Perivascular invasion of primary human glioblastoma cells in organotypic human brain slices: human cells migrating in human brain.

INTRODUCTION: Glioblastoma (GBM) is an aggressive primary brain cancer. Lack of effective therapy is related to its highly invasive nature. GBM invasion has been studied with reductionist systems that do not fully recapitulate the cytoarchitecture of the brain. We describe a human-derived brain organotypic model to study the migratory properties of GBM IDH-wild type ex vivo. METHODS: Non-tumor brain samples were obtained from patients undergoing surgery (n = 7). Organotypic brain slices were prepared, and green fluorescent protein (GFP)-labeled primary human GBM IDH-wild type cells (GBM276, GBM612, GBM965) were placed on the organotypic slice. Migration was evaluated via microscopy and immunohistochemistry. RESULTS: After placement, cells migrated towards blood vessels; initially migrating with limited directionality, sending processes in different directions, and increasing their speed upon contact with the vessel. Once merged, migration speed decreased and continued to decrease with time (p < 0.001). After perivascular localization, migration is limited along the blood vessels in both directions. The percentage of cells that contact blood vessels and then continue to migrate along the vessel was 92.5% (- 3.9/ + 2.9)% while the percentage of cells that migrate along the blood vessel and leave was 7.5% (- 2.9/ + 3.9) (95% CI, Clopper-Pearson (exact); n = 256 cells from six organotypic cultures); these percentages are significantly different from the random (50%) null hypothesis (z = 13.6; p < 10-7). Further, cells increase their speed in response to a decrease in oxygen tension from atmospheric normoxia (20% O2) to anoxia (1% O2) (p = 0.033). CONCLUSION: Human organotypic models can accurately study cell migration ex vivo. GBM IDH-wild type cells migrate toward the perivascular space in blood vessels and their migratory parameters change once they contact vascular structures and under hypoxic conditions. This model allows the evaluation of GBM invasion, considering the human brain microenvironment when cells are removed from their native niche after surgery.

The Effect of Plating on Adjacent Segments in Anterior Cervical Discectomy and Fusions in Patients with Degenerative Spine Disease: A Retrospective Cohort Study.

Introduction: Plate distance is correlated with an increased incidence of adjacent segment pathologies (ASP). However, a correct plate-to-disk distance >5 mm is often not achieved. Therefore, this study aimed to quantify the effect of short plate-to-disk distance on the development of ASP using epidemiological measures in patients with cervical degenerative spine disease undergoing single-level anterior cervical discectomy and fusion (ACDFs). Methods: Medical records of all patients with cervical degeneration undergoing single-level ACDF with plating (between January 2015 and December 2017), and a follow-up of at least 1 year, were reviewed retrospectively. Radiologic and clinical outcomes were assessed preoperatively, postoperatively, and at last follow-up. The plate-to-adjacent disk distance was measured, and epidemiological measures were calculated to quantify the risk on adjacent-level ossification development (ALOD) and adjacent segment degeneration (ASD). Results: Thirty-eight (47.5%) of the 80 patients developed ALOD, and 12 (15.0%) developed ASD after a 2-year follow-up. The incidence of ALOD was significantly lower if the plate was >5 mm away from the adjacent disk space compared to <5 mm (cranial adjacent segment, 22.5% vs. 51.3% [P=0.010] and caudal, 21.4% vs. 47.8% [P=0.029]). A correct plate-to-disk distance resulted in a relative risk reduction of 57.2% for the cranial segment and 56.0% for the caudal segment, with a number needed to treat of 4. The ASD was only observed in the cranial adjacent segments, and a correct plate-to-disk distance resulted in a relative risk reduction of 32.1% and a number needed to treat of 18. Conclusions: Only four patients need to be treated with a correct plate-to-disk distance to avoid one case of ALOD. Therefore, it is advisable to keep the plate at a distance >5 mm away from the adjacent disk.

Current and Future Frontiers of Molecularly Defined Oligodendrogliomas.

Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.

Predicting access to postoperative treatment after glioblastoma resection: an analysis of neighborhood-level disadvantage using the Area Deprivation Index (ADI).

PURPOSE: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%). METHODS: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups. RESULTS: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed. CONCLUSION: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma.

IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model.

OBJECTIVE: Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH-wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile). METHODS: Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 - VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse. RESULTS: A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98-0.99; p = 0.02; and HR 0.98, 95% CI 0.96-0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively. CONCLUSIONS: The impact of SMR on OS for patients with IDH-wild-type GBM is influenced by the degree of tumor invasiveness. The authors' results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH-wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

Influence of supramarginal resection on survival outcomes after gross-total resection of IDH-wild-type glioblastoma.

OBJECTIVE: The authors' goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma after gross-total resection (GTR). METHODS: The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed. RESULTS: In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01-2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13-1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27-0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52-0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98-0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35-0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45-1.21; p = 0.234). CONCLUSIONS: SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.

OBJECTIVE: High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. METHODS: The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19-76) years were included in the analysis. Eighteen patients had H3 K27M mutation-positive tumors, and 12 had H3 K27M mutation-negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation-positive tumors (p = 0.017). CONCLUSIONS: Although H3 K27M mutant-positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant-positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant-negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

Cervical chordomas: multicenter case series and meta-analysis.

BACKGROUND: En bloc spondylectomy is the gold standard for surgical resection of sacral chordomas (CHO), but the effect of extent of resection on recurrence and survival in patients with CHO of the cervical spine remains elusive. METHODS: MEDLINE, Embase, Scopus, and Cochrane were systematically reviewed. Patients with cervical CHO treated at three tertiary-care academic institutions were reviewed for inclusion. We performed an individual participant data meta-analysis to assess the overall survival (OS) and progression free survival (PFS) after en bloc-gross total resection (GTR) and intralesional-GTR compared to subtotal resection (STR). We then performed an intention-to-treat analysis including all patients with attempted en bloc resection in the en bloc group, regardless of the surgical margins. RESULTS: There was a total of 13 series including 161 patients with cervical CHO, including our current series of 22 patients. GTR (en bloc-GTR + intralesional-GTR) was associated with a significant decrease in the risk of local progression (pooled hazard ratio (PHR) = 0.22; 95% CI 0.08-0.59; p = 0.003) and risk of death (PHR 0.31; 95%; CI 0.12-0.83; p = 0.020). A meta-regression analyses determined that intralesional-GTR improved PFS (PHR 0.35; 95% CI 0.16-0.76; p = 0.009) as well as OS (PHR 0.25; 95% CI 0.08-0.79; p = 0.019) when compared to STR. En bloc-GTR was associated with a significant reduction in the risk of local progression (PHR 0.06; 95% CI 0.01-0.77; p = 0.030), but not a decreased OS (PHR 0.50; 95% CI 0.19-1.27; p = 0.145). Our intention-to-treat analyses revealed a near significant improvement in OS for the en bloc group (PHR: 0.15; 95% CI 0.02-1.22; p = 0.054), and nearly identical improvement in PFS. Radiation data was not available for the studies included in the meta-analysis. CONCLUSION: This is the first and only meta-analysis of patients with cervical CHO. We found that both en bloc-GTR and intralesional-GTR resulted in improved local tumor control when compared to STR.

Intraoperative Seizure Detection During Active Resection of Glioblastoma Through a Novel Hollow Circular Electrocorticography Array.

BACKGROUND AND IMPORTANCE: Data supporting the use of electrocorticography (ECoG) monitoring during electrical stimulation in awake craniotomies for resection of supratentorial neoplasms is robust, but its applicability during active resection is often limited by the inability to keep the array in place. Given the known survival benefit of gross total resection in glioma surgery, novel approaches to surgical monitoring are warranted to maximize safe resection and optimize surgical outcomes in patients with glioblastoma. CLINICAL PRESENTATION: A 68-yr-old right-handed woman presented to the emergency department with confusion. Imaging studies revealed a bifrontal intra-axial brain lesion. She underwent a left-sided awake craniotomy procedure with cortical and subcortical mapping. During surgical resection, multiple electrographic seizures were detected on continuous ECoG monitoring with a customized 22-channel high-density hollow circular array. She remained without clinical evidence of seizures at 3 mo after surgery. CONCLUSION: We report a unique case of serial electrographic seizures detected during continuous intraoperative ECoG monitoring during active surgical resection of a glioblastoma using a novel circular hollow array during an awake craniotomy. The use of continuous ECoG monitoring during active resection may provide additional data, with potential influence in outcomes for patients undergoing resection of high-grade glial neoplasms.

Treatment of posterior circulation non-saccular aneurysms with flow diversion versus stent-assisted coiling: a systematic review and meta-analysis.

Treatment of non-saccular aneurysms of the posterior circulation poses a great challenge with unpredictable outcomes due to the absence of a true aneurysm neck and the presence of perforating vessels. In this article, we aim to compare endovascular treatment of unruptured posterior circulation non-saccular aneurysms with stent-assisted coiling (SAC) and flow diversion (FD) in terms of occlusion rate and clinical outcomes. A systematic search of electronic databases from inception to August 2019 identified 484 articles for screening. After proper inclusion/exclusion criteria, 15 articles were included and data were extracted and analyzed using meta-analysis of proportions. The pooled cohort consisted of 430 aneurysms: 128 (29.7%) treated with SAC in 5 studies and 302 (70.3%) treated with FD in 11 studies. Complete/near-complete occlusion was achieved in 83% after FD (95% CI 0.75 to 0.90; I2=45%) and 84% after SAC (95% CI 0.72 to 0.91; I2=22%), with no significant difference between techniques (p=0.95). Periprocedural complications were observed in 18% after FD (95% CI 0.14 to 0.23; I2=0%) and 6% after SAC (95% CI 0.02 to 0.13; I2=0%); the subgroup analysis was statistically significant (p=0.008). Furthermore, no statistically significant difference was observed in favorable clinical outcomes between groups. These results suggest similar efficacy in occlusion rate and favorable clinical outcome for posterior circulation non-saccular aneurysms treated with SAC and FD. Stroke was the most common complication regardless of treatment modality, and a lower periprocedural complication rate was noted with SAC. Further studies are needed with the primary focus of reducing the risk of stroke with either modality.

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences.

INTRODUCTION: Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of small case series and individual reports. Hence, survival outcome data are limited. The Objective of this study is to explore the influence of sex, age, and number of lesions on overall survival (OS) in patients with MM. METHODS: We obtained demographic and clinical data from the surveillance, epidemiology, and end results program (SEER) on adult patients diagnosed with meningiomas from 1975 to 2017. Univariable and multivariable analyses were conducted to assess whether number of lesions, age, and sex had a significant influence on OS. RESULTS: 99,918 cases were included. Results showed that MM patients had a significantly decreased OS when compared to patients with a single lesion (median OS of 94 and 180 months, respectively; p < 0.001). Further analysis showed a progressive decrease on OS for every additional lesion; 2 (HR 1.659 [CI 95% 1.612-1.708], p < 0.001), 3 (HR 1.877 [CI 95% 1.773-1.988], p < 0.001), and ≥ 4 (HR 2.116 [CI 95% 1.886-2.373], p < 0.001). When assessing for sex differences, female patients had increased OS (HR 0.778 [CI 95% 0.743-0.815], p < 0.001) and decreased risk of developing MM (HR 0.809 [CI 95% 0.784-0.835], p < 0.001). CONCLUSION: Increasing number of meningiomas has a significant negative impact on OS, with a progressive decrease on survival for every additional lesion. Furthermore, female patients had increased OS and decreased risk to develop MM.

Intracranial Myxoid Mesenchymal Tumor/Myxoid Subtype Angiomatous Fibrous Histiocytoma: Diagnostic and Prognostic Challenges.

BACKGROUND AND IMPORTANCE: In the setting of intracranial neoplasms, EWSR1-cAMP Response Element-Binding Protein (CREB) transcription factor family fusions have been described in myxoid mesenchymal tumors, extremely rare entities with a close histopathologic and immunologic resemblance to myxoid subtype angiomatoid fibrous histiocytomas (AFH). Controversy exists on whether these central nervous system lesions are a subtype of myxoid AFH or a completely separate entity, which entitles a distinct clinical behavior and, consequently, a different approach to management. Upon review of the literature, only 14 cases of intracranial tumors harboring an EWSR1-CREB family fusion were identified, with only 3 cases presenting in middle-aged adults, none of which reported an EWSR1-CREM fusion mutation. Significant variability in reported radiographic and histopathological characteristics, as well as in clinical outcomes, was noted. Their similarity with other soft tissue tumors, added to the scarce information on its clinical behavior, represents a great diagnostic and therapeutic challenge to the treating physician. CLINICAL PRESENTATION: We present a rare case of EWSR1-CREM mutated intracranial myxoid mesenchymal tumor/myxoid subtype AFH presenting as persistent headaches in a 36-yr-old woman with radiographic evidence of rapid growth and extensive vasogenic edema, for which she underwent surgical resection. CONCLUSION: This represents a unique case of EWSR1-CREM mutated intracranial myxoid mesenchymal tumor presenting in adulthood, with evidence of aggressive behavior.

Mitotic Index and Progression-Free Survival in Atypical Meningiomas.

Extent of resection and tumor grade are considered the most important predictors of progression-free survival (PFS) in meningiomas. However, adjuvant therapy for atypical meningiomas remains controversial, with variable PFS rates of up to 40%. The current mitotic index (MI) range for atypical meningiomas is broad, comprising all tumors with >4 and <20 mitotic count per 10 high-power fields, leading to substantial within-grade variation of recurrence risk, especially in borderline histologic cases, creating discordance between the clinical course and the application of the classification criteria. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a search of electronic databases from inception to July 2019 identified 121 articles for screening. After proper exclusion criteria, 7 articles were included for data extraction and analysis using meta-analysis of proportions. The MI was the variable of interest in the multivariate regressions and analyzed as a predictor of recurrence using hazard ratios (HRs) (95% confidence intervals). Separate random effect models were used for studies reporting the MI as a continuous or categorical variable. The pooled study results in this meta-analysis demonstrate a homogeneous statistically significant correlation between the MI and the rate of local recurrence after surgical resection regardless of the reporting method (continuous: HR = 1.20; categorical: HR = 2.65). However, significant limitations were noted, including the lack of a standardized method for MI calculation and heterogeneity of MI reports. We encourage the community to report their experience with the MI with greater precision and uniformity to further assess the influence of the MI on PFS within atypical meningiomas.

Awake Craniotomy with Cortical and Subcortical Speech Mapping for Supramarginal Cavernoma Resection.

Awake craniotomy allows mapping of eloquent brain regions and monitoring neurocognitive functioning intraoperatively to maximize extent of resection and minimize cognitive morbidity.1,2 During resection of cavernous malformations in eloquent areas, intraoperative cognitive monitoring can also allow for safer maximal excision of the hemosiderin ring, which is correlated with improved seizure-free outcome.3,4 We present the case of a 33-year-old right-handed male with a new-onset seizure who presented to his local emergency department after experiencing visual hallucinations before losing consciousness. Computed tomography scan of the head revealed a calcified lesion in the left temporal/parietal area. Presurgical workup revealed left hemispheric language dominance and language activation within the overlying supramarginal gyrus representing phonologic working memory on functional magnetic resonance imaging.5 Diffusion tensor imaging identified the arcuate fasciculus and lateral portion of the superior longitudinal fasciculus to be intimately associated with the deep margin of the lesion.6 After consent was obtained, we performed an awake craniotomy and resection of the lesion through a transsulcal approach, with eloquent cortical mapping using a novel high-density circular grid,7,8 as well as subcortical stimulation/mapping and continuous intraoperative cognitive monitoring using multiple language paradigms; the patient was baselined on these paradigms preoperatively (Video 1). Several phonologic/paraphasic errors were made during resection of the hemosiderin ring, likely related to mechanical manipulation. The patient was discharged to home on postoperative day 4 with outpatient speech therapy for speech hesitancy. At 1-week postoperative testing, language skills were considered within normal limits.

Meningiomas in the elderly.

Meningiomas are benign tumors that arise from the meningo-epithelial cells of the arachnoid dura and account for approximately one-third of all adult intracranial tumors. With the evolution of diagnostic imaging and the average life span increasing, meningiomas are being detected more frequently in an older population. In the elderly population, defined by patients aged 60 years or older, meningiomas are the most incidentally detected benign primary brain tumor. As a patient ages, the rate of growth of the meningioma decreases, while comorbidities increase, making the elderly population a unique group when it comes to decision-making for treatment. Treatment options for intracranial meningiomas in the elderly include surgery, radiosurgery, or observation. Although age may have some part in treatment considerations, comorbidities, overall state of health, and tumor characteristics play a more significant role in patient outcome. This chapter will investigate the incidence, evaluation, treatment, and outcomes of intracranial meningiomas in the elderly population.

A 360° electronic device for recording high-resolution intraoperative electrocorticography of the brain during awake craniotomy.

OBJECTIVE: Epilepsy is common among patients with supratentorial brain tumors; approximately 40%-70% of patients with glioma develop brain tumor-related epilepsy (BTRE). Intraoperative localization of the epileptogenic zone during surgical tumor resection (real-time data) may improve intervention techniques in patients with lesional epilepsy, including BTRE. Accurate localization of the epileptogenic signals requires electrodes with high-density spatial organization that must be placed on the cortical surface during surgery. The authors investigated a 360° high-density ring-shaped cortical electrode assembly device, called the "circular grid," that allows for simultaneous tumor resection and real-time electrophysiology data recording from the brain surface. METHODS: The authors collected data from 99 patients who underwent awake craniotomy from January 2008 to December 2018 (29 patients with the circular grid and 70 patients with strip electrodes), of whom 50 patients were matched-pair analyzed (25 patients with the circular grid and 25 patients with strip electrodes). Multiple variables were then retrospectively assessed to determine if utilization of this device provides more accurate real-time data and improves patient outcomes. RESULTS: Matched-pair analysis showed higher extent of resection (p = 0.03) and a shorter transient motor recovery period during the hospitalization course (by approximately 6.6 days, p ≤ 0.05) in the circular grid patients. Postoperative versus preoperative Karnofsky Performance Scale (KPS) score difference/drop was greater for the strip electrode patients (p = 0.007). No significant difference in postoperative seizures between the 2 groups was present (p = 0.80). CONCLUSIONS: The circular grid is a safe, feasible tool that grants direct access to the cortical surgical surface for tissue resection while simultaneously monitoring electrical activity. Application of the circular grid to different brain pathologies may improve intraoperative epileptogenic detection accuracy and functional outcomes, while decreasing postoperative complications.

Health Care Expenditures of Medicare Beneficiaries with Normal Pressure Hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is an underdiagnosed and undertreated condition affecting the elderly population and with costs associated with its surgical management reported to be less than those associated with conservative management. OBJECTIVE: To determine if the rate of diagnosis of NPH has improved over the last decade, the rate of treatment has increased, and if surgical treatment costs and socioeconomic factors related to receipt of treatment have changed over time compared with conservative therapy. METHODS: A retrospective study based on data from a nationally representative random sample of 2,378,637 Medicare beneficiaries (2006-2010) was performed. Shunt surgery, shunt revision, replacement, and removal were analyzed as independent variables. RESULTS: A total of 2321 patients with NPH were included, with 580 (24.99%) receiving a first shunt procedure. The adjusted effect of the procedure is that total 5-year expenditures are $11,676 more per patient (P < 0.001) than expenditures associated with nonsurgical management. Shunt revision ($22,715, P < 0.01) and/or replacement ($46,607, P < 0.001) add significantly to 5-year expenditures. Socioeconomic factors including African American race (P = 0.006); age 75-79 years (P = 0.024), 80-84 years (P < 0.001), and ≥85 years (P < 0.001); and Medicaid (P < 0.001) have significant negative associations with shunt surgery. CONCLUSIONS: There was a 1.66-fold increase in the rate of diagnosis of NPH, from 0.12% in 1999 to 0.2% in 2008. The total costs per surgical patient rose by approximately 145% to 160% comparing 2001 and 2010. This increase was mainly due to hospital (by 167% to 168%) and home health costs (by 118% to 148%). Providing appropriate care across the socioeconomic spectrum warrants further study and requires identifying the factors that limit access to care.

Submandibular Approach for Single-Stage Craniovertebral Junction Ventral Decompression and Stabilization: A Preliminary Cadaveric Study of Technical Feasibility.

BACKGROUND: The craniovertebral junction (CVJ) may be affected by several diseases. It is an anatomically complex region, involving the osteoligamentous, vascular, and nervous structures, which makes surgery challenging. In a case of ventral compression, an anterior approach is preferable, although posterior fixation is often required. Anterior transmucosal approaches are associated with high rates of complications. However, decompression and fixation by the use of retropharyngeal extramucosal approaches may be challenging. OBJECTIVE: To investigate the feasibility of a single-stage, anterior, extramucosal submandibular (SM) approach modification to the CVJ for simultaneous decompression and stabilization. MATERIALS AND METHODS: This was a preliminary cadaveric feasibility study on 2 injected specimens. A variation of the SM approach with a short "boomerang" incision, microsurgical decompression of the ventral CVJ, and a new hybrid construct for an anterior atlantoaxial stabilization was investigated. The surgical approach, the decompression, and the instrumentation technique have been described. In addition, intraprocedural images and radiographs and also postprocedural computed tomographic images were collected. Furthermore, surgical exposure, working corridors and angles, and decompression grade were measured. RESULTS: The SM approach provided wide exposure of the ventral CVJ and the possibility for instrumentation and decompression by removing the anterior arch of C1 and the odontoid process. CONCLUSION: A single- stage anterior extramucosal SM approach for decompression and stabilization of the CVJ is feasible and could result in shorter surgical duration, avoiding the complications related to both the transmucosal approach and the prone position, although specific related risks exist. Mechanical investigation of this hybrid system and in vivo studies are needed to confirm our results.

Endoscope-assisted contralateral transmaxillary approach to the clivus and the hypoglossal canal: technical case report.

Clival lesions are still considered surgically complex due to their anatomical location. Critical structures, such as the internal carotid arteries (ICAs), cavernous sinuses, cranial nerves, and brainstem, may be encased within the lesion. Although advances in endoscopic endonasal approaches have provided new routes to these lesions, exposure and resection of clival tumors through the endonasal route remain a technical challenge. Here, the authors report a left-sided endoscopic transmaxillary approach to access the right aspect of the clivus and the hypoglossal canal.A 35-year-old woman presented with progressive right 6th cranial nerve palsy. MRI revealed a contrast-enhancing right petroclival chondrosarcoma that involved Meckel's cave and extended into the right hypoglossal canal. An endoscopic-contralateral-transmaxillary approach through a left sublabial incision was used to access the right petroclival region and right hypoglossal canal. A left maxillary osteoplastic flap was elevated to expose the left maxillary sinus. This was followed by a left medial maxillectomy, gaining access to the left posterior nasal cavity. The posterior third of the left inferior turbinate and nasal septum were removed to access the right side of the petroclival region. Near-total resection was achieved without any vascular or neurological complications. A thin shell of residual tumor was left behind due to involvement of vital structures, such as the ICA, and further treated with proton-beam radiotherapy.The endoscopic-contralateral-transmaxillary approach provides a direct surgical corridor and good lateral visualization of the skull base vasculature. This approach allows wide maneuverability around the ICA and hypoglossal canal, which, in this case, allowed maximal tumor resection with full preservation of neurological function.

The Radiographic Effects of Surgical Approach and Use of Retractors on the Brain After Anterior Cranial Fossa Meningioma Resection.

OBJECTIVE: There is an increasing trend toward skull base (SB) approaches and retractorless surgery to minimize brain manipulation during surgery. We evaluated the radiographic changes over time after surgical resection of anterior cranial fossa meningiomas with and without both SB approaches and/or fixed retractor systems. METHODS: All adults undergoing primary resection of an anterior cranial fossa World Health Organization grade I meningioma through a craniotomy at a single academic tertiary-care institution from 2010 to 2015 were retrospectively reviewed. Magnetic resonance imaging scans were reviewed and contrast-enhanced tumor and fluid-attenuated inversion recovery (FLAIR) volumes were measured. Matched-pair analyses between patients who underwent SB and non-SB approaches, as well as retractorless and retractor-assisted (RA) surgery, were made. RESULTS: Of the 136 total patients, 20 (15%), 12 (9%), 46 (34%), and 58 (43%) underwent SB/retractorless, SB/RA, non-SB/retractorless, and non-SB/RA surgery, respectively. Patients who underwent non-SB and RA surgery each independently had longer times to FLAIR resolution than those who underwent SB (20.9 vs. 5 months; P = 0.04) and retractorless (12 vs. 5.2 months; P = 0.02) surgery, respectively. Patients who underwent both non-SB and RA surgery had the longest median time to FLAIR resolution (30 months vs. 4 months in SB/retractorless, 3.6 months in SB/RA, and 3 months in non-SB/retractorless; P < 0.05). CONCLUSIONS: The use of SB approaches in combination with retractorless surgery may decrease the duration needed for FLAIR resolution after surgery. The results from this study therefore advocate SB approaches and retractorless surgery along the anterior SB when possible.