Patients affected by glioma frequently experience epileptic discharges; however, the causes of brain tumor–related epilepsy (BTRE) are still not completely understood. We investigated the mechanisms underlying BTRE by analyzing the effects of exosomes released by U87 glioma cells and by patient-derived glioma cells. Rat hippocampal neurons incubated for 24 hours with these exosomes exhibited increased spontaneous firing, while their resting membrane potential shifted positively by 10–15 mV. Voltage clamp recordings demonstrated that the activation of the Na ⁺ current shifted toward more hyperpolarized voltages by 10–15 mV. To understand the factors inducing hyperexcitability, we focused on exosomal cytokines. Western blot and ELISAs showed that TNF-α was present inside glioma-derived exosomes. Remarkably, incubation with TNF-α fully mimicked the phenotype induced by exosomes, with neurons firing continuously, while their resting membrane potential shifted positively. Real-time PCR revealed that both exosomes and TNF-α induced overexpression of the voltage-gated Na ⁺ channel Nav1.6, a low-threshold Na ⁺ channel responsible for hyperexcitability. When neurons were preincubated with infliximab, a specific TNF-α inhibitor, the hyperexcitability induced by exosomes and TNF-α was drastically reduced. We propose that infliximab, an FDA-approved drug to treat rheumatoid arthritis, could ameliorate the conditions of glioma patients with BTRE.

Intraoperative seizures (IOS) represent a complication during surgery of diffuse low-grade gliomas (DLGGs), particularly in cases of awake craniotomy, history of tumor-related epilepsy (TRE), and cortical mapping

Introduction: Glioma Grade 4 (GG4) tumors, which include both IDH-mutated and IDH wild-type astrocytomas, are the most prevalent and aggressive form of primary brain tumor. Radiomics is gaining ground in neuro-oncology. The integration of this data into machine learning models has the potential to improve the accuracy of prognostic models for GG4 patients. Karnofsky Performance Status (KPS), an established preoperative prognostic factor for survival, is commonly used in these patients. In this study, we developed a nomogram to identify patients with improved functional performance as indicated by an increase in KPS after surgery by analyzing radiomic features from preoperative 3D MRI scans. Methods: Quantitative imaging features were extracted from the -3D T1 GRE sequence of 157 patients from a single center and were used to develop the machine learning (ML) model. To improve applicability and create a nomogram, multivariable logistic regression analysis was performed to build a model incorporating clinical characteristics and radiomics features. Results: We labeled 55 cases in which KPS was improved after surgery (35%, KPS-flag = 1). The resulting model was evaluated according to test series results. The best model was obtained by XGBoost using the features extracted by pyradiomics, with a Matthew coefficient score (MCC) of 0.339 (95% CI: 0.330–0.3483) in cross-validation. The out-of-sample evaluation on the test set yielded an MCC of 0.302. A nomogram evaluating the improvement of KPS post-surgery was built based on statistically significant variables from multivariate logistic regression including clinical and radiomics data (c-index = 0.760, test set). Conclusions: MRI radiomic analysis represents a powerful tool to predict postoperative functional outcomes, as evaluated by KPS.

Background/Objectives: Ventriculoperitoneal shunting is a validated procedure for the treatment of idiopathic normal-pressure hydrocephalus. To select shunt-responsive patients, infusion and tap tests can be used. Only gait is evaluated after the procedure to establish a potential improvement. In this study, we present our Hydro-Real-Time Neuropsychological Testing protocol to assess the feasibility of performing an ultra-fast assessment of patients during the infusion and tap test. Methods: We tested 57 patients during the infusion and tap test to obtain real-time feedback on their cognitive status. Data were obtained immediately before the infusion phase (T0), when the pressure plateau was reached (T1), and immediately after cerebrospinal fluid subtraction (T2). Based on cerebrospinal fluid dynamics, 63.15% of the patients presented a resistance to outflow > 12 mmHg/mL/min, while 88% had a positive tap test response. Results: Compared to T0, cerebrospinal fluid removal significantly improved performance on tasks exploring executive functions (counting backward, p < 0.001; verbal fluency, p < 0.001). Patients were significantly faster at counting backward at T2 vs. T1 (p < 0.05) and at T2 vs. T0 (p < 0.001) and were significantly faster at counting forward at T2 vs. T1 (p < 0.005), suggesting an improvement in speed at T2. There was a significantly smaller index at T1 vs. T0 (p = 0.005) and at T2 vs. T0 (p < 0.001), suggesting a more marked improvement in patients’ executive abilities at T2 and a smaller improvement at T1. Regarding verbal fluency, patients were worse at T1 vs. T0 (p < 0.001) and at T2 vs. T0 (p < 0.001). Conclusions: Patients’ performance can be monitored during the infusion and tap test as significant changes in executive functions are observable. In future, this protocol might help improve patients’ selection for surgery.

Intraoperative neurophysiological monitoring (IONM) is widely used during brainstem surgery to reduce the risk of neurological injury, although its prognostic value in adult brainstem glioma (BSG) surgery remains unclear. We retrospectively analyzed 22 consecutive adults who underwent surgery for BSGs with multimodal IONM between 2010 and 2023. Monitoring included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), brainstem auditory evoked potentials (BAEPs), corticobulbar MEPs (CoMEPs), and cranial nerves electromyography. The primary endpoint was the association between intraoperative neurophysiological changes and postoperative neurological functional status at hospital discharge, assessed with the modified McCormick Scale (mMCS). Secondary endpoints included postoperative complications and length of hospital stay. SSEP warning criteria were met in 10 patients (45.5%), while 10 patients (45.5%) experienced a ≥50% reduction in MEP amplitude in at least one monitored muscle. Despite these findings, neither SSEP nor MEP amplitude changes were significantly associated with postoperative neurological status. Transcranial MEP stimulation thresholds increased significantly during surgery (p = 0.007), and threshold elevation was associated with postoperative complications (Kendall’s τ = 0.498, p = 0.007). BAEP recordings remained stable throughout all procedures. Conventional amplitude-based IONM changes were not associated with early neurological outcome after adult BSG resection. In contrast, increases in MEP stimulation threshold may represent a sensitive indicator of postoperative complications. Further prospective studies are warranted.

Background/Objectives: Performing presurgical functional magnetic resonance imaging (fMRI) mapping in young patients is considered a challenge for clinicians, as fMRI maps are the sole source of information about the functional organization of cognitive functions/areas, especially when an awake craniotomy is not possible, as is often the case for pediatric populations. The literature on the fMRI tasks used in pediatric populations with brain injuries shows a certain heterogeneity in the approaches (task-based or resting states) and tasks, with a preference for motor/language mapping: tasks assessing extra-language functions are lacking. Methods: We have designed fMRI tasks focused on language and extra-language functions, which can be easily be applied when clinicians need to perform presurgical mapping. We present a retrospective case series of 17 patients. Results: Seventeen young patients (13.4 ± 2.8 years; range 7–16) were included in the study, for whom fMRI was performed. All underwent successful fMRI mapping by completing fMRI tasks selected based on their lesion site. The number of tasks performed by each patient significantly correlated with their age (r(17) = 0.561, p = 0.019). The patients tolerated the assessment and had good motion control: their movement parameters were minimal (range of rotation of −0.015–0.01 degrees; range of translation of −0.8–0.2 mm). The most administered fMRI tasks were tongue motor localizer (60%) and object naming (70%), with some patients performing extra-language function mapping involving visuo-spatial processing, selective attention, memory, and inhibition. Conclusions: This is an exploratory study given the sample size. fMRI measurements were considered feasible, as patients were able to complete the tasks under clinically realistic conditions. We discuss the clinical implication/usefulness of administering tasks for a personalized functional assessment of the young patient before surgery.