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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.

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.

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; 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; BackgroundBrain-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.MethodsWe 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.ResultsEach 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.ConclusionsWe 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.

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Background In jargonaphasia, speech is fluent but meaningless. While neuropsychological evaluation may distinguish a neologistic component characterised by non-word production and a semantic component where pronounced words are real but speech is senseless, how this relates to the underlying white matter anatomy is debated. Objective To identify white matter pathways causally involved in jargonaphasia. Methods We retrospectively screened the intraoperative brain mapping data of 571 awake oncological resections using direct cortico-subcortical electrostimulation. Jargonaphasia was induced in 17 patients (19 sites) during a naming task. Stimulation sites were normalized to the Montreal Neurological Institute template space and used to generate individual disconnectome maps. Non-parametric voxelwise one and two sample t-tests were performed to identify the underlying white matter anatomy. Results Jargonaphasia was induced only during stimulation of the left hemisphere. No cortical stimulation generated jargonaphasia. Subcortical sites causally associated with jargonaphasia clustered in 3 regions: in the temporal lobe (middle to inferior temporal gyri; n = 12), in the parietal lobe (supramarginal gyrus; n = 3) and in the temporal stem (n = 4). Disconnectome analysis indicated the inferior-fronto-occipital fasciculus (IFOF) was damaged in both neologistic and semantic jargonaphasia, while the involvement of the arcuate fasciculus was specific to neologistic jargonaphasia. Conclusion For the first time, we show that jargonaphasia is induced by white matter stimulation, hinting at disconnection. As IFOF disconnection unites both variants, these may represent a continuum of disorders distinguished by semantic impairment. Conversely, damage to the arcuate fasciculus in addition to the IFOF is specific to neologistic jargonaphasia, thus suggesting a dual-disconnection syndrome.

International audience; Neurooncology is a young specialty which initially dealt mostly with glioblastoma patients with a short overall survival (OS). Yet, recently the scope gradually expanded by taking care of lower-grade glioma (LGG) patients with a longer OS (1). Historically, these patients were managed with a “wait and see attitude” claiming “benignity” despite 6 to 7 years OS (2, 3). Therefore, quality of care was mainly based on physician’s subjectivity and not on the natural history, leading to beliefs that early surgery was not adapted due to “normal neurological examination”.Twenty years later, it is now admitted that (i) beyond seizures, LGG patients suffer from cognitive and behavioral deficits at diagnosis even in incidental cases (4) (ii) this tumor will inescapably transform in higher grades, explaining the use of “lower-grade glioma” (mixing II/III) expression (5) (iii) early surgery is a main therapeutic factor (significant correlation between extent of resection and OS) (6, 7) (iv) early radiotherapy, at least given alone, is not associated with decreased mortality (6, 8). These changes resulted in a longer life expectancy now over 15 to 16 years (9–11).Moreover, neurooncologists had to pay more attention to quality of life (QoL) for patients who must learn to live with a chronic neoplastic disease.On the other hand, because LGG will systematically recur, further adapted treatments have to be administrated (12). However, heterogeneity of progression patterns (13) makes the prediction of timescales of proliferation, migration, and degeneration at the individual level impossible.To provide more reliable prognostic factors, advances in molecular biology led to a new classification designed for more appropriate decisions (14). Surprisingly, although genetics was initially a tool to better dissociate types of LGG with distinct prognosis, molecular biology rapidly became the first parameter in guidelines (15). Although useful, by taking mostly account of genetics criteria and extrapolating a correlation to specific OS based upon statistical analysis, there is a risk to neglect tumor-host interactions, patient’s wishes, and long-term QoL.Here, the main purpose is to redefine what “best quality of care” means by considering both tumor characteristics and patient’s personal criteria. The ultimate goal is to give the choice of therapeutic orientation at each step thanks to honest although complex and time-consuming information highlighting oncofunctional balance and various strategies individually adapted over time in parallel with changes in tumor behavior and patient’s expectations.

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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.

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.

Purpose The practical management of cavernous angioma located within eloquent brain area before, during and after surgical resection is poorly documented. We assessed the practical pre-operative, intra-operative, and post-operative management of cavernous angioma located within eloquent brain area. Method An online survey composed of 61 items was sent to 26 centers to establish a multicenter international retrospective cohort of adult patients who underwent a surgical resection as the first-line treatment of a supratentorial cavernous angioma located within or close to eloquent brain area. Results 272 patients from 19 centers (mean 13.6 ± 16.7 per center) from eight countries were included. The pre-operative management varied significantly between centers and countries regarding the pre-operative functional assessment, the pre-operative epileptological assessment, the first given antiepileptic drug, and the time to surgery. The intra-operative environment varied significantly between centers and countries regarding the use of imaging systems, the use of functional mapping with direct electrostimulations, the extent of resection of the hemosiderin rim, the realization of a post-operative functional assessment, and the time to post-operative functional assessment. The present survey found a post-operative improvement, as compared to pre-operative evaluations, of the functional status, the ability to work, and the seizure control. Conclusions We observed a variety of practice between centers and countries regarding the management of cavernous angioma located within eloquent regions. Multicentric prospective studies are required to solve relevant questions regarding the management of cavernous angioma-related seizures, the timing of surgery, and the optimal extent of hemosiderin rim 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 Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.

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.

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'.

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.

International audience; Direct electrical stimulation (DES) is used to perform functional brain mapping during awake surgery and in epileptic patients. DES may be coupled with the measurement of Evoked Potentials (EP) to study the conductive and integrative properties of activated neural ensembles and probe the spatiotemporal dynamics of short- and long-range networks. However, its electrophysiological effects remain by far unknown. We recorded ECoG signals on two patients undergoing awake brain surgery and measured EP on functional sites after cortical stimulations and were the firsts to record three different types of EP on the same patients. Using low-intensity (1–3 mA) to evoke electrogenesis we observed that: (i) “true” remote EPs are attenuated in amplitude and delayed in time due to the divergence of white matter pathways; (ii) “false” remote EPs are attenuated but not delayed: as they originate from the same electrical source; (iii) Singular but reproducible positive components in the EP can be generated when the DES is applied in the temporal lobe or the premotor cortex; and (iv) rare EP can be triggered when the DES is applied subcortically: these can be either negative, or surprisingly, positive. We proposed different activation and electrophysiological propagation mechanisms following DES, based on the nature of activated neural elements and discussed important methodological pitfalls when measuring EP in the brain. Altogether, these results pave the way to map the connectivity in real-time between the DES and the recording sites; to characterize the local electrophysiological states and to link electrophysiology and function. In the future, and in practice, this technique could be used to perform electrophysiological mapping in order to link (non)-functional to electrophysiological responses with DES and could be used to guide the surgical act itself.

accepted 2020-08-04; International audience; Recurrence quantification analysis (RQA) is an acknowledged method for the characterization of experimental time series. We propose a parametric version of RQA, pRQA, allowing a fast processing of spatial arrays of time series, once each is modeled by an autoregressive stochastic process. This method relies on the analytical derivation of asymptotic expressions for five current RQA measures as a function of the model parameters. By avoiding the construction of the recurrence plot of the time series, pRQA is computationally efficient. As a proof of principle, we apply pRQA to pattern recognition in multichannel electroencephalographic (EEG) data from a patient with a brain tumor.

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.

Transopercular approach to the insula is indicated for resection of insular low-grade gliomas, particularly for Yasargil's 3B, 5A, and 5B types. Nevertheless, the infrequent location and its challenging approach make it difficult to master the surgery. Consequently, a realistic laboratory training model might help to acquire key surgical skills. In this video, we describe a cadaveric-based model simulating the resection of a temporo-insular low-grade glioma. Kingler's fixation technique was used to fix the cadaver head before injecting red and blue colorants for a realistic vascular appearance. Hemisphere was frozen for white matter tract dissection. Tractography and intraoperative eloquent areas were extrapolated from a glioma patient by using a neuronavigation system. Then, a fronto-temporal craniotomy was performed through a question mark incision, exposing from inferior temporal gyrus up to middle frontal gyrus. After cortical anatomic landmark identification, eloquent areas were extrapolated creating a simulated functional cortical map. Then, transopercular noneloquent frontal and temporal corticectomies were performed, followed by subpial resection. Detailed identification of Sylvian vessels and insular cortex was demonstrated. Anatomic resection limits were exposed, and implicated white matter bundles, uncinate and fronto-occipital fascicles, were identified running through the temporal isthmus. Finally, a temporo-mesial resection was performed. In summary, this model provides a simple, cost-effective, and very realistic simulation of a transopercular approach to the insula, allowing the development of surgical skills needed to treat insular tumors in a safe environment. Besides, the integration of simulated navigation has proven useful in better understanding the complex white matter anatomy involved. Cadaver donation, subject or relatives, includes full consent for publication of the images. For the purpose of this video, no ethics committee approval was needed. Images correspond to a cadaver head donation. Cadaver donation, subject or relatives, includes full consent for any scientific purposes involving the corpse. The consent includes image or video recording. Regarding the intraoperative surgical video and tractography, the patient gave written consent for scientific divulgation prior to surgery.

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.

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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.

International audience; Although radiation therapy (RT) is a main treatment of brain tumors, delayed cerebral toxicity may lead to cognitive deteriorations with adverse effects on quality of life. Despite technological advances in RT, the concept of brain connectome has not yet been incorporated in the strategy of irradiation. Because white matter tracts represent the main limitation of neuroplasticity, tumor surgery is increasingly performed with awake cortical-subcortical mapping. Here, the purpose is to reinforce the link between cognitive neurosciences and neurooncology, which is critical for neurosurgeons but also for medical oncologists, especially brain radiation oncologists. The goal is to optimize RT planning by sparing individual critical neural networks. A redefinition of "organs at risk" should be proposed, beyond the few structures (such as brainstem, optic pathway, pituitary gland, hippocampi) which are classically preserved for brain radiation, by considering the structural and functional connectivity in order to evolve toward a RT "à la carte".

Simple Summary Beyond intraoperative electrostimulation mapping in awake patients (the gold-standard for brain tumor surgery), non-invasive FNI/TMS can be repeated before and after resection(s). These techniques enable longitudinal investigation of neural reorganization, especially in low-grade gliomas, which can generate neuroplasticity in patients with usually no or slight neurological deficits, despite neoplasm within “eloquent” structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time were evidenced, with structural changes as well as modifications of intra-hemispheric and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation. Abstract Intraoperative direct electrostimulation mapping (DEM) is currently the gold-standard for glioma surgery, since functional-based resection allows an optimization of the onco-functional balance (increased resection with preserved quality of life). Besides intrasurgical awake mapping of conation, cognition, and behavior, preoperative mapping by means of functional neuroimaging (FNI) and transcranial magnetic stimulation (TMS) has increasingly been utilized for surgical selection and planning. However, because these techniques suffer from several limitations, particularly for direct functional mapping of subcortical white matter pathways, DEM remains crucial to map neural connectivity. On the other hand, non-invasive FNI and TMS can be repeated before and after surgical resection(s), enabling longitudinal investigation of brain reorganization, especially in slow-growing tumors like low-grade gliomas. Indeed, these neoplasms generate neuroplastic phenomena in patients with usually no or only slight neurological deficits at diagnosis, despite gliomas involving the so-called “eloquent” structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time have been evidenced, with structural changes as well as modifications of intra-hemispheric (in the ipsi-lesional and/or contra-lesional hemisphere) and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation.

OBJECTIVEIntraoperative brain mapping with neurocognitive monitoring during awake surgery is currently the standard pattern of care for patients with diffuse low-grade glioma (DLGG), allowing a maximization of the extent of resection (EOR) while preserving quality of life. This study evaluated the feasibility of DLGG resections performed with intraoperative cognitive monitoring via the assistance of a translator for patients speaking foreign languages, and compared the surgical functional and oncological outcomes according to the possibility of direct communication with the surgical team.METHODSForeign patients who underwent awake surgery with intraoperative electrical mapping with the assistance of a translator for the resection of a DLGG in the authors’ institution between January 2010 and December 2020 were included. Patients whose native language included one of the three languages spoken by the surgical team (i.e., French, English, or Spanish) were excluded. The patients were classified into two groups. Group 1 was composed of patients able to communicate in at least one of these three languages in addition to their own native language. Group 2 was composed of patients who spoke none of these languages, and therefore were unable to communicate directly with the operating staff. The primary outcome was the patients’ ability to return to work 3 months after surgery.RESULTSEighty-four patients were included, of whom 63 were classified in group 1 and 21 in group 2. Eighteen different native languages were tested in the operating theater. Awake mapping was successful, with elicitation of transitory disturbances in all patients. There was no significant difference in the 3-month return-to-work status between the two groups (95% in group 1 [n = 58/61] vs 88% in group 2 [n = 15/17]; p = 0.298). Similarly, no significant difference between the two groups was found regarding the intraoperative tasks performed, the mean duration of the surgery, and the rate of permanent postoperative deficit. A significantly greater EOR was observed in group 1 patients in comparison to group 2 patients (90.4% ± 10.6% vs 87.7% ± 6.1%; p = 0.029).CONCLUSIONSReal-time translation by an interpreter during awake resection of glioma is feasible and safe in foreign patients. Nonetheless, when no direct verbal communication is possible between the surgical team and the patient, the EOR is less.

International audience; In this data article, we provide the dataset which served as the basis for our related research article "Mapping critical cortical hubs and white matter pathways by direct electrical stimulation: an original functional atlas of the human brain" [1], which represents the first probabilistic cortical and subcortical atlas of critical structures mediating human brain functions based on direct electrical stimulation (DES) in patients undergoing awake brain surgery. 1162 cortical and 659 subcortical DES-derived responses were recorded during testing of 16 functional domains in 256 patients undergoing awake surgery. Normalized [Montreal Neurological Institute (MNI) 152] spatial coordinates for cortical and subcortical responses, and probabilistic heat maps for each functional domain, were computed using methods previously developed by our group [2,3]. Source data, including the MNI-normalized coordinates of all 1821 DES-derived cortical and subcortical data points, and multi-planar (MNI-152, T1 1mm) videos showing the probabilistic distribution of each functional domain are provided. This novel dataset can improve and refine our understanding about the functional anatomy of critical brain networks, and these data are made available for medical and neuroscience applications.

International audience; Over the past two decades, it has been demonstrated that brain mapping in an awake patient is a very reliable tool for brain tumor resection, allowing us to maximize the extent of resection while minimizing the functional risk.1 This methodology is becoming more and more popular, and different teams have introduced many new tasks in their intraoperative battery, for motor functions2 as well as for cognitive functions.3,4 While the aim of preserving functions better and better cannot be blamed, it should be kept in mind that selecting for each case a personalized minimal set of tasks is crucial: the awake surgery team has to find an optimal trade-off between the number of tasks incorporated in the intraoperative battery and the limited amount of time of the awake period (about 2 h, in keeping with the onset of the patient's tiredness, which renders monitoring unreliable). More than that, there is a risk of introducing tasks that would be too sensitive, in the sense that the removal of a positive site would not necessarily lead to a permanent deficit of the function, meaning that brain mapping would restrict the extent of resection for no good reasons. We, thus, would like to highlight in this letter that the introduction of a new task tapping a specific sensorimotor, cognitive, or emotional process should follow a strict scientific plan.

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

International audience; Background: Functional preoperative planning for resection of intrinsic brain tumors in eloquent areas is still a challenge. Predicting subcortical functional framework is especially difficult. Direct electrical stimulation (DES) is the recommended technique for resection of these lesions. A reliable probabilistic atlas of the critical cortical epicenters and subcortical framework based on DES data was recently published.Objective: To propose a pipeline for the automated alignment of the corticosubcortical maps of this atlas with T1-weighted MRI.Methods: To test the alignment, we selected 10 patients who underwent resection of brain lesions by using DES. We aligned different cortical and subcortical functional maps to preoperative volumetric T1 MRIs (with/without gadolinium). For each patient we quantified the quality of the alignment, and we calculated the match between the location of the functional sites found at DES and the functional maps of the atlas.Results: We found an accurate brain extraction and alignment of the functional maps with both the T1 MRIs of each patient. The matching analysis between functional maps and functional responses collected during surgeries was 88% at cortical and, importantly, 100% at subcortical level, providing a further proof of the correct alignment.Conclusion: We demonstrated quantitatively and qualitatively the reliability of this tool that may be used for presurgical planning, providing further functional information at the cortical level and a unique probabilistic prevision of distribution of the critical subcortical structures. Finally, this tool offers the chance for multimodal planning through integrating this functional information with other neuroradiological and neurophysiological techniques.

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; Objective: Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain, and guide tumour resection during awake neurosurgery. Nonetheless, the electrophysiological effects of DES remain largely unknown, both locally and remotely.Approach: In this study, we lowered the DES frequency to 1-10 Hz and we used a differential recording mode of electro-corticographic (ECoG) signals to improve the focality with a simple algorithm to remove the artefacts due to the response of the acquisition chain.Main results: Doing so, we were able to observe different components in the evoked potentials triggered by simulating the cortex or the subcortical white matter pathways near the recording electrodes and by stimulating the cortex remotely from the recording site. More particularly, P0 and N1 components were repeatedly observed on raw ECoG signals without the need to average the data.Significance: This new methodology is important to probe the electrophysiological states and the connectivity of the brain in vivo and in real time, namely to perform electrophysiological brain mapping on human patients operated in the neurosurgical room and to better understand the electrophysiological spreading of DES.

International audience; BACKGROUND:The sagittal stratum (SS) is a critical neural crossroad traversed by several white matter tracts that connect multiple areas of the ipsilateral hemisphere. Scant information about the anatomical organization of this structure is available in literature. The goal of this study was to provide a detailed anatomical description of the SS and to discuss the functional implications of the findings when a surgical approach through this structure is planned.METHODS:Five formalin-fixed human brains were dissected under the operating microscope by using the fiber dissection technique originally described by Ludwig and Klingler.RESULTS:The SS is a polygonal crossroad of associational fibers situated deep on the lateral surface of the hemisphere, medial to the arcuate/superior longitudinal fascicle complex, and laterally to the tapetal fibers of the atrium. It is organized in three layers: a superficial layer formed by the middle and inferior longitudinal fascicles, a middle layer corresponding to the inferior fronto-occipital fascicle, and a deep layer formed by the optic radiation, intermingled with fibers of the anterior commissure. It originates posteroinferiorly to the inferior limiting sulcus of the insula, contiguous with the fibers of the temporal stem, and ends into the posterior temporo-occipito-parietal cortex.CONCLUSION:The white matter fiber dissection reveals the tridimensional architecture of the SS and the relationship between its fibers. A detailed understanding of the anatomy of the SS is essential to decrease the operative risks when a surgical approach within this area is undertaken.

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.

OBJECTIVEThe sagittal stratum is divided into two layers. In classic descriptions, the stratum sagittale internum corresponds to optic radiations (RADs), whereas the stratum sagittale externum corresponds to fibers of the inferior longitudinal fasciculus. Although advanced for the time it was proposed, this schematic organization seems simplistic considering the recent progress on the understanding of cerebral connectivity and needs to be updated. Therefore, the authors sought to investigate the composition of the sagittal stratum and to detail the anatomical relationships among the macroscopic fasciculi.METHODSThe authors performed a layer-by-layer fiber dissection from the superolateral aspect to the ventricular cavity in 20 cadaveric human hemispheres.RESULTSDiverse bundles of white matter were observed to contribute to the sagittal stratum and their spatial arrangement was highly consistent from one individual to another. This was the case of the middle longitudinal fasciculus, the inferior fronto-occipital fasciculus, the RADs, and other posterior thalamic radiations directed to nonvisual areas of the cerebral cortex. In addition, small contributions to the sagittal stratum came from the anterior commissure anteriorly and the inferior longitudinal fasciculus inferiorly.CONCLUSIONSA general model of sagittal stratum organization in layers is possible, but the composition of the external layer is much more complex than is mentioned in classic descriptions. A small contribution of the inferior longitudinal fasciculus is the main difference between the present results and the classic descriptions in which this bundle was considered to entirely correspond to the stratum sagittale externum. This subject has important implications both for fundamental research and neurosurgery, as well as for the development of surgical approaches for the cerebral parenchyma and ventricular system.

BACKGROUND: The postoperative outcomes and the predictors of seizure control are poorly studied for supratentorial cavernous angiomas (CA) within or close to the eloquent brain area. OBJECTIVE: To assess the predictors of preoperative seizure control, postoperative seizure control, and postoperative ability to work, and the safety of the surgery. METHODS: Multicenter international retrospective cohort analysis of adult patients benefitting from a functional-based surgical resection with intraoperative functional brain mapping for a supratentorial CA within or close to eloquent brain areas. RESULTS: A total of 109 patients (66.1% women; mean age 38.4 ± 12.5 yr), were studied. Age >38 yr (odds ratio [OR], 7.33; 95% confidence interval [CI], 1.53-35.19; P =. 013) and time to surgery > 12 mo (OR, 18.21; 95% CI, 1.11-296.55; P =. 042) are independent predictors of uncontrolled seizures at the time of surgery. Focal deficit (OR, 10.25; 95% CI, 3.16-33.28; P

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.

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Diffuse low-grade gliomas (DLGG) are cerebral tumors occurring in young adults, with an inescapable progression to higher grade of malignancy, resulting in functional impairment and death. DLGG evolve in several phases: an asymptomatic period despite a slow radiological growth; a period in which inaugural symptoms occur, usually epilepsy with possible mild cognitive disorders; then a phase with malignant transformation generating disabling neurological deficits; and ultimately the terminal stage. Early maximal surgical resection significantly increases overall survival while preserving quality of life. Surgeries are conducted under local anesthesia in order to map neural networks crucial for brain functions, and with the goal to use neuroplasticity mechanisms by sparing cerebral connectivity. Adjuvant oncological treatments such as chemotherapy and/or radiotherapy are kept for partial resection or non-operable recurrences. Because of an increase of incidentally discovered DLGG, explained by a facilitated access to brain imaging, awake surgery has been proposed in asymptomatic patients, with the aim of maximizing the rate of total or even "supratotal" resection in smaller tumors. Outcomes have been optimized, both regarding oncological results thanks to minimization of malignant transformation, as well as regarding functional results, with neither neurological deficit nor epilepsy in this sub-group of incidental DLGG. Thus, it seems legitimate to set up a screening by cerebral MRI in the population from 20 to 40years, to propose adapted therapeutic strategies based upon an upfront radical surgery, and so to create the foundations of a prophylactic and personalized functional neuro-oncologie.

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.

Introduction Surgical resection of supratentorial cavernous angiomas located in eloquent areas poses a significant risk to the patient of postoperative neurological impairment and justifies intraoperative functional monitoring. Methods Multicentre retrospective series of adult patients with cavernous angiomas located within eloquent areas and treated with functional-based surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions. Results Fifty patients (18 males, mean 36.3 ± 10.8 year-old) underwent surgical resection with intraoperative cortico-subcortical functional mapping using direct electrostimulation under awake conditions for a cavernous angioma located in eloquent areas with a mean postoperative follow-up of 21.0 ± 21.2 months. At presentation, the cavernous angioma had previously resulted in severe impairment (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%, reduced Karnofsky Performance Status score of 70 or less in 24%, inability to work in 52%). Functional-based surgical resection allowed complete removal of the cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative seizures and other complications were rare, and similarly so across all centres included in this series. Postoperatively, we found functional improvement in 84% of patients (reduced Karnofsky Performance Status score of 70 or less in 6%, uncontrolled seizures in 16%, and inability to work in 11%). Conclusion Functional-based surgical resection aids the safe and complete resection of cavernous angiomas located in eloquent areas while minimizing the surgical risks. Functional mapping has to be considered in such challenging cases.