Planned Subtotal Resection following Stereotactic Radiosurgery of Koos 3 and 4 Vestibular Schwannomas.

Background/Objectives: Surgical resection of medium to large vestibular schwannomas (VSs, Koos grade 3 and 4) is a widely used approach, although stereotactic radiosurgery (SRS) is increasingly proposed as initial treatment. The quality of life-centered approach is challenged in cases where tumor growth control cannot be achieved with SRS, thus necessitating salvage surgery. We present a series of eight consecutive patients who required surgery due to continued tumor growth after SRS. Methods: Of the 146 patients with VS grades 3 and 4 initially treated with SRS, only eight patients (mean age, 54 ± 7.2 years; range, 42-63 years) required subsequent surgery. Their mean tumor volume was 9.9 ± 3.2 cm3. The mean time from SRS to first tumor progression and planned subtotal resection was 23 ± 5.9 months and 45 ± 17.5 months, respectively. SRS was not performed after the surgery in favor of a "wait and rescan" approach. Tumor residue was monitored on follow-up magnetic resonance imaging. In all patients, tumor growth control after planned subtotal resection was maintained at 63 ± 19.8 months. Results: None of the 146 patients had serious complications after SRS. In the eight patients who required surgery, tumor growth between 22% and 212% (mean, 4 cm3) was reported within 26 to 84 months after SRS. Before salvage surgery, they scored 1 point on the House-Brackmann scale. Subtotal excision was performed, and VIIth nerve function was preserved in all patients. At 63 ± 19.8 months, 3 patients had a House-Brackmann score of 1, four patients had a score of 2, and one patient had a score of 3. Conclusions: Surgical excision of medium to large VS after SRS can be relatively safe, provided that a quality of life-centered approach of subtotal resection is used.

Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2-3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

A comparison of different machine-learning techniques for the selection of a panel of metabolites allowing early detection of brain tumors.

Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I-IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476-0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients.

External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort.

PURPOSE: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales. METHODS: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year. RESULTS: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively. CONCLUSION: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.

Relevance of Routine Postoperative CT Scans Following Aneurysm Clipping-A Retrospective Multicenter Analysis of 423 Cases.

AIM: Postoperative head computed tomography (POCT) is routinely performed in numerous medical institutions, mainly to identify possible postsurgical complications. This study sought to assess the clinical appropriateness of POCT in asymptomatic and symptomatic patients after ruptured or unruptured aneurysm clipping. METHODS: This is a retrospective multicenter study involving microsurgical procedures of ruptured (RA) and unruptured intracranial aneurysm (UA) surgeries performed in the Centers associated with the Pomeranian Department of the Polish Society of Neurosurgeons. A database of surgical procedures of intracranial aneurysms from 2017 to 2020 was created. Only patients after a CT scan within 24 h were included. RESULTS: A total of 423 cases met the inclusion criteria for the analysis. Age was the only significant factor associated with postoperative blood occurrence on POCT. A total of 37 (8.75%) cases of deterioration within 24 h with urgent POCT were noted, 3 (8.1%) required recraniotomy. The highest number necessary to predict (NNP) one recraniotomy based on patient deterioration was 50 in the RA group. CONCLUSION: We do not recommend POCTs in asymptomatic patients after planned clipping. New symptom onset requires radiological evaluation. Simultaneous practice of POCT after ruptured aneurysm treatment within 24 h is recommended.

Canonical NF-κB signaling pathway and GRO-α/CXCR2 axis are activated in unruptured intracranial aneurysm patients.

Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.

Plasma concentration of Bisphenol A and leptin in patients with meningioma and glioma: A pilot study.

PURPOSE: Recent increase in incidence of meningiomas suggests the need to search for new risk factors. Leptin, a potentially pro-angiogenic and proliferative agent, could be a candidate for this role, as its expression correlates with body mass index (BMI). Because development of meningioma has also been linked to sex hormones, bisphenol A (BPA), a known xenoestrogen, can also be taken into consideration as a potential risk factor. The aim of this study was to determine plasma concentrations of both substances in patients with meningiomas and to match it to patients with gliomas - a group of brain tumors less hormone- and BMI-dependent. MATERIALS & METHODS: Concentrations of BPA and leptin were measured in plasma of 24 patients with low grade meningioma and in 29 patients with glioma, using gas chromatography-mass spectrometry (GC-MS) and ELISA kits, respectively. The concentrations of both substances in patients with neoplasms were interpreted in relation to their concentration in healthy population, published in recent reports. RESULTS: Free and conjugated BPA were present in both meningioma and glioma patients. Moreover, their concentrations far exceeded those reported in the healthy population. Nevertheless, the level of leptin revealed to be significantly higher in meningioma patients than in glioma patients. CONCLUSIONS: Occurrence of both meningioma and glioma may be accompanied by increased concentrations of leptin and BPA. Further large-scale studies are needed to clarify whether the presence of both substances may play a role in pathogenesis or influence clinical course in patients with brain neoplasms.

IL-6 Quotient (The Ratio of Cerebrospinal Fluid IL-6 to Serum IL-6) as a Biomarker of an Unruptured Intracranial Aneurysm.

BACKGROUND: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth. METHODS: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers' instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6. RESULTS: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p<0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p<0.001). In both the study and control group, the blood-brain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227). CONCLUSION: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.

Endoscopic transconjunctival optic nerve sheath fenestration for progressive idiopathic visual field deficit: a case report.

Intra-orbital optic nerve sheath fenestration (ONSF) is an effective option in patients with progressive vision loss due to idiopathic intracranial hypertension. Most proposed techniques involve surgical trauma and require disinsertion of the medial rectus muscle; thus, less invasive surgical procedures are needed. Here, a feasible and effective technique of endoscopic intra-orbital ONSF through a conjunctival incision is presented, in a patient with a progressively compromised visual field, papilloedema, and distended subarachnoid space around the optic nerves. The retrobulbar segment of the optic nerve was exposed for incision, avoiding manipulation of the lateral orbital rim bones and irritation of the ciliary microvessels and nerves. The patient regained the entire visual field. ONSF was safely and effectively performed endoscopically through a narrow corridor gained by brushing away the orbital fat with minimal traction on the medial rectus muscle. The small postoperative wound was associated with faster and easier convalescence, and less tissue trauma versus conventional open approaches.

Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour.

INTRODUCTION: Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours. PATIENTS AND METHODS: Protein concentration in primary brain tumour (n = 49) and non-tumoural subjects (n = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-µm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein. RESULTS: The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients. CONCLUSIONS: Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients' survival.