Anterolateral keyhole transorbital routes to the skull base: a comparative anatomical study.

OBJECTIVE: Although keyhole transorbital approaches are gaining traction, their indications have not been adequately studied comparatively. In this study the authors have defined them also as transwing approaches-meaning that they use the different facies of the sphenoid wing for cranial entry-and sought to compare the four major ones: 1) lateral orbitocraniotomy through a lateral canthal incision (LatOrb); 2) modified orbitozygomatic approach through a palpebral incision (ModOzPalp); 3) modified orbitozygomatic approach through an eyebrow incision (ModOzEyB); and 4) supraorbital craniotomy through an eyebrow incision (SupraOrb), coupled with its expanded version (SupraTransOrb). METHODS: Cadaveric dissections were performed at the neuroanatomy lab. To delineate the skull base exposure, four formalin-fixed heads were used, with two sides dedicated to each approach. The outer limits were assessed via image guidance and were mapped and illustrated accordingly. A fifth head was dissected purely endoscopically, just to facilitate an overview of the transwing concept. Qualitative features were also rigorously examined. RESULTS: The LatOrb proves to be more versatile in the middle cranial fossa (MCF), whereas the anterior cranial fossa (ACF) exposure is limited to a small area above the sphenoid ridge. An anterior clinoidectomy is possible; however, the exposure of the roof of the optic canal is suboptimal. The ModOzPalp adequately exposes both the ACF and MCF. Its lateral trajectory allows the inferior to superior view, yet there is restricted access to the medial anterior skull base (olfactory groove). The ModOzEyB also provides extensive exposure of the ACF and MCF, but has a more superior to inferior trajectory compared to the ModOzPalp, making it more appropriate for pathology reaching the medial anterior skull base or even the contralateral side. The anterior clinoidectomy is performed with improved visualization of the optic canal. The SupraOrb provides mainly anterior cranial base exposure, with minimal middle fossa. An anterior clinoidectomy can be performed, but without any direct observation of the superior orbital fissure. Some MCF access can be accomplished if the lateral sphenoid wing is drilled inferiorly, leading to its highly versatile variant, the SupraTransOrb. CONCLUSIONS: All the aforementioned approaches use the sphenoid wing as skull base corridor from a specific orientation point; hence these are designated as transwing approaches. Their peculiarities mandate careful case selection for the effective and safe completion of the surgical goals.

The effect of thermal therapy on the blood-brain barrier and blood-tumor barrier.

The blood-brain and blood-tumor barriers represent highly specialized structures responsible for tight regulation of molecular transit into the central nervous system. Under normal circumstances, the relative impermeability of the blood-brain barrier (BBB) protects the brain from circulating toxins and contributes to a brain microenvironment necessary for optimal neuronal function. However, in the context of tumors and other diseases of central nervous system, the BBB and the more recently appreciated blood-tumor barrier (BTB) represent barriers that prevent effective drug delivery. Overcoming both barriers to optimize treatment of central nervous system diseases remains the subject of intense scientific investigation. Although many newer technologies have been developed to overcome these barriers, thermal therapy, which dates back to the 1890 s, has been known to disrupt the BBB since at least the early 1980s. Recently, as a result of several technological advances, laser interstitial thermal therapy (LITT), a method of delivering targeted thermal therapy, has gained widespread use as a surgical technique to ablate brain tumors. In addition, accumulating evidence indicates that laser ablation may also increase local BBB/BTB permeability after treatment. We herein review the structure and function of the BBB and BTB and the impact of thermal injury, including LITT, on barrier function.

Laser Interstitial Thermal Therapy.

Laser interstitial thermal therapy (LITT) is a minimally invasive and cytoreductive neurosurgical technique that has gained significant momentum in the last decade. Several technological enhancements such as MRI thermometry and improved laser probe design have enabled feasibility and improved the safety of LITT procedures. Numerous reports have been published describing the treatment of lesions ranging from tumors to epileptogenic foci, but the indications for LITT continue to evolve. We describe the general physical and biological concepts underlying LITT, clinical workflow, and established and emerging indications.

T2-Weighted-Fluid-Attenuated Inversion Recovery Hyperintensity on Magnetic Resonance Imaging Is Associated With Aggressive Symptoms in Patients With Dural Arteriovenous Fistulas.

Background and Purpose- Several angiographic factors of dural arteriovenous fistulas (dAVFs) are associated with aggressive presentation and poor natural history. We examined the association of magnetic resonance imaging T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) hyperintensity with aggressive presentation. Methods- A cohort of dAVF patients from 2 centers was retrospectively examined. T2/FLAIR hyperintensity was determined by blinded, de-identified review and compared with angiographic grade and presenting symptoms. Results- T2/FLAIR hyperintensity was only identified in dAVF patients with cortical venous drainage (CVD). Among patients with CVD, those with T2/FLAIR hyperintensity were more likely to present with aggressive symptoms (20/23, 87.0%) than those without (6/21, 28.5%), P<0.001. All cured dAVFs with symptom resolution and available post-treatment imaging had resolution of T2/FLAIR hyperintensity. Conclusions- T2/FLAIR hyperintensity strongly correlates with aggressive presentation and CVD in dAVF patients, and may identify a subset that would benefit from early treatment.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Comparative cost analysis of endovascular and open approaches for elective treatment of middle cerebral artery aneurysms.

BACKGROUND: Intracranial aneurysms of the middle cerebral artery can be treated using several open surgical and endovascular approaches. Given the growing evidence of clinical equipoise between these various treatment strategies, there is a need to assess the costs associated with each. METHODS: Cost of aneurysm treatment was divided into two categories for comparison. "Initial cost" comprised the total in-hospital expenses for initial aneurysm treatment and "total cost" comprised initial aneurysm treatment and all expenses relating to readmission due to treatment-related complications, prescribed catheter angiograms for monitoring of treatment stability, and any retreatments needed for a given aneurysm. The open surgical group was subdivided into a pterional approach group and a lateral supraorbital (LSO) approach group for. RESULTS: Median initial cost was $37,152 (IQR $31,318-$44,947) for aneurysms treated with the pterional approach, $29,452 (IQR $27,779-$32,826) for aneurysms treated with the LSO approach, and $19,587 (IQR $14,125-$30,521) for aneurysms treated with endovascular approaches. The median total cost was $39,737 (IQR $33,891-$62,259) for aneurysms treated with the pterional approach, $31,785 (IQR $29,513-$41,099) for aneurysms treated with the LSO approach, and $24,578 (IQR $18,977-$34,547) for aneurysms treated with endovascular approaches. Analysis of variance test demonstrated variance across groups for both initial and total cost (p = 0.004, p = 0.008, respectively). In our subsequent analysis, initial cost and total cost were higher in the pterional group than the endovascular group (p = 0.003 and p = 0.006, respectively). CONCLUSIONS: Endovascular treatment of elective aneurysms has a significantly lower cost than open surgical treatment with the pterional approach, but not with the LSO approach. For aneurysms not amenable to endovascular treatment, a minimally invasive LSO approach carries a lower cost burden than a pterional approach.

Identification and Management of Aggressive Meningiomas.

Meningiomas are common primary central nervous system tumors derived from the meninges, with management most frequently entailing serial monitoring or a combination of surgery and/or radiation therapy. Although often considered benign lesions, meningiomas can not only be surgically inaccessible but also exhibit aggressive growth and recurrence. In such cases, adjuvant radiation and systemic therapy may be required for tumor control. In this review, we briefly describe the current WHO grading scale for meningioma and provide demonstrative cases of treatment-resistant meningiomas. We also summarize frequently observed molecular abnormalities and their correlation with intracranial location and recurrence rate. We then describe how genetic and epigenetic features might supplement or even replace histopathologic features for improved identification of aggressive lesions. Finally, we describe the role of surgery, radiotherapy, and ongoing systemic therapy as well as precision medicine clinical trials for the treatment of recurrent meningioma.

Corrigendum: Identification and management of aggressive meningiomas.

[This corrects the article DOI: 10.3389/fonc.2022.851758.].

Surgical management of colloid cysts of the third ventricle: a single-institution comparison of endoscopic and microsurgical resection.

OBJECTIVE: Colloid cysts of the third ventricle are histologically benign lesions that can cause obstructive hydrocephalus and death. Historically, colloid cysts have been removed by open microsurgical approaches. More recently, minimally invasive endoscopic and port-based techniques have offered decreased complications and length of stay, with improved patient satisfaction. METHODS: A single-center retrospective analysis of patients with colloid cysts who underwent surgery at a large tertiary care hospital was performed. The cohort was assessed based on the surgical approach, comparing endoscopic resection to open microsurgical resection. The primary endpoint was rate of perioperative complications. Univariate analysis was used to assess several procedure-related variables and the cost of treatment. Multivariate analysis was used to assess predictors of perioperative complications. Total inpatient cost for each case was extracted from the health system financial database. RESULTS: The study included 78 patients with colloid cysts who underwent resection either via an endoscopic approach (n = 33) or through a craniotomy (n = 45) with an interhemispheric-transcallosal or transcortical-transventricular approach. Nearly all patients were symptomatic, and half had obstructive hydrocephalus. Endoscopic resection was associated with reduced operative time (3.2 vs 4.9 hours, p < 0.001); lower complication rate (6.1% vs 33.1%, p = 0.009); reduced length of stay (4.1 vs 8.9 days, p < 0.001); and improved discharge to home (100% vs 75.6%, p = 0.008) compared to microsurgical resection. Coagulated residual cyst wall remnants were more common after endoscopic resection (63.6% vs 19.0%, p < 0.001) although this was not associated with a significantly increased rate of reoperation for recurrence. The mean follow-up was longer in the microsurgical resection group (3.1 vs 4.9 years, p = 0.016). The total inpatient cost of endoscopic resection was, on average, one-half (47%) that of microsurgical resection. When complications were encountered, the total inpatient cost of microsurgical resection was 4 times greater than that of endoscopic resection where no major complications were observed. The increased cost-effectiveness of endoscopic resection remained during reoperation. CONCLUSIONS: Endoscopic resection of colloid cysts of the third ventricle offers a significant reduction in perioperative complications when compared to microsurgical resection. Endoscopic resection optimizes nearly all procedure-related variables compared to microsurgical resection, and reduces total inpatient cost by > 50%. However, endoscopic resection is associated with a significantly increased likelihood of residual coagulated cyst wall remnants that could increase the rate of reoperation for recurrence. Taken together, endoscopic resection represents a safe and effective minimally invasive approach for removal of colloid cysts.

Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response.

BACKGROUND: Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples. METHODS: Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers. RESULTS: In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples. CONCLUSIONS: Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura.

Resting-State Functional Magnetic Resonance Imaging Networks as a Quantitative Metric for Impact of Neurosurgical Interventions.

Objective: Resting-state functional MRI (rs-fMRI) has been used to evaluate brain network connectivity as a result of intracranial surgery but has not been used to compare different neurosurgical procedures. Laser interstitial thermal therapy (LITT) is an alternative to conventional craniotomy for the treatment of brain lesions such as tumors and epileptogenic foci. While LITT is thought of as minimally invasive, its effect on the functional organization of the brain is still under active investigation and its impact on network changes compared to conventional craniotomy has not yet been explored. We describe a novel computational method for quantifying and comparing the impact of two neurosurgical procedures on brain functional connectivity. Methods: We used a previously described seed-based correlation analysis to generate resting-state network (RSN) correlation matrices, and compared changes in correlation patterns within and across RSNs between LITT and conventional craniotomy for treatment of 24 patients with singular intracranial tumors at our institution between 2014 and 2017. Specifically, we analyzed the differences in patient-specific changes in the within-hemisphere correlation patterns of the contralesional hemisphere. Results: In a post-operative follow-up period up to 2 years within-hemisphere connectivity of the contralesional hemisphere after surgery was more highly correlated to the pre-operative state in LITT patients when compared to craniotomy patients (P = 0.0287). Moreover, 4 out of 11 individual RSNs demonstrated significantly higher degrees of correlation between pre-operative and post-operative network connectivity in patients who underwent LITT (all P < 0.05). Conclusion: Rs-fMRI may be used as a quantitative metric to determine the impact of different neurosurgical procedures on brain functional connectivity. Global and individual network connectivity in the contralesional hemisphere may be more highly preserved after LITT when compared to craniotomy for the treatment of brain tumors.

Long, Noncoding RNA Dysregulation in Glioblastoma.

Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs. Of these transcripts, the majority-long, noncoding RNAs (lncRNAs)-are greater than 200 nucleotides in length and are necessary for various roles in the cell. It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs. Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging. The cooperation between genetic and epigenetic alterations drives rapid adaptation that allows therapeutic evasion and recurrence. Given the large repertoire of lncRNAs in normal brain tissue and the well-described roles of lncRNAs in molecular and cellular processes, these transcripts are important to consider in the context of GBM heterogeneity and treatment resistance. Herein, we review the general mechanisms and biological roles of lncRNAs, with a focus on GBM, as well as RNA-based therapeutics currently in development.

Clinical Staging to Estimate the Probability of Severe Postoperative Complications in Patients With Vestibular Schwannoma.

Importance: Vestibular schwannomas have long been treated as a homogeneous entity. Clinical symptoms at presentation may help elucidate the underlaying pathophysiologic characteristics of tumor subtypes. Describing the heterogeneity of these benign tumors may assist in predicting clinical outcomes associated with their treatment. Objective: To create a tumor staging system that incorporates symptoms at presentation and tumor size to predict severe surgical complications. Design, Setting, and Participants: A retrospective cohort of patients at a single-center tertiary referral center from January 1, 1998, to October 13, 2020, was studied. Patients diagnosed with sporadic vestibular schwannoma surgically treated at Washington University in St Louis, Missouri, were included. Main Outcomes and Measures: Severe surgical complications within 30 days of surgery as determined by the Clavien-Dindo classification system. Patients experiencing a complication of grade 3 or above were determined to have a severe complication. Results: Of 185 patients evaluated, 40 (22%) had severe postoperative complications. Twenty of the 40 patients (50%) were women; mean (SD) age was 46 (13) years. Patients with severe complications were more likely to have large tumors (>2.5 cm in largest diameter), vestibular symptoms, and recent hearing loss at presentation. Using conjunctive consolidation, a 4-stage clinical severity staging system that incorporates clinical symptoms and tumor size at presentation was created to predict severe complications. The clinical severity staging system demonstrated an improvement in the ability to discriminate severe complications (C index, 0.754; 95% CI, 0.67-0.84) from a model of tumor size alone (C index, 0.706; 95% CI 0.62-0.79). Conclusions and Relevance: This cohort study found that, among patients with vestibular schwannoma, symptoms present at initial evaluation, in addition to tumor size, served as predictors of severe postoperative complications. A new clinical severity staging system incorporating symptoms at presentation can be helpful for clinicians to identify patients at high risk for severe postoperative complications.

Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma.

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance.

TERT, a promoter of CNS malignancies.

As cells replicate their DNA during mitosis, telomeres are shortened due to the inherent limitations of the DNA replication process. Maintenance of telomere length is critical for cancer cells to overcome cellular senescence induced by telomere shortening. Telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of telomerase, an RNA-dependent DNA polymerase that lengthens telomeric DNA to maintain telomere homeostasis. TERT promoter mutations, which result in the upregulation of TERT transcription, have been identified in several central nervous system (CNS) tumors, including meningiomas, medulloblastomas, and primary glial neoplasms. Furthermore, TERT promoter hypermethylation, which also results in increased TERT transcription, has been observed in ependymomas and pediatric brain tumors. The high frequency of TERT dysregulation observed in a variety of high-grade cancers makes telomerase activity an attractive target for developing novel therapeutics. In this review, we briefly discuss normal telomere biology, as well as the structure, function, and regulation of TERT in normal human cells. We also highlight the role of TERT in cancer biology, focusing on primary CNS tumors. Finally, we summarize the clinical significance of TERT promoter mutations in cancer, the molecular mechanisms through which these mutations promote oncogenesis, and recent advances in cancer therapies targeting TERT.

Transradial intraoperative cerebral angiography: a multicenter case series and technical report.

BACKGROUND: Use of the radial artery as an access site for neurointerventional procedures is gaining popularity after several studies in interventional cardiology have demonstrated superior patient safety, decreased length of stay, and patient preference compared with femoral artery access. The transradial approach has yet to be characterized for intraoperative cerebral angiography. OBJECTIVE: To report a multicenter experience on the use of radial artery access in intraoperative cerebral angiography, including case series and discussion of technical nuances. METHODS: 27 patients underwent attempted transradial cerebral angiography betweenMay 2017 and May 2019. Data were collected regarding technique, patient positioning, vessels selected, technical success rate, and access site complications. RESULTS: 24 of the 27 patients (88.8%) underwent successful transradial intraoperative cerebral angiography. 18 patients (66.7%) were positioned supine, 6 patients (22.2%) were positioned prone, 1 patient (3.7%) was positioned lateral, and 2 patients (7.4%) were positioned three-quarters prone. A total of 31 vessels were selected including 13 right carotid arteries (8 common, 1 external, 4 internal), 11 left carotid arteries (9 common and 2 internal), and 6 vertebral arteries (5 right and 1 left). Two patients (7.4%) required conversion to femoral access in order to complete the intraoperative angiogram (1 due to arterial vasospasm and 1 due to inadvertent venous catheterization). One procedure (3.7%) was aborted because of inability to obtain the appropriate fluoroscopic views due to patient positioning. No patient experienced stroke, arterial dissection, or access site complication. CONCLUSIONS: Transradial intraoperative cerebral angiography is safe and feasible with potential for improved operating room workflow ergonomics, faster patient mobility in the postoperative period, and reduced costs.

Therapeutic enhancement of blood-brain and blood-tumor barriers permeability by laser interstitial thermal therapy.

BACKGROUND: The blood-brain and blood-tumor barriers (BBB and BTB), which restrict the entry of most drugs into the brain and tumor, respectively, are a significant challenge in the treatment of glioblastoma. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique increasingly used clinically for tumor cell ablation. Recent evidence suggests that LITT might locally disrupt BBB integrity, creating a potential therapeutic window of opportunity to deliver otherwise brain-impermeant agents. METHODS: We established a LITT mouse model to test if laser therapy can increase BBB/BTB permeability in vivo. Mice underwent orthotopic glioblastoma tumor implantation followed by LITT in combination with BBB tracers or the anticancer drug doxorubicin. BBB/BTB permeability was measured using fluorimetry, microscopy, and immunofluorescence. An in vitro endothelial cell model was also used to corroborate findings. RESULTS: LITT substantially disrupted the BBB and BTB locally, with increased permeability up to 30 days after the intervention. Remarkably, molecules as large as human immunoglobulin extravasated through blood vessels and permeated laser-treated brain tissue and tumors. Mechanistically, LITT decreased tight junction integrity and increased brain endothelial cell transcytosis. Treatment of mice bearing glioblastoma tumors with LITT and adjuvant doxorubicin, which is typically brain-impermeant, significantly increased animal survival. CONCLUSIONS: Together, these results suggest that LITT can locally disrupt the BBB and BTB, enabling the targeted delivery of systemic therapies, including, potentially, antibody-based agents.

A Multi-Institutional Analysis of Factors Influencing Surgical Outcomes for Patients with Newly Diagnosed Grade I Gliomas.

OBJECTIVE: To assess the impact of intraoperative magnetic resonance imaging (iMRI), extent of resection (EOR), and other factors on overall survival (OS) and progression-free survival (PFS) for patients with newly diagnosed grade I gliomas. METHODS: A multicenter database was queried to identify patients with grade I gliomas. Retrospective analyses assessed the impact of patient, treatment, and tumor characteristics on OS and PFS. RESULTS: A total of 284 patients underwent treatment for grade I gliomas, including 248 resections (205 with iMRI, 43 without), 23 biopsies, and 13 laser interstitial thermal therapy treatments. Log-rank analyses of Kaplan-Meier plots showed improved 5-year OS (P = 0.0107) and PFS (P = 0.0009) with increasing EOR, and a trend toward improved 5-year OS for patients with lower American Society of Anesthesiologists score (P = 0.0528). Greater EOR was associated with significantly increased 5-year PFS for pilocytic astrocytoma (P < 0.0001), but not for ganglioglioma (P = 0.10) or dysembryoplastic neuroepithelial tumor (P = 0.57). Temporal tumors (P = 0.04) and location of "other" (P = 0.04) were associated with improved PFS, and occipital/parietal tumors (P = 0.02) were associated with decreased PFS compared with all other locations. Additional tumor resection was performed after iMRI in 49.7% of cases using iMRI, which produced gross total resection in 64% of these additional resection cases. CONCLUSIONS: Patients with grade I gliomas have extended OS and PFS, which correlates positively with increasing EOR, especially for patients with pilocytic astrocytoma. iMRI may increase EOR, indicated by the rate of gross total resection after iMRI use but was not independently associated with increased OS or PFS.

Impact of Intraoperative Magnetic Resonance Imaging and Other Factors on Surgical Outcomes for Newly Diagnosed Grade II Astrocytomas and Oligodendrogliomas: A Multicenter Study.

BACKGROUND: Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative magnetic resonance imaging (iMRI) in the resection of grade II gliomas. OBJECTIVE: To assess the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly diagnosed grade II astrocytomas and oligodendrogliomas. METHODS: Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS and PFS. RESULTS: A total of 232 resections (112 astrocytomas and 120 oligodendrogliomas) were analyzed. Oligodendrogliomas had longer OS (P < .001) and PFS (P = .01) than astrocytomas. Multivariate analyses demonstrated improved OS for gross total resection (GTR) vs subtotal resection (STR; P = .006, hazard ratio [HR]: .23) and near total resection (NTR; P = .02, HR: .64). GTR vs STR (P = .02, HR: .54), GTR vs NTR (P = .04, HR: .49), and iMRI use (P = .02, HR: .54) were associated with longer PFS. Frontal (P = .048, HR: 2.11) and occipital/parietal (P = .003, HR: 3.59) locations were associated with shorter PFS (vs temporal). Kaplan-Meier analyses showed longer OS with increasing extent of surgical resection (EOR) (P = .03) and 1p/19q gene deletions (P = .02). PFS improved with increasing EOR (P = .01), GTR vs NTR (P = .02), and resections above STR (P = .04). Factors influencing adjuvant treatment (35.3% of patients) included age (P = .002, odds ratio [OR]: 1.04) and EOR (P = .003, OR: .39) but not glioma subtype or location. Additional tumor resection after iMRI was performed in 105/159 (66%) iMRI cases, yielding GTR in 54.5% of these instances. CONCLUSION: EOR is a major determinant of OS and PFS for patients with grade II astrocytomas and oligodendrogliomas. Intraoperative MRI may improve EOR and was associated with increased PFS.

Timing and nature of in-house postoperative events following uncomplicated elective endovascular aneurysm treatment.

OBJECT: Most patients with asymptomatic intracranial aneurysms treated with endovascular methods are closely observed overnight in an intensive care unit setting for complications, including ischemic and hemorrhagic stroke, cardiac dysfunction, and groin access complications. The purpose of this study was to analyze the timing, nature, and rate of in-house postoperative events. METHODS: Patients who underwent endovascular treatment or retreatment of unruptured cerebral aneurysms from March 2002 to June 2012 were identified from a prospective case log and their medical records were reviewed. The presentation, patient characteristics, aneurysm size and location, and method of endovascular treatment of each cerebral aneurysm were recorded. Patients with adverse intraprocedural events including perforation and thromboembolism were excluded from this analysis. Overnight postprocedural monitoring was performed in a neurological intensive care unit or postanesthesia care unit for all patients, with discharge planned for postoperative Day 1. Postprocedural events occurring during hospitalization were categorized as intracranial hemorrhage, ischemic stroke, groin hematoma resulting in additional treatment or prolonged hospital stay, retroperitoneal hematoma, and cardiac events. The time from the completion of the procedure to event discovery was recorded. RESULTS: A total of 687 endovascular treatments of unruptured cerebral aneurysms were performed. Nine treatments were excluded from our analysis due to intraprocedural events. Endovascular procedures included coiling alone, stent-assisted coiling, balloon-assisted coiling, balloon-assisted embolization with a liquid embolic agent, and placement of a flow diversion device with or without coiling. Twenty-seven treatments (4.0%) resulted in postprocedural complications: 3 intracranial hemorrhages, 6 ischemic strokes, 4 cardiac events, 5 retroperitoneal hematomas, and 9 groin hematomas. The majority (20 [74.0%]) of these 27 complications were detected within 4 hours from the procedure. These included 1 hemorrhage, 4 ischemic strokes, 4 cardiac events, 2 retroperitoneal hematomas, and 9 groin hematomas. All cardiac events and groin hematomas were detected within 4 hours. Four (14%) of the 27 complications were detected between 4 and 12 hours, 1 (3.7%) between 12 and 24 hours, and 2 (7.4%) more than 24 hours after the procedure. The complications detected more than 4 hours from the conclusion of the procedure included 2 minor intracranial hemorrhages causing headache and resulting in no permanent deficits, 2 mild ischemic strokes, and 3 asymptomatic retroperitoneal hematomas identified by falling hematocrit levels that required no further intervention or treatment. CONCLUSIONS: The large majority of significant postprocedural events after uncomplicated endovascular aneurysm intervention occur within the first 4 hours; these events become less frequent with increasing time. Transfer to a floor bed after 4-12 hours for further observation is reasonable to consider in some patients.