A Promising Breakthrough: The Potential of VORASIDENIB in the Treatment of Low-grade Glioma.

INTRODUCTION: Gliomas are common malignant brain tumors characterized by diffuse brain infiltration. World Health Organization grade II and grade III diffuse gliomas are considered lower-grade gliomas (LGGs) and have isocitrate dehydrogenase (IDH) mutations. LGGs are challenging due to their infiltrative nature, making them capable of progressing into higher-grade malignancies. Vorasidenib is a novel therapeutic agent targeting mutant IDH1/2, sparking interest in the field. MECHANISM OF ACTION: Vorasidenib inhibits mutant IDH1/2 through a unique mechanism, reducing the production of the oncometabolite 2-hydroxyglutarate (2-HG). This alteration affects key enzymes and DNA methylation, impacting tumor growth and invasion. Preclinical Evidence: Preclinical studies show vorasidenib's efficacy in inhibiting mutant IDH1/2 and 2-HG production in glioma models. It suppresses tumor growth, making it a potential treatment option. CLINICAL EVIDENCE: Early clinical trials demonstrate vorasidenib's clinical activity in non-enhancing gliomas. It reduces 2-hydroxyglutarate levels and tumor cell proliferation, with an objective response rate and prolonged progression-free survival. The drug's safety profile is favorable. Challenges and Future Directions: Challenges include identifying predictive biomarkers and optimizing sequencing or combinations with existing therapies. Further research is needed to establish long-term effectiveness, evaluate side effects, and explore combinations with immunotherapy. CONCLUSION: orasidenib significantly advances LGG treatment, targeting a prevalent mutation and slowing tumor growth. Promising preclinical and clinical evidence and manageable side effects suggest its potential impact on LGG management. However, more research, including large trials, is needed to confirm its efficacy and role in treatment.

Clival Metastases: Single-Center Retrospective Case Series and Literature Review.

Background/Objectives: Clivus metastases from distant neoplasms are uncommon occurrences both in clinical practice and the neurosurgical literature. Surgical management is debated, particularly about the role of surgery and the preferable approach. The aim of this study was to report our surgical experience and review the concerning literature. Methods: Our institutional registry was retrospectively reviewed, and patients who underwent surgical treatment for clival metastasis from 1998 to 2023 were included. A PRISMA systematic review of the literature was performed. Results: Four patients were enrolled, and all of them underwent an endoscopic endonasal approach (EEA). Three presented with cranial nerve (CN) VI palsy. The aim of surgery was biopsy in all cases. No complications were reported. Mean overall survival (OS) was 6 ± 1 months. The systematic review retrieved 27 papers reporting 39 patients who underwent the surgical treatment of clivus metastases. Most of them (79.5%) presented with CN palsies, and EEA was the preferred approach in 92.3% of the cases, to perform a biopsy in most patients (59%). Two hemorrhagic complications (5.1%) were reported, and the mean OS was 9.4 ± 5.6 months. Conclusions: Clival metastases are uncommonly observed, in most cases, during advanced stages of oncological disease. The aim of surgery should be the confirmation of diagnosis and symptomatic relief, balancing the risk-benefit ratio in a multidisciplinary context. EEA is the approach of choice, and it should be carried out in experienced tertiary skull base centers.

Connectome-Based Neurosurgery in Primary Intra-Axial Neoplasms: Beyond the Traditional Modular Conception of Brain Architecture for the Preservation of Major Neurological Domains and Higher-Order Cognitive Functions.

Despite the therapeutical advancements in the surgical treatment of primary intra-axial neoplasms, which determined both a significative improvement in OS and QoL and a reduction in the incidence of surgery-induced major neurological deficits, nowadays patients continue to manifest subtle post-operative neurocognitive impairments, preventing them from a full reintegration back into social life and into the workforce. The birth of connectomics paved the way for a profound reappraisal of the traditional conception of brain architecture, in favour of a model based on large-scale structural and functional interactions of a complex mosaic of cortical areas organized in a fluid network interconnected by subcortical bundles. Thanks to these advancements, neurosurgery is facing a new era of connectome-based resections, in which the core principle is still represented by the achievement of an ideal onco-functional balance, but with a closer eye on whole-brain circuitry, which constitutes the foundations of both major neurological functions, to be intended as motricity; language and visuospatial function; and higher-order cognitive functions such as cognition, conation, emotion and adaptive behaviour. Indeed, the achievement of an ideal balance between the radicality of tumoral resection and the preservation, as far as possible, of the integrity of local and global brain networks stands as a mandatory goal to be fulfilled to allow patients to resume their previous life and to make neurosurgery tailored and gentler to their individual needs.

A Brief History of Stereotactic Atlases: Their Evolution and Importance in Stereotactic Neurosurgery.

Following the recent acquisition of unprecedented anatomical details through state-of-the-art neuroimaging, stereotactic procedures such as microelectrode recording (MER) or deep brain stimulation (DBS) can now rely on direct and accurately individualized topographic targeting. Nevertheless, both modern brain atlases derived from appropriate histological techniques involving post-mortem studies of human brain tissue and the methods based on neuroimaging and functional information represent a valuable tool to avoid targeting errors due to imaging artifacts or insufficient anatomical details. Hence, they have thus far been considered a reference guide for functional neurosurgical procedures by neuroscientists and neurosurgeons. In fact, brain atlases, ranging from the ones based on histology and histochemistry to the probabilistic ones grounded on data derived from large clinical databases, are the result of a long and inspiring journey made possible thanks to genial intuitions of great minds in the field of neurosurgery and to the technical advancement of neuroimaging and computational science. The aim of this text is to review the principal characteristics highlighting the milestones of their evolution.

Social Media for Global Neurosurgery. Benefits and limitations of a groundbreaking approach to communication and education.

Introduction: Social media have become ubiquitous and their role in medicine is quickly growing. They provide an open platform by which members share educational material, clinical experiences, and collaborate with educational equity. Research question: To characterize the role of social media in neurosurgery, we analyzed metrics of the largest neurosurgical group (Neurosurgery Cocktail), collected relevant data about activities, impact and risks of this groundbreaking technology. Material and methods: We extracted Facebook metrics from 60-day time sample, including users demographics and other platform-specific values such as active members and number of posts within 60 days. A quality assessment of the posted material (clinical case reports and second opinions) was obtained establishing four main quality-criteria: privacy violation; quality of imaging; clinical and follow up data. Results: By December 2022, the group included 29.524 members (79.8% male), most (29%) between 35 and 44 years of age. Over 100 countries were represented. A total of 787 posts were published in 60 days with an average of 12.7 per day. In 173 clinical cases presented through the platform, some issue with privacy was recorded in 50.9%. The imaging was considered insufficient in 39.3%, clinical data in 53.8%; follow up data were missing in 60.7%. Discussion and conclusion: The study provided a quantitative evaluation of impact, flaws and limitations of social medial for healthcare. Flaws were mostly data breach and insufficient quality of case reports. There are actions to correct these flaws that can be easily taken to provide a greater credibility and efficacy to the system.