Update on the role of S100B in traumatic brain injury in pediatric population: a meta-analysis.

OBJECTIVE: Cranial computed tomography (CT) scan is the most widely used tool to rule out intracranial lesions after pediatric traumatic brain injury (TBI). However, in pediatric population, the radiation exposure can lead to an increased risk of hematological and brain neoplasm. Defined in 2019 National Institute for Health and Care Excellence (NICE) guidelines as "troponins for the brain", serum biomarkers measurements, particularly S100B, have progressively emerged as a supplementary tool in the management of TBI thanks to their capacity to predict intracranial post-traumatic lesions. METHODS: This systematic review was conducted following the PRISMA protocol (preferred reporting items for systematic reviews and meta-analyses). No chronological limits of study publications were included. Studies reporting data from children with TBI undergoing serum S100B measurement and computed tomography (CT) scans were included. RESULTS: Of 380 articles screened, 10 studies met the inclusion criteria. Patients admitted with mild-TBI in the Emergency Department (ED) were 1325 (80.25%). The overall pooled sensitivity and specificity were 98% (95% CI, 92-99%) and 45% (95% CI, 29-63%), respectively. The meta-analysis revealed a high negative predictive value (NVP) (99%; 95% CI, 94-100%) and a low positive predictive value (PPV) (41%; 95% CI, 16-79%). Area under the curve (AUC) was 76% (95% CI, 65-85%). The overall pooled negative predictive value (NPV) was 99% (95% CI, 99-100%). CONCLUSIONS: The measurement of serum S100B in the diagnostic workflow of mTBI could help informed decision-making in the ED setting, potentially safely reducing the use of CT scan in the pediatric population. The high sensitivity and excellent negative predictive values look promising and seem to be close to the values found in adults. Despite this, it must be pointed out the high heterogeneity (> 90%) found among studies. In order for S100B to be regularly introduced in the pediatric workflow for TBI, it is important to conduct further studies to obtain cut-off levels based on pediatric reference intervals.

Ventriculoatrial shunt remains a safe surgical alternative for hydrocephalus: a systematic review and meta-analysis.

Hydrocephalus is a commonly encountered pathology in the neurosurgical practice. Since the first permanent ventriculo-subarachnoid-subgaleal shunt described by Mikulicz in 1893, there were multiple attempts to find solutions for draining the excess production/less reabsorption of the cerebrospinal fluid (CSF) from the brain. Nowadays, the most common technique is the ventriculoperitoneal shunt (VPS), whereas the ventriculoatrial shunt (VAS) is applied only in some rare conditions. To date there are still no specific guidelines or strong evidence in literature that guide the surgeon in the choice between the two methods, and the decision usually relies on the confidence and expertise of the surgeon. Considering the lack of established recommendations, this systematic review and meta-analysis aims to evaluate the effectiveness and safety of these two shunting techniques. This systematic review was conducted following the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). No chronological limits of study publications were included. Prospective and retrospective clinical studies, and reports of case series with at least five patients per group and reporting data on comparison between VAS and VPS techniques were eligible for inclusion. Nine studies reporting 3197 patients meeting the inclusion and exclusion criteria were identified and included in the quantitative synthesis. The risk of shunt dysfunction/obstruction was significantly lower in the VAS group [odds ratio (OR) 0.49, 95%-CI 0.34-0.70, I2 0%]. The risk of infection was not significantly different between the two groups (OR 1.02, 95%-CI 0.59-1.74, I2 0%). The risk of revision was not significantly different between the two groups; however, the heterogeneity between the studies was significant (OR 0.73, 95%-CI 0.36-1.49, I2 91%). Additionally, the risk of death was not significantly different between the two groups; however, the heterogeneity between the studies was high (OR 1.93, 95%-CI 0.81-4.62, I2 64%). VAS remains a safe surgical alternative for hydrocephalus. The results of this study highlight a lower risk of shunt dysfunction/obstruction variable in the VAS group, with no significant statistical differences regarding the occurrence of at least one infection-related complication. In consequence, the choice between these two techniques must be tailored to the specific characteristics of the patient.Protocol Registration: The review protocol was registered and published in Prospective Register of Systematic Reviews (PROSPERO) ( www.crd.york.ac.uk/PROSPERO ) website with registration number: CRD42023479365.

Application of the NSE score (Neurology-Stability-Epidural compression assessment) to establish the need for surgery in spinal metastases of elderly patients: a multicenter investigation.

PURPOSE: This retropective multicentric study aims to investigate the clinical applicability of the NSE score in the elderly, to verify the role of this tool as an easy help for decision making also for this class of patients. METHODS: All elderly patients (> 65 years) suffering from spinal metastases undergoing surgical or non-surgical treatment at the authors' Institutions between 2015 and 2022 were recruited. An agreement group (AG) and non-agreement group (NAG) were identified accordingly to the agreement between the NSE score indication and the performed treatment. Neurological status and axial pain were evaluated for both groups at follow-up (3 and 6 months). The same analysis was conducted specifically grouping patients older than 75 years. RESULTS: A strong association with improvement or preservation of clinical status (p < 0.001) at follow-up was obtained in AG. The association was not statistically significant in NAG at the 3-month follow-up (p 1.00 and 0.07 respectively) and at 6 months (p 0.293 and 0.09 respectively). The group of patients over 75 years old showed similar results in terms of statistical association between the agreement group and better outcomes. CONCLUSION: Far from the need or the aim to build dogmatic algorithms, the goal of preserving a proper performance status plays a key role in a modern oncological management: functional outcomes of the multicentric study group showed that the NSE score represents a reliable tool to establish the need for surgery also for elderly patients.

The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Facial nerve outcome score: a new score to predict long-term facial nerve function after vestibular schwannoma surgery.

Introduction: Patients' quality of life (QoL), facial nerve (FN), and cochlear nerve (CN) (if conserved) functions should be pursued as final outcomes of vestibular schwannoma (VS) surgery. In regard to FN function, different morphologic and neurophysiological factors have been related to postoperative outcomes. The aim of the current retrospective study was to investigate the impact of these factors on the short- and long-term FN function after VS resection. The combination of preoperative and intraoperative factors resulted in designing and validating a multiparametric score to predict short- and long-term FN function. Methods: A single-center retrospective analysis was performed for patients harboring non-syndromic VS who underwent surgical resection in the period 2015-2020. A minimum follow-up period of 12 months was considered among the inclusion criteria. Morphological tumor characteristics, intraoperative neurophysiological parameters, and postoperative clinical factors, namely, House-Brackmann (HB) scale, were retrieved in the study. A statistical analysis was conducted to investigate any relationships with FN outcome and to assess the reliability of the score. Results: Seventy-two patients with solitary primary VS were treated in the period of the study. A total of 59.8% of patients showed an HB value < 3 in the immediate postoperative period (T1), reaching to 76.4% at the last follow-up evaluation. A multiparametric score, Facial Nerve Outcome Score (FNOS), was built. The totality of patients with FNOS grade A showed an HB value < 3 at 12 months, decreasing to 70% for those with FNOS grade B, whereas 100% of patients with FNOS grade C showed an HB value ≥ 3. The ordinal logistic regression showed three times increasing probability to see an HB value ≥ 3 at 3-month follow-up for each worsening point in FNOS score [Exp(B), 2,999; p < 0.001] that was even more probable [Exp(B), 5.486; p < 0.001] at 12 months. Conclusion: The FNOS score resulted to be a reliable score, showing high associations with FN function both at short- and long-term follow-up. Although multicenter studies would be able to increase its reproducibility, it could be used to predict the FN damage after surgery and the potential of restoring its function on the long-term period.

Muscle synergies in Parkinson's disease before and after the deep brain stimulation of the bilateral subthalamic nucleus.

The aim of this study is to quantitatively assess motor control changes in Parkinson's disease (PD) patients after bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS), based on a novel muscle synergy evaluation approach. A group of 20 PD patients evaluated at baseline (before surgery, T0), at 3 months (T1), and at 12 months (T2) after STN-DBS surgery, as well as a group of 20 age-matched healthy control subjects, underwent an instrumented gait analysis, including surface electromyography recordings from 12 muscles. A smaller number of muscle synergies was found in PD patients (4 muscle synergies, at each time point) compared to control subjects (5 muscle synergies). The neuromuscular robustness of PD patients-that at T0 was smaller with respect to controls (PD T0: 69.3 ± 2.2% vs. Controls: 77.6 ± 1.8%, p = 0.004)-increased at T1 (75.8 ± 1.8%), becoming not different from that of controls at T2 (77.5 ± 1.9%). The muscle synergies analysis may offer clinicians new knowledge on the neuromuscular structure underlying PD motor types of behavior and how they can improve after electroceutical STN-DBS therapy.

Hardware-Related Skin Erosion in Deep Brain Stimulation for Parkinson's Disease: How Far Can We Go? An Illustrative Case Report.

Skin erosion is a hardware-related complication commonly described after deep brain stimulation (DBS). Hardware exposure is often associated with the development of infection that can lead to implant removal. However, in selected cases, it is possible to manage skin erosion without having to remove the hardware. This article presents the case of a patient with recurrent skin erosions above the IPG, who underwent multiple surgeries. Given the failure of less invasive approaches, a more complex surgery with the employment of a pedunculated flap of pectoralis major in order to cover the IPG was attempted. Nevertheless, the IPG removal was finally unavoidable, resulting in a rapid decline in clinical performance. This illustrative case suggests how, in patients with sustained stimulation who benefit from a good degree of autonomy, it may be useful to use invasive surgical techniques to resolve skin erosions and save the DBS system. In spite of everything, sometimes complete or partial removal of the implant still becomes unavoidable, but this can lead to a severe worsening of PD symptoms. Definitive removal of the system should therefore be considered only in cases of frank infection or after failure of all other approaches.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.

Virtual-Augmented Reality and Life-Like Neurosurgical Simulator for Training: First Evaluation of a Hands-On Experience for Residents.

Background: In the recent years, growing interest in simulation-based surgical education has led to various practical alternatives for medical training. More recently, courses based on virtual reality (VR) and three-dimensional (3D)-printed models are available. In this paper, a hybrid (virtual and physical) neurosurgical simulator has been validated, equipped with augmented reality (AR) capabilities that can be used repeatedly to increase familiarity and improve the technical skills in human brain anatomy and neurosurgical approaches. Methods: The neurosurgical simulator used in this study (UpSurgeOn Box, UpSurgeOn Srl, Assago, Milan) combines a virtual component and a physical component with an intermediate step to provide a hybrid solution. A first reported and evaluated practical experience on the anatomical 3D-printed model has been conducted with a total of 30 residents in neurosurgery. The residents had the possibility to choose a specific approach, focus on the correct patient positioning, and go over the chosen approach step-by-step, interacting with the model through AR application. Next, each practical surgical step on the 3D model was timed and qualitatively evaluated by 3 senior neurosurgeons. Quality and usability-grade surveys were filled out by participants. Results: More than 89% of the residents assessed that the application and the AR simulator were very helpful in improving the orientation skills during neurosurgical approaches. Indeed, 89.3% of participants found brain and skull anatomy highly realistic during their tasks. Moreover, workshop exercises were considered useful in increasing the competency and technical skills required in the operating room by 85.8 and 84.7% of residents, respectively. Data collected confirmed that the anatomical model and its application were intuitive, well-integrated, and easy to use. Conclusion: The hybrid AR and 3D-printed neurosurgical simulator could be a valid tool for neurosurgical training, capable of enhancing personal technical skills and competence. In addition, it could be easy to imagine how patient safety would increase and healthcare costs would be reduced, even if more studies are needed to investigate these aspects. The integration of simulators for training in neurosurgery as preparatory steps for the operating room should be recommended and further investigated given their huge potential.

Fluorescence-Guided Surgery in Glioblastoma: 5-ALA, SF or Both? Differences between Fluorescent Dyes in 99 Consecutive Cases.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor's borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. METHODS: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. RESULTS: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). CONCLUSIONS: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage.

Dissecting Aneurysm of the L1 Radiculomedullary Artery Associated with Subarachnoid Hemorrhage: A Case Report.

BACKGROUND: Both spinal artery aneurysm and spinal subarachnoid hemorrhage represent a very rare event. METHODS: We report a case of a ruptured dissecting aneurysm of the right L1 radiculomedullary artery associated with subarachnoid hemorrhage and severe motor weakness. RESULTS: An urgent decompressive hemilaminectomy was performed due to worsening in motor deficit. A subsequent spinal angiography showed a dissection of radiculomedullary artery of L1 on the right side, treated conservatively. CONCLUSION: Nowadays, therapeutic strategies for this aneurysm remain controversial. Conservative strategy can represent a valid alternative.

A New Implantable Closed-Loop Clinical Neural Interface: First Application in Parkinson's Disease.

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson's disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBSR System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson's disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place.

Effect of Waste Polyethylene and Wax-Based Additives on Bitumen Performance.

Over the last years, the replacement of traditional polymer modifiers with waste plastics has attracted increasing interest. The implementation of such technology would allow a drastic reduction of both production cost and landfill disposal of wastes. Among all, polyethylene-based plastics have been proved suitable for this purpose. The research activities presented in this paper aim to assess the synergistic effect of polyethylene and Fischer-Tropsch waxes on the viscoelastic properties and performance of the bitumen. In order to reduce the blending time, waxes, and polyethylene need to be added simultaneously. In fact, the presence of the waxes reduces the polarity of the bitumen matrix and increases the affinity with the polymer promoting its dispersion. Results demonstrate that the chain length of the waxes, the form of the added waste polyethylene, and the blending protocol have critical effects on the time-evolution of such properties. Short-chain waxes have a detrimental impact on the rutting resistance regardless of the blending protocol. On the contrary, long-chain waxes improve the overall behavior of the polyethylene-modified binders and, in particular, the resistance to permanent deformations.

Waste Rubber from End-of-Life Tires in 'Lean' Asphalt Mixtures-A Laboratory and Field Investigation in the Arid Climate Region.

Waste rubber from end-of-life tires has been proved to be an excellent source of polymeric material for paving applications. Over the years, however, the rubberized asphalt technology has never been used in 'lean' (low bitumen content) asphalt mixtures typically used in arid regions. This study offers an insight on the potential benefits and drawbacks resulting from this technology if applied in such 'lean' mixes. Results show that the 'lean' nature of those asphalt mixes eliminates the potential benefits given by the modified bitumen for rutting performance. Instead, the aggregates gradation plays a major role in the response of the materials, with gap-graded mixtures often outperforming those with a dense-graded gradation. On the contrary, fatigue cracking resistance is affected by the bitumen properties, and rubberized asphalt perform better than others. The performance-based analysis suggests that the current specifications tend to overachieve the goal of reducing permanent deformation while cracking becomes a major concern which can be solved by using rubberized asphalt. In the field, gap-graded asphalt with rubberized bitumen showed the best response in terms of skid resistance and noise reduction.

Nanocomposite Conductive Bioinks Based on Low-Concentration GelMA and MXene Nanosheets/Gold Nanoparticles Providing Enhanced Printability of Functional Skeletal Muscle Tissues.

There is a growing need to develop novel well-characterized biological inks (bioinks) that are customizable for three-dimensional (3D) bioprinting of specific tissue types. Gelatin methacryloyl (GelMA) is one such candidate bioink due to its biocompatibility and tunable mechanical properties. Currently, only low-concentration GelMA hydrogels (≤5% w/v) are suitable as cell-laden bioinks, allowing high cell viability, elongation, and migration. Yet, they offer poor printability. Herein, we optimize GelMA bioinks in terms of concentration and cross-linking time for improved skeletal muscle C2C12 cell spreading in 3D, and we augment these by adding gold nanoparticles (AuNPs) or a two-dimensional (2D) transition metal carbide (MXene nanosheets) for enhanced printability and biological properties. AuNP and MXene addition endowed GelMA with increased conductivity (up to 0.8 ± 0.07 and 0.9 ± 0.12 S/m, respectively, compared to 0.3 ± 0.06 S/m for pure GelMA). Furthermore, it resulted in an improvement of rheological properties and printability, specifically at 10 °C. Improvements in electrical and rheological properties led to enhanced differentiation of encapsulated myoblasts and allowed for printing highly viable (97%) stable constructs. Taken together, these results constitute a significant step toward fabrication of 3D conductive tissue constructs with physiological relevance.

Atypical Gait Cycles in Parkinson's Disease.

It is important to find objective biomarkers for evaluating gait in Parkinson's Disease (PD), especially related to the foot and lower leg segments. Foot-switch signals, analyzed through Statistical Gait Analysis (SGA), allow the foot-floor contact sequence to be characterized during a walking session lasting five-minutes, which includes turnings. Gait parameters were compared between 20 PD patients and 20 age-matched controls. PDs showed similar straight-line speed, cadence, and double-support compared to controls, as well as typical gait-phase durations, except for a small decrease in the flat-foot contact duration (-4% of the gait cycle, p = 0.04). However, they showed a significant increase in atypical gait cycles (+42%, p = 0.006), during both walking straight and turning. A forefoot strike, instead of a "normal" heel strike, characterized the large majority of PD's atypical cycles, whose total percentage was 25.4% on the most-affected and 15.5% on the least-affected side. Moreover, we found a strong correlation between the atypical cycles and the motor clinical score UPDRS-III (r = 0.91, p = 0.002), in the subset of PD patients showing an abnormal number of atypical cycles, while we found a moderate correlation (r = 0.60, p = 0.005), considering the whole PD population. Atypical cycles have proved to be a valid biomarker to quantify subtle gait dysfunctions in PD patients.

Let Me See: Correlation between 5-ALA Fluorescence and Molecular Pathways in Glioblastoma: A Single Center Experience.

BACKGROUND: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion's edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. OBJECTIVE: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. METHODS: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. RESULTS: A trend of grade 2 fluorescence (i.e., "strong") was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. CONCLUSION: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.