Multifocal glioblastoma and hormone replacement therapy in a transgender female.

Background: Glioblastoma multiforme represents approximately 60% of all brain tumors in adults. This malignancy shows a high level of biological and genetic heterogeneity associated with exceptional aggressiveness, leading to poor patient survival. One of the less common presentations is the appearance of primary multifocal lesions, which are linked with a worse prognosis. Among the multiple triggering factors in glioma progression, the administration of sex steroids and their analogs has been studied, but their role remains unclear to date. Case Description: A 43-year-old transgender woman who has a personal pathological history of receiving intramuscular (IM) hormone treatment for 27 years based on algestone/estradiol 150 mg/10 mg/mL. Three months ago, the patient suddenly experienced hemiplegia and hemiparesis in her right lower extremity, followed by a myoclonic focal epileptic seizure, vertigo, and a right frontal headache with a visual analog scale of 10/10. Magnetic resonance imaging images revealed an intra-axial mass with poorly defined, heterogeneous borders, and thick borders with perilesional edema in the left parietal lobe, as well as a rounded hypodense image with well-defined walls in the right internal capsule. The tumor was resected, and samples were sent to the pathology department, which confirmed the diagnosis of wild-type glioblastoma. Conclusion: This report identifies prolonged use of steroid-based hormone replacement therapy as the only predisposing factor in the oncogenesis of multifocal glioblastoma. It is an example that highlights the importance for physicians not to consider pathologies related to the human immunodeficiency virus rather than neoplasms in transgender patients in view of progressive neurological deterioration.

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.

A Patient With Epilepsy, Ganglioglioma, and Oligodendroglioma With Anaplastic Foci in the Same Left Frontoparietal Lesion: A Case Report.

Gangliogliomas are central nervous system (CNS) tumors with a neuronal and glial component considered grade 1 according to the World Health Organization (WHO) classification. On the other hand, oligodendrogliomas are diffuse infiltrating gliomas (CNS WHO grade 2 or 3) characterized by both an isocitrate dehydrogenase mutation and 1p/19q co-deletion. There have been some cases with the coexistence of these two tumors. Here, we present the case of a low-growing left frontoparietal brain tumor with a definite diagnosis of ganglioglioma (CNS WHO grade 1) and oligodendroglioma (CNS WHO grade 2) with areas of anaplastic oligodendroglioma (CNS WHO grade 3) in a patient with long-standing epilepsy.

Schizophrenia-Like Psychosis Presented in a Patient With a Temporal Lobe Tumor: A Case Report.

Psychiatric symptoms caused by brain lesions are not uncommon nowadays, caused by several different pathologies such as Alzheimer's, dementia, vascular and oncological diseases, etc. and they are known as neuropsychiatric or neurobehavioral symptoms, overlapping as mental health disorders. The most common primary brain tumors are gliomas, and the most common neuropsychiatric symptoms caused by them are depression, anxiety disorder, schizophrenia-like psychosis, anorexia nervosa, or cognitive dysfunction. We present a case of a 46-year-old male with no psychiatric familial history who started with a schizophrenia-like psychosis with hallucinations and, in consequence, killed his mother, symptoms which, after almost eight years, were known to be caused by a brain tumor.

Frontal aslant tract: Anatomy and tractography description in the Mexican population.

Background: The aim of the study was to describe the origin, course, and termination of frontal aslant tract (FAT) in the Mexican population of neurosurgical referral centers. Methods: From January 2018 to May 2019, we analyzed 50 magnetic resonance imaging (MRI) studies in diffusion tensor imaging sequences of patients of the National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez." Five brains were fixed by the Klingler method and dissected in the neurosurgery laboratory of the Hospital Civil de Guadalajara to identify the origin, trajectory, and ending of the FAT. Results: FAT was identified in 100% of the MRI and brain dissections. The origin of the FAT was observed in 63% from the supplementary premotor area, 24% from the supplementary motor area, and 13% in both areas. Its ending was observed in the pars opercularis in 81%, pars triangularis in 9%, and in both pars opercularis and ventral premotor area in 10% in the magnetic resonance images, with a left side predominance. In the hemispheres dissections, the origin of FAT was identified in 60% from the supplementary premotor area, 20% from the supplementary motor area, and 20% in both areas. Its ending was observed in the pars opercularis in 80% and the pars triangularis in 20%. It was not identified as an individual fascicle connected with the contralateral FAT. Conclusion: In the Mexican population, FAT has a left predominance; it is originated more frequently in the supplementary premotor area, passes dorsal to the superior longitudinal fascicle II and the superior periinsular sulcus, and ends more commonly in the pars opercularis.

Tumor-Like Brain Lesions Associated With Variants of Uncertain Significance Compared to Previous Studies: A Case Report.

TREX1 is a gene that encodes an exonuclease on the C-terminal strand at the 3 Ì end for DNA repair. Multiple syndromes associated with the alteration of this gene have been described, focusing in this case on retinal vasculopathy with cerebral leukodystrophy (RVCL). We present the case of a 44-year-old female patient with a familial history of cerebral pseudotumors. At the time of diagnosis, the patient presented weakness in the lower limbs and dysesthesias of the right body at the beginning of the clinical picture, without visual alterations or retinal changes at fundus examination. A cranial magnetic resonance imaging (MRI) study showed a pseudotumoral lesion at the inferior frontal gyrus with a report of a choline peak in spectroscopy, ring enhancement in contrasted T1 sequence, and apparent central necrosis. A molecular study shows a mutation in c2136G>A, c.799dup, and c.5312A>G related to genes expressing PDE6A, TREX1, and VCAN proteins, respectively, mutations that have not been previously reported.

Pregnancy and brain tumors; a systematic review of the literature.

The incidence of primary brain tumors during pregnancy is uncommon. The etiology of these can range from different genetic syndromes such as Li Fraumeni, neurofibromatosis type I, and hormonal associated tumors. The number of meningiomas gradually tends to increase during pregnancy, suggesting a relationship between non-malignant meningiomas and hormonal changes. Clinical features are non specific or can be misinterpreted with pregnancy symptoms such as headache, vomiting and dizziness. It is worth mentioning that the symptoms due to intracranial tumors are no different in pregnant compared with non pregnant patients. However, retrospective studies in glioma behavior suggested that both tumor volume and growth, increased during pregnancy. These changes were correlated with clinical worsening and increased frequency of seizures. The diagnosis requires a proper neurologic exploration and the support of imaging studies. Treatment of tumors is very controversial since we look for the preservation of both mother and fetus. In theory, the best therapy for the mother will also be the best therapy for the fetus. During pregnancy, ideally the treatment is symptomatic, to preserve the fetus, and definite treatment may be performed after birth; the latter is not always accomplished since patients may present with impending herniation or a malignant tumor for which immediate management is necessary. We intend to give an updated review in the literature on the adequate treatment of brain tumors during pregnancy and the anesthetic management during the definite treatment. Literature data was obtained from Pubmed using the search terms: "Pregnancy", "Brain", "Tumors". A total of forty-three articles were selected.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Angiotensinogen rs5050 germline genetic variant as potential biomarker of poor prognosis in astrocytoma.

INTRODUCTION: Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. METHODS: A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. RESULTS: Median follow-up was 41 months (range 1-48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. CONCLUSIONS: In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva.

Renin angiotensin system and its role in biomarkers and treatment in gliomas.

Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with adjuvant therapy have a mean overall survival of 15 months and 100% recurrence. The renin-angiotensin system (RAS), the primary regulator of cardiovascular circulation, exhibits local action and works as a paracrine system. In the context of this local regulation, the expression of RAS peptides and receptors has been detected in different kinds of tumors, including gliomas. The dysregulation of RAS components plays a significant role in the proliferation, angiogenesis, and invasion of these tumors, and therefore in their outcomes. The study and potential application of RAS peptides and receptors as biomarkers in gliomas could bring advantages against the limitations of current tumoral markers and should be considered in the future. The targeting of RAS components by RAS blockers has shown potential of being protective against cancer and improving immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for beneficial effects and are being considered for use in treatment protocols. This review aims to summarize the background behind how RAS plays a role in gliomagenesis and explore the evidence that could lead to their use as biomarkers and treatment adjuvants.

[The woman in neurosurgery at the national institute of neurology and neurosurgery]. / La mujer en neurocirugía en el Instituto Nacional de Neurología y Neurocirugía (INNN).

Women have always had a hard time in the history of medicine; Dr. Isabel Blackwell was the first woman in history to practice medicine. Dr. Diana Beck became the world´s first female neurosurgeon. The first Latin American female neurosurgeon was Dr. María Cristina García Sancho y Álvarez-Tostado. All of these women had to face a large number of social, cultural, and economic obstacles in their path; however, this situation has changed gradually. Dr. Ana Lilia Siordia Karam was the first neurosurgeon to graduate from INNN. Nineteen years later the second female neurosurgeon at this institute was Dr. María Petra Herrera Guerrero. During their time at this institute they endured a lot of difficulties, especially with most of their coworkers; however, some coworkers treated them with respect and no gender distinction. Nowadays, four of the 25 total neurosurgery residents at INNN are women, and even though some of them have had to endure acts of gender discrimination, the general situation has changed. With work and respect, women have managed to have a larger role in the surgical field. We hope that in the near future a gender discrimination-free environment will be achieved in medicine and its specialties.

Bolsa de Bogotá resistente en abdomen abierto / Bogota bag, resistant in open abdomen

Objetivo: Presentar una modificación a la colocación de la bolsa de Bogotá, que además de mantener las útiles características de esta técnica, adiciona más fuerza de sostén o resistencia a la capa de polivinilo en los pacientes con abdomen abierto. Sede: Hospital de segundo nivel de atención. Hospital General de Zona 53 Instituto Mexicano del Seguro Social. Diseño: Estudio piloto. Análisis estadístico: Porcentaje como medida de resumen para variables cualitativas. Pacientes y métodos: En el periodo de diciembre 2008 a marzo 2010 se trataron seis pacientes con esta técnica modificada de la bolsa de Bogotá. Edades comprendidas de 40 a 78 años, tres hombres, cinco pacientes con sepsis abdominal y el restante con pérdida de pared abdominal. Se incluyeron pacientes en quienes hubiera indicación de abdomen abierto y consecuente posibilidad de reintervención. Con nuestra técnica se buscó movilización y deambulación temprana de los pacientes y una forma segura de soporte del contenido abdominal, sin el uso de vendaje abdominal compresivo necesario para evitar evisceración, como suele pasar en la colocación de la bolsa de Bogotá tradicional, además el prevenir evisceración en un caso con apoyo ventilatorio. Resultados: En cinco pacientes se tuvo antecedente de 1 ó 2 cirugías previas. Sólo en un paciente se aplicó esta modificación en la primera cirugía. Hubo una muerte no relacionada al procedimiento debido a insuficiencia hepática. Este caso tuvo apoyo ventilatorio, soportado por la bolsa de Bogotá modificada sin evisceración. En los cinco pacientes restantes esta modificación permitió la movilización y deambulación temprana sin requerir vendaje abdominal. No se reintervino a ningún paciente, y el cierre de pared se realizó como hernia ventral planeada. El 100% de los pacientes toleraron la movilización temprana y/o uso de apoyo ventilatorio sin evisceración. Conclusiones: Esta modificación logra mayor funcionalidad de la bolsa de Bogotá, destacando la mayor resistencia y, en consecuencia, la movilización y deambulación temprana y sin riesgo de evisceración.