Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review.

BACKGROUND: Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG. METHODS: A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted. RESULTS: A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases. CONCLUSION: LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.

Comparative analysis of bevacizumab and LITT for treating radiation necrosis in previously radiated CNS neoplasms: a systematic review and meta-analysis.

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

Machine learning applications in craniosynostosis diagnosis and treatment prediction: a systematic review.

Craniosynostosis refers to the premature fusion of one or more of the fibrous cranial sutures connecting the bones of the skull. Machine learning (ML) is an emerging technology and its application to craniosynostosis detection and management is underexplored. This systematic review aims to evaluate the application of ML techniques in the diagnosis, severity assessment, and predictive modeling of craniosynostosis. A comprehensive search was conducted on the PubMed and Google Scholar databases using predefined keywords related to craniosynostosis and ML. Inclusion criteria encompassed peer-reviewed studies in English that investigated ML algorithms in craniosynostosis diagnosis, severity assessment, or treatment outcome prediction. Three independent reviewers screened the search results, performed full-text assessments, and extracted data from selected studies using a standardized form. Thirteen studies met the inclusion criteria and were included in the review. Of the thirteen papers examined on the application of ML to the identification and treatment of craniosynostosis, two papers were dedicated to sagittal craniosynostosis, five papers utilized several different types of craniosynostosis in the training and testing of their ML models, and six papers were dedicated to metopic craniosynostosis. ML models demonstrated high accuracy in identifying different types of craniosynostosis and objectively quantifying severity using innovative metrics such as metopic severity score and cranial morphology deviation. The findings highlight the significant strides made in utilizing ML techniques for craniosynostosis diagnosis, severity assessment, and predictive modeling. Predictive modeling of treatment outcomes following surgical interventions showed promising results, aiding in personalized treatment strategies. Despite methodological diversities among studies, the collective evidence underscores ML's transformative potential in revolutionizing craniosynostosis management.

The use of advanced neuroimaging modalities in the evaluation of low-grade glioma in adults: a literature review.

Low-grade gliomas encompass a subgroup of cancerous glial cell growths within the central nervous system and are distinguished by their slow growth and relatively low malignant potential. Despite their less aggressive nature, these tumors can still cause significant neurological symptoms through the compression of surrounding neural and vascular structures and, in some instances, undergo malignant transformation. For these reasons, timely and appropriate evaluation and management of low-grade gliomas is critical. Medical imaging stands as a cornerstone for evaluating patients with low-grade gliomas because of its noninvasive nature and ability to provide a vast amount of information about the underlying lesion. With the growing number of neuroimaging techniques and their capabilities, there is a lack of clear guidance on which techniques to utilize for the assessment of low-grade gliomas and what their respective core use cases should be. In this literature review, the authors discuss in significant depth the available evidence pertaining to the use of advanced neuroimaging techniques in the evaluation and management of low-grade gliomas. Specifically, they review the specificity, sensitivity, accuracy, and use cases of magnetic resonance spectroscopy (MRS), perfusion MR imaging (perfusion MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), as well as other emerging imaging techniques. They conclude that most of the advanced neuroimaging techniques are reliable in differentiating low- from high-grade gliomas, whereas MRS and DTI may further support molecular subclassification of the tumor. PET has been best employed for the purpose of tumor biopsy, whereas fMRI and DTI can be particularly valuable in preoperative surgical planning, as they delineate the functionally eloquent brain regions that need to be preserved during tumor resection. MRS, PET, SPECT, and perfusion MRI are best suited to monitor tumor progression, as their respective metrics closely correlate with the underlying metabolic activity of the tumor. Together, these techniques offer a vast amount of information and serve as tools for neurologists and neurosurgeons managing patients with low-grade gliomas.

Outcomes of HSV-1 encephalitis infection in glioblastoma: An integrated systematic analysis.

INTRODUCTION: Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma (GBM) due to similar radiographic imaging and clinical presentation. Limited data exist on the co-occurrence of GBM and HSV-1. To better describe the pathophysiology of HSV-1 superinfections in GBM, we performed a comprehensive review of GBM cases with superimposed HSV-1. METHODS: A comprehensive literature search of six electronic databases with apriori search criteria was performed to identify eligible cases of GBM with HSV-1. Relevant clinic-radiographic data were collected, Kaplan-Meier estimates, Fisher's exact test, and logistic regression analyses were used. RESULTS: We identified 20 cases of HSE in GBM with an overall survival (OS) of 8.0 months. The median age of presentation was 63 years (range: 24-78 years) and the median interval between GBM or HSE diagnosis was 2 months (range: 0.05-25 months). HSE diagnosis before GBM diagnosis was a predictor for improved survival (HR: 0.06; 95% CI: [0.01-0.54]; p < 0.01). There is a significant reduction in OS in patients with concomitant HSE and GBM compared to the cancer genome atlas (TCGA) cohort (median OS: 8 months vs. 14.2 months; p < 0.05). Finally, HSV does not directly infect GBM cells but indirectly activates a local immune response in the tumor microenvironment. CONCLUSIONS: Superimposed HSE in GBM may contribute to a significant reduction in OS compared to uninfected controls, potentially activating proto-oncogenes during active infection and latency. Preoperative HSE may induce an antiviral immune response, which may serve as a positive prognostic factor. Prompt antiviral treatment upon co-occurrence is necessary.

Clinical course of ventriculoperitoneal shunting for hydrocephalus following glioblastoma surgery: a systematic review and meta-analysis.

BACKGROUND: Surgical resection of glioblastoma (GBM) remains a cornerstone in the current treatment paradigm. The postoperative evolution of hydrocephalus necessitating ventriculoperitoneal shunting (VPS) continues to be defined. Correspondingly the objective of this study was to aggregate pertinent metadata to better define the clinical course of VPS for hydrocephalus following glioblastoma surgery in light of contemporary management. METHODS: Searches of multiple electronic databases from inception to November 2023 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were pooled by random-effects meta-analyses where possible. RESULTS: A total of 12 cohort studies satisfied all selection criteria, describing a total of 6,098 glioblastoma patients after surgery with a total of 261 (4%) of patients requiring postoperative VPS for hydrocephalus. Meta-analysis demonstrated the estimated pooled rate of symptomatic improvement following VPS was 78% (95% CI 66-88), and the estimated pooled rate of VPS revision was 24% (95% CI 16-33). Pooled time from index glioblastoma surgery to VPS surgery was 4.1 months (95% CI 2.8-5.3), and pooled survival time for index VPS surgery was 7.3 months (95% CI 5.4-9.4). Certainty of these outcomes were limited by the heterogenous and palliative nature of postoperative glioblastoma management. CONCLUSIONS: Of the limited proportion of glioblastoma patients requiring VPS surgery for hydrocephalus after index surgery, 78% patients are expected to show symptom improvement, and 24% can expect to undergo revision surgery. An individualized approach to each patient is required to optimize both index glioblastoma and VPS surgeries to account for anatomy and goals of care given the poor prognosis of this tumor overall.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Two-stage radiosurgery for large brain metastases: a systematic review and meta-analysis of clinical outcomes.

OBJECTIVE: Brain metastases (BMs) are the most common intracranial tumors. In several cases, they present as large masses, which are related to a worse prognosis and more complex therapeutic alternatives. Staged radiosurgery is reported to achieve local control with minimal radiation-related adverse events in BMs. However, no methodological consensus has been achieved in its use for large brain metastases (LBMs; > 2 cm). Therefore, the authors aimed to determine the effectiveness and safety of 2-stage Gamma Knife radiosurgery (GKRS) for LBMs, in order to optimize patients' postoperative course. METHODS: A systematic review of available literature was run in PubMed/MEDLINE, Scopus, Web of Science, Cochrane (OvidSP), and Google Scholar for works published up to December 14, 2022. Nonrandomized clinical trials, case series, and cohort studies were included. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) and Joanna Briggs Institute tools. Pooled mean difference and rates estimates were calculated by a random-effects model meta-analysis. The degree of heterogeneity was expressed using the I2 statistic. A subgroup analysis was performed. Ultimately, the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment. RESULTS: Fourteen studies met the eligibility criteria (cohorts, case series, and nonrandomized clinical trials), including 958 patients. A total pooled mean volume reduction of 6.27 cm3 (95% CI 5.67-6.88 cm3) and 54.36% (95% CI 39.92%-68.79%) after 2-stage GKRS was reported. Pooled rates of complete response (44.63%; 95% CI 26.50%-64.31%), neurological mortality (16.19%; 95% CI 7.68%-30.98%), and all-cause mortality (47.92%; 95% CI 28.04%-68.49%) were calculated. Overall certainty of evidence ranged from very low to moderate. CONCLUSIONS: Two-stage GKRS is an effective and safe approach for the treatment of LBMs. Nevertheless, the lack of available literature and the weak methodological approaches used determine a low to very low certainty of evidence and cannot provide robust evidence to recommend this intervention. Therefore, it is necessary to conduct higher-quality primary studies.

Surgical management of brain metastasis from ovarian cancer: a systematic review and case series.

OBJECTIVE: Ovarian cancer is a rare origin of brain metastasis (BM), with an incidence of only 1%-3%. Consequently, the literature is sparse, and no treatment consensus guideline is available for ovarian BM. The authors conducted a systematic review of ovarian BM and performed a combined pooled cohort survival analysis with their case series. METHODS: A systematic review of PubMed, Scopus, and Web of Science consistent with PRISMA guidelines along with an institutional retrospective chart review was conducted. Inclusion criteria for the systematic review included patients with confirmed BM and primary ovarian cancer, reported perioperative complications and outcomes, differentiated histology, and explicitly reported individual patient data. Reviews, commentaries, technical notes, and articles without English-language translations were excluded. The Newcastle-Ottawa Quality Assessment Scale was used independently by the first and second authors to assess the quality of each article. The authors performed univariate and multivariate analyses of several survival prognostic factors. Kaplan-Meier curves were generated for significant prognostic factors in the univariate analysis. RESULTS: A total of 48 patients with individual data across 34 studies and 8 patients from the authors' institution were included. All patients (n = 56) underwent resection for BM; 83.9% received adjuvant radiotherapy following surgery and 41.1% of patients received adjuvant chemotherapy. The median progression-free survival was 12 months (range 2-43 months). The median overall survival was 9 months (range 1-49 months). On univariate analysis, a single BM and no extracranial metastasis conferred a survival benefit, while clear cell carcinoma as the primary histology corresponded to worsened OS. Multivariable analysis showed that age > 50 years (p = 0.002) and > 1 BM (p < 0.001) were risk factors for poor prognosis. Protective factors included the addition of the following multimodal adjuvant therapy with surgery: radiotherapy (p = 0.002), chemotherapy and radiotherapy (p = 0.005), and stereotactic radiosurgery (p = 0.002). CONCLUSIONS: Although the scarcity of published individual patient data hinders the determination of optimal management, the authors' analysis highlights that multimodal therapies, a single cranial lesion, and age < 50 years are associated with increased survival for patients with ovarian BMs.

Same-day discharge after craniotomy for brain tumor resection: enhancing patient selection through a prognostic scoring 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 cm3) 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.

Intraoperative 5-ALA fluorescence-guided resection of high-grade glioma leads to greater extent of resection with better outcomes: a systematic review.

IMPORTANCE: High-grade gliomas (HGG) are the most aggressive and common malignant brain tumors in adults. They have a dismally fatal prognosis. Even if gross total resection of the enhancing tumor is achieved, inevitably, invading tumor cells that are indistinguishable to the un-aided eye are left behind, which eventually leads to tumor recurrence. 5-aminolevulinic acid (5-ALA) is an increasingly utilized intraoperative fluorescent imaging agent for patients with HGG. It enhances visualization of HGG tissue. Despite early promising randomized clinical trial data suggesting a survival benefit for 5-ALA-guided surgery, the growing body of literature must be analyzed to confirm efficacy on patient outcomes. OBJECTIVE: To perform a systematic review of the literature to evaluate whether there is a beneficial effect upon survival and extent of resection due to the utilization of 5-ALA in HGG surgery. EVIDENCE REVIEW: Literature regarding 5-ALA usage in HGG surgery was reviewed according to the PRISMA guidelines. Two databases, PubMed and SCOPUS, were searched for assorted combinations of the keywords "5-ALA," "high-grade glioma," "5-aminolevulinic acid," and "resection" in July 2020 for case reports and retrospective, prospective, and randomized clinical trials assessing and analyzing 5-ALA intraoperative use in patients with HGG. Entailed studies on PubMed and SCOPUS were found for screening using a snowball search technique upon the initially searched papers. Systematic reviews and meta-analyses were excluded from our PRISMA table. FINDINGS: 3756 previously published studies were screened, 536 of which were further evaluated, and ultimately 45 were included in our systematic review. There were no date restrictions on the screened publications. Our literature search was finalized on July 16, 2020. We found an observed increase in the overall survival (OS) and progression-free survival (PFS) of the 5-ALA group compared to the white light group, as well as an observed increase in the OS and PFS of complete resections compared to incomplete resections. Of the studies that directly compared the use of 5-ALA to white light (13 of the total analyzed 45, or 28.9%), 5-ALA lead to a better PFS and OS in 88.4 and 67.5% of patients, respectively. When the studies that reported postoperative neurologic outcomes of surgeries using 5-ALA vs. white light were analyzed, 42.2% of subjects demonstrated 5-ALA use was associated with less post-op neurological deficits, whereas 34.5% demonstrated no difference between 5-ALA and without. 23.3% of studies showed that intraoperative 5-ALA guided surgeries lead to more post-op neurological deficits. CONCLUSIONS AND RELEVANCE: Utilization of 5-ALA was found to be associated with a greater extent of resection in HGG surgeries, as well as longer OS and PFS. Postop neurologic deficit rates were mixed and inconclusive when comparing 5-ALA groups to white light groups. 5-ALA is a useful surgical adjunct for resection of HGG when patient safety is preserved.

Same-day discharge after brain tumor resection: a prospective pilot study.

PURPOSE: Outpatient brain surgery has many advantages for the psychological and physical wellbeing of patients, as well as reduced costs to the health care system. Compared with inpatient admissions, same day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. We aim to establish a prospectively collected quality outcomes database to examine the outcomes of patients that undergo brain tumor resection and are discharged home the same day as surgery. METHODS: We have established a prospectively collected quality outcomes database to examine the outcomes of all patients that underwent brain tumor resection by a single neurosurgeon (R.J.K) at our institution from August 2020 to August 2021 and were discharged home the same day as surgery. RESULTS: Over the one-year period this study was conducted, 37 of 334 patients met inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after an overnight observation. No postoperative complications were noted at two-week postoperative follow-up. CONCLUSION: In select patients undergoing brain tumor surgery, same day discharge should be considered. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history. Once discharged, open communication with the patient and their family is critical to detect complications that should trigger rehospitalization and intervention.

Glioblastoma multiforme in patients with human immunodeficiency virus: an integrated review and analysis.

INTRODUCTION: As lifespans for persons living with HIV (PLWH) have improved over the last decade, there has been a simultaneous increase in non-AIDS-related cancer in that group. However, there is a paucity of data regarding the incidence of glioblastoma multiforme (GBM) in PLWH. Better understanding of the oncogenesis, natural history, and treatment outcomes of GBM in PLWH should lead to improved treatment strategies. METHODS: We performed a comprehensive literature search of six electronic databases to identify eligible cases of GBM among PLWH. Kaplan-Meier estimates, Fisher's exact test, and logistic regression were used to interrogate the data. Epidemiologic data on global HIV prevalence was obtained from the 2016 UNAIDS incidence report, and CNS cancer incidence was obtained from the GDB 2016 Brain and Other CNS Cancer Collaborators. RESULTS: There is an inverse relationship between the incidence of HIV and CNS cancer globally. Median overall survival (OS) from GBM diagnosis was 8 months. Estimates for survival at 1 and 2 years were 28 and 5%, respectively. There were no statistically significant predictors of OS in this setting. There was a significant difference (p < 0.01) in OS in PLWH and GBM when compared to TCGA age matched cohorts. CONCLUSION: The diagnosis of GBM in PLWH is severely underreported in the literature. Despite maximal treatment, OS in this patient population is significantly less than in HIV-negative people. There was a poor prognosis of GBM in PLWH, which is inconsistent with previous reports. Further investigation is required for PLWH and concomitant GBM. Analyses must consider if HAART is maintained in PLWH during GBM treatment.

Concurrent intraventricular intracranial myxoid mesenchymal tumor and ependymoma in a long-term Ewing sarcoma survivor.

Intracranial myxoid mesenchymal tumor, FET::CREB fusion positive is a rare, recently described central nervous system neoplasm. It is characterized by EWSR1::CREB family transcription factor fusion, typically arises in children and adolescents, and is locally aggressive even after gross total resection. Currently, there are little data available to guide management and gauge long-term prognosis. Furthermore, there have been no reports of these lesions occurring simultaneously with other intracranial neoplasms or in patients with a history of malignancy. Here we describe the first case of a very unusual patient with intracranial myxoid mesenchymal tumor of the right lateral ventricle with a concurrent fourth ventricular ependymoma who had a remote history of Ewing sarcoma of the right fibula.

Traumatic brain injury and subsequent brain tumor development: a systematic review of the literature.

The role of prior head trauma in stimulating brain tumor development has been previously described in the literature but continues to be debated. The goal of this study was to conduct a systematic review interrogating the contemporary literature to delineate any possible relationship between traumatic brain injury and brain tumor development. A systematic review exploring development of post-TBI brain tumor was conducted by searching electronic databases. Abstracts from articles were read and selected for full-text review according to criteria previously established in the scientific literature. Relevant full-text articles were divided into case reports and single-arm studies and epidemiological studies. Of 1070 resultant articles, 18 case reports and single-arm studies (level of evidence of IV and V) with 45 patients were included. The most common cause of TBI was traffic accidents. The average period between TBI and subsequent tumor diagnosis was 12.8 years. Meningiomas represented the largest share of tumors, followed by gliomas. Most post-TBI brain tumors developed in the frontal and temporal lobes. Fifteen epidemiological studies were also interrogated from a variety of countries (level of evidence of III). Case-control studies were more common than cohort studies. There were 9 of 15 studies proposed a possible relationship between history of head trauma and development of brain tumor. The relationship between head trauma and neoplastic growth continues to be heavily debated. There are certainly case reports and epidemiological studies in the literature that suggest a correlational relationship between the two. However, there is no concrete evidence of a causal relationship between TBI and brain tumors. More research is needed to definitively delineate the extent of any such relationship.

Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics.

As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.

Transcortical resection of a giant bilobed falcine meningioma.

INTRODUCTION: Falcine meningiomas present significant surgical challenges because they often involve the falx bilaterally, are concealed by a significant amount of normal brain parenchyma and are frequently deep in location and in close proximity to the anterior cerebral arteries. Many prefer the interhemispheric approach for these lesions, but this operative corridor is not without risk as venous infarctions and cortical injury can occur. CLINICAL PRESENTATION: We present an alternative technique utilizing a transcortical approach to resect a giant, bilobed falcine meningioma in a 68-year-old female who presented with progressive abulia, urinary incontinence, and bilateral lower extremity weakness over 2 years. A unilateral right frontal craniotomy and a corticectomy through the right superior frontal gyrus was used to safely resect the entire tumor. The patient tolerated the procedure well and was discharged home without issue. Pathology demonstrated that the lesion was an atypical meningioma and she subsequently received adjuvant fractionated radiotherapy. At 2-year follow-up, she has no neurologic deficits, never developed any postoperative seizures and has not had any evidence of tumor recurrence. CONCLUSION: The transcortical approach can be used as a safe alternative for resecting falcine meningiomas without adding significant undue risk to the patient.

Prognosticating survival of pineal parenchymal tumors of intermediate differentiation (PPTID) by grade.

BACKGROUND: Pineal parenchymal tumors of intermediate differentiation (PPTID) are a rare group of pineal parenchymal tumors classified by histology as either World Health Organization (WHO) Grades 2 or 3. The rarity of these tumors in adults has left a number of clinical management questions open. Correspondingly, the aim of this study was to aggregate a large PPTID cohort with sufficient statistical power from a large national cancer database to analyze prognostic parameters. METHODS: All PPTID patients aged over 18 years in the U.S. National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized and survival was modeled using Kaplan-Meier and Cox regression analyses. RESULTS: A total of 103 adult PPTID patients were identified in the NCDB with 63 (61%) WHO Grade 2 and 40 (39%) WHO Grade 3 tumors. Overall, mean age was 53 ± 18 years with even gender distribution. A total of 75 (73%) patients underwent surgical resection for diagnosis, with gross total resection (GTR) was the most common resection outcome in 50/75 (67%). Chemotherapy was utilized in 18 (17%) patients, and radiation therapy in 37 (36%) patients. Overall, 5-year survival rate was estimated to be 54% (95% CI 42-64%), with mean survival was 84 (95% CI 69-99) months. Patients with Grade 2 tumors survived statistically longer than Grade 3 tumor counterparts (P < 0.01). Overall, older age (HR 1.09, P < 0.01) was associated with shorter survival, whereas GTR (HR 0.43, P = 0.02) was associated with longer survival. Both these parameters were significant within Grade 2 and Grade 3 subgroup analyses as well. CONCLUSIONS: PPTID are rare tumors with expected mean survival more than 5 years, although Grade 2 tumors are expected to survive longer than Grade 3 tumors. Age and gross total resection are significant independent predictors of survival in PPTID overall, as well as within Grade 2 and Grade 3 subgroups separately. The prognostic role and benefit of adjuvant therapy is yet to be elucidated, mandating more molecular and biologic research be done to further optimize clinical management in the future.

Current experimental therapies for atypical and malignant meningiomas.

INTRODUCTION: Atypical (WHO grade II) and malignant meningiomas (WHO Grade III) are a rare subset of primary intracranial tumors. Given their relatively high recurrence rate after surgical resection and radiotherapy, there has been a recent push to explore other adjuvant treatment options for these treatment-refractory tumors. Recent advances in molecular sequencing of tumors have elucidated new pathways and drug targets which are currently being studied. This article provides a thorough overview of novel investigational therapeutics including targeted therapy, immunotherapy, and new technological modalities for atypical and malignant meningiomas. METHODS: We performed a comprehensive review of the available literature regarding preclinical and clinical evidence for emerging treatments for high grade meningiomas from 1980 to 2020 including contemporaneous clinical trials. RESULTS: There is encouraging preclinical evidence regarding the efficacy of the emerging treatments discussed in this article. Several clinical trials are currently recruiting patients to translate targeted molecular therapy for meningiomas. Several clinical studies have suggested a clinical benefit of combinatorial treatment for these treatment-refractory tumors. CONCLUSION: With numerous active clinical trials for high grade meningiomas, a meaningful improvement in the outcomes for these tumors may be on the horizon.

Unilateral Fourth Nerve Palsy due to Presumed Metastatic Melanoma.

ABSTRACT: An 81-year-old man with a history of metastatic melanoma presented with sudden onset of painless, binocular vertical diplopia. The clinical examination was consistent with a right fourth nerve palsy. An MRI of the head revealed a mass dorsal to the right tectum at the level of the inferior colliculus. An MRI just 4 months prior did not show a lesion in that location. An MRA of the head did not show an aneurysm. This is a rare case of an isolated fourth nerve palsy believed to be due to metastatic melanoma compressing the nerve along the dorsal midbrain.