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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.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/cirurgia , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/etnologia , Adulto , Idoso , Etnicidade/genética , Hispânico ou Latino/genética , Mutação , Grupos Raciais/genética , Genômica , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose TumoralRESUMO
Gliomas with CDKN2A mutations are known to have worse prognosis but imaging features of these gliomas are unknown. Our goal is to identify CDKN2A specific qualitative imaging biomarkers in glioblastomas using a new informatics workflow that enables rapid analysis of qualitative imaging features with Visually AcceSAble Rembrandtr Images (VASARI) for large datasets in PACS. Sixty nine patients undergoing GBM resection with CDKN2A status determined by whole-exome sequencing were included. GBMs on magnetic resonance images were automatically 3D segmented using deep learning algorithms incorporated within PACS. VASARI features were assessed using FHIR forms integrated within PACS. GBMs without CDKN2A alterations were significantly larger (64 vs. 30%, p = 0.007) compared to tumors with homozygous deletion (HOMDEL) and heterozygous loss (HETLOSS). Lesions larger than 8 cm were four times more likely to have no CDKN2A alteration (OR: 4.3; 95% CI 1.5-12.1; p < 0.001). We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/patologia , Homozigoto , Deleção de Sequência , Glioma/patologia , Proteínas Inibidoras de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Informática , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , MutaçãoRESUMO
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.
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Neoplasias Encefálicas , Fragilidade , Neoplasias Meníngeas , Humanos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Fragilidade/complicações , Neoplasias Meníngeas/cirurgia , Complicações Pós-Operatórias/etiologia , Prognóstico , Resultado do TratamentoRESUMO
The incidence of brain metastases (BM) amongst cancer patients has been increasing due to improvements in therapeutic options and an increase in overall survival. Molecular characterization of tumors has provided insights into the biology and oncogenic drivers of BM and molecular subtype-based screening. Though there are currently some screening and surveillance guidelines for BM, they remain limited. In this comprehensive review, we review and present epidemiological data on BM, their molecular characterization, and current screening guidelines. The molecular subtypes with the highest BM incidence are epithelial growth factor receptor-mutated non-small cell lung cancer (NSCLC), BRCA1, triple-negative (TN), and HER2+ breast cancers, and BRAF-mutated melanoma. Furthermore, BMs are more likely to present asymptomatically at diagnosis in oncogene-addicted NSCLC and BRAF-mutated melanoma. European screening standards recommend more frequent screening for oncogene-addicted NSCLC patients, and clinical trials are investigating screening for BM in hormone receptor+, HER2+, and TN breast cancers. However, more work is needed to determine optimal screening guidelines for other primary cancer molecular subtypes. With the advent of personalized medicine, molecular characterization of tumors has revolutionized the landscape of cancer treatment and prognostication. Incorporating molecular characterization into BM screening guidelines may allow physicians to better identify patients at high risk for BM development and improve patient outcomes.
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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.
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Neoplasias Meníngeas , Meningioma , Humanos , Estados Unidos , Meningioma/patologia , Classe Social , Hospitalização , Tempo de Internação , Neoplasias Meníngeas/patologia , Disparidades em Assistência à SaúdeRESUMO
Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviors (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissect the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. Here, we report that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum reveals differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings uncover a cell-type-specific impact of the loss of fragile X messenger ribonucleoprotein (FMRP) on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS.
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Transtorno do Espectro Autista , Síndrome do Cromossomo X Frágil , Animais , Humanos , Camundongos , Síndrome do Cromossomo X Frágil/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Neurônios/metabolismo , Sinapses/metabolismo , Camundongos Knockout , Modelos Animais de DoençasRESUMO
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.
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Neoplasias Meníngeas , Meningioma , Neoplasias Supratentoriais , Humanos , Meningioma/genética , Meningioma/cirurgia , Meningioma/complicações , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/complicações , Mutação/genética , Genômica , Neoplasias Supratentoriais/genética , Neoplasias Supratentoriais/cirurgiaRESUMO
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.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Procedimentos Neurocirúrgicos , Estudos RetrospectivosRESUMO
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.
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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.
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INTRODUCTION: Spinal myxopapillary ependymomas (SME) are rare WHO grade II neoplasms of the spinal cord. Despite their good prognosis, they have a high propensity for metastasis and recurrence, although the presentation of SME as multifocal is uncommon. CASE PRESENTATION: Here we describe a rare case of a 34-year-old man who presented with painful bilateral radiculopathy with sexual dysfunction and altered sensation with defecation. The patient also reported worsening weakness of bilateral lower extremities when climbing stairs. Biopsy results revealed multifocal SME in the lumbar and sacral spine that was treated with staged surgical resection and post-operative focal radiation therapy. DISCUSSION: We discuss and evaluate surgical resection and the role of postoperative radiotherapy for SME. We also review the literature surrounding multifocal SME presenting in adults.
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Ependimoma , Neoplasias da Medula Espinal , Adulto , Ependimoma/diagnóstico , Ependimoma/patologia , Ependimoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Resultado do TratamentoRESUMO
Solitary fibrous tumors (SFTs) are rare soft tissue neoplasms that can impact the central nervous system (CNS). SFTs comprise <1% of all primary CNS tumors. Here, we describe a rare case of intradural, extramedullary SFT arising within the thoracic spine that was treated with surgical resection. Histological features were evaluated and revealed a highly cellular tumor with positive expression of BCL2, CD34, CD99, and STAT6 proteins that are consistent with a diagnosis of SFT. We discuss the use of surgical intervention for long-term disease control of spinal SFT and evaluate the role of postoperative radiation therapy in management strategies. Lastly, we review the literature reports of intradural, extramedullary SFTs in the thoracic spine. The importance of molecular characterization by histopathology to properly determine diagnosis and prognosis is emphasized.
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Supplementary motor area (SMA) syndrome refers to varying degrees of transient hemiparesis and mutism following insult to the medial posterior frontal lobe. We describe a rare case of an isolated lower limb SMA deficit with associated pre- and post-operative multimodality neurophysiological monitoring data. We review the literature on SMA somatotopy and the prognostic abilities of intraoperative motor evoked potentials in suspected SMA dysfunction. A 45-year-old male underwent staged resection of a complex parasagittal WHO grade II meningioma involving the posterior superior frontal gyrus bilaterally. Intraoperative neurophysiological monitoring with transcranial motor evoked potentials (TCMEP) and direct cortical motor evoked potentials (DCMEP) were used during both stages of resection. The patient developed an isolated left foot drop despite unchanged DCMEP and TCMEP data obtained during the first stage of the procedure. During the second stage of resection 3 days later, repeat neurophysiological monitoring confirmed intact corticospinal tracts. Deep peroneal somatosensory evoked potentials (SSEPs) revealed good morphology, appropriate latency and amplitudes during the second stage of resection. These results suggested a diagnosis of focal SMA dysfunction. Left foot drop persisted 7 days post-operatively. At one month follow up, the patient was neurologically intact with full strength noted in all muscle groups of the left lower extremity. An improved understanding of the somatotopic organization of the SMA with additional neuromonitoring data can allow neurosurgeons to better predict and understand perioperative SMA dysfunctions.
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Córtex Motor , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Humanos , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Tratos PiramidaisRESUMO
PURPOSE: Supratotal resection (SpTR) of high-grade glioma (HGG), in which surgical removal of the tumor is extended outside the margins of the preoperative radiographic abnormality, has been suggested to improve overall survival (OS) and progression free survival (PFS) in patients harboring tumors of non-eloquent cortex when compared to gross total resection (GTR). While current literature demonstrates these findings without an increase in post-operative complications or neurological deficits, there remains a paucity of data examining the neuropsychological outcomes of SpTR for HGG. As quality of life dramatically influences survival rates in these patients, it is crucial for neurosurgeons, neuro-oncologists, and neuropsychiatrists to understand the behavioral and cognitive outcomes following SpTR, such that optimal treatment strategies can be tailored for each patient. METHODS: We performed a comprehensive review of the available literature regarding survival, neuropsychological, and quality of life (QOL) outcomes following SpTR for HGG. We also review neuropsychological and QOL outcomes following GTR for HGG to serve as a framework for better understanding potential implications of SpTR. RESULTS: While results are limited following SpTR for HGG, available data suggests similar outcomes to those seen in patients undergoing GTR of HGG, as well as low-grade glioma. These include a short-term decline in neuropsychological functioning post-surgically with a return to baseline across most neurocognitive domains occurring within several months. Memory and attention remain relatively diminished at long term follow-up. CONCLUSIONS: Limited data exist examining postoperative cognitive and behavioral outcomes following SpTR for HGG. While the available data suggests a return to baseline for many neurocognitive domains, attention and memory deficits may persist. However, sample sizes are relatively small and have not been examined in the context of QOL and OS/PFS. More rigorous pre- and post-surgical neuropsychological assessment will help shed light on the long-term cognitive and behavioral effects of SpTR in the setting of HGG and inform clinical care and counseling when SpTR is considered.