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Objective: Epilepsy is commonly associated with low-grade gliomas (LGGs), impacting patients' well-being. While resection is the primary treatment, seizures can persist postoperatively in 27%-55% of cases. The authors aimed to evaluate an electrocorticography (ECoG) and navigated transcranial magnetic stimulation (nTMS)-tailored supratotal resection (ETT-SpTR) for LGG in controlling seizures, preserving neurological function, and enhancing treatment effectiveness., Methods: The authors retrospectively analyzed a prospectively enrolled cohort of patients with LGG presenting with epileptic seizures with ictal/interictal activity on electroencephalography (EEG) who underwent resective surgery. The authors performed preoperative nTMS to identify functional cortical areas. ECoG was used to guide the removal of the high-risk epilepsy cortical areas (HREAs). Patients were divided into two groups: group I, the control group, underwent gross-total resection alone, whereas group II patients underwent removal of HREAs identified by ECoG (ETT-SpTR). Resection avoided functionally eloquent areas as identified on nTMS, checked with cortical mapping. Postoperative seizure outcome was assessed using the Engel classification., Results: Fifteen patients who underwent LGG resection between January and July 2023 were included. Among 24 identified nTMS-positive points, none were included in the resection. Overall, 73.3% of patients (11/15) showed positive intraoperative ECoG, with better outcomes in group II (85.7% Engel class IA) than in group I (25% Engel class IA) at the follow-up (p = 0.02, OR 0.5 [95% CI 0.035-7.10], RR 0.19 [95% CI 0.03-1.2]). Seizure control was significantly better in group II, with no notable differences in postoperative transient neurological deficits between the two groups (p = 0.45). No permanent neurological deficits were observed during follow-up. Statistical analysis revealed significant differences between the two groups (p < 0.05)., Conclusions: This preliminary study affirms the predictive value of TMS for postoperative neurological status and safety in epileptic patients. Intraoperative ECoG effectively identified peritumoral HREAs. ETT-SpTR significantly improved epileptic outcomes, preserving functions without permanent neurological worsening. Additional resection targets the HREAs in the temporal, frontal, and parietal lobes.

Objective: The onco-functional balance represents the primary goal in neuro-oncology. The increasing use of navigated transcranial magnetic stimulation (nTMS) allows the noninvasive characterization of cortical functional anatomy, and its reliability for motor and language mapping has previously been validated. Calculation and arithmetic processing has not been studied with nTMS so far. In this study, the authors present their preliminary data concerning nTMS calculation., Methods: The authors designed a monocentric prospective study, adopting an internal protocol to use nTMS for preoperative planning, including arithmetic processing. When awake surgery was possible, according to the patients' conditions, nTMS points were used to guide direct cortical stimulation (DCS), i.e., the gold standard for cortical mapping. Navigated TMS-based tractography was used for surgical planning. Statistical analyses on the nTMS and DCS points were performed., Results: From February 2021 to October 2023, 61 procedures for nTMS calculation mapping were performed. The clinical evaluation, including pre- and postoperative evaluations (3 months after surgery), demonstrated a good clinical outcome with preservation of arithmetic function and recovery (92.8% of patients). Between the awake and asleep surgery groups, the postoperative clinical results were comparable at the 3-month follow-up, with > 90% of the patients achieving improved calculation function. The surgical strategy adopted was aimed at sparing nTMS positive points in asleep procedures, whereas nTMS and DCS positive points were not removed in awake procedures. Overall, 62% of the positive points for calculation functions were exposed by craniotomy and 85% were spared during surgery. None of the patients developed nTMS-related seizures. Diffusion tensor imaging fiber tracking based on nTMS positive points for calculation was used. The white matter fiber tracts involved in calculation functions were the arcuate fasciculus (56%) and frontal aslant tract (22%). When nTMS and DCS points were compared in awake surgery (n = 10 patients), a sensitivity of 31.71%, specificity of 85.76%, positive predictive value of 22.41%, negative predictive value of 90.64%, and accuracy of approximately 69% were achieved., Conclusions: Based on the authors' preliminary data, nTMS can be an advantageous tool to study cognitive functions, aimed at minimizing neurological impairment. The postoperative clinical outcome for patients who underwent operation with nTMS was very good. Considering these results, nTMS has proved to be a feasible method to map cognitive areas including those for calculation functions. Further analyses are needed to validate these data. Finally, other cognitive functions (e.g., visuospatial) may be explored with nTMS.

Objective: Intravenous sodium fluorescein (SF) is increasingly used during surgery of gliomas and brain metastases to improve tumor resection. Currently, SF is believed to permeate the brain regions where the blood-brain barrier (BBB) is damaged and to accumulate in the extracellular space but not in tumor or healthy cells, making it possible to demarcate tumor margins to guide resection. By evaluating the immune contexture of a number of freshly resected gliomas and brain metastases from patients undergoing SF-guided surgery, the authors recurrently observed fluorescence-positive cells. Therefore, the aim of this study was to determine if SF accumulates inside the cells of the tumor microenvironment (TME), and if so, in which type of cells, and whether incorporation can also be observed in the leukocytes of peripheral blood., Methods: Freshly resected tumor specimens were dissociated to single cells and analyzed by multiparametric flow cytometry. Peripheral blood leukocytes, macrophages, and a glioma cell line were treated with SF in vitro, and their cell uptake was assessed by multiparametric and imaging flow cytometry and by confocal microscopy., Results: The ex vivo and in vitro analyses revealed that SF accumulates intracellularly in leukocytes as well as in tumor cells, but with a high variability of incorporation in the different cell subsets analyzed. Myeloid cells showed the highest level of fluorescence. In vitro uptake experiments showed that SF accumulation increases over time. The imaging analyses confirmed the internalization of the compound inside the cells., Conclusions: SF is not just a marker of BBB damage, but its intracellular detection suggests that it selectively accumulates intracellularly. Future efforts should target the mechanisms of its differential uptake by the different TME cell types in depth.