Neurosurgery increasingly employs Mixed Reality (MR) to support procedures such as External Ventricular Drain (EVD) placement, a task that requires high spatial accuracy, real-time anatomical orientation, and precise trajectory planning. To address these challenges, we present NeuroMix, an MR-based simulator designed to strengthen independent procedural skills without relying on intraoperative visual aids. After an initial pilot study with 10 participants, we conducted a full-scale experiment with 36 medical residents to evaluate three training modalities: CT-only (No Aid), CT with 2D overlay (2D Aid), and CT with 2D overlay plus animated 3D trajectory guidance (2D–3D Aid). All training was performed in a virtual environment using Meta Quest 3, followed by an unaided testing phase in which participants executed EVD placement on a physical phantom using real instruments. An additional control group of 12 residents received no MR training. Our findings show that participants trained with combined 2D–3D visual aids achieved a 44

Complete resection of the epileptogenic zone (EZ) is the strongest predictor of seizure freedom in drug-resistant epilepsy (DRE). However, even in MRI-positive cases with anatomo-electro-clinical concordance, the EZ may not be clearly delineated, complicating intraoperative decision-making. Intraoperative ultrasound (ioUS) provides real-time anatomical feedback, while depth-electrode intraoperative electrocorticography (iECoG) enables electrophysiological delineation of epileptogenic tissue beyond the cortical surface, sampling deep regions not accessible to subdural electrodes. Their integration may improve intraoperative precision in defining resection limits and optimizing resective surgery. This study describes the workflow and feasibility of combining ioUS and depth-electrode iECoG for intraoperative guidance in MRI-positive focal DRE with an ill-defined EZ. In all cases, concordant anatomo-electro-clinical data identified a single EZ for which SEEG was not required, yet the suspected EZ remained poorly delineated. ioUS was used for real-time lesion visualization, verification of electrode trajectories, and guidance of resection depth and extent. Pre- and post-resective depth-electrode iECoG and ioUS were used in combination to delineate the resection margins, by identifying interictal epileptiform discharges (IEDs) and confirming lesion boundaries and resection completeness. Six patients underwent resective surgery using the combined ioUS–iECoG workflow. The technique was feasible and safe in all cases, with no intraoperative or postoperative complications (37 depth-electrode insertions). iECoG revealed IEDs in four patients (66

In drug-resistant epilepsy, Stereo-Electroencephalography (SEEG) monitoring is one of the most effective techniques to identify the Epileptogenic Zone (EZ), the fundamental prerequisite for epilepsy surgery. Despite recent technological advances, SEEG recordings remain difficult to interpret, and SEEG-guided surgery still achieves success rates below 70%. In this work, we develop a novel computational framework for SEEG analysis, with the ultimate aim of improving the accuracy in EZ definition. Specifically, we investigate the hypothesis that epileptogenic regions exhibit a tendency to behave independently and thus desynchronize from neighboring brain structures before seizure onset. To this end, we design the Desynchronization Index (DI), an algorithm that identifies the Epileptogenic Zone (EZ) as the subset of channels that disconnect from the SEEG network during the ictal transition. We evaluate the DI algorithm against Epileptogenicity Index (EI), one of the most common tools for EZ definition, on a clinical dataset of 20 patients, considering the channels that were thermocoagulated at the end of SEEG monitoring as the detection target. Our results show that DI overcomes EI in terms of area under the ROC curve (AUC =0.86 vs. AUC =0.83), while combining the two algorithms into a single framework leads to the best performance (AUC =0.88). Overall, the DI algorithm underscores anomalous connectivity patterns that are difficult to detect through visual inspection, improving the accuracy in the EZ definition and providing new insights into the dynamics of seizure generation.

Objective To assess the feasibility of estimating lateralization and localization of the epileptogenic zone (EZ) in temporal and extratemporal lobe epilepsy by combining Electric Source Imaging (ESI) with functional connectivity analysis of high-density EEG from the preictal to the ictal phase. MethodsAdults with drug-resistant focal epilepsy and at least one recorded seizure during 40- or 64 channels EEG monitoring were retrospectively included. Granger causality and hubness centrality were computed over the 10-s preictal interval and the first 5 s of the ictal period, with ictal onset defined as the first EEG change identified by experienced epileptologists. The reference standard for EZ localization was based on resective surgical outcome or stereo-EEG findings. Results Thirteen patients (7 females; median age 35 years) were included. Connectivity analyses showed higher concordance with clinical findings during the preictal phase than during the ictal phase for both lateralization (91% vs 46%) and localization (73% vs 27%). Performance was highest in temporal (7/7 lateralization; 6/7 localization) and frontal lobe epilepsy (2/2 for both), and lower in parieto-occipital epilepsy (1/2 and 0/2, respectively). In two cases with poor surgical outcome or no surgical indication, connectivity findings were discordant with clinical estimates. Conclusions: Connectivity analysis across the preictal to ictal transition provides relevant lateralizing and localizing information, particularly in temporal and frontal lobe epilepsy, and may reveal clinically meaningful discordance. Significance: Integrating high-density EEG, ESI, and functional connectivity during the phase preceding the first EEG change may support non-invasive presurgical evaluation.

Stereoelectroencephalography (SEEG) plays a central role in the presurgical evaluation of drug-resistant epilepsy, and accurate planning of avascular trajectories is essential because hemorrhage represents the procedure's most relevant complication. This retrospective single-centre study assessed the spatial correspondence between gadolinium-enhanced MRI (Gd-MRI) and digital subtraction angiography (DSA) across vascular territories relevant to SEEG trajectory planning. Nine adult patients (mean age 36.3 ± 11.4 years) underwent both MRI and DSA between 2021 and 2022 after ethics approval and informed consent. Thirteen arterial and venous segments were analyzed, yielding 130 Cartesian displacement measurements after multimodal registration. Displacements ≤0.5 mm were reported as <0.5 mm for interpretability, while continuous values were retained for descriptive and inferential analyses. Of the 130 measurements, 88 (67.7%) fell within this threshold, while 42 (32.3%) exceeded it. Significant displacements were found in both insular M2 branches (0.91 ± 0.69 mm, p = 0.001; 0.63 ± 0.66 mm, p = 0.007), in the pericallosal artery (0.63 ± 0.50 mm, p = 0.002), and in the distal vein of Trolard (1.39 ± 0.78 mm, p < 0.001), which also showed the maximum misalignment (2.4 mm). A caudo-cranial trend was identified, with larger discrepancies involving the more superficial cortical vessels, whose injury during electrode placement carries the highest risk of clinically significant hemorrhage. These findings indicate that MRI and DSA are broadly concordant but may differ in regions that are critical for trajectory safety. This observation is hypothesis-generating and may be relevant to SEEG trajectory planning, given the anatomical vulnerability of the cortical entry zone.

To evaluate the long-term efficacy of vagus nerve stimulation (VNS) in reducing tonic-clonic seizures (TCS), drop attacks, and seizure clusters in adults with drug-resistant epilepsy (DRE). This retrospective, single-center study included adults with DRE who received VNS and had ≥ 12 months of follow-up. Data were collected pre-implantation (T0), at 12 months (T1), and last follow-up (T2). Outcomes included reduction in total seizure frequency and severity, frequency of TCS and drop attacks, and frequency/duration of seizure clusters. Battery replacement and tolerability were also assessed. Eighty-seven subjects (51 males, median age 33 at T0) with a mean follow-up of 8 years were analyzed. At T2, 54

BACKGROUND AND OBJECTIVES:Microvascular decompression (MVD) is considered the gold standard surgical treatment for drug-resistant trigeminal neuralgia (TN), providing sustained pain relief. Teflon is the most widely adopted interposing material but may be associated with specific complications requiring revision surgery. This study aimed to compare clinical outcomes between Teflon and autologous muscle grafts as interposing materials in MVD, integrating evidence from an institutional series and current literature. METHODS:A retrospective analysis was performed on an institutional cohort of patients with primary TN who underwent MVD using autologous muscle grafts between May 2010 and January 2023. In parallel, a systematic review and meta-analysis were conducted following preferred reporting items for systematic reviews and meta-analyses guidelines, identifying studies that reported recurrence rates and complications after MVD with either Teflon or muscle as interposing materials. Only studies with explicit eligibility criteria and extractable outcome data were included for secondary analyses. Kaplan-Meier survival curves analyzed recurrence-free survival and 2-way analysis of variance compared preoperative and postoperative Barrow Neurological Institute score changes where patient-level or retrievable data were available. RESULTS:The analysis included 123 patients from our institutional cohort and 13 288 patients from 69 eligible studies, totaling 13 411 patients who underwent MVD between 1980 and 2023 (38 case series, 7 prospective cohorts, 1 case-control, and 23 retrospective cohorts). Among these, 11 711 received Teflon and 1577 received muscle grafts as interposing material. Muscle graft was associated with a significantly lower risk of pain recurrence compared with Teflon (odds ratio = 1.550, 95% CI: 1.209-1.987, P < .01), although recurrence occurred earlier with muscle (mean: 1.55 years) than with Teflon (mean: 2.62 years; hazard ratio = 3.786, 95% CI: 2.414-5.937, P < .01). No significant difference was observed between groups regarding postoperative pain outcomes (F = 0.22, P = .67). CONCLUSION:Autologous muscle graft is a valid alternative to Teflon as an interposing material in MVD for TN, offering similar immediate pain relief and a lower risk of recurrence, despite a shorter time to recurrence.

Seizures are a common and challenging symptom in brain tumors, affecting approximately 60% of patients. Tumor-related epilepsy (TRE) in glioma patients requires personalized and dynamic management in a multidisciplinary environment, especially for its intricate pathophysiology and unpredictable disease evolution. This investigation provides an updated overview about the pathophysiological mechanisms and treatment options of TRE associated with gliomas, based on expert contributions belonging to different areas. By combining the most recent discoveries and expert opinions, this study seeks to provide useful advice for TRE management in glioma patients. To improve patient outcomes and quality of life, prospective, standardized, multicentric studies should be promoted to optimize TRE patient care and refine therapeutic approaches.

OBJECTIVE:To study the current practice of epilepsy surgery in Italy and the relative impact of coronavirus disease 2019 (COVID-19) pandemic on it. METHODS:We launched a survey through the Italian National Virtual Epilepsy Institute, to identify centers with epilepsy surgery programs and collect data on the current preoperative and surgical practices. We reported changes in surgical volumes and complications and seizure outcomes between 2018 and 2022, that is, before and after the COVID-19 pandemic in Italy. RESULTS:A total of 21 of the 26 surveyed centers (80.7%) responded. Eleven centers (52.4%) reported having an established epilepsy surgery program, with most performing complex procedures, such as multilobar, disconnective, and hemispheric interventions. However, only a few carry out minimally invasive surgeries. Presurgical evaluation protocols vary across centers, but in keeping with international standards. Globally, 618 surgeries were performed in children and 621 in adults (total 1239) between 2018 and 2022. The most frequent type of surgery was unilobar extratemporal lobectomy for children (38.7%, p < 0.0001) and unilobar temporal lobectomy for adults (63.3%, p < 0.0001). Hemispheric surgeries were more frequent in children than in adults (11.5% vs 2.1%, p = 0.001), whereas interventions in unrevealing magnetic resonance (MRI) cases were more frequent in adults than in children (p = 0.030). At the onset of COVID-19outbreak in Italy (March 2020), we observed a significant decrease in the total number of operations compared to 2019, especially for hemispheric interventions (p = 0.027). Surgical volumes resumed in 2021, particularly for temporal lobe epilepsies and in adult cohorts. Surgical complications increased significantly in 2020 (Incidence Rate Ratio [IRR] = 13.13), whereas seizure outcome did not change significantly between 2018 and 2022. SIGNIFICANCE:Advanced pre- and postsurgical evaluation protocols are currently implemented across Italy, with a great variability between centers. Starting in 2021, epilepsy surgery volumes have regained their pre-pandemic levels, albeit with a slight loss of complexity, whereas seizure outcome has remained stable.

External Ventricular Drain (EVD) placement is a complex neurosurgical task that requires identifying a target point within the brain and accurately positioning a catheter at the appropriate angle. While Mixed Reality (MR) technologies have seen limited adoption in the operating room, they offer significant potential for developing training systems that enhance skill acquisition and retention in unaided conditions. A current gap in research concerns the effectiveness of multimodal guidance systems that incorporate both visual and audio-based MR cues. In this paper, we present an MR-based simulator for EVD placement training and evaluate the impact of three MR-guided training modalities: (1) a baseline condition using only 2D CT scans and a 2D catheter projection; (2) a visual guidance modality incorporating a 3D trajectory overlay; and (3) an embodied-audio guidance modality featuring a virtual agent delivering spoken instructions and feedback. Participants underwent a digital training phase using one of the three modalities, followed by an unaided EVD placement on a physical phantom with a real catheter to evaluate skill transfer and retention. Results indicate that both advanced MR modalities significantly improve procedural accuracy, execution speed and receive higher scores in usability and technology acceptance compared to the baseline. Notably, training with 3D visual trajectory guidance led to significantly higher unaided placement accuracy, indicating stronger skill retention. However, multimodal guidance demonstrated equivalent execution speed, while showing a trend toward lower overall cognitive load.

BACKGROUND:Glioblastoma isocitrate dehydrogenase IDH-wildtype (GBM IDHwt) in elderly patients presents challenges due to biological heterogeneity and under-representation in clinical trials. Despite rising incidence, prognostication remains inadequate, with treatment decisions based on subjective criteria. OBJECTIVE:To determine clinical, radiological, surgical, and molecular determinants of survival in elderly GBM IDHwt patients and explore prognostic utility of machine learning (ML) models using clinical and pretreatment data. METHODS:We analyzed 155 patients aged ≥70 years with confirmed GBM IDHwt who underwent neurosurgery at a tertiary care institution. We examined variables related to clinical presentation, imaging, surgery, and molecular markers using multivariate regression and Histogram Gradient Boosting Regression ML models. Two ML models were developed: one incorporating full dataset variables, and another focusing on preoperative features. RESULTS:Median overall survival (OS) was 11.3 months for patients undergoing resection and 3.7 months for biopsy. Independent predictors of prolonged OS included gross total resection (GTR), O6-methylguanine-DNA methyltransferase promoter methylation, nonacute symptom onset, and concomitant radiotherapy with temozolomide (RT + TMZ). ML models confirmed RT + TMZ and GTR as strongest predictors, while Karnofsky Performance Status showed negative importance. Body mass index (BMI) emerged as impactful; and the pretreatment model emphasized BMI and cognitive decline. CONCLUSIONS:This study confirmed prognostic relevance of GTR, O6-methylguanine-DNA methyltransferase methylation, and RT + TMZ combination. Baseline Karnofsky Performance Status and age did not demonstrate independent prognostic value, while BMI and cognitive decline were potential preoperative predictors. Our findings advocate a multidimensional, data-driven approach to preoperative risk stratification in elderly GBM patients, which may facilitate individualized treatment strategies.

Stereo-EEG is not just a diagnostic examination but a complex methodology, requiring an accurate synthesis of many data (anatomical, clinical, neurophysiological, cognitive, metabolic, and genetic). The implantation scheme is decided based on a hypothesis (or hypotheses) of epileptogenic zone localization. Subsequently, intracerebral electrical stimulation is used to define the extent of highly functional cortical regions and to reproduce the clinical symptoms and signs associated with seizures. Finally, stereo-EEG-guided thermocoagulation is used, with the dual purpose of stopping/reducing the seizures and determining the prognosis of possible resective (curative) surgery. The centers in Italy that use stereo-EEG derive from the French school of Bancaud and Talairach. Nevertheless, each one has interpreted, on the basis of its own specificity and talent, a new methodology and philosophy of implantation. The present work presents the state of the art of stereo-EEG use in Italy, with detail of the stereo-EEG program of the Munari center in Milano, as well as those of Florence, Bologna and Rome.

BACKGROUND:Tumors involving motor-eloquent brain regions pose a significant surgical challenge, as maximizing resection while preserving motor function requires a delicate balance. Neuromodulation-induced cortical prehabilitation (NICP) has emerged as a potential strategy to promote functional reorganization before surgery, potentially expanding the margins of safe resection. OBJECTIVE:This pilot study aimed to investigate whether accelerated, low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right primary motor cortex (M1) could induce functional and microstructural changes in the motor network. METHODS:Two healthy subjects underwent a seven-day intervention consisting of twice-daily sessions of inhibitory rTMS over the right M1 (14 sessions in total). Pre- and post-intervention imaging included resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Functional changes were assessed descriptively using seed-based and ROI-to-ROI connectivity analyses. Microstructural changes were evaluated through tract-specific comparisons of fractional anisotropy (FA). RESULTS:Both subjects exhibited increased interhemispheric functional connectivity and strengthening of compensatory motor pathways, including the supplementary motor areas and bilateral precentral and postcentral gyri. DTI revealed tract-specific changes in FA, with evidence of microstructural modulation in regions such as the SMA, corpus callosum, and corticospinal tract. The magnitude and spatial distribution of changes varied between individuals. CONCLUSION:These preliminary findings provide exploratory support for the hypothesis that inhibitory rTMS can induce functional and structural reorganization of the motor network. The combined use of rs-fMRI and DTI highlights the potential of NICP as a prehabilitation strategy in neurosurgical contexts. Further studies in clinical populations are warranted.

In this work, we propose a new computational framework to assist neurophysiologists in Stereoelectroencephalography (SEEG) analysis, with the final aim of improving the definition of the Epileptogenic Zone (EZ) in patients with drug-resistant epilepsy. We design a new algorithm, named Desynchronization Index (DI), that classifies as most epileptogenic those SEEG channels that show independent behavior during the seconds preceding the seizure propagation. We test the proposed DI algorithm against the Epileptogenic Index (EI) algorithm on a clinical dataset of 11 patients, considering the neurophysiological evaluation of the EZ as the clinical ground truth. Our results denote that DI overcomes EI in terms of area under the ROC curve (AUC=0.81 vs AUC=0.74) while combining the two algorithms as a unique tool leads to the best performance (AUC=0.87). The DI algorithm underscores connectivity dynamics that can hardly be identified with a pure visual analysis, increasing the accuracy of the EZ definition compared to traditional methods. This technique can lead to the definition of a new effective biomarker of the EZ, reducing the burden required by the SEEG review in the case of extensive implants and improving our understanding of the dynamics leading to the generation of seizures.

Abstract Objective To investigate the Italian experience on the surgical and radiosurgical treatment of drug‐resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011–2021 in six Italian epilepsy surgery centers, and to compare safety and efficacy profiles of the different techniques. Methods We collected pseudo‐anonymized patient's data with at least 12 months of follow‐up. Surgical outcome was defined according to Engel classification of seizure outcome. Univariate analysis was performed to assess the risk of post‐operative seizures, categorized in dichotomous variable as favorable and unfavorable; explanatory variables were considered. Mann–Whitney or Chi‐squared test were used to assess the presence of an association between variables (p < 0.05). Results Full presurgical and postoperative data about 42 patients from 6 epilepsy surgery centers were gathered. Engel class I was reached in the 65.8% and 66.6% of patients with gelastic and non‐gelastic seizures, respectively. Other than daily non‐gelastic seizures were associated with seizure freedom (p = 0.01), and the radiological type presented a trend toward significance (p = 0.12). Significance Endoscopic disconnection and laser interstitial thermal therapy are effective in the treatment of HH‐related epilepsy, with a tolerable safety profile. Both gelastic and non‐gelastic seizures can be treated, also in patients with a long history of seizures. Plain Language Summary This study collected data about 42 patients with HH‐related epilepsies. Endoscopic disconnection and laser therapy are both effective and safe in the treatment of hypothalamic hamartoma‐related epilepsies.

INTRODUCTION:Uterine cervical cancer, predominantly caused by HPV, is the fourth most common malignancy in women, rarely leading to Central Nervous System (CNS) metastases with a poor prognosis. This study analyzes 137 cases, focusing on the clinical progression, treatment efficacy, and survival outcomes, highlighting the need for a multi-disciplinary approach to extend patient survival in the face of inconsistent evidence and management practices. MATERIALS AND METHODS:This systematic review meticulously adhered to PRISMA guidelines, analysing all existing evidence on CNS metastasis from Uterine Cervical Cancer (UCC) through a comprehensive literature search up to August 2023. Articles were selected based on stringent criteria, including compliance with CARE and STROBE guidelines. The study employed rigorous statistical analyses, including the Shapiro-Wilk, T-Student, and ANOVA tests, alongside Kaplan-Meier curves, to evaluate variables like patient age, lesion location, and treatment efficacy. RESULTS:A review of 137 UCC patients revealed CNS metastases predominantly in the cerebral lobes, with headache and hemiparesis as common symptoms. The study found no significant survival difference across histopathological subtypes, but surgery, with or without WBRT, significantly improved outcomes. Age over 50 was associated with better survival, while the FIGO stage at diagnosis correlated with recurrence-free survival. Overall, surgical intervention on CNS lesions was the most significant factor for improved survival. CONCLUSION:This study reveals that CNS metastases from UCC are critical, with younger patients at worse prognosis. It suggests surgery plus WBRT or SRS as effective treatments and calls for targeted CNS screening and more research for better outcomes.

Objective Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) is an invasive procedure based on stereotactic lesioning of cortical targets in the brain using bipolar current through electrode contacts within the SEEG implant. To date, several RF-TC protocols have been described in the literature; however, a consensus has yet to be reached. This work aims to analyze the electrical parameters during RF-TC processes, offering a method to objectively describe and compare different SEEG-guided RF-TC protocols. Methods The study included patients who underwent RF-TC procedures at the IRCCS Istituto delle Scienze Neurologiche di Bologna from February 2022 to May 2023. During each procedure, modifications of the following parameters were measured: voltage, current, impedance, and electric power. An ad-hoc algorithm was implemented to detect abrupt impedance raises, which reflects the occurrence of the thermocoagulation. A two-sample t-test was used to compare parameter curves in RF-TC of different brain structures. Results A total of ninety-two RF-TC procedures were performed in eight patients according to a standardized protocol. During each procedure, impedance levels started at about 700Ω and rose up to 1300Ω, displaying an erratic pattern characterized by one or multiple raises. All measured parameters exhibited similar trends until the first peak, after which changes were influenced by the frequency of impedance raises. No significant correlations were observed between parameter modifications in distinct anatomical sites of RF-TC. Significance The systematic analysis of electrical parameters may represent a reliable tool to compare different RF-TC protocols, paving the way for identifying optimal configurations for SEEG-guided RF-TC procedures in the future.