Refining the predictive value of preoperative apparent diffusion coefficient (ADC) by whole-tumor analysis for facial nerve outcomes in vestibular schwannomas.

BACKGROUND: Apparent diffusion coefficient (ADC) in MRI has been shown to correlate with postoperative House-Brackmann (HB) scores in patients with vestibular schwannoma despite limited methodology. To rectify limitations of single region of interest (ROI) sampling, we hypothesize that whole-tumor ADC histogram analysis will refine the predictive value of this preoperative biomarker related to postoperative facial nerve function. METHODS: Of 155 patients who underwent resection of vestibular schwannoma (2014-2020), 125 patients were included with requisite clinical and radiographic data. After volumetric analysis and whole-tumor ADC histogram, regression tree analysis identified ADC cutoff for significant differences in HB grade. Outcomes were extent of resection, facial nerve function, hospital length of stay (LOS), and complications. RESULTS: Regression tree analysis defined three quantitative ADC groups (× 10-6 mm2/s) as high (> 2248.77; HB 1.7), mid (1468.44-2248.77; HB 3.1), and low (< 1468.44; HB 2.3) range (p 0.04). The mid-range ADC group had significantly worse postoperative HB scores and longer hospital LOS. Large tumor volume was independently predictive of lower rates of gross total resection (p <0.0001), higher postoperative HB score (p 0.002), higher rate of complications (p 0.04), and longer LOS (p 0.003). CONCLUSIONS: Whole-tumor histogram yielded a robust regression tree analysis that defined three ADC groups with significantly different facial nerve outcomes. This likely reflects tumor heterogeneity better than solid-tumor ROI sampling. Whole-tumor ADC warrants further study as a useful radiographic biomarker in patients with vestibular schwannoma who are considering surgical resection.

Neurologic outcomes for adult spinal cord ependymomas stratified by tumor location: a retrospective cohort study and 2-year outlook.

Determine whether craniocaudal spinal cord tumor location affects long-term neurologic outcomes in adults diagnosed with spinal ependymomas (SE). A retrospective cohort analysis of patients aged ≥ 18 years who underwent surgical resection for SE over a ten-year period was conducted. Tumor location was classified as cervical, thoracic, or lumbar/conus. Primary endpoints were post-operative McCormick Neurologic Scale (MNS) scores at < 3 days, 6 weeks, 1 year, and 2 years. One-way ANOVA was performed to detect significant differences in MNS scores between tumor locations. Twenty-eight patients were identified. The average age was 44.2 ± 15.4 years. Sixteen were male, and 13 were female. There were 10 cervical-predominant SEs, 13 thoracic-predominant SEs, and 5 lumbar/conus-predominant SEs. No significant differences were observed in pre-operative MNS scores between tumor locations (p = 0.73). One-way ANOVA testing demonstrated statistically significant differences in post-operative MNS scores between tumor locations at < 3 days (p = 0.03), 6 weeks (p = 0.009), and 1 year (p = 0.003); however, no significant difference was observed between post-operative MNS scores at 2 years (p = 0.13). The mean MNS score for patients with thoracic SEs were higher at all follow-up time points. Tumors arising in the thoracic SE are associated with worse post-operative neurologic outcomes in comparison to SEs arising in other spinal regions. This is likely multifactorial in etiology, owing to both anatomical differences including spinal cord volume as well as variations in tumor characteristics. No significant differences in 2-year MNS scores were observed, suggesting that patients ultimately recover from neurological insult sustained at the time of surgery.

Metastatic Lesions of the Brain and Spine.

Brain and spinal metastases are common in cancer patients and are associated with significant morbidity and mortality. Continued advancement in the systemic care of cancer has increased the life expectancy of patients, and consequently, the incidence of brain and spine metastasis has increased. There has been an increase in the understanding of oncogenic mutations, and research has also demonstrated spatial and temporal mutations in patients that may drive overall treatment resistance and failure. Combinatory treatments with radiation, surgery, and newer systemic therapies have continued to increase the life expectancy of patients with brain and spine metastases. Given the overall complexity of brain and spine metastases, this chapter aims to give a comprehensive overview and cover important topics concerning brain and spine metastases. This will include the molecular, genetic, radiographic, surgical, and non-surgical treatments of brain and spinal metastases.

Surgical outcomes in large vestibular schwannomas: should cerebellopontine edema be considered in the grading systems?

PURPOSE: Large (> 3 cm) vestibular schwannomas pose complexity in surgical management because of narrow working corridors and proximity to the cranial nerves, brainstem, and inner ear structures. With current vestibular schwannoma classifications limited in information regarding cerebellopontine edema, our retrospective series examined this radiographic feature relative to clinical outcomes and its possible role in preoperative scoring. METHODS: Of 230 patients who underwent surgical resection of vestibular schwannoma (2014-2020), we identified 107 patients with Koos grades 3 or 4 tumors for radiographic assessment of edema in the middle cerebellar peduncle (MCP), brainstem, or both. Radiographic images were graded and patients grouped into Koos grades 3 or 4 or our proposed grade 5 with edema. Tumor volumes, radiographic features, clinical presentations, and clinical outcomes were evaluated. RESULTS: The 107 patients included 22 patients with grade 3 tumors, 39 with grade 4, and 46 with grade 5. No statistical differences were noted among groups for demographic data or complication rates. Unlike grades 3 and 4 patients, grade 5 patients presented with worse hearing (p < 0.001), larger tumors (p < 0.001), lower rates of gross total resection (GTR), longer hospital stays, and higher rates of balance dysfunction. CONCLUSION: With edema detected in 43% of this cohort, special considerations are warranted for grade 5 vestibular schwannomas given the preoperative findings of worse hearing, lower GTR rates, longer hospital stays, and 96% who pursued postoperative balance therapy. We propose that grade 5 with edema offers a more nuanced interpretation of a radiographic feature that holds relevance to treatment selection and patient outcomes.

Concomitant Temozolomide plus radiotherapy for high-grade and recurrent meningioma: a retrospective chart review.

BACKGROUND: High-grade and recurrent meningiomas are often treatment resistant and pose a therapeutic challenge after surgical and radiation therapy (RT) failure. Temozolomide (TMZ) is a DNA alkylating agent that appears to have a radiosensitizing effect when used in combination with RT and may be worthwhile in meningioma treatment. Thus, we investigated the potential efficacy of concomitant RT plus TMZ compared to historical controls of just RT used in the treatment of high-grade and recurrent meningiomas. METHODS: We performed a retrospective analysis of patients with meningioma treated at the University of Colorado with TMZ chemoradiation. Progression free survival (PFS) and overall survival (OS) were calculated from the start of chemoradiation to local recurrence or death, respectively. RESULTS: Eleven patients (12 tumors) were treated with chemoradiation with a median follow-up of 41.5 months. There were two WHO grade 1, eight grade 2 and two grade 3 meningiomas. Three patients died during the follow-up period-one being disease related (11.1%). Two patients had meningioma recurrence-at 2.3 months (WHO grade 3), and 5.4 years (WHO grade 2). Three-year OS and PFS for grade 2 meningiomas were each 88%. Historical controls demonstrate a 3-year median OS and PFS of 83% and 75.8%, respectively. CONCLUSIONS: Treatment options are limited for meningiomas after local failure. In this study, TMZ chemoradiation demonstrated no significant difference in PFS and OS in the treatment of grade 2 meningiomas compared to historic controls. Further study is warranted to find novel methods for the treatment of malignant and recurrent meningiomas.

Third Ventricle Volume Predicts Functional Outcome in Chronic Subdural Hematoma.

OBJECTIVES: There is a lack of evidence demonstrating the utility of computed tomography (CT) to predict chronic subdural hematoma (CSDH) clinical outcomes. We aim to analyze the role of tomographic volumetric analysis in patients with CSDH. METHODS: We performed a retrospective study of patients undergoing burr-hole craniostomy (BHC) for CSDH over five years at a tertiary care center. Degree of midline shift, radiographic density, subdural hematoma volume, acute blood volume, and third ventricle (3VV) and fourth ventricle (4VV) volume were estimated using semiautomatic segmentation of preoperative CT. Postoperative functional outcome was measured by two endpoints: National Institute of Health Stroke Scale (NIHSS) at discharge and short-term modified Rankin Scale (mRS) at 6-week follow-up. Univariate and multivariate analyses were performed using nonparametric tests. Discriminative capacity and optimal thresholds of independent variables were calculated by means of receiving-operative curves (ROC). RESULTS: A total of 79 patients were included for analysis with a median age of 78.5 years. Greater preoperative 3VV independently correlated with poor discharge NIHSS (p = .01) and short-term mRS (p = .03). A cutoff value of 0.545 mL demonstrated the highest sensitivity (77.1%) and specificity (88.8%) with an odds ratio for an mRS functional dependence of 9.29 (p = .001). CONCLUSIONS: Greater preoperative tomographic 3VV independently prognosticates poor discharge NIHSS and 6-week mRS. A threshold 3VV of 0.545 mL can be used to identify patients at higher risk of being dependent at first protocolized follow-up.

Using a Robotic-Assisted Approach for Stereotactic Laser Ablation Corpus Callosotomy: A Technical Report.

BACKGROUND: Corpus callosotomy for medically intractable epilepsy is an effective ablative procedure traditionally achieved using either standard open craniotomy or with less-invasive approaches. Advances in robotic-assisted stereotactic guidance for neurosurgery can be applied for LITT for corpus callosotomy. CLINICAL PRESENTATIONS: Two patients were included in this study. One was a 25-year-old female patient with extensive bi-hemispheric malformations of cortical development and medically refractory epilepsy, and the other was an 18-year-old male with medically refractory epilepsy and atonic seizures, who underwent a complete corpus callosotomy using robotic-assisted stereotactic guidance for LITT. RESULTS: Both patients underwent successful intended corpus callosotomy with volumetric analysis demonstrating a length disconnection of 74% and a volume disconnection of 55% for patient 1 and a length disconnection of 83% and a volume disconnection of 33% for patient 2. Postoperatively, both patients had clinical reductions in seizure. CONCLUSION: Our experience demonstrates that robotic guidance systems can safely and effectively be adapted for minimally invasive LITT corpus callosotomy.

Application of sodium fluorescein for spinal cord lesions: intraoperative localization for tissue biopsy and surgical resection.

Sodium fluorescein (NaFL) has been used to aid in the resection of primary and secondary lesions within the brain. Comparatively, there is limited research on clinical applications for lesions within the spinal cord. Fluorescein-guided microsurgery may increase the ability to localize and safely surgically treat spinal lesions. Twelve patients with spinal cord lesions received fluorescein sodium 10% (Alcon Laboratories INC, Fort Worth, TX, USA) at 3 mg/kg prior to surgical resection. Intraoperative visualization of fluorescence was performed using a Zeiss Pentero (Carl Zeiss AG, Oberkochen, Germany) microscope equipped with a Yellow560 filter or a Leica OH6 (Leica Microsystems, Wetzlar, Germany) equipped with a FL560 filter. Administration of NaFL resulted in lesional fluorescent contrast extravasation and facilitated surgical resection and localization in all twelve patients. In patients with a goal of complete resection, NaFL aided in complete resection of the spinal lesions in seven patients. In surgical resection patients, pathology was consistent with WHO grade I myxopapillary ependymoma in one patient, WHO grade II ependymoma in five patients, and nerve sheath tumor in one patient. In the other five patients, NaFL allowed for intraoperative tissue identification and successful tissue biopsy. In patients undergoing biopsy, tissue samples were positive for an intramedullary abscess, EBV-driven lymphoproliferative disease, and primary glial neoplasms. Fluorescein is a helpful microsurgical tool in guiding surgical resection and in the localization of intramedullary spinal lesions. Further research is necessary to explore fluorescein sodium applications in the resection of spinal cord lesions.

Endocrinological outcomes after transcranial resection of tuberculum sellae meningiomas: a systematic review and meta-analysis.

Tuberculum sellae meningiomas (TSMs) arise from the anterior skull base. Endocrine status after TSM resection is an important determinant of quality of life. We sought to better characterize the risk of postoperative endocrinopathy for patients with TSM undergoing open transcranial approach (TCA) microsurgical resection. A systematic review was conducted following MOOSE and PRISMA guidelines. Results were screened against predefined criteria, which included studies evaluating endocrinopathy rates after open transcranial microsurgery for TSM. Outcome incidence was calculated using random-effect meta-analysis of proportions. Eight studies met the inclusion criteria, comprising 406 patients. The average age of the cohort was 52.2 years, and a majority (70%) of the patients were female. The pooled incidence of postoperative transient diabetes insipidus (DI) was 7.5% (95% CI 2.9-12%; p = 0.001; I2 = 75.9%) and permanent DI was 1.6% (95% CI 0.3-2.7%; p = 0.01; I2 = 0%). The pooled rate of postoperative hypopituitarism was 3.6% (95% CI 1.6-5.7%; p < 0.001; I2 = 22.2%), while the incidence of hyperprolactinemia was 1.3% (95% CI 0.1 = 2.6%; p = 0.036; I2 = 8.74%). The incidence of SIADH was 4% in one study but was not included in the meta-analysis. Endocrinopathy after TSM microsurgical resection is rare, but the available studies' poor quality of evidence and inconsistent methodology may reflect that it is underreported in the literature. Nevertheless, clinicians should consider the risk of hormonal impairment and counsel their patients accordingly when selecting a TCA for these lesions.

Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series.

OBJECTIVE: Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution's experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e., the trigeminal nerve, offending tumor, or both. METHODS: Between the years 2009 and 2021, 21 patients with TN secondary to benign (n = 13) or malignant (n = 8) tumors underwent SRS. Barrow Neurological Institute (BNI) pain intensity scale scores were collected from patient electronic medical records at baseline, initial follow-up, and 1 and 3 years post-SRS. The interval change in BNI scale score (ΔBNI) at the various follow-up time points was also calculated to assess the durability of pain relief following SRS. RESULTS: The median follow-up period was 24 (range 0.5-155) months. Five patients (24%) received treatment to the trigeminal nerve only, 10 (48%) received treatment to the tumor only, and 6 (29%) had treatment to both the nerve and tumor. The overall radiation dosage ranged from 14 to 60 Gy delivered in 1-5 fractions, with a median overall dose of 26 Gy. The median dose to the tumor was 22.5 (range 14-35) Gy, delivered in 1-5 fractions. Of the treatments targeting the tumor, 25% were delivered in a single fraction with doses ranging from 14 to 20 Gy, 60% were delivered in 3 fractions with doses ranging from 18 to 27 Gy, and 15% were delivered in 5 fractions with doses ranging from 25 to 35 Gy. The most common dose regimen for tumor treatment was 24 Gy in 3 fractions. The median biologically effective dose (with an assumed alpha/beta ratio of 10 [BED10]) for tumor treatments was 43.1 (range 13.3-60.0) Gy. There was a significant difference in the proportion of patients with recurrent pain (ΔBNI score ≥ 0) at the time of last follow-up across the differing SRS treatment targets: trigeminal nerve only, tumor only, or both (p = 0.04). At the time of last follow-up, the median ΔBNI score after SRS to the nerve only was -1, 0 after SRS to tumor only, and -2 after SRS to both targets. CONCLUSIONS: SRS offers clinical symptomatic benefit to patients with TN secondary to tumor. For optimal pain relief and response durability, treatment targeting both the tumor and the trigeminal nerve appears to be most advantageous.

Hydroxyapatite cement cranioplasty for reconstruction of translabyrinthine approach: aesthetic results, long-term satisfaction, quality of life, and complications.

BACKGROUND: Translabyrinthine approaches (TLAs) for resection of skull base neoplasms are complex with variable reconstruction techniques. Fat grafts in conjunction with hydroxyapatite bone cement techniques have seldom been described in terms of possible superiority to other skull base reconstruction techniques. We sought to determine the impact of this skull base reconstruction technique on clinical outcomes and patient's satisfaction. METHOD: We performed a retrospective analysis of all patients who underwent translabyrinthine approaches for resection of CPA lesions over a 5-year period. Both post-op objective and subjective markers of reconstruction, as well as postoperative complications, were collected and analyzed. RESULTS: Sixty-nine patients were included, 34 underwent reconstruction with hydroxyapatite and fat (rHAC) and 35 with fat alone (rF). rHAC was associated with fewer cranial wound superficial infection/dehiscence (0% vs 14.3%; p = 0.029) and shorter length of stay (mean ± standard deviation) (6.9 ± 7.4 vs 4.4 ± 3.7 days, p = 0.008). Postoperative subjective characterization of rHAC demonstrated improved satisfaction scores (1.38 ± 0.5 vs 1.83 ± 1; p = 0.049) and fewer reports of post-operative irregularities (11.5% vs 37.5%; p = 0.017). CONCLUSION: The use of hydroxyapatite for cranial reconstruction after translabyrinthine approaches has improved patient satisfaction and decreased cranial defects in our small series. Postoperative complications are consistent with other described methods, but with shorter hospital stay, decreased risk of superficial wound dehiscence/infection, and a perceived superiority in preventing percutaneous post-op CSF leaks.

Long-term disease control and treatment outcomes of stereotactic radiosurgery in cavernous sinus meningiomas.

BACKGROUND: Most of the current knowledge on the clinical effects of stereotactic radiosurgery (SRS) on the treatment of cavernous sinus meningiomas (CSM) is based on series with limited follow-up. However, determining the role of radiation in a tumor with slow disease progression such as CSM necessitates long term follow up. OBJECTIVE: To review and pool metadata in the literature to determine the long-term outcomes of SRS with respect to clinical and radiographic tumor control of CSM. METHODS: A systematic search was conducted following MOOSE guidelines. Results were screened against predefined criteria, which excluded studies with a median follow-up less than 5 years. The incidences of each outcome were calculated using random-effects metanalysis of proportions. RESULTS: Seven studies met the inclusion criteria, comprising 645 patients. The median follow-up was 74 months (range 62-87). Progression-free-survival at 5, 10, and 15 years was 93.4% (95% CI 89.1-96.7%), 84.9% (95% CI 77-91.4%), and 81.3% (95% CI 74-87.7%), respectively. Clinical response to SRS at last follow-up defined as improvement of cranial nerve deficits was found in in 36.4% (95% CI 26.3-47.1%) of patients, while worsening or onset of new cranial nerve deficits was found in 11.5% (95% CI 7.9-15.7%). Radiological regression was found in 57.8% (95% CI 43-71.8%), while tumor progression was found in 8.5% (95% CI 5.2-12.6%). CONCLUSION: SRS achieves excellent disease control and radiographic response in CSM. Although the risk of long-term cranial neuropathies is minimal, it is relatively higher to what has been previously reported in early series with limited follow-up.

The 100 most-cited articles on vestibular schwannoma: historical perspectives, current limitations, and future research directions.

There has been a steady increase of vestibular schwannoma (VS) research in the body of literature. To delineate the most impactful works on VS, a bibliometric analysis is warranted. The Thomson Reuters Web of Sciences database was queried to identify all articles on VS published to June 2020. The articles were sorted in descending order of the number of citations. Titles and abstracts of the top 100 most-cited articles were screened to identify the research area, publication year, author, and country of publication. Our query yielded 6477 research publications. The 100 most-cited articles were cited 15804 times. The most productive decade was the 1990s (40% of the top 100 articles). Twenty-five journals contributed to all included articles. Journal of Neurosurgery contributed most of the articles (20%). Most common contributing country was the USA (60%). "Operative treatment" was the most common research topic (68%), followed by other aspects such as medical management (13%), epidemiology (12%), diagnosis (5%), or translational medicine (2%). The current analysis highlights the importance of the multimodal approach in the study and treatment of VS. While emphasizing the relevance of including highly cited articles in the current education of VS, our results point out the deficiency in certain research areas with high impact in other fields of neuro-oncology, such as translational medicine and molecular epigenetics.

Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire.

Although immune signaling has emerged as a defining feature of the glioma microenvironment, how the underlying structure of the glioma-infiltrating T-cell population differs from that of the blood from which it originates has been difficult to measure directly in patients. High-throughput sequencing of T-cell receptor (TCR) repertoires (TCRseq) provides a population-wide statistical description of how T cells respond to disease. We have defined immunophenotypes of whole repertoires based on TCRseq of the α- and ß-chains from glioma tissue, nonneoplastic brain tissue, and peripheral blood from patients. Using information theory, we partitioned the diversity of these TCR repertoires into that from the distribution of VJ cassette combinations and diversity due to VJ-independent factors, such as selection due to antigen binding. Tumor-infiltrating lymphocytes (TILs) possessed higher VJ-independent diversity than nonneoplastic tissue, stratifying patients according to tumor grade. We found that the VJ-independent components of tumor-associated repertoires diverge more from their corresponding peripheral repertoires than T-cell populations in nonneoplastic brain tissue, particularly for low-grade gliomas. Finally, we identified a "signature" set of TCRs whose use in peripheral blood is associated with patients exhibiting low TIL divergence and is depleted in patients with highly divergent TIL repertoires. This signature is detectable in peripheral blood, and therefore accessible noninvasively. We anticipate that these immunophenotypes will be foundational to monitoring and predicting response to antiglioma vaccines and immunotherapy.

Preservation of olfaction in anterior midline skull base meningiomas: a comprehensive approach.

BACKGROUND: Olfaction is an undervalued sense in neurosurgery. Attempted surgical resection of anterior cranial fossa meningiomas puts the olfactory pathway at risk. Preservation of olfaction may increase the postoperative quality of life. Objective assessment of olfaction may inform clinical decision-making and influence the selection of operative approaches for surgical resection. METHODS: We reviewed all patients who underwent surgical resection for midline anterior skull base meningiomas from July 1, 2014, through December 31, 2017. Patient demographics, tumor size, operative approach, pre- and postoperative deficits, and Simpson grade were collected and analyzed. Postoperative olfaction was assessed by clinical evaluation as well as objective evaluation using the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Twenty-eight patients (10 male, 18 female) were included with an average age of 53.8 years (range 27-80 years). Twenty-six patients underwent craniotomy for resection, while 2 patients had endoscopic approaches. Average tumor volume was 402.1 cm3 (6.6-2507.7 cm3). Preoperatively, five patients (17.8%) presented with olfactory impairment. Objectively, 50% of patients (14/28) consented and completed the UPSIT. The average postoperative UPSIT score was 25.8/40 (9/40-38/40). Two patients not identified on clinical assessment alone demonstrated postoperative olfactory deficit on UPSIT (2/14). CONCLUSION: There are limited published studies evaluating olfaction in patients who undergo skull-based approaches for anterior fossa meningiomas. Our series showed the highest olfaction preservation rate (87.5%) using a comprehensive strategy and multitude of surgical approaches based on the olfactory function and tumor characteristics.

Correction to: Preservation of olfaction in anterior midline skull base meningiomas: a comprehensive approach.

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Biomarkers for glioma immunotherapy: the next generation.

The term "biomarker" historically refers to a single parameter, such as the expression level of a gene or a radiographic pattern, used to indicate a broader biological state. Molecular indicators have been applied to several aspects of cancer therapy: to describe the genotypic and phenotypic state of neoplastic tissue for prognosis, to predict susceptibility to anti-proliferative agents, to validate the presence of specific drug targets, and to evaluate responsiveness to therapy. For glioblastoma (GBM), immunohistochemical and radiographic biomarkers accessible to the clinical lab have informed traditional regimens, but while immunotherapies have emerged as potentially disruptive weapons against this diffusely infiltrating, heterogeneous tumor, biomarkers with strong predictive power have not been fully established. The cancer immunotherapy field, through the recently accelerated expansion of trials, is currently leveraging this wealth of clinical and biological data to define and revise the use of biomarkers for improving prognostic accuracy, personalization of therapy, and evaluation of responses across the wide variety of tumors. Technological advancements in DNA sequencing, cytometry, and microscopy have facilitated the exploration of more integrated, high-dimensional profiling of the disease system-incorporating both immune and tumor parameters-rather than single metrics, as biomarkers for therapeutic sensitivity. Here we discuss the utility of traditional GBM biomarkers in immunotherapy and how the impending transformation of the biomarker paradigm-from single markers to integrated profiles-may offer the key to bringing predictive, personalized immunotherapy to GBM patients.

Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways.

Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer.

Preoperative ethmoid artery ligation facilitates resection of large sub-frontal meningiomas.

Optimal vascular control during neurosurgical resection of large sub-frontal meningioma is hindered by limited early access to the ethmoidal arteries. Pre-operative ligation of the ethmoidal arteries 1) induces tumor necrosis simplifying resection and 2) minimizes blood loss and operative time. Early arterial ligation is an advantage of endoscopic approaches to transnasal resection of anterior skull base meningiomas that is not appreciated in open approaches with larger meningioma. Here we present a case of a colossal meningioma where minimally invasive pre-operative ligation of ethmoidal arteries prior to a traditional open surgical approach allowed for improved vascular control and decreased surgical time.

Immunocompetent isolated cerebral mucormycosis presenting with obstructive hydrocephalus: illustrative case.

BACKGROUND: Isolated cerebral mucormycosis is rare in immunocompetent adults and is only sparsely reported to be associated with obstructive hydrocephalus. OBSERVATIONS: Here, the authors report a case of obstructive hydrocephalus secondary to central nervous system mucormycosis without other systems or rhino-orbital involvement and its technical surgical management. A 23-year-old, incarcerated, immunocompetent patient with history of intravenous (IV) drug use presented with syncope. Although clinical and radiographic findings failed to elucidate an infectious pathology, endoscopy revealed an obstructive mass lesion at the level of the third ventricle, which, on microbiological testing, was confirmed to be Rhizopus fungal ventriculitis. Perioperative cerebrospinal fluid diversion, endoscopic third ventriculostomy, endoscopic biopsy technique, patient outcomes, and the literature are reviewed here. The patient received intrathecal and IV amphotericin B followed by a course of oral antifungal treatment and currently remains in remission. LESSONS: The patient's unique presentation and diagnosis of isolated cerebral mucormycosis reveal this pathogen as a cause of ventriculitis and obstructive hydrocephalus in immunocompetent adult patients, even in the absence of infectious sequelae on neuroimaging.