Atypical meningiomas compared to other WHO Grade 2 meningiomas: Histological features and prognosis.

OBJECTIVES: To study each atypical feature in atypical meningioma versus other grade 2 meningiomas and its possible relation to recurrence. METHODS: This is a retrospective study of patients with WHO grade 2 meningioma operated in our institution between 01/2008 and 12/2020. The rate of recurrence, reoperation and readmission were recorded during the follow-up period. A statistical analysis was done to determine the significance of each pathological feature in regard to recurrence. RESULTS: A total of 74 patients were included as WHO grade 2 meningioma with 60 (81%) patients having an AM and 14 (19%) patients with chordoid or clear cell meningioma. The mean age was 51 years±14. The most common location was meningioma abutting the frontal lobe (convexity). Major atypical features were more noted in the AM, however, there was no significant difference between AM and other types of meningioma. Increased Nuclear cytoplasmic ratio and cellularity were found significantly more in AM. The recurrence rate was 16.2%. No specific pathology feature (major or minor) nor the type of Grade 2 meningioma was significantly related to recurrence. CONCLUSION: The types of WHO grade 2 meningiomas have similar prognosis and recurrence rates. There is no significant difference between the atypical features in indicating a more aggressive nature or risk of recurrence in grade 2 meningiomas.

A comprehensive correlation of the KI-67 proliferation index to patient´s, imaging and tumor features and its value in predicting long-term course of patients with newly diagnosed intracranial meningiomas.

To analyze the correlation of KI-67-Proliferation Index (KI-67-PI) with preoperative patients and MRI characteristics, WHO grading, histological subtype and long-term-course of patients with newly diagnosed intracranial meningiomas (IM). In this single-center retrospective study, all consecutive patients with IM were analyzed from January 2007 to August 2019. Patient´s demographics (age, sex), imaging parameters (location, volume, edema, necrosis), and tumor features (WHO grade, histology) were assessed and correlated with KI-67-PI. Long-term data were retrieved from patient's last follow-up visits. This study included 463 IM in 457 surgically treated patients. Males exhibited a higher KI-67-PI than females (7.31 ± 0.22 vs. 5.37 ± 0.53; p < 0.01, Mann-Whitney U Test). Age positively correlated with KI-67-PI in both sexes (p < 0.01, Spearman), with older patients having a higher KI-67-PI. KI-67-PI was significantly higher in convexity IM compared to frontobasal IM (7.15 ± 5.56 vs. 4.66 ± 2.94; p < 0.05, ANOVA, Tukey´s HSD), while no difference in KI-67-PI expression was found when other locations were compared to each other (Tukey´s HSD). Higher KI-67-PI was significantly correlated with larger tumor volume (p < 0.01, Spearman), larger tumor necrosis and larger peritumoral edema (p < 0.01, Kruskal-Wallis). Patients with recurrent IM had a significantly higher KI-67-PI than patients without recurrence (8.24 ± 5.88 vs. 5.14 ± 3.53; p < 0.01, ANOVA, Tukey´s HSD) during a mean follow-up period of 80.92 ± 38.1 months. Atypical and anaplastic IM exhibited significantly higher KI-67-PI compared to all other WHO grade 1 histological subtypes (12.09 ± 0.73 vs. 4.51 ± 0.13; p < 0.01, Kruskal-Wallis test) and KI-67-PI was significantly higher in anaplastic IM compared to atypical meningioma (19.67 ± 1.41 vs. 11.01 ± 0.38; p < 0.01, ANOVA). Higher KI-67-PI is not only associated with atypical and anaplastic subtypes of IM, but is also significantly higher in males, positively correlates with patients age, larger tumor volume, lager peritumoral edema and necrosis on preoperative MRI and predicts tumor recurrence. Therefore, KI-67-PI may serve as a decision indicator for adjuvant treatment in patients with IM.

Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis.

Meningioma is the most common type of primary brain tumor which presents with a variety of neurological manifestations. Surgical resection tends to be the preferred treatment. The occurrence of seizures after resection is common, which occur either early, within seven days of operation, or late. Our meta-analysis investigated the possible predictors of early and late postoperative seizures. We assessed the relevant observational studies on predictors of postoperative seizures published in PubMed, Scopus, and Web of Science from January 2000 to September 2022, and those that met inclusion criteria were included. We calculated the association between potential predicting factors and postoperative seizures, odds ratios (ORs) with 95% confidence intervals (CIs) applying either random or fixed-effect models. The early and late postoperative seizures were evaluated individually. Thirteen observational studies involving 4176 patients were included. Seizures occurred in 250 (6%) and 584 (14%) patients, respectively, in the early and late postoperative phases. Shared predictors for early and late seizures included tumors involving the motor cortex (OR = 2.7; 95% CI: 1.67-4.38, OR = 2.46; 95% CI: 1.68-3.61), postoperative neurological deficit (OR = 4.68; 95% CI: 2.67-8.22, OR = 2.01; 95% CI: 1.39-2.92), and preoperative seizures (OR = 2.52; 95% CI: 1.82-3.49, OR = 4.35; 95% CI: 3.29-5.75). Peritumoral edema (OR = 1.99; 95% CI: 1.49-2.64) was a significant factor only among late postoperative seizure patients while surgical complications (OR = 3.77; 95% CI: 2.39-5.93) was a significant factor solely for early postoperative seizures. Meningioma patients commonly experience early and late postoperative seizures. Identifying predictors of postoperative seizures is essential to diagnose and manage them effectively.

Intra-operative extracorporeal irradiation of tumour-invaded craniotomy bone flap in meningioma: a case series.

BACKGROUND: Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought to examine the rate of tumour recurrence and other selected outcomes in patients undergoing meningioma resection and EITC. METHODS: Retrospective single-centre study of adult patients undergoing meningioma resection and EITC between January 2015 and November 2022 at a tertiary neurosurgical centre. Patient demographics, surgery data, tumour data, use of adjuvant therapy, surgical complications, and tumour recurrences were collected. RESULTS: Eighteen patients with 11 (61%) CNS WHO grade 1, 6 (33%) grade 2, and 1 (6%) grade 3 meningiomas were included. Median follow-up was 42 months (range 3-88). Five (28%) patients had a recurrence, but none were associated with the bone flap. Two (11%) wound infections requiring explant surgery occurred. Six (33%) patients required a further operation. Two operations were for recurrences, one was for infection, one was a washout and wound exploration but no evidence of infection was found, one patient requested the removal of a small titanium implant, and one patient required a ventriculoperitoneal shunt for a persistent CSF collection. There were no cases of bone flap resorption and cosmetic outcome was not routinely recorded. CONCLUSION: EITC is feasible and fast to perform with good outcomes and cost-effectiveness compared to other reconstructive methods. We observed similar recurrence rates and lower infection rates requiring explant compared to the largest series of cranioplasty in meningioma. Cosmetic outcome is universally under-reported and should be reported in future studies.

Descriptive epidemiology of 30,223 histopathologically confirmed meningiomas in France: 2006-2015.

BACKGROUND AND OBJECTIVES: Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. METHODS: We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. RESULTS: 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). CONCLUSION: The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.

Middle third falcine meningiomas-surgical nuances for cortical venous preservation.

PURPOSE: To improve postoperative outcome in middle third falcine meningiomas by cortical venous preservation. BACKGROUND: Falcine meningiomas arise from the falx and do not involve the superior sagittal sinus (SSS). Their complete resection is often associated with the risk of venous infarction in the eloquent cortex due to overlying superficial cortical veins on the tumors. METHOD: We report one case of middle third falcine meningioma, where we used the posterior interhemispheric corridor for tumor approach. CONCLUSION: Use of the posterior interhemispheric approach, carefully raised bone flap, along with sharp dissection and vein reinforcement using fibrin glue can help to preserve the cortical veins while resecting the falcine meningiomas.

Meningioma: current updates on genetics, classification, and mouse modeling.

Meningiomas, the most common primary brain tumors in adults, are often benign and curable by surgical resection. However, a subset is of higher grade, shows aggressive growth behavior as well as brain invasion, and often recurs even after several rounds of surgery. Increasing evidence suggests that tumor classification and grading primarily based on histopathology do not always accurately predict tumor aggressiveness and recurrence behavior. The underlying biology of aggressive treatment-resistant meningiomas and the impact of specific genetic aberrations present in these high-grade tumors is still only insufficiently understood. Therefore, an in-depth research into the biology of this tumor type is warranted. More recent studies based on large-scale molecular data such as whole exome/genome sequencing, DNA methylation sequencing, and RNA sequencing have provided new insights into the biology of meningiomas and have revealed new risk factors and prognostic subtypes. The most common genetic aberration in meningiomas is functional loss of NF2 and occurs in both low- and high-grade meningiomas, whereas NF2-wildtype meningiomas are enriched for recurrent mutations in TRAF7, KLF4, AKT1, PI3KCA, and SMO and are more frequently benign. Most meningioma mouse models are based on patient-derived xenografts and only recently have new genetically engineered mouse models of meningioma been developed that will aid in the systematic evaluation of specific mutations found in meningioma and their impact on tumor behavior. In this article, we review recent advances in the understanding of meningioma biology and classification and highlight the most common genetic mutations, as well as discuss new genetically engineered mouse models of meningioma.

Analysis of risk factors affecting wound healing and wound infection after meningioma resection.

To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.

Chronic hyperglycemia and intracranial meningiomas.

Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.

Plasma extracellular vesicles in meningioma patients following radiotherapy as liquid biopsy- a prospective explorative biomarker study (ARO 2023-05/AG-NRO-07).

BACKGROUND: While surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring. METHODS: In total, 60 patients with meningiomas and an indication of radiotherapy (RT) and macroscopic tumor on the planning MRI will be enrolled. Blood samples will be obtained before the start, during, and after radiotherapy, as well as during clinical follow-up every 6 months. Extracellular vesicles will be isolated from the blood samples, quantified and correlated with the clinical treatment response or progression. Further, nanopore sequencing-based DNA methylation profiles of plasma EV-DNA will be generated for methylation-based meningioma classification. DISCUSSION: This study will explore the dynamic of plasma EVs in meningioma patients under/after radiotherapy, with the objective of identifying potential biomarkers of (early) tumor progression. DNA methylation profiling of plasma EVs in meningioma patients may enable molecular risk stratification, facilitating a molecularly-guided target volume delineation and adjusted dose prescription during RT treatment planning.

Microsurgical resection of a large petroclival meningioma through an extended retrosigmoid approach: how I do it.

BACKGROUND: Petroclival meningiomas are challenging tumors. Several skull base approaches have been proposed in the last decades, with variable rates of postoperative morbidity and extent of resection. METHODS: We herein reported the step-by-step microsurgical resection of a large petroclival meningioma through an extended retrosigmoid approach. Detailed surgical technique has been accompanied by a 2D operative video. CONCLUSION: The extended retrosigmoid approach allowed for a safe gross total resection of the tumor, as confirmed by the postoperative MRI. The patient did not experience any new postoperative deficit, despite a transient diplopia, and was discharged on postoperative day 7.

[Facial nerve protection in surgery for rare tumors of the internal auditory canal].

Objective:To explore strategies for preserving facial nerve function during surgeries for rare tumors of the internal auditory canal. Methods:A total of 235 cases of internal auditory canal tumors treated between 2010 and 2023 were included, encompassing vestibular schwannomas, cavernous hemangiomas, meningiomas, and other rare tumors. Various data, including clinical presentations, imaging classifications, and treatment processes, were meticulously analyzed to delineate the characteristics of rare tumors and assess pre-and postoperative facial nerve function. Results:Among all internal auditory canal tumors, vestibular schwannomas accounted for 91.9%. In rare tumors, facial nerve schwannomas constituted 5.3%, cavernous hemangiomas 26.3%, meningiomas 15.8%, and arterial aneurysms 10.5%. Significantly, patients with cavernous hemangiomas displayed pronounced invasion of the facial nerve by the tumor, in contrast to other tumor types where clear boundaries with the facial nerve were maintained. During surgery, individualized approaches and strategies for facial nerve protection were implemented for different tumor types, involving intraoperative dissection, tumor excision, and facial nerve reconstruction. Conclusion:Preservation of the facial nerve is crucial in the surgical management of rare tumors of the internal auditory canal. Accurate preoperative diagnosis, appropriate timing of surgery, selective surgical approaches, and meticulous intraoperative techniques can maximize the protection of facial nerve function. Personalized treatment plans and strategies for facial nerve functional reconstruction are anticipated to enhance surgical success rates, reduce the risk of postoperative facial nerve dysfunction, and ultimately improve the quality of life for patients.

Successful Surgical Treatment of a Giant Intraventricular Meningioma: A Case Report and Literature Review.

In our study, we document the case of a 48-year-old patient who presented at our clinic with various neurological disturbances. Magnetic Resonance Imaging revealed the presence of an intraventricular meningioma located in the body of the left lateral ventricle measuring 60 mm in diameter. This tumor was classified as a giant meningioma, accompanied by a significant amount of digitiform-type edema. A surgical procedure was conducted, resulting in a gross total resection of the tumor. Histopathological analysis identified the tumor as a fibrous meningioma. Postoperative assessments, as well as follow-ups conducted at 3 months and 1 year post-surgery, indicated considerable neurological improvement. The patient exhibited a remission of hemiparesis and gait disturbances along with a marginal improvement in the status of expressive aphasia. This case report underscores the significance of achieving total and safe resection of the tumor and includes an analysis of various cases from the literature, particularly focusing on those that describe minimally invasive surgical approaches and highlight the benefits of radiosurgery in the treatment of giant intraventricular meningiomas.

Transpalpebral mini-orbitozygomatic approach for nonvascular skull base lesions: a single neurosurgeon's experience.

OBJECTIVE: The authors aim to describe the advantages, utility, and disadvantages of the transpalpebral mini-orbitozygomatic (MOZ) approach for tumors of the lateral and superior orbit, orbital apex, anterior clinoid, anterior cranial fossa, middle cranial fossa, and parasellar region. METHODS: The surgical approach from skin incision to closure is described while highlighting key technical and anatomical considerations, and cadaveric dissection demonstrates the surgical steps and focuses on important anatomy. Intraoperative images were included to supplement the cadaveric dissection. A retrospective review of adults who had undergone the MOZ approach for nonvascular pathology performed by a single neurosurgeon from 2017 to 2023 was included in this institutional review board-approved study. Descriptive statistics was used to summarize the data. Four representative cases were included to demonstrate the utility of the MOZ approach. RESULTS: The study included 65 patients (46 female, 19 male), average age 54.84 years, who had undergone transpalpebral MOZ surgery. Presenting symptoms included visual changes (53.8% of cases), vision loss (23.1%), diplopia (21.8%), and proptosis (13.8%). The optic nerve and optic chiasm were involved in 32.3% and 10.8% of cases, respectively. The most common pathology was meningioma (81.5% of cases), and gross-total resection was achieved in 50% of all cases. Major complications included an infection and a carotid injury. Improvement of preoperative symptoms was reported in 92.2% of cases. Visual acuity improved in 12 patients. The mean follow-up was 8.57 ± 8.45 months. CONCLUSIONS: The MOZ approach is safe and durable. The transpalpebral incision provides better cosmesis and functional outcomes than those of standard anterolateral approaches to the skull base. Careful consideration of the limits of the approach is paramount to appropriate application on a case-by-case basis. Further quantitative anatomical studies can help to define and compare the utility of the approach to open cranio-orbital and endoscopic transorbital approaches.

Transorbital neuroendoscopic surgery for treatment of sphenoid wing meningiomas extending to the cavernous sinus: clinical implications and a technical illustration.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of transorbital neuroendoscopic surgery (TONES) in the management of sphenoid wing meningiomas (SWMs) with cavernous sinus and orbital invasion. METHODS: The authors conducted a retrospective review of 32 patients with SWMs treated at Gazi University using TONES from October 2019 to May 2023. The study includes clinical applications to elucidate the endoscopic transorbital approach. Surgical techniques focused on safe subtotal resection, aiming to minimize residual tumor volume for subsequent radiosurgery. Data were collected on patient demographics, tumor characteristics, surgical procedures, complications, and postoperative outcomes, including radiological imaging and ophthalmological evaluations. RESULTS: Surgical dissections delineated a three-phase endoscopic transorbital approach: extraorbital, intraorbital, and intracranial. In the clinical application, gross-total resection was not achieved in any patient because of planned postoperative Gamma Knife radiosurgery. The mean follow-up period was 16.3 months. Of 30 patients with preoperative proptosis, 25 experienced postoperative improvement. No new-onset extraocular muscle paresis or visual loss occurred postoperatively. The average hospital stay was 1.15 days, with minimal complications and no significant morbidity or mortality. CONCLUSIONS: Total resection of SWMs invading the cavernous sinus and orbit is associated with substantial risks, particularly cranial nerve deficits. TONES offers a minimally invasive alternative, reducing morbidity compared with transcranial approaches, and represents a significant advancement in the surgical management of SWMs, especially those extending into the cavernous sinus and orbit. The approach provides a safe, effective, and patient-centric approach, prioritizing subtotal resection to minimize neurological deficits while preparing patients for adjunctive radiosurgery. This study positions TONES as a transformative surgical technique, aligning therapeutic efficacy with neurovascular preservation and postoperative recovery.

Clinical outcomes and complications of eyelid versus eyebrow approaches to supraorbital craniotomy: systematic review and indirect meta-analysis.

OBJECTIVE: Eyebrow supraorbital craniotomy is a versatile keyhole technique for treating intracranial pathologies. The eyelid supraorbital approach, an alternative approach to an eyebrow supraorbital craniotomy, has not been widely adopted among most neurosurgeons. The purpose of this systematic review and meta-analysis was to perform a pooled analysis of the complications of eyebrow or eyelid approaches for the treatment of aneurysms, meningiomas, and orbital tumors. METHODS: A systematic review of the literature in the PubMed, Embase, and Cochrane Review databases was conducted for identifying relevant literature using keywords such as "supraorbital," "eyelid," "eyebrow," "tumor," and "aneurysm." Eyebrow supraorbital craniotomies with or without orbitotomies and eyelid supraorbital craniotomies with orbitotomies for the treatment of orbital tumors, intracranial meningiomas, and aneurysms were selected. The primary outcomes were overall complications, cosmetic complications, and residual aneurysms and tumors. Secondary outcomes included five complication domains: orbital, wound-related, scalp or facial, neurological, and other complications. RESULTS: One hundred three articles were included in the synthesis. The pooled numbers of patients in the eyebrow and eyelid groups were 4689 and 358, respectively. No differences were found in overall complications or cosmetic complications between the eyebrow and eyelid groups. The proportion of residuals in the eyelid group (11.21%, effect size [ES] 0.26, 95% CI 0.12-0.41) was significantly higher (p < 0.05) than that in the eyebrow group (6.17%, ES 0.10, 95% CI 0.08-0.13). A subgroup analysis demonstrated significantly higher incidences of orbital, wound-related, and scalp or facial complications in the eyelid group (p < 0.05), but higher other complications in the eyebrow group. Performing an orbitotomy substantially increased the complication risk. CONCLUSIONS: This is the first meta-analysis that quantitatively compared complications of eyebrow versus eyelid approaches to supraorbital craniotomy. This study found similar overall complication rates but higher rates of selected complication domains in the eyelid group. The literature is limited by a high degree of variability in the reported outcomes.