Citations

OBJECTIVE Epilepsy affects nearly 50 million individuals worldwide, with one-third of cases resistant to antiseizure medications. For these patients, surgical intervention offers a potential path to seizure freedom. While resective surgery has been the gold standard, laser interstitial thermal therapy (LITT) has emerged as a minimally invasive alternative. The aim of this study was to evaluate the efficacy and safety of LITT versus resective surgery in patients with nontumoral epilepsy. METHODS A systematic review and meta-analysis were conducted using PubMed, Embase, and Scopus, including studies comparing seizure freedom rates, complications, and procedural outcomes between LITT and open surgery in nontumoral epilepsy. Eleven studies met the inclusion criteria, comprising 389 LITT and 557 open surgery patients with varying epilepsy etiologies, including temporal lobe epilepsy, focal cortical dysplasia, and tuberous sclerosis. Statistical analysis was performed using a random-effects model to assess seizure freedom, complications, and reoperation rates. RESULTS Open surgery demonstrated higher rates of complete seizure freedom, although not reaching significance (68.1% vs 53.7%, RR 0.81, p = 0.07). This outcome was sensitive to influential analysis and reached significance in the epileptogenic zone–directed resection subgroup analysis. Although adequate seizure freedom was comparable between the groups (LITT: 63.0% vs open: 74.0%, RR 0.90, p = 0.11), the open surgery group had higher rates of control in the pediatric and non–temporal lobe epilepsy subgroups. Complication rates were significantly higher in the open surgery group (30.0% vs 18.3%, RR 0.55, p < 0.01). LITT patients had significantly shorter hospital stays (3.4 vs 6.8 days, standardized mean difference −0.93, p < 0.01). Reoperation rates were comparable between groups (13.1% for LITT vs 13.4%, RR 1.59, p = 0.26). CONCLUSIONS While LITT offers a less invasive approach with reduced hospitalization and morbidity, open surgery remains slightly superior in achieving long-term seizure freedom. Patient selection remains critical, and further studies are needed to refine decision-making criteria based on epilepsy subtype and lesion characteristics.

Abstract Background DNA methylation profiling can be used to robustly predict postsurgical outcomes and response to radiotherapy (RT) for meningioma patients. To allow for seamless integration of these complementary models into clinical practice, a practical framework is needed. Methods We leveraged a cohort of nearly 2000 surgically-treated meningiomas with DNA methylation profiling and clinical outcomes data. Existing methylation-based prediction models were dichotomized to yield four risk groups: low and high recurrent risk, each with RT sensitive and resistant subgroups. Risk groups were correlated with progression-free survival in the context of existing biomarkers including extent of resection and WHO grade. Results We first demonstrated that all risk groups benefit from gross total resection. All “high-risk, RT sensitive” tumors (n = 306, 15.7%) also benefited from adjuvant RT: after GTR, median PFS increased from 4.68 (4.13-9.48) years to not reached (P = .003); after subtotal resection (STR), from 2.12 (1.59-3.02) to 4.09 (3.41-not reached) years (P = .004). “Low-risk, RT sensitive cases” (n = 1207, 61.8%) also benefited from RT after STR (median PFS 7.39 (6.66-12.8) vs. 16.53 (10.35-not reached) years, P = .03), suggesting that RT be considered in these patients. Neither “low-risk RT resistant” (n = 84, 4.3%) nor “high-risk RT resistant” (n = 356, 18.2%) cases benefited from RT, and the latter group was associated with universally poor outcomes. Conclusions We identify methylation-defined risk groups of meningioma for which additional benefit is gained from adjuvant RT, leading to a clinical decision-making framework for straightforward integration of molecular models into clinical practice.

Abstract INTRODUCTION While TERT promoter mutation (TPM) has been established as a marker of clinically aggressive meningiomas, this alteration is rare and found in less than 5% of all cases. However, a larger subset of meningiomas may exhibit aberrant TERT expression in the absence of TPMs. This study investigated the effect of TERT gene expression on clinical outcome in meningioma patients. METHODS Clinical and molecular data were retrospectively collected on 1241 meningiomas, split into a Toronto discovery cohort and a multi-institutional validation cohort. Sanger sequencing and bulk RNA sequencing were used to determine TPM status and TERT gene expression. The effect of TERT expression on progression-free survival (PFS) was assessed using Kaplan-Meier and Cox regression analysis. RESULTS While meningiomas with TPM showed expectedly higher TERT gene expression compared to wildtype (TP-WT) cases (p&lt;0.0001), TERT expression was still detected in 28.7% (157/547) of TP-WT meningiomas. Meningiomas with TERT expression showed significantly worse PFS compared to meningiomas without any TERT expression. In fact, WHO grade 1 meningiomas with TERT expression had PFS outcomes resembling WHO grade 2 meningiomas lacking TERT expression (p=0.59). In turn, WHO grade 2 meningiomas with TERT expression had clinical outcomes similar to WHO grade 3 meningiomas without TERT expression (p=0.42). Furthermore, the proportion of meningiomas expressing TERT as well as overall TERT expression levels increased with increasing WHO grade. Multivariable analysis showed that TERT expression was significantly associated with worse PFS even when controlling for other known predictors of clinical outcome including TPM, CDKN2A/B loss, 1p/22q status and WHO grade (HR 1.85 [95% CI 1.33-2.57], p=0.00024). CONCLUSION TERT expression is a novel independent biomarker of outcome for meningiomas identifiable in up to one-third of cases that may be utilized to reclassify tumours to a higher WHO grade.

Abstract Background Adolescent and young adult (AYA) patients remain underrepresented in neuro-oncology research. Despite being the second most common primary brain tumor in this population, meningiomas have not been studied using age-specific molecular analyses. DNA methylation-based classification and prognostic tools have transformed meningioma care. This study aimed to evaluate the performance of these tools across age groups. Methods We analyzed 1,568 meningiomas with DNA methylation and clinical data, including 18 pediatric patients (&lt;15 years), 195 AYA patients (15-39 years), and 1,355 adult patients (&gt;39 years). Pediatric and AYA (P/AYA) tumors were combined and compared with adult tumors. The performance of established molecular classifiers and recurrence predictors, as well as differences in chromosomal copy number alterations were compared across age groups. Results While histologic grading was comparable between cohorts, P/AYA tumors displayed significantly fewer aggressive molecular groups and lower frequencies of chromosomal arm losses, including 1p, 6q, and 14q. The adult-trained recurrence predictor failed in the P/AYA population (AUC 0.57), despite similar score distributions. Retraining the model on an age-specific cohort using an identical analytic framework improved performance (AUC 0.79) and enabled effective stratification of progression-free survival (P = 0.00054). Importantly, 1p loss retained prognostic significance within the P/AYA group, supporting its clinical utility. Conclusions Molecular tools developed in adult-dominant cohorts do not generalize to younger patients due to both biological divergence and exclusion from model development. These findings underscore the need for age-specific molecular frameworks and highlight the imperative of including P/AYA populations in precision neuro-oncology research to ensure lifespan-equitable care.

Abstract Background Subsequent to a diagnosis of a brain tumor, psychological distress has been associated with negative effects on mental health as well as suicidality. The magnitude of such impact has been understudied in the literature. We conducted a systematic review to examine the impact of a brain tumor on suicidality (both ideation and attempts). Methods In accordance with the PRISMA guidelines, we searched for relevant peer-reviewed journal articles on PubMed, Scopus, and Web of Science databases from inception to October 20, 2022. Studies investigating suicide ideation and/or attempt among patients with brain tumors were included. Results Our search yielded 1,998 articles which were screened for eligibility. Seven studies consisting of 204,260 patients were included in the final review. Four studies comprising 203,906 patients (99.8%) reported elevated suicidal ideation and suicide attempt incidence compared with the general population. Prevalence of ideation and attempts ranged from 6.0% to 21.5% and 0.03% to 3.33%, respectively. Anxiety, depression, pain severity, physical impairment, glioblastoma diagnosis, male sex, and older age emerged as the primary risk factors associated with increased risk of suicidal ideation and attempts. Conclusion Suicidal ideation and attempts are increased in patients and survivors of brain tumors compared to the general population. Early identification of patients exhibiting these behaviors is crucial for providing timely psychiatric support in neuro-oncological settings to mitigate potential harm. Future research is required to understand pharmacological, neurobiological, and psychiatric mechanisms that predispose brain tumor patients to suicidality.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports. OBJECTIVE: To report a multicenter experience assessing microsurgery safety/efficacy. METHODS: Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021). RESULTS: Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%. Favorable last follow-up modified Rankin Scale of 0 to 2 was recorded in 81.6% of the patients with procedural complications of 2.6%. CONCLUSION: Craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point. This approach was associated with a high rate of angiographic cure and favorable clinical outcomes.

Intracranial extension of temporomandibular joint (TMJ) ganglion cysts is very rare. Two previously reported cases presented clinically due to effects on cranial nerves and had obvious association with the TMJ on imaging. To the authors’ knowledge, intracranial extension of a TMJ ganglion cyst presenting with seizures and mimicking a primary brain tumor has not been previously reported. The patient underwent resection of a presumptive primary cystic temporal lobe tumor, but the lesion had histopathological features of a nonneoplastic cyst with a myxoid content. He was followed with serial imaging for 5 years before regrowth of the lesion caused new episodes of seizures requiring a repeat operation, during which the transdural defect was repaired after the adjacent segment of the TMJ was curetted. A thorough review of all imaging studies and the histopathological findings from the repeat operation led to the correct diagnosis of a TMJ ganglion cyst. This case highlights an unusual presentation of this rare lesion, as well as its potential for recurrence. TMJ ganglion cysts should be included in the differential diagnosis of cystic tumors involving the anterior temporal lobe, presenting with or without seizures. Focused imaging evaluation of the TMJ can be helpful to rule out the possible role of associated TMJ lesions.

Chordomas are neoplasms that typically arise from midline skeletal structures and rarely originate within the intradural compartment of the CNS. A chordoma arising from the corpus callosum has not been previously described. The authors report the surgical management of a chordoma originating within the splenium of the corpus callosum. To determine the incidence and distribution of intracranial intradural chordoma, a literature search for additional cases was performed. MEDLINE was searched using the MeSH keyword “chordoma,” yielding 2010 articles. These articles were screened for cases of primary intradural chordoma rostral to the craniocervical junction, which led to the identification of 46 relevant articles. The authors report the case of a 69-year-old man who initially presented with nonspecific neurological symptoms including spatial disorientation and cognitive decline. These symptoms eventually prompted intracranial imaging, including MRI, which revealed a ring-enhancing, heterogeneous, cystic mass localized within the splenium of the corpus callosum and extending into the bilateral ventricles. The lesion was believed to represent a high-grade glioma and the patient underwent a left interhemispheric approach and subtotal resection. After pathologic evaluation confirmed a diagnosis of an anaplastic chordoma, the patient underwent further resection. A gross-total resection (GTR) was achieved with a transfalcine approach to the contralateral portion of the tumor. Postoperatively, the patient had a partial left homonymous quadrantanopsia, but was otherwise at his neurological baseline. Proton beam radiotherapy was performed to the resection cavity but diffuse intraventricular disease ensued. The results of a literature search suggest that a chordoma arising in the corpus callosum has not been previously described. The present case demonstrates that chordomas can occur in the corpus callosum, and illustrates the utility of a transfalcine approach for GTR of lesions in this location, as well as the need for improved strategies to prevent intraventricular dissemination.

OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)—a constituent of cruciferous vegetables with a multitargeted effect—as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell–induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.