Glioblastoma (GBM) is an aggressive brain tumor characterized by an immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance and disease progression. Background: Tumor-associated macrophages (TAMs), comprising both resident microglia and bone marrow–derived macrophages, play a central role in supporting tumor growth, angiogenesis, and immune evasion. Most TAMs adopt an M2-like immunosuppressive phenotype, making them a promising target for immunomodulatory strategies in GBM. Method: According to PRISMA guidelines, we conducted a systematic literature review and recruited eligible studies focused on therapeutic approaches targeting TAMs in GBM, emphasizing mechanisms of action, efficacy, and challenges. Data extraction focused on therapeutic classes, outcomes, and TAM-related biomarkers. Results: We identified 30 studies meeting the inclusion criteria. These therapies are categorized into three main strategies: inhibition of TAM recruitment, enhancement of TAM-mediated phagocytosis, and reprogramming of TAMs. Combination strategies, including TAM-targeting with checkpoint inhibitors, nanoparticles, and oncolytic viruses, show synergistic effects in preclinical models. Conclusions: Targeting TAMs represents a multifaceted strategy for GBM treatment. Current evidence underscores the need for combination approaches integrating TAM modulation with existing standard-of-care therapies. Clinical translation remains limited due to challenges such as TAM heterogeneity, plasticity, immunosuppressive therapies, and restricted drug delivery across the blood–brain barrier. Future directions should highlight personalized treatments based on detailed TME profiling. Combining TAM-targeted therapies with agents modulating metabolic or immune pathways, and leveraging advanced delivery systems and spatial transcriptomics may improve efficacy.

Glioblastoma (GBM) is a primary CNS tumor that is highly lethal in adults and has limited treatment options. Despite advancements in understanding the GBM biology, the standard treatment for GBM has remained unchanged for more than a decade. Only 6.8% of patients survive beyond five years. Telomerase, particularly the hTERT promoter mutations present in up to 80% of GBM cases, represents a promising therapeutic target due to its role in sustaining telomere length and cancer cell proliferation. This review examines the biology of telomerase in GBM and explores potential telomerase-targeted therapies. We conducted a systematic review following the PRISMA-P guidelines in the MEDLINE/PubMed and Scopus databases, from January 1995 to April 2024. We searched for suitable articles by utilizing the terms “GBM”, “high-grade gliomas”, “hTERT” and “telomerase”. We incorporated studies addressing telomerase-targeted therapies into GBM studies, excluding non-English articles, reviews, and meta-analyses. We evaluated a total of 777 records and 46 full texts, including 36 studies in the final review. Several compounds aimed at inhibiting hTERT transcription demonstrated promising preclinical outcomes; however, they were unsuccessful in clinical trials owing to intricate regulatory pathways and inadequate pharmacokinetics. Direct hTERT inhibitors encountered numerous obstacles, including a prolonged latency for telomere shortening and the activation of the alternative lengthening of telomeres (ALT). The G-quadruplex DNA stabilizers appeared to be potential indirect inhibitors, but further clinical studies are required. Imetelstat, the only telomerase inhibitor that has undergone clinical trials, has demonstrated efficacy in various cancers, but its efficacy in GBM has been limited. Telomerase-targeted therapies in GBM is challenging due to complex hTERT regulation and inadequate inhibitor pharmacokinetics. Our study demonstrates that, despite promising preclinical results, no Telomerase inhibitors have been approved for GBM, and clinical trials have been largely unsuccessful. Future strategies may include Telomerase-based vaccines and multi-target inhibitors, which may provide more effective treatments when combined with a better understanding of telomere dynamics and tumor biology. These treatments have the potential to be integrated with existing ones and to improve the outcomes for patients with GBM.

While intraoperative neurophysiological monitoring (IONM) is considered a standard for intramedullary spinal cord tumor surgery, the effective role of IONM in intradural extramedullary (IDEM) tumors is still debated. We present the results of 60 patients affected by IDEM tumors undergoing surgery with the aid of IONM. Each patient was evaluated according to the modified McCormick scale (MMS) at admission, discharge and at follow-up. During surgery, motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were studied using the Medtronic NIM-eclipse^® 32-channel system (Medtronic Xomed, Inc. 6743 Southpoint Drive North Jacksonville FL USA). Patients’ age, gender and tumor location did not affect MMS modifications. Tumors involving more than three levels had an increased likelihood of MMS worsening, while meningioma pathology was associated with worse preoperative and 1-year follow-up MMS. No MEP amplitude ratio was able to predict clinical variations, while intraoperative SEP worsening was associated with 100% risk of poor MMS at discharge and with 50% risk of poor MMS at long-term follow-up. In our opinion, SEP monitoring is a valid tool that may contribute to the preservation of the patient’s neurological status. MEP monitoring is not mandatory in IDEM surgery while more studies are required to explore the feasibility and the role of D-wave in this kind of surgery.

Epilepsy treatment primarily involves antiseizure medications (ASMs) to eliminate seizures and improve the quality of life, but many patients develop drug-resistant epilepsy (DRE), necessitating alternative interventions. This study aimed to evaluate the long-term efficacy and safety of vagus nerve stimulation (VNS) in managing DRE. We retrospectively analyzed data from 105 adult patients treated at Agostino Gemelli Hospital from 1994 to 2022. Among the 73 patients with follow-up data, 80.8% were responders, experiencing significant reductions in seizure frequency over an average follow-up period of 9.4 years. Although 19.2% were non-responders, many of these patients still opted for generator replacements due to improvements in quality of life, such as fewer falls and shorter post-ictal periods. The overall complication rate was 12.3%, with most complications being mild and manageable. These findings suggest that VNS offers substantial long-term benefits for patients with DRE, improving seizure control and quality of life. This study underscores the importance of VNS as a viable long-term treatment option for DRE, highlighting its potential to significantly enhance patient outcomes and quality of life.

Preservation of facial nerve function (FNF) during neurosurgery for cerebellopontine angle (CPA) tumors is paramount in elderly patients. Corticobulbar facial motor evoked potentials (FMEPs) allow assessment intraoperatively of the functional integrity of facial motor pathways, thus improving safety. We aimed to evaluate the significance of intraoperative FMEPs in patients 65 years and older. A retrospective cohort of 35 patients undergoing CPA tumors resection was reported; outcomes of patients aged 65–69 years vs. ≥70 years were compared. FMEPs were registered both from upper and lower face muscles, and amplitude ratios (minimum-to-baseline, MBR; final-to-baseline, FBR; and recovery value, FBR minus MBR) were calculated. Overall, 78.8% of patients had a good late (at 1 year) FNF, with no differences between age groups. In patients aged ≥70 years, MBR significantly correlated with late FNF. At receiver operating characteristics (ROC) analysis, in patients aged 65–69 years, FBR (with 50% cut-off value) could reliably predict late FNF. By contrast, in patients aged ≥70 years, the most accurate predictor of late FNF was MBR, with 12.5% cut-off. Thus, FMEPs are a valuable tool for improving safety in CPA surgery in elderly patients as well. Considering literature data, we noticed higher cut-off values for FBR and a role for MBR, which suggests an increased vulnerability of facial nerves in elderly patients compared to younger ones.

The aim of the present study was to conduct a systematic review on the role of intraoperative neuro-monitoring (IONM) in microvascular decompression (MVD) surgery for patients affected by trigeminal neuralgia (TN) specifically regarding its impact on clinical outcomes and whether its use may aid in identifying the site of neurovascular conflict (NVC). We reviewed the literature following PRISMA guidelines to identify and critically assess relevant studies. The review question was formulated according to the PICO framework as follows: “For patients affected by TN undergoing MVD (P), does IONM (I), compared to surgery without neuromonitoring (C), correlate with clinical outcomes? Moreover, can IONM be useful in identifying the NVC (O) site?”. The literature search yielded a total of 504 results. After removing duplicates (n = 187), 317 papers were screened. Following title and abstract screening, 307 records were excluded. Ultimately, 10 studies were deemed relevant to the research purpose. IONM plays a significant role in MVD for TN, improving surgical precision, enhancing patient safety, and providing real-time prognostic insights. The included studies have demonstrated its utility in preventing complications and identifying the culprit vessel responsible for NVC during MVD.To the best of our knowledge, this is the first systematic review highlighting the role of IONM in MVD performed for TN and its impact on postoperative clinical outcomes and the intraoperative identification of the NVC. Further prospective studies are needed to standardize IONM protocols and refine its application in MVD, ensuring personalized treatment even in complex cases.