Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase implicated in a wide variety of regulatory cellular functions. PP2A is abundant in the mammalian nervous system, and dysregulation of its cellular functions is associated with myriad neurodegenerative disorders. Additionally, PP2A has oncologic implications, recently garnering attention and emerging as a therapeutic target because of the antitumor effects of a potent PP2A inhibitor, LB100. LB100 abrogation of PP2A is believed to exert its inhibitory effects on tumor progression through cellular chemo- and radiosensitization to adjuvant agents. An updated and unifying review of PP2A biology and inhibition with LB100 as a therapeutic strategy for targeting cancers of the nervous system is needed, as other reviews have mainly covered broader applications of LB100. In this review, we discuss the role of PP2A in normal cells and tumor cells of the nervous system. Furthermore, we summarize current evidence regarding the therapeutic potential of LB100 for treating solid tumors of the nervous system.

OBJECTIVE: Neurosurgery, among other surgical fields, is amid a shift in patient management with enhanced recovery and same-day discharge (SDD) protocols slowly becoming more popular and feasible. While such protocols reduce the risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate. The authors aimed to better quantify selection criteria through a prospective follow-up study of patients undergoing brain tumor resection with SDD. METHODS: Three arms of analysis were carried out. First, clinical data of SDD patients were prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived. RESULTS: Over the duration of the study, 31 of 334 patients were selected for SDD while 59 qualified for SDD by previously defined criteria but were not selected at the surgeon’s discretion. There was no difference in outcomes between the two groups, and there were no postoperative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (left-sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume ≤ 11.75 cm ³ ) were included in a predictive scoring system for successful SDD. The scoring system was found to significantly predict high or low likelihood for successful SDD when tested on the mixed prospective cohort. CONCLUSIONS: This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. This clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.

Background: Enhanced recovery after surgery (ERAS) programs are a model of care that aim to improve patient outcomes, reduce complications, and facilitate recovery while reducing healthcare-associated costs and admission length. While such programs have been developed in other surgical subspecialties, there have yet to be guidelines published specifically for laser interstitial thermal therapy (LITT). Here we describe the first multidisciplinary ERAS preliminary protocol for LITT for the treatment of brain tumors. Methods: Between the years 2013 and 2021, 184 adult patients consecutively treated with LITT at our single institution were retrospectively analyzed. During this time, a series of pre, intra, and postoperative adjustments were made to the admission course and surgical/anesthesia workflow with the goal of improving recovery and admission length. Results: The mean age at surgery was 60.7 years with a median preoperative Karnofsky performance score of 90 ± 13. Lesions were most commonly metastases (50%) and high-grade gliomas (37%). The mean length of stay was 2.4 days, with the average patient being discharged 1.2 days after surgery. There was an overall readmission rate of 8.7% with a LITT-specific readmission rate of 2.2%. Three of 184 patients required repeat intervention in the perioperative period, and there was one perioperative mortality. Conclusions: This preliminary study shows the proposed LITT ERAS protocol to be a safe means of discharging patients on postoperative day 1 while preserving outcomes. Although future prospective work is needed to validate this protocol, results show the ERAS approach to be promising for LITT.

The Mitogen-activated protein kinase kinase (MEK) protein family has dual-specificity protein kinases with a myriad of cellular functions that include but are not limited to cell survival, cell division, immunologic response, angiogenesis, and cellular senescence. MEK is crucial in the MAPK signaling pathway, regulating different organ systems, including the CNS. Increased activation and dysregulation of the MEK pathway is reportedly observed in 30% of all malignancies. The diversity of MEK renders it a prime target for inhibition in treating cancer. MEK inhibition has been studied in the context of melanoma, non-small cell lung cancer, breast cancer, and colorectal cancer, among others. The standard treatment for glioblastoma (resection, temozolomide, and radiation) remains relatively futile, which warrants alternative treatment options. Therefore, MEK inhibition has garnered more attention in recent years as investigators have explored its role in treating the most aggressive and most common primary brain tumor, glioblastoma. MEK inhibitors have shown efficacy in pre-clinical investigations as well as some promise in clinical trials which have demonstrated improved overall and progression-free survival. This underscores the potential of MEK inhibition in glioblastoma therapy and represents an area that likely warrants further research. However, there are few comprehensive and unifying reviews discussing the current state of MEK inhibition in glioblastoma therapy. We begin this review by detailing the normal function of MEK as it pertains to the CNS. We then compiled relevant pre-clinical and clinical studies to investigate recent research discussing the role of MEK inhibition in glioblastoma therapy.