Skull Base Research Articles

Assessment of Vidian canal morphology in axial section and its associated structures using cone beam computed tomography: A descriptive study

The Vidian Nerve (VN), a branch of the trigeminal nerve, passes by the Vidian Canal (VC), located at the base of the skull. The VC branches into the greater petrosal nerve and the VN in the pterygopalatine fossa, where the greater petrosal nerve carries parasympathetic fibers to the lacrimal glands and nasal mucosa, and the VN carries sensory fibers from the nasopharynx, nasal cavity, and palate. In this study, 60 subjects of both sexes who underwent cone beam computed tomography (CBCT) were selected by a convenient sampling technique. The data were subjected to statistical analysis following the examination of the various parameters in the axial sections. Among the various morphological characteristics appraised in the axial section, there was no significant sexual dimorphism, except for the angle between the VC and the medial wall of the maxillary sinus, which shows statistical significance. The present study aims to investigate morphometric analysis and its associated structures, offering insightful information about the complex structure of the Vidian canal (VC), which provides adequate knowledge for surgeons to plan with more caution complex skull base procedures, and eventually to lower the therapeutical risks associated with it.

Virtual reality for patient informed consent in skull base tumors and intracranial vascular pathologies: A pilot study.

With the growing demand for shared decision-making and patient-centered care, optimal informed consent (IC) has gained relevance. Virtual reality (VR) has seen significant technological advancements, and its medical applications currently include surgical planning and medical education. This pilot study investigates the feasibility of VR-enhanced informed consent (VR-IC) in neurosurgery to improve preoperative IC and patient satisfaction. We included patients aged 18 to 75years who were scheduled for skull base meningioma or brain aneurysm surgery between May and December 2023. Exclusion criteria were visual/auditory impairments and severe cognitive/psychiatric disorders. Patients received standard IC followed by VR-IC using patient-specific VR models of their pathology. After an initial demonstration by the surgeon, the patients used the VR station independently. A questionnaire with 18 questions on a 5-point Likert scale assessed the subjective impression of VR-IC. Ten patients participated in the study, with six (60%) undergoing aneurysm clipping and four (40%) undergoing skull base meningioma resection. The mean age of the participants was 58years (± 15, range 27 to 75years), with four female patients (40%). Patients overall rated the VR-informed consent (VR-IC) positively with a mean of 4.22 (± 0.84). There was a better understanding of their pathology (mean 4.30 ± 0.92) and the planned procedure (mean 3.95 ± 1.04). Trust in the surgeon was rated with a mean of 3.47 (± 0.94). Only minimal side effects from the VR experience including dizziness or discomfort were noted (mean 4.60 ± 0.22). None of the participants dropped out of the study. VR-enhanced informed consent is feasible and improves patient understanding and satisfaction without significant side effects. These findings will guide the planning of a randomized controlled trial to validate the benefits of VR-IC in neurosurgery further.

Comment on: Characteristics of Posterior Ethmoidal Artery and Its Relationship with Anterior Ethmoidal Artery and Skull Base on CT Scan

Comment on: Characteristics of Posterior Ethmoidal Artery and Its Relationship with Anterior Ethmoidal Artery and Skull Base on CT Scan

Real-time intraoperative ultrasound imaging of the posterior pituitary gland during endoscopic endonasal approach.

Pituitary adenomas are amongst the most common benign central nervous system tumors, and often require resection via an endoscopic endonasal approach (EEA). Two of the most common associated complications are central diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both are thought to be caused by manipulation of the posterior pituitary gland (PPG), making intraoperative visualization and preservation of this structure critical. Intraoperative endoscopic endonasal ultrasound (IEUS) may present an optimal tool for this purpose. This study aims to describe the appearance and morphology of the PPG on IEUS. This study included all pituitary adenoma surgeries during which IEUS was utilized and the PPG was visualized between 1/1/2022, and 12/31/2023. Demographic, clinical, pathological, and radiological data were retrospectively collected. The PPG was described as either hypoechoic, isoechoic, or hyperechoic as compared to the anterior pituitary gland and adenoma, and the morphology of the PPG was further classified as ellipse or crescent shaped. The PPG was hypoechoic in all 43 cases included in our final cohort (100.0%). Morphologically, the PPG appeared elliptical in 27 cases (62.8%), and crescent shaped in 16 cases (37.2%). The PPG can typically be visualized by IEUS as a hypoechoic structure immediately anterior to the posterior wall of the sella turcica, with elliptical morphology being the most common appearance. These characteristics can be used by the skull base surgeon to more confidently identify the position and morphology of the PPG intraoperatively for its' preservation.

COMPLEXITY OF PITUITARY ADENOMA SURGERY

Introduction Pituitary adenomas are the most common intraselllar tumors, representing 16% of all intracranial lesions. Although the symptomatology is very complex, it requires a multimodal treatment plan, in order to cover all corners of this combined pathology. Mostly the treatment is surgical, hormonal or combined. The transnazosphenoidal corridor offers a optimal visualitation of the anatomic location (via microscope or endoscope) but also comes with a variety of morbidities, one of the most important being the cerebrospinalfluid fistula (CSF leak). Objective We effectuated a retrospective cohort study in which we included patients with pituitary adenoma who were operated in the Clinic of Neurosurgery from Targu-Mures Emergency County Hospital between January 2018 and April 2024 with full documentation, including complications (apoplexy, infections, CSF fistula etc.). Results A total of 45 patients passed the inclusion criteria with a predominance of female patients (60%, n=27) with a mean age of 55.77 years. Analizing the clinical and paraclinical data, there were 39 patients with macroadenoma (vs. microadenoma n=6), with the dominant symptomatology being headache (86.66%) and visual disturbances (66.66%). In 32 cases the transnazosphenoidal (TSS) approach was used (1 case endoscopic and 31 cases microscopic), in 10 cases pure transcranian with modified pterional or subfrontal craniotomy and in 3 cases there was a combined approach. Postoperative complications were encountered in 8 cases (17.77%), and death in 1 case. 6 patients presented postoperative CSF fistula. In 16 cases we encountered postoperative Diabetes Insipidus with a significant difference in the tumor volume favoring this manifestation (p=0.0001). There was no significance found between the volume of the tumor and postoperative CSF leak (p=0.665). In 31 cases (68.88%) the TSS approach was used and the closing of the sphenoid sinus and cranial base was effectuated in a classic manner with fat, fascia and muscle; in additional cases specified glues were used. Conclusions Our study wants to reflect on the importance of anterior/middle cranial base closure, taking into account the possible postoperative complications. It is important to be aware of the technique of different nasoseptal flaps in order to prevent CSF fistula and reduce postoperative complications.

Extra-Axial Poorly Differentiated Chordoma Initially Misdiagnosed as Epithelioid Sarcoma.

Poorly differentiated chordoma is an exceedingly rare, aggressive subtype of chordoma. These tumors typically arise in the axial skeleton of young patients, most commonly the skull base, followed by the cervical spine. Herein, we present a 60-year-old patient with longstanding knee pain and nondiagnostic imaging, initially thought to be due to osteoarthritis. No discrete mass-forming lesion was identified by radiology. Synovial histology at the time of arthroplasty revealed a multinodular proliferation of epithelioid-to-histiocytoid cells with a moderate amount of eosinophilic-to-clear, vacuolated cytoplasm. Scattered cells with high-grade nuclear atypia were present. A diagnosis of metastatic carcinoma was considered due to immunohistochemical positivity for keratin and GATA3. However, a diagnosis of epithelioid sarcoma was rendered based on clinical context, morphology, and loss of immunohistochemical expression for SMARCB1 (INI1). However, upon re-review of the tumor, brachyury was retrospectively added to the immunohistochemistry panel and showed strong positivity, thus prompting amendment of the initial diagnosis of epithelioid sarcoma to extra-axial poorly differentiated chordoma. Given the rarity of this diagnosis, molecular testing was performed which revealed a unique SMARCB1 molecular profile with a single-nucleotide variant in addition to the commonly reported loss of chromosome 22q. This report of an ultra-rare sarcoma in an uncommon anatomic site highlights multiple potential pitfalls in the diagnosis of poorly differentiated chordoma, emphasizes the importance of brachyury immunohistochemistry in rendering a correct interpretation, and underscores an opportunity for further molecular analysis to better define the molecular profile of this entity.

Nasoseptal Flap Reuse for Reconstruction in Revision Endoscopic Skull Base Surgery

Abstract Introduction The nasoseptal flap (NSF) is the “workhorse” for reconstruction in endoscopic skull base surgery. It creates a reliable, watertight closure to prevent cerebrospinal fluid (CSF) leaks. The flap's robust vascular pedicle allows for it to be taken down and reused in subsequent reconstructive surgeries if needed. Previous literature has demonstrated successful reuse of the flap up to 24 months after initial surgery. The present study analyzes a cohort of patients with NSFs that were reused up to 12 years following the initial surgery. Methods A retrospective analysis was performed on patients who underwent revision endoscopic skull base surgery for recurrent tumor at a tertiary academic skull base center. Patient demographics, tumor type, length of time between first and second surgery, and outcomes were evaluated. Results A total of 15 patients were identified between 2012 and 2022 who underwent revision endoscopic skull base surgery with previous NSFs that were reused for reconstruction. The time interval between surgeries ranged from 9 months to 12 years. There were 12 pituitary adenomas, 2 Rathke's cleft cysts, and 1 craniopharyngioma. One patient developed a CSF leak 5 days postoperatively, which was repaired with an abdominal fat graft, synthetic dural substitute, and a middle turbinate flap. The operative technique for the take-down and reuse of the NSF will be demonstrated. Conclusion The NSF can be taken down and reused in revision endoscopic skull base cases, even several years after the initial surgery, with excellent coverage of the defect and low incidence of postoperative CSF leak.

Postoperative rhinosinusitis and microbiological outcomes following endoscopic endonasal approaches: A retrospective analysis of 300 patients.

Endoscopic endonasal approaches (EEAs) are an efficient way to manage skull base lesions; however, studies regarding postoperative rhinosinusitis are limited. This study analyzed the incidence of postoperative rhinosinusitis, the associated risk factors, microbial species, and antibiotic usage in patients who underwent EEA. Patients who underwent EEAs at a tertiary referral hospital between July 2015 and May 2019 were retrospectively evaluated. Postoperative rhinosinusitis was defined as the presence of a purulent nasal discharge on postoperative endoscopic examination. The mucopus was aspirated and subjected to bacterial culture analysis. The culture results of various groups were analyzed. This study included 300 patients, and the incidence of post-EEA rhinosinusitis was 59.7%. History of endonasal surgery was an independent predictive factor for post-EEA rhinosinusitis [OR 2.547 (1.284-5.052), p= 0.007]. Lesions in the anterior skull base were associated with prolonged use of antibiotics for rhinosinusitis during postoperative care [OR 3.914 (1.329-11.524), p=0.013]. Staphylococcus aureus was the most common causative pathogen, followed by methicillin-resistant Staphylococcus aureus (MRSA) (20.7%), Pantoea dispersa (14.4%), and Pseudomonas aeruginosa (11.7%). P. aeruginosa was more significant in the complex reconstruction group than in the control group. While most patients with post-EEA rhinosinusitis experienced a transient clinical course, one female patient underwent ESS for prolonged rhinosinusitis. Rhinosinusitis is common in the postoperative stage of the EEA. As it usually lasts for a short duration and is treatable with proper medication, aggressive nasal care during the postoperative period is required to prevent related nasal morbidities.

Diffusion-Weighted Imaging Does Not Differentiate Between Bacterial and Fungal Skull Base Osteomyelitis.

Apparent diffusion coefficient (ADC) value helps in differentiating infections from neoplasms on magnetic resonance imaging (MRI). We investigate the diffusion-weighted images in skull base osteomyelitis (SBO) to evaluate if ADC values can differentiate fungal and bacterial SBO and to analyse the microbiology of all SBO patients. Retrospective observational study. Quaternary care referral centre. A retrospective review of 142 patients diagnosed and treated for SBO patients from January 2010 to May 2023 was done. Chi-square or Fisher's exact test was used to compare ADC values of bacterial and fungal SBO. The most common pathogens isolated were Pseudomonas (42.2%), Aspergillus (30.98%), and S. aureus (23.94%). The average ADC value of affected soft tissues among patients was 1.13 ± 0.26 × 10-3 mm2/s compared to the average ADC value of normal soft tissue, 1.34 ± 0.31 × 10-3 mm2/s. There was no statistical significance when comparing the average ADC values of bacterial and fungal SBO patients (p value = 0.142). This study suggests that though infection due to Pseudomonas was the commonest, it was detected only in 42.2% of patients. More than half of the cases had organisms other than Pseudomonas, demanding the clinician to obtain deeper biopsies early in the course of the disease for microbiological analysis. DWI does not help differentiate bacterial and fungal SBO, again emphasising the need for deeper tissue biopsies in all these patients to assist in the early identification of the pathogen.

QOL-25. DIGITAL PHENOTYPING OF PERIOPERATIVE MOBILITY METRICS IN PATIENTS UNDERGOING SURGICAL RESECTION OF SKULL BASE TUMORS

Abstract Current methods to assess quality of life and recovery after surgery for skull base tumors are limited and often biased by subjective patient-reported assessments, while objective, in-situ assessments are lacking. Smartphone-based digital phenotyping has been increasingly studied across pathologies, utilizing built-in technologies to measure behavioral patterns pertaining to sleep, physical mobility, social interactions, and cognitive functioning, among others. Here, we report our initial experience with smartphone-based digital phenotyping in patients who underwent resection of skull base lesions. Patients seen at our multi-disciplinary skull base center were enrolled under an institutional board-approved protocol and installed the Beiwe application, which passively collected GPS data 20 days pre- and up to 140 days post-surgery. Variables measured included time spent at home, number of separate significant places visited outside home, daily walking time, and daily number of steps taken. 26 patients were enrolled, comprised of 14 pituitary adenomas, 8 meningiomas, and 4 vestibular schwannomas. All patients demonstrated increased time spent at home, fewer number of significant locations visited, decreased walking time, and decreased total steps in the immediate post-operative period. For pituitaries, mean return to baseline for these variables was 25.7, 24.3, 80.2, and 88.9 days, respectively. For meningiomas, return to baseline was 56.5, 214.4, 45.0, and 45.6 days, respectively. For vestibular schwannomas, return to baseline was 219, 39.9, 35.1, and 36.4 days, respectively. This study demonstrates initial efficacy of digital phenotyping for a cohort of patients undergoing surgical resection of skull base lesions, based on passively collected smartphone GPS data during the peri-operative period. This is part of a larger, ongoing study enrolling surgical patients as well as non-operative controls for comparison. Such peri-operative mobility metrics may potentially be refined to predict postoperative outcomes following surgery such as improvement of neurological symptoms, postoperative CSF leak, infection, dysnatremia, and hospital length of stay.

EPID-35. COLLISION TUMORS AT THE SKULL BASE: UNVEILING A PETROCLIVAL MENINGIOMA COEXISTING WITH A GROWTH HORMONE-PRODUCING PITUITARY ADENOMA

Abstract Collision tumors are rare occurrences characterized by coexistence of two histologically different tumor types within the same anatomical location. While collision tumors involving skull base meningiomas and pituitary adenomas are uncommon, they pose distinct diagnostic challenges. We report the case of a 57-year-old female initially diagnosed with petroclival meningioma WHO 1, subsequently found to harbor a collision tumor with a growth hormone-producing pituitary adenoma. The patient initially presented with aphasia, right-sided weakness, and gait instability, prompting a diagnosed of left petroclival mass with left temporal horn entrapment. Patient underwent craniotomy and partial resection of the tumor in 2022 and was diagnosed with meningothelial meningioma, WHO1. The patient had history of uncontrolled diabetes and physical features of large hands with hypertrophied terminal phalangeal tufts but patient reported that she has had similar hands since childbirths for decades. Screening pituitary function tests were ordered due to the petroclival meningioma involving suprasellar region, revealing significantly elevated growth hormone, and insulin-like growth factor-1(IGF-1) levels, raising suspicion for pituitary adenoma. Subsequent endoscopic resection of the sellar mass via a transsphenoidal approach in 2024 confirmed the presence of somatotroph pituitary neuroendocrine tumor. Retrospectively growth hormone producing pituitary adenoma likely contributed to patient’s uncontrolled diabetes and coarse, large hands. This case highlights the importance of a high index of suspicion for collision tumors, particularly in patients with skull base tumors involving supra sellar region, especially when presenting with atypical clinical features.

TMIC-51. NEUROIMMUNE-COMPETENT ORGANOID MODELING OF MICROGLIA/TUMOR INTERACTIONS AND DRUG RESPONSIVENESS

Abstract INTRODUCTION Due to its highly aggressive and infiltrative nature, lack of effective treatment options and localization in the skull base, diffuse intrinsic pontine glioma (DIPG) is universally fatal with less than a year median survival time. Studying how DIPG cells interact with brain cells in its microenvironment, including microglia which is the primary brain immune cell type, may lead to new therapeutic strategies to halt the invasion of DIPG into brain tissue. We developed a clinically relevant human immunocompetent brain organoid-DIPG fusion model for investigating the tumor invasion process at the cellular and molecular levels. METHODS Neuronal progenitor and GFP-labeled myeloid precursor cells were derived from human embryonic stem cells and combined to self-assemble and co-develop over two months into microglia-containing brain organoids (MiCBOs). The development of the MiCBOs as well as the distribution and motility of the microglia within the brain organoid was characterized by confocal and multiphoton microscopy, immunofluorescence staining and Western Blots. Confocal live-cell imaging was used to investigate the invasion of TdTomato-labeled tumor cells into MiCBO. We further performed single-cell RNA-Sequencing (scRNA-Seq) analysis to gain insight into the cell-specific gene expression changes after the confrontation of the MiCBOs with tumor spheroids. RESULTS MiCBOs contain viable, widely distributed and highly motile microglia as well as functionally mature neurons, highly resembling those in the human brain. scRNA-Seq showed distinct gene expression patterns in both microglia and tumor cells after confronting MiCBOs with DIPG spheroids, suggesting candidate signaling pathways between those two cell types. CONCLUSION Our novel MiCBO-DIPG fusion model provides a pathophysiologically-relevant system to elucidate molecular mechanisms underlying cell-cell interactions during tumor invasion in a human brain tissue context. This scalable model can be adapted to drug screening applications to identify therapeutics that modulate neuroimmune/tumor interactions and to establish the therapeutic index for anti-cancer medications.

NCMP-03. ASSOCIATION OF PROGESTERONE CONTRACEPTION WITH TUMOR-RELATED VISUAL IMPAIRMENT IN PREMENOPAUSAL WOMEN WITH MENINGIOMA REFERRED FOR RADIATION

Abstract BACKGROUND Meningiomas express ER/PR, but hormonal risk is poorly characterized and not always considered. We hypothesized that hormonal contraceptives lead to tumor-related visual deficits in premenopausal women referred for radiation. METHODS We conducted a retrospective case-control study with primary endpoint visual deficit prior to radiation for meningioma in women age ≤55. Key risk factors determined included age, grade, skull base location, hormonal supplementation / contraception, and neurofibromatosis / prior radiation (NF/priorRT). Univariate and multivariate (including factors with p<0.05 on univariate) logistic regression was performed to analyze associations with visual deficit. RESULTS 64 women (median age 46) receiving RT from 2012-2024 at a single academic institution were included. 45 (70%) had skull base tumors, 33 (52%) used estrogen or progesterone, and 23 (36%) used unopposed progesterone only, 15 specifically medroxyprogesterone acetate (Provera). Visual deficit was present in 35 patients (55%) and was independently associated with both skull base location (p=0.002, OR 11.5) and unopposed progesterone only use (p=0.008, OR 12) but not estrogen or progesterone use on multivariate analysis. Proportion with progesterone only use was 57% vs. 11% in patients with vs. without visual deficit (chi-sq p<0.001). In 5 with ER/PR testing, 3 were PR+ (all with visual deficits and history of medroxyprogesterone acetate) and 2 were PR- (neither with visual deficits nor hormone use). 13 women (20%) were actively using progesterone during RT. 17 women have been contacted at time of analysis, and 4 discontinued progesterone. CONCLUSIONS Progesterone increases risk for meningioma-related visual deficits in premenopausal women referred for radiotherapy, with a disproportionate number on Provera specifically. These data highlight the importance of age-appropriate counseling, consistent pathologic assessment of ER/PR status, and greater awareness of this issue amongst neurosurgeons and radiation oncologists.

Comparison of whole-body 18F-FDG-PET/CT with 18F-FDG-PET/CT limited to skull base to upper abdomen for primary staging of lung cancer - a retrospective explorative analysis.

The gold standard for ruling out distant metastases as part of primary staging in lung cancer is whole-body 18F-FDG-PET/CT, but this method is resource-intensive. Recent evidence suggests that examining only the thorax and upper abdomen may be sufficient 1 2 3. If a limited 18F-FDG-PET/CT approach proves effective for proper staging, it could lead to quicker examinations and reduced radiation exposure. This study aimed to determine whether limited 18F-FDG-PET/CT is adequate for the primary staging of lung cancer.In this study, a retrospective analysis of 161 patients (87 men, 74 women; age range 31-88 y) with recent or suspected lung cancer who had undergone a whole-body 18F-FDG-PET/CT examination for primary staging at our clinic between 2018 and 2022 was conducted. None of these patients showed evidence of extrathoracic metastases before the 18F-FDG-PET/CT examination. The images were divided into three regions: "head-neck" (HN), "thorax-upper abdomen" (TUA), and "lower abdomen-hip" (LAH). TNM staging based on the HN plus TUA region was compared with TNM staging based on the whole body.Among the 161 subjects, 7 (4%) showed malignancy-suspect lesions in HN, 110 (68%) in TUA and 7 (4%) had suspected distant metastases in LAH. The TNM staging based on HN plus TUA corresponded to TNM staging based on the whole body in 161 (100%) examinations. This finding aligns with similar results in previous literature. 18F-FDG-PET/CT limited to HN and TUA yielded accurate staging in all cases. Adopting this method could facilitate the examination and correct staging of more individuals, reducing exam waiting times and physician reporting time and minimising radiation exposure.

EPID-26. STEREOTACTIC RADIOSURGERY FOR CRANIAL NERVE METASTASES: A SINGLE INSTITUTION EXPERIENCE

Abstract Cranial nerve metastases (CNM) can be primary via leptomeningeal metastasis or secondary by spread due to head and neck cancers or due to distant tumor metastasis to the skull base. In addition, they may cause cranial nerve-related symptoms that can impact patient quality of life. We performed a single-center retrospective cohort study of all patients with CNM treated with SRS at our institution between April 2003 and February 2021. Demographic and clinical information were retrieved from the electronic medical record. Median follow-up was 12.9 months. Our study cohort consisted of 9 patients with primary CNM and 8 with secondary CNM – for a total of 17 patients, with a total of 33 lesions (23 primary, 10 secondary). Eleven patients (64.7%) had symptoms caused by cranial nerve metastases. Symptoms were resolved in 5 of 11 patients (45.5%) after SRS. Patients with secondary CNM were more likely to have cranial nerve symptoms and more likely to have resolution of symptoms following SRS. The median time between SRS and symptom improvement was 3 months. Local tumor control was achieved in 30 of 33 lesions (90.9%). Local tumor control at 6 months and at 1 year were 100%. Our study suggests that SRS may be a safe and effective treatment for cranial nerve metastasis providing 90.9% local tumor control at final follow-up, and symptomatic stability or improvement in 90.9% of symptomatic cases. Patients with secondary CNM may stand to benefit more from a symptom management standpoint.

DDDR-49. REPURPOSING OF THE ANTI-VIRAL DRUG RIBAVIRIN AS A POTENTIAL MENINGIOMA THERAPEUTIC

Abstract INTRODUCTION High grade meningiomas provide significant challenges to treatment. Recent works have demonstrated meningiomas to express higher levels of the epigenetic regulator enhancer of zeste homolog 2 (EZH2), as well as the protein eIF4E, a key player in translation. These two molecules are demonstrated targets of the well tolerated antiviral drug, ribavirin, which has recently shown promise as an anti-neoplastic agent. Based on these findings we sought to investigate the effect of ribavirin on meningioma tumorigenesis utilizing in vitro and in vivo meningioma models. METHODS Several immortalized human meningioma cell lines, three immortalized mouse meningioma cell lines, and a panel of human primary cell cultures were assessed. Cell proliferation, cell colony formation, clonogenic assay, and cell death were assessed. Furthermore, we tested ribavirin efficacy in vivo utilizing two aggressive high grade syngeneic orthotopic allograft meningioma models in FVB WT mice. RESULTS We provide evidence that ribavirin significantly impairs meningioma cell growth and proliferation, and induces cell death in vitro. Most importantly, we demonstrate that ribavirin alone significantly improves the survival of mice orthotopically implanted with MGS2 cells. Ribavirin-treated animals exhibited a significantly increased median survival (67 days) compared to controls (41 days; p=0.0009;) in an orthotopic convexity meningioma xenograft model. Furthermore, ribavirin treatment resulted in increased survival in an orthotopic skull base meningioma xenograft model. CONCLUSION Our work establishes that ribavirin is effective against meningioma in vitro and in vivo. Ribavirin treatment reduced proliferation in all cell lines tested, in both high and low grade models, induced cell death, and prolonged survival in two aggressive in vivo models, potentially via modulation of the EZH2 and eIF4E pathways. Given the lack of medical therapy for high grade meningiomas, these findings provide a framework for further investigation into ribavirin’s effects on meningioma tumorigenesis, and demonstrate ribavirin as a potential new therapeutic option in the treatment of meningioma.

EPID-09. THE NATURAL HISTORY AND MOLECULAR ARCHITECTURE OF INCIDENTAL MENINGIOMAS

Abstract The prevalence of asymptomatic, incidental meningiomas is increasing due to greater frequency of brain imaging. This retrospective cohort study of adult patients presenting at a single institution from 1996-2020 integrated clinical data, serial magnetic resonance imaging (MRI) volumetrics, DNA methylation profiling, and targeted gene expression profiling to define the natural history and molecular architecture of incidental meningiomas. Volumetrics were calculated from contrast-enhanced brain MRIs at time of diagnosis compared to serial surveillance MRIs (average 3 MRIs per patient pre-intervention, range: 1-12) DNA methylation groups and gene expression risk scores were defined for 123 samples that underwent resection. Time-to-event analyses were performed for progression-free survival (PFS), symptom-free survival (SFS), and treatment-free survival (TFS). The cohort included 238 meningiomas from 207 patients. Median age at diagnosis was 59 years and 81.5% of patients were female. Median clinical and imaging follow-up were 9.1 and 6.7 years, respectively, during which time 50.8% progressed. Median maximum diameter and volume at diagnosis were 2.20 cm and 4.25 cm3, respectively, and median pre-treatment volumetric growth rate was 19.2% per year. Median pre-treatment PFS and TFS were 3.10 and 1.27 years, respectively, and median SFS and post-treatment PFS were not reached. Cox proportional hazards regression identified maximum diameter at diagnosis as a significant predictor of worse pre-treatment PFS (multivariate HR 1.65 per 1 cm [95% CI 1.19–2.28], p=0.0027) and worse TFS (multivariate HR 1.44 per 1 cm [95% CI 1.17–1.76], p<0.001). Skull base tumors had with worse SFS (multivariate HR 2.48 [95% CI 1.02–6.00], p=0.045). Molecular and histological features among incidental meningiomas that ultimately underwent resection (n=176, 74.0%) were reassuring (89.2% WHO grade 1, 10.2% WHO grade 2). These findings suggest maximum diameter at diagnosis of incidental meningiomas is significantly associated with earlier progression and eventual treatment, and skull base tumors have earlier symptom development.

BIOM-60. UNDERSTANDING THE INTERSECTION OF RACE, SEX, AND GENOMIC PROFILES IN MENINGIOMA PATHOPHYSIOLOGY

Abstract BACKGROUND While meningioma incidence and outcomes vary by sex and race, the potential underlying molecular differences possibly contributing to these disparities are less understood. Herein, we explore the clinical and genomic characteristics of meningiomas across groups characterized by age and sex. METHODS We analyzed adult patients with primary meningiomas resected from 2012 to 2023. Patients underwent whole exome sequencing, and demographic data were categorized into four groups based on self-reported race and sex, which included White females, White Males, Black females, and Black males. The primary analyses involved comparisons of tumor characteristics, socioeconomic status (median zip code income, % with high school diploma, health insurance status, distance from hospital), genomics, and recurrence rates. RESULTS The study included 509 primary meningiomas. White females exhibited low-risk genomic profiles characterized by driver mutations in KLF4 (+/- TRAF7) (p=0.010) and POLR2A (p=0.045), with no associated CNVs (p=0.410). This benign molecular profile correlated with lower WHO grades (p=0.013) and a lower incidence of recurrence (p=0.0003). Black females had meningiomas enriched with Hedgehog pathway mutations (p=0.0035) and a predilection for the anterior skull base (p=0.034), leading to an increased risk of recurrence (p=0.026). White males showed an aggressive genomic profile, including chromosome 1p loss (p=0.025) and 10q loss (p=0.067), associated with a high risk of recurrence (p=0.0002). Black males had meningiomas with chromosome 14q loss (p=0.0002), the highest incidence of high-grade meningiomas (p=0.048), and a 4.5-fold increased risk of recurrence (OR 4.5 [1.6-11.8]; p=0.006). Black males also experienced the worst progression-free survival (HR 5.5 [2.5-12.4]; p<0.0001), independent of WHO grade, extent of resection, and socioeconomic status. CONCLUSIONS Each demographic has a distinct molecular profile that correlates with clinical behavior in a race and sex-specific manner. Black males are disproportionately affected by biologically aggressive meningiomas, leading to higher tumor grade and recurrence rates.

The Relationship Between Orthodontic Malocclusion and Morphological Features of Sella Turcica Bridging and Ponticulus Posticus

Background and Objectives: Recent years have been marked by a search for new relationships between malocclusions and the morphological features of the cranial base and upper cervical spine. The aim of this study was to evaluate the relationship between skeletal orthodontic malocclusions and the morphological features of sella turcica bridging (STB) and ponticulus posticus (PP). Materials and Methods: The study sample consisted of 300 randomly selected pre-orthodontic treatment patients aged 7–40 years. Cephalometric analysis was performed twice by two researchers. The patients were divided into three groups according to the type of skeletal malocclusion. Statistical analysis was performed using SPSS 29.0 software. Results: The prevalence of incomplete PP was 40%, and the prevalence of complete PP was 11.33% and was significantly more common in males (56.7%). STB had a prevalence of 52.67% (15.67% complete, 37.0% partial), with a significantly higher prevalence in females (60.1%, p < 0.001). PP and STB were more common in Class II patients, followed by Class I and Class III. However, only PP showed a statistically significant difference (p = 0.042). According to logistic regression, men were twice as likely to have an open groove of PP (p = 0.015), while females had higher odds of partial and complete STB (p < 0.05). Class II malocclusion increases the odds of type 2 and type 4 PP as well as partial STB. However, it was not statistically significant (p > 0.05). Conclusions: The morphological features of sella turcica bridging and ponticulus posticus were related to sex and the orthodontic skeletal pattern. Ponticulus posticus was more prevalent in males, while sella turcica bridging was more prevalent in females; both conditions were more common in patients with a Class II skeletal pattern. Males were more likely to have an open groove of ponticulus posticus, whereas females were twice as likely to have both forms of sella turcica bridging.

Sphenoid Ridge in Fetuses: Size Analysis, Classification, and Clinical Implications.

To identify the size and angle of the sphenoid ridge (SR) in fetuses. Skull bases of 32 fetuses (11 males / 21 females) aged 17 to 32 weeks of gestations were included the study. The angle of SR (SRA), length of LW (SRL), and also LW widths at the midline (SRW-ML), at the midpoint (SRW-MP), and at the lateral point (SRW-L) were measured. SRL, SRA, SRW-ML, SRW-MP, and SRW-L were measured as 22.98±4.62mm, 150.69±8.05 degrees, 6.57±1.46mm, 4.68±1.07mm, and 2.68±0.71mm, respectively. No significant difference was observed between the measurements in terms of sex and sides. Apart from SRA, the parameters were greater in the third-trimester fetuses than the second-trimester fetuses. SRA was similar in both trimester fetuses. SRA did not alter with advancing gestational weeks, but the other increased. In fetuses, only one configuration regarding SRA types was observed. Type A was observed in all fetuses. Linear function was calculated as y=1.411 + 0.902×age for SRL, y=-0.137 + 0.281×age for SRW-ML, and y=1.024 + 0.069×age for SRW-L. Our study provides beneficial data for neurosurgeons and anatomists to understand the development of SR in the prenatal period. The authors' regression equations for determining the growth dynamics of the ridge may be used to estimate SR parameters.