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BackgroundStrong interactions between art and health are well-known. While advances in brain surgery resulted in an improved preservation of sensorimotor, visuospatial, language and cognitive functions, creative abilities received less attention. However, creativity may represent a critical issue to resume an optimal quality of life, especially in artists. Here, a unique case of sudden change in creative style in a painter who underwent glioma resection is described. This prompts to explore further creative thinking and its clinical implications in routine practice.MethodsA 36-year-old right-handed woman experienced inaugural seizures, allowing the discovery of a right frontal lesion. The patient was a professional painter and did not complain about any decline in her creativity. The preoperative neurological examination was normal.ResultsSurgery was achieved with a maximal tumor resection through a frontal lobectomy. A WHO grade II oligodendroglioma was diagnosed. A regular surveillance was performed without adjuvant oncological treatment. The patient did not exhibit postoperative functional deterioration and she returned to normal activities including painting during 15 years. Remarkably, even though her creative activity was judged by the patient herself to be rich and satisfying, her style drastically changed from surrealism and mysticism to cubism whereas she was not able to explain why.ConclusionThis is the first report of acute modification of the painting style following frontal lobectomy for a low-grade glioma, supporting that brain resective surgery may impact creativity. While neglected for many decades, this complex human ability should be evaluated more regularly in neurosurgical practice, particularly in artists.

IntroductionNeurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy.Methods and analysisPatients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery.Ethics and disseminationEthics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses.Clinical trial registrationClinicalTrials.gov, identifier NCT05844605.

PurposeThe management of recurrent WHO grades II–III (rGII–III) glioma is not well established. This study describes the clinical outcomes in patients who received bevacizumab as rescue treatment.MethodsIn this retrospective study, the main inclusion criteria were as follows: adult patients with histologicaly proved rGII–III glioma according 2016 WHO classification treated with bevacizumab from 2011 to 2019, T1 contrast enhancement on MRI. Efficacy was assessed using the high-grade glioma 2017 Response Assessment in Neuro-Oncology criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsEighty-one patients were included (M/F ratio: 1.7, median age at diagnosis: 38 years) among whom 46 (56.8%) had an initial diagnosis of grade II glioma. Previous treatments included at least one surgical intervention, radiotherapy (98.8%), and ≥ 2 chemotherapy lines (64.2%). After bevacizumab initiation, partial response, stable disease, and progressive disease were observed in 27.2%, 22.2%, and 50.6% of patients. The median PFS and OS were 4.9 months (95% confidence interval [CI] 3.7–6.1) and 7.6 months (95% CI 5.5–9.9). Bevacizumab severe toxicity occurred in 12.3%. Twenty-four (29.6%) patients discontinued bevacizumab without radiological progression. Oligodendroglioma and age ≥ 38 years at diagnosis were more frequent in this subgroup (odds ratio = 0.24, 95% CI 0.07–0.84, p = 0.023 and 0.36, 95% CI 0.13–0.99, p = 0.042). Ten of these 24 patients were alive at 12 months and two patients at 8 years after bevacizumab initiation, without any subsequent treatment.ConclusionBevacizumab can be an option for heavily pretreated patients with rGII–III glioma with contrast enhancement. In our study, bevacizumab displayed prolonged activity in a subgroup of patients.

Early maximal surgical resection is the first treatment in diffuse low-grade glioma (DLGG), because the reduction of tumor volume delays malignant transformation and extends survival. Awake surgery with intraoperative mapping and behavioral monitoring enables to preserve quality of life (QoL). However, because of the infiltrative nature of DLGG, relapse is unavoidable, even after (supra)total resection. Therefore, besides chemotherapy and radiotherapy, the question of reoperation(s) is increasingly raised, especially because patients with DLGG usually enjoy a normal life with long-lasting projects. Here, the purpose is to review the literature in the emerging field of iterative surgeries in DLGG. First, long-term follow-up results showed that patients with DLGG who underwent multiple surgeries had an increased survival (above 17 years) with preservation of QoL. Second, the criteria guiding the decision to reoperate and defining the optimal timing are discussed, mainly based on the dynamic intercommunication between the glioma relapse (including its kinetics and pattern of regrowth) and the reactional cerebral reorganization—i.e., mechanisms underpinning reconfiguration within and across neural networks to enable functional compensation. Third, how to adapt medico-surgical strategy to this individual spatiotemporal brain tumor interplay is detailed, by considering the perpetual changes in connectome. These data support early reoperation in recurrent DLGG, before the onset of symptoms and before malignant transformation. Repeat awake resection(s) should be integrated in a global management including (neo)adjuvant medical treatments, to enhance long-lasting functional and oncological outcomes. The prediction of potential and limitation of neuroplasticity at each step of the disease must be improved to anticipate personalized multistage therapeutic attitudes.

Awake surgery for brain gliomas improves resection while minimizing morbidity. Although intraoperative mapping was originally used to preserve motor and language functions, the considerable increase of life expectancy, especially in low-grade glioma, resulted in the need to enhance patients’ long-term quality of life. If the main goal of awake surgery is to resume normal familial and socio-professional activities, preventing hemiparesis and aphasia is not sufficient: cognitive and emotional functions must be considered. To monitor higher-order functions, e.g., executive control, semantics or mentalizing, further tasks were implemented into the operating theater. Beyond this more accurate investigation of function-specific neural networks, a better exploration of the inter-system communication is required. Advances in brain connectomics led to a meta-network perspective of neural processing, which emphasizes the pivotal role of the dynamic interplay between functional circuits to allow complex and flexible, goal-directed behaviors. Constant multi-tasking with time constraint in awake patients may be proposed during intraoperative mapping, since it provides a mirror of the (dys)synchronization within and across neural networks and it improves the sensitivity of behavioral monitoring by increasing cognitive demand throughout the resection. Electrical mapping may hamper the patient to perform several tasks simultaneously whereas he/she is still capable to achieve each task in isolation. Unveiling the meta-network organization during awake mapping by using a more ecological multi-demand testing, more representative of the real-life conditions, constitutes a reliable way to tailor the surgical onco-functional balance based upon the expectations of each patient, enabling him/her to resume an active life with long-lasting projects.

For many decades, interactions between diffuse lower-grade glioma (LGG) and brain connectome were neglected. However, the neoplasm progression is intimately linked to its environment, especially the white matter (WM) tracts and their myelin status. First, while the etiopathogenesis of LGG is unclear, this tumor seems to appear during the adolescence, and it is mostly located within anterior and associative cerebral areas. Because these structures correspond to those which were myelinated later in the brain maturation process, WM myelination could play a role in the development of LGG. Second, WM fibers and the myelin characteristics also participate in LGG diffusion, since glioma cells migrate along the subcortical pathways, especially when exhibiting a demyelinated phenotype, which may result in a large invasion of the parenchyma. Third, such a migratory pattern can induce functional (neurological, cognitive and behavioral) disturbances, because myelinated WM tracts represent the main limitation of neuroplastic potential. These parameters are critical for tailoring an individualized therapeutic strategy, both (i) regarding the timing of active treatment(s) which must be proposed earlier, before a too wide glioma infiltration along the WM bundles, (ii) and regarding the anatomic extent of surgical resection and irradiation, which should take account of the subcortical connectivity. Therefore, the new science of connectomics must be integrated in LGG management, based upon an improved understanding of the interplay across glioma dissemination within WM and reactional neural networks reconfiguration, in order to optimize long-term oncological and functional outcomes. To this end, mechanisms of activity-dependent myelin plasticity should be better investigated.

Objective: Surgical approach to low-grade glioma (LGG) involving the posterior insula is challenging, especially in the left hemisphere, with a high risk of sensorimotor, language, or visual deterioration. In this study, a case series of 5 right-handed patients harboring a left posterior insular LGG is reported, by detailing a transcorticosubcortical approach.Method: The five surgeries were achieved in awake patients using cortical and axonal electrostimulation mapping. The glioma was removed through the left rolandic and/or parietal opercula, with preservation of the subcortical connectivity.Results: The cortical mapping was positive in the five patients, enabling the selection of an optimal transcortical approach, via the anterolateral supramarginal gyrus in four patients and/or via the lateral retrocentral gyrus in three cases (plus through the left superior temporal gyrus in one case). Moreover, the white matter tracts were identified in all cases, i.e., the lateral part of the superior longitudinal fasciculus (five cases), the arcuate fasciculus (four cases), the thalamocortical somatosensory pathways (four cases), the motor pathway (one case), the semantic pathway (three cases), and the optic tract (one case). Complete resection of the LGG was achieved in two patients and near-total resection in three patients. There were no postoperative permanent sensorimotor, language, or visual deficits.Conclusion: A transcortical approach through the parietorolandic operculum in awake patients represents safe and effective access to the left posterior insular LGG. Detection and preservation of the functional connectivity using direct electrostimulation of the white matter bundles are needed in this cross-road brain region to prevent otherwise predictable postsurgical impairments.

The inferior fronto-occipital fasciculus (IFOF) is one of the longest association fiber tracts of the brain. According to the most recent anatomical studies, it may be formed by several layers, suggesting a role in multiple cognitive functions. However, to date, no attempt has been made to dissociate the functional contribution of the IFOF subpathways. In this study, real-time, cortico-subcortical mapping with direct electrostimulation was performed in 111 patients operated on in wide-awake surgery for a right low-grade glioma. Patients performed two behavioral tasks during stimulation, tapping, respectively, mentalizing and visual semantic cognition—two functions supposed to be partly mediated by the IFOF. Responsive white matter sites were first subjected to a clustering analysis to assess potential topological differences in network organization. Then they were used as seeds to generate streamline tractograms based on the HC1021 diffusion dataset (template-based approach). The tractograms obtained for each function were overlapped and contrasted to determine whether some fiber pathways were more frequently involved in one or the other function. The obtained results not only provided strong evidence for a role of the right IFOF in both functions, but also revealed that the tract is dissociable into two functional strata according to a ventral (semantic) and dorsal (mentalizing) compartmentalization. Besides, they showed a high degree of anatomo-functionnal variability across patients in the functional implication of the IFOF, possibly related to symmetrical/hemispheric differences in network organization. Collectively, these findings support the view that the right IFOF is a functionally multi-layered structure, with nevertheless interindividual variations.

BackgroundTo 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.MethodsA 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.ResultsA 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.ConclusionThis large monocentric series spread over a long time clarifies the effects of different therapeutic strategies and their combination in the management of DLGG.

For a long time, the relevance of the information provided by direct electrostimulation (DES) for mapping brain functions was debated. Recently, major advances in intraoperative DES for guiding resection of cerebral tumors in awake patients enabled the validation of this method and its increased utilization in basic neurosciences. Indeed, in addition to the cortical stimulation used for many decades in epilepsy surgery, axonal mapping was developed thanks to DES of the white matter tracts, giving original insights into the neural connectivity. Moreover, functional results collected during intrasurgical mapping have been correlated with neuropsychological performances before and after DES-guided resection, and with perioperative neuroimaging data. Thus, it was evidenced that DES offers the unique opportunity to identify both cortical and subcortical structures critical for cerebral functions. Here, the first aim is to propose a three-level model of DES-generated functional disruption, able to explain the behavioral consequences elicited during awake surgery, i.e., (i) DES of an input/output unimodal (e.g., somatosensory or motor) network inducing “positive” responses (as involuntary movement); (ii) DES of a distributed specialized network inducing a within-system disruption leading to specific “negative” disorders (e.g., exclusive language deficit with no other disorders); (iii) DES generating an inter-system disruption leading to more complex behavioral disturbances (e.g., the inability to perform dual-task while each function can be performed separately). Second, in light of this model, original findings gained from DES concerning the human connectome, complementary to those provided by functional neuroimaging (FNI), are reviewed. Further longitudinal multimodal investigations are needed to explore neuroplasticity mechanisms.

The inferior longitudinal fasciculus (ILF) is a long-range, associative white matter pathway that connects the occipital and temporal-occipital areas of the brain to the anterior temporal areas. In view of the ILF’s anatomic connections, it has been suggested that this pathway has a major role in a relatively large array of brain functions. Until recently, however, the literature data on these potential functions were scarce. Here, we review the key findings of recent anatomic, neuromodulation, and neuropsychological studies. We also summarize reports on how this tract is disrupted in a wide range of brain disorders, including psychopathologic, neurodevelopmental, and neurologic diseases. Our review reveals that the ILF is a multilayered, bidirectional tract involved in processing and modulating visual cues and thus in visually guided decisions and behaviors. Accordingly, sudden disruption of the ILF by neurologic insult is mainly associated with neuropsychological impairments of visual cognition (e.g., visual agnosia, prosopagnosia, and alexia). Furthermore, disruption of the ILF may constitute the pathophysiologic basis for visual hallucinations and socio-emotional impairments in schizophrenia, as well as emotional difficulties in autism spectrum disorder. Degeneration of the ILF in neurodegenerative diseases affecting the temporal lobe may explain (at least in part) the gradual onset of semantic and lexical access difficulties. Although some of the functions mediated by the ILF appear to be relatively lateralized, observations from neurosurgery suggest that disruption of the tract’s anterior portion can be dynamically compensated for by the contralateral portion. This might explain why bilateral disruption of the ILF in either acute or progressive disease is highly detrimental in neuropsychological terms.