Preoperative meningioma vascularity index is associated with significantly increased intraoperative blood loss and greater risk of subtotal resection.

OBJECTIVE: Surgical recovery of meningiomas relies on a variety of factors, including tumor volume, vascularity, embolization status, and blood loss during excision. Although hypervascular meningiomas can potentially be amendable to embolization, methods for determining optimal vascularity for this procedure are currently lacking. Our group previously established the meningioma vascularity index (MVI) as a marker of tumor vascularity. In this study, we aim to build on our previous work and further examine the relationship between MVI and intraoperative estimated blood loss (EBL). METHODS: A retrospective data extraction was conducted between August 2010 and October 2019 from patients undergoing craniotomy for meningioma. Of the 85 intracranial meningiomas included, 39 were embolized. Demographic data, extent of resection, embolization status, and EBL were among the extracted variables. Flow void volumes were measured on T2-weighted MRI images using a segmentation software with a voxel-based segmentation method. RESULTS: MVI was a predictor of EBL within the entire cohort, when controlling for tumor volume (R2 adjusted = 0.26; P = 0.027). A high MVI (> 2.01 cm3) was associated with higher likelihood of receiving subtotal resection (STR) (OR 4.07, 95% CI 1.17-14.15; P = 0.035). Although the mean MVI and tumor volume were higher in the embolized cohort (P = 0.009 and P = 0.005), there were no significant differences in EBL, or blood transfusion rates regardless of embolization status. CONCLUSIONS: MVI may be used as a non-invasive radiological marker to gauge meningioma vascularity, predict EBL, and guide the decision-making process when it comes to embolization and surgical planning.

Modern surgical management of incidental gliomas.

PURPOSE: Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may experience no tumor-related symptoms and be incidentally diagnosed. These incidental low-grade gliomas (iLGG) maintain controversial treatment course despite scientific advancements. Here we highlight the recent advancements in classification, neuroimaging, and surgical management of these tumors. METHODS: A review of the literature was performed. The authors created five subtopics of focus: histological criteria, diagnostic imaging, surgical advancements, correlation of surgical resection and survival outcomes, and clinical implications. CONCLUSIONS: Alternating studies suggest that these tumors may experience higher mutational rates than their counterparts. Significant progress in management of gliomas, regardless of the grade, has been made through modern neurosurgical treatment modalities, diagnostic neuroimaging, and a better understanding of the genetic composition of these tumors. An optimal treatment approach for patients with newly diagnosed iLGG remains ill-defined despite multiple studies arguing in favor of safe maximal resection. Our review emphasizes the not so benign nature of incidental low grade glioma and further supports the need for future studies to evaluate survival outcomes following surgical resection.

Endoscopic endonasal approach for resection of a recurrent spheno-orbital meningioma resulting in complete resolution of visual symptoms: A case report and review of literature.

PURPOSE: Spheno-orbital meningiomas are rare tumors, accounting for up to 9% of all intracranial meningiomas. Patients commonly present with proptosis, and visual deficits. These slow growing tumors are hard to resect due to extension into several anatomical compartments, resulting in recurrence rates as high as 35-50%. Although open surgical approaches have been historically used for resection, a handful of endoscopic approaches have been reported in recent years. We aimed to review the literature and describe a case of spheno-orbital meningioma with severe vision loss which was resected with an endoscopic endonasal approach achieving complete resolution of visual symptoms. METHODS: A systematic review of literature was conducted in accordance with the PRISMA guidelines. PubMed, Cochrane, and Web of Science databases were queried for spheno-orbital meningiomas resected via an endoscopic endonasal approach. Furthermore, the presentation, surgical management, and post-operative outcomes of a 53-year-old female with a recurrent spheno-orbital meningioma are described. RESULTS: The search yielded 26 articles, of which 8 were included, yielding 19 cases. Average age at presentation was 60.5 years (range: 44-82), and 68.4% of patients were female. More than half of the cases achieved subtotal resection. Common complications associated with endoscopic endonasal surgery included CN V2 or CN V2/V3 hypoesthesia. Following surgical intervention, visual acuity and visual field remained stable or improved in the majority of the patients. CONCLUSION: Endoscopic approaches are slowly gaining momentum for treatment of spheno-orbital meningiomas. Further studies on the clinical benefits of this approach on patient outcomes and post-operative complications is warranted.

Lumbar spinal ganglion cyst: A systematic review with case illustration.

PURPOSE: Ganglion cysts are benign soft tissue lesions found in joints, most commonly wrists. The incidence for juxtafacet cysts, the condition under which spinal ganglion cysts are categorized, is between 0.06% and 5.8%. Spinal ganglion cysts often arise in the most mobile segment of the lumbar spine, L4-L5. Patients commonly present with pain, radiculopathy, and weakness. Conservative management is used, but surgical resection is the most common treatment modality. We aim to review the literature and present a rare case of an L2-L3 situated spinal ganglion cyst, treated with maximal safe resection. METHODS: A systematic review of literature was conducted in accordance with PRISMA guidelines. PubMed, Web of Science, and Cochrane databases were queried using Boolean operators and search terms, "spinal ganglion cyst, lumbar ganglion cyst, and lumbar juxtafacet cyst". Presentation, surgical management, and postoperative course of a 29-year-old male with an L2-L3 spinal ganglion cyst are also described. RESULTS: The search yielded 824 articles; 23 met inclusion criteria. These papers consisted of 27 spinal ganglion cyst cases with disaggregated patient data. 63.0% of patients were male, and 53.4 years (range: 23-86) was the average age at presentation. Mean symptom duration was 1.9 years (range: 3 days-12 years). 70.4% of patients reported complete symptom resolution. 14.8% of cases noted neural foramen involvement. CONCLUSIONS: Spinal ganglion cysts are benign lesions typically presenting with radiculopathy. Maximal safe resection is an effective treatment modality with low complication rates. Future studies are needed to understand if neural foramen involvement leads to increased symptom severity.

The cellular prion protein interacts with and promotes the activity of Na,K-ATPases.

The prion protein (PrP) is best known for its ability to cause fatal neurodegenerative diseases in humans and animals. Here, we revisited its molecular environment in the brain using a well-developed affinity-capture mass spectrometry workflow that offers robust relative quantitation. The analysis confirmed many previously reported interactions. It also pointed toward a profound enrichment of Na,K-ATPases (NKAs) in proximity to cellular PrP (PrPC). Follow-on work validated the interaction, demonstrated partial co-localization of the ATP1A1 and PrPC, and revealed that cells exposed to cardiac glycoside (CG) inhibitors of NKAs exhibit correlated changes to the steady-state levels of both proteins. Moreover, the presence of PrPC was observed to promote the ion uptake activity of NKAs in a human co-culture paradigm of differentiated neurons and glia cells, and in mouse neuroblastoma cells. Consistent with this finding, changes in the expression of 5'-nucleotidase that manifest in wild-type cells in response to CG exposure can also be observed in untreated PrPC-deficient cells. Finally, the endoproteolytic cleavage of the glial fibrillary acidic protein, a hallmark of late-stage prion disease, can also be induced by CGs, raising the prospect that a loss of NKA activity may contribute to the pathobiology of prion diseases.

Superior Semicircular Canal Dehiscence Revision Surgery Outcomes: A Single Institution's Experience.

BACKGROUND: Superior semicircular canal dehiscence (SSCD) is an abnormality of the otic capsule, which normally overlies the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. Given the complexity of the disease, there are patients who experience less favorable surgical outcomes and require revision surgery. The purpose of this study was to report to the rate of postoperative symptomatic improvement in patients who required revision surgery. METHODS: A retrospective analysis of patients undergoing SSCD surgical repair at a single institution was performed. Information on patient demographics, primary and secondary surgical approaches, surgical outcomes, and follow-up length was collected. RESULTS: Seventeen patients underwent 20 revision surgeries. There were eleven (65%) females and six (35%) males. Mean age of the cohorts was 50 years (range 30-68 years), and mean follow-up length was 6.8 months (range 0.1-31.1 months). Cerebrospinal fluid leak was noted in 67% of cases. The greatest postoperative symptomatic resolution was reported in oscillopsia (100%), headache (100%), and internal sound amplification (71%), while the least postoperative symptomatic resolution was reported in tinnitus (42%), aural fullness (40%), and dizziness (29%). CONCLUSIONS: Revision surgery can provide symptomatic improvement in select SSCD patients; however, patients should be cautioned about the possibility of less favorable outcomes than in index surgery. Revision surgeries are associated with a considerably higher rate of perioperative cerebrospinal fluid leak.

HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis.

BACKGROUND: Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). RESULTS: A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39-0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27-1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12-27%), intracranial disease control rate 62% (95% CI, 55-69%), intracranial complete response rate 0% (95% CI, 0-0.01%), and grade 3+ adverse event rate 26% (95% CI, 11-45%). Risk of bias was high in 40% (39/97) of studies. CONCLUSION: These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

The prion protein is embedded in a molecular environment that modulates transforming growth factor ß and integrin signaling.

At times, it can be difficult to discern if a lack of overlap in reported interactions for a protein-of-interest reflects differences in methodology or biology. In such instances, systematic analyses of protein-protein networks across diverse paradigms can provide valuable insights. Here, we interrogated the interactome of the prion protein (PrP), best known for its central role in prion diseases, in four mouse cell lines. Analyses made use of identical affinity capture and sample processing workflows. Negative controls were generated from PrP knockout lines of the respective cell models, and the relative levels of peptides were quantified using isobaric labels. The study uncovered 26 proteins that reside in proximity to PrP. All of these proteins are predicted to have access to the outer face of the plasma membrane, and approximately half of them were not reported to interact with PrP before. Strikingly, although several proteins exhibited profound co-enrichment with PrP in a given model, except for the neural cell adhesion molecule 1, no protein was highly enriched in all PrP-specific interactomes. However, Gene Ontology analyses revealed a shared association of the majority of PrP candidate interactors with cellular events at the intersection of transforming growth factor ß and integrin signaling.

A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition.

The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1. ZIP6 also interacts with ZIP10 and the two ZIP transporters exhibit interdependency during their expression. ZIP6 contributes to the integration of NCAM1 in focal adhesion complexes but, unlike cells lacking PrP, ZIP6 deficiency does not abolish polysialylation of NCAM1. Instead, ZIP6 mediates phosphorylation of NCAM1 on a cluster of cytosolic acceptor sites. Substrate consensus motif features and in vitro phosphorylation data point toward GSK3 as the kinase responsible, and interface mapping experiments identified histidine-rich cytoplasmic loops within the ZIP6/ZIP10 heteromer as a novel scaffold for GSK3 binding. Our data suggests that PrP and ZIP6 inherited the ability to interact with NCAM1 from their common ZIP ancestors but have since diverged to control distinct posttranslational modifications of NCAM1.

Strains of Pathological Protein Aggregates in Neurodegenerative Diseases.

The presence of protein aggregates in the brain is a hallmark of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Considerable evidence has revealed that the pathological protein aggregates in many neurodegenerative diseases are able to self-propagate, which may enable pathology to spread from cell-to-cell within the brain. This property is reminiscent of what occurs in prion diseases such as Creutzfeldt-Jakob disease. A widely recognized feature of prion disorders is the existence of distinct strains of prions, which are thought to represent unique protein aggregate structures. A number of recent studies have pointed to the existence of strains of protein aggregates in other, more common neurodegenerative illnesses such as AD, PD, and related disorders. In this review, we outline the pathobiology of prion strains and discuss how the concept of protein aggregate strains may help to explain the heterogeneity inherent to many human neurodegenerative disorders.