI scans were common after endovascular treatment for symptomatic intracranial atherosclerotic stenosis, and occurrence may be associated with cigarette smoking and the number of operative attempts. Clinical trial registration no. ChiCTR2100052925 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Russell in this issue.

Predictors of hyperperfusion syndrome after stent implantation in symptomatic intracranial atherosclerotic stenosis.

Background: Hyperperfusion syndrome (HPS) is a serious complication after stent implantation in symptomatic intracranial atherosclerotic stenosis (ICAS). This study aims to explore the predictive value of preprocedural computed tomography perfusion (CTP) for HPS after intracranial stenting. Methods: In this retrospective case-control study we collected data from consecutive patients from June 2012 to September 2019 who underwent stent implantation due to severe symptomatic ICAS. Patients who underwent CTP before the procedure were enrolled. CTP was postprocessed using the automated RAPID software to assess the preoperative cerebral perfusion. According to the presence or absence of HPS, the patients were classified into two groups: the HPS group and the non-HPS group. The baseline data, lesion characteristics, and preoperative CTP parameters between the two groups were compared. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal predictor of HPS. Results: Among the 170 eligible patients, 6 patients (3.53%) had HPS, including 3 who presented with intracranial hemorrhages (ICHs), 1 who had dysphoria, 1 who had delirium, and 1 who had a headache. There were no significant differences in baseline and lesion characteristics between the HPS and non-HPS groups. Compared with the non-HPS group, the HPS group had a significantly higher volume of time-to-maximum (Tmax) >4 s (429.5 vs. 93 mL; P=0.006) and Tmax >6 s (200 vs. 0 mL; P=0.003). The optimal volume threshold for maximizing sensitivity in predicting HPS was 65.5 mL with Tmax >4 s [area under the curve (AUC), 0.832; 95% confidence interval (CI): 0.650 to 1.000; P=0.006]. Conclusions: Tmax >4 s volume may be a predictor of HPS after stent implantation in symptomatic ICAS. Further prospective studies should be conducted to confirm our conclusion.

Machine learning of genomic features in organotropic metastases stratifies progression risk of primary tumors.

Metastatic cancer is associated with poor patient prognosis but its spatiotemporal behavior remains unpredictable at early stage. Here we develop MetaNet, a computational framework that integrates clinical and sequencing data from 32,176 primary and metastatic cancer cases, to assess metastatic risks of primary tumors. MetaNet achieves high accuracy in distinguishing the metastasis from the primary in breast and prostate cancers. From the prediction, we identify Metastasis-Featuring Primary (MFP) tumors, a subset of primary tumors with genomic features enriched in metastasis and demonstrate their higher metastatic risk and shorter disease-free survival. In addition, we identify genomic alterations associated with organ-specific metastases and employ them to stratify patients into various risk groups with propensities toward different metastatic organs. This organotropic stratification method achieves better prognostic value than the standard histological grading system in prostate cancer, especially in the identification of Bone-MFP and Liver-MFP subtypes, with potential in informing organ-specific examinations in follow-ups.

Classification of Pituitary Adenomas Invading the Cavernous Sinus Assisted by Three-Dimensional Multimodal Imaging and Its Clinical Application.

Introduction To help diagnose and evaluate the prognosis of pituitary adenoma with cavernous sinus (CS) invasion and guide endonasal endoscopic surgery (EES) assisted by intraoperative navigation (ION) with three-dimensional multimodal imaging (3D-MMI). We propose a classification of CS invasion based on 3D-MMI. Methods We picked some appropriate cases and reconstructed the 3D-MMI and then classified them into 3 grades according to the stereo relationship among ICA, tumor and CS in 3D-MMI. Then, we applied different strategies according to their grade to remove pituitary adenomas that invaded the CS. Results All 38 patients were divided into 3 grades. Tumors compressing the ICA and CS without CS invasion were divided into grade 1. Tumors encasing the ICA and invading the superior-posterior compartment and/or anterior-inferior compartment but without distinct separation of the ICA and CS lateral wall were deemed as grade 2. Tumors encasing the ICA and filling the lateral compartment of the CS that dissociated the lateral wall from the ICA were deemed as grade 3. The 3D-MMI enabled adequate spatial visualization of the ICA, CS and tumors. All patients were operated on under the guidance of ION with 3D-MMI. Conclusion Classification based on 3D-MMI can better demonstrate the relationships among tumor, ICA and CS in a stereo and multi-angle view, which will have significance in guiding the surgical strategy.

De Novo Germline and Somatic Variants Convergently Promote Endothelial-to-Mesenchymal Transition in Simplex Brain Arteriovenous Malformation.

[Figure: see text].

LncRNA PITPNA-AS1 stimulates cell proliferation and suppresses cell apoptosis in glioblastoma via targeting miR-223-3p/EGFR axis and activating PI3K/AKT signaling pathway.

Glioblastoma (GBM) is a kind of malignant primary brain tumor, which is difficult to cure. Continuous researches have underlined that long non-coding RNAs (lncRNAs) get widely involved in the occurrence and progression of tumors, and glioblastoma is included. In this paper, we identified lncRNA PITPNA antisense RNA 1 (PITPNA-AS1) and explored its in-depth regulatory mechanism in glioblastoma cells. Firstly, RT-qPCR examined that PITPNA-AS1 was highly expressed in glioblastoma. Then, PITPNA-AS1 role in glioblastoma was assessed via functional assays. The results demonstrated that depletion of PITPNA-AS1 inhibited the proliferation and promoted the apoptosis of glioblastoma cells. After confirming that PITPNA-AS1 mainly existed in cell cytoplasm, we conducted mechanism assays which disclosed that PITPNA-AS1 sequestered microRNA-223-3p (miR-223-3p) and modulated epidermal growth factor receptor (EGFR) expression, thereby participating in the activation of PI3K/AKT signaling pathway. Eventually, rescue assays validated PITPNA-AS1 sponged miR-223-3p to promote EGFR expression, thus activating PI3K/AKT signaling pathway to accelerate proliferation and inhibit apoptosis of GBM cells. Overall, PITPNA-AS1 played an oncogenic role in glioblastoma which might be developed as a potential biomarker for glioblastoma diagnosis and treatment in the future.[Figure: see text].

Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation.

Cerebral cavernous malformations (CCMs) are vascular disorders that affect up to 0.5% of the total population. About 20% of CCMs are inherited because of familial mutations in CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10, whereas the etiology of a majority of simplex CCM-affected individuals remains unclear. Here, we report somatic mutations of MAP3K3, PIK3CA, MAP2K7, and CCM genes in CCM lesions. In particular, somatic hotspot mutations of PIK3CA are found in 11 of 38 individuals with CCMs, and a MAP3K3 somatic mutation (c.1323C>G [p.Ile441Met]) is detected in 37.0% (34 of 92) of the simplex CCM-affected individuals. Strikingly, the MAP3K3 c.1323C>G mutation presents in 95.7% (22 of 23) of the popcorn-like lesions but only 2.5% (1 of 40) of the subacute-bleeding or multifocal lesions that are predominantly attributed to mutations in the CCM1/2/3 signaling complex. Leveraging mini-bulk sequencing, we demonstrate the enrichment of MAP3K3 c.1323C>G mutation in CCM endothelium. Mechanistically, beyond the activation of CCM1/2/3-inhibited ERK5 signaling, MEKK3 p.Ile441Met (MAP3K3 encodes MEKK3) also activates ERK1/2, JNK, and p38 pathways because of mutation-induced MEKK3 kinase activity enhancement. Collectively, we identified several somatic activating mutations in CCM endothelium, and the MAP3K3 c.1323C>G mutation defines a primary CCM subtype with distinct characteristics in signaling activation and magnetic resonance imaging appearance.

Classification of brain arteriovenous malformations located in motor-related areas based on location and anterior choroidal artery feeding.

OBJECTIVE: Surgical management of arteriovenous malformations (AVMs) involving motor cortex or fibre tracts (M-AVMs) is challenging. This study aimed to construct a classification system based on nidus locations and anterior choroidal artery (AChA) feeding to pre-surgically evaluate motor-related and seizure-related outcomes in patients undergoing resection of M-AVMs. METHODS AND MATERIALS: A total of 125 patients who underwent microsurgical resection of M-AVMs were retrospectively reviewed. Four subtypes were identified based on nidus location: (I) nidus involving the premotor area and/or supplementary motor areas; (II) nidus involving the precentral gyrus; (III) nidus involving the corticospinal tract (CST) and superior to the posterior limb of the internal capsule; (IV) nidus involving the CST at or inferior to the level of posterior limb of the internal capsule. In addition, we divided type IV into type IVa and type IVb according to the AChA feeding. Surgical-related motor deficit (MD) evaluations were performed 1 week (short-term) and 6 months (long-term) after surgery. RESULTS: The type I patients exhibited the highest incidence (62.0%) of pre-surgical epilepsy among the four subtypes. Multivariate analysis showed that motor-related area subtypes (p=0.004) and diffuse nidus (p=0.014) were significantly associated with long-term MDs. Long-term MDs were significantly less frequent in type I than in the other types. Type IV patients acquired the highest proportion (four patients, 25.0%) of long-term poor outcomes (mRS >2). Type IVb patients showed a significantly higher incidence of post-surgical MDs than type IVa patients (p=0.041). The MDs of type III or IV patients required more recovery time. Of the 62 patients who had pre-surgical seizures, 90.3% (56/62) controlled their seizures well and reached Engel class I after surgery. CONCLUSIONS: Combining the consideration of location and AChA feeding, the classification for M-AVMs is a useful approach for predicting post-surgical motor function and decision-making.

Evaluating the association of preoperative parecoxib with acute pain trajectories after video-assisted thoracoscopic surgery: a single-centre cohort study in Taiwan.

OBJECTIVE: The efficacy of parecoxib as pre-emptive analgesia still remains controversial. This study aimed to investigate how pre-emptive analgesia with parecoxib affected postoperative pain trajectories over time in patients undergoing thoracic surgery. DESIGN: Retrospective cohort study. SETTING: A single medical centre in Taiwan. PARTICIPANTS: We collected 515 patients undergoing video-assisted thoracoscopic surgery at a tertiary medical centre between September 2016 and August 2017. INTERVENTIONS: Pre-emptive parecoxib before surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: Daily numeric rating pain scores in the first postoperative week. RESULTS: A total of 196 (38.1%) of the recruited patients received parecoxib preoperatively. The latent curve analysis revealed that woman, higher body weight and postoperative use of parecoxib were associated with increased baseline level of pain scores over time (p=0.035, 0.005 and 0.048, respectively) but epidural analgesia and preoperative use of parecoxib were inclined to decrease it (both p<0.001). Regarding the decreasing trends of changes in daily pain scores, older age and epidural analgesia tended to steepen the slope (p=0.014 and <0.001, respectively). Preoperative use of parecoxib were also related to decreased frequency of rescue morphine medication (HR=0.4; 95% CI 0.25 to 0.65). CONCLUSIONS: Pre-emptive analgesia with parecoxib was associated with decreased baseline pain scores but had no connection with pain decreasing trends over time. Latent curve analysis provided insights into the dynamic relationships among the analgesic modalities, patient characteristics and postoperative pain trajectories.

The CTSC-RAB38 Fusion Transcript Is Associated With the Risk of Hemorrhage in Brain Arteriovenous Malformations.

Brain arteriovenous malformations (bAVMs) are congenital anomalies of blood vessels that cause intracranial hemorrhage in children and young adults. Chromosomal rearrangements and fusion genes play an important role in tumor pathogenesis, though the role of fusion genes in bAVM pathophysiological processes is unclear. The aim of this study was to identify fusion transcripts in bAVMs and analyze their effects. To identify fusion transcripts associated with bAVM, RNA sequencing was performed on 73 samples, including 66 bAVM and 7 normal cerebrovascular samples, followed by STAR-Fusion analysis. Reverse transcription polymerase chain reaction and Sanger sequencing were applied to verify fusion transcripts. Functional pathway analysis was performed to identify potential effects of different fusion types. A total of 21 fusion transcripts were detected. Cathepsin C (CTSC)-Ras-Related Protein Rab-38 (RAB38) was the most common fusion and was detected in 10 of 66 (15%) bAVM samples. In CTSC-RAB38 fusion-positive samples, CTSC and RAB38 expression was significantly increased and activated immune/inflammatory signaling. Clinically, CTSC-RAB38 fusion bAVM cases had a higher hemorrhage rate than non-CTSC-RAB38 bAVM cases (p < 0.05). Our study identified recurrent CTSC-RAB38 fusion transcripts in bAVMs, which may be associated with bAVM hemorrhage by promoting immune/inflammatory signaling.

Single-Cell Atlas Reveals Complexity of the Immunosuppressive Microenvironment of Initial and Recurrent Glioblastoma.

The Glioblastoma (GBM) immune microenvironment plays a critical role in tumor development, progression, and prognosis. A comprehensive understanding of the intricate milieu and its interactions remains unclear, and single-cell analysis is crucially needed. Leveraging mass cytometry (CyTOF), we analyzed immunocytes from 13 initial and three recurrent GBM samples and their matched peripheral blood mononuclear cells (pPBMCs). Using a panel of 30 markers, we provide a high-dimensional view of the complex GBM immune microenvironment. Hematoxylin and eosin staining and polychromatic immunofluorescence were used for verification of the key findings. In the initial and recurrent GBMs, glioma-associated microglia/macrophages (GAMs) constituted 59.05 and 27.87% of the immunocytes, respectively; programmed cell death-ligand 1 (PD-L1), T cell immunoglobulin domain and mucin domain-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), interleukin-10 (IL-10) and transforming growth factor-ß (TGFß) demonstrated different expression levels in the GAMs among the patients. GAMs could be subdivided into different subgroups with different phenotypes. Both the exhausted T cell and regulatory T (Treg) cell percentages were significantly higher in tumors than in pPBMCs. The natural killer (NK) cells that infiltrated into the tumor lesions expressed higher levels of CXC chemokine receptor 3 (CXCR3), as these cells expressed lower levels of interferon-γ (IFNγ). The immune microenvironment in the initial and recurrent GBMs displayed similar suppressive changes. Our study confirmed that GAMs, as the dominant infiltrating immunocytes, present great inter- and intra-tumoral heterogeneity and that GAMs, increased exhausted T cells, infiltrating Tregs, and nonfunctional NK cells contribute to local immune suppressive characteristics. Recurrent GBMs share similar immune signatures with the initial GBMs except the proportion of GAMs decreases.

High Dimensional Mass Cytometry Analysis Reveals Characteristics of the Immunosuppressive Microenvironment in Diffuse Astrocytomas.

The tumor immune microenvironment (TIME) plays a pivotal role in tumor development, progression, and prognosis. However, the characteristics of the TIME in diffuse astrocytoma (DA) are still unclear. Leveraging mass cytometry with a panel of 33 markers, we analyzed the infiltrating immune cells from 10 DA and 4 oligodendroglioma (OG) tissues and provided a single cell-resolution landscape of the intricate immune microenvironment. Our study profiled the composition of the TIME in DA and confirmed the presence of immune cells, such as glioma-associated microglia/macrophages (GAMs), CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and natural killer cells. Increased percentages of PD-1+ CD8+ T cells, TIM-3+ CD4+ T cell subpopulations, Tregs and pro-tumor phenotype GAMs substantially contribute to the local immunosuppressive microenvironment in DA. DAs and OGs share similar compositions in terms of immune cells, while GAMs in DA exhibit more inhibitory characteristics than those in OG.

Plasticity in language cortex and white matter tracts after resection of dominant inferior parietal lobule arteriovenous malformations: a combined fMRI and DTI study.

OBJECTIVE: The dominant inferior parietal lobe (IPL) contains cortical and subcortical structures that serve language processing. A high incidence of postoperative short-term aphasia and good potential for language reorganization have been observed. The authors' goal was to study the plasticity of the language cortex and language-related fibers in patients with brain arteriovenous malformations (BAVMs) located in the IPL. METHODS: A total of 6 patients who underwent microsurgical treatment of an IPL BAVM were prospectively recruited between September 2016 and May 2018. Blood oxygen level-dependent functional MRI (BOLD-fMRI) and diffusion tensor imaging (DTI) were performed within 1 week before and 6 months after microsurgery. Language-related white matter (WM) eloquent fiber tracts and their contralateral homologous fiber tracts were tracked. The Western Aphasia Battery was administered to assess language function. The authors determined the total number of fibers and mean fractional anisotropy (FA) indices for each individual tract. In addition, they calculated the laterality index (LI) between the activated language cortex voxels in the lesional and contralesional hemispheres and compared these indices between the preoperative and postoperative fMR and DT images. RESULTS: Of the 6 patients with IPL BAVMs, all experienced postoperative short-term language deficits, and 5 (83.3%) recovered completely at 6 months after surgery. Five patients (83.3%) had right homologous reorganization of BOLD signal activations in both Broca's and Wernicke's areas. More fibers were observed in the arcuate fasciculus (AF) in the lesional hemisphere than in the contralesional hemisphere (1905 vs 254 fibers, p = 0.035). Six months after surgery, a significantly increased number of fibers was seen in the right hemispheric AF (249 fibers preoperatively vs 485 postoperatively, p = 0.026). There were significantly more nerve fibers in the postoperative left inferior frontooccipital fasciculus (IFOF) (874 fibers preoperatively vs 1186 postoperatively, p = 0.010). A statistically significant increase in right hemispheric dominance of Wernicke's area was observed. The overall functional LI showed functional lateralization of Wernicke's area in the right hemisphere (LI ≤ -0.20) in all patients. CONCLUSIONS: The authors' findings provide evidence for the functional reorganization by recruiting the right hemispheric homologous region of Broca's and Wernicke's areas, right hemispheric AFs, and left hemispheric IFOFs following resection of IPL BAVMs.Clinical trial registration no.: NCT02868008 (clinicaltrials.gov).

CyTOF Analysis Reveals a Distinct Immunosuppressive Microenvironment in IDH Mutant Anaplastic Gliomas.

The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD.

Establishment and quality evaluation of a glioma biobank in Beijing Tiantan Hospital.

BACKGROUND: We established a glioma biobank at Beijing Tiantan Hospital in November, 2010. Specialized residents have been trained to collect, store and manage the biobank in accordance with standard operating procedures. METHODS: One hundred samples were selected to evaluate the quality of glioma samples stored in the liquid nitrogen tank during different periods (from 2011 to 2015) by morphological examination, RNA integrity determination, DNA integrity determination and housekeeping gene expression determination. RESULTS: The majority of samples (95%) had high RNA quality for further analysis with RIN ≥6. Quality of DNA of all samples were stable without significant degradation. CONCLUSION: Storage conditions of our biobank are suitable for long-term (at least five years) sample preservation with high molecular quality.

Surgical Outcomes of Cavernous Sinus Syndrome in Pituitary Adenomas.

OBJECTIVE: The type of pituitary adenoma with a manifestation that includes cavernous sinus syndrome is rare. Based on the clinical data of 70 patients, this study investigated the pathogenesis, imaging characteristics, and prognostic factors of pituitary adenoma with cavernous sinus syndrome. METHODS: We conducted a retrospective analysis of the characteristics of patients with pituitary adenoma with cavernous sinus syndrome who received surgical treatment. The patients were classified into different prognosis groups according to the time required for them to recover from the cavernous sinus syndrome. Univariate analyses were conducted for the correlations between the prognosis and factors. RESULTS: Of the 3598 cases of pituitary adenomas, 70 (1.95%) presented cavernous sinus syndrome. Of the patients, 55.7% recovered within 2 weeks of surgery, 24.3% recovered from 2 weeks to 1 year after surgery, and 20% had not returned to normal after more than 1 year after surgery. Univariate analyses showed that shorter disease duration (P < 0.001), lower Knosp grade (P = 0.045), a transsphenoidal approach (P < 0.001), and associated pituitary apoplexy (P = 0.012) were predictive factors of early postoperative recovery. CONCLUSIONS: The prognosis of cavernous sinus syndrome differs depending on the mechanism of the syndrome. There was no significant difference in the prognosis between patients with total pituitary adenoma resection and subtotal resection. Timely surgery within 100 days of symptom occurrence, Knosp grade 0-2, and associated pituitary apoplexy are predictive factors of good prognosis.

Rosette-Forming Glioneuronal Tumor Originating From the Spinal Cord: Report of 2 Cases and Literature Review.

Rosette-forming glioneuronal tumor (RGNT) is a recently recognized and rarely encountered tumor occurring in the fourth ventricle. RGNT was first described as a new entity for the distinct clinicopathologic features by Komori et.al. in 2002. Histologically, it is composed of 2 distinct features: a glial component, resembling pilocytic astrocytoma, and a neurocytic component forming neurocytic rosettes and/or perivascular rosettes. We report 2 extremely rare cases of RGNT arising from the spinal cord, which were misdiagnosed as ependymoma and astrocytoma preoperatively. Symptoms included dissociated sensory disturbances and episodic pain and fatigue of 2 years' duration in case 1, as well as motor disturbance for 2 months' duration in case 2. Magnetic resonance imaging (MRI) revealed these masses in the thoracolumbar (T7-L1) and cervicothoracic (C3-C7) spinal cord. The solid component appeared hypointense in T1-weighted MRI sequences, hyperintense in the T2-weighted MRI sequences, and heterogeneous in MRI images enhanced with gadolinium contrast medium in both cases. Gross total resection was performed via a median laminectomy. Postoperative pathological examination confirmed the diagnosis of RGNT. In addition, extensive analysis of genetic mutations was performed to explore the relationship with glioma, including telomerase reverse transcriptase promoter, isocitrate dehydrogenase 1/2, BRAF-V600E, and O(6)-methylguanine-DNA methyltransferase promoter. No radiotherapy or chemotherapy were performed in these two cases. As of the latest follow-up, both patients had a good prognosis. Given the widely varying clinical characteristics of, prognosis of, and treatments for spinal tumors, differential diagnosis is of great importance before surgery. Consideration of the tumor location and the patient's age and sex, in combination with the imaging features, may be the best approach to narrowing the differential diagnosis. Surgery is the preferred treatment for RGNT. We do not recommend to implement adjuvant radiotherapy and chemotherapy in these patients except the invasive or recurrent tumors. Further examination and routine follow-up should be recommended to estimate the long-term prognosis.