Brain tumor surgery guided by navigated transcranial magnetic stimulation mapping for arithmetic calculation.

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.

Neurocognitive Assessment of Mathematics-Related Capacities in Neurosurgical Patients.

A precise neuropsychological assessment is of the utmost importance for neurosurgical patients undergoing the surgical excision of cerebral lesions. The assessment of mathematical abilities is usually limited to arithmetical operations while other fundamental visuo-spatial aspects closely linked to mathematics proficiency, such as the perception of numerical quantities and geometrical reasoning, are completely neglected. We evaluated these abilities with two objective and reproducible psychophysical tests, measuring numerosity perception and non-symbolic geometry, respectively. We tested sixteen neuro-oncological patients before the operation and six after the operation with classical neuropsychological tests and with two psychophysical tests. The scores of the classical neuropsychological tests were very heterogeneous, possibly due to the distinct location and histology of the tumors that might have spared (or not) brain areas subserving these abilities or allowed for plastic reorganization. Performance in the two non-symbolic tests reflected, on average, the presumed functional role of the lesioned areas, with participants with parietal and frontal lesions performing worse on these tests than patients with occipital and temporal lesions. Single-case analyses not only revealed some interesting exceptions to the group-level results (e.g., patients with parietal lesions performing well in the numerosity test), but also indicated that performance in the two tests was independent of non-verbal reasoning and visuo-spatial working memory. Our results highlight the importance of assessing non-symbolic numerical and geometrical abilities to complement typical neuropsychological batteries. However, they also suggest an avoidance of reliance on an excessively rigid localizationist approach when evaluating the neuropsychological profile of oncological patients.

Sodium fluorescein uptake by the tumor microenvironment in human gliomas and brain metastases.

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.

Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase.

BACKGROUND: Drug-resistant epilepsy is a common condition in patients with brain neoplasms. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathogenetic mechanisms, the increase in glutamate concentration has been proposed. Glutamate transporters, glutamine synthetase and pyruvate carboxylase are involved in maintaining the physiological concentration of glutamate in the intersynaptic spaces. In our previous research on angiocentric gliomas, we demonstrated that all tumors lacked the expression of the main glutamate transporter EAAT2, while the expression of glutamine synthetase and pyruvate carboxylase was mostly preserved. METHODS: In the present study, we evaluated the immunohistochemical expression of EAAT2, glutamine synthetase and pyruvate carboxylase in a heterogeneous series of 25 long-term epilepsy-associated tumors (10 dysembryoplastic neuroepithelial tumors, 7 gangliogliomas, 3 subependymal giant cell astrocytomas, 3 rosette forming glioneuronal tumors, 1 diffuse astrocytoma MYB- or MYBL1-altered and 1 angiocentric glioma). In order to evaluate the incidence of variants in the SLC1A2 gene, encoding EAAT2, in a large number of central nervous system tumors we also queried the PedcBioPortal. RESULTS: EAAT2 protein expression was lost in 9 tumors (36 %: 3 dysembryoplastic neuroepithelial tumors, 1 ganglioglioma, 3 subependymal giant cell astrocytomas, 1 diffuse astrocytoma MYB- or MYBL1-altered and 1 angiocentric glioma). Glutamine synthetase protein expression was completely lost in 2 tumors (8 %; 1 ganglioglioma and 1 diffuse astrocytoma MYB- or MYBL1-altered). All tumors of our series but rosette forming glioneuronal tumors (in which neurocytic cells were negative) were diffusely positive for pyruvate carboxylase. Consultation of the PedcBioPortal revealed that of 2307 pediatric brain tumors of different histotype and grade, 20 (< 1%) had variants in the SLC1A2 gene. Among the SLC1A2-mutated tumors, there were no angiocentric gliomas or other LEATs CONCLUSIONS: In conclusion, unlike angiocentric gliomas where the EAAT2 loss is typical and constant, the current study shows the loss of EAAT2 expression only in a fraction of the LEATs. In these cases, we may hypothesize some possible epileptogenic role of the EAAT2 loss. The retained expression of pyruvate carboxylase may contribute to determining a pathological glutamate excess unopposed by glutamine synthetase that resulted expressed to a variable extent in the majority of the tumors. Furthermore, we can assume that the EAAT2 loss in brain tumors in general and in LEATs in particular is more conceivably epigenetic.

Heads-Up Micronavigation Reliability of Preoperative Transcranial Magnetic Stimulation Maps for the Motor Function: Comparison With Direct Cortical Stimulation.

BACKGROUND AND OBJECTIVES: We aimed to assess the reliability of preoperative navigated transcranial magnetic stimulation (nTMS) maps for motor function as visualized intraoperatively with augmented reality heads-up display and to assess its accuracy via direct point-by-point comparison with the gold-standard direct cortical stimulation (DCS). METHODS: From January 2022 to January 2023, candidates for surgical removal of lesions involving the motor pathways underwent preoperative nTMS assessment to obtain cortical maps of motor function. Intraoperatively and before tumor removal, nTMS maps were superimposed on the cortical surface, and DCS was performed on positive points with increasing current intensity until obtaining a positive response at 16 mA. The outcome of each stimulation was recorded to obtain discrimination metrics. RESULTS: Twelve patients were enrolled (5 females [42%] vs 7 males [58%], mean age 62.9 ± 12.8 years), for a total of 304 investigated points. Agreement between nTMS and DCS was moderate (κ = 0.43, P < .005), with 0.66 (0.53-0.78) sensitivity, 0.87 (0.82-0.90) specificity, 0.50 (0.39-0.62) positive predictive values, 0.93 (0.89-0.95) negative predictive value, and 0.83 (0.79-0.87) accuracy. A loss of accuracy was observed with higher DCS current intensities. CONCLUSION: We performed a point-by-point validation of preoperative nTMS maps for motor function using augmented reality visualization. The high negative predictive value and low positive predictive values highlight nTMS reliability to visualize safe cortical zones but not to identify critical functional areas, confirming previous findings of nTMS maps for the language function and suggesting the need for combined use of nTMS maps and DCS for optimal maximal safe resection.

The immune cell landscape of glioblastoma patients highlights a myeloid-enriched and immune suppressed microenvironment compared to metastatic brain tumors.

Introduction: Brain metastases (BrM), which commonly arise in patients with melanoma, breast cancer and lung cancer, are associated with a poor clinical prognosis. In this context, the tumor microenvironment (TME) plays an important role since it either promotes or inhibits tumor progression. Our previous studies have characterized the immunosuppressive microenvironment of glioblastoma (GBM). The aim of this study is to compare the immune profiles of BrM and GBM in order to identify potential differences that may be exploited in their differential treatment. Methods: Tumor and/or blood samples were taken from 20 BrM patients and 19 GBM patients. Multi-parametric flow cytometry was used to evaluate myeloid and lymphoid cells, as well as the expression of immune checkpoints in the TME and blood. In selected cases, the immunosuppressive ability of sorted myeloid cells was tested, and the ex vivo proliferation of myeloid, lymphoid and tumor cell populations was analyzed. Results: High frequencies of myeloid cells dominated both the BrM and GBM landscapes, but a higher presence of tumor-associated macrophages was observed in GBM, while BrM were characterized by a significant presence of tumor-infiltrating lymphocytes. Exhaustion markers were highly expressed in all T cells from both primary and metastatic brain tumors. Ex vivo analysis of the cell cycle of a single sample of a BrM and of a GBM revealed subsets of proliferating tumor cells and blood-derived macrophages, but quiescent resident microglial cells and few proliferating lymphocytes. Macrophages sorted from a single lung BrM exhibited a strong immunosuppressive activity, as previously shown for primary GBM. Finally, a significant expansion of some myeloid cell subsets was observed in the blood of both GBM and BrM patients. Discussion: Our results define the main characteristics of the immune profile of BrM and GBM, which are distinguished by different levels of immunosuppressive myeloid cells and lymphocytes devoid of effector function. Understanding the role of the different cells in establishing the metastatic setting is critical for improving the therapeutic efficacy of new targeted immunotherapy strategies.

Is the Patient State Index a reliable parameter as guide to anaesthesiology in cranial neurosurgery? A first intraoperative study and a literature review.

BACKGROUND: Patient State Index (PSI) and Suppression Ratio (SR) are two indices calculated by quantitative analysis of EEG used to estimate the depth of anaesthesia but their validation in neurosurgery must be done. Our aim was to investigate the congruity PSI and SR with raw EEG monitoring in neurosurgery. METHODS: We included 34 patients undergoing elective cranial neurosurgery. Each patient was monitored by a SedLine device (PSI and SR) and by raw EEG. To appraise the agreement between PSI, SR and EEG Suppr%, Bland-Altman analysis was used. We also correlated the PSI and SR recorded at different times during surgery to the degree of suppression of the raw EEG data by Spearman's rank correlation coefficient. For a comparison with previous data we made an international literature review according to PRISMA protocol. RESULTS: At all recording times, we found that there is a strong agreement between PSI and raw EEG. We also found a significant correlation for both PSI and SR with the EEG suppression percentage (p < 0.05), but with a broad dispersion of the individual values within the confidence interval. CONCLUSION: The Masimo SedLine processed EEG monitoring system can be used as a guide in the anaesthetic management of patients during elective cranial neurosurgery, but the anaesthesiologist must be aware that previous correlations between PSI and SR with the suppression percentage may not always be valid in all individual patients. The use of an extended visual raw EEG evaluated by an expert electroencephalographer might help to provide better guidance.

Intraoperative Mapping of the Sensory Root of the Trigeminal Nerve in Patients with Pontocerebellar Angle Pathology.

OBJECTIVE: The aim of the present study was to determine the position of the 3 sensory branches of the trigeminal nerve in the preganglionic tract using intraoperative neurophysiological mapping. METHODS: We included consecutive adult patients who underwent neurosurgical treatment of cerebellopontine angle lesions. The trigeminal nerve was antidromically stimulated at 3 sites along its circumference with different stimulus intensities at a distance of ≤1 cm from the brainstem. The sensory nerve action potentials (SNAPs) were recorded from each main trigeminal branch (V1 [ophthalmic branch], V2 [maxillary branch], and V3 [mandibular branch]). RESULTS: We analyzed 13 patients. The stimulation points at which we obtained the greatest number of congruous and exclusive SNAPs (SNAPs only on the stimulated branch) was the stimulation point for V3 (20.7%). The stimulation intensity at which we obtained the highest number of congruent and exclusive SNAPs with the stimulated branch was 0.5 mA. CONCLUSIONS: Using our recording conditions, trigeminal stimulation is a reliable technique for mapping the V3 and V1 branches using an intensity not exceeding 0.5. However, reliable identification of the fibers of V2 is more difficult. Stimulation of the trigeminal nerve can be a reliable technique to identify the V3 and V1 branches if rhizotomy of these branches is necessary.

Microscope neuronavigation-guided microsurgical fenestration of quadrigeminal cistern arachnoid cysts: how I do it.

BACKGROUND: Management options for treatment of quadrigeminal arachnoid cysts (QAC) include microsurgical/endoscopic fenestration or shunt. There is an open debate about which method is the best. Microsurgical fenestration is well suited for treatment of QAC with predominant infratentorial component and without hydrocephalus making endoscopic procedures more challenging. METHOD: We describe the microsurgical technique and related anatomy to fenestrate infratentorial QAC through supracerebellar infratentorial approach. We also discuss our experiences with this approach, some of the drawbacks and nuances. CONCLUSION: Navigation-guided microsurgical fenestration of infratentorial QAC is the authors' surgical approach of choice for treating these rare challenging lesions when not associated with hydrocephalus.

Feasibility of Intraoperative Visual Evoked Potential Monitoring by Cortical Strip Electrodes in Patients During Brain Surgery: A Preliminary Study.

OBJECTIVE: The role of visual evoked potentials (VEPs) monitoring during neurosurgical procedure in patient remains unclear. The purpose of our study was to determine the feasibility of intraoperative VEP recording using a strip cortical electrode during surgical resection of intracranial lesions. METHODS: In this prospective, monocentric, observational study, we enrolled consecutive patients undergoing neurosurgical procedure for intracranial lesions. After dural opening, a cortical strip was positioned on the lateral occipital surface. Flash VEPs were continuously recorded using both subdermal corkscrew electrodes and strip electrodes. An electroretinogram was also recorded to guarantee delivery of adequate flash stimuli to the retina. RESULTS: We included 10 patients affected by different intracranial lesions. Flash VEPs were recorded using subdermal corkscrew electrodes in all patients except 1 in whom they were never identified during the recording. Flash VEPs were recorded using strip electrodes in all patients and showed a polyphasic morphology with a significantly larger amplitude compared with that of flash VEPs measured using subdermal corkscrew electrodes. No patient reported worsened postoperative vision and a >50% decrease in the VEPs amplitude was never registered. CONCLUSIONS: We have reported for the first time in the literature that VEP monitoring during a neurosurgical procedure is feasible via a cortical strip located on the occipital surface. The technique demonstrated greater stability and a larger amplitude compared with recordings with scalp electrodes, facilitating identification of any changes. Studies with more patients are needed to assess the clinical reliability of the technique.

Surgery of optic-chiasmatic tumors assisted by sodium fluorescein yellow fluorescence and visual evoked potentials monitoring.

BACKGROUND: Tumours of the anterior visual pathways are challenging to operate because of the crucial balance between extent of resection and sight preservation. Sodium Fluoresceine (SF) has already been reported in maximizing brain tumour resection but not when the optic-chiasmatic region is involved. The role of Visual Evoked Potentials (VEPs) in optic-chiasmatic tumours is still debated. The simultaneous use of both technique in this setting has not been reported so far. The aim of our work is to analyse the intraoperative combination of the use of SF and VEPs in the anterior visual pathway tumour surgery. METHODS: Clinical and Intra-operative data from six surgical procedures on four patients affected by optic-chiasmatic tumours with preoperative visual deficits were retrospectively analysed. RESULTS: In 5 procedures VEPs remained intraoperatively stable and no postoperative worsening of visual function was reported. In 1 case an intraoperative VEPs deterioration was predictive of a postoperative visual worsening. In all cases, tumour was fluorescent, and SF was intraoperatively helpful in guiding resection. The pattern of fluorescence was different according to the lesion histology. CONCLUSIONS: Based on our preliminary experience, the simultaneous combination of SF and VEPs in surgery of the optic pathway tumours seems helpful to maximize tumour resection and predict postoperative functional outcome. Since we presented a small series, larger studies are needed to confirm our data.

The immunosuppression pathway of tumor-associated macrophages is controlled by heme oxygenase-1 in glioblastoma patients.

The immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) is mainly driven by tumor-associated macrophages (TAMs). We explored whether their sustained iron metabolism and immunosuppressive activity were correlated, and whether blocking the central enzyme of the heme catabolism pathway, heme oxygenase-1 (HO-1), could reverse their tolerogenic activity. To this end, we investigated iron metabolism in bone marrow-derived macrophages (BMDMs) isolated from GBM specimens and in in vitro-derived macrophages (Mφ) from healthy donor (HD) blood monocytes. We found that HO-1 inhibition abrogated the immunosuppressive activity of both BMDMs and Mφ, and that immunosuppression requires both cell-to-cell contact and soluble factors, as HO-1 inhibition abolished IL-10 release, and significantly reduced STAT3 activation as well as PD-L1 expression. Interestingly, not only did HO-1 inhibition downregulate IDO1 and ARG-2 gene expression, but also reduced IDO1 enzymatic activity. Moreover, T cell activation status affected PD-L1 expression and IDO1 activity, which were upregulated in the presence of activated, but not resting, T cells. Our results highlight the crucial role of HO-1 in the immunosuppressive activity of macrophages in the GBM TME and demonstrate the feasibility of reprogramming them as an alternative therapeutic strategy for restoring immune surveillance.

Functional outcomes, extent of resection, and bright/vague fluorescence interface in resection of glioblastomas involving the motor pathways assisted by 5-ALA.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence can maximize perirolandic glioblastoma (GBM) resection with low rates of postoperative sequelae. Our purpose was to present the outcomes of our experience and compare them with other literature reports to investigate the potential influence of different intraoperative monitoring strategies and to evaluate the role of intraoperative data on neurological and radiological outcomes in our series. METHODS: We retrospectively analyzed our prospectively collected database of GBM involving the motor pathways. Each patient underwent tumor exeresis with intraoperative 5-ALA fluorescence visualization. Our monitoring strategy was based on direct stimulation (DS), combined with cortical or transcranial MEPs. The radiological outcome was evaluated with CRET vs. residual tumor, and the neurological outcome as improved, unchanged, or worsened. We also performed a literature review to compare our results with state-of-the-art on the subject. RESULTS: Sixty-five patients were included. CRET was 63.1%, permanent postoperative impairment was 1.5%, and DS's lowest motor threshold was 5 mA. In the literature, CRET was 25-73%, permanent postoperative impairment 3-16%, and DS lowest motor threshold was 1-3 mA. Our monitoring strategy identified a motor pathway in 60% of cases in faint fluorescent tissue, and its location in bright/faint fluorescence was predictive of CRET (p < 0.001). A preoperative motor deficit was associated with a worse clinical outcome (p < 0.001). Resection of bright fluorescent tissue was stopped in 26%, and fluorescence type of residual tumor was associated with higher CRET grades (p < 0.001). CONCLUSIONS: Based on the data presented and the current literature, distinct monitoring strategies can achieve different onco-functional outcomes in 5-ALA-guided resection of a glioblastoma (GBM) motor pathway. Intraoperatively, functional and fluorescence data close to a bright/vague interface could be helpful to predict onco-functional outcomes.

Surgical Resolution of Trigeminal Neuralgia Complicating Vestibular Schwannoma Removal.

This work illustrates the case of surgical treatment of trigeminal neuralgia (TN), as a tardive complication after vestibular schwannoma (VS) removal (Koos III, Figure 1), in a female patient. After VS surgery, the postoperative computed tomography scan did not show any significant complication, although a thin blood clot was present in the surgical bed (Figure 2). However, 3 months later, our patient developed a TN involving the territories V2-V3. Medical therapies were ineffective. Several magnetic resonance imaging scans confirmed a left dislocation of the brainstem (Figures 3 and 4), probably due to the previous clot retraction. The anatomic-functional preservation of the left Tn was documented using the laser-evoked potentials. Fifteen months after surgery, our patient underwent a second operation aimed at exploring the Tn territory, with the use of the intraoperative monitoring and mapping the fifth and seventh cranial nerves. A neurovascular conflict, caused by scar tissue involving the superior cerebellar artery, a small vein, and the Tn, was detected and surgically solved (Figure 5). Postoperative analgesic treatment was progressively reduced and suspended. The case is illustrated and explained in the Video 1. The paucity of cases reported in the literature lead us to think that TN as complication of VS removal is underestimated because it may be responsive to medical treatment. Laser-evoked potentials may be useful to study the integrity of the Tn, ensuring that no anatomic damage has been done during surgery. On the basis of our experience, surgery can be an effective treatment option when TN is not responsive to medical therapy and the anatomic-functional integrity of the Tn has been preserved.

An Overview of Intracranial Ependymomas in Adults.

Ependymomas are rare primary central nervous system tumors. They can form anywhere along the neuraxis, but in adults, these tumors predominantly occur in the spine and less frequently intracranially. Ependymal tumors represent a heterogenous group of gliomas, and the WHO 2016 classification is based essentially on a grading system, with ependymomas classified as grade I, II (classic), or III (anaplastic). In adults, surgery is the primary initial treatment, while radiotherapy is employed as an adjuvant treatment in some cases of grade II and in all cases of anaplastic ependymoma; chemotherapy is reserved for recurrent cases. In recent years, important and interesting advances in the molecular characterization of ependymomas have been made, allowing for the identification of nine molecular subgroups of ependymal tumors and moving toward subgroup-specific patients with improved risk stratification for treatment-decisions and future prospective trials. New targeted agents or immunotherapies for ependymoma patients are being explored for recurrent disease. This review summarizes recent molecular advances in the diagnosis and treatment of intracranial ependymomas including surgery, radiation therapy and systemic therapies.

Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy.

The cell composition of the glioblastoma (GBM) microenvironment depends on the recruitment of myeloid cells from the blood, promoting tumor progression by inducing immunosuppression. This phenomenon hampers immunotherapies and investigating its complexity may help to tailor new treatments. Peripheral blood and tissue specimens from the central and marginal tumor areas were collected from 44 primary and 19 recurrent GBM patients. Myeloid and lymphoid cell subsets and the levels of immunosuppressive markers were defined by multiparametric flow cytometry. Multiplexed immunohistochemistry was used to confirm the differences in the immune infiltrate and to analyze the cell spatial distribution. Relapsing GBM showed an increased presence of blood-derived macrophages in both tumor areas and a higher frequency of infiltrating lymphocytes, with a high level of exhaustion markers. The expansion of some myeloid-derived suppressor cell (MDSC) subsets in the blood was found in both primary and recurrent GBM patients. A significant inverse correlation between infiltrating T cells and an MDSC subset was also found. In patients with recurrent GBM after standard first-line therapy, the immune-hostile tumor microenvironment and the levels of some MDSC subsets in the blood persisted. Analysis of the immune landscape in GBM relapses aids in the definition of more appropriate stratification and treatment.

Two dissociable semantic mechanisms predict naming errors and their responsive brain sites in awake surgery. DO80 revisited.

How do we choose words, and what affects the selection of a specific term? Naming tests such as the DO80 are frequently used to assess language function during brain mapping in awake surgery. The present study aimed to explore whether specific semantic errors become more probable under the stimulation of specific brain areas. Moreover, it meant to determine whether specific semantic characteristics of the items may evoke specific types of error. A corpus-based qualitative semantic analysis of the DO80 items, and the emitted naming errors to those items during direct cortical electrostimulation (DCE) revealed that the number of hyperonyms (i.e. 'vehicle' for car') of an item predicted the emission of a synonym ('automobile' for 'car'). This association occurred mainly in frontal tumor patients, which was corroborated by behavior to lesion analyses. In contrast, the emission of co-hyponyms was associated with tumors located in temporal areas. These two behavior-lesion associations thus dissociated, and were also dependent on item semantic characteristics. Co-hyponym errors might generate from the disruption in a temporal semantic-to-lexical process, and the production of synonyms could be the result of an impairment in a frontal lexical-selection mechanism. A hypothesis on the lexical selection mechanisms exerted by the inferior frontal gyrus is proposed. Crucially, the present data suggest the need for more restrictive naming tasks, with items conditioned by tumor location.