Marco Rossi

Molecularly defined oligodendrogliomas are rare tumors whose prognosis has improved over time because of more effective treatments. However, several aspects of management are still controversial, and studies with long-term follow-up are needed. The main aim of this study was to analyze and compare the natural history and management of patients with OG2 and OG3 and define which factors have the strongest effect on outcome. We reviewed an institutional retrospective cohort (1996-2024) of patients with molecularly defined OG2 and OG3 according to World Health Organization 2021. We retrieved information on baseline clinical features, MRI characteristics (i.e., presence and pattern of contrast enhancement), extent of resection, initial treatment modalities after surgery, and management at progression. The relationships of these factors with progression-free survival (PFS) and overall survival (OS) were studied with univariate and multivariate analyses. Among 240 patients with IDH-mutant 1p/19q-codeleted oligodendrogliomas, grade 2 tumors were 149 (62.1%) and grade 3 were 91 (37.9%) with a median age of 42 and 44 years, respectively. Male/female ratio was 73/76 (49%/51%). Among patients with OG3, 70/91 (77%) exhibited a diffuse grade 3 histology (OG3d), whereas 21/91 (23%) had focal grade 3 areas only (OG3f). Overall, patients with OG2 and OG3 had similar median PFS (57.6 months, CI 53.2-61.9, vs 59.8 months, CI 41.9-77.6, p = 0.25), and prolonged median OS (274 months vs not reached). However, patients with OG3 exhibited a shorter time to radiotherapy at progression and their survival probability declined more rapidly within the first decade after surgery. The extent of resection was the only factor that significantly affected both PFS and OS in a multivariate analysis (for PFS, hazard ratio [HR] 0.90, 0.62-0.99, p = 0.026; for OS, HR 0.29, 0.13-0.79, p = 0.016), whereas tumor grade did not. Temozolomide alone as initial treatment of high-risk OG2 and OG3 with large residual tumor after surgery was not detrimental for survival. The same was true for observation in a small group of young patients with nonenhancing OG3 who have undergone complete resection and with only focal areas of malignancy (OG3f). This large retrospective cohort of IDH-mutant 1p/19q-codeleted oligodendrogliomas receiving standard treatments could serve as a benchmark for comparison with new IDH inhibitors in future clinical studies.

Orienting visuospatial attention towards relevant stimuli is vital for effective environmental interactions. Current attentional control models rely on functional neuroimaging, which is correlational, and lesion studies in stroke patients, affected by localization bias. Studying patients undergoing awake neurosurgery for brain tumour resection offers a unique chance to overcome these limitations and possibly enhance current neurofunctional models. We combined Lesion-Symptom-Mapping (LSM) in 163 brain tumour patients and Direct Electrical Stimulation (DES) in 47 patients during awake neurosurgery to unveil the network causally associated with visuospatial exploratory/selective attention. LSM and DES convergently identified a right dorsomedial frontal region linked to visuospatial neglect, potentially functioning as a pre-oculomotor hub for contralateral attentional deployment. Moreover, stimulation of right ventrolateral white matter was associated with visuospatial errors in both hemifields. Finally, we provided a tool that effectively detects and preserves frontal connectivity for visuospatial exploratory/selective attention in neurosurgical settings.

Since the pivotal studies of neurophysiologists in the early 20th century, research on brain functions in non-human primates has provided valuable insights into the neural mechanisms subserving neurological function. By using data acquired on non-human primates as a reference, important progress in knowledge of the human brain and its functions has been achieved. The translational impact allowed by this scientific effort must be recognized in the implementation of the current surgical techniques particularly in support of the neurosurgical approach to brain tumors. In the surgical treatment of brain tumors, the ability to maximally extend the resection allows an improvement in overall survival, progression-free survival, and quality of life of patients. The main goal, and, at the same time, the main challenge, of oncological neurological surgery is to avoid permanent neurological deficit while reaching maximal resection, particularly when the tumor infiltrates the neural network subserving motor functions. Brain mapping techniques were developed using neurophysiological probes to identify the areas and tracts subserving sensorimotor function, ensuring their preservation during the resection. During the last 20 years, starting from the classical “Penfield” technique, brain mapping has been progressively implemented. Among the major advancements was the introduction of high-frequency direct electrical stimulation. Its refinement, along with the complementary use of low-frequency stimulation, allowed a further refinement of stimulation protocols. In this narrative review, we propose an analysis of the process through which the knowledge acquired through experiments on non-human primates influenced and changed the current approach to neurosurgical procedures. We then describe the main brain mapping techniques used in the resection of tumors located within sensorimotor circuits. We also detail how these techniques allowed the acquisition of new data on the properties of areas and tracts underlying sensorimotor control, in turn fostering the design of new tools to navigate within cortical and subcortical areas, that were before deemed to be “sacred and untouchable.”

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield’s motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the ‘plis de passage’ of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space to seed functional MRI connectivity across 9000 resting-state functional MRI scans, which demonstrated the connectivity of these sites with the somato-cognitive action network. Intraoperative recordings during direct electrical central sulcus stimulation further identified inter-effector regions corresponding to plis de passage locations. This work provides a critical step towards an improved understanding of the somato-cognitive action network in both structural and functional terms. Furthermore, our work has the potential to guide the development of refined motor cortex stimulation techniques for treating brain disorders and operative resective techniques for complex surgery of the motor cortex.

Background: Accurate prognosis of glioblastoma is crucial for better-informed treatment decisions, potentially leading to improved disease management. We investigated whether clinical variables, tumor size, and location, can serve as prognostic factors. Methods: A retrospective, multicenter study enrolled 1318 adult patients with histopathologically confirmed glioblastoma undergoing first-time surgery, with survival censored for 188 patients. Pre-operative brain MRIs were used to compute tumor size and derive advanced radiological features describing tumor location, later refined by expert-based opinion. Post-operative MRIs were used to measure the enhancing residual tumor volume. The prognostic quality of all variables, measurements, and features was assessed as inputs of three survival regression models (CoxPH, Random Survival Forests, DeepSurv) to predict overall survival, under five timepoints of patient treatment: onset presentation, assessment by multidisciplinary board, intervention planning, post-intervention evaluation, and chemoradiotherapy planning. Model evaluation was performed with the C-index, Brier Score over Time, and Integrated Brier Score. Results: Multivariable Cox analysis identified most clinical variables and tumor size as strong predictors of patient survival, with varying hazard ratios across timepoints. DeepSurv was consistently the top performing model under all possible inputs and at all timepoints, yielding mean test C-index scores ranging from 61.71% to 70.29%, and mean Integrated Brier Scores ranging from 8.57% to 7.63%. Conclusion: Clinical variables, tumor size, and location carry prognostic value for the overall survival of patients with glioblastoma. The best predictive performance was observed under a Deep Survival model using all variables at the stage of chemoradiotherapy planning.

Background: Supratotal-resection (SpTR) is a promising surgical strategy in lower-grade gliomas (LGGs). SpTR assessment, feasibility and distinctive features, as well as clinical benefit at first and second surgery and on overall survival must be better characterized. The critical percentage of resection exceeding FLAIR margins to obtain clinical benefit and its impact on long-term functional performance are also undefined. Methods: Included were 704 patients with primary and 439 with recurrent LGGs seen between 2010 and 2019, who underwent resection with brain-mapping technique (BMT) aimed at achieving a SpTR without any “a-priori” selection. Extent-of-resection, evaluated on 3D-FLAIR-MR and categorized according to residual tumor and cavity volume, was associated with progression-free survival (PFS) and malignant(M)PFS at first and second surgery and overall survival by univariate, multivariate, and propensity-score analysis. Functional performance was assessed by neuropsychological (NPS) evaluation. Results: SpTR evaluation requires volumetric assessment enhanced by brain deformation measurement in parietal tumors; SpTR rate accounts on average for 50.2% and 35.7% at first and second surgery is higher in grade-2, frontal, and temporal locations (at expenses of total resection [TR]). Compared to TR, SpTR reduces and postpones first and second recurrences in all molecular subtypes and grades, delays MPFS without difference in rate, and prolongs overall survival (OS). A degree of SpTR > 120% associates with the lowest recurrence risk. SpTR associates with the best NPS longitudinal course. Conclusions: This study supports the feasibility of SpTR in LGGs, its benefit at first and second surgery regardless of molecular subtypes, and on OS, significantly reducing recurrence when SpTR > 120%; SpTR also associates with the best patients’ functional outcome.

Background and ObjectivesPatients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) ...

Multiple factors can affect the accuracy of neuronavigation, that is a relevant issue, particularly for frameless stereotactic procedures, where precision and optimal image-guidance is crucial for the surgical performance, workflow, and outcome. To investigate the impact of AIRO Mobile Computer Tomography in frameless stereotactic approaches. A retrospective study on 12 patients was performed. All the procedures were deployed using a frameless stereotactic technique, both for the collection of biopsy pathological specimens for diagnosis and insertion of drainage in the treatment of intracranial cystic lesions. Twelve patients (eight males, four females) underwent the frameless stereotactic procedure. Mean age at surgery was 55 (±5 SE). The mean volume of the lesion was 23.85 cm³ (±3.13). Six diagnostic biopsies and six cyst drainages were performed. The mean trajectory length was 75.9 ± 11.8 mm. Three posterior fossa lesions (27%) were approached through a retro-sigmoidal burr-hole. A craniotomy for draining a haematoma was performed after detection with AIRO-CT. No permanent neurological dysfunction, in-hospital or 30-day mortality were recorded. The AIRO-CT resulted feasible with a potential utility for stereotactic procedures. We showed how it could grant the efficacy of the stereotactic procedures reducing some technical and physical sources of inaccuracy, also enhancing safety and allowing prompt detection and management of intraoperative complications.

OBJECTIVE: Resection of glioma in the nondominant hemisphere involving the motor areas and pathways requires the use of brain-mapping techniques to spare essential sites subserving motor control. No clear indications are available for performing motor mapping under either awake or asleep conditions or for the best mapping paradigm (e.g., resting or active, high-frequency [HF] or low-frequency [LF] stimulation) that provides the best oncological and functional outcomes when tailored to the clinical context. This work aimed to identify clinical and imaging factors that influence surgical strategy (asleep motor mapping vs awake motor mapping) and that are associated with the best functional and oncological outcomes and to design a “motor mapping score” for guiding tumor resection in this area. METHODS: The authors evaluated a retrospective series of patients with nondominant-hemisphere glioma—located or infiltrating within 2 cm anteriorly or posteriorly to the central sulcus and affecting the primary motor cortex, its fibers, and/or the praxis network—who underwent operations with asleep (HF monopolar probe) or awake (LF and HF probes) motor mapping. Clinical and imaging variables were used to design a motor mapping score. A prospective series of patients was used to validate this motor mapping score. RESULTS: One hundred thirty-five patients were retrospectively analyzed: 69 underwent operations with asleep (HF stimulation) motor mapping, and 66 underwent awake (LF and HF stimulation and praxis task evaluation) motor mapping. Previous motor (strength) deficit, previous treatment (surgery/radiotherapy), tumor volume > 30 cm ³ , and tumor involvement of the praxis network (on MRI) were identified and used to design the mapping score. Motor deficit, previous treatment, and location within or close to the central sulcus favor use of asleep motor mapping; large tumor volume and involvement of the praxis network favor use of awake motor mapping. The motor mapping score was validated in a prospective series of 52 patients—35 underwent operations with awake motor mapping and 17 with asleep motor mapping on the basis of the score indications—who had a low rate of postoperative motor-praxis deficit (3%) and a high extent of resection (median 97%; complete resection in > 70% of patients). CONCLUSIONS: Extensive resection of tumor involving the eloquent areas for motor control is feasible, and when an appropriate mapping strategy is applied, the incidence of postoperative motor-praxis deficit is low. Asleep (HF stimulation) motor mapping is preferable for lesions close to or involving the central sulcus and/or in patients with preoperative strength deficit and/or history of previous treatment. When a patient has no motor deficit or previous treatment and has a lesion (> 30 cm ³ ) involving the praxis network, awake mapping is preferable.