Doing more with less: surgical results of pediatric posterior fossa tumors from a single center in Latin America.

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.

Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.

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.

SEOM-GEINO clinical guidelines for grade 2 gliomas (2023).

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.

Glioma of the optic nerve and chiasm: a case report / Glioma óptico-quiasmático: um relato de caso

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.

Astrocytoma Mimicking Herpetic Meningoencephalitis: The Role of Non-Invasive Multimodal Monitoring in Neurointensivism.

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.

Long-term epilepsy associated-tumors (LEATs): what is new? / Tumores associados a epilepsia de longa duração: o que há de novo?

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.

Pilocytic astrocytoma in adults: Histopathological, immunohistochemical and molecular study with clinical association.

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.

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex.

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.

Posterior fossa tumors in children: current insights.

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.

The 2021 World Health Organization classification of gliomas: an imaging approach.

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.

Pathophysiological evaluation of pilocytic astrocytoma in adults: Histopathological and immunohistochemical analysis.

Pilocytic astrocytoma is a central nervous system tumor of slow growth, which represents 5 % of all gliomas and most often develops in the cerebellum (42-60 %), but can also arise in other neural areas, such as the optic pathway or hypothalamus (9-30 %); brainstem (9 %); spinal cord (2 %). In the pediatric population, this tumor is the second most common cause of neoplasms and, on the other hand, in adults, it is often rare, probably due to its aggressiveness in these individuals. Studies reveal that the origin of pilocytic astrocytoma is characterized by a fusion between the BRAF gene and the KIAA1549 locus, and the application of the immunohistochemistry technique for the analysis of BRAF protein expression can be a valuable tool for diagnostic purposes. Due to the relative rarity of this disease in adults, there are few publications on the most effective diagnostic and treatment strategies for this tumor. The general objective of this study was to analyze the histopathological and immunohistochemical characteristics of pilocytic astrocytoma in these patients. For this, a retrospective study of patients aged over 17 years with a diagnosis of pilocytic astrocytoma was carried out at the Department of Pathology of UNIFESP/EPM, from 1991 to 2015. In order to define BRAF positivity in the immunohistochemical analysis, at least three consecutive fields with more than 50 % immunostaining were used as criteria and, thus, it was inferred that the 7 cases analyzed were considered positive for the cytoplasmic marker BRAF V600E. Histopathological analysis associated with BRAF immunostaining is of paramount importance as a diagnostic method in these cases. However, future molecular studies will be necessary both for a better understanding of the aggressiveness and prognostic of this tumor and for research involving specific therapies for pilocytic astrocytoma in adults.

Intracranial Tumors in the First Year of Life.

Intracranial tumors in the first year of life are rare and, in this age group, are the second most common type of pediatric cancer after leukemias. As the more common solid tumor in neonates and infants, they present some peculiarities such as the high incidence of malignancies. Routine ultrasonography made easier to detect intrauterine tumors, but diagnosis can be delayed due to the lack or scarcity of recognizable symptoms. These neoplasms are often very large and highly vascular. Their removal is challenging, and there is a higher rate of morbidity and mortality than seen in older children, adolescents, and adults. They also differ from older children with respect to location, histological features, clinical behavior, and management. Pediatric low-grade gliomas represent 30% of the tumors in this age group and comprise circumscribed and diffuse tumors. They are followed by medulloblastoma and ependymoma. Other non-medulloblastoma embryonal neoplasms, former known as PNETS, are also commonly diagnosed in neonates and infants. Teratomas have an expressive incidence in newborns but decline gradually until the end of the first year of life. Immunohistochemical, molecular, and genomic advances are impacting the understanding and targeting of the treatment of some tumors, but, despite all these advances, the extent of resection remains the most important factor in the prognosis and survival of almost all types of tumors. The outcome is difficult to estimate, and 5-year survival ranges from one-quarter to three-quarters of the patients.

The 2021 World Health Organization classification of gliomas: an imaging approach / Nova classificação das neoplasias gliais segundo a Organização Mundial da Saúde 2021, com enfoque radiológico

Abstract 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.

Resumo 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.

Cerebellar pilocytic astrocytoma. Retrospective cohort study assessing postoperative functional outcome, cerebellar mutism and hydrocephalus.

Objective: Analyze a series of pediatric patients with cPAs evaluating factors that may modify or determine the final outcome in terms of neurological status, CMS and hydrocephalus. Materials and methods: Single Center, retrospective cohort study of surgical patients with cPA and at least 12 months of follow-up. Clinical, imaging and surgical features, histopathology and adjuvancy were assessed. Clinical outcome was categorized using the FSS and modified Bloom-Scale in the short and long term. Recurrency, PFS and mortality were also analyzed. Results: A total of 100 patients with a mean follow-up of 53.9 months, with no gender predilection, and a mean age of 7.6 years were included. The most frequent location was central and 24% of the tumors presented brainstem invasion. 79 patients had hydrocephalus at diagnosis and 48% required preoperative treatment. RT was achieved in 67% of cases. CMS was observed in 15 patients, statistically associated with location, pontine invasion, preoperative Bloom-score, and postoperative meningitis/ventriculitis. The functional "outcome" was correlated with complications such as meningitis/ventriculitis and cerebellar hematoma, mutism and recurrence. Recurrence was observed in 26% of cases and surgical reintervention was the chosen therapy. Conclusion: The treatment of cPAs in pediatric patients is associated with relatively favorable results. Recurrence, CMS and surgical complications play a prognostic value in the outcome and therefore must be managed appropriately. Early treatment with the intention of GTR should be considered, opting, if this is not possible, to leave a tumor residue over neurological damage. The treatment of hydrocephalus in the preoperative instance requires individualized management.

Deep DNA sequencing of MGMT, TP53 and AGT in Mexican astrocytoma patients identifies an excess of genetic variants in women and a predictive biomarker.

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Resección de astrocitoma fibrilar cerebeloso con apoyo endoscópico. Presentación de un caso

Se presentó paciente femenina de 7 años de edad, con antecedentes de salud aparente, atendida en el Hospital Pediátrico Docente "Pedro Agustín Pérez", de provincia Guantánamo. Al interrogatorio, la madre refirió semana de evolución con cefalea y vómitos. Cumplió tratamiento con analgésicos y antieméticos sin resolución de dicho cuadro. El estudio de resonancia magnética nuclear de cráneo informó en T1, corte axial, una lesión ocupativa de espacio, hipointensa, de aspecto quístico de fosa posterior, en hemisferio cerebeloso derecho, que comprimía el IV ventrículo, lo que causó una hidrocefalia obstructiva secundaria. Se realizó ventriculostomía con derivación ventriculoperitoneal y resección macroscópica de lesión con apoyo endoscópico. Se confirmó por estudio histopatológico el diagnóstico de astrocitoma fibrilar cerebeloso.

A seven years old female patient was evaluated at the Hospital Pediátrico Docente "Pedro Agustín Pérez", in Guantánamo, with a history of an apparent health situation. The patient´s mother referred a week with headache and vomiting. Patient underwent an analgesics and antiemetics treatment without resolution of symptoms. A magnetic resonance imaging study of the brain showed in T1 scan, in the axial section, a space-occupying, hypointense, and appearance of posterior fossa cystic lesion, in the right cerebellar hemisphere, which was compressing the IV ventricle, causing obstructive hydrocephalus secondary. Ventriculostomy routing ventriculoperitoneal shunt and macroscopic resection of lesion with endoscopic support included was performed. Cerebellar fibrillary astrocytoma was the diagnosis confirmed by histopathological study.

Paciente do sexo feminino, 7 anos, com histórico aparente de saúde, atendida no Hospital Pediátrico Docente "Pedro Agustín Pérez", na província de Guantánamo. Ao ser questionada, a mãe relatou uma semana de evolução com cefaléia e vômitos. Efetuou tratamento com analgésicos e antieméticos sem resolução dos referidos sintomas. O estudo de ressonância magnética nuclear do crânio relatou em T1, corte axial, lesão hipointensa, expansiva, de aspecto cístico em fossa posterior, no hemisfério cerebelar direito, que comprimia o quarto ventrículo, causando hidrocefalia obstrutiva secundária. Foi realizada ventriculostomia com derivação ventriculoperitoneal e ressecção macroscópica da lesão com suporte endoscópico. O diagnóstico de astrocitoma fibrilar cerebelar foi confirmado pelo estudo histopatológico.

Automated Classification of Intramedullary Spinal Cord Tumors and Inflammatory Demyelinating Lesions Using Deep Learning.

Accurate differentiation of intramedullary spinal cord tumors and inflammatory demyelinating lesions and their subtypes are warranted because of their overlapping characteristics at MRI but with different treatments and prognosis. The authors aimed to develop a pipeline for spinal cord lesion segmentation and classification using two-dimensional MultiResUNet and DenseNet121 networks based on T2-weighted images. A retrospective cohort of 490 patients (118 patients with astrocytoma, 130 with ependymoma, 101 with multiple sclerosis [MS], and 141 with neuromyelitis optica spectrum disorders [NMOSD]) was used for model development, and a prospective cohort of 157 patients (34 patients with astrocytoma, 45 with ependymoma, 33 with MS, and 45 with NMOSD) was used for model testing. In the test cohort, the model achieved Dice scores of 0.77, 0.80, 0.50, and 0.58 for segmentation of astrocytoma, ependymoma, MS, and NMOSD, respectively, against manual labeling. Accuracies of 96% (area under the receiver operating characteristic curve [AUC], 0.99), 82% (AUC, 0.90), and 79% (AUC, 0.85) were achieved for the classifications of tumor versus demyelinating lesion, astrocytoma versus ependymoma, and MS versus NMOSD, respectively. In a subset of radiologically difficult cases, the classifier showed an accuracy of 79%-95% (AUC, 0.78-0.97). The established deep learning pipeline for segmentation and classification of spinal cord lesions can support an accurate radiologic diagnosis. Supplemental material is available for this article. © RSNA, 2022 Keywords: Spinal Cord MRI, Astrocytoma, Ependymoma, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Deep Learning.

The Transcriptomic Landscape of Pediatric Astrocytoma.

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes IDH1/2 and H3F3A has recently been incorporated into the classification guidelines. Although mutations in H3F3A are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in IDH1/2 genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method.

Lesión difusa de médula espinal, ¿cirugía o tratamiento paliativo?: a propósito de un caso

Las lesiones difusas de médula son raras y un reto diagnóstico. Los gliomas de bajo grado son los de mayor prevalencia y los astrocitomas primarios, el subtipo más frecuente. Presentamos el caso de un varón de 36 años, con tiempo de enfermedad de 13 años de dolor cervical insidioso, progresa con hemiparesia derecha y, posteriormente, paraparesia severa con pérdida de control de esfínteres. Mediante una RMN total de columna se evidenciaron lesiones neoproliferativas difusas abarcando todos los segmentos medulares. Se realizó una biopsia a cielo abierto en segmento T1-T2, la patología diagnosticó glioma de bajo grado. El tratamiento es controversial y se descartó la cirugía por la alta morbilidad. Se optó por radioterapia y quimioterapia por su rol importante en el control de la enfermedad.

Diffuse spinal cord injuries are rare and pose a diagnostic challenge. Low-grade gliomas are the most prevalent type, with primary astrocytomas being the most frequent subtype. We present the case of a 36-year-old man with a 13-year history of squeezing neck pain, which progressed with right hemiparesis and later with severe paraparesis and loss of sphincter control. A whole spine MRI scan showed diffuse neoproliferative lesions that spread throughout all the spinal cord segments. An open biopsy of the lesion in the T1-T2 segment was performed. The pathology report stated low-grade glioma. Treatment is controversial, so surgery was ruled out due to high morbidity. Radiotherapy and chemotherapy were chosen because they play an important role in controlling the disease.

[Tuberous sclerosis complex: diagnosis and current treatment]. / Complejo de esclerosis tuberosa: diagnóstico y tratamiento actual.

Tuberous sclerosis complex is an autosomal dominant genetic multisystemic disorder caused primarily by mutations in one of the two tumor suppressor genes TSC1 or TSC2, resulting in increased activation of the mTOR pathway. Regarding clinical manifestations, a wide range of phenotypic variability exists, with symptoms constellations that may differ in affected organs (brain, skin, heart, eyes, kidneys, lungs), age of presentation and severity, but usually with great impact in biopsychosocial aspects of health and in quality of life. Main clinical neurological features are epilepsy (frequently, antiepileptic drug-resistant epilepsy), neuropsychiatric disorders, and subependymal giant cell astrocytomas. Recently, many therapeutic strategies have developed, including preventive treatment of epilepsy, new options for treatment of epilepsy as cannabidiol, mTOR inhibitors, ketogenic diet, and a more precise epilepsy surgery. Subependymal giant cell astrocytomas may require surgical procedures or mTOR inhibitors treatment. mTOR inhibitors may also be useful for other comorbidities. To improve quality of life of patients with tuberous sclerosis complex, it is essential to be able to deliver an integrated approach by specialized multidisciplinary teams, coordinated with primary care physicians and health professionals, that include access to treatments, attention of psychosocial aspects, and an adequate health care transition from pediatric to adult care.

El complejo de esclerosis tuberosa es un trastorno genético autosómico dominante multisistémico, causado primariamente por mutaciones en uno de los genes supresores de tumores TSC1 o TSC2, que generan una sobre-activación de la vía mTOR. En relación a las manifestaciones clínicas, existe una gran variabilidad fenotípica, con constelaciones de síntomas que pueden diferir tanto en los órganos afectados (encéfalo, piel, corazón, ojos, riñones, pulmones), como en la edad de presentación y la gravedad, pero que generalmente impactan fuertemente en los aspectos biopsicosociales y en la calidad de vida. Las principales manifestaciones clínicas neurológicas incluyen la epilepsia (con frecuencia, fármaco-resistente), los trastornos neuropsiquiátricos y los síntomas relacionados a los astrocitomas de células gigantes. En los últimos años han surgido nuevos abordajes terapéuticos, incluyendo el tratamiento preventivo de la epilepsia, nuevas opciones de tratamiento para la epilepsia como el uso de cannabidiol, de inhibidores de mTOR, la terapia cetogénica y cirugía de epilepsia. Los astrocitomas de células gigantes pueden requerir tratamientos quirúrgicos o con inhibidores de mTOR. Estos últimos también pueden utilizarse para el tratamiento de otras comorbilidades. Para mejorar la calidad de atención de los pacientes con esclerosis tuberosa, el desafío es poder brindar un abordaje integral por equipos interdisciplinarios especializados, en coordinación con sus médicos de cabecera y los equipos de salud del primer nivel de atención, que incluya el acceso a los tratamientos, la atención de los aspectos psicosociales, y una adecuada transición desde la atención pediátrica a la de adultos.