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.

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.

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.

Unveiling the Current Understanding of Idiopathic Spinal Cord Herniation: A Systematic Review.

Background: Idiopathic spinal cord herniation (ISCH) is a rare condition that is characterized by ventral herniation of the spinal cord through a defect in the dura mater into the epidural space, with no identifiable cause. ISCH is frequently underdiagnosed, and the information available in case reports is limited. To provide an overview of the clinical manifestations and diagnosis of this condition, this study aims to conduct a review of reported cases of ISCH. Methods: A literature review was carried out using seven databases. The search was conducted using the keywords "Idiopathic spinal cord herniation" OR "Idiopathic Ventral Spinal Cord Herniation" AND "Case report" OR "case series." Results: A total of 92 relevant papers reporting 224 cases, besides the index case, were determined. Of the cases, 58.5% were females and the mean age was 50.7 (SD 13.2) years. Symptoms, diagnoses, and outcomes were similar between genders. The most common clinical signs included motor symptoms (82.6%), instability (61.3%), hypoesthesia (59.2%), and disturbance of thermal sensitivity (47.3%). Brown-Séquard syndrome was observed in 27.2% of the cases, and surgical treatment was employed in 89.7% of the cases. Conclusions: ISCH is a pathology that is principally treated with surgical approach. This study provides valuable insights into the clinical manifestations and diagnosis of ISCH, which can aid in the early recognition and treatment of this rare condition.

The rule of five: A novel anatomical landmark for approaching cavernous sinus content.

Background: The main objective of this study is to enhance neurosurgeons' anatomical knowledge by providing specific anatomical references of the cavernous sinus (CS). However, it is essential to clarify that our study does not seek to establish an absolute intraoperative rule due to the inherent anatomical variability that must be considered. Methods: Fifty-three cadaveric specimens were procured from the Forensic Institute (Bogotá) and subjected to dissection through an extradural approach. The measurements were taken in two distinct phases. The first phase involved the measurement of various anatomical structures in 25 specimens with respect to the anterior and posterior clinoids. The second phase, which was conducted 5 years later, involved the measurement of the distance between the foramen rotundum and the foramen ovale in 28 specimens using the L&W tools microcaliper. Results: In 25 specimens, a perpendicular imaginary line was drawn from the lateral tip of the anterior clinoid to the floor of the medial fossa. This facilitated access to the Parkinson's triangle, which is located between the IV cranial nerve and the ophthalmic V1 nerve, revealing a constant distance of 5 mm between the lateral tip of the anterior clinoid and the IV cranial nerve. Furthermore, in 28 specimens, the mean distance from the foramen rotundum to the foramen ovale was found to be 1.3 cm bilaterally. Conclusion: The rule of five is a valuable tool for comprehensively understanding the anatomy of the CS, providing a reference point for the different normal anatomical structures within the CS.

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.

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.

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.

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.