Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.

Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors.

Frailty indices predict mortality, complications and functional improvements in supratentorial meningioma patients over 80 years of age.

PURPOSE: To assess whether the Modified 5 (mFI-5) and 11 (mFI-11) Factor Frailty Indices associate with postoperative mortality, complications, and functional benefit in supratentorial meningioma patients aged over 80 years. METHODS: Baseline characteristics were collected from eight centers. Based on the patients' preoperative status and comorbidities, frailty was assessed by the mFI-5 and mFI-11. The collected scores were categorized as "robust (mFI=0)", "pre-frail (mFI=1)", "frail (mFI=2)", and "significantly frail (mFI≥3)". Outcome was assessed by the Karnofsky Performance Scale (KPS); functional benefit was defined as improved KPS score. Additionally, we evaluated the patients' functional independence (KPS≥70) after surgery. RESULTS: The study population consisted of 262 patients (median age 83 years) with a median preoperative KPS of 70 (range 20 to 100). The 90-day and 1-year mortality were 9.0% and 13.2%; we recorded surgery-associated complications in 111 (42.4%) patients. At last follow-up within the postoperative first year, 101 (38.5%) patients showed an improved KPS, and 183 (69.8%) either gained or maintained functional independence. "Severely frail" patients were at an increased risk of death at 90 days (OR 16.3 (CI95% 1.7-158.7)) and one year (OR 11.7 (CI95% 1.9-71.7)); nine (42.9%) of severely frail patients died within the first year after surgery. The "severely frail" cohort had increased odds of suffering from surgery-associated complications (OR 3.9 (CI 95%) 1.3-11.3)), but also had a high chance for postoperative functional improvements by KPS≥20 (OR 6.6 (CI95% 1.2-36.2)). CONCLUSION: The mFI-5 and mFI-11 associate with postoperative mortality, complications, and functional benefit. Even though "severely frail" patients had the highest risk morbidity and mortality, they had the highest chance for functional improvement.

Simulated driving in the epilepsy monitoring unit: Effects of seizure type, consciousness, and motor impairment.

People with epilepsy face serious driving restrictions, determined using retrospective studies. To relate seizure characteristics to driving impairment, we aimed to study driving behavior during seizures with a simulator. Patients in the Yale New Haven Hospital undergoing video-electroencephalographic monitoring used a laptop-based driving simulator during ictal events. Driving function was evaluated by video review and analyzed in relation to seizure type, impairment of consciousness/responsiveness, or motor impairment during seizures. Fifty-one seizures in 30 patients were studied. In terms of seizure type, we found that focal to bilateral tonic-clonic or myoclonic seizures (5/5) and focal seizures with impaired consciousness/responsiveness (11/11) always led to driving impairment; focal seizures with spared consciousness/responsiveness (0/10) and generalized nonmotor (generalized spike-wave bursts; 1/19) usually did not lead to driving impairment. Regardless of seizure type, we found that seizures with impaired consciousness (15/15) or with motor involvement (13/13) always led to impaired driving, but those with spared consciousness (0/20) or spared motor function (5/38) usually did not. These results suggest that seizure types with impaired consciousness/responsiveness and abnormal motor function contribute to impaired driving. Expanding this work in a larger cohort could further determine how results with a driving simulator may translate into real world driving safety.

Radiotherapy for meningiomas.

Meningiomas are the most common primary central nervous system neoplasm. Despite promising recent progress in elucidating the genomic landscape and underlying biology of these histologically, molecularly, and clinically diverse tumors, the mainstays of meningioma treatment remain maximal safe resection and radiation therapy. The aim of this review of meningioma radiotherapy is to provide a concise summary of the history, current evidence, and future for application of radiotherapy in meningioma treatment.

The integrated multiomic diagnosis of sporadic meningiomas: a review of its clinical implications.

INTRODUCTION: Meningiomas are generally considered "benign," however, these tumors can demonstrate variability in behavior and a surprising aggressiveness with elevated rates of recurrence. The advancement of next-generation molecular technologies have led to the understanding of the genomic and epigenomic landscape of meningiomas and more recent correlations with clinical characteristics and behavior. METHODS: Based on a thorough review of recent peer-reviewed publications (PubMed) and edited texts, we provide a molecular overview of meningiomas with a focus on relevant clinical implications. RESULTS: The identification of specific somatic driver mutations has led to the classification of several major genomic subgroups, which account for more than 80% of sporadic meningiomas, and can be distinguished using noninvasive clinical variables to help guide management decisions. Other somatic genomic modifications, including non-coding alterations and copy number variations, have also been correlated with tumor characteristics. Furthermore, epigenomic modifications in meningiomas have recently been described, with DNA methylation being the most widely studied and potentially most clinically relevant. Based on these molecular insights, several clinical trials are currently underway in an effort to establish effective medical therapeutic options for meningioma. CONCLUSION: As we enhance our multiomic understanding of meningiomas, our ability to care for patients with these tumors will continue to improve. Further biological insights will lead to additional progress in precision medicine for meningiomas.

Outcomes following stereotactic radiosurgery for foramen magnum meningiomas: a single-center experience and systematic review of the literature.

OBJECTIVE: Foramen magnum meningiomas (FMMs) pose a unique challenge given their intimate anatomical relationship with the craniovertebral junction. While resection has been studied extensively, much less has been reported about the use of stereotactic radiosurgery (SRS) for FMMs. This study includes what is to the authors' knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs. METHODS: A retrospective chart review was conducted at a single major academic institution, and a systematic review was performed according to PRISMA guidelines. The initial search on the PubMed and Scopus databases yielded 530 results. Key data extracted from both databases included Karnofsky Performance Status (KPS) score and neurological deficits at presentation, tumor location, treatment indication, target volume, single versus multiple fractions, marginal and maximum doses, isodose line, clinical and radiographic follow-up times, and primary (clinical stability and local control at last follow-up) and secondary (mortality, adverse radiation events, time to regression, progression-free survival) outcomes. RESULTS: The study patients included 9 patients from the authors' institution and 165 patients across 4 studies who received SRS for FMMs. The weighted median age at treatment was 60.2 years, and 73.9% of patients were female. Common presenting symptoms included headache (33.9%), dizziness/ataxia (29.7%), cranial nerve deficit(s) (27.9%), numbness (22.4%), weakness (15.2%), and hydrocephalus (4.2%). Lateral/ventrolateral (64.2%) was the most common tumor location. SRS was utilized as the primary therapy in 63.6% of patients and as salvage (21.8%) or adjuvant (14.5%) therapy for the rest of the patients. Most patients (91.5%) were treated with a single fraction. A tumor with a weighted median target volume of 2.9 cm3 was treated with a weighted median marginal dose, maximum dose, and isodose line of 12.9 Gy, 22.8 Gy, and 58%, respectively. Clinical stability and local control at last follow-up were achieved in 98.8% and 97.0% of patients, respectively. Only one possible adverse radiation event occurred, and no mortality directly related to the tumor or SRS was reported. CONCLUSIONS: In this retrospective analysis and systematic review, the authors demonstrate SRS to be an effective and safe treatment option for carefully selected patients with FMMs.

Type of bony involvement predicts genomic subgroup in sphenoid wing meningiomas.

PURPOSE: As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature. METHODS: Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as no bone invasion (Type I), hyperostosis only (Type II), tumor invasion only (Type III), or both hyperostosis and tumor invasion (Type IV). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Machine-learning approaches were used to predict genomic subgroups based on pre-operative clinical features. RESULTS: Among 64 SWMs, 53% had Type-II, 9% had Type-III, and 14% had Type-IV bone involvement; nine SOMs were identified. Tumors with invasion (i.e., Type III or IV) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor NF2 mutations (OR 27.6; p: 0.004), while hyperostosis only were over 4 times more likely to have a TRAF7 mutation (OR 4.5; p: 0.023). SOMs were a significant predictor of underlying TRAF7 mutation (OR 10.21; p: 0.004). CONCLUSIONS: SWMs with invasion into bone tend to be higher grade and are more likely to be NF2 mutated, while SOMs and those with hyperostosis are associated with TRAF7 variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers and grade.

Rhythmic 3-4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures.

Absence seizures are transient episodes of impaired consciousness accompanied by 3-4 Hz spike-wave discharge on electroencephalography (EEG). Human functional magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical decreases in the blood oxygen-level dependent (BOLD) signal that may play an important role in the pathophysiology of these seizures. Animal models could provide an opportunity to investigate the fundamental mechanisms of these changes, however they have so far failed to consistently replicate the cortical fMRI decreases observed in human patients. This may be due to important differences between human seizures and animal models, including a lack of cortical development in rodents or differences in the frequencies of rodent (7-8 Hz) and human (3-4 Hz) spike-wave discharges. To examine the possible contributions of these differences, we developed a ferret model that exhibits 3-4 Hz spike-wave seizures in the presence of a sulcated cortex. Measurements of BOLD fMRI and simultaneous EEG demonstrated cortical fMRI increases during and following spike-wave seizures in ferrets. However unlike human patients, significant fMRI decreases were not observed. The lack of fMRI decreases was consistent across seizures of different durations, discharge frequencies, and anesthetic regimes, and using fMRI analysis models similar to human patients. In contrast, generalized tonic-clonic seizures under the same conditions elicited sustained postictal fMRI decreases, verifying that the lack of fMRI decreases with spike-wave was not due to technical factors. These findings demonstrate that 3-4 Hz spike-wave discharge in a sulcated animal model does not necessarily produce fMRI decreases, leaving the mechanism for this phenomenon open for further investigation.

Ictal spread of medial temporal lobe seizures with and without secondary generalization: an intracranial electroencephalography analysis.

OBJECTIVE: Secondary generalization of seizures has devastating consequences for patient safety and quality of life. The aim of this intracranial electroencephalography (icEEG) study was to investigate the differences in onset and propagation patterns of temporal lobe seizures that remained focal versus those with secondary generalization, in order to better understand the mechanism of secondary generalization. METHODS: A total of 39 seizures were analyzed in nine patients who met the following criteria: (1) icEEG-video monitoring with at least one secondarily generalized tonic-clonic seizure (GTCS), (2) pathologically proven hippocampal sclerosis, and (3) no seizures for at least 1 year after anteromedial temporal lobe resection. Seizures were classified as focal or secondary generalized by behavioral analysis of video. Onset and propagation patterns were compared by analysis of icEEG. RESULTS: We obtained data from 22 focal seizures without generalization (FS), and 17 GTCS. Seizure-onset patterns did not differ between FS and GTCS, but there were differences in later propagation. All seizures started with low voltage fast activity, except for seven seizures in one patient (six FS, one GTCS), which started with sharply contoured theta activity. Fifteen of 39 seizures started from the hippocampus, and 24 seizures (including six seizures in a patient without hippocampal contacts) started from other medial temporal lobe areas. We observed involvement or more prominent activation of the posterior-lateral temporal regions in GTCS prior to propagation to the other cortical regions, versus FS, which had no involvement or less prominent activation of the posterior lateral temporal cortex. Occipital contacts were not involved at the time of clinical secondary generalization. SIGNIFICANCE: The posterior-lateral temporal cortex may serve as an important "gateway" controlling propagation of medial temporal lobe seizures to other cortical regions. Identifying the mechanisms of secondary generalization of focal seizures could lead to improved treatments to confine seizure spread.

Neurosurgery trainee well-being in a pediatric neurosurgery hospital: baseline data to motivate toward implementing change.

OBJECTIVE: The aim of this study was to obtain aggregated baseline pediatric neurosurgery well-being data at a tertiary care institution. METHODS: An institutional grant funded the completion of the Maslach Burnout Inventory (MBI) by 100% (n = 13) of the trainees during a 1-year period, including 1 pediatric neurosurgery fellow and 12 residents from 4 regional neurosurgery training programs. Aggregated and anonymized group results included frequency scores ranging from 0 (never) to 6 (every day). The mean ± SD group scores were compared to the general population of > 11,000 people in the human services professions. Burnout profiles were calculated on the basis of MBI scale scores by using established comparisons to standardized normal values. Burnout profile types include engaged, ineffective, overextended, disengaged, and burnout. RESULTS: The mean ± SD score for emotional exhaustion was 2.6 ± 1.1 for trainees compared with 2.3 ± 1.2 in the comparison population. The mean ± SD score for depersonalization was 1.6 ± 1 compared with 1.7 ± 1.2 in the comparison population. The mean ± SD score for personal accomplishment was 4.9 ± 0.7 compared with 4.3 ± 0.9 in the comparison population. Profiles were classified as engaged (n = 6), ineffective (n = 3), overextended (n = 3), and burnout (n = 1). CONCLUSIONS: Problematic profiles were present for more than half (7 [53.8%]) of pediatric neurosurgery trainees who cited higher emotional exhaustion than the general population of healthcare providers. Trainees scored lower in depersonalization and higher in personal accomplishment compared with the general population, which are both protective against burnout. Targeting factors that contribute to emotional exhaustion may have an impact on improving the overall well-being of pediatric neurosurgery trainees.

Extent of resection and progression-free survival in vestibular schwannoma: a volumetric analysis.

OBJECTIVE: To preserve facial nerve function in vestibular schwannoma (VS) microsurgery, some have advocated subtotal resection (STR) if the tumor is densely adherent to a thinned facial nerve. The objective of this study was to determine if residual volume is associated with progression and whether there is a threshold residual volume that should be pursued during STR to prevent recurrence. A secondary objective of this study was to determine whether facial nerve function at last follow-up was associated with extent of resection (EOR). METHODS: Clinical and radiographic data were retrospectively collected from the records of 164 patients with VS who underwent resection. Tumor volumes were measured using Visage, and standard statistical methods were used. The House-Brackmann scale was used to assess changes in facial nerve function before surgery and at last follow-up. RESULTS: Sixty-one patients (37%) received gross-total resection (GTR) and 103 (63%) received STR. The median clinical and radiographic follow-ups were 49 and 48 months, respectively. The median residual volume was 0.5 cm3 after STR. Kaplan-Meier actuarial survival analysis revealed a 96.3% 5-year progression-free survival (PFS) rate after GTR, which was greater than that after STR (84.5%, p = 0.03). Recursive partitioning analysis of patients receiving STR revealed a residual volume of 0.60 cm3 as the optimal threshold for recurrence. Patients with residual volume ≥ 0.60 cm3 had a 76.0% 5-year PFS, regardless of adjuvant SRS, which was lower than that for patients undergoing GTR (96.3%) or STR (95.6%) with residual volumes < 0.60 cm3 (p < 0.01). On Cox regression analysis, residual volume ≥ 0.60 cm3 (HR 14.4, p = 0.01) was independently associated with progression, even when accounting for patient age, adjuvant radiosurgery, and preoperative tumor size. In 112 patients with at least 24 months of follow-up after their last treatment, tumor control was achieved in 111 (99.1%) patients at a median last follow-up of 71 months. Worse facial nerve function at the last follow-up was independently associated with prior treatment for VS (adjusted OR 3.7, p = 0.04), but not residual volume cohort or preoperative tumor volume. CONCLUSIONS: Residual volume > 0.60 cm3 after VS resection was independently associated with tumor progression, even accounting for adjuvant SRS. These data support maximizing the EOR during VS surgery, even if GTR cannot be safely achieved.

Optimizing the use of Ki-67 proliferative index as a prognostic biomarker in meningiomas using digital analysis.

OBJECTIVE: Ki-67 immunohistochemistry is widely used as a prognostic marker in meningiomas, but visual estimations tend to be imprecise. Whether the average Ki-67 over an entire slide, a particular block, or areas of high staining (hotspots) is prognostic for recurrence-free survival (RFS) and overall survival (OS) is unknown. This study aimed to generate evidence-based recommendations for the optimal use of Ki-67 immunohistochemistry in the workup of meningiomas. METHODS: All tissue blocks from a retrospective cohort of 221 patients with primary meningioma (141 WHO grade 1, 64 WHO grade 2, 16 WHO grade 3) were immunostained for Ki-67 and scanned using automated digital analysis software. QuPath was used to quantify the average Ki-67 proliferation index per slide as well as the Ki-67 hotspot in a 2.2-mm2 area within each slide. The best block was defined subjectively by a neuropathologist as the most representative tissue block from each case. The pathology report Ki-67 was determined by visual estimation. Age, sex, WHO grade, extent of resection, tumor location, and quantitative Ki-67 labeling were tested to determine risk factors for RFS and OS. RESULTS: Multivariable analyses demonstrated that WHO grade 2 (HR 2.42, p = 0.018), subtotal resection (HR 8.16, p < 0.0001), near-total resection (HR 2.24, p = 0.041), QuPath Ki-67 averaged across all blocks (HR per % increase = 1.72, p = 0.030), and pathology report Ki-67 (HR per % increase = 1.05, p = 0.0026) were associated with shorter RFS. The average Ki-67 in the best block, maximum across all slides, and maximum hotspot in the best block were not associated with RFS. Only male sex was independently associated with shorter OS (HR 8.52, p = 0.0003). The pathology report Ki-67 was, on average, 6.5 times higher than the QuPath average. CONCLUSIONS: These data on Ki-67 in meningiomas indicate the following: 1) visual estimation substantially overestimates Ki-67, 2) digital quantification of average Ki-67 across all tissue blocks provides more prognostic information than small hotspot regions or an entire single block, and 3) Ki-67 is not informative for OS. The results suggest that best practices for incorporating Ki-67 into meningioma prognostication include digital quantification of average Ki-67 over multiple blocks.

Paclitaxel and Carboplatin in Combination with Low-intensity Pulsed Ultrasound for Glioblastoma.

PURPOSE: We recently reported on clinical trials for patients with recurrent glioblastoma where low-intensity pulsed ultrasound and microbubbles (LIPU/MB) improved paclitaxel or carboplatin delivery into the brain. Here, we report variable local tumor control with paclitaxel at the maximal/target dose in our phase I trial (NCT04528680). To address this, we investigated the combination of paclitaxel with carboplatin in preclinical glioma models. EXPERIMENTAL DESIGN: We performed MRI-based analysis to evaluate disease control in patients from our trial. We studied the cytotoxicity of paclitaxel and carboplatin against 11 human glioma lines as monotherapy and in combination at concentrations derived from human intraoperative studies. Synergy was assessed with the Loewe model and the survival benefit evaluated in two xenografts. We examined the effects on cell cycle progression, DNA damage, and apoptosis. RESULTS: Patients treated with paclitaxel and LIPU/MB exhibited variable local tumor control, which correlated with overall survival. We observed limited cross-resistance to paclitaxel and carboplatin in glioma lines, with almost a third of them being exclusively susceptible to one drug. This combination led to susceptibility of 81% of lines and synergy in 55% of them. The combination proved more efficacious in two intracranial xenografts when administered with LIPU/MB, leading to complementary effects on cell cycle arrest. CONCLUSIONS: Combining paclitaxel and carboplatin in gliomas may be more efficacious than monotherapy, as in other cancers, due to synergy and independent susceptibility to each drug. These results form the basis for an ongoing phase II trial (NCT04528680) where we investigate this combination with LIPU/MB.

The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care.

Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart's description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.

Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma.

BACKGROUND AND OBJECTIVE: Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a "low-risk" group, but some low-risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression values in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. METHODS: This was a retrospective, international, multicenter cohort study that included WHO grade 1 meningiomas that underwent GTR, as first treatment, based on postoperative magnetic resonance imaging. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low-risk meningiomas. RESULTS: In total, 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. The median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence was 90.5%, and median time to recurrence was 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. Of these genes, PGK1 had the largest effect size. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low-risk meningiomas with significant differences in local freedom from recurrence (hazard ratio 2.5, 95% CI 1.2-5.1, P = .016). CONCLUSION: Gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Obesity and meningioma: a US population-based study paired with analysis of a multi-institutional cohort.

OBJECTIVE: Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort. METHODS: National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS. RESULTS: From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043). CONCLUSIONS: Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.

BACKGROUND AND OBJECTIVES: Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm 3 ), medium (10-50 cm 3 ), and large (>50 cm 3 ). RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm 3 ; large PTBE volume correlated with poor preoperative KPS status ( P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

Predictors of salvage therapy for parasagittal meningiomas treated with primary surgery, radiosurgery, or surgery plus adjuvant radiotherapy.

OBJECTIVE: Parasagittal meningiomas (PM) are treated with primary microsurgery, radiosurgery (SRS), or surgery with adjuvant radiation. We investigated predictors of tumor progression requiring salvage surgery or radiation treatment. We sought to determine whether primary treatment modality, or radiologic, histologic, and clinical variables were associated with tumor progression requiring salvage treatment. METHODS: Retrospective study of 109 consecutive patients with PMs treated with primary surgery, radiation (RT), or surgery plus adjuvant RT (2000-2017) and minimum 5 years follow-up. Patient, radiologic, histologic, and treatment data were analyzed using standard statistical methods. RESULTS: Median follow up was 8.5 years. Primary treatment for PM was surgery in 76 patients, radiation in 16 patients, and surgery plus adjuvant radiation in 17 patients. Forty percent of parasagittal meningiomas in our cohort required some form of salvage treatment. On univariate analysis, brain invasion (OR: 6.93, p < 0.01), WHO grade 2/3 (OR: 4.54, p < 0.01), peritumoral edema (OR: 2.81, p = 0.01), sagittal sinus invasion (OR: 6.36, p < 0.01), sagittal sinus occlusion (OR: 4.86, p < 0.01), and non-spherical shape (OR: 3.89, p < 0.01) were significantly associated with receiving salvage treatment. On multivariate analysis, superior sagittal sinus invasion (OR: 8.22, p = 0.01) and WHO grade 2&3 (OR: 7.58, p < 0.01) were independently associated with receiving salvage treatment. There was no difference in time to salvage therapy (p = 0.11) or time to progression (p = 0.43) between patients receiving primary surgery alone, RT alone, or surgery plus adjuvant RT. Patients who had initial surgery were more likely to have peritumoral edema on preoperative imaging (p = 0.01). Median tumor volume was 19.0 cm3 in patients receiving primary surgery, 5.3 cm3 for RT, and 24.4 cm3 for surgery plus adjuvant RT (p < 0.01). CONCLUSION: Superior sagittal sinus invasion and WHO grade 2/3 are independently associated with PM progression requiring salvage therapy regardless of extent of resection or primary treatment modality. Parasagittal meningiomas have a high rate of recurrence with 80.0% of patients with WHO grade 2/3 tumors with sinus invasion requiring salvage treatment whereas only 13.6% of the WHO grade 1 tumors without sinus invasion required salvage treatment. This information is useful when counseling patients about disease management and setting expectations.

Seizure localization using three-dimensional surface projections of intracranial EEG power.

Intracranial EEG (icEEG) provides a critical road map for epilepsy surgery but it has become increasingly difficult to interpret as technology has allowed the number of icEEG channels to grow. Borrowing methods from neuroimaging, we aimed to simplify data analysis and increase consistency between reviewers by using 3D surface projections of intracranial EEG poweR (3D-SPIER). We analyzed 139 seizures from 48 intractable epilepsy patients (28 temporal and 20 extratemporal) who had icEEG recordings, epilepsy surgery, and at least one year of post-surgical follow-up. We coregistered and plotted icEEG ß frequency band signal power over time onto MRI-based surface renderings for each patient, to create color 3D-SPIER movies. Two independent reviewers interpreted the icEEG data using visual analysis vs. 3D-SPIER, blinded to any clinical information. Overall agreement rates between 3D-SPIER and icEEG visual analysis or surgery were about 90% for side of seizure onset, 80% for lobe, and just under 80% for sublobar localization. These agreement rates were improved when flexible thresholds or frequency ranges were allowed for 3D-SPIER, especially for sublobar localization. Interestingly, agreement was better for patients with good surgical outcome than for patients with poor outcome. Localization using 3D-SPIER was measurably faster and considered qualitatively easier to interpret than visual analysis. These findings suggest that 3D-SPIER could be an improved diagnostic method for presurgical seizure localization in patients with intractable epilepsy and may also be useful for mapping normal brain function.