Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.

Background: Due to the peculiar location of central neurocytoma, gross total resection is often challenging, and adjuvant radiotherapy is sometimes indicated. Factors associated with outcome are not well addressed in the literature Methods: A multicenter retrospective cohort study among 11 centers in Saudi Arabia including histologically confirmed central neurocytoma between 2000-2022. Results: A total of 104 patients were included. Pre-operative mRS was 0-2 in 93% of the cases. Gross total resection (GTR) was achieved in 50.7%. Radiotherapy was needed in 40% and Ventriculoperitoneal shunt in 38.6%. Favorable outcome was observed in 81.7%. Factors associated with worse outcome included initial mRs of ≥3, tumor size ≥50 mm, and atypical/anaplastic histology. Disease progression was observed in 18 (17.8%). Five-year absolute survival rate was 91.55%. The only significant predictor of disease progression was the presence of atypical features or anaplasia (P .007). Extent of surgical resection (P 0.877) wasn’t associated with disease progression. Post operative radiotherapy didn’t alter residual progression in patients with subtotal resection (P .170) nor the recurrence rate in those with GTR (.365) Conclusions: Central Neurocytoma cases have a high survival rate with a favourable mRs score at long-term follow up. The extent of resection didn’t alter disease progression nor did the adjuvant radiotherapy

Background: Primary melanocytic neoplasms of the central nervous system (PMN-CNS) are rare lesions of variable aggressiveness originating from leptomeningeal melanocytes. They present as either circumscribed or diffuse lesions within the CNS. Given the limited number of reported cases, survival and recurrence outcomes are poorly understood. Methods: A retrospective chart review of all local adult (≥18 years) cases of PMN-CNS in British Columbia, Canada (1993-present). Results: We identified 11 cases, median age at diagnosis was 60 years (IQR: 45-64), 72% female. Tumor location included cerebrum (54.5%), spine (36.4%) and multifocal (9.1%). Four cases (36%) had confirmed GNAQ/GNA11 mutations and six cases (54.5%) were negative for BRAF V600E mutations. Operative outcomes were: gross total resection (27.3%), subtotal resection (63.6%) and biopsy-only (9.1%). Surgery was followed by adjuvant fractionated radiotherapy in 10 (91%) cases. Seven cases (63.6%) received adjuvant chemotherapy and/or immunotherapy, specifically ipilimumab and nivolumab (n=6) and temozolomide (n=1). Radiographic recurrence was observed in 7 (63.6%) cases at a median 11 (IQR: 3.5-14) months postoperatively. Median survival was 24 months (IQR: 4-103). Conclusions: Findins from this case series will assist in prognostication for PMN-CNS. Further multicenter international case series are needed to better understand these very rare neoplasms.

Background: Identifying the pituitary gland during surgery for pituitary neuroendocrine tumors (PitNET) is crucial for preserving gland tissue and reducing postoperative hormonal dysfunction. This study aimed to develop and validate a machine learning (ML) tool to identify the pituitary gland during endoscopic endonasal surgery. Methods: Anonymized surgical videos from PitNET resections were trimmed to key phases, starting after dura opening and ending before skull base reconstruction. Frames were manually annotated to delineate the pituitary gland’s location. The ML model’s performance was evaluated using a single hold-out set method. Results: A total of 2316 frames from 52 videos were annotated, with 60%, 20%, and 20% allocated to training, validating, and testing the ML model, respectively. Performance metrics were as follows: accuracy of 97.8%, specificity of 98.7%, recall of 27%, precision of 18.6%, and an F1-score of 0.22. Conclusions: This study highlights the feasibility of using ML to identify the pituitary gland in PitNET surgeries. While the model is highly accurate in distinguishing gland from non-gland tissue, its low precision indicates a propensity to misclassify adjacent background tissue as pituitary gland.Further refinements could enhance its precision, making it a valuable tool for improving intraoperative anatomical recognition and postoperative hormonal outcomes.

Background: Meningiomas are the most common intracranial extra-axial lesion. Reports of meningioma regression exist, often in the context of known hormonal or vascular fluctuations, though very few describe complete resolution. Though rare, extra-axial mimics such as lymphoma and chloroma may also spontaneously regress. Methods: Electronic medical records were used to access patient information in accordance with our local ethics review board. Results: A 29-year-old male presenting with new onset seizures was found to have a 22.7 x 26.6 mm left temporal extra-axial lesion, radiologically consistent with meningioma. Due to wait times and patient preference, repeat pre-operative imaging was not available prior to surgical resection 13 months later, though an interim CT had confirmed persistence of the tumour’s size 1 month after diagnosis. Decision was made to proceed with resection; however, intraoperatively, no lesion was identified. Post-operative imaging demonstrated complete disappearance of the lesion, and follow-up imaging has shown no recurrence. Conclusions: This case highlights the possibility of spontaneous resolution of extra-axial lesions and emphasizes the importance of serial imaging prior to resection.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Background: Glioma trials may use selective criteria, limiting their generalizability to real-world patients. This systematic review and meta-analysis quantifies the prevalence of these criteria and evaluates their impact on trial outcomes, assessing whether reducing selectivity to improve generalizability and applicability is feasible without compromising safety or efficacy. Methods: 51 glioma trials were extracted from the National Clinical Trial (NCT) database on June 1st, 2024. Eligibility criteria were classified as selective—defined as likely to exclude patients who could benefit, or generalizable—justified due to potential harm or trial focus. The selective criteria were analyzed for correlation with median overall survival (mOS). Results: The average number of selective criteria per study was 6.8 (range: 0–14, median: 7). The most common were “No prior malignancy with a specified disease-free period” (N=29), “Exclusion based on Karnofsky score” (N=27), and “No prior brain radiotherapy” (N=16). Meta-analysis showed no significant correlation between the number of selective criteria and mOS (p = .327). Conclusions: Selective criteria are common in glioma trials, particularly exclusions based on prior malignancies, performance status, and past treatments. However, their lack of correlation with mOS indicates minimal impact on outcomes. These findings suggest reducing selectivity in trial criteria may improve generalizability and applicability without compromising safety or efficacy.

Background: Artery of Percheron (AOP) infarct is a rare but devastating complication following endoscopic transnasal transsphenoidal surgery (ETTS) for pituitary adenoma resection, characterized by decreased level of consciousness, mydriasis, and cognitive impairment. We reported two new and one remote case in a single institution. Methods: A retrospective case analysis and literature review was conducted. All patients had MRI-confirmed bilateral paramedian thalamic and/or midbrain infarcts following primary or redo ETTS for pituitary adenomas. Results: 8 total cases were identified, with a mean age of 45.8 years (SD: 6.06), including 6 females (75%) and 2 males (25%), undergoing initial (6/8, 75%) or repeat (2/8, 25%) ETTS for pituitary macroadenomas. Tumour consistency was solid in 6/8 (75%), hemorrhagic in 1/8 (12.5%) and cystic in 1/8 (12.5%). MRI showed bilateral paramedian thalamic infarcts (8/8 100%), with midbrain extension in 5/8 (62.5%). Intraoperative CSF leaks occurred in 6 of 8 (75%). The mean Glasgow Outcome Scale (GOS) score was 3 (range 2-4, SD: 0.37) at a mean follow-up of 8.6 (SD: 5.5) months. Conclusions: AOP infarcts are rare following ETTS for pituitary adenomas. Possible associations include large tumour size, firm consistency, and intraoperative CSF leak. Clinical outcomes are typically poor and characterized by severe long-term disability.

Background: Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) is a well-established tool for improving tumor visualization in glioma surgery. However, its applications in non-glioma pathologies remain underexplored and require further investigation. Methods: A retrospective review of patients who underwent FGS with 5-ALA between January 2022 and September 2024 was conducted to assess its utility in non-glioma tumors. Results: Among 232 FGS procedures, 13 (5.6%) involved non-glioma pathologies. We categorized our patients into three different levels: high, moderate, and no response based on intra-operative 5-ALA fluorescence visualization. Our patients showed a high 5-ALA fluorescence in 10 cases (77%), mainly in the following tumors: choroid plexus papilloma, atypical teratoid rhabdoid tumor, metastatic adenocarcinoma as well as atypical meningiomas. Moderate 5-ALA fluorescence was seen in 2 cases (15%). While no 5-ALA fluorescence was seen in one case of CNS lymphoma. 90% of procedures with high response had total resection. Conclusions: Fluorescence-guided surgery (FGS) using 5-ALA has demonstrated effectiveness in enhancing tumor visualization beyond gliomas. This retrospective review highlights the potential applications of 5-ALA in various non-glioma pathologies. These findings emphasize the need for further research to refine the use of 5-ALA FGS in diverse pathologies, optimize patient selection, and expand its utility in neurosurgical oncology.

Background: This scoping review investigates factors influencing local control in patients with metastatic brain disease undergoing adjuvant stereotactic radiosurgery (SRS) to surgical cavities. Methods: Seven databases (Ovid Medline, PubMed, Web of Science, EMBASE, BIOSIS, Scopus, Global Health, Cochrane) were searched up to August 2, 2021, using terms related to radiosurgery and brain metastasis. A three-level screening identified relevant studies. Data extraction included study type, population, SRS details, and outcomes. Variables recorded were histopathology, resection degree, number of metastases, SRS platform, dose parameters, cavity volume, margin, time to SRS, local control at 12/24 months, overall, and progression-free survival. Significant predictors were noted. Results: From 10,633 articles, 22 studies with 1,749 cavities. Local control at 12 months was 50–100% (median 82%, IQR 73–84.4%). Distant progression at 12 months was 36–64% (median 45.5%, IQR 38–51%) and at 24 months 39–76% (median 53%, IQR 46–55%). Histology, radiation dose, tumor size, extent of resection, treatment timing, tumor depth, and dural/pial attachment impacted local control, whereas primary disease status, surgical corridor coverage, and tumor location did not. Conclusions: Modifiable SRS treatment and patient selection factors need further investigation. This review emphasizes the necessity for consensus and guides future trials and guidelines to enhance metastatic brain disease management outcomes.

Background: Minimally invasive endoscopic techniques via the transorbital approach (ETOA) is emerging as an alternative approach for addressing skull base tumours. This study aims to showcase our institution’s 8 year experience in using ETOA, detailing the surgical technique employed and presenting comprehensive patient outcomes. Methods: A retrospective analysis was conducted on data from 32 patients who underwent ETOA within the past eight years. Demographic data was obtained as well as information on surgical approaches, intra-operative findings, recurrence and complications. Results: 33 ETOA procedures were performed on 29 patients, with an average age of 45, 14 of whom were women. The superior orbital corridor was utilized in 100% of cases, and in 79.17%, ETOA was complemented by a transnasal approach. Spheno-orbital meningioma accounted for the most common surgical indication (36.36%, n=12, followed by lateral frontal sinus mucocele (18.75%, n=6). The median length of stay was one day.Transient V1 numbness was the primary complication (33%, n=8), and 18.75% (n=6) necessitated another surgery. Notably, no mortality was associated with this procedure. Conclusions: Our institution’s experience underscores the notable safety and effectiveness of ETOA, The main complications being transient V1 numbness, proptosis, transient diplopia. Revision surgery was only required in 6 out of 33 cases.

Background: Hybrid Nerve Sheath Tumours (HNST) were introduced in the WHO Blue Book in the 2016 edition. Since that time, extracranial HNST are commonly identified but intracranial lesions are rare. Methods: A systematic review of the literature was completed. Additionally, chart reviews were completed on two cases of HNST identified at our academic center. Results: 3 reports of intracranial HNST located on a cranial nerve have been published to date. 2 cases of cranial nerve associated HNST have been identified at our academic centre. Conclusions: HNSTs may be underreported in the cranial region.

Background: Vestibular schwannoma (VS) are the most common tumour of the CPA with an annual incidence of 17.4/1 million. They typically demonstrate slow growth over time and as such, observation is a reasonable approach to management. A portion of these tumour remain static and approximately 5-10% of these tumours will demonstrate spontaneous regression while under observation, including those associated with neurofibromatosis type-2.

Previous case series (N= 13-14) have attempted to identify predictive factors for tumour growth and regression, but few have reached significance or demonstrated reproducible findings. Methods: Using a clinical database of VS treated by one team at our institution, we identified 40 patients who have demonstrated significant spontaneous regression or complete resolution of their VS. All patients received a survey by mail and telephone. Results: Radiographic descriptions were collected on 40 patients. Surveys were completed by 18 participants and an additional 18 control patients who demonstrated growth and underwent surgical resection. Conclusions: This is the largest case series we know of to date describing radiographic and clinical presentations of patients shrinking vestibular schwannoma. It is also the only study known to date to consider patient factors by survey in an attempt to identify protective factors.

Background: Molecular characterization of spatially heterogeneous tumors, such as primary brain tumors, requires precise, contamination-free tissue collection. This study develops a novel biopsy instrument enabling efficient, spatially registered tissue collection across tumors and surgical cavities, advancing personalized tumor characterization and treatment. Methods: Iterative modeling and 3D printing were used to develop prototypes, which underwent proof-of-concept and phantom testing. Final device evaluation compared the novel capsule biopsy tool to Yasargil tumor grasping forceps, with six neurosurgeons and six students conducting tests on porcine brain. Additionally, intraoperative samples were collected, with spatial coordinates recorded on preoperative scans. Results: The design features a capsule that attaches to the end of a Frazier suction. When suction is applied, an internal piston secures the sample, which can later be released before or after tissue fixation. The capsule method reduced variability in sample weight and collection time compared to Yasargil forceps, maintaining tissue integrity without contamination or instrument failure. Notably, students demonstrated proficiency comparable to experienced surgeons, highlighting the tool’s ease of use. Conclusions: This low-cost, optically tracked biopsy tool provides an efficient, reliable method for spatially precise tissue collection, meeting the demands of precision medicine and translational research.

Background: This local study aims to address gaps in understanding factors influencing local control in patients with brain metastases treated with adjuvant Gamma Knife Radiosurgery Methods: A retrospective analysis used a local, prospectively kept Gamma Knife database. Sixty-three patients treated with GK SRS were included. Variables included demographics, tumor characteristics, SRS parameters, and outcomes such as local control, recurrence, survival, and adverse effects. Results: At 12 months, local control was 66.7%, decreasing to 57.1% at 24 months. Distant progression occurred in 58.7%, leptomeningeal disease in 15.9%, and adverse radiation effects in 20.6%. The 12-month survival rate was 63.5%, dropping to 38.1% at 24 months. None of the examined factors significantly influenced local control. Local progression within the first year of treatment was associated with a 5.0-fold increased risk of death at 24 months, while distant intracranial progression showed a 6.0-fold increased risk at 12 months and an 8.2-fold increased risk at 24 months. Conclusions: While the parameters we examined were not linked to local control, intracranial progression significantly impacted survival. This real-world cohort provides valuable insights into the challenges of managing brain metastases. Further work is needed to refine the current treatment strategies for intracranial progression and ultimately improve survival outcomes.

Background: This study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leaks and assess their outcomes following endoscopic endonasal approach (EEA) for resection of skull base tumors. Methods: A retrospective review was conducted of patients who underwent EEA for resection of intradural pathology between October 2001 and October 2023. Data on demographics, approach type, reconstruction technique, tumor pathology, complications and outcomes were analyzed. Results: A total of 542 patients were included, with 80.1% undergoing surgery for sellar or suprasellar pathology. Lumbar drains were used in 14.9%, and dural sealants in 57.7%. Forty patients (7.3%) developed postoperative CSF leaks, with the highest rate in sellar or suprasellar lesions (5.9%). CSF leaks were associated with longer hospital stays (p < 0.001), higher 30-day readmission rates (p < 0.001), increased sepsis risk (p = 0.021), and higher rates of diabetes insipidus (p < 0.001). Lumbar drains increased the incidence of CSF leaks (p = 0.021), while nasoseptal flap reconstruction reduced leak rates (p = 0.0015). Higher BMI and intraoperative CSF leaks were also significant risk factors (p = 0.001) Conclusions: CSF leaks are associated with increased complications and extended hospital stays, highlighting the need for vigilant intraoperative monitoring and targeted strategies.

Background: Surgical access to the clival region is challenging, but advanced endoscopic endonasal approaches (EEA) provide a minimally invasive corridor. This study aimed to review the clinical outcomes of patients who underwent EEA for skull base lesions involving the clivus and to analyze prognostic factors. Methods: A retrospective review was conducted of patients who underwent EEA for resection of clival lesions between October 2001 and October 2023. Data on demographics, approach type, reconstruction technique, tumor pathology and outcomes were collected. Results: Forty-six patients underwent transclival EEA. The majority had ASA scores II and III (71.7%), with clival chordomas being the most common pathology (37%). Cranial nerve impairment was present in 65% of patients, and 80% showed improvement post-surgery. The mean procedure duration was 308 minutes, with a mean blood loss of 424 mL. A lumbar drain was used in 10.9%, and 76.1% received a pedicled nasoseptal flap for reconstruction. Complete tumor resection was achieved in 74% of malignant cases. Postoperative CSF leaks occurred in 4.3%, and the mean length of stay was 12.2 days. Higher readmission rates were associated with ASA IV classification (p=0.006). Conclusions: EEA to the clival region is safe and effective, with low perioperative complications and high rates of postoperative improvement.

Background: This study aims to review the clinical outcomes, extent of resection, complications, and prognostic factors in patients undergoing endonasal endoscopic resection (EEA) of anterior cranial base meningiomas. Methods: We conducted a retrospective review of 25 patients who underwent EEA resection of these lesions between 2001 and 2023. We assessed the extent of resection, complications, postoperative outcomes, and key technical aspects of the procedure. Results: 84% of patients were classified as ASA class III. Additionally, 64% of patients presented with visual disturbances. The mean blood loss was 472 ml. Intraoperative lumbar drains were used in 40% of cases, and dural sealants in 56%. A pedicled nasal flap was employed for reconstruction in 92% of cases. One vascular injury was documented, and 16% of patients developed a cerebrospinal fluid (CSF) leak in the postoperative period The degree of resection varied according to tumor location. Prognostic factors for achieving gross total resection, functional improvement, and key factors for reconstruction are discussed. The rate of CSF leaks decreased dramatically in the later years of the series Conclusions: Cranial base meningiomas can be successfully managed via a purely endoscopic endonasal approach, with acceptable morbidity and mortality rates.

Background: Biochemical cure in functional pituitary adenomas (FPA) is crucial for reducing patient morbidity and improving quality of life following endoscopic endonasal procedures (EEA). The extent of resection plays a key role in achieving these outcomes. However, even with the aid of intraoperative navigation, complete resection of tumor components can be challenging due to the difficulty in distinguishing them from normal pituitary tissue. Indocyanine green (ICG) fluorescence has been used effectively in various cranial and spinal procedures, but its role in endoscopic skull base surgery has not yet been routinely established Methods: In this study, we describe our experience using ICG during EEA for the resection of FPA. Results: We discuss the fluorescence profiles of both adenomas and normal gland tissue. ICG helped identify additional tumor tissue that was not initially detected after macroscopic adenoma resection. It also allowed for perfusion assessment of the pituitary gland and nasoseptal flaps. No complications were observed following the ICG injection, and biochemical cure was achieved in more than 90% of cases. Conclusions: Our experience suggests that ICG is a safe and promising tool, improving both the extent of resection and endocrinologic outcomes in patients undergoing EEA for FPA.

Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.