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OBJECTIVE Mutations in NF2 are the most common somatic driver mutation in sporadic meningiomas. NF2 mutant meningiomas preferentially arise along the cerebral convexities—however, they can also be found in the posterior fossa. The authors investigated whether NF2 mutant meningiomas differ in clinical and genomic features based on their location relative to the tentorium. METHODS Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic NF2 mutant meningiomas were reviewed and analyzed. RESULTS A total of 191 NF2 mutant meningiomas were included (165 supratentorial, 26 infratentorial). Supratentorial NF2 mutant meningiomas were significantly associated with edema (64.0% vs 28.0%, p < 0.001); higher grade—i.e., WHO grade II or III (41.8% vs 3.9%, p < 0.001); elevated Ki-67 (55.0% vs 13.6%, p < 0.001); and larger volume (mean 45.5 cm3 vs 14.9 cm3, p < 0.001). Furthermore, supratentorial tumors were more likely to harbor the higher-risk feature of chromosome 1p deletion (p = 0.038) and had a larger fraction of the genome altered with loss of heterozygosity (p < 0.001). Infratentorial meningiomas were more likely to undergo subtotal resection than supratentorial tumors (37.5% vs 15.8%, p = 0.021); however, there was no significant difference in overall (p = 0.2) or progression-free (p = 0.4) survival. CONCLUSIONS Supratentorial NF2 mutant meningiomas are associated with more aggressive clinical and genomic features as compared with their infratentorial counterparts. Although infratentorial tumors have higher rates of subtotal resection, there is no associated difference in survival or recurrence. These findings help to better inform surgical decision-making in the management of NF2 mutant meningiomas based on location, and may guide postoperative management of these tumors.

Objective Sphenoid wing meningiomas (SWMs) can present surgical challenges, in that they are often obscured by overlying brain, encase critical neurovascular structures, and obliterate cerebrospinal fluid (CSF) cisterns. While brain retraction can enable access, its use can have potentially deleterious effects. We report the benefits and outcomes of the criteria we have developed for use of cerebrospinal diversion to perform retractorless surgery for SWMs. Design Technical report. Setting Yale School of Medicine and Yale New Haven Hospital. Participants Between May, 2019 and December, 2020, ten consecutive patients were included who met the presented criteria for SWM surgery with preoperative lumbar drain (LD) placement. Main Outcome Measures Length of hospital stay, surgical complications, and extent of resection. Results We have developed the following criteria for LD placement in patients with SWMs such that LDs are preoperatively placed in patients with tumors with one or more of the following criteria: (1) medial location along the sphenoid wing, (2) vascular encasement resulting in obliteration of the optic carotid cistern and/or proximal sylvian fissure, and/or (3) the presence of associated edema. CSF release, after craniotomy and sphenoid wing removal, allowed for optimization of exposure, leading to the maximal safe extent of tumor resection without brain retraction or any complications. Conclusions Preoperative LD placement is effective in allowing for maximal extent of resection of SWMs and may be considered in cases where local CSF release is not possible. This technique is useful in those tumors located more medially, with encasement of the vasculature and/or associated with edema.

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.

Objective While adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored. Methods Clinical data of 48 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed. Results The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P < 0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores ( Conclusions Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.

BACKGROUND Hyperactive cranial neuropathies refractory to medical management can often be debilitating to patients. While microvascular decompression (MVD) surgery can provide relief to such patients when an aberrant vessel is compressing the root entry zone (REZ) of the nerve, the arteries of elderly patients over 65 years of age can be less amenable to manipulation because of calcifications and other morphological changes. A dolichoectatic vertebral artery (DVA), in fact, can lead to multiple cranial neuropathies; therefore, a strategy for MVDs in elderly patients is useful. OBSERVATIONS A 76-year-old man presented with medically refractory trigeminal neuralgia (TN) and hemifacial spasm (HFS). A DVA was the conflicting vessel at the left REZs of the trigeminal and facial nerves. The authors performed a retrosigmoid craniotomy for MVD of the DVA with Teflon padding at both REZs in approximately 1 hour of operative time. The patient was free of facial pain and spasm immediately after surgery and at follow-up. LESSONS The authors described the case of an elderly patient with both TN and HFS caused by compression of a DVA. Simultaneous MVD with Teflon padding at both REZs provided symptomatic relief with limited surgical time. This can be a particularly useful and straightforward surgical strategy in the elderly population.

Background Multiple meningiomas (MMs) rarely occur sporadically. It is unclear whether each individual tumor in a single patient behaves similarly. Moreover, the molecular mechanisms underlying the formation of sporadic MMs and clonal formation etiology of these tumors are poorly understood. Methods Patients with spatially separated MMs without prior radiation exposure or a family history who underwent surgical resection of at least two meningiomas were included. Unbiased, comprehensive next generation sequencing was performed, and relevant clinical data was analyzed. Results Fifteen meningiomas and one dural specimen from six patients were included. The majority of tumors (12/15) were WHO Grade I; one patient had bilateral MMs, one of which was Grade II, while the other was Grade I. We found 11/15 of our cohort specimens were of NF2-loss subtype. Meningiomas from 5/6 patients had a monoclonal origin, with the tumor from the remaining patient showing evidence for independent clonal formation. We identified a novel case of non-NF2 mutant MM with monoclonal etiology. MMs due to a monoclonal origin did not always display a homogenous genomic profile, but rather exhibited heterogeneity due to branching evolution. Conclusions Both NF2-loss and non-NF2 driven MMs can form due to monoclonal expansion and those tumors can acquire inter-tumoral heterogeneity through branched evolution. Grade I and II meningiomas can occur in the same patient. Thus, the molecular make-up and clinical behavior of one tumor in MMs, cannot reliably lend insight into that of the others and suggests the clinical management strategy for MMs should be tailored individually.

INTRODUCTION Approximately 50% of sporadic meningiomas, which originate throughout the neuroaxis, harbor bi-alleic NF2 loss. We sought to determine whether NF2 mutant meningiomas originating from different intracranial locations relative to the tentorium differ with regards to their genomic profile and clinical behavior. METHODS Clinical and whole exome sequencing data (WES) for all patients who underwent resection of NF2 mutant meningiomas and consented to WES were reviewed and analyzed. RESULTS 258 NF2 mutant meningiomas were included and subdivided into supra- (sNF2) versus infra-tentorial (iNF2) groups (230 versus 28, respectively). Supratentorial location was significantly associated with genomically unstable tumors (percent genome altered median 12% vs. 1%, p< 0.001) and were more likely to harbor the more aggressive feature of chromosome 1p deletion (31.4% vs. 8.3%, p= 0.036). These malignant genomic features correlated with an increased incidence of high risk clinical features, including higher-grade (i.e. WHO Grade II/III) (48.9% vs. 7.14%, p < 0.001) and elevated Ki-67 (58.9% vs. 16.6%, p< 0.01), as well as larger volume (median 26.21 cm3 vs. 9.84 cm3, p< 0.001) and edema (65.8% vs. 25.9%, p= 0.001) in sNF2 meningiomas as compared with iNF2 tumors, respectively. Not surprisingly, although there was no difference in extent of resection between the groups (gross total resection (GTR), 96.26% vs. 96.15%, p= 0.45), patients with sNF2 tumors had more associated deaths (14.6% vs. 0%, p= 0.03) and a marginally shorter overall survival (p= 0.061). GTR was associated with longer progression-free survival (p= 0.037). CONCLUSION Within the homogeneous group of somatic NF2 mutated meningiomas, infratentorial tumors are seemingly more benign in their genomic make-up and clinical manifestation as compared to ones located in the supratentorial location. While GTR is useful to both groups in preventing recurrence, this benefit may be especially important in the clinically and genomically higher risk sNF2 tumors.

BACKGROUND While socioeconomic factors for racial disparities amongst sporadic meningioma patients have been explored, other potential influences are poorly understood. We sought to identify whether the genomic make-up is different amongst meningioma patients of different races and how they correlate with clinical variables. METHODS All patients who underwent surgery for sporadic meningioma and consented for whole exome sequencing were eligible. Genomic and clinical data were reviewed and analyzed. RESULTS 537 intracranial meningiomas from 483 patients with the following racial profile were included: 75% White, 14% Black, 8% Latinx, 3% Asian. Compared with others, Whites were older at the time of diagnosis (p = 0.038) and surgery (p = 0.015). Black and Latinx patients were more likely to present with vision abnormalities (p = 0.006). Whites were more likely to have convexity meningiomas (p = 0.003), while Blacks were more likely to have tumors along the anterior fossa (p = 0.002) with associated somatic Hedgehog (HH) driver mutations (p = 0.008). Both Black and Latinx patients were more likely to have TRAF7 mutated meningiomas (p = 0.006). The highest number of copy number variations was seen in Blacks (p = 0.011) and this correlated with Blacks being more likely to have high-grade tumors, followed by Whites, Asians, and then Latinx (p = 0.020). Black patients trended toward decreased progression-free survival than others (median survival: 57 vs. 130 months; p = 0.06) despite similar extent of resection. CONCLUSION Overall, when mutational subgroup and location are considered, Black patients are more likely to have anterior skull base meningiomas with associated visual issues and corresponding somatic HH and TRAF7 mutations. With regards to tumor grade, Blacks harbor more aggressive sporadic meningiomas with a larger prevalence of high-grade meningiomas and associated underlying chromosomal instability compared to others. These findings have implications for meningioma care especially in minority populations, who may harbor more aggressive tumors.

While adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored.Clinical data of 48 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed.The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores (70) showed significant improvement at postoperative 6 weeks (P0.0001). Patients with complications (P = 0.038) were more likely to have lower KPS at postoperative 6 weeks.Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.