Extra-temporal pediatric low-grade gliomas and epilepsy.

Low-grade gliomas, especially glioneuronal tumors, are a common cause of epilepsy in children. Seizures associated with low-grade pediatric tumors are medically refractory and present a significant burden to patients. Often, morbidity and patients´ quality of life are determined rather by the control of seizures than the oncological process itself and the resolution of epilepsy represents an important part in the treatment of LGGs. The pathogenesis of tumor-related seizures in focal LGG tumors is multifactorial, and mechanisms differ probably among patients and tumor types. Pediatric low-grade tumors associated with epilepsy include a series of neoplasms that have a pure astrocytic or glioneuronal lineage. They are usually benign tumors with a neocortical localization typically in the temporal lobes, but also in other supratentorial locations. Gangliogliomas and dysembryoplastic neuroepithelial tumors (DNET) are the most common entities together with astrocytic gliomas (pilocytic astrocytomas and pleomorphic xanthoastrocytoma) and angiocentric gliomas, and dual pathology is found in up to 40% of glioneuronal tumors. The treatment of low-grade gliomas and associated epilepsy is based mainly on resection and the extent of surgery is the main predictor of postoperative seizure control in patients with a LGG. Long-term epilepsy-associated tumors (LEATs) tend to be well-circumscribed, and therefore, the chances for a complete resection and epilepsy control with a safe approach are very high. New treatments have emerged as alternatives to open microsurgical approaches, including laser thermal ablation or the use of BRAF inhibitors. Future advances in identifying seizure-related biomarkers and molecular tumor pathways will facilitate targeted treatment strategies that will have a deep impact both in oncologic and epilepsy outcomes.

Single-Center Complication Analysis Associated with Surgical Replacement of Implantable Pulse Generators in Deep Brain Stimulation.

BACKGROUND/AIMS: Internal pulse generator (IPG) replacement is considered a relatively minor surgery but exposes the deep brain stimulation system to the risk of infectious and mechanical adverse events. We retrospectively reviewed complications associated with IPG replacement surgery in our center and reviewed the most relevant publications on the issue. METHODS: A retrospective analysis of all the IPG replacements performed in our center from January 2003 until March 2018 was performed. A logistic regression model was used to analyze the risk factors associated with IPG infections at our center. RESULTS: A total of 171 IPG replacements in 93 patients were analyzed. The overall rate of replacement complications was 8.8%, whereas the rate of infection was 5.8%. IPG removal was required in 8 out of 10 infected cases. An increased risk of infection was found in patients with subcutaneous thoracic placement of the IPG (OR 5.3, p = 0.016). The most commonly isolated germ was Staphylococcus coagulase negative (60%). We found a non-significant trend towards increased risk of infection in patients with more than 3 replacements (p = 0.07). CONCLUSIONS: Infection is the most frequent complication related to IPG replacement. Staphylococcus coagulase negative is the most commonly isolated bacteria causing the infection. According to our results, the subcutaneous thoracic placement represents a greater risk of infection compared to subcutaneous abdominal placement.

Aneurysmal subarachnoid haemorrhage: Volumetric quantification of the blood distribution pattern to accurately predict the ruptured aneurysm location.

BACKGROUND: In spontaneous subarachnoid haemorrhage (SAH) accurate determination of the bleeding source is paramount to guide treatment. Traditionally, the bleeding pattern has been used to predict the aneurysm location. Here, we have tested a software-based tool, which quantifies the volume of intracranial blood and stratifies it according to the regional distribution, to predict the location of the ruptured aneurysm. METHODS: A consecutive series of SAH patients admitted to a single tertiary centre between 2012-2018, within 72 h of onset, harbouring a single intracranial aneurysm. A semi-automatized method of blood quantification, based on the relative density increase, was applied to initial non-contrast CTs. Five regions were used to define the bleeding patterns and to correlate them with aneurysm location: perimesencephalic, interhemispheric, right/left hemisphere and intraventricular. RESULTS: 68 patients were included for analysis. There was a strong association between the distribution of blood and the aneurysm location (p < 0.001). In particular: ACom and interhemispheric fissure (p < 0.001), MCA and ipsilateral hemisphere (p < 0.001), ICA and ipsilateral hemisphere and perimesencephalic cisterns (p < 0.001), PCom and hemispheric, perimesencephalic and intraventricular (p = 0.019), and PICA and perimesencephalic and intraventricular (p < 0.001). The internal diagnostic value was high (AUROC ≥ 0.900) for these locations. CONCLUSION: Regional automatised volumetry seems a reliable and objective tool to quantify and describe the distribution of blood within the subarachnoid spaces. This tool accurately predicts the location of the ruptured aneurysm; its use may be prospectively considered in the emergency setting when speed and simplicity are attained.

Temporo-Parieto-Occipital Disconnection by Robot-Assisted Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for Refractory Epilepsy in a Pediatric Patient: Proof-of-Principle Case Report and Surgical Nuances.

OBJECTIVE: Magnetic resonance imaging-guided laser interstitial thermal therapy (MRIgLITT) has been proven safe and effective for the treatment of focal epilepsy of different etiologies. It has also been used to disconnect brain tissue in more extensive or diffuse epilepsy, such as corpus callosotomy and hemispherotomy. METHODS: In this study, we report a case of temporo-parieto-occipital disconnection surgery performed using MRIgLITT assisted by a robotic arm for refractory epilepsy of the posterior quadrant. A highly realistic cadaver simulation was performed before the actual surgery. RESULTS: The patient was a 14-year-old boy whose seizures began at the age of 8. The epilepsy was a result of a left perinatal ischemic event that caused a porencephalic cyst, and despite receiving multiple antiepileptic drugs, the patient continued to experience daily seizures which led to the recommendation of surgery. CONCLUSIONS: A Wada test lateralized language in the right hemisphere. Motor and sensory function was confirmed in the left hemisphere through magnetic resonance imaging functional studies and NexStim. The left MRIgLITT temporo-parieto-occipital disconnection disconnection was achieved using 5 laser fibers. The patient followed an excellent postoperative course and was seizure-free, with no additional neurological deficits 24 months after the surgery.

Completion of disconnective surgery for refractory epilepsy in pediatric patients using robot-assisted MRI-guided laser interstitial thermal therapy.

OBJECTIVE: Since 2007, the authors have performed 34 hemispherotomies and 17 posterior quadrant disconnections (temporoparietooccipital [TPO] disconnections) for refractory epilepsy at Sant Joan de Déu Barcelona Children's Hospital. Incomplete disconnection is the main cause of surgical failure in disconnective surgery, and reoperation is the treatment of choice. In this study, 6 patients previously treated with hemispherotomy required reoperation through open surgery. After the authors' initial experience with real-time MRI-guided laser interstitial thermal therapy (MRIgLITT) for hypothalamic hamartomas, they decided to use this technique instead of open surgery to complete disconnective surgeries. The objective was to report the feasibility, safety, and efficacy of MRIgLITT to complete hemispherotomies and TPO disconnections for refractory epilepsy in pediatric patients. METHODS: Eight procedures were performed on 6 patients with drug-resistant epilepsy. Patient ages ranged between 4 and 18 years (mean 10 ± 4.4 years). The patients had previously undergone hemispherotomy (4 patients) and TPO disconnection (2 patients) at the hospital. The Visualase system assisted by a Neuromate robotic arm was used. The ablation trajectory was planned along the residual connection. The demographic and epilepsy characteristics of the patients, precision of the robot, details of the laser ablation, complications, and results were prospectively collected. RESULTS: Four patients underwent hemispherotomy and 2 underwent TPO disconnection. Two patients, including 1 who underwent hemispherotomy and 1 who underwent TPO disconnection, received a second laser ablation because of persistent seizures and connections after the first treatment. The average precision of the system (target point localization error) was 1.7 ± 1.4 mm. The average power used was 6.58 ± 1.53 J. No complications were noted. Currently, 5 of the 6 patients are seizure free (Engel class I) after a mean follow-up of 20.2 ± 5.6 months. CONCLUSIONS: According to this preliminary experience, laser ablation is a safe method for complete disconnective surgeries and allowed epilepsy control in 5 of the 6 patients treated. A larger sample size and longer follow-up periods are necessary to better assess the efficacy of MRIgLITT to complete hemispherotomy and TPO disconnection, but the initial results are encouraging.

The impact of 1.5-T intraoperative magnetic resonance imaging in pediatric tumor surgery: Safety, utility, and challenges.

Objective: In this study, we present our experience with 1.5-T high-field intraoperative magnetic resonance imaging (ioMRI) for different neuro-oncological procedures in a pediatric population, and we discuss the safety, utility, and challenges of this intraoperative imaging technology. Methods: A pediatric consecutive-case series of neuro-oncological surgeries performed between February 2020 and May 2022 was analyzed from a prospective ioMRI registry. Patients were divided into four groups according to the surgical procedure: intracranial tumors (group 1), intraspinal tumors (group 2), stereotactic biopsy for unresectable tumors (group 3), and catheter placement for cystic tumors (group 4). The goal of surgery, the volume of residual tumor, preoperative and discharge neurological status, and postoperative complications related to ioMRI were evaluated. Results: A total of 146 procedures with ioMRI were performed during this period. Of these, 62 were oncology surgeries: 45 in group 1, two in group 2, 10 in group 3, and five in group 4. The mean age of our patients was 8.91 years, with the youngest being 12 months. ioMRI identified residual tumors and prompted further resection in 14% of the cases. The mean time for intraoperative image processing was 54 ± 6 min. There were no intra- or postoperative security incidents related to the use of ioMRI. The reoperation rate in the early postoperative period was 0%. Conclusion: ioMRI in pediatric neuro-oncology surgery is a safe and reliable tool. Its routine use maximized the extent of tumor resection and did not result in increased neurological deficits or complications in our series. The main limitations included the need for strict safety protocols in a highly complex surgical environment as well as the inherent limitations on certain patient positions with available MR-compatible headrests.

Cost-Effectiveness of Low-Field Intraoperative Magnetic Resonance in Glioma Surgery.

OBJECT: Low-field intraoperative magnetic resonance (LF-iMR) has demonstrated a slight increase in the extent of resection of intra-axial tumors while preserving patient`s neurological outcomes. However, whether this improvement is cost-effective or not is still matter of controversy. In this clinical investigation we sought to evaluate the cost-effectiveness of the implementation of a LF-iMR in glioma surgery. METHODS: Patients undergoing LF-iMR guided glioma surgery with gross total resection (GTR) intention were prospectively collected and compared to an historical cohort operated without this technology. Socio-demographic and clinical variables (pre and postoperative KPS; histopathological classification; Extent of resection; postoperative complications; need of re-intervention within the first year and 1-year postoperative survival) were collected and analyzed. Effectiveness variables were assessed in both groups: Postoperative Karnofsky performance status scale (pKPS); overall survival (OS); Progression-free survival (PFS); and a variable accounting for the number of patients with a greater than subtotal resection and same or higher postoperative KPS (R-KPS). All preoperative, procedural and postoperative costs linked to the treatment were considered for the cost-effectiveness analysis (diagnostic procedures, prosthesis, operating time, hospitalization, consumables, LF-iMR device, etc). Deterministic and probabilistic simulations were conducted to evaluate the consistency of our analysis. RESULTS: 50 patients were operated with LF-iMR assistance, while 146 belonged to the control group. GTR rate, pKPS, R-KPS, PFS, and 1-year OS were respectively 13,8% (not significative), 7 points (p < 0.05), 17% (p < 0.05), 38 days (p < 0.05), and 3.7% (not significative) higher in the intervention group. Cost-effectiveness analysis showed a mean incremental cost per patient of 789 € in the intervention group. Incremental cost-effectiveness ratios were 111 € per additional point of pKPS, 21 € per additional day free of progression, and 46 € per additional percentage point of R-KPS. CONCLUSION: Glioma patients operated under LF-iMR guidance experience a better functional outcome, higher resection rates, less complications, better PFS rates but similar life expectancy compared to conventional techniques. In terms of efficiency, LF-iMR is very close to be a dominant technology in terms of R-KPS, PFS and pKPS.

Double hemispheric Microdialysis study in poor-grade SAH patients.

Delayed cerebral ischemia (DCI) is a dreadful complication present in 30% of subarachnoid hemorrhage (SAH) patients. DCI prediction and prevention are burdensome in poor grade SAH patients (WFNS 4-5). Therefore, defining an optimal neuromonitoring strategy might be cumbersome. Cerebral microdialysis (CMD) offers near-real-time regional metabolic data of the surrounding brain. However, unilateral neuromonitoring strategies obviate the diffuse repercussions of SAH. To assess the utility, indications and therapeutic implications of bilateral CMD in poor grade SAH patients. Poor grade SAH patients eligible for multimodal neuromonitoring were prospectively collected. Aneurysm location and blood volume were assessed on initial Angio-CT scans. CMD probes were bilaterally implanted and maintained, at least, for 48 hours (h). Ischemic events were defined as a Lactate/Pyruvate ratio >40 and Glucose concentration <0.7 mmol/L. 16 patients were monitored for 1725 h, observing ischemic events during 260 h (15.1%). Simultaneous bilateral ischemic events were rare (5 h, 1.9%). The established threshold of ≥7 ischemic events displayed a specificity and sensitivity for DCI of 96.2% and 83.3%, respectively. Bilateral CMD is a safe and useful strategy to evaluate areas at risk of suffering DCI in SAH patients. Metabolic crises occur bilaterally but rarely simultaneously. Hence, unilateral neuromonitoring strategies underestimate the risk of infarction and the possibility to offset its consequences.

Malignant Glioma Developed on a Patient Under Deep Brain Stimulation: Pitfalls in Management.

BACKGROUND: Glioblastoma (GBM) is the most common aggressive malignant primary brain tumor, rarely concurrent in patients who require deep brain stimulation (DBS) implants. Despite the high incidence of these circumstances alone, the coexistence of both in a patient has been seldom reported. In this paper, we report a case of a patient suffering from a movement disorder treated with DBS who developed a GBM. CASE DESCRIPTION: A patient with bilateral DBS of the globus pallidus internus for refractory secondary dystonia developed a GBM close to the electrode leads, 2.5 years after implantation. The clinical findings, medical management and pitfalls, and possible relationship between the DBS device and the tumor development are discussed. We withdrew the system to perform brain magnetic resonance imaging safely. This revealed an extended lesion that was biopsied. The removal led to a clinical worsening that resulted in fatality, without the possibility of receiving adjuvant treatment. The available literature shows similar management, which depends mainly on the stimulation system used. CONCLUSIONS: We advise the use of magnetic resonance imaging-safe devices; otherwise, we recommend keeping the system and proceeding with computed tomography imaging for diagnostic and management if necessary. The true relationship between chronic DBS stimulation and GBM is to be clarified.

Combined Use of 5-Aminolevulinic Acid and Intraoperative Low-Field Magnetic Resonance Imaging in High-Grade Glioma Surgery.

OBJECTIVE: We sought to assess the impact of 5-aminolevulinic acid (5-ALA) and low-field intraoperative magnetic resonance imaging (iMRI) on the extent of resection of high-grade gliomas (HGGs). Results are compared with those obtained when using 5-ALA and iMRI separately. METHODS: We retrospectively included patients with an HGG eligible for gross total resection (GTR) from January 2013 to January 2018. Patients were included according to 5-ALA surgical guidance (5A-group), iMRI (iMRI-group), or both (5A-iMRI-group). Surgical variables were registered, and presurgical and postsurgical radiologic and clinical variables were analyzed. Extent of resection ≥90%, complications, and new permanent neurologic deficit were compared using the chi-squared and analysis of variance tests. Other variables studied were mortality, average hospital stay, surgical time, and Karnofsky Performance Scale status before and after surgery. RESULTS: Most of the 118 procedures carried out were in men (59.2%). The mean age was 58 years. Sixty patients (50.8%) were operated on using exclusively 5-ALA assistance (5A-group), 19 (16.1%) using iMRI (iMRI-group), and 39 (33%) combining both techniques (5A-IMRI-group). There were no statistically significant differences among 3 groups regarding extent of resection ≥90% (73% 5A, 73.7% iMRI, 71.8% 5A-iMRI, P = 0.94); complication rates (18.3% 5A, 5.3% iMRI, 7.7% 5A-iMRI, P = 0.17); new or worsening of preexisting neurologic deficit at 1-month follow-up (13.3% 5A, 10.5% iMRI, 15.4% 5A-iMRI, P = 0.26); average hospital stay in days (9.5 5A, 6.4 iMRI, 7.6 5A-iMRI, P = 0.18); Karnofsky Performance Scale; nor surgical time in minutes (212.4 5A, 187.9 iMRI, 201.4 5A-iMRI, P = 0.13). CONCLUSIONS: In our experience, combined use of iMRI and 5-ALA does not improve the studied variables when compared with those technologies when used separately, even though a slight tendency of a superior effectiveness is observed when using iMRI individually.

[Extended endoscopic endonasal surgery for clival chordoma and chondrosarcoma: Our experience in 14 cases]. / Cirugía endoscópica endonasal extendida para cordomas y condrosarcomas de clivus: nuestra experiencia en 14 casos.

OBJECTIVE: To report our experience in the management of chordoma and chondrosarcoma with extended endoscopic endonasal surgery. METHOD: We performed a retrospective analysis of a series of 14 patients with clival chordoma or chondrosarcoma who had extended endoscopic endonasal surgery from 2008 to 2016 performed by the same multidisciplinary team. RESULTS: We had fourteen patients (male/female 2:1), with a mean age of 49years for chordoma and 32 for chondrosarcoma. The most common clinical presentation was diplopia in 78.5% of cases, followed by dysphagia in 28.6%. Histologically, 71.4% were chordomas and 28.6% were chondrosarcomas. In addition, invasion of at least two thirds or more of the clivus was found in 81% of the cases; in 57.1% there was intradural invasion, and in 35.7% invasion of the sella turcica. In 42.8% of cases, the degree of resection was total and in 21.5% subtotal. The most common complication was CSF fistula, occurring in 28.6% of the cases, with only one case requiring surgery to repair it. Adjuvant treatment with Proton Beam was performed in 35.7% of cases and with conventional radiotherapy in 21.5%. Mean follow-up was 53.5months and tumour recurrence or progression was found in 21.5% of the cases, two of which had not received adjuvant treatment. There were no deaths. CONCLUSION: The extended endoscopic endonasal approach (EEEA) performed by an experienced team is a good alternative for the management of these lesions. Intradural invasion may be related to an increased risk of complications and worse clinical presentation, in addition to a lower rate of total resection.

Cirugía endoscópica endonasal extendida para cordomas y condrosarcomas de clivus: nuestra experiencia en 14 casos / Extended endoscopic endonasal surgery for clival chordoma and chondrosarcoma: Our experience in 14 cases

Objetivo: Reportar la experiencia del manejo de los cordomas y condrosarcomas por abordaje endoscópico endonasal extendido. Método: Se realizó un análisis retrospectivo de una serie de 14 pacientes afectos de cordomas o condrosarcomas clivales operados mediante un abordaje endoscópico endonasal extendido por un mismo equipo multidisciplinar, en el intervalo de tiempo desde 2008 hasta 2016. Resultados: Catorce pacientes (hombre/mujer 2:1) con una media de edad de 49años en los cordomas y de 32años en los condrosarcomas. La presentación clínica más frecuente fue la diplopía (78,5% de los casos), seguida de la disfagia (28,6%). Histológicamente se reportaron como cordomas el 71,4% y como condrosarcomas el 28,6%. Además, se encontró en el 81% de los casos invasión de al menos dos o más tercios del clivus, en el 57,1% invasión intradural y en el 35,7% invasión sellar. En el 42,8% de los casos el grado de resección fue total y en el 21,5%, subtotal. La complicación más frecuente fue la fístula de LCR, que se presentó en el 28,6% de los casos, habiendo que intervenir solo a un paciente. En el 35,7% de los casos se indicó tratamiento coadyuvante con Proton Beam y en el 21,5% radioterapia convencional. La media de seguimiento fue de 53,5meses, y se encontró recurrencia o progresión tumoral en el 21,5% de los casos, dos de los cuales no había recibido coadyuvancia. No hubo fallecimientos. Conclusión: El abordaje endoscópico endonasal extendido, realizado por un equipo experimentado, es una buena alternativa de manejo para estas lesiones. La invasión intradural podría estar relacionada con un mayor riesgo de complicaciones y una mayor afectación clínica al diagnóstico, así como con una menor tasa de resección total

Objective: To report our experience in the management of chordoma and chondrosarcoma with extended endoscopic endonasal surgery. Method: We performed a retrospective analysis of a series of 14 patients with clival chordoma or chondrosarcoma who had extended endoscopic endonasal surgery from 2008 to 2016 performed by the same multidisciplinary team. Results: We had fourteen patients (male/female 2:1), with a mean age of 49years for chordoma and 32 for chondrosarcoma. The most common clinical presentation was diplopia in 78.5% of cases, followed by dysphagia in 28.6%. Histologically, 71.4% were chordomas and 28.6% were chondrosarcomas. In addition, invasion of at least two thirds or more of the clivus was found in 81% of the cases; in 57.1% there was intradural invasion, and in 35.7% invasion of the sella turcica. In 42.8% of cases, the degree of resection was total and in 21.5% subtotal. The most common complication was CSF fistula, occurring in 28.6% of the cases, with only one case requiring surgery to repair it. Adjuvant treatment with Proton Beam was performed in 35.7% of cases and with conventional radiotherapy in 21.5%. Mean follow-up was 53.5months and tumour recurrence or progression was found in 21.5% of the cases, two of which had not received adjuvant treatment. There were no deaths. Conclusion: The extended endoscopic endonasal approach (EEEA) performed by an experienced team is a good alternative for the management of these lesions. Intradural invasion may be related to an increased risk of complications and worse clinical presentation, in addition to a lower rate of total resection