The potential of miRNA-based approaches in glioblastoma: An update in current advances and future perspectives.

Glioblastoma (GBM) is the most common malignant central nervous system tumor. The emerging field of epigenetics stands out as particularly promising. Notably, the discovery of micro RNAs (miRNAs) has paved the way for advancements in diagnosing, treating, and prognosticating patients with brain tumors. We aim to provide an overview of the emergence of miRNAs in GBM and their potential role in the multifaceted management of this disease. We discuss the current state of the art regarding miRNAs and GBM. We performed a narrative review using the MEDLINE/PUBMED database to retrieve peer-reviewed articles related to the use of miRNA approaches for the treatment of GBMs. MiRNAs are intrinsic non-coding RNA molecules that regulate gene expression mainly through post-transcriptional mechanisms. The deregulation of some of these molecules is related to the pathogenesis of GBM. The inclusion of molecular characterization for the diagnosis of brain tumors and the advent of less-invasive diagnostic methods such as liquid biopsies, highlights the potential of these molecules as biomarkers for guiding the management of brain tumors such as GBM. Importantly, there is a need for more studies to better examine the application of these novel molecules. The constantly changing characterization and approach to the diagnosis and management of brain tumors broaden the possibilities for the molecular inclusion of novel epigenetic molecules, such as miRNAs, for a better understanding of this disease.

Symptomatic spinal metastasis of a supratentorial glioblastoma in a pediatric patient: a case report and comprehensive review of the literature.

Spinal metastasis of Glioblastoma is a rare occurrence, especially in pediatric patients, and extremely rare to become symptomatic. The pathology is poorly understood and remains with unclear dissemination mechanisms. The treatment approaches are varied and multimodal therapy (surgery, chemotherapy, and radiotherapy) can be employed to manage this type of metastasis. We report a case of a 17-year-old female who underwent a gross-total resection of a right frontal glioblastoma and had adjuvant therapy with chemo- and radiotherapy. In the sixth month of follow-up, the patient presented a paraparesis, and a distant recurrence at T7-T8 was detected. The patient was treated with gross-total resection of the tumor through a laminectomy. The histopathological results were consistent with an isocitrate dehydrogenase (IDH) wildtype GBM metastasis. The patient was treated with multimodal therapy, including surgery, radiotherapy, and chemotherapy. A complementary comprehensive review of current available literature on this topic is also presented.

Shaping the curve from the microscopic transsphenoidal to the endoscopic endonasal approach for the sellar region.

OBJECTIVE: This study aimed to investigate the limitations, barriers, and complications in the early transition from the microscopic transsphenoidal approach (MTA) to the endonasal endoscopic approach (EEA) to the skull base in our institution. METHODS: Technical challenges, as well as clinical features and complications, were compared between MTA, EEA, and mixed cases during the early surgical curve. RESULTS: The period from the early learning curve was 1 year until the EEA protocol was used routinely. A total of 34 patients registered a resection using a transsphenoidal approach. Eighteen patients underwent EEA, 11 underwent MTA, and five underwent a mixed endonasal and microscopic approach. Non-significant differences were found in endocrine outcomes between the three groups. Patients with unchanged or improved visual function were higher in the EEA group (p = 0.147). Non-significant differences were found in terms of the extent of resection (EOR) between groups (p = 0.369). Only 1 (2.9%) patient in the whole series developed a post-operative CSF leaking that resolved with medical management, belonging to the EEA group (5.5%). CONCLUSIONS: The early phase of the learning curve did not affect our series significantly in terms of the EOR, endocrine status, and visual outcomes.

OBJETIVO: Investigar las limitaciones, las barreras y las complicaciones en la transición del abordaje transesfenoidal microscópico (ATM) al abordaje endonasal endoscópico (AEE) para la base del cráneo en nuestra institución. MÉTODO: Se compararon las características clínicas y las complicaciones entre ATM, AEE y casos mixtos durante la curva quirúrgica temprana. RESULTADOS: El periodo desde la curva de aprendizaje inicial fue de 1 año hasta que se utilizó el protocolo AEE de forma sistemática. Un total de 34 pacientes tuvieron una resección por vía transesfenoidal. A 18 pacientes se les realizó AEE, a 11 ATM y a 5 abordaje mixto endonasal y microscópico. Se encontraron diferencias no significativas en los resultados endocrinos entre los tres grupos. Los pacientes con función visual sin cambios o mejorada fueron más en el grupo AEE (p = 0.147). No se encontraron diferencias significativas respecto a la extensión de la resección (p = 0.369). Solo 1 (2.9%) paciente desarrolló una fístula de líquido cefalorraquídeo que se resolvió con manejo médico, perteneciente al grupo AEE (5.5%). CONCLUSIONES: La fase inicial de la curva de aprendizaje no afectó significativamente a nuestra serie en términos de extensión de la resección, estado endocrino y resultados visuales.

Preoperative tractography algorithm for safe resection of tumors located in the descending motor pathways zone.

Background: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs. Methods: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records. Results: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 years (range, 19-81 years). A complete radiological resection was achieved in nine patients, a subtotal resection in five, a partial resection in three, and a biopsy in two. Histopathological diagnoses included 10 patients with high-grade glioma and nine with low-grade glioma. A total of 16 perirolandic locations (10 frontal and six frontoparietal) were recorded, as well as two in the insula and one in the basal ganglia. In 9 patients (47.3%), the lesion was in the dominant hemisphere. The median preoperative and postoperative Karnofsky Performance Scores were 78 and 80, respectively. Motor function was unchanged or improved over time in 15 cases (78.9%). Conclusion: This protocol of DTI reconstruction for glioma removal near the DMP shows good results in low-term neurological functional outcomes.

Standardization of Strategies to Perform a Parafascicular Tubular Approach for the Resection of Brain Tumors in Eloquent Areas.

OBJECTIVE: The aim of this work is to define a methodological strategy for the minimally invasive tubular retractor (MITR) parafascicular transulcal approach (PTA) for the management of brain tumors sited in eloquent areas. METHODS: An observational prospective study was designed to evaluate the benefits of PTA associated with MITRs, tractography and intraoperative cortical stimulation. They study was conducted from June 2018 to June 2021. Information regarding white matter tracts was processed, preventing a potential damage during the approach and/or resection. All patients older than 18 years who had a single brain tumor lesion were included in the study. Patients with a preoperative Karnofsky Performance Scale (KPS) score greater than 70% and a Glasgow Coma Scale (GCS) score > 14 points were included. RESULTS: 72 patients were included in the study, the mean age was 49.6, the most affected gender was male, 12.5% presented aphasia, 11.1% presented paraphasia, 41.6% had motor deficit, 9.7% had an affection in the optic pathway, the most frequently affected region was the frontal lobe (26.3%), the most frequent lesions were high-grade gliomas (34.7%) and the measurement of the incisions was on average 5.58 cm. Of the patients, 94.4% underwent a total macroscopic resection and 90.2% did not present new postoperative neurological deficits. In all cases, a PTA was used. CONCLUSION: Tubular minimally invasive approaches (MIAs) allow one to perform maximal safe resection of brain tumors in eloquent areas, through small surgical corridors. Future comparative studies between traditional and minimally invasive techniques are required to further investigate the potential of these surgical nuances.

Postnatal Surgical Correction of Myelomeningoceles: Preoperative and Intraoperative Risk Factors Associated with Postoperative Neurologic Outcomes.

OBJECTIVE: Open spina bifida or myelomeningocele (MMC) is a congenital defect that results from failure of caudal neurulation. We present a case series of patients who were treated with postnatal surgical correction for MMC, evaluating the possible preoperative and intraoperative risk factors associated with neurologic outcomes. METHODS: A retrospective chart review of patients who underwent postnatal surgical correction for MMCs over 11 years at our institution was performed. MMCs were classified based on their morphologic configuration into 3 types. Type I includes defects without a sac and there is cerebrospinal fluid (CSF) leak. Type II includes where there is a sac ≤4 cm, with or without CSF leak. Type III includes defects with a sac that are greater than 4 cm. RESULTS: Fifty patients were included. The median age of gestation at surgery was 37.4 weeks. There were 30 females (60%). All mothers received adequate folate supplementation. All patients underwent surgical correction in the first 48 hours. Lower extremity motor function at the last clinical follow-up was normal in 34 patients (68%). CSF leak, infection, and mortality were 8%, 2%, and 0%, respectively. Twenty-one patients (42%) underwent ventriculoperitoneal shunt for hydrocephalus. CONCLUSIONS: Despite there being no statistically significant associations with a timely closure, all cases were treated within the first 48 hours and this could influence the low complication rate. Individuals of Hispanic background who received appropriate folate supplementation still had high rates of MMC and we posit that this may be caused in part by a genetic/molecular predisposition.

The reverse question mark and L.G. Kempe incisions for decompressive craniectomy: A case series and narrative review of the literature.

Background: Decompressive craniectomy (DC) is a lifesaving procedure, relieving intracranial hypertension. Conventionally, DCs are performed by a reverse question mark (RQM) incision. However, the use of the L. G. Kempe's (LGK) incision has increased in the last decade. We aim to describe the surgical nuances of the LGK and the standard RQM incisions to treat patients with severe traumatic brain injury (TBI), intracranial hemorrhage (ICH), empyema, and malignant ischemic stroke. Furthermore, to describe, surgical limitations, wound healing, and neurological outcomes related to each technique. Methods: To describe a prospective acquired, case series including patients who underwent a DC using either an RQM or an LGK incision in our institution between 2019 and 2020. Results: A total of 27 patients underwent DC. Of those, ten patients were enrolled. The mean age was 42.1 years (26-71), and 60% were male. Five patients underwent DC using a large RQM incision; three had severe TBI, one ICH, and one ischemic stroke. The other five patients underwent DC using an LGK incision (one ICH, one subdural empyema, and one ischemic stroke). About 50% of patients presented severe headaches associated with vomiting, and six presented altered mental status (drowsy or stuporous). Motor deficits were present in four cases. In patients with ischemic or hemorrhagic stroke, symptoms were directly related to the stroke location. Hospital stays varied between 13 and 22 days. No readmissions were recorded, and no fatal outcome was documented during the follow-up. Conclusion: The utility of the LGK incision is comparable with the classic RQM incision to treat acute brain injuries, where an urgent decompression must be performed. Some of these cases include malignant ischemic strokes, ICH, and empyema. No differences were observed between both techniques in terms of prevention of scalp necrosis and general cosmetic outcomes.

Resección Tubular Microquirúrgica de un Subependimoma Extenso del Ventrículo Lateral Izquierdo: Video Operatorio en 2D / Microsurgical Tubular Resection of an Extensive Subependymoma of the Left Lateral Ventricle: Operative Video in 2D

Introducción: Los subependimomas intracraneales son raros, representan el 0.2-0.7% de todos los tumores del sistema nervioso central1,2 y se originan en los ventrículos laterales en el 30-40% de los casos.3 Los síntomas usualmente se asocian a hipertensión endocraneana secundaria a hidrocefalia obstructiva.4 La resección completa del tumor es curativa en esta patología.5 El abordaje trans-surcal es seguro para lesiones ventriculares profundas y el uso de los retractores tubulares minimizan la retracción del parénquima cerebral evitando la compresión directa con valvas. Esto permite disminuir la presión del tejido cerebral que puede ocluir los vasos y producir isquemia local generando una lesión neurológica permanente. Descripción del caso: Se presenta el caso de una paciente de 66 años, diestra, con cefalea crónica que aumenta en frecuencia en el último mes. La resonancia cerebral contrastada muestra un tumor extenso en el ventrículo lateral izquierdo con signos de hidrocefalia obstructiva. Intervención: Se coloca la paciente en posición supina. Se hace una incisión bicoronal y se hace un abordaje trans-surcal F1/F2 izquierdo. Se coloca un retractor tubular guiado con el puntero de neuronavegación, introduciéndolo directamente en el parénquima cerebral y fijándolo al soporte de Leyla. Se colocó un catéter de ventriculostomía contralateral y se retira a las 48 horas sin complicaciones asociadas. La resonancia contrastada postoperatoria demuestra una resección completa del tumor. El análisis de patología reveló un subependimoma grado I de la clasificación de la Organización Mundial de la Salud. La paciente presentó transitoriamente apatía y pérdida del control del esfínter urinario que resolvieron completamente a las 3 semanas después de la cirugía. Se firmó un consentimiento firmado para la publicación de la información utilizada en este trabajo. Conclusión: La resección completa microscópica de un subependimoma extenso del ventrículo lateral izquierdo es factible a través de un abordaje tubular transulcal.

Introduction: Intracranial subependymomas are rare, representing only 0.2-0.7% of all central nervous system tumors1,2 and arise in the lateral ventricles in 30-40% of the cases.3 Symptoms depend on tumor location and usually arise when the cerebrospinal fluid (CSF) is blocked, generating a consequent intracranial hypertension.4 Microsurgical gross-total resection is possible and curative for these tumors.5 The transcortical/trans-sulcal approach is a safe approach for the access of deep-seated intraventricular lesions. The use of tubular retractor systems minimizes retraction injury when passing through the cortex and deep white matter tracts. This allows a decrease in the pressure on brain tissue that can occlude the brain vessels and produce local ischemia and a consequent permanent neurological injury. Case description: This is a case of a 66-year-old woman who presented chronic headaches that increased in frequency in the last month. Enhanced-brain MRI demonstrated a large left ventricular lesion with signs of obstructive hydrocephalus. Procedure: Patient was positioned supine. A bicoronal incision was used to perform a left frontal craniotomy. An F1/F2 transcortical/trans-sulcal approach was used. A guided tubular retractor is placed with the neuronavigation pointer, inserting it directly into the brain parenchyma and fixing it to the Leyla support. Postoperative postcontrast MRI demonstrated a complete resection of the tumor. Histopathological analysis revealed a subependymoma (World Health Organization Grade I). The patient presented transient apathy and loss of urinary sphincter control that completely resolved 3 weeks after surgery. Written informed consent was obtained for publication of information used for this work. Conclusions: A complete microsurgical resection of a large left ventricular subependymoma is feasible through a trans-sulcal tubular approach.

Identification of Preoperative Language Tracts for Intrinsic Frontotemporal Diseases: A Pilot Reconstruction Algorithm in a Middle-Income Country.

OBJECTIVE: Diffusion tensor imaging (DTI) tractography provides useful information that can be used to optimize surgical planning and help avoid injury during subcortical dissection of eloquent tracts. The objective is to provide a safe, timely, and affordable algorithm for preoperative DTI language reconstruction for intrinsic frontotemporal diseases. METHODS: We reviewed a prospectively acquired database of preoperative DTI reconstruction for resection of left frontotemporal lesions over 3 years at Hospital de San José and Hospital Infantil Universitario San José, Fundación Universitaria de Ciencias de la Salud, Bogota, Colombia. Preoperative and postoperative clinical and radiographic features were determined from retrospective chart review. A comprehensive review of the structural and functional anatomy of the language tracts was performed. Separate reconstruction of both ventral (semantic) and dorsal (phonologic) stream pathways is described: arcuate fasciculus, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus. RESULTS: Between January 2015 and January 2018, 44 tumor cases were found to be resected with preoperative fiber tracking planning and neuronavigation-guided surgery. Ten patients (7 women, 3 men) aged 28-65 years underwent resection of an intrinsic frontotemporal lesion with preoperative DTI tractography reconstruction of language tracts. Eight cases (80%) were high-grade gliomas and 2 (20%) were cavernous malformations. In 5 cases (50%), the lesion was in the frontal lobe and in 5 (50%), it was in the temporal lobe. The extent of resection was classified as gross total resection (100%), subtotal resection (>90%), or partial resection (<90%). Gross total resection was achieved in 5 cases (50%), subtotal resection was achieved in 4 cases (40%), and partial resection in the remaining case (10%). Compromised tracts included superior longitudinal fasciculus in 7 (70%), inferior longitudinal fasciculus in 4 (40%), the arcuate fasciculus in 3 (30%), and uncinate fasciculus in 1 (10%). Language function was unchanged or improved in 90% of patients. New-onset postoperative language decline occurred in 1 patient, who recovered transient phonemic paraphasias 1 month after resection. The mean follow-up time was 7 months (range, 4-12 months). Residual tumors were treated with radiation and/or with chemotherapy as indicated in an outpatient setting. CONCLUSIONS: We present a safe and efficacious preoperative DTI language reconstruction algorithm that could be used as a feasible treatment strategy in a challenging subset of tumors in low- to middle-income countries.