Impact on natural history of atypical meningioma after changes in 2016 edition of the world health organization (WHO) classification of central nervous system tumors: a literature review.

Meningiomas and their WHO histological diagnostic criteria is complex, especially for grade 2 tumors presenting a interobserver discordance as high as 12.2%. The 2016 edition of the WHO Classification of CNS tumors recommended brain invasion as a stand-alone grading criterion for diagnosing an atypical grade 2 meningioma (AM). To provide an overview of the classification of 2016 WHO impact on the natural history of atypical meningioma (AM) relative to previous classification. To achieve this goal, we selected articles from the period 2017-2024 in Medline search on atypical meningiomas and analyzed them after following the following criteria: 1) reports with confirmed histopathological diagnosis according to WHO 2016 and or 2021 criteria; 2) series and case reports; 3) detailed and individualized clinical outcomes for AM; and 4) papers written in English; after that a total of 3445 patients reported in 67 manuscripts from worldwide centers from 2017 to March 2024 were analyzed. The patient's age at the time of surgery ranged from 1 month to 97 years (mean 52.28 ± 18.7 years). The most common tumor site was the convexity, accounting for 67.8%, followed by the skull base in 30.6%, ventricle in 1%, and spine in 0.6%; Gross total resection (GTR) was performed in 71.25% and subtotal resection (STR) in 28.75%; 1021 patients (29.63%) underwent adjuvant radiotherapy, and 22 patients (0.6%) were treated with adjuvant chemotherapy; tumor recurrence was reported in 1221 patients (35.44%) and 859 deaths (24.93%). 1) AM prevalence in females; 2) AM age distribution similar to the distribution of meningiomas in general; 3) AM recurrence rate of 35.44%, despite the high rate of GTR, which was higher than previously reported; 4) deepening knowledge in molecular mechanism of tumor progression will provide alternative therapeutic approaches for AM.

Cancer stem cells in meningiomas: novel insights and therapeutic implications.

Meningiomas (MGs), which arise from meningothelial cells of the dura mater, represent a significant proportion of primary tumours of the central nervous system (CNS). Despite advances in treatment, the management of malignant meningioma (MMG) remains challenging due to diagnostic, surgical, and resection limitations. Cancer stem cells (CSCs), a subpopulation within tumours capable of self-renewal and differentiation, are highlighted as key markers of tumour growth, metastasis, and treatment resistance. Identifying additional CSC-related markers enhances the precision of malignancy evaluations, enabling advancements in personalised medicine. The review discusses key CSC biomarkers that are associated with high levels of expression, aggressive tumour behaviour, and poor outcomes. Recent molecular research has identified CSC-related biomarkers, including Oct-4, Sox2, NANOG, and CD133, which help maintain cellular renewal, proliferation, and drug resistance in MGs. This study highlights new therapeutic strategies that could improve patient prognosis with more durable tumour regression. The use of combination therapies, such as hydroxyurea alongside diltiazem, suggests more efficient and effective MG management compared to monotherapy. Signalling pathways such as NOTCH and hedgehog also offer additional avenues for therapeutic development. CRISPR/Cas9 technology has also been employed to create meningioma models, uncovering pathways related to cell growth and proliferation. Since the efficacy of traditional therapies is limited in most cases due to resistance mechanisms in CSCs, further studies on the biology of CSCs are warranted to develop therapeutic interventions that are likely to be effective in MG. Consequently, improved diagnostic approaches may lead to personalised treatment plans tailored to the specific needs of each patient.

Surgery alone versus surgery plus adjuvant radiotherapy for WHO grade 2 meningioma: meta-analysis of reconstructed time-to-event data.

INTRODUCTION: WHO Grade 2 meningiomas present diagnostic and management challenges. Surgery, particularly gross total resection (GTR), is crucial, often followed by adjuvant radiotherapy (RT); however, there are clinical equipoise and ongoing randomized trials of RT after GTR. METHODS: This systematic review evaluates the efficacy of gross total resection (GTR) and GTR plus adjuvant radiotherapy (RT) for WHO grade 2 meningiomas, adhering to PRISMA guidelines. It excludes irrelevant studies, conducts a thorough search until January 2024, and specifically analyzes overall survival (OS) and progression-free survival (PFS) outcomes for WHO grade 2 meningiomas. Statistical analysis adopts a two-stage approach with the R package "IPDfromKM," and quality assessment is conducted using the ROBINS-I tool. RESULTS: In our analysis of 23 studies involving 3822 WHO grade 2 meningioma patients, GTR + RT resulted in a significantly longer PFS (HR: 0.849, 95% CI: 0.730 to 0.988, p = 0.035) compared to GTR alone. Although OS trended better with GTR + RT (HR: 0.79, 95% CI: 0.57 to 1.11, p = 0.173), the difference was not statistically significant, suggesting the need for further investigation. CONCLUSION: Our study reveals a benefit to adjuvant RT for improving PFS for WHO grade 2 meningiomas. Integrating molecular characteristics into treatment strategies will refine the management of these tumors in the future.

Resection vs. coagulation of dural attachment in patients with spinal meningioma: an updated systematic review and meta-analysis.

BACKGROUND: The Simpson grading scale assumes dural resection (grade I) is more effective against recurrence than coagulation (grade II). However, the results of recent studies have raised doubts about this effectiveness in spinal meningiomas. Therefore, we aimed to perform a meta-analysis comparing outcomes between Simpson grades I and II in spinal meningiomas. METHODS: According to the PRISMA statement, we systematically searched PubMed, EMBASE, and Web of Science for studies involving patients with spinal meningiomas who underwent Simpson grades I, II, III, or IV. Outcomes were radiological tumor recurrence, postoperative neurological deficits, and procedure-related complications. RESULTS: We included 54 studies with a total of 3334 patients. Simpson grades I, II, III, and IV were performed in 674 (20%), 2205 (66%), 254 (8%), and 201 (6%) patients, respectively. The follow-up ranged from 9 to 192 months, and 95.4% of all tumors were WHO grade 1. There was no difference in radiological tumor recurrence (OR 0.80, 95% CI: 0.46-1.36, P = 0.41; I2 = 0%), postoperative neurological deficits (OR 0.74, 95% CI: 0.32-1.75, P = 0.50; I2 = 0%) or procedure-related complications (OR 2.22, 95% CI: 0.80-6.13, P = 0.12; I2 = 3%) between Simpson grades I and II. Furthermore, no significant difference in postoperative neurological deficits or procedure-related complications was detected when comparing all Simpson's to each other. However, radiological tumor recurrences in Simpson I and II were significantly lower than in III and IV, with Simpson III outperforming IV (OR 0.19, 95% CI: 0.09-0.40, P < 0.01; I2 = 0%). CONCLUSION: Simpson grade I is not more effective than grade II in any outcome, although both are superior to III and IV in tumor recurrence. Our results might suggest that dural coagulation is preferable over resection when the latter carries a higher risk of complications.

Exploring the Biological Overlapping Between Brain Calcifications and Tumorgenesis.

This article discusses a rare case of coexistent meningiomas and Primary familial brain calcification (PFBC). PFBC is a neurodegenerative disease characterized by brain calcifications and a variety of neuropsychiatric symptoms and signs, with pathogenic variants in specific genes. The study explores the potential link between PFBC and meningiomas, highlighting shared features like intralesional calcifications and common genes such as MEA6. The article also revisits PFBC patients developing other brain tumors, particularly gliomas, emphasizing the intersection of oncogenes like PDGFB and PDGFRB in both calcifications and tumor progression. In recent investigations, attention has extended beyond brain tumors to breast cancer metastasis, unveiling a noteworthy connection. These findings suggest a broader connection between brain calcifications and tumors, encouraging a reevaluation of therapeutic approaches for PFBC.

Surgical treatment of pituitary neuroendocrine tumors with coexisting intracranial lesions: A case series and review of the literature.

Background: Pituitary neuroendocrine tumors (PitNETs) are a diverse group of benign neoplasms that account for a significant proportion of intracranial tumors (13%). The coexistence of PitNET with other intracranial lesions, such as meningiomas and intracranial aneurysms, has been constantly reported in the literature; yet, the pathophysiological mechanisms remain unknown, and the appropriate management is controversial. This study aims to describe the clinical characteristics, surgical treatment, and outcomes of patients with PitNET with coexisting intracranial lesions in a single healthcare center. Methods: A retrospective analysis was conducted on 12 patients who underwent surgical treatment for PitNET and another intracranial lesion at our single tertiary referral center over 15 years from January 2008 to May 2023. Results: Among these coexisting lesions, aneurysms were the most commonly found (41.67%), followed by meningiomas (33.33%). Surgical intervention for both lesions was performed in a single-stage procedure for most cases (75%), employing transcranial, endoscopic endonasal, and combined approaches. We found low preoperative Karnofsky Performance Scale scores in three patients, with significant differences in functional outcomes. Conclusion: These findings contribute to the limited knowledge about PitNET coexisting with other intracranial lesions and emphasize the importance of patient-tailored, multidisciplinary management in these unusual scenarios.

Visual outcomes in tuberculum sellae meningiomas comparing transcranial and endoscopic endonasal approaches.

Background: Tuberculum sellae meningiomas (TSM) account for 3-10% of intracranial meningiomas. Visual loss is the presenting symptom in up to 80% of cases. Surgical management poses a great challenge due to tumor proximity to neurovascular structures such as the optic nerve and the internal carotid artery (ICA); hence, there is controversy regarding the optimal approach. The aim of this study is to determine differences in visual outcomes between transcranial (TCA) and endoscopic endonasal (EEA) approaches. Methods: A retrospective study including 29 patients with TSM surgically treated by TCA or EEA between 2011 and 2023 in a single referral center was conducted. Pre-and post-operative neuro-ophthalmologic evaluations, focusing on visual acuity and campimetry, were evaluated. Results: Sixteen (55.16%) patients were intervened through a TCA and the remaining 13 (44.84%) via an EEA. The lesions in each group were similar in terms of pre- operative volume (15.12 vs 12.9 cm3, p = 0.497) and neurovascular invasion (optic canal invasion 48.26 vs 41.37%, p = 0.664; ICA 44.81 vs 31.03%, p = 0.797). There were no significant differences in visual outcomes between both approaches; TCA presented an improvement of 5.18 points in visual fields (p = 0.140), whereas EEA had an improvement of 17.39 points in visual acuity (p = 0.114). Conclusion: EEA seems to offer greater improvement in visual acuity than TCA. However, the ideal approach should be individualized; taking into account the tumor's volume and invasiveness, as well as the patient's visual complaints.

Case report: Mirror paraclinoid aneurysm associated with mirror clinoidal meningioma.

Introduction: Clinoidal meningiomas and paraclinoid aneurysms are individually uncommon, with the coexistence of mirror paraclinoid aneurysms and clinoidal meningiomas presenting an even rarer scenario. While the association between meningiomas and aneurysms is documented, the simultaneous presence of mirror lesions for both pathologies is not reported in the literature. Clinical presentation: We report a 62-year-old female with a three-month history of moderate bifrontal headaches. Magnetic Resonance Angiography (MRA) revealed mirror paraclinoid aneurysms, prompting surgical intervention. During the procedure, mirror clinoidal meningiomas were incidentally discovered. The left aneurysm was addressed first due to higher rupture risk, followed by the right aneurysm 3 months later. Both meningiomas were confirmed as Transitional Meningiomas (Grade 1; OMS, 2021). The aneurysms were successfully clipped, and the patient had an excellent postoperative outcome. Conclusion: This case represents a unique occurrence of mirror ophthalmic segment internal carotid artery aneurysms associated with mirror clinoidal meningiomas, a combination not previously reported. Despite the limitations of MRA in detecting small meningiomas, it remains a valuable non-invasive screening tool for neurovascular diseases. The case underscores the need for further research to elucidate the association between cerebral aneurysms and meningiomas.

Radiation therapy for optic nerve sheath meningiomas: Local control and treatment related visual changes.

Objective: Our primary objective is to evaluate the local control of optic nerve sheath meningiomas (ONSMs) treated with ionizing radiation and related visual changes after treatment. Our secondary objective is to describe the clinical characteristics and perform an analysis of the treatment impact on the functional status of this group of patients. Methods: We present our series of 19 patients treated with ionizing radiation therapy at our radio-neurosurgery unit between 2016 and 2022. The setting, ophthalmological follow-up, morbidity, and survival are analyzed and discussed. Results: Patients were followed up, and the impact of treatment on local disease control, visual alterations of the affected eye, and functional status of the patient were analyzed. The progression-free survival (PFS) median was 60 months (95% CI 50.3-69.6 months). The estimated PFS rates at 48 and 66 months were 100% and 66%, respectively. At diagnosis, nine (47.3%) eyes were in amaurosis and ten (52.6%) with vision. Of the ten patients without amaurosis at the time of diagnosis, three (30%) maintained unchanged visual acuity, and seven (70%) had decreased visual acuity; three of them developed amaurosis during the first year after treatment (p = 0.018). Conclusions: Using ionizing radiation therapy is a successful treatment for the local control of ONSMs. This therapeutic modality can compromise the visual acuity of the affected eye and improve dyschromatopsia and campimetry defects. The life prognosis is good for these patients, with a zero mortality rate, but their vision prognosis is poor.

Schwannoma-like Breast Metastasis in the Meckel Cave: Case Report / Metástase de mama semelhante a um schwannoma no cavo de Meckel: Relato de caso

Tumors of the Meckel cave are very rare lesions, especially if they are malignant. We report the case of a patient who presented with a breast metastasis in the Meckel cave and a clinical presentation similar to that of a fifth nerve schwannoma.

Os tumores do cavo de Meckel são lesões muito raras, especialmente se forem malignos. Relatamos o caso de uma paciente que apresentou metástase mamária no cavo de Meckel e quadro clínico semelhante a schwannoma do quinto nervo.

Augmented reality for intracranial meningioma resection: a mini-review.

Augmented reality (AR) integrates computer-generated content and real-world scenarios. Artificial intelligence's continuous development has allowed AR to be integrated into medicine. Neurosurgery has progressively introduced image-guided technologies. Integration of AR into the operating room has permitted a new perception of neurosurgical diseases, not only for neurosurgical planning, patient positioning, and incision design but also for intraoperative maneuvering and identification of critical neurovascular structures and tumor boundaries. Implementing AR, virtual reality, and mixed reality has introduced neurosurgeons into a new era of artificial interfaces. Meningiomas are the most frequent primary benign tumors commonly related to paramount neurovascular structures and bone landmarks. Integration of preoperative 3D reconstructions used for surgical planning into AR can now be inserted into the microsurgical field, injecting information into head-up displays and microscopes with integrated head-up displays, aiming to guide neurosurgeons intraoperatively to prevent potential injuries. This manuscript aims to provide a mini-review of the usage of AR for intracranial meningioma resection.

Postoperative Seizure Prophylaxis in Meningioma Resection: A Systematic Review and Meta-Analysis.

BACKGROUND: Seizures in the early postoperative period may impair patient recovery and increase the risk of complications. The aim of this study is to determine whether there is any advantage in postoperative seizure prophylaxis following meningioma resection. METHODS: This systematic review was conducted in accordance with PRISMA guidelines. PUBMED, Web of Science, Embase, Science Direct, and Cochrane were searched for papers until April 2023. RESULTS: Among nine studies, a total of 3249 patients were evaluated, of which 984 patients received antiepileptic drugs (AEDs). No significant difference was observed in the frequency of seizure events between patients who were treated with antiepileptic drugs (AEDs) and those who were not. (RR 1.22, 95% CI 0.66 to 2.40; I2 = 57%). Postoperative seizures occurred in 5% (95% CI: 1% to 9%) within the early time period (<7 days), and 9% (95% CI: 1% to 17%) in the late time period (>7 days), with significant heterogeneity between the studies (I2 = 91% and 97%, respectively). In seizure-naive patients, the rate of postoperative seizures was 2% (95% CI: 0% to 6%) in the early period and increased to 6% (95% CI: 0% to 15%) in the late period. High heterogeneity led to the use of random-effects models in all analyses. CONCLUSIONS: The current evidence does not provide sufficient support for the effectiveness of prophylactic AED medications in preventing postoperative seizures in patients undergoing meningioma resection. This underscores the importance of considering diagnostic criteria and conducting individual patient analysis to guide clinical decision-making in this context.

Falcine meningioma: FEBAIR principles in a "Grade Zero" concept application - 2D operative video.

Background: Falcine meningiomas account for 5% of intracranial meningiomas. They may involve the eloquent cortex as well as vascular structures. Gross-total resection with additional margins has been shown to be beneficial to patients and has been associated with a reduction in disease recurrence. Case Description: A 57-year-old patient presented with recurrent frontal headaches that worsened when lying down. Magnetic resonance imaging showed a large lesion with homogeneous enhancement attached to the anterior third of the falx cerebri at the right frontal lobe, causing significant compression, and suggesting a meningioma. Conclusion: This operative video highlights the application of 1st-time, exposure, bone removal, arachnoid, irrigation, and reconstruction principles for safely and effectively removing a large falcine meningioma using the "grade zero" concept for maximal resection.

Enhancing meningioma resection: a comprehensive study on the safety and effectiveness of Onyx™ presurgical embolization.

Presurgical embolization (PE) has emerged as an interesting strategy to help turn brain tumor resection more amenable. This study aims to systematically review the safety and effectiveness of Onyx™ PE in meningioma resection. We followed Cochrane Collaboration and PRISMA for systematic review and meta-analysis, querying PUBMED, Cochrane Library, Web of Science, and Embase databases. Major complications were defined as other artery occlusion, visual deficits due to PE, or non temporary nerve damage, while minor included transitory conditions and others without clinical implications. A total of 186 patients were included, in which 120 were WHO grade I (80%), II (16%), and III (4%). Patient baseline characteristics and complications were distributed in groups without or with individual patient data analysis. Individual Patient Data Meta-Analysis (IPDMA) was performed on the last category, comprising 51 meningiomas that underwent Onyx™ PE. Among available data, 70%, 17%, and 13% were WHO grade I, II, and III, respectively. Considering all studies, tumor characteristics regarding grade underscored a certain homogeneity. Complications occurred at a rate of 9% (95% CI, 4 to 14%; I2 = 35%), with the rate of major complications significantly lower at only 1% (95% CI, 0 to 3%; I2 = 32%), whereas of minor complications was 7% (95% CI, 3 to 10%; I2 = 0%). Mean surgery blood loss was 668.7 (95% CI, 534.9 to 835.8; I2 = 0%) in IPDMA. Onyx™ PE is promising for safer surgical meningioma resection, despite limitations. Further studies are required to validate efficacy, enhance patient selection, and refine techniques.

A rare case of a right infratentorial meningioma and a left giant posterior communicating thrombosed aneurysm.

Background: Giant intracranial aneurysms cause symptoms due to mass effect and can mimic other lesions in imaging studies. The coexistence of tumors and aneurysms is relatively rare, with meningiomas being the predominant tumors found in such cases. The relationship between these two entities is complex and represent a neurosurgical challenge. Case Description: A 61-year-old woman presented with intermittent headache, vertigo, right peripheral facial palsy, hearing loss, and left hemiparesis. Magnetic resonance imaging revealed two lesions: a supratentorial paraclinoid lesion in the left frontotemporal region and a right infratentorial extra-axial mass, suggestive of a meningioma. The patient underwent a two-staged surgical intervention to address both lesions. Conclusion: In this particular case, the lesions were located on different sides and in different cranial compartments, making it even rarer.

Parasagittal Meningiomas: Prognostic Factors for Recurrence.

The term parasagittal meningioma applies to those tumors that are associated with the superior sagittal sinus (SSS), originating from the dura mater in close relation to the parasagittal wall or angle, with no intervening brain tissue, possibly extending to the dura of the convexity and/or falx cerebri.(Cushing et al., Meningiomas: their classification, regional behaviour, life history, and surgeical and results. Hafner, 1938) They make up about 20-30% of all meningiomas. There is a vast literature correlating the Simpson grade of resection with later recurrence. Frequent involvement of the superior sagittal sinus (SSS) by these tumors means that the optimal treatment recommended in the literature-complete resection, including of the dural base-is one of the most challenging.

Surgical corridors to foramen magnum meningiomas: a mini-review.

Gross-total resection of foramen magnum meningiomas remains the gold standard of treatment and should be performed whenever possible. The transcondylar approach (and its variations) represents the most used approach for meningiomas located in the lateral or anterior borders of the foramen magnum. Endoscopic transclivus approaches represent a useful option in selected cases of anterior midline foramen magnum meningiomas, to be performed in centers with advanced experience in endoscopic skull base surgery, with the caveats of increased risk of postoperative cerebrospinal fluid leak. Alternatively, radiosurgery remains an option for well-selected cases, especially for the management of asymptomatic patients with small enlarging tumors. Advances in molecular profiling, as well as genetic analysis, may guide adjuvant treatment.

Multidisciplinary approach to anaplastic and metastatic meningioma: A case report and review of the literature.

Background: Meningiomas are slow-growing neoplasms, accounting for 20% of all primary intracranial neoplasms and 25% of all intraspinal tumors. Atypical and anaplastic meningiomas are infrequent, representing fewer than 5% of all meningiomas. Unusually, they can show aggressive behavior, and extracranial metastases are extremely rare, representing approximately 0.1% of all reported cases. Case Description: Fifty-six-year-old male patient diagnosed with atypical basal frontal meningioma with multiple resections, both endoscopic endonasal and transcranial. After hypofractionated radiosurgery, the patient showed new tumor recurrence associated to right cervical level II ganglionic metastasis. We opted for complete resection of the meningioma and reconstruction with anterior rectus abdominis muscle flap, as well as selective cervical ganglionectomy. Anatomical pathology showed neoplastic proliferation of meningothelial cells in syncytial cytoplasm, oval or spherical nuclei with slight anisocariosis and hyperchromasia, and intranuclear vacuoles, all compatible with anaplastic meningioma. Conclusion: Due to a lack of consensus on how to treat a metastatic malignant meningioma, this pathology requires a multidisciplinary approach, and treatment needs to be adapted to each particular case. Complete resection of the lesion is the primary goal, and this requires complex procedures involving endocranial as well as extracranial surgeries, which result in composite defects difficult to resolve. Microvascular free flaps are considered the gold standard in reconstructions of large skull base defects, with high success rates and few complications.

Advances in Central Nervous System Tumor Classification.

Historically, the classification of tumors of the central nervous system (CNS) relies on the histologic appearance of cells under a microscope; however, the molecular era of medicine has resulted in new diagnostic paradigms anchored in the intrinsic biology of disease. The 2021 World Health Organization (WHO) reformulated the classification of CNS tumors to incorporate molecular parameters, in addition to histology, to define many tumor types. A contemporary classification system with integrated molecular features aims to provide an unbiased tool to define tumor subtype, the risk of tumor progression, and even the response to certain therapeutic agents. Meningiomas are heterogeneous tumors as depicted by the current 15 distinct variants defined by histology in the 2021 WHO classification, which also incorporated the first moelcular critiera for meningioma grading: homozygous loss of CDKN2A/B and TERT promoter mutation as criteria for a WHO grade 3 meningioma. The proper classification and clinical management of meningioma patients requires a multidisciplinary approach, which in addition to the information on microscopic (histology) and macroscopic (Simpson grade and imaging), should also include molecular alterations. In this chapter, we present the most up-to-date knowledge in CNS tumor classification, particularly in meningioma, in the molecular era and how it could affect their future classification and clinical management of patients with these diseases.