Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Leptomeningeal carcinomatosis (LC) is defined as infiltration of the leptomeninges by metastatic carcinoma and often represents the end stage of cancer disease. In breast cancer, LC is associated with a median survival of approximately 6-8 weeks without specific treatment. It could increase by only few months with personalized treatment plans. Usually, the median time of onset of leptomeningeal spread is 18 months and it is diagnosed in up to 70% of patients with active and progressive systemic disease. We present an uncommon case of LC in a patient with history of breast cancer with a 10 year-disease-free condition and an overall survival after LC diagnosis of 10 months. Central Nervous System (CNS) Magnetic Resonance Imaging (MRI) showed contrast enhancement of medullary cone and cauda. Despite the negativity of cytological analysis of Cerebral-Spinal Fluid (CSF), the patient underwent meningeal and radicular biopsy in November 2019. The neuropathological examination confirmed the diagnosis of LC. The patient was started on the aromatase inhibitor anastrozole. A whole body contrast Computed Tomography (CT) scan at three months follow-up was negative for further disease dissemination. The patient is currently under oncological and radiological follow-up after more than 10 months from diagnosis. Although nowadays diagnosis of LC is prompted by cytological examination of CSF, its negativity should not halt the diagnostic process. In the presence of a high clinical suspicion of LC, we suggest the biopsy of lesion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The activities related to intrathecal baclofen (ITB) therapy could not be interrupted at the outbreak of COVID-19 pandemic due to possible life-threatening related complications such as withdrawal and over dosage syndromes. In this study we reported the different adopted strategies to manage patients with an ITB implanted infusion pump during the pandemic period and studied the impact of these strategies on experiences reported from patients and their caregivers, assessed through a specific survey., Methods: Thirty-five patients (mean age: 43.71±12.33 years) were included. Their clinical and medical data were recorded and observed from March 2020 to March 2021 and different strategies implemented in order to limit patients and providers risk of exposure to COVID-19. The impact of these strategies was assessed trough a survey that was performed after the first two months of pandemic (coinciding with the period of general lockdown) and after one year from the pandemic onset., Results: We observed a statistically significant improvement of the following items: difficulties in reaching medical clinic (P=0.0072), continuation of physical therapy (P=0.0021) and feelings of anxiety in medical conditions (P=0.0006). Considering the difficulties in communications with the medical staff we obtained optimal scores both at the beginning of pandemic and after one year from the pandemic onset without significant difference., Conclusions: Our survey showed that the adopted strategies provided a feeling of confidence and safety among ITB patients and their caregivers during the COVID-19 pandemic. We think that a clear communication is always of paramount importance to manage these patients.