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Background and ObjectivesWomen with a World Health Organization grade II glioma (GIIG) often question clinicians about the effects of pregnancy on their disease. Previous reports have indicated a higher risk of glioma progression during and after pregnancy. Here, the aim was to investigate postpregnancy outcomes and predictive factors affecting overall survival in female patients who underwent GIIG surgery.MethodsInclusion criteria were adult women who have been pregnant after a GIIG resection and with a stable oncologic status at the time of pregnancy (no ongoing oncologic treatment, no contrast enhancement, no debilitating clinical condition). Relevant cases were identified from a databank (1998–2021) of patients who underwent surgical resection for a histologically confirmed GIIG in our department.ResultsAmong 345 women with GIIG in their reproductive years (age p = 0.046 and p = 0.0026, respectively).DiscussionTumor residual volume and tumor speed growth are strong predictive factors conditioning postpregnancy long-term survival in patients with GIIG. Identifying patients at risk is critical to provide relevant counsel to women with GIIG with a desire for motherhood.

Reoperations in patients with recurrent low-grade gliomas (RLGG) were proposed to control tumor residual and delay the risk of malignant transformation over time.To investigate neurocognitive outcomes in patients with RLGG who underwent a second surgery with awake monitoring.In this retrospective study, patients who underwent a second awake surgery for RLGG were included. Patients had presurgical and 3-mo postsurgical neuropsychological assessments. Data were converted into Z-scores and combined by the cognitive domain. Number of patients with cognitive deficits (Z-score-1.65), variations of Z-scores, and extent of resection (EOR) were analyzed.Sixty-two patients were included (mean age: 41.2 ± 10.0 yr). None had permanent neurological deficits postoperatively. Eight patients (12.9%) had a cognitive deficit preoperatively. Four additional patients (6.5%) had a cognitive deficit 3 mo after reoperation. Among other patients, 13 (21.0%) had a mild decline without cognitive deficits while 29 (46.8%) had no change of their performances and 8 (12.9%) improved. Overall, 94.2% of the patients returned to work. There were no correlations between EOR and Z-scores. Total/subtotal resections were achieved in 91.9% of the patients (mean residual: 3.1 cm3). Fifty-eight patients (93.5%) were still alive after an overall follow-up of 8.3 yr.Reoperation with awake monitoring in patients with RLGG was compatible with an early recovery of neuropsychological abilities. Four patients (6.5%) presented a new cognitive deficit at 3 mo postoperatively. Total/subtotal resections were achieved in most patients. Based on these favorable outcomes, reoperation should be considered in a more systematic way.

Background The role of surgery for incidentally discovered diffuse incidental low-grade gliomas (iLGGs) is debatable and poorly documented in current literature. Objective The aim was to identify factors that influence survival for patients that underwent surgical resection of iLGGs in a large multicenter population. Methods Clinical, radiological, and surgical data were retrospectively analyzed in 267 patients operated for iLGG from 4 neurosurgical Centers. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and tumor recurrence (TR). Results The OS rate was 92.41%. The 5- and 10-year estimated OS rates were 98.09% and 93.2%, respectively. OS was significantly longer for patients with a lower preoperative tumor volume (P = .001) and higher extent of resection (EOR) (P = .037), regardless the WHO-defined molecular class (P = .2). In the final model, OS was influenced only by the preoperative tumor volume (P = .006), while TR by early surgery (P = .028). A negative association was found between preoperative tumor volumes and EOR (rs = −0.44, P < .001). The median preoperative tumor volume was 15 cm3. The median EOR was 95%. Total or supratotal resection of T2-FLAIR abnormality was achieved in 61.62% of cases. Second surgery was performed in 26.22%. The median time between surgeries was 5.5 years. Histological evolution to high-grade glioma was detected in 22.85% of cases (16/70). Permanent mild deficits were observed in 3.08% of cases. Conclusions This multicenter study confirms the results of previous studies investigating surgical management of iLGGs and thereby strengthens the evidence in favor of early surgery for these lesions.

International audience; Introduction: Thanks to early extensive surgical resection combined with medical oncological therapies, life expectancy dramatically increased in low-grade glioma (LGG), with an overall survival currently over the past fifteen years. Therefore, patients should be able to maintain valuable family and socio-professional activities.Areas covered: For many decades, cognitive and emotional aspects were neglected by surgical and medical neurooncologists. The goal of surgery was to avoid hemiplegia and/or aphasia, with no considerations regarding behavior. However, because LGG patients live longer, they must be cognitively and affectively able to make long-term projects. Preservation of higher-order functions should be considered systematically in LGG surgery by means of awake cognitive/emotional mapping and monitoring.Expert opinion: The aim is to incorporate recent advances in neurosciences, which proposed revisited models of cerebral processing relying on a meta-network perspective, into the pre-, intra- and post-operative procedure. In this connectomal approach, brain functions result from complex interactions within and between neural networks. This improved understanding of a constant instability of the neural system allows a better cognitive/emotional assessment before and after each treatment over years, in order to preserve personality and adaptive behavior for each LGG patient, based on his/her own definition of quality of life. It is time to create oncological neurosciences.

International audience; Background: Incidentally discovered suspected diffuse low-grade gliomas (LGGs) on brain imaging pose a challenge to neurosurgeons. Modern surgical series of LGGs favor early prophylactic surgery with a maximal extent of resection. However, some nonevolutive lesions may mimic LGGs on magnetic resonance imaging (MRI).Objective: To determine objective criteria to advocate surgical resection of an incidentally discovered suspected LGG based upon MRI findings.Methods: The prospective cohort of patients referred to our institution for an incidental finding suggestive of LGG was retrospectively reviewed. Stable lesions underwent systematic serial MRI follow-up, while evolutive lesions underwent prophylactic surgery under awake conditions. Initial clinico-radiological features were compared between stable and evolutive lesions in order to determine predictive criteria of further evolution.Results: Among 101 patients referred for surgical resection of incidentally discovered suspected LGG in our center, 19 patients (18.8%) had nonevolutive MRI lesions after a mean follow-up of 46.9 ± 34.9 mo. Insular topography (P = .003), higher mean volume at discovery (19.2 vs 5.2 cm3, P < .001), and adjacent sulcal effacement (P = .001) were associated with evolutive lesions. Histopathological diagnosis of LGG was confirmed in all surgical cases.Conclusion: Increasing volume is an effective predictor of LGG diagnosis in incidental MRI findings, as all patients who subsequently underwent surgery had confirmed histopathological diagnosis of diffuse glioma. Approximately 18.8% of incidental findings were stable over time. Insular topography, adjacent sulcal effacement, and volume greater than 4.5 cm3 were predictive of further radiological progression. These significant elements will help neurosurgeons to define personalized strategies in this complex setting of incidental discovery.

For a long time, return to work (RTW) has been neglected in patients harboring a diffuse low-grade glioma (LGG). However, a majority of LGG patients worked at time of diagnosis. Moreover, these patients now live longer given current treatment paradigms, especially thanks to early maximal surgery.We systematically searched available medical databases for studies that reported data on RTW in patients who underwent resection for LGG.A total of 30 studies were selected: 19 considered RTW (especially rate and timing) as an outcome and 11 used scales of health-related quality of life (HRQoL) which included work-related aspects. Series that considered RTW as a main endpoint were composed of 1014 patients, with postoperative RTW rates ranging from 31 to 97.1% (mean 73.1%). Timing to RTW ranged from 15 days to 22 months (mean 6.3 months). Factors related to an increased proportion of RTW were: younger age, better neurologic status, having a white-collar occupation, working pre-operatively, being the sole breadwinner, the use of awake surgery, and greater extent of resection. Female sex, older age, poor neurologic status, pre-operative history of work absences, slow lexical access speed, and postoperative seizures were negatively related to RTW. No studies that used HRQoL scales directly investigated RTW rate or timing.RTW was scarcely analyzed in LGG patients who underwent resection. However, because they are usually young, with no or only mild functional deficits and have a longer life expectancy, postoperative RTW should be assessed more systematically and accurately as a main outcome. As majority (61.5-100%) of LGG patients were working at time of surgery, the responsibility of neurosurgeons is to bring these patients back to their previous activities according to his/her wishes. RTW might also be included as a critical endpoint for future prospective studies and randomized control trials on LGGs.

PURPOSE Gliomas are life-threatening brain tumors, and the extent of surgical resection is one of the strongest influences on survival rate. However, the proper distinction of infiltrated tissue remains elusive. The aim of this study was to use multimodal analyses to demarcate peritumoral tissue (PT) from tumoral (TT) and healthy tissue (HT). METHODS A total of 40 patients with histologically confirmed glioma were recruited. We analyzed resting-state functional magnetic resonance imaging (rs-fMRI) using the voxel-based mean blood-oxygen-level-dependent (BOLD) signal and the corresponding structural MRI (s-MRI) alongside RNA sequencing, whole-exome sequencing, and histology results of biopsy samples obtained from PT, HT, and TT. RESULTS We demarcated a functionally defined PT area where the mean BOLD signal gradually decreased near the edge of the tumor and extended beyond the TT borders (as defined by s-MRI), which was confirmed on a case-by-case basis. Correspondingly, genetic analyses showed a gene expression pattern and mutational landscape of the PT that were distinct from that seen in HT and TT. The genetic characterization of PT relative to HT and TT converged with the MRI-defined PT zones. This was confirmed in three individual cases after additional histologic analysis. A wider PT was associated with a longer progression-free survival, which suggests PT might act as an intermediate area between TT and HT. CONCLUSION Combined multimodal imaging and genetic analyses can allow for an objective demarcation of the PT in glioma and a robust classification of the degree of infiltration of the PT. These findings could help improve both neurosurgical resection and radio-oncologic therapy.

International audience; Executive functions (EF) may be significantly impaired following low-grade glioma (LGG) surgery, especially in the event of white matter (WM) disruption. The aim of this study was to identify the connective tracts associated with EF impairments after LGG surgery, and to provide new insights into the WM network architecture of EF. EF measurements were collected in 270 patients at the chronic postoperative phase. This comprised cognitive flexibility, verbal inhibition and fluency abilities (phonological and categorical). The scores were z-corrected for age and educational level, and further submitted to a principal component analysis (PCA). Tracwise and disconnectome-behavior analyses were then performed using EF measures independently but also the extracted components from PCA. For the first analyses, 15 tracts of interest were selected. Two principal components were extracted from the behavioral data, interpreted as 'EF' and 'language' components. Robust, bonferroni-corrected correlations were established between the EF component and Layers II and III of the left superior longitudinal fasciculus, and between phonological fluency/inhibition and the same tracts. Less powerful but still significant correlations were also observed with the left frontal aslant and fronto-striatal tracts. These results were confirmed by disconnectome-behavior analyses. Our results indicate that surgically-related disruption of the fronto-parietal and the frontal cortico-subcortical connectivity, and of the frontal aslant tract, is related to long-lasting EF impairments. In addition to providing new insights into the WM pathways supporting EF, these findings are especially useful for both surgical planning and the predictive approach of neuropsychological disorders in the context of LGG surgery.

Background and Objective The goal of this study is to show using 5 illustrative cases that the transcortical route for resection of mediobasal temporal region (MBTR) lesions is safe and effective when performed with awake functional mapping and knowledge of the relevant subcortical anatomy. Although several have been proposed, there is a paucity of reports on transcorticosubcortical approaches to these lesions, particularly in patients with posterior-superior extension. We present a case series of 5 patients with left posterior MBTR gliomas and summarize the relevant subcortical anatomy knowledge of what is a prerequisite for safe resection. Methods Five patients with left posterior MBTR gliomas underwent awake resection with functional corticosubcortical electric mapping. Details of the approach are presented with a review of relevant anatomy. Results Gross total resection was achieved in 4 patients. One patient who had previously undergone radiation therapy had a subtotal resection. There were 4 cases of World Health Organization grade II glioma and 1 case of World Health Organization grade IV glioma. All patients underwent preoperative and postoperative neurologic and neuropsychological assessment and there were no new or worsening sensorimotor, visual, language, or cognitive deficits. Conclusions The transcorticosubcortical approach is a safe and effective approach to lesions of the posterior MBTR. The approach is safe and effective even in patients with superior extension, if the surgical approach is predicated on knowledge of individual functional anatomy. Awake resection with cortical and axonal mapping with well-selected paradigms is invaluable in maximizing extent of resection and ensuring patient safety.

Historically, the study of patients with spatial neglect has provided fundamental insights into the neural basis of spatial attention. However, lesion mapping studies have been unsuccessful in establishing the potential role of associative networks spreading on the dorsal-medial axis, mainly because they are uncommonly targeted by vascular injuries. Here we combine machine learning-based lesion-symptom mapping, disconnection analyses and the longitudinal behavioral data of 128 patients with well-delineated surgical resections. The analyses show that surgical resections in a location compatible with both the supplementary and the cingulate eye fields, and disrupting the dorsal-medial fiber network, are specifically associated with severely diminished performance on a visual search task (i.e., visuo-motor exploratory neglect) with intact performance on a task probing the perceptual component of neglect. This general finding provides causal evidence for a role of the frontal-medial network in the voluntary deployment of visuo-spatial attention., The authors show that damage to both the supplementary and the cingulate eye fields specifically causes visuo-motor exploratory neglect. This suggests that the medial eye field network contributes to the voluntary control of spatial attention

Background Awake surgery with intraoperative electrical mapping emerged as a gold-standard approach in newly diagnosed diffuse low-grade glioma (DLGG) to optimize the extent of resection (EOR) while sparing critical brain structures. However, no study has assessed to what extent cognitive recovery occurs following awake mapping-guided neurosurgery in a large, longitudinal, and homogeneous series of DLGG. Methods A longitudinal study on the cognitive status of 157 DLGG patients was performed. Neuropsychological assessments were done before and three months after awake mapping-based surgery. Z-scores and variations of Z-scores were computed to determine the number of patients with cognitive deficit(s) or decline. Clinical, surgical, and histopathological variables were studied to investigate factors contributing to neurocognitive outcomes. Results Eighty-seven patients (55.4%) had preoperative cognitive impairments. Statistical analysis between the preoperative (baseline) and postoperative assessments demonstrated a significant difference in three domains (Executive, Psychomotor Speed and Attention, Verbal Episodic Memory). Eighty-six percent of patients exhibited no postoperative cognitive decline, and among them, 10% exhibited cognitive improvement. The mean EOR was 92.3%±7.8%. The EOR, postoperative volume, and tumor lateralization had a significant association with cognitive decline. No patients demonstrated permanent postoperative neurologic deficits, but 5.8% did not resume their preoperative professional activities. The 5-year survival rate was 82.2%. Conclusions This is the largest series ever reported with systematic longitudinal neuropsychological assessment. 86% of patients demonstrated no cognitive decline despite large resections and only 5.8% did not return to work. This work supports the practice of awake surgery with cognitive mapping as safe and effective in DLGG patients.

International audience; Although clinical neurology was mainly erected on the dogma of localizationism, numerous reports have described functional recovery after lesions involving presumed non-compensable areas in an inflexible view of brain processing. Here, the purpose is to review new insights into the functional connectome and the mechanisms underpinning neural plasticity, gained from intraoperative direct electrostimulation mapping and real-time behavioral monitoring in awake patients, combined with perioperative neuropsychological and neuroimaging data. Such longitudinal anatomo-functional correlations resulted in the reappraisal of classical models of cognition, especially by highlighting the dynamic interplay within and between neural circuits, leading to the concept of meta-network (network of networks), as well as by emphasizing that subcortical connectivity is the main limitation of neuroplastic potential. Beyond their contribution to basic neurosciences, these findings might also be helpful for an optimization of care for brain-damaged patients, such as in resective oncological or epilepsy neurosurgery in structures traditionally deemed inoperable (e.g., in Broca's area) as well as for elaborating new programs of functional rehabilitation, eventually combined with transcranial brain stimulation, aiming to change the connectivity patterns in order to enhance cognitive competences following cerebral injury.

International audience; Awake surgery is difficult in glioma patients with preoperative aphasia. A 29-year-old right-handed bilingual (Spanish/English) patient experienced intractable seizures with severe language disorders due to a voluminous left fronto-temporo-insular tumor. We performed awake procedure with initial laborious language mapping, but with real-time improvement throughout the debulking, allowing preservation of the connectivity. A substantial residue was left. Postoperative cognitive rehabilitation resulted in a dramatic functional improvement, in both languages, permitting a complementary awake surgery, this time with a perfect collaboration of the patient. This multistep strategy enabled 92% of resection while enhancing quality of life with language recovery and epilepsy control.

International audience

Simple Summary Glioblastoma multiforme is the most aggressive form of brain tumor and is still incurable. These neoplasms are particularly difficult to treat efficiently because of their highly heterogeneous and resistant characteristics. Advances in genomics have highlighted the complex molecular landscape of these tumors and the need to further develop effective and targeted therapies for each patient. A specific population of cells with enriched stem cell properties within tumors, i.e., glioblastoma stem cells (GSC), drives this cellular heterogeneity and therapeutical resistance, and thus constitutes an attractive target for the design of innovative treatments. However, the signals driving the maintenance and resistance of these cells are still unclear. We provide new findings regarding the expression of two transcription factors in these cells and directly in glioblastoma patient samples. We show that these proteins downregulate GSC growth and ultimately participate in the progression of gliomas. The forthcoming results will contribute to a better understanding of gliomagenesis. Abstract Glioblastomas (GBM) are high-grade brain tumors, containing cells with distinct phenotypes and tumorigenic potentials, notably aggressive and treatment-resistant multipotent glioblastoma stem cells (GSC). The molecular mechanisms controlling GSC plasticity and growth have only partly been elucidated. Contact with endothelial cells and the Notch1 pathway control GSC proliferation and fate. We used three GSC cultures and glioma resections to examine the expression, regulation, and role of two transcription factors, SLUG (SNAI2) and TAL1 (SCL), involved in epithelial to mesenchymal transition (EMT), hematopoiesis, vascular identity, and treatment resistance in various cancers. In vitro, SLUG and a truncated isoform of TAL1 (TAL1-PP22) were strongly upregulated upon Notch1 activation in GSC, together with LMO2, a known cofactor of TAL1, which formed a complex with truncated TAL1. SLUG was also upregulated by TGF-β1 treatment and by co-culture with endothelial cells. In patient samples, the full-length isoform TAL1-PP42 was expressed in all glioma grades. In contrast, SLUG and truncated TAL1 were preferentially overexpressed in GBMs. SLUG and TAL1 are expressed in the tumor microenvironment by perivascular and endothelial cells, respectively, and to a minor extent, by a fraction of epidermal growth factor receptor (EGFR) -amplified GBM cells. Mechanistically, both SLUG and truncated TAL1 reduced GSC growth after their respective overexpression. Collectively, this study provides new evidence for the role of SLUG and TAL1 in regulating GSC plasticity and growth.

International audience; There is a lack of class I evidence concerning the impact of surgery in the treatment of diffuse low-grade glioma; the early maximal resection with preservation of eloquent brain areas has been accepted as the first therapeutic option. We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and protocol. Inclusion criteria: only case series with at least 100 patients containing supratentorial hemispheric diffuse low-grade glioma (according to any of the WHO classification used in papers published between 2000 to 2019), with pre- and postoperative MRI study were included in the qualitative and quantitative analyses. The extent of resection should be defined based on MRI at least in two categories and correlated with patients' outcomes (with univariate or multivariate analyses) using overall survival (OS) or malignant progression-free survival (MPFS). A total of 18 series with 4386 patients, published in 20 papers, were included in this systematic review. All the series that evaluates the relation between the extent of resection (EOR) and OS showed a statistically significant improvement of OS at univariate and/or multivariate analyzes with a greater EOR. Six studies showed a statistically significant improvement of MPFS with a greater EOR. We demonstrate that when a more rigorous analysis of EOR is performed, a benefit of a more aggressive resection on OS and MPFS is observed. Our review about EOR in different molecular groups of DLGG also suggests a benefit of maximum safe resection for all different subtypes, even though "radical surgery" may be associated with better OS and MPFS in tumors with a more aggressive signature.

The precuneus is a functionally heterogeneous area located on the medial face of the parietal cortex, wedged between the occipital cortex and the paracentral lobule. In view of its topological positioning, this associative cortex is well-placed to play an important role in multisensory integration, specific aspects of which participate to bodily awareness. However, this potential implication remains unestablished. We assessed bodily awareness longitudinally in 14 rare patients who underwent a surgery for a low-grade glioma mainly infiltrating the precuneus. To determine the brain locus the most frequently affected in patients showing bodily awareness disorders, we first contrasted the resection cavity distributions of patients with versus without bodily awareness disorders. We next applied ‘lesion network mapping’ to identify the networks functionally coupled with lesion locations causing bodily awareness disorder. Bodily awareness disorders were observed in half of patients after surgery, especially alien hand, macrosomatognosia and fading limb. Importantly, a dissociation was revealed between the antero-dorsal precuneus (bodily awareness disorders) and postero-dorsal precuneus (no bodily awareness disorders). Furthermore, bodily awareness disorder-related regions were specifically connected to a network of sensorimotor regions while others were connected with the default network. Altogether, the present findings indicate a critical role of the antero-dorsal precuneus in specific aspects of bodily awareness and in the maintenance of body schema.

International audience; Few studies addressed the evolution of brain activity before and after brain tumor resection. Using a fMRI naming task, we evaluated possible underlying plasticity phenomena. Thirty-two patients with left low-grade gliomas (16 women; age = 38.6 ± 8.31 years) and 19 healthy controls (7 women; age = 42.4 ± 12.1) were included in the study. An overt picture-naming task (DO80) was performed pre and post (3 months) surgery, as well as within the MRI in a covert manner. Exams included an injected 3DT1, a T2FLAIR, a DTI and a GE-EPI (task) sequence. Activations maps were compared with picture naming score, FA and MD maps were estimated, a VLSM analysis was performed on tumor masks, and disconnectome maps were reconstructed. Pre-surgery, the left parahippocampal gyrus (LPH) was inversely associated with task performance. Increased pre-post surgery left lingual gyrus (LLG) activity was found related to decreased picture naming performance. The evolution of left lingual gyrus (LLG) activity was negatively associated with the evolution of picture naming performance. In controls, the LPH was functionally connected to the right precentral gyrus (RPCG) and slightly to the LLG. This was not clearly retrieved in the patient group. Preoperatively, the LLG was connected to the left planum temporale and to the right lingual gyrus. The same result was found for controls. Postoperatively, the LLG was only connected to the RPCG. No association was found between evolution of FA/MD and evolution of picture naming performance. There is not one unique pattern of pre- and postoperative plasticity concerning picture-naming performance in DLGG patients.

International audience; The surgical resection of insular gliomas remains a challenge. Middle cerebral artery perforating arteries and deep functional pathways affect the extent of resection and the rate of post-operative morbidity. The authors performed a systematic review and meta-analysis of the literature examining early and permanent post-operative deficits in patients who underwent resection of insular gliomas using awake craniotomy with direct electrical stimulation (DES) versus surgery under general anesthesia. A systematic search of three databases was performed for studies published between 1990 and 2018. Random-effect meta-analysis was used to pool the rate of early and permanent post-operative deficits. Random-effect meta-regression was used to examine the association between the rate of post-operative deficit and the anesthesia protocol. We included eight studies evaluating 227 patients with insular glioma. The rate of permanent sequelae was lower after awake craniotomy with DES (3.5% vs 15.7%; P = .001), and early deficits were lower after surgery under general anesthesia (27.3% vs 47.7%; P = .04). Awake surgery was significantly more common among patients with tumor located within the dominant hemisphere (P < .001). No significant association arose between the rates of post-operative deficits and the use of intraoperative neuronavigation and the neurophysiological monitoring. Furthermore, neither extent of resection nor tumor histology influenced the onset of permanent sequelae. Awake craniotomy with DES is associated with a significantly lower rate of permanent neurological morbidity after an early increase of transient post-operative deficits. These data support the use of awake mapping in insular glioma resection.

Diffuse low-grade glioma (DLGG) is a brain neoplasm that migrates within the connectome and that becomes malignant if left untreated. Early and maximal safe surgical resection by means of awake mapping enables a significant improvement of survival and quality of life. Supramaximal functional-based resection seems to prevent DLGG malignant transformation. Neuroplasticity is helpful to remove DLGG in eloquent areas. When radical excision cannot be achieved due to invasion of critical neural networks, cerebral remapping over time may lead to a reoperation with an optimized resection. To discover and treat DLGG earlier, a screening in the general population should be considered.

Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. Methods An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. Results The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. Conclusions The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.

Brain awake surgery with cognitive monitoring for tumor removal has become a standard of treatment for functional purpose. Yet, little attention has been given to patients’ interpretation and awareness of their own responses to selected cognitive tasks during direct electrostimulation (DES). We aim to report disruptions of self-evaluative processing evoked by DES during awake surgery. We further investigate cortico-subcortical structures involved in self-assessment process and report the use of an intraoperative self-assessment tool, the self-confidence index (SCI). Seventy-two patients who had undergone awake brain tumor resections were selected. Inclusion criteria were the occurrence of a DES-induced disruption of an ongoing task followed by patient’s failure to remember or criticize these impairments, or a dissociation between patient’s responses to an ongoing task and patient’s SCI. Disruptions of self-evaluation were frequently associated with semantic disorders and critical sites were mostly found along the left/right ventral semantic streams. Disconnectome analyses generated from a tractography-based atlas confirmed the high probability of the inferior fronto-occipital fasciculus to be transitory ‘disconnected’. These findings suggest that white matters pathways belonging to the ventral semantic stream may be critically involved in human self-evaluative processing. Finally, the authors discuss the implementation of the SCI task during multimodal intraoperative monitoring.

OBJECTIVE Maximal safe resection is the first treatment in diffuse low-grade glioma (DLGG). Due to frequent tumor recurrence, a second surgery has already been reported, with favorable results. This study assesses the feasibility and functional and oncological outcomes of a third surgery in recurrent DLGG. METHODS Patients with DLGG who underwent a third functional-based resection using awake mapping were consecutively selected. They were classified into group 1 in cases of slow tumor regrowth or group 2 if a radiological enhancement occurred during follow-up. All data regarding clinicoradiological features, histomolecular results, oncological treatment, and survival were collected. RESULTS Thirty-one patients were included, with a median age of 32 years. There were 20 astrocytomas and 11 oligodendrogliomas in these patients. Twenty-one patients had medical oncological treatment before the third surgery, consisting of chemotherapy in 19 cases and radiotherapy in 8 cases. No neurological deficit persisted after the third resection except mild missing words in 1 patient, with 84.6% of the patients returning to work. The median follow-up duration was 13.1 ± 3.4 years since diagnosis, and 3.1 ± 2.9 years since the third surgery. The survival rates at 7 and 10 years were 100% and 89.7%, respectively, with an estimated median overall survival of 17.8 years since diagnosis. A comparison between the groups showed that the Karnofsky Performance Scale score dropped below 80 earlier in group 2 (14.3 vs 17.1 years, p = 0.01). Median residual tumor volume at the third surgery was smaller (2.8 vs 14.4 cm3, p = 0.003) with a greater extent of resection (89% vs 70%, p = 0.003) in group 1. CONCLUSIONS This is the first consecutive series showing evidence that, in select patients with progressive DLGG, a third functional-based surgery can be achieved using awake mapping with low neurological risk and a high rate of total resection, especially when reoperation is performed before malignant transformation.

CERVOXY CLIN; International audience; The sagittal stratum (SS) is a large sheet-like structure where major axonal fiber tracts cross, though its anatomical delineations are still debated. Here we investigated the poorly studied anatomo-functional organization of the right SS using direct electrical stimulation (DES) in patients undergoing wide-awake surgery for a cerebral glioma. Seventeen patients were included. There were six males, the mean age was 38 years old. One patient underwent surgery twice. Fourteen patients were right-handed and one was ambidextrous. Behavior tasks were used to monitor online the patients’ functions during DES, including visual and somesthetic processes, semantics, language, spatial and social cognition. Beyond the cortical DES, the mapping of axonal pathways evoked various functional responses. At the level of the core of the right SS, there were visual disturbances, visual hemi-agnosia, semantic paraphasia, left spatial neglect, confusion and comprehension difficulties, anomia, and mentalizing disturbances. At the level of the surrounding axonal pathways, there were left spatial neglect, anomia, vertigo, dysesthesia, and hearing disturbances. Our functionally defined three-dimensional map indicates that this complex region has a multilayered functional architecture, and supports an organization founded on two anatomical systems: a core system formed by the optic radiations, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus, and a peripheral one composed of surrounding or intersecting white matter tracts, including the superior longitudinal fasciculus/arcuate fasciculus, thalamocortical radiations, auditory radiations, and parieto-insular vestibular system. These results should prompt neurosurgeons to achieve awake DES mapping within the right SS because of the likelihood of causing multiple and irreversible structural disconnections.

OBJECTIVE Early surgery in presumed asymptomatic patients with incidental low-grade glioma (ILGG) has been suggested to improve maximal resection rates and overall survival. However, no study has reported on the impact of such preventive treatment on cognitive functioning. The aim of this study was to investigate neuropsychological outcomes in patients with ILGG who underwent preventive surgery. METHODS This was a retrospective analysis of a consecutive series of patients with ILGG who underwent awake surgery and who had presurgical and 3-month postsurgical neuropsychological assessments. Data were normalized into z-scores and regrouped by cognitive domains. Clinicoradiological data, histomolecular profile, and differences in z-scores (Δz-scores) were analyzed. RESULTS Forty-seven patients were included (mean age 39.2 ± 11.3 years). Twenty-eight patients (59.6%) underwent supratotal or total resections. All patients were still alive after a mean follow-up of 33.0 ± 30.8 months. Forty-one patients (87.2%) had stable (n = 34, 72.3%) or improved (Δz-score > 1; n = 7, 14.9%) neurocognitive outcomes after surgery. Six patients (12.8%) presented a slight impairment (Δz-score < −1) in at least one cognitive domain. The mean presurgical and postsurgical z-scores were comparable except in the psychomotor speed and attention domain. A significant correlation between presurgical executive functioning and tumor volume was reported, whereas the extent of resection and histomolecular profile did not impact neuropsychological outcomes. CONCLUSIONS Early surgical treatment in presumed asymptomatic patients with ILGG was associated with stable or improved neuropsychological outcomes in 87.2% of patients at 3 months, with only mild cognitive decline observed in 6 patients. In return, supratotal or total resections were achieved in most patients, and all patients were still alive at the end of the follow-up.

International audience; Background: Cognitive functioning is generally well preserved in patients with diffuse low-grade glioma (DLGG), even in the case of extended tumor and resection. To date, the question of personality changes in these patients has received little attention. Our aim was to investigate to what extent certain aspects of personality and behaviors could be affected by DLGG resection.Methods: We used self-reported personality questionnaires (NOEPI-R and TCI-R) and hetero-evaluation of executive behavioral changes in a large sample of 98 patients operated on for DLGG. To compare the patients' scores from the personality questionnaires, we recruited 47 healthy controls participants. To identify the putative neural networks associated with behavioral changes, a combination of voxel-wise and tract-wise lesion-symptom mapping was performed.Results: First, results revealed no difference between patients and controls for each subdimension of the NOEPI-R. Regarding the TCI-R, the character dimensions and three out of four temperament dimensions did not differ. Second, behavioral changes (Irritability, Hypoactivity, Anticipative disorders, and disinterest) were reported between 40 and 50% of cases. Third, some personality dimensions (as neuroticism) were strongly predictive of postoperative behavioral disorders (as hypoactivity). Lastly, specific behavioral changes were associated with selective damage to cortical (left inferior frontal gyrus, supplementary motor area, and right fusiform gyrus) and white matter (left inferior fronto-occipital and uncinate fasciculi, right cingulum) structures.Conclusion: This study demonstrates that extensive lesions caused by DLGGs and their surgical resection have no or minor impact on patients' personality. However, specific personality dimensions are strongly predictive of behavioral disorders suggesting that the observed surgically related behavioral changes are modulated by the personality profile. Finally, the lesion mapping analyses indicate that damage to differential cortical or white matter structures leads to distinct patterns of behavioral abnormalities.

International audience; Background: To report survival, spontaneous prognostic factors, and treatment efficacy in a French monocentric cohort of diffuse low-grade glioma (DLGG) patients over 35 years of follow-up.Methods: A monocentric retrospective study of 339 patients diagnosed with a new DLGG between 01/01/1982 and 01/01/2017 was created. Inclusion criteria were patient age ≥18 years at diagnosis and histological diagnosis of WHO grade II glioma (according to 1993, 2007, and 2016 WHO classifications). The survival parameters were estimated using the Kaplan-Meier method with a 95% confidence interval. Differences in survival were tested for statistical significance by the log-rank test. Factors were considered significant when p ≤ 0.1 and p ≤ 0.05 in the univariate and multivariate analyses, respectively.Results: A total of 339 patients were included with a median follow-up of 8.7 years. The Kaplan-Meier median overall survival was 15.7 years. At the time of radiological diagnosis, Karnofsky Performance Status score and initial tumor volume were significant independent prognostic factors. Oncological prognostic factors were the extent of resection for patients who underwent surgery and the timing of radiotherapy for those concerned. In this study, patients who had delayed radiotherapy (provided remaining low grade) did not have worse survival compared with patients who had early radiotherapy. The functional capabilities of the patients were preserved enough so that they could remain independent during at least three quarters of the follow-up.Conclusion: This large monocentric series spread over a long time clarifies the effects of different therapeutic strategies and their combination in the management of DLGG.

Brain-to-brain evoked potentials constitute a new methodology that could help to understand the network-level correlates of electrical stimulation applied for brain mapping during tumor resection. In this paper, we aimed to describe the characteristics of axono-cortical evoked potentials recorded from distinct, but in the same patient, behaviorally eloquent white matter sites.We report the intraoperative white matter mapping and axono-cortical evoked potentials recordings observed in a patient operated on under awake condition of a diffuse low-grade glioma in the left middle frontal gyrus. Out of the eight behaviorally eloquent sites identified with 60-Hz electrical stimulation, five were probed with single electrical pulses (delivered at 1 Hz), while recording evoked potentials on two electrodes, covering the inferior frontal gyrus and the precentral gyrus, respectively. Postoperative diffusion-weighted MRI was used to reconstruct the tractograms passing through each of the five stimulated sites.Each stimulated site generated an ACEP on at least one of the recorded electrode contacts. The whole pattern-i.e., the specific contacts with ACEPs and their waveform-was distinct for each of the five stimulated sites.We found that the patterns of ACEPs provided unique electrophysiological signatures for each of the five white matter functional sites. Our results could ultimately provide neurosurgeons with a new tool of intraoperative electrophysiologically based functional guidance.

Purpose: Awake surgery is an established technique for resection of low-grade gliomas, while its possible benefit for resection of high-grade gliomas (HGGs) needs further confirmations. This retrospective study aims to compare overall survival, extent of resection(EOR) and cognitive outcome in two groups of HGGs patients submitted to asleep or awake surgery. Methods: Thirty-three patients submitted to Gross Total Resection of contrast-enhancing area of HGGs were divided in two homogeneous groups: awake (AWg; N = 16) and asleep surgery (ASg; N = 17). All patients underwent toan extensive neuropsychological assessment before surgery (time_1), 1-week (time_2) and 4-months (time_3) after surgery. We performed analyses to assess differences in cognitive performances between groups, cognitive outcomes in each group and EOR. A comparison of overallsurvival(OS) between the twogroups was conducted. Results: Statisticalanalyses showed no differences between groups at time_2 and time_3 in each cognitive domain, excludingselective attentionthat resulted higher in the AWg before surgery. Regarding cognitive outcomes, we found a reversible worsening of memory and constructional praxis, and a significant recovery at time_3, similar for both groups. Assessment of time_3 in respect to time_1 never showed differences (all ps >.074). Moreover we found a significant lower level of tumor infiltration after surgery for AWg (p

PURPOSE OF REVIEW: Because diffuse low-grade glioma (DLGG) is constantly migrating in the brain until malignant transformation, the historic wait-and-watch attitude was replaced by an early therapeutic management. Moreover, advances in cognitive neurosciences allowed an improved understanding of neuroplasticity reactional to DLGG growth. Here, the aim is to reevaluate the role of surgery regarding both oncological and functional outcomes. RECENT FINDINGS: Recent data evidenced the significant benefit of maximal well tolerated resection on survival and quality of life (QoL). By removing a diffuse neoplastic disease up to eloquent neural networks identified by intraoperative awake mapping and cognitive monitoring, overall survival is about the double compared with biopsy, whereas the rate of severe persistent deficits was significantly reduced. Postoperative QoL may even be improved owing to functional rehabilitation and epilepsy control. SUMMARY: Early and functional mapping-guided surgery is currently the first treatment in DLGG. Surgical resection(s) should be integrated in a global personalized management that must be tailored to the brain connectome of each patient. To optimize the oncofunctional balance, the next step is a screening, to detect and to treat DLGG patients earlier, and to increase the rate of 'supramarginal excision' in the setting of a 'prophylactic connectomal neurooncological surgery'.

International audience; BACKGROUND:Therapeutic strategy concerning incidental low-grade glioma (ILGG) is still debated. Early "prophylactic" surgery has been proposed in asymptomatic patients with favorable neurological and oncological outcomes.OBJECTIVE:To assess postoperative ability to resume employment following awake surgery in asymptomatic ILGG patients. To assess extent of resection (EOR), timeline for adjuvant oncological treatment, and survival.METHODS:A total of 74 patients with ILGG who underwent awake surgery with intraoperative mapping were prospectively included, with a minimum follow-up of 12 mo. All clinicoradiological data were collected, and statistical correlations with return to work (RTW) were performed.RESULTS:A total of 66 patients (97.1%) among 68 patients with preoperative professional activities resumed their employment including 62 (91.2%) within 12 mo. Mean time before RTW was 6.8 mo (median: 6 mo, range: 1-36). Two patients experienced seizure-related legal issues impacting their RTW. Clinicoradiological features did not correlate with RTW apart from postoperative seizures (P = .02). Mean EOR was 95.7%. A total of 43 patients (58.1%) underwent supratotal/total resections. All patients recovered from transient deficits at 3 mo. No patients received consecutive adjuvant treatment. A total of 24 patients (32.4%) were reoperated, 24 patients received chemotherapy, and 7 patients (9.5%) received radiotherapy, on average 73.1 mo after surgery. Mean follow-up was 67 mo (range 12-240). Four patients (5.4%) died during the follow-up.CONCLUSION:We observed a high rate of RTW (97.1%, including 91.2% within 12 mo) after awake surgery in ILGG patients. Delayed resumption of work was due to employer not clearing them for RTW, personal choice, and, in rare occasions, related to seizures.

International audience; BACKGROUND:In diffuse glioma, a multistage approach with iterative tailored surgical resections can be considered.OBJECTIVE:To compare results of iterative intrasurgical brain mappings to investigate the potential and limitation of neuroplasticity at the individual stage, and to highlight to what extent it can influence the therapeutic strategy.METHODS:Glioma patients who underwent 2 consecutive awake surgeries with cortical and subcortical stimulation were classified into group 1 (n = 23) if cortical mappings exhibited high level of plasticity (displacement of ≥2 sites) or into group 2 (n = 19) with low level of plasticity.RESULTS:Clinical characteristics did not differ significantly between both groups. The borders of the tumors were mostly sharp in group 1 (82.6%) and rather indistinct in group 2 (84.2%), (P = .00001). Tumor remnants were more often cortical (± subcortical) in group 1 (39.1%) and more often purely subcortical in group 2 (68.4%; P = .009). In group 1, the time needed to recover independence was significantly shorter at reoperation (37.6 h vs 78.3 h after the first surgery, P = .00003) while this difference was not significant in group 2. The iterative extents of resection (EOR) remain comparable in group 1 (94% vs 92%, P = .40) but were significantly smaller in group 2 at reoperation (94% vs 88%, P = .05).CONCLUSION:More efficient plasticity mechanisms are facilitated by cortical tumors with sharp borders, are associated with an increase of EOR at reoperation and with earlier functional recovery. Tumoral invasion of the white matter tracts represents the main limitation of neuroplasticity: this connectomal constraint limits EOR during second surgery.

Objective Little is known about the functional role of the white matter connections running within and around the right inferior parietal lobule (IPL). We used direct electrostimulation during awake surgery to investigate this connectivity and to avoid permanent deficit after resection for right IPL gliomas. Methods We reviewed patients who underwent awake mapping for a glioma involving the right IPL. Resection was achieved up to functional corticosubcortical boundaries detected by electrostimulation. Results of the intraoperative mapping were confronted to preoperative and postoperative magnetic resonance imaging to perform anatomofunctional correlations. Results Fourteen consecutive patients were enrolled (9 men; mean age, 44 years). Cortically, the resection was limited anteriorly by the retrocentral somatosensory area (11 patients) or by the precentral motor cortex (3 patients). Subcortically, the thalamocortical pathways were identified anteriorly in all patients. Articulatory disturbances were elicited anteriorly and laterally (6 patients) corresponding to the superior longitudinal fasciculus part III. Deeper and superiorly, stimulating the superior longitudinal fasciculus part II or the arcuate fasciculus induced spatial disorders (6 patients). More laterally and posteriorly, disrupting the inferior fronto-occipital fasciculus induced nonverbal semantic disorders (7 patients). Six patients had visual deficits while the optic radiations were stimulated. A total or subtotal resection was achieved in all patients but one. There were no permanent impairments, except an expected left superior quadrantanopia in 4 patients. Conclusions This is the first surgical series focusing on right IPL gliomas. The complex functional connectivity detected within and around this region fully supports the use of intraoperative multimodal functional mapping for optimizing outcomes.

International audience; OBJECTIVE: To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. METHODS: We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. RESULTS: The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. SIGNIFICANCE: Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery.

Introduction Surgical resection in premotor areas can lead to supplementary motor area syndrome as well as a permanent deficit. However, recent findings suggest a putative role of the negative motor network in those dysfunctions. Our objective was to compare the functional results in two groups of adult patients who underwent the resection of a frontal glioma with and without resection of the negative motor networks. Material and methods Twelve patients (total of 13 surgeries) were selected for awake surgery for a frontal glioma. Negative motor responses were monitored during surgery at the cortical and subcortical levels. Sites eliciting negative motor responses were first identified then spared (n = 8) or removed (n = 5) upon oncological requirements. Results In the group with removal of the negative motor network (n = 5), all patients presented a complete supplementary motor area syndrome with akinesia and mutism. At 3 months, they all presented bimanual coordination dysfunction and fine movement disorders. In the group with preservation of the negative motor network (n = 8), all patients presented transient and slight disorders of speech or upper limb, they all recovered completely at 3 months. Discussion The negative motor network is a part of a modulatory motor network involved in the occurrence of the supplementary motor area syndrome and the permanent deficit after resection in premotor areas. Then, intraoperative functional cortico-subcortical mapping using direct electrostimulation under awake surgery seems mandatory to avoid deficit in bimanual coordination and fine movements during surgery in premotor areas.

Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.

International audience; This work was indeed motivated by the necessity to get a better picture of the anesthetic practice for awake craniotomy, which is considered now the gold standard for DLGG resection.

Highlights • Patients post DLGG surgery use attentional resources to compensate deficit. • Functional plasticity occurs at secondary regions at distance from the lesion. • Picture naming requires the integration of multiple resting-state networks. • The right hemisphere plays also an important role in language processing. • A whole brain approach with clinical input in case of lesion is the way forward., The dynamic connectome perspective states that brain functions arise from the functional integration of distributed and/or partly overlapping networks. Diffuse low-grade gliomas (DLGG) have a slow infiltrating character. Here we addressed whether and how anatomical disconnection following DLGG growth and resection might interfere with functional resting-state connectivity, specifically in relation to picture naming. Thirty-nine native French persons with a left DLGG were included. All underwent awake surgical resection of the tumor using direct brain electrostimulation to preserve critical eloquent regions. The anatomical disconnectivity risk following the DLGG volume and the resection, and the functional connectivity of resting-state fMRI images in relation to picture naming were evaluated prior to and three months after surgery. Resting-state connectivity patterns were compared with nineteen healthy controls. It was demonstrated that picture naming was strongly dependent on the semantic network that emerged from the integration and interaction of regions within multiple resting-state brain networks, in which their specific role could be explained in the light of the broader resting-state network they take part in. It emphasized the importance of a whole brain approach with specific clinical data input, during resting-state analysis in case of lesion. Adaptive plasticity was found in secondary regions, functionally connected to regions close to the tumor and/or cavity, marked by an increased connectivity of the right and left inferior parietal lobule with the left inferior temporal gyrus. In addition, an important role was identified for the superior parietal lobe, connected with the frontal operculum, suggesting functional compensation by means of attentional resources in order to name a picture via recruitment of the frontoparietal attention network.

ObjectiveDiffuse low-grade gliomas (DLGG) are defined by continuous growth and an almost unavoidable malignant transformation. Foci of malignant glioma can be found within DLGG samples obtained from surgical resections. As the medical management of patients is classically based on the higher tumor grade, an immediate adjuvant treatment is usually proposed. To determine whether postponing the medical treatment in selected patients is feasible, we conducted a single-center retrospective study.MethodsThis was a single-center retrospective analysis of a consecutive series of DLGG managed with this conservative strategy. Inclusion criteria were at least 1 focus of malignant tumor (grade III–IV, WHO 2016), no previous chemotherapy or radiotherapy, no less than a subtotal resection of the fluid-attenuated inversion recovery tumor volume, no intention of treating with immediate adjuvant therapy, and minimum 2 years of follow-up. The time interval to the following oncologic medical treatment was analyzed, as well as the functional and survival results.ResultsForty-four patients met the inclusion criteria (median age 36, median time interval from diagnosis 7 months). Most tumors (88%) were IDH-mutant and 1p19q intact (59%); 9 presented with grade IV foci. With a median follow-up of 6.7 years, 75% of patients received a subsequent medical treatment, after a median time of 3.4 years since surgery. At the time of analysis, 9 patients (20.0%) had died (5- and 7-year survival rates: 95% and 67.0%). Most surviving patients were still active professionally, without seizures.ConclusionsPostponing the medical treatment in DLGG with foci of malignant tumor following total or subtotal resection should be considered in selected patients.

International audience; Negative motor responses (NMRs) are defined as movement arrests induced by direct electrical stimulation of the brain. The NMRs manifest themselves after the disruption of a corticosubcortical network involved in motor control, referred to as the ‘negative motor network’. At present, the spatial topography of the negative motor areas (NMAs) is poorly known. Hence, the objectives of the present study were to establish the first probabilistic map of the NMAs of the upper limbs and face, identify potential subareas, and investigate the NMAs’ relationships with the primary motor cortex. A total of 117 patients with low grade glioma underwent awake surgery with direct electrostimulation. The Montreal Neurological Institute coordinates of sites eliciting NMRs (face and upper limbs) were registered. A probabilistic map was created, and subareas were identified in a cluster analysis. Each cluster was then plotted on the Glasser atlas and the 1200 Subjects Group Average Data from the Human Connectome Project, in order to study connectivity and compare the results with recent parcellation data. We elicited 386 NMRs (mean ± standard deviation current intensity: 2.26 ± 0.5 mA) distributed throughout the precentral gyrus in both hemispheres. In each hemisphere, we found two clusters for facial NMRs. For upper limb NMRs, we found two clusters in the right hemisphere; and three in the left. Each cluster overlapped with parcellations from the Glasser atlas. For the face, the NMAs were associated with areas 55b and 6v. For the upper limbs, the NMAs were linked to areas 6v, 6d, and 55b. Each NMA cluster showed a specific pattern of functionally connected areas, such as the inferior frontal gyrus, supplementary motor area, parietal areas, and posterior superior temporal gyrus. The white matter pathways projecting to these subareas involved the frontal aslant tract and the frontostriatal tract—both of which are well known to be associated with NMRs. This study constitutes the largest series to date of NMRs mapped to the lateral surface of both hemispheres. Rather than being randomly distributed, the NMAs appeared to be well structured and corresponded to parcellations identified by functional neuroimaging. Moreover, the white matter pathways known to drive NMRs are also connected to regions encompassing NMAs. Taken as a whole, our results suggest that NMAs belong to a large-scale modulatory motor network. Our new probabilistic map might constitute a valuable tool for use in further clinical and fundamental studies of motor control.

International audience

International audience; Early and maximal safe surgical resection optionally followed by adjuvant treatment is currently recommended in diffuse low-grade glioma (DLGG). Although this management delays malignant transformation (MT), recurrence will most often occur. Because this relapse usually arises locally, reoperation can be considered, with possible further chemotherapy/radiotherapy. However, due to a prolonged overall survival, a large spectrum of unusual recurrence patterns begins to emerge during long-term follow-up, beyond the classical slow and local tumor re-growth. We review various atypical patterns of DLGG relapse, we discuss their pathophysiological mechanisms and how to adapt the treatment(s). Those patterns include very diffuse, ipsi- or bilateral gliomatosis-like progression, multicentric recurrence with emergence of remote low-grade or high-grade glioma, leptomeningeal dissemination, acute (early or delayed) local MT or bulky relapse into the operating cavity. This landscape of recurrence patterns may allow physicians to elaborate new tailored therapeutic strategies and scientists to develop original hypotheses for basic research.

ObjectiveThe present study aimed to elucidate the neural correlates of the deafferentation cognitive model of verbal perseveration (VP) by analyzing the connectomics of the sites where electric stimulation elicited VP during awake left glioma surgery.MethodsWe retrospectively reviewed the anatomic sites that generated VP when electrically stimulated in a series of 21 patients operated on while awake for a left glioma. Each stimulation point was manually located on the postoperative MRI and then registered to the Montreal Neurological Institute template. Connectomics of these sites were further analyzed with Tractotron and disconnectome maps.ResultsVP stimulation sites were located within the white matter surrounding the posterosuperior head of the caudate nucleus, as well as within the white matter of the external capsule and the superolateral wall of the temporal horn of the ventricle. Furthermore, Tractotron and disconnectome maps revealed the connectome of these stimulation sites: the inferior fronto-occipital fasciculus, frontostriatal tract, and anterior thalamic radiations.ConclusionOn the basis of these results and other data, we propose the following anatomic implementation of the deafferentation cognitive model: the lexico-semantic system, comprising different areas linked together through direct cortico-cortical connections, sends information to the striatum; the striato-thalamic system acts as a tunable filter of this lexico-semantic input; and the thalamus projects back to the lexico-semantic system, amplifying the targeted response and inhibiting its competitors.

International audience; Diffuse low-grade gliomas (DLGG) are brain tumors of young adults. They affect the quality of life of the inflicted patients and, if untreated, they evolve into higher grade tumors where the patient's life is at risk. Therapeutic management of DLGGs includes chemotherapy, and tumor diameter is particularly important for the follow-up of DLGG evolution. In fact, the main clinical basis for deciding whether to continue chemotherapy is tumor diameter growth rate. In order to reliably assist the doctors in selecting the most appropriate time to stop treatment, we propose a novel clinical decision support system. Based on two mathematical models, one linear and one exponential, we are able to predict the evolution of tumor diameter under Temozolomide chemotherapy as a first treatment and thus offer a prognosis on when to end it. We present the results of an implementation of these models on a database of 42 patients from Nancy and Montpellier University Hospitals. In this database, 38 patients followed the linear model and four patients followed the exponential model. From a training data set of a minimal size of five, we are able to predict the next tumor diameter with high accuracy. Thanks to the corresponding prediction interval, it is possible to check if the new observation corresponds to the predicted diameter. If the observed diameter is within the prediction interval, the clinician is notified that the trend is within a normal range. Otherwise, the practitioner is alerted of a significant change in tumor diameter.