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Glioma cells hijack developmental programs to control cell state. Here, we uncover a glioma cell state-specific metabolic liability that can be therapeutically targeted. To model cell conditions at brain tumor inception, we generated genetically engineered murine gliomas, with deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling astrocyte differentiation during brain development. N1IC tumors harbored quiescent astrocyte-like transformed cell populations while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. Further, N1IC transformed cells exhibited increased mitochondrial lipid peroxidation, high ROS production and depletion of reduced glutathione. This altered mitochondrial phenotype rendered the astrocyte-like, quiescent populations more sensitive to pharmacologic or genetic inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Treatment of patient-derived early-passage cell lines and glioma slice cultures generated from surgical samples with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles. Collectively, these findings reveal a specific therapeutic vulnerability to ferroptosis linked to mitochondrial redox imbalance in a subpopulation of quiescent astrocyte-like glioma cells resistant to standard forms of treatment.
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The authors describe the awake surgical mapping of music skills for patients who require resection in brain areas that may support musical abilities. A 65-year-old man was diagnosed with an anterolateral right temporal nonenhancing lesion, likely a diffusely infiltrating glioma, after presenting with several episodes of altered taste and smell and one episode of loss of consciousness. The patient specializes in music and music technology and has composed scores for films. An awake surgery was planned in a semiseated position. Prerecorded melodies were designed preoperatively as a surrogate for a composition skill task. These consisted of 10- to 15-second musical clips played during bipolar electrical stimulation of the overlying cortex and were divided into three segments: listen, play, and accuracy check. During the "listen" phase, the patient listened to a musical prompt. During the "play" phase, he played a musical response on a keyboard. Stimulation at multiple temporal neocortical sites was negative for any alteration in task performance. The patient did well postoperatively with excellent clinical and radiographic results and returned to composing music without functional compromise. Musical composition tasks can be performed safely intraoperatively for patients with musical expertise. Whether stimulating more posterior nondominant temporal neocortex or other cortical or white matter locations can disrupt this task remains undetermined.
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Neoplasias Encefálicas , Glioma , Música , Masculino , Humanos , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Vigília , Glioma/cirurgia , Encéfalo , Mapeamento Encefálico/métodosRESUMO
INTRODUCTION: Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data. METHODS: Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells. RESULTS: Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing. CONCLUSION: Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Animais , Humanos , Glioblastoma/tratamento farmacológico , NG-Nitroarginina Metil Éster/uso terapêutico , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Óxido Nítrico Sintase , Óxido Nítrico/uso terapêuticoRESUMO
BACKGROUND: Topotecan is cytotoxic to glioma cells but is clinically ineffective because of drug delivery limitations. Systemic delivery is limited by toxicity and insufficient brain penetrance, and, to date, convection-enhanced delivery (CED) has been restricted to a single treatment of restricted duration. To address this problem, we engineered a subcutaneously implanted catheter-pump system capable of repeated, chronic (prolonged, pulsatile) CED of topotecan into the brain and tested its safety and biological effects in patients with recurrent glioblastoma. METHODS: We did a single-centre, open-label, single-arm, phase 1b clinical trial at Columbia University Irving Medical Center (New York, NY, USA). Eligible patients were at least 18 years of age with solitary, histologically confirmed recurrent glioblastoma showing radiographic progression after surgery, radiotherapy, and chemotherapy, and a Karnofsky Performance Status of at least 70. Five patients had catheters stereotactically implanted into the glioma-infiltrated peritumoural brain and connected to subcutaneously implanted pumps that infused 146 µM topotecan 200 µL/h for 48 h, followed by a 5-7-day washout period before the next infusion, with four total infusions. After the fourth infusion, the pump was removed and the tumour was resected. The primary endpoint of the study was safety of the treatment regimen as defined by presence of serious adverse events. Analyses were done in all treated patients. The trial is closed, and is registered with ClinicalTrials.gov, NCT03154996. FINDINGS: Between Jan 22, 2018, and July 8, 2019, chronic CED of topotecan was successfully completed safely in all five patients, and was well tolerated without substantial complications. The only grade 3 adverse event related to treatment was intraoperative supplemental motor area syndrome (one [20%] of five patients in the treatment group), and there were no grade 4 adverse events. Other serious adverse events were related to surgical resection and not the study treatment. Median follow-up was 12 months (IQR 10-17) from pump explant. Post-treatment tissue analysis showed that topotecan significantly reduced proliferating tumour cells in all five patients. INTERPRETATION: In this small patient cohort, we showed that chronic CED of topotecan is a potentially safe and active therapy for recurrent glioblastoma. Our analysis provided a unique tissue-based assessment of treatment response without the need for large patient numbers. This novel delivery of topotecan overcomes limitations in delivery and treatment response assessment for patients with glioblastoma and could be applicable for other anti-glioma drugs or other CNS diseases. Further studies are warranted to determine the effect of this drug delivery approach on clinical outcomes. FUNDING: US National Institutes of Health, The William Rhodes and Louise Tilzer Rhodes Center for Glioblastoma, the Michael Weiner Glioblastoma Research Into Treatment Fund, the Gary and Yael Fegel Foundation, and The Khatib Foundation.
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Glioblastoma , Glioma , Humanos , Topotecan/efeitos adversos , Glioblastoma/tratamento farmacológico , Convecção , Recidiva Local de Neoplasia/tratamento farmacológico , Glioma/patologiaRESUMO
Understanding dexamethasone's effect on the immune microenvironment in glioma patients is of key importance. We performed a comprehensive literature review using the NCBI PubMed database for all articles meeting the following search criteria. ((dexamethasone[All Fields]) AND (glioma or glioblastoma)[Title/Abstract]) AND (immune or T cell or B cell or monocyte or neutrophil or macrophage). Forty-three manuscripts were deemed relevant to the topic at hand. Multiple clinical studies have linked dexamethasone use to decreased overall survival while preclinical studies in murine glioma models have demonstrated decreased tumor-infiltrating lymphocytes after dexamethasone administration.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Animais , Neoplasias Encefálicas/tratamento farmacológico , Dexametasona/uso terapêutico , Glioma/tratamento farmacológico , Humanos , Imunoterapia , Linfócitos do Interstício Tumoral , Camundongos , Medicina de Precisão , Microambiente TumoralRESUMO
BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of approximately 15 months. Semaphorin 3A (Sema3A), known for its axon guidance and antiangiogenic properties, has been implicated in GBM growth. We hypothesized that Sema3A directly inhibits brain tumor stem cell (BTSC) proliferation and drives invasion via Neuropilin 1 (Nrp1) and Plexin A1 (PlxnA1) receptors. METHODS: GBM BTSC cell lines were assayed by immunostaining and PCR for levels of Semaphorin 3A (Sema3A) and its receptors Nrp1 and PlxnA1. Quantitative BrdU, cell cycle and propidium iodide labeling assays were performed following exogenous Sema3A treatment. Quantitative functional 2-D and 3-D invasion assays along with shRNA lentiviral knockdown of Nrp1 and PlxnA1 are also shown. In vivo flank studies comparing tumor growth of knockdown versus control BTSCs were performed. Statistics were performed using GraphPad Prism v7. RESULTS: Immunostaining and PCR analysis revealed that BTSCs highly express Sema3A and its receptors Nrp1 and PlxnA1, with expression of Nrp1 in the CD133 positive BTSCs, and absence in differentiated tumor cells. Treatment with exogenous Sema3A in quantitative BrdU, cell cycle, and propidium iodide labeling assays demonstrated that Sema3A significantly inhibited BTSC proliferation without inducing cell death. Quantitative functional 2-D and 3-D invasion assays showed that treatment with Sema3A resulted in increased invasion. Using shRNA lentiviruses, knockdown of either NRP1 or PlxnA1 receptors abrogated Sema3A antiproliferative and pro-invasive effects. Interestingly, loss of the receptors mimicked Sema3A effects, inhibiting BTSC proliferation and driving invasion. Furthermore, in vivo studies comparing tumor growth of knockdown and control infected BTSCs implanted into the flanks of nude mice confirmed the decrease in proliferation with receptor KD. CONCLUSIONS: These findings demonstrate the importance of Sema3A signaling in GBM BTSC proliferation and invasion, and its potential as a therapeutic target.
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Neoplasias Encefálicas/patologia , Receptores ErbB/genética , Genes erbB-1 , Glioblastoma/patologia , Glioma/patologia , Proteínas de Neoplasias/fisiologia , Semaforina-3A/fisiologia , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Vetores Genéticos/genética , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/genética , Glioma/metabolismo , Xenoenxertos , Humanos , Lentivirus/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Neuropilina-1/biossíntese , Neuropilina-1/genética , Neuropilina-1/fisiologia , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/fisiologia , Organismos Livres de Patógenos EspecíficosRESUMO
Meningiomas are the most prevalent primary tumor of central nervous system origin, and although most of these neoplasms are benign, a small proportion exemplifies an aggressive profile characterized by high recurrence rates, pleomorphic histology, and overall resistance to standard treatment. Standard initial therapy for malignant meningiomas includes maximal safe surgical resection followed by focal radiation. The role for chemotherapy during recurrence of these aggressive meningiomas is less clear. Prognosis is poor, and recurrence of malignant meningiomas is high. This article provides an overview of atypical and anaplastic "malignant" meningiomas, their treatment, and ongoing research looking for more effective treatments.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirurgia , Neoplasias Meníngeas/cirurgia , Resultado do Tratamento , Prognóstico , Sistema Nervoso CentralRESUMO
BACKGROUND: Current trends in surgical neuro-oncology show that early discharges are safe and feasible with shorter lengths of stay (LOS) and fewer thromboembolic complications, fewer hospital-acquired infections, reduced costs, and greater patient satisfaction. Traditionally, infratentorial tumor resections have been associated with longer LOS and limited data exist evaluating predictors of early discharge in these patients. The objective was to assess patients undergoing posterior fossa craniotomies for tumor resection and identify variables associated with postoperative day 1 (POD1) discharge. METHODS: A retrospective review of posterior fossa craniotomies for tumor resection at our institution was performed from 2011 to 2020. Laser ablations, nontumoral pathologies, and biopsies were excluded. Demographic, clinical, surgical, and postoperative data were collected. RESULTS: One hundred and seventy-three patients were identified and 25 (14.5%) were discharged on POD1. Median length of stay (LOS) was 6 days. The POD1 discharges had significantly better preoperative Karnofsky performance scores (P < 0.001) and modified Rankin scores (P = 0.002) and more frequently presented electively (P = 0.006) and without preoperative neurologic deficits (P = 0.021). No statistically significant difference in 30-day readmissions and rates of PE, UTI, and DVT was found. Univariate logistic regression identified better preoperative functional status, elective admission, and lack of preoperative hydrocephalus as predictors of POD1 discharge, however only the latter remained significant in the multivariable model (P = 0.001). CONCLUSIONS: Discharging patients on POD1 is feasible following posterior fossa tumor resection in a select group of patients. Although we found that the only independent predictor for a longer LOS was preoperative hydrocephalus, larger, prospective studies are needed to confirm these findings.
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Neoplasias Encefálicas , Hidrocefalia , Neoplasias Infratentoriais , Humanos , Alta do Paciente , Neoplasias Infratentoriais/cirurgia , Neoplasias Infratentoriais/complicações , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações , Craniotomia/efeitos adversos , Estudos Retrospectivos , Hidrocefalia/cirurgia , Tempo de Internação , Complicações Pós-Operatórias/etiologiaRESUMO
Brain tumor incidence is on the rise, and glioblastoma comprises the majority of primary tumors. Despite maximal safe resection and adjuvant chemoradiation, median survival for high-grade glioma remains poor. For this reason, it is important to develop and incorporate new treatment strategies. Oncolytic virotherapy has emerged as a viable new therapeutic entity to fill this gap. Preclinical research has shown oncolytic virotherapy to be a robust and effective treatment option for brain tumors, and clinical trials for both adult and pediatric high-grade glioma are underway. The unique and protected environment of the nervous system, in part due to the blood-brain barrier, prevents traditional systemic therapies from achieving adequate penetration. Brain tumors are also heterogenous in nature due to their diverse molecular profiles, further complicating systemic treatment efforts. Oncolytic viruses may serve to fill this gap in brain tumor treatment given their amenability to genetic modification and ability to target unique tumor epitopes. In addition, direct inoculation of the oncolytic virus agent to the tumor bed following surgical resection absolves risk of systemic side effects and ensures adequate delivery. As virotherapy transitions from bench to bedside, it is important to discuss factors to make this transition more seamless. In this article, we describe the current clinical evidence as it pertains to oncolytic virotherapy and the treatment of brain tumors as well as factors to consider for its incorporation into neurosurgical workflow.
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Employing the full arsenal of therapeutics to treat brain tumors is limited by the relative impermeability of the blood-brain and blood-tumor barriers. In physiologic states, the blood-brain barrier serves a protective role by passively and actively excluding neurotoxic compounds; however, this functionality limits the penetrance of therapeutics into the tumor microenvironment. Focused ultrasound technology provides a method for overcoming the blood-brain and blood-tumor barriers through ultrasound frequency to transiently permeabilize or disrupt these barriers. Concomitant delivery of therapeutics has allowed for previously impermeable agents to reach the tumor microenvironment. This review details the advances in focused ultrasound in both preclinical models and clinical studies, with a focus on its safety profile. We then turn towards future directions in focused ultrasound-mediated therapies for brain tumors.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/patologia , Ultrassonografia , Imageamento por Ressonância Magnética/métodos , Microambiente TumoralRESUMO
Background: There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods: We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results: Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (P = .0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, P = .72). Readmission rates, wound infections, and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%), and third semesters (47.86%). Conclusions: Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.
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OBJECTIVE: We aimed to describe our institutional case series of 9 surgically treated uterine brain metastases and perform a survival analysis through a systematic review and a pooled individual patient data study. METHODS: This study was divided into 2 sections: 1) a retrospective, single center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising in the uterus with brain metastases and 2) a systematic review of the literature between 1980 and 2021 regarding treatment outcomes of individual patients with intracranial metastasis of uterine origin. Pooled cohort survival analysis was done via univariate and Cox regression multivariable analysis and Kaplan-Meier curves. RESULTS: Final statistical analysis included a total of 124 pooled cohort patients: one hundred fifteen patients from literature review studies plus 9 patients from our institution. Median age at the time of diagnosis was 54 years. Median time from diagnosis of the primary cancer to brain metastasis was 19 months (0-166 months). Surgery and radiotherapy resulted in the highest median OS of 11 months (P < 0.001). Multivariable analyses indicated that the presence of more than one central nervous systemlesion had an increased risk on OS (P = 0.003). Microsurgery, stereotactic radiosurgery, and whole brain radiotherapy remain the evidence-based mainstay applicable to the treatment of multiple brain metastases. CONCLUSIONS: Brain metastases of cancer arising in the uterus appear to result most often in multiple lesions with dismal prognosis. The seemingly most efficacious treatment modality is surgery and radiotherapy. However, this treatment is often not an option when more than 1 or 2 brain lesions are present.
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Neoplasias Encefálicas , Radiocirurgia , Neoplasias Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/terapia , Radiocirurgia/métodos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.
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Ferroptose , Glioma , Humanos , Animais , Camundongos , Metionina , Cisteína , Proteômica , Racemetionina , Glioma/tratamento farmacológicoRESUMO
Glioma cells hijack developmental transcriptional programs to control cell state. During neural development, lineage trajectories rely on specialized metabolic pathways. However, the link between tumor cell state and metabolic programs is poorly understood in glioma. Here we uncover a glioma cell state-specific metabolic liability that can be leveraged therapeutically. To model cell state diversity, we generated genetically engineered murine gliomas, induced by deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling cellular fate. N1IC tumors harbored quiescent astrocyte-like transformed cell states while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. N1IC cells exhibit distinct metabolic alterations, with mitochondrial uncoupling and increased ROS production rendering them more sensitive to inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Importantly, treating patient-derived organotypic slices with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles.
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BACKGROUND: Dorsal arachnoid webs (DAWs) are rare pathological abnormalities of the arachnoid layer of the spinal cord that can result in pain and myelopathy. OBJECTIVE: To present clinical, imaging, and pathological characteristics of patients diagnosed with DAW, case illustrations, and a review of the literature. METHODS: Seventeen cases of DAW between 2015 and 2019 at a tertiary medical center were retrospectively identified through a case log search. Patient characteristics, preoperative imaging, operative notes, and pathology reports were collected. Our main outcome assessed was postoperative resolution of symptoms. Odds ratios were used to determine associations between preoperative signs and symptoms with postoperative symptom resolution. RESULTS: The mean age of the cohort was 50.5 years (IQR = 16) and presented primarily with back pain (64.7%). On imaging, all patients were found to have the "scalpel sign," and nearly half had a syrinx present (41.2%). All DAWs were located in the thoracic spine, with the most common location being the midthoracic (70.6%). The mean follow-up length for all patients was 4.3 months. There were no preoperative symptoms significantly associated with postoperative symptom resolution; however, a trend was noted with the presence of a preoperative syrinx. Pathology samples consistently demonstrated fibroconnective or collagenous tissue with no evidence of inflammation or neoplasm. CONCLUSION: DAW is a rare pathology that can result in myelopathy or inappropriate interventions if misdiagnosed. Surgical intervention using laminectomy with intradural exploration should be considered in symptomatic patients with DAW because it is curative with a strong chance of preoperative symptom resolution with relatively low complication rates.
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Cistos Aracnóideos , Doenças da Medula Espinal , Siringomielia , Cistos Aracnóideos/cirurgia , Dor nas Costas/cirurgia , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Medula Espinal/cirurgia , Coluna Vertebral/cirurgia , Siringomielia/cirurgiaRESUMO
Background: Large-scale brain networks and higher cognitive functions are frequently altered in neuro-oncology patients, but comprehensive non-invasive brain mapping is difficult to achieve in the clinical setting. The objective of our study is to evaluate traditional and non-traditional eloquent areas in brain tumor patients using a machine-learning platform. Methods: We retrospectively included patients who underwent surgery for brain tumor resection at our Institution. Preoperative MRI with T1-weighted and DTI sequences were uploaded into the Quicktome platform. We categorized the integrity of nine large-scale brain networks: language, sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention, salience and limbic. Network integrity was correlated with preoperative clinical data. Results: One-hundred patients were included in the study. The most affected network was the central executive network (49%), followed by the default mode network (43%) and dorsal attention network (32%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (3.42 vs 2.19, P < .001), compared to patients without deficits. Furthermore, we found that patients without neurologic deficits had an average 2.19 networks affected and 1.51 networks at-risk, with most of them being related to non-traditional eloquent areas (P < .001). Conclusion: Our results show that large-scale brain networks are frequently affected in patients with brain tumors, even when presenting without evident neurologic deficits. In our study, the most commonly affected brain networks were related to non-traditional eloquent areas. Integrating non-invasive brain mapping machine-learning techniques into the clinical setting may help elucidate how to preserve higher-order cognitive functions associated with those networks.
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OBJECT: Rathke cleft cysts (RCCs) are benign masses arising from the embryological Rathke pouch, and are commonly treated by transsphenoidal surgery. The authors retrospectively compared RCC extent of resection-either gross-total resection (GTR) or decompression-to the primary outcome measure, which was recurrences resulting in repeat surgery, and the secondary outcome measure, which was complications. METHODS: Seventy-four patients presenting to the neurosurgical department with RCC were analyzed retrospectively. Sixty-eight patients had a total of 78 surgical procedures, with the diagnosis of RCC confirmed by histological investigation; of these, 61 patients had adequate operative notes for the authors to evaluate extent of resection. Groups were separated into GTR (32 patients) or decompression (subtotal resection or fenestration into the sphenoid sinus; 29 patients) based on operative notes and postoperative imaging. The mean follow-up duration was 60.5 ± 72.1 months (the mean is expressed ± SD throughout). RESULTS: The average age at the time of the initial surgery was 42.8 ± 17.4 years, and 70% of patients were female. The mean cyst diameter preoperatively was 16.9 ± 17.8 mm. Eight patients had repeat surgery, our primary outcome measure; 3 repeat operations occurred in the GTR group, and 5 in the decompression group. There was no significant difference in recurrence when comparing groups (GTR 9%, decompression 17%; p = 0.36). There were no major complications; however, analysis of postoperative minor complications revealed that 11 (34%) GTRs resulted in surgical complications, whereas the decompression cohort accounted for only 3 complications (10%) (p = 0.03), with diabetes insipidus (6) and CSF leaks (5) being the most common. Gross-total resection also resulted in an increase in postoperative hyperprolactinemia compared with decompression (p = 0.03). CONCLUSIONS: It appears that RCCs require repeat surgery in 13% of cases, and attempted GTR does not appear to reduce the overall rate of recurrence. However, more aggressive resections are associated with more complications in this series.
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Cistos do Sistema Nervoso Central/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Cistos do Sistema Nervoso Central/complicações , Descompressão Cirúrgica/efeitos adversos , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
When technically feasible, the preferred revascularization procedure in patients with adult moyamoya disease is a superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass. The caliber of the STA has been reported as a prognostic factor for a successful bypass, with smaller-caliber STA being more likely to fail. We describe a novel approach to this circumstance in which preoperative embolization of external carotid artery (ECA) branches is used to augment blood flow through a small STA as a prelude to bypass surgery. We report 2 cases: a 42-year-old female presenting with symptomatic ischemic and radiographically progressive moyamoya disease and a 23-year-old female presenting with advanced moyamoya disease secondary to diabetes. Preoperative angiography demonstrated small-caliber STAs in each case, and primary revascularization was deemed difficult. Preoperative ECA embolization was undertaken to shunt blood toward the STA, thereby increasing its flow and caliber. In both cases, angiography after embolization demonstrated a 20%-45% increase in STA size, and doppler ultrasound indicated a 14%-50% increase in flow. Subsequently, both patients underwent successful STA-MCA bypass combined with encephalomyosynangiosis without complications. Of 167 STA-MCA bypasses performed by the senior author, embolization was performed in 7 unique patients on 9 sides. ECA embolization may be a beneficial adjunct when considering a direct bypass in the setting of a small STA. It can increase blood flow through the STA, making the operation technically easier and enhancing the patency of the bypass.
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Isquemia Encefálica/terapia , Artéria Carótida Externa/fisiopatologia , Revascularização Cerebral , Embolização Terapêutica , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/terapia , Artérias Temporais/cirurgia , Adulto , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Artéria Carótida Externa/diagnóstico por imagem , Circulação Cerebrovascular , Feminino , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/fisiopatologia , Cuidados Pré-Operatórios , Radiografia , Fluxo Sanguíneo Regional , Resultado do Tratamento , Ultrassonografia Doppler , Adulto JovemRESUMO
Germ cell tumors account for up to 53% of the malignant lesions found in the pineal region and are typically managed with a combination of radiation therapy and chemotherapy. Malignant somatic transformation of intracranial germ cell tumors is exceedingly rare and has only been reported on two other occasions. Here the authors present the case of a pineal yolk sac tumor that failed optimum first-line treatment and underwent malignant somatic transformation to an enteric mucinous adenocarcinoma requiring surgical intervention. This video demonstrates the technical nuances of the occipital transtentorial approach and the safe microsurgical dissection of lesions within the pineal region. The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2151.
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OBJECTIVE: High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. METHODS: The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19-76) years were included in the analysis. Eighteen patients had H3 K27M mutation-positive tumors, and 12 had H3 K27M mutation-negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation-positive tumors (p = 0.017). CONCLUSIONS: Although H3 K27M mutant-positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant-positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant-negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.