Variations in the genomic profiles and clinical behavior of meningioma by racial and ethnic group.

OBJECTIVE: The influence of socioeconomic factors on racial disparities among patients with sporadic meningiomas is well established, yet other potential causative factors warrant further exploration. The authors of this study aimed to determine whether there is significant variation in the genomic profile of meningiomas among patients of different races and ethnicities and its correlation with clinical outcomes. METHODS: The demographic, genomic, and clinical data of patients aged 18 years and older who had undergone surgery for sporadic meningioma between September 2008 and November 2021 were analyzed. Statistical analyses were performed to detect differences across all racial/ethnic groups, as were direct comparisons between Black and non-Black groups plus Hispanic and non-Hispanic groups. RESULTS: This study included 460 patients with intracranial meningioma. Hispanic patients were significantly younger at surgery (53.9 vs 60.2 years, p = 0.0006) and more likely to show symptoms. Black patients had a higher incidence of anterior skull base tumors (OR 3.2, 95% CI 1.7-6.3, p = 0.0008) and somatic hedgehog mutations (OR 5.3, 95% CI 1.6-16.6, p = 0.003). Hispanics were less likely to exhibit the aggressive genomic characteristic of chromosome 1p deletion (OR 0.28, 95% CI 0.07-1.2, p = 0.06) and displayed higher rates of TRAF7 somatic driver mutations (OR 2.96 95% CI 1.1-7.8, p = 0.036). Black patients had higher rates of recurrence (OR 2.6, 95% CI 1.3-5.2, p = 0.009) and shorter progression-free survival (PFS; HR 2.9, 95% CI 1.6-5.4, p = 0.002) despite extents of resection (EORs) similar to those of non-Black patients (p = 0.745). No significant differences in overall survival were observed among groups. CONCLUSIONS: Despite similar EORs, Black patients had worse clinical outcomes following meningioma resection, characterized by a higher prevalence of somatic hedgehog mutations, increased recurrence rates, and shorter PFS. Meanwhile, Hispanic patients had less aggressive meningiomas, a predisposition for TRAF7 mutations, and no difference in PFS. These findings could inform the care and treatment strategies for meningiomas, and they establish the foundation for future studies focusing on the genomic origins of these observed differences.

Frailty and postoperative outcomes in brain tumor patients: a systematic review subdivided by tumor etiology.

PURPOSE: Frailty has gained prominence in neurosurgical oncology, with more studies exploring its relationship to postoperative outcomes in brain tumor patients. As this body of literature continues to grow, concisely reviewing recent developments in the field is necessary. Here we provide a systematic review of frailty in brain tumor patients subdivided by tumor type, incorporating both modern frailty indices and traditional Karnofsky Performance Status (KPS) metrics. METHODS: Systematic literature review was performed using PRISMA guidelines. PubMed and Google Scholar were queried for articles related to frailty, KPS, and brain tumor outcomes. Only articles describing novel associations between frailty or KPS and primary intracranial tumors were included. RESULTS: After exclusion criteria, systematic review yielded 52 publications. Amongst malignant lesions, 16 studies focused on glioblastoma. Amongst benign tumors, 13 focused on meningiomas, and 6 focused on vestibular schwannomas. Seventeen studies grouped all brain tumor patients together. Seven studies incorporated both frailty indices and KPS into their analyses. Studies correlated frailty with various postoperative outcomes, including complications and mortality. CONCLUSION: Our review identified several patterns of overall postsurgical outcomes reporting for patients with brain tumors and frailty. To date, reviews of frailty in patients with brain tumors have been largely limited to certain frailty indices, analyzing all patients together regardless of lesion etiology. Although this technique is beneficial in providing a general overview of frailty's use for brain tumor patients, given each tumor pathology has its own unique etiology, this combined approach potentially neglects key nuances governing frailty's use and prognostic value.

Associations of race and socioeconomic status with outcomes after intracranial meningioma resection: a systematic review and meta-analysis.

PURPOSE: Social determinants of health broadly affect healthcare access and outcomes. Studies report that minorities and low socioeconomic status (SES) patients undergoing intracranial meningioma resection demonstrate worse outcomes and higher mortality rates. This systematic review and meta-analysis summarizes the available research reporting racial and SES disparities in intracranial meningioma resection outcomes. METHODS: A systematic review was conducted using PRISMA guidelines and included peer-reviewed, English-language articles from the United States between 2000 and 2022 that reported racial and SES disparities in meningioma outcomes. Outcomes included overall survival (OS), extent of resection (EOR), hospitalization costs, length of stay (LOS), 30-day readmission, recurrence, and receipt of surgery and adjuvant radiotherapy. A quantitative meta-analysis was performed only on survival outcomes by race. All other variables were summarized as a systematic review. RESULTS: 633 articles were identified; 19 studies met inclusion criteria. Black or low SES patients were more likely to have increased hospitalization costs, rates of 30-day readmission, LOS, recurrence and less likely to undergo surgery, gross total resection, and adjuvant radiotherapy for their tumors. Six studies were used for the quantitative meta-analysis of race and OS. Compared to White patients, Black patients had significantly worse survival outcomes, and Asian patients had significantly better survival outcomes. CONCLUSION: Disparities in outcomes exist for patients who undergo surgery for meningioma, such that Black and low SES patients have worse outcomes. The literature is quite sparse and contains confounding relationships not often accounted for appropriately. Further studies are needed to help understand these disparities to improve outcomes.

Clinical and genomic differences in supratentorial versus infratentorial NF2 mutant meningiomas.

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.

Surgical strategies for intracranial meningioma in the molecular era.

INTRODUCTION: Surgical resection has long been the treatment of choice for meningiomas and is considered curative in many cases. Indeed, the extent of resection (EOR) remains a significant factor in determining disease recurrence and outcome optimization for patients undergoing surgery. Although the Simpson Grading Scale continues to be widely accepted as the measure of EOR and is used to predict symptomatic recurrence, its utility is under increasing scrutiny. The influence of surgery in the definitive management of meningioma is being re-appraised considering the rapid evolution of our understanding of the biology of meningioma. DISCUSSION: Although historically considered "benign" lesions, meningioma natural history can vary greatly, behaving with unexpectedly high recurrence rates and growth which do not always behave in accordance with their WHO grade. Histologically confirmed WHO grade 1 tumors may demonstrate unexpected recurrence, malignant transformation, and aggressive behavior, underscoring the molecular complexity and heterogeneity. CONCLUSION: As our understanding of the clinical predictive power of genomic and epigenomic factors matures, we here discuss the importance of surgical decision-making paradigms in the context of our rapidly evolving understanding of these molecular features.

Vascular steal and associated intratumoral aneurysms in highly vascular brain tumors: illustrative case.

BACKGROUND: Intratumoral aneurysms in highly vascular brain tumors can complicate resection depending on their location and feasibility of proximal control. Seemingly unrelated neurological symptoms may be from vascular steal that can help alert the need for additional vascular imaging and augmenting surgical strategies. OBSERVATIONS: A 29-year-old female presented with headaches and unilateral blurred vision, secondary to a large right frontal dural-based lesion with hypointense signal thought to represent calcifications. Given these latter findings and clinical suspicion for a vascular steal phenomenon to explain the blurred vision, computed tomography angiography was obtained, revealing a 4 × 2-mm intratumoral aneurysm. Diagnostic cerebral angiography confirmed this along with vascular steal by the tumor from the right ophthalmic artery. The patient underwent endovascular embolization of the intratumoral aneurysm, followed by open tumor resection in the same setting without complication, minimal blood loss, and improvement in her vision. LESSONS: Understanding the blood supply of any tumor, but highly vascular ones in particular, and the relationship with normal vasculature is undeniably important in avoiding potentially dangerous situations and optimizing maximal safe resection. Recognition of highly vascular tumors should prompt thorough understanding of the vascular supply and relationship of intracranial vasculature with consideration of endovascular adjuncts when appropriate.

Epstein-Barr virus-associated primary intracranial leiomyosarcoma in an immunocompetent patient: illustrative case.

BACKGROUND: Primary intracranial leiomyosarcomas (PILMSs) are extremely rare tumors arising from smooth muscle connective tissue. PILMSs have been shown to be associated with Epstein-Barr virus (EBV). Thus far, EBV-associated PILMS has been exclusively described in immunocompromised patients. OBSERVATIONS: A 40-year-old male presented with a 2-year history of left-sided headaches, nausea, and vomiting. Magnetic resonance imaging demonstrated a large, heterogeneously enhancing, lobulated, dura-based mass arising from the left middle cranial fossa with associated edema and mass effect. The patient underwent an uncomplicated resection of suspected meningioma; neuropathology revealed the exceedingly rare diagnosis of EBV-associated PILMS. Follow-up testing for human immunodeficiency virus (HIV) and other immunodeficiencies confirmed the patient's immunocompetent status. LESSONS: Primary intracranial smooth muscle tumors are often misdiagnosed as meningiomas due to their similar appearance on imaging. PILMSs have a poor prognosis and gross total resection is the mainstay of treatment in the absence of clear recommendations for management. Prompt diagnosis and resection are important; therefore, these tumors should be included in the differential of dura-based tumors, especially among immunocompromised patients. Although EBV-associated PILMSs usually occur in immunocompromised individuals, their presence cannot be ruled out in immunocompetent patients.

Radiological and clinical outcomes of pituitary apoplexy: comparison of conservative management versus early surgical intervention.

OBJECTIVE: Early surgical intervention for patients with pituitary apoplexy (PA) is thought to improve visual outcomes and decrease mortality. However, some patients may have good clinical outcomes without surgery. The authors sought to compare the radiological and clinical outcomes of patients with PA who were managed conservatively versus those who underwent early surgery. METHODS: Patients with symptomatic PA were identified. Radiological, endocrinological, and ophthalmological data were reviewed. Patients with progressive visual deterioration or ophthalmoplegia were candidates for early surgery (within 7 days). Patients without visual symptoms or whose symptoms improved on high-dose steroids were treated conservatively. Log-rank and univariate analysis compared clinical and radiological outcomes between those receiving early surgery and those who underwent intended conservative management. RESULTS: Sixty-four patients with PA were identified: 47 (73.4%) underwent intended conservative management, while 17 (26.6%) had early surgery. Patients receiving early surgery had increased rates of impaired visual acuity (VA; 64.7% vs 27.7%, p = 0.009); visual field (VF) deficits (64.7% vs 19.2%, p = 0.002); and cranial neuropathies (58.8% vs 29.8%, p < 0.05) at presentation. Tumor volumes were greater in the early surgical cohort (15.1 ± 14.8 cm3 vs 4.5 ± 10.3 cm3, p < 0.001). The median clinical and radiological follow-up visits were longer in the early surgical cohort (70.0 and 64.4 months vs 26.0 and 24.7 months, respectively; p < 0.001). Among those with VA/VF deficits, visual outcomes were similar between both groups (p > 0.9). The median time to VA improvement (2.0 vs 3.0 months, p = 0.9; HR 0.9, 95% CI 0.3-3.5) and the median time to VF improvement (2.0 vs 1.5 months; HR 0.8, 95% CI 0.3-2.6, p = 0.8) were similar across both cohorts. Cranial neuropathy improvement was more common in conservatively managed patients (HR 4.8, 95% CI 1.5-15.4, p < 0.01). Conservative management failed in 7 patients (14.9%) and required surgery. PA volumes spontaneously regressed in 95.0% of patients (38/40) with successful conservative management, with a 6-month regression rate of 66.2%. Twenty-seven patients (19 in the conservative and 8 in the early surgical cohorts) responded to a prospectively administered Visual Function Questionnaire-25 (VFQ-25). VFQ-25 scores were similar across both cohorts (conservative 95.5 ± 3.8, surgery 93.2 ± 5.1, p = 0.3). Younger age, female sex, and patients with VF deficits or chiasmal compression were more likely to experience unsuccessful conservative management. Surgical outcomes were similar for patients receiving early versus delayed surgery. CONCLUSIONS: These data suggest that a majority of patients with PA can be successfully managed without surgical intervention assuming close neurosurgical, radiological, and ophthalmological follow-up is available.

Low frequency of delayed ischemic events on MRI after flow diversion for intracranial aneurysms.

BACKGROUND: The rate of silent ischemia detected on Magnetic Resonance Imaging (MRI) in the long-term follow-up period following endovascular treatment of intracranial aneurysms with the Pipeline Embolization Device (PED) is not well established. The purpose of this study was to evaluate the occurrence rate of silent ischemia detected on MRI in patients undergoing treatment of intracranial aneurysms with PED receiving at least 6 months of MRI follow-up. METHODS: We evaluated our institution's database of patients receiving PED treatment of intracranial aneurysms. Imaging records were searched to identify which patients received an MRI at least six-months postoperatively. MR images were reviewed for evidence of new infarction and medical records were reviewed to determine the clinical outcome. RESULTS: Of the 68 patients with MR imaging following aneurysm treatment with PED, 40 patients had an MRI at least six months following treatment with the PED. Of patients with MRI at ≥6 months following PED treatment, 2/40 (5.0%) had a new infarct. Of these, one had a lacunar infarct which was likely non-embolic and one patient had a punctate infarction in the contralateral centrum semiovale. None of these infarcts were symptomatic. CONCLUSIONS: In this study, a small number of silent ischemic events (5.0%) was found on routine long-term follow-up MRI of patients undergoing flow diversion. These events did not lead to any neurologic deficits. Our findings add to the available evidence on the long-term safety of flow diversion for the treatment of intracranial aneurysms.

Endoscopic endonasal approach for craniovertebral junction pathology: a review of the literature.

OBJECT: The transoral approach is the gold standard for ventral decompression of the brainstem caused by craniovertebral junction (CVJ) pathology. This approach is often associated with significant morbidity, related to swallowing and respiratory complications. The endoscopic endonasal approach was introduced to reduce the rate of these complications. However, the exact role of this approach in the treatment of CVJ pathology is not well defined. METHODS: A comprehensive literature search was performed to identify series of patients with pathology of the CVJ treated via the endoscopie endonasal approach. Data on patient characteristics, indications for treatment, complications, and outcome were obtained and analyzed. RESULTS: Twelve studies involving 72 patients were included. The most common indications for treatment were rheumatoid pannus (38.9%) and basilar invagination (29.2%). Cerebrospinal fluid leak was found in 18% of cases intraoperatively and 4.2% of cases postoperatively. One case of meningitis complicated by sepsis and death represents the procedure-related mortality of 1.4%. Of the patients without preoperative swallowing impairment, 95% returned to oral feeding on the 3rd postoperative day. Ninety-three percent of patients experienced improvement in neurological symptoms after the procedure. CONCLUSIONS: The endonasal endoscopie approach is effective for the treatment of neural compression caused by CVJ pathology. It offers advantages such as lower rates of postoperative dysphagia and respiratory complications when compared with the more traditional transoral approach. However, these 2 approaches should be seen as complementary rather than alternatives. Patient-related factors as well as the surgeon's expertise must be considered when making treatment decisions.

A cause of atypical intracranial subarachnoid hemorrhage: posterior spinal artery aneurysms.

BACKGROUND: Approximately 1 % of cases of intracranial subarachnoid hemorrhage (SAH) are caused by spinal vascular pathologies. Among them, isolated spinal artery aneurysms are uncommon and a limited number of cases have been reported in the literature. METHODS: This is a report of two cases and review of the literature. RESULTS: Both patients presented with an atypical intracranial SAH and were also found to have spinal SAH caused by a ruptured posterior spinal aneurysm. CONCLUSION: Isolated spinal artery aneurysms represent a rare cause of intracranial SAH. Symptoms such as back pain and lower-extremity weakness can be clues to the adequate diagnosis. Surgical or endovascular treatment should be pursued in all patients, as the risk of rebleeding is non-negligible.

Resection of cervical ependymoma.

Intramedullary ependymomas are surgically curable tumors. However, their surgical resection poses several challenges. In this intraoperative video we illustrate the main steps for the surgical resection of a cervical intramedullary ependymoma. These critical steps include: adequate exposure of the entire length of the tumor; use of the intraoperative ultrasound; identification of the posterior median sulcus and separation of the posterior columns; Identification of the plane between the spinal cord and the tumor; mobilization and debulking of the tumor and disconnection of the vascular supply (usually from small anterior spinal artery branches). Following these basic steps a complete resection can be safely achieved in many cases. The video can be found here: http://youtu.be/QMYXC_F4O4U.

Resection of spinal hemangioblastoma.

Spinal cord hemangioblastomas occur as sporadic lesions or in the setting of Von Hippel-Lindau disease. In this intraoperative video we present a case of sporadic cervical cord hemangioblastoma and illustrate the main surgical steps to achieve safe and complete resection which include: identification and division of the feeding arteries; careful circumferential dissection of the tumor from the surrounding gliotic cord; identification, isolation and division of the main venous drainage and single piece removal of the tumor. The video can be found here: http://youtu.be/I7DxqRrfTxc.

Are parenchymal AVMs congenital lesions?

A long-held dogma in neurosurgery is that parenchymal arteriovenous malformations (AVMs) are congenital. However, there is no strong evidence supporting this theory. An increasing number of documented cases of de novo formation of parenchymal AVMs cast doubt on their congenital nature and suggest that indeed the majority of these lesions may form after birth. Further evidence suggesting the postnatal development of parenchymal AVMs comes from the exceedingly rare diagnosis of these lesions in utero despite the widespread availability of high-resolution imaging modalities such as ultrasound and fetal MRI. The exact mechanism of AVM formation has yet to be elucidated, but most likely involves genetic susceptibility and environmental triggering factors. In this review, the authors report 2 cases of de novo AVM formation and analyze the evidence suggesting that they represent an acquired condition.

Craniotomy for anterior cranial fossa meningiomas: historical overview.

The surgical treatment of meningiomas located at the base of the anterior cranial fossa is often challenging, and the evolution of the surgical strategy to resect these tumors parallels the development of craniotomy, and neurosurgery in general, over the past century. Early successful operations to treat these tumors were pioneered by prominent figures such as Sir William Macewen and Francesco Durante. Following these early reports, Harvey Cushing made significant contributions, allowing a better understanding and treatment of meningiomas in general, but particularly those involving the anterior cranial base. Initially, large-sized unilateral or bilateral craniotomies were necessary to approach these deep-seated lesions. Technical advances such as the introduction of electrosurgery, the operating microscope, and refined microsurgical instruments allowed neurosurgeons to perform less invasive surgical procedures with better results. Today, a wide variety of surgical strategies, including endoscopic surgery and radiosurgery, are used to treat these tumors. In this review, the authors trace the evolution of craniotomy for anterior cranial fossa meningiomas.

Asymptomatic carotid artery stenosis: time to rethink our therapeutic options?

Asymptomatic carotid artery stenosis is a well-recognized risk factor for ischemic stroke, and its prevalence increases with age. In the late 1980s and in the 1990s, well-designed randomized trials established a definite advantage for carotid endarterectomy in reducing the risk of ipsilateral stroke when compared with medical therapy alone. However, medical treatment of cardiovascular disease has improved significantly over the past 2 decades, and this has, in turn, resulted in a decline of the stroke risk in patients with asymptomatic carotid artery stenosis treated medically. This improvement in medical therapy casts doubts on the effectiveness of large-scale invasive treatment in patients with asymptomatic carotid artery stenosis. Several studies have been conducted to identify possible subgroups of patients with asymptomatic stenosis who are at higher risk of stroke in order to maximize the potential benefits of invasive treatment. Ongoing large-scale trials comparing best current medical therapy to available invasive treatments, such as carotid endarterectomy and carotid artery stenting, are likely to shed some light on this debated topic in the near future. In this review, the authors summarize the current controversy surrounding the ideal management of asymptomatic carotid artery stenosis.