Search

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.

Background Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma, remains after resection and radiotherapy and the tumoral microenvironment become stiffer. GSC invasion is reported as stiffness sensitive and associated with altered N-glycosylation pattern. Glycocalyx thickness modulates integrins mechanosensing, but details remain elusive and glycosylation enzymes involved are unknown. Here, we studied the association between matrix stiffness modulation, GSC migration and MGAT5 induced N-glycosylation in fibrillar 3D context. Method To mimic the extracellular matrix fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). GSCs neurosphere were plated on NFSs, allowing GSCs migration and MGAT5 was deleted using CRISPR-Cas9. Results We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression and maturation of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1–6) branching, suppressed the stiffness dependence of migration on 166 kPa NFS as well as the associated FA and EMT protein expression. Conclusion MGAT5 catalysing multibranched N-glycans is a critical regulators of stiffness induced invasion and GSCs mechanotransduction, underpinning MGAT5 as a serious target to treat cancer.

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.

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.

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

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; 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; 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; 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.

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.

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.

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.

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; 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".

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

International audience; Background: Direct electrical stimulation (DES) is used to perform functional brain mapping during awake surgery but its electrophysiological effects remain by far unknown.Hypothesis: DES may be coupled with the measurement of Evoked Potentials (EPs) to study the conductive and integrative properties of activated neural ensembles and probe the spatiotemporal dynamics of short- and long- range networks.Methods: We recorded ECoG signals on two patients undergoing awake brain surgery and measured EPs on functional sites after cortical stimulations, using combinations of stimulation parameters.Results: EPs were similar in shape but delayed in time and attenuated in amplitude when elicited from a different gyrus or remotely from the recording site. We were able to trigger remote EPs using low stimulation intensities.Conclusion: We propose different activation and electrophysiological propagation mechanisms following DES based on activated neural elements.

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; 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.

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.

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.

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.

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.

International audience; BACKGROUND:Advances in the oncologic and functional results of insular surgery have been reported recently. Such successes have been made possible by the advent of the transopercular approach under awake monitoring and by improved anatomic and functional knowledge of white matter pathways surrounding the insula. Nonetheless, given the rarity of insular tumors, it is difficult to get familiar with the complex 3-dimensional anatomy of the different neuronal and vascular structures encountered during a transopercular insular resection. We thus propose to develop a laboratory model allowing to train transopercular approaches of the insula.METHODS:Two hemispheres prepared with Klinger's technique were dissected under light microscope, preserving all pial membranes. The different steps of the dissection were video recorded.RESULTS:Preservation of pial membranes enabled us to simulate subpial resection, both during operculum removal and during insular cortex resection. The medial wall of the resection was defined by the inferior-fronto-occipital fasciculus, protecting from the lenticulostriate arteries.CONCLUSION:In this paper, we show that Klinger dissection with preservation of pial membranes provides a realistic model of insular surgery, allowing surgeons to learn and train on this highly specialized surgery.

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.

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.

International audience; BACKGROUND:Preoperative interpretation of resectability of diffuse nonenhancing glioma is primarily based on individual surgical expertise.OBJECTIVE:To compare the accuracy and precision between observed resections and preoperative estimates of neurosurgeons and a resection probability map (RPM). We hypothesize that the RPM estimates is as good as senior neurosurgeons.METHODS:A total of 234 consecutive patients were included from 2 centers, who had resective surgery with functional mapping between 2006 and 2012 for a supra-tentorial nonenhancing glioma. Extent of resection (EOR) and residual tumor volume (RTV) were segmented and an RPM was constructed in standard brain space. Three junior and three senior neurosurgeons estimated EOR and RTV, blinded for postoperative results. We determined the agreement between the estimates and calculated the diagnostic accuracy of the neurosurgeons and the RPM to predict the observed resections.RESULTS:Preoperative estimates of resection results by junior and senior neurosurgeons were significantly biased towards overestimation of EOR (4.2% and 11.2%) and underestimation of RTV (4.3 and 9.0 mL), whereas estimates of the RPM were unbiased (-2.6% and -.2 mL, respectively). The limits of agreement were wide for neurosurgeons and for the RPM. The RPM was significantly more accurate in identifying patients in whom an EOR >40% was observed than neurosurgeons.CONCLUSION:Neurosurgeons estimate preoperative resectability before surgery of a nonenhancing glioma rather accurate-with a small bias-and imprecise-with wide limits of agreement. An RPM provides unbiased resectability estimates, which can be useful for surgical decision-making, planning, and education.

Glioblastoma Multiforme (GBM) invasiveness renders complete surgical resection impossible and highly invasive Glioblastoma Initiating Cells (GICs) are responsible for tumour recurrence. Their dissemination occurs along pre-existing fibrillary brain structures comprising the aligned myelinated fibres of the corpus callosum (CC) and the laminin (LN)-rich basal lamina of blood vessels. The extracellular matrix (ECM) of these environments regulates GIC migration, but the underlying mechanisms remain largely unknown. In order to recapitulate the composition and the topographic properties of the cerebral ECM in the migration of GICs, we have set up a new aligned polyacrylonitrile (PAN)-derived nanofiber (NF) scaffold. This system is suitable for drug screening as well as discrimination of the migration potential of different glioblastoma stem cells. Functionalisation with LN increases the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchymal migration of GBM in vivo, is the upregulation of galectin-3 and integrin-β1 in Gli4 cells migrating on our NF scaffold. Downregulation of Calpain-2 in GICs migrating in vivo along the CC and in vitro on LN-coated NF underlines a difference in the turnover of focal adhesion (FA) molecules between single-cell and collective types of migration.

International audience; Background: Herpes simplex encephalitis (HSE) and glioblastoma multiforme (GBM) co-occurrence has been described in few cases presenting immunocompromised status related to chemotherapy or chemoradiotherapy. Focal encephalitis over surgical edge of resection occurring shortly after GBM resection is rarely reported, and such infection has never been reported in low-grade glioma with secondary malignant transformation (i.e., secondary GBM). Here, we report a case of HSE misdiagnosed in the early postoperative course following a secondary GBM resection. We also provide a review of the literature about HSE occurring after glioma surgery. Case description: We report a case of an acute HSE with a fatal outcome occurring shortly after surgery for a secondary GBM. The patient presented with hyperthermia 12 days after the surgery and was treated with empirical antibiotics. She later suffered from seizure and neurologic deterioration, leading to death despite delayed antiviral administration. Magnetic resonance imaging revealed considerable fluid-attenuated inversion-recovery signal progression at the edge of the surgical resection and polymerase chain reaction amplification of herpes simplex virus (HSV) 1 DNA was positive. Conclusions: Clinicians should be aware of the existing co-occurrence between HSV infections and GBM during the postoperative course. Cerebrospinal fluid analysis with HSV polymerase chain reaction testing should be promptly undertaken, and some keys clinical elements should justify early empirical treatment, including acyclovir administration. The significant prognostic implication of HSE complicating GBM must raise the attention of neurosurgeon and neuro-oncologist about this entity.

International audience; Low-grade glioma (LGG) usually occurs in young patients who enjoy an active family, social, and professional life. Because awake surgery for patients with LGG has resulted in significant improvement in both functional and oncological outcomes and because the surgery per se is not very expensive, it is currently performed in many countries worldwide. Nonetheless, in addition to the necessity of tailoring the surgical strategy to the patient (e.g., neurological and cognitive status) and tumor (e.g., brain location and volume) characteristics, the legal, cultural, and socioeconomic parameters could also play a key role in the therapeutic strategy. These include clear information to the patient and relatives during the first meeting, the adapted selection of tasks for awake mapping, and active collaboration of the patient throughout the resection and during the early postoperative rehabilitation. In the present study, our goal was to analyze these socioenvironmental aspects, which have been neglected for many decades, in LGG management, with a special emphasis on epilepsy and the awake procedure. These criteria are relevant with respect to the diagnosis, surgery, functional remediation, and long-term follow-up for patients who now benefit from a longer life expectancy. However, although such factors are essential to resume an active life, including returning to work, they vary greatly across countries. Therefore, they should be considered more systematically to allow for greater reproducibility of results of awake surgery worldwide.

A 30-year-old right-handed female medical doctor experienced generalized seizures. MRI showed a left operculo-insular low-grade glioma. Awake resection was proposed. During the cortical mapping, counting and naming task combined with right upper limb movement enabled the identification of the ventral premotor cortex and negative motors areas. The so-called Broca’s area was not eloquent. Subpial dissection was performed by avoiding coagulation until the inferior fronto-occipital fasciculus and the junction between the output projection fibers and the anterior part of the superior longitudinal fasciculus III were reached. The patient resumed a normal familial and socio-professional life despite the resection of Broca’s area.The video can be found here: https://youtu.be/OALk0tvctQw.