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OBJECTIVE: We aim to report the epidemiology, surgical outcomes, and survival rates of pediatric patients with posterior fossa tumors in a large single-center case series. METHODS: A retrospective analysis was conducted on pediatric patients who underwent surgical treatment for posterior fossa tumors between January 2011 and January 2019. RESULTS: A total of 135 pediatric patients, with an average age of 7.5 years at diagnosis and a mean follow-up of 35.7 months, were included in the study. Most tumors were located within the midline, with ventriculomegaly observed in 71.4% of the patients. Pilocytic astrocytomas encompassed the majority of tumors (34.1%), followed by medulloblastomas (27.4%) and ependymomas (11.8%). Gross total resection (GTR) was achieved in 71.8% of the patients, with a recurrence rate of 20%. Surgical complications were observed in 25.9% of the patients. GTR significantly impacted 5-year overall survival (OS) and 4-year progression-free survival (PFS) in patients with posterior fossa tumors. Patients who underwent GTR had a 5-year OS of 89.7%, compared to 72.7% for near-total resection and 70.8% for subtotal resection. The 4-year PFS for patients who underwent GTR was 82.5%, whereas it was 63.6% for patients who underwent near-total resection and 54.2% for patients who underwent subtotal resection. CONCLUSION: Surgical resection remains the main treatment for pediatric posterior fossa tumors, and higher resection rates are linked to better survival outcomes. Despite limited resources for molecular diagnosis, our institution has demonstrated that a specialized neurooncological center with a high surgical volume can still achieve favorable survival outcomes for these patients.

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The endoplasmic reticulum maintains proteostasis, which can be disrupted by oxidative stress, nutrient deprivation, hypoxia, lack of ATP, and toxicity caused by xenobiotic compounds, all of which can result in the accumulation of misfolded proteins. These stressors activate the unfolded protein response (UPR), which aims to restore proteostasis and avoid cell death. However, endoplasmic response-associated degradation (ERAD) is sometimes triggered to degrade the misfolded and unassembled proteins instead. If stress persists, cells activate three sensors: PERK, IRE-1, and ATF6. Glioma cells can use these sensors to remain unresponsive to chemotherapeutic treatments. In such cases, the activation of ATF4 via PERK and some proteins via IRE-1 can promote several types of cell death. The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.

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The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available.

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ABSTRACT This article reports the case of an 11-year-old male patient with a history of proptosis and low progressive visual acuity in the left eye. He presented with a best corrected visual acuity of 20/25 in the right eye and light perception in the left eye. Exotropia and limitation in adduction were observed in the left eye. On automated perimetry, inferiortemporal quadrantopsia was observed in the right eye, while total scotoma was observed in the left eye. On magnetic resonance imaging, there was an expansive lesion in the left optic nerve, extending to the brainstem with chiasmatic involvement. This article aims to report a case of optic pathway glioma, as well as to discuss its clinical findings and their interconnection with the current literature.

RESUMO Este artigo relata o caso de um paciente do sexo masculino, 11 anos de idade, com história de proptose e baixa de acuidade visual progressiva. Ao exame oftalmológico apresentava melhor acuidade visual de 20/25 em olho direito e percepção de luz em olho esquerdo. Existia exotropia e limitação à adução no olho esquerdo. À campimetria automatizada, observou-se quadrantopsia temporal inferior em olho direito e escotoma total em olho esquerdo. À ressonância magnética, evidenciou-se lesão expansiva em trajeto do nervo óptico esquerdo estendendo-se até região do tronco encefálico, com acometimento quiasmático. O objetivo deste artigo é relatar o glioma de vias ópticas, bem como discutir os achados e sua interligação com a literatura atual.

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Neuromonitoring is a critical tool for emergency rooms and intensive care units to promptly identify and treat brain injuries. The case report of a patient with status epilepticus necessitating orotracheal intubation and intravenous lorazepam administration is presented. A pattern of epileptiform activity was detected in the left temporal region, and intravenous Acyclovir was administered based on the diagnostic hypothesis of herpetic meningoencephalitis. The neurointensivist opted for multimodal non-invasive bedside neuromonitoring due to the complexity of the patient's condition. A Brain4care (B4C) non-invasive intracranial compliance monitor was utilized alongside the assessment of an optic nerve sheath diameter (ONSD) and transcranial Doppler (TCD). Based on the collected data, a diagnosis of intracranial hypertension (ICH) was made and a treatment plan was developed. After the neurosurgery team's evaluation, a stereotaxic biopsy of the temporal lesion revealed a grade 2 diffuse astrocytoma, and an urgent total resection was performed. Research suggests that monitoring patients in a dedicated neurologic intensive care unit (Neuro ICU) can lead to improved outcomes and shorter hospital stays. In addition to being useful for patients with a primary brain injury, neuromonitoring may also be advantageous for those at risk of cerebral hemodynamic impairment. Lastly, it is essential to note that neuromonitoring technologies are non-invasive, less expensive, safe, and bedside-accessible approaches with significant diagnostic and monitoring potential for patients at risk of brain abnormalities. Multimodal neuromonitoring is a vital tool in critical care units for the identification and management of acute brain trauma as well as for patients at risk of cerebral hemodynamic impairment.

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Abstract Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.

Resumo Tumores associados a epilepsia de longa duração constituem uma série de neoplasias asatrocitárias ou glioneuronais que comumente incidem em crianças, adolescentes e jovens adultos e que são histologicamente benignos (OMS grau 1), de localização neocortical e predominantemente situados nos lobos temporais. Clinicamente, a epilepsia crônica refratária é, de modo geral, o único sintoma. Gangliogliomas (GG) e tumores neuroepiteliais disembrioplásticos (DNT) são as entidades mais representativas associadas a astrocitomas pilocíticos (AP) e gliomas angiocêntricos (GA). Estudos moleculares recentes permitiram a definição de novas entidades clínico-patológicas reconhecidas pela classificação de tumores cerebrais da OMS 2021. Algumas delas, como o astrocitoma difuso MIB ou MIBL1 alterados, o tumor neuroepitelial polimorfo do jovem (PLNTY) e o tumor neuronal multilocular e vacuolizado (MVNT) são atualmente considerados tumores associados a epilepsia de longa duração. A relação entre este grupo de tumores e epilepsia é ainda debatida e há um consenso geral sobre o benefício prognóstico de intervenção cirúrgica precoce.

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Pilocytic astrocytoma is the most common primary CNS neoplasm in children and adolescents, rare after the first two decades of life. While some authors report a favorable prognosis in the adult age group with the tumor, others have associated it with higher mortality. The molecular alteration most observed in cases of pilocytic astrocytoma in the pediatric group is the BRAF-KIAA1549 gene fusion, and there are still few studies confirming the presence of this fusion in the adult population. This work investigated genetic alterations involving the 7q34 region in BRAF gene in 21 adult individuals with pilocytic astrocytoma, by FISH. In addition, was identified the immunohistochemical expression of BRAFV600E, correlating these findings with histopathological and clinical ones. BRAF-KIAA1549 fusion appeared in only one case, while in two other cases were found deletions related to the FAM131B-BRAF fusion, suggesting that maybe the latter is more frequently in this population. Through the evaluation of immunoreactivity, 71% of the cases were considered positive and 29% negative. Cases considered positive for BRAFV600E immunoreactivity can potentially be treated through drug therapy with BRAF inhibitors; however, it is always recommended to carry out a molecular study for diagnostic confirmation. This is the first Brazilian study that aimed to investigate possible genetic alterations in the BRAF gene in pilocytic astrocytomas, specifically in adults. Only 1 patient died, but due to operative complications and not the disease itself, suggesting a good evolution of these individuals.

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Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies. Methods: We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility. Results: ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-ß and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs. Conclusions: Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.

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While in adults most intracranial tumors develop around the cerebral hemispheres, 45 to 60% of pediatric lesions are found in the posterior fossa, although this anatomical region represents only 10% of the intracranial volume. The latest edition of the WHO classification for CNS tumors presented some fundamental paradigm shifts that particularly affected the classification of pediatric tumors, also influencing those that affect posterior fossa. Molecular biomarkers play an important role in the diagnosis, prognosis, and treatment of childhood posterior fossa tumors and can be used to predict patient outcomes and response to treatment and monitor its effectiveness. Although genetic studies have identified several posterior fossa tumor types, differing in terms of their location, cell of origin, genetic mechanisms, and clinical behavior, recent management strategies still depend on uniform approaches, mainly based on the extent of resection. However, significant progress has been made in guiding therapy decisions with biological or molecular stratification criteria and utilizing molecularly targeted treatments that address specific tumor biological characteristics. The primary focus of this review is on the latest advances in the diagnosis and treatment of common subtypes of posterior fossa tumors in children, as well as potential therapeutic approaches in the future.   Conclusion: Molecular biomarkers play a central role, not only in the diagnosis and prognosis of posterior fossa tumors in children but also in customizing treatment plans. They anticipate patient outcomes, measure treatment responses, and assess therapeutic effectiveness. Advances in neuroimaging and treatment have significantly enhanced outcomes for children with these tumors. What is Known: • Central nervous system tumors are the most common solid neoplasms in children and adolescents, with approximately 45 to 60% of them located in the posterior fossa. • Multimodal approaches that include neurosurgery, radiation therapy, and chemotherapy are typically used to manage childhood posterior fossa tumors What is New: • Notable progress has been achieved in the diagnosis, categorization and management of posterior fossa tumors in children, leading to improvement in survival and quality of life.

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The purpose of this pictorial essay is to describe the recommendations of the 2021 World Health Organization classification for adult-type and pediatric-type gliomas and to discuss the main modifications in relation to the previous (2016) classification, exemplified by imaging, histological, and molecular findings in nine patients followed at our institutions. In recent years, molecular biomarkers have gained importance in the diagnosis and classification of gliomas, mainly because they have been shown to correlate with the biological behavior and prognosis of such tumors. It is important for neuroradiologists to familiarize themselves with this new classification of central nervous system tumors, so that they can use this knowledge in evaluating and reporting the imaging examinations of patients with glioma.

O propósito deste ensaio iconográfico é descrever e discutir as novas recomendações da Organização Mundial da Saúde de 2021, referente aos gliomas dos tipos adulto e infantil, e suas principais diferenças com a classificação anterior (2016), exemplificadas com imagens de nove casos de pacientes atendidos nas nossas instituições. Recentemente, há uma crescente significância dos marcadores moleculares no diagnóstico e classificação dos gliomas e tumores do sistema nervoso central, principalmente pela correlação com o comportamento biológico e o prognóstico. É importante que os neurorradiologistas estejam familiarizados com a nova classificação dos tumores do sistema nervoso central para a prática clínica, na avaliação e emissão de laudos e opiniões nas imagens dos pacientes com gliomas.