Differential tractography and whole brain connectometry in primary motor area gliomas resection: A feasibility study.

OBJECTIVE: Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). METHODS: DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. RESULTS: We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). CASE 1: There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). CASE 2: There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. CONCLUSIONS: Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient's networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes.

Ventriculoatrial Shunt Versus Ventriculoperitoneal Shunt: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) is usually the primary choice for cerebrospinal fluid shunting for most neurosurgeons, while ventriculoatrial shunt (VAS) is a second-line procedure because of historical complications. Remarkably, there is no robust evidence claiming the superiority of VPS over VAS. Thus, we aimed to compare both procedures through a meta-analysis. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, the authors systematically searched the literature for articles comparing VAS with VPS. The included articles had to detail one of the following outcomes: revisions, infections, shunt-related mortality, or complications. In addition, the cohort for each shunt model had to encompass more than 4 patients. RESULTS: Of 1872 articles, 16 met our criteria, involving 4304 patients, with 1619 undergoing VAS and 2685 receiving VPS placement. Analysis of revision surgeries showed no significant difference between VAS and VPS (risk ratio [RR] = 1.10, 95% CI: 0.9-1.34; I2 = 84%, random effects). Regarding infections, the analysis also found no significant difference between the groups (RR = 0.67, 95% CI: 0.36-1.25; I2 = 74%, random effects). There was no statistically significant disparity between both methods concerning shunt-related deaths (RR = 2.11, 95% CI: 0.68-6.60; I2 = 56%, random effects). Included studies after 2000 showed no VAS led to cardiopulmonary complications, and only 1 shunt-related death could be identified. CONCLUSION: Both methods show no significant differences in procedure revisions, infections, and shunt-related mortality. The literature is outdated, research in adults is lacking, and future randomized studies are crucial to understand the profile of VAS when comparing it with VPS. The final decision on which distal site for cerebrospinal shunting to use should be based on the patient's characteristics and the surgeon's expertise.

Augmented reality for intracranial meningioma resection: a mini-review.

Augmented reality (AR) integrates computer-generated content and real-world scenarios. Artificial intelligence's continuous development has allowed AR to be integrated into medicine. Neurosurgery has progressively introduced image-guided technologies. Integration of AR into the operating room has permitted a new perception of neurosurgical diseases, not only for neurosurgical planning, patient positioning, and incision design but also for intraoperative maneuvering and identification of critical neurovascular structures and tumor boundaries. Implementing AR, virtual reality, and mixed reality has introduced neurosurgeons into a new era of artificial interfaces. Meningiomas are the most frequent primary benign tumors commonly related to paramount neurovascular structures and bone landmarks. Integration of preoperative 3D reconstructions used for surgical planning into AR can now be inserted into the microsurgical field, injecting information into head-up displays and microscopes with integrated head-up displays, aiming to guide neurosurgeons intraoperatively to prevent potential injuries. This manuscript aims to provide a mini-review of the usage of AR for intracranial meningioma resection.

The state of art of awake craniotomy in Latin American countries: a scoping review.

BACKGROUND AND OBJECTIVE: Awake craniotomy (AC) is a valuable technique for surgical interventions in eloquent areas, but its adoption in low- and middle-income countries faces challenges like limited infrastructure, trained personnel shortage, and inadequate funding. This scoping review explores AC techniques in Latin American countries, focusing on patient characteristics, tumor location, symptomatology, and outcomes. METHODS: A scoping review followed PRISMA guidelines, searching five databases in English, Spanish, and Portuguese. We included 28 studies with 258 patients (mean age: 43, range: 11-92). Patterns in AC use in Latin America were analyzed. RESULTS: Most studies were from Brazil and Mexico (53.6%) and public institutions (70%). Low-grade gliomas were the most common lesions (55%), most of them located in the left hemisphere (52.3%) and frontal lobe (52.3%). Gross-total resection was achieved in 34.3% of cases. 62.9% used an Asleep-Awake-Asleep protocol, and 14.8% used Awake-Awake-Awake. The main complication was seizures (14.6%). Mean post-surgery discharge time was 68 h. Challenges included limited training, infrastructure, and instrumentation availability. Strategies discussed involve training in specialized centers, seeking sponsorships, applying for awards, and multidisciplinary collaborations with neuropsychology. CONCLUSION: Improved accessibility to resources, infrastructure, and adequate instrumentation is crucial for wider AC availability in Latin America. Despite disparities, AC implementation with proper training and teamwork yields favorable outcomes in resource-limited centers. Efforts should focus on addressing challenges and promoting equitable access to this valuable surgical technique in the region.

Understanding the molecular profiling of diffuse gliomas classification: A brief overview.

Background: Gliomas represent almost 30% of all primary brain tumors and account for 80% of malignant primary ones. In the last two decades, significant progress has been made in understanding gliomas' molecular origin and development. These advancements have demonstrated a remarkable improvement in classification systems based on mutational markers, which contribute paramount information in addition to traditional histology-based classification. Methods: We performed a narrative review of the literature including each molecular marker described for adult diffuse gliomas used in the World Health Organization (WHO) central nervous system 5. Results: The 2021 WHO classification of diffuse gliomas encompasses many molecular aspects considered in the latest proposed hallmarks of cancer. The outcome of patients with diffuse gliomas relies on their molecular behavior and consequently, to determine clinical outcomes for these patients, molecular profiling should be mandatory. At least, the following molecular markers are necessary for the current most accurate classification of these tumors: (1) isocitrate dehydrogenase (IDH) IDH-1 mutation, (2) 1p/19q codeletion, (3) cyclin-dependent kinase inhibitor 2A/B deletion, (4) telomerase reverse transcriptase promoter mutation, (5) α-thalassemia/ mental retardation syndrome X-linked loss, (6) epidermal growth factor receptor amplification, and (7) tumor protein P53 mutation. These molecular markers have allowed the differentiation of multiple variations of the same disease, including the differentiation of distinct molecular Grade 4 gliomas. This could imply different clinical outcomes and possibly impact targeted therapies in the years to come. Conclusion: Physicians face different challenging scenarios according to the clinical features of patients with gliomas. In addition to the current advances in clinical decision-making, including radiological and surgical techniques, understanding the disease's molecular pathogenesis is paramount to improving the benefits of its clinical treatments. This review aims to describe straightforwardly the most remarkable aspects of the molecular pathogenesis of diffuse gliomas.

DICER1-associated central nervous system sarcoma: A comprehensive clinical and genomic characterization of case series of young adult patients.

Background: DICER1 alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary DICER1-associated CNS sarcoma" (DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy. Methods: We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed. Results: Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic DICER1 variants were present in two patients, 75% of cases had more than one somatic alteration in DICER1, and the most frequent commutation was TP53. Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in KRAS and NF1. Overall survival was 30.8 months. Conclusions: DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in TP53, NF1, and PTEN, and most alterations at progression were related to MAPK, RAS and PI3K signaling pathways.

Gait Apraxia and Hakim's Disease: A Historical Review.

In 1965, Prof. Salomón Hakim described, for the first time, a condition characterized by normal pressure hydrocephalus and gait alterations. During the following decades, definitions such as "Frontal Gait", "Bruns' Ataxia" and "Gait Apraxia" have been frequently used in pertinent literature in the attempt to best define this peculiar motor disturbance. More recently, gait analysis has further shed light on the typical spatiotemporal gait alterations that characterize this neurological condition, but a clear and shared definition of this motor condition is still lacking. In this historical review, we described the origins of the terms "Gait Apraxia", "Frontal Gait" and "Bruns' Ataxia", starting with the first works of Carl Maria Finkelburg, Fritsch and Hitzig and Steinthal during the second half of the 19th century and ending with Hakim's studies and his formal definition of idiopathic normal pressure hydrocephalus (iNPH). In the second part of the review, we analyze how and why these definitions of gait have been associated with Hakim's disease in the literature from 1965 to the present day. The definition of "Gait and Postural Transition Apraxia" is then proposed, but fundamental questions about the nature and mechanisms underlying this condition remain unanswered.

Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas / Importancia pronóstica de las mutaciones del gen promotor de la transcriptasa inversa de la telomerasa en los meningiomas de alto grado

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Importancia pronóstica de las mutaciones del gen promotor de la transcriptasa inversa de la telomerasa en los meningiomas de alto grado / Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were the only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

Skull base osteomyelitis mimicking skull base tumor in immunocompetent pediatric patient: case report.

Central skull base osteomyelitis (CSBO) is a rare complication of infection in pediatric patients, especially when there are no comorbidities like immunosuppression or metabolic illness. The diagnosis of CSBO is a challenge in children, and imaging findings can mimic skull base tumor. We describe the clinical history and image diagnosis of a case in a 6-year-old girl with no relevant history who presented an extensive skull base lesion. She underwent tumor resection surgery. The intraoperative finding confirmed clivus osteomyelitis, and the histopathological studies discarded malignancy. After diagnosis, the patient completed 6-week antibiotic treatment with adequate evolution. In conclusion, CSBO should be considered within the differential diagnoses due to the fact that it can mimic skull base lesions and it may present without relevant history.

Ventriculo-atrial shunt. Comparison of an ultrasound-guided peel-away technique versus conventional technique in the management of normal pressure hydrocephalus: A retrospective cohort.

BACKGROUND: Normal pressure hydrocephalus (NPH) is a common neurodegenerative syndrome among the elderly characterized by ventriculomegaly and the classic triad of symmetric gait disturbance, cognitive decline and urinary incontinence. To date, the only effective treatment is a cerebrospinal fluid shunting procedure that can either be ventriculo-atrial, ventriculo-peritoneal, or lumbo-peritoneal shunt. The conventional ventriculo-atrial shunt uses venodissection, whereas the peel-away is a percutaneous ultrasound (US)-guided technique that shows some advantages over conventional technique. We sought to compare perioperative complication rates, mean operating time and clinical outcomes for both techniques in NPH patients at our institution. METHODS: A retrospective cohort-type analytical study was conducted, using clinical record data of patients diagnosed with NPH and treated at our center from January 2009 to September 2019. Parameters to be compared include: Perioperative complication rates, intraoperative bleeding, mortality, and mean operating time. Perioperative complication rates are those device-related such as shunt infection, dysfunction, and those associated with the procedure. Complications are further classified in immediate (occurring during the first inpatient stay), early (within the first 30 days of surgery), and late (after day 30 of surgery). RESULTS: A total of 123 patients underwent ventriculo-atrial shunt. Eighty-two patients (67%) underwent conventional venodissection technique and 41 patients (33%) underwent a peel-away technique. Immediate complications were 3 (3.6%) and 0 for conventional and peel-away groups, respectively. Early complications were 0 and 1 (2.4%) for conventional and peel-away groups, respectively. Late complications were 5 (6.1%) and 2 (4.9%) for conventional and peel-away groups, respectively. Mean operating time was lower in the peel-away group (P = 0.0000) and mortality was 0 for both groups. CONCLUSION: Ventriculo-atrial shunt is an effective procedure for patients with NPH. When comparing the conventional venodissection technique with a percutaneous US-guided peel-away technique, the latter offers advantages such as shorter operating time and lower perioperative complication rates.

Salomón Hakim, MD (1922-2011): A honeymoon with Neurosurgery.

Salomón Hakim (1922-2011) was a Colombian neurosurgeon and brain scientist This biography examines the social and cultural background through which he emerged as an inquisitive and multi-dimensional surgeon-scientist, and his lifelong contributions to the specialty of neurosurgery. With empirical knowledge in applied medical physics, electronics, electricity and chemistry, he understood the paradoxical phenomenon of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. This ultimately led Hakim to describe in exquisite detail the physics of the cranial cavity and brain hydrodynamics. His name is intertwined with the identification of the entity of a syndrome which had not previously been addressed in the medical literature: Normal Pressure Hydrocephalus (Hakim's syndrome). Additionally, he designed and built various models of valved shunting devices to treat the condition (eg the Hakim programmable valve). Through his selflessness and cogent work, Hakim left a legacy and intellectual heritage that has allowed many colleagues worldwide to save thousands of lives who would be otherwise condemned to oblivion.

Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation.

BACKGROUND: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer. METHODS: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial next-generation sequencing panel in liquid biopsy. RESULTS: There were ten males (66.7%), and the median patient's age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR. CONCLUSIONS: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

Cerebrospinal fluid closing pressure-guided tap test for the diagnosis of idiopathic normal pressure hydrocephalus: A descriptive cross-sectional study.

BACKGROUND: Tap test improves symptoms of idiopathic normal pressure hydrocephalus (iNPH); hence, it is widely used as a diagnostic procedure. However, it has a low sensitivity and there is no consensus on the parameters that should be used nor the volume to be extracted. We propose draining cerebrospinal fluid (CSF) during tap test until a closing pressure of 0 cm H2O is reached as a standard practice. We use this method with all our patients at our clinic. METHODS: This is a descriptive cross-sectional study where all patients with presumptive diagnosis of iNPH from January 2014 to December 2019 were included in the study. We used a univariate descriptive analysis and stratified analysis to compare the opening pressure and the volume of CSF extracted during the lumbar puncture, between patients in whom a diagnosis of iNPH was confirmed and those in which it was discarded. RESULTS: A total of 92 patients were included in the study. The mean age at the time of presentation was 79.4 years and 63 patients were male. The diagnosis of iNPH was confirmed in 73.9% patients. The mean opening pressure was 14.4 cm H2O mean volume of CSF extracted was 43.4 mL. CONCLUSION: CSF extraction guided by a closing pressure of 0 cm H2O instead of tap test with a fixed volume of CSF alone may be an effective method of optimizing iNPH symptomatic improvement and diagnosis.

Systemic management of malignant meningiomas: A comparative survival and molecular marker analysis between Octreotide in combination with Everolimus and Sunitinib.

PURPOSE: To compare the effectiveness of octreotide/everolimus vs. sunitinib for the systemic treatment of recurrent aggressive meningiomas. METHODS: 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRß and VEGFR2, their expression was correlated with outcomes. RESULTS: Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5-42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2-21.1) and 9.1 months (95%CI 6.8-16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1st/2nd/3rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRß and negative VEGFR2 expression were associated with longer survival both in OS and PFS. CONCLUSION: Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRß expression are associated with better outcomes.

Xantoastrocitoma pleomórfico anaplásico recurrente y respuesta a la combinación de carmustine y bevacizumab, un reporte de caso / Recurrent pleomorphic anaplastic xanthoastrocytoma and response to combination of carmustine and bevacizumab, a case report

RESUMEN Se expone el caso de una mujer de 19 años a quien se le realizó el diagnóstico de un xantoastrocitoma pleomórfico anaplásico parietooccipital izquierdo, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Dicho tumor debuta generalmente con crisis convulsivas y sus características histológicas patognomónicas son el pleomorfismo celular, la vacuolización lipídica de su citoplasma y la reactividad a la proteína ácida fibrilar glial (PAFG) y S100. El estudio de nuevos marcadores que puedan brindar otras oportunidades terapéuticas ha permitido encontrar mutaciones en el oncogén BRAF. Este tumor presenta una variante anaplásica más agresiva que se trata con cirugía y quimiorradiación. En nuestro caso, después de varias progresiones a otras intervenciones, se utilizó bevacizumab y carmustine como tratamiento de segunda línea con respuesta completa.

SUMMARY The case of a young woman of 19-years-old is presented; whom the diagnosis was made of a left parietal-occipital xanthoastrocytoma pleomorphic anaplastic; this neoplasia is rare and usually affects the pediatric and young adult population. This generally debuts with seizures and their pathognomonic histologic characteristics are the pleomorphic cells with cytoplasmatic lipid vacuolation and the reactivity of glial fibrillary acidic protein (GFAP) and S100. The study of new markers that may provide other therapeutic opportunities has allowed finding mutations in the BRAF oncogene. This tumor has a more aggressive anaplastic variant that is treated with surgery and chemoradation. In our case after several progressions to other interventions, we used bevacizumab and carmustine as second-line treatment obtaining complete response.

Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma.

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.

Genotyping low-grade gliomas among Hispanics.

BACKGROUND: Low-grade gliomas (LGGs) are classified by the World Health Organization as astrocytoma (DA), oligodendroglioma (OD), and mixed oligoastrocytoma (OA). TP53 mutation and 1p19q codeletion are the most-commonly documented molecular abnormalities. Isocitrate dehydrogenase (IDH) 1/2 mutations are frequent in LGGs; however, IDH-negative gliomas can also occur. Recent research suggests that ATRX plays a significant role in gliomagenesis. METHODS: We investigated p53 and Olig2 protein expression, and MGMT promoter methylation, 1p19q codeletion, IDH, and ATRX status in 63 Colombian patients with LGG. The overall survival (OS) rate was estimated and compared according to genotype. RESULTS: The most common histology was DA, followed by OD and OA. IDH1/2 mutations were found in 57.1% and MGMT+ (positive status of MGMT promoter methylation methyl-guanyl-methyl-transferase gene) in 65.1% of patients, while overexpression of p53 and Olig2 was present in 30.2% and 44.4%, respectively, and 1p19q codeletion in 34.9% of the patients. Overexpression of ATRX was analyzed in 25 patients, 16% tested positive and were also mutations in isocitrate dehydrogenase and negative 1p19q-codelition. The median follow-up was 15.8 months (95% CI, 7.6-42.0) and OS was 39.2 months (95% CI, 1.3-114). OS was positively and significantly affected by MGMT+, 1p19q codeletion, surgical intervention extent, and number of lobes involved. Multivariate analysis confirmed that MGMT methylation status and 1p19q codeletion affected OS. CONCLUSIONS: This is the first study evaluating the molecular profile of Hispanic LGG patients. Findings confirmed the prognostic relevance of MGMT methylation and 1p19q codeletion, but do not support IDH1/2 mutation as a relevant marker. The latter may be explained by sample size and selection bias. ATRX alterations were limited to patients with DA and were mutations in isocitrate dehydrogenase and negative 1p19q-codelition.