INTRODUCTION:Transcranial direct current stimulation (tDCS) has shown encouraging results in patients with Disorders of Consciousness (DoC), yet its efficacy and mechanisms remain unclear. This study aimed to evaluate the effects of left dorsolateral prefrontal cortex (DLPFC) tDCS on Coma Recovery Scale-Revised (CRS-R) scores and EEG activity in severely brain-injured DoC patients. METHODS:In a double-blind, sham-controlled crossover design, 2 mA anodal and sham tDCS were randomly administered over the left DLPFC (right orbito-frontal cathode) for 20 min. CRS-R scores, event-related potentials using the local-global paradigm and resting EEG were recorded before and after each stimulation. Follow-up assessments occurred at 6 weeks and 6 months. RESULTS:Between November 2018 and April 2022, 20 patients were included (12 in a Minimally Conscious State (MCS), 7 in a Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS), and one patient who emerged from MCS (emergence from MCS (eMCS)). Group-level analysis across all patients revealed a significant treatment effect on CRS-R scores (p = 0.02). Nine patients (45%; 6 MCS, 3 VS/UWS) responded to tDCS, with five (25%; 3 MCS, 2 VS/UWS) exhibiting new behavioural items absent in pre- and post-sham evaluations. However, no patient demonstrated a change in consciousness state (e.g., transition from VS/UWS to MCS), nor was any improvement observed at 6-week or 6-month. EEG analysis showed increased complexity, gamma-band power, and delta-band cortico-cortical functional connectivity post-tDCS. Multivariate EEG analyses did not show a significant effect of tDCS on the prediction of conscious state, and ERP assessments using the local-global paradigm revealed no modulation of novelty detection responses following stimulation. Simulation analyses on individual brain anatomical structures revealed that responders displayed stronger tDCS-induced electric fields within a Fronto-parietal network than non-responders. CONCLUSION:Despite the limited sample size, our results provide additional evidence in favour of the behavioural and electrophysiological effects of tDCS in DoC patients.

Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation—functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals that specific modalities, such as functional assessments, provide comprehensive insights into the currently evaluated state of consciousness, the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centres with different acquisition parameters. Importantly, we demonstrate that model performance improves with an increase in the number of modalities. We observe a higher inter-modality disagreement for minimally conscious state patients and those patients who improve. Lastly, we observe a difference in feature importances between diagnosis and prognosis, with an interaction between modality and anatomical structures: some subcortical markers tend to contribute more to prognosis, while other cortical markers are more informative for diagnosis. This integrative multimodal and machine learning methodology presents a promising avenue for a more nuanced understanding of disorders of consciousness, contributing to enhanced diagnostic precision, prognostic capabilities and the personalization of rehabilitative strategies in clinical practice.

Sleep has traditionally been conceptualized as a state of cognitive disconnection, yet emerging evidence indicates that decision-making capacities persist across sleep stages. Here, we elucidate the computational mechanisms underlying real-time lexical decision-making during polysomnographically-verified sleep, using facial electromyography and hierarchical drift diffusion modeling in both healthy individuals and participants with narcolepsy. We found that lexical decision-making was preserved during N1 and lucid REM sleep, but relied on distinct computational strategies: in N1 sleep, both enhanced sensory-motor processing and increased evidence accumulation supported decisions about words, whereas in lucid REM sleep, lexical decisions were driven exclusively by evidence accumulation processes. Cross-state comparisons revealed two fundamental principles: (1) Selective preservation-during N1 sleep, lexical decisions for words were maintained while those for pseudowords were selectively impaired, indicating that cognitive resources during sleep are preferentially allocated to meaningful stimuli; (2) Parallel strategic adaptations-during lucid REM sleep, participants increased their decision thresholds, requiring more evidence before responding, which helped maintain accuracy even though the efficiency of evidence accumulation was reduced. Our findings demonstrate that, rather than a passive decline, sleep involves dynamic and state-specific reconfiguration of the computational mechanisms underlying decision-making, with important implications for understanding consciousness and cognitive flexibility.

Does being awake necessarily mean being conscious of something? This study investigates the phenomenon of mind blanking (MB), characterized by an "emptiness of mind," comparing it with mind wandering (MW) and on-task (ON) states. Using a sustained attention task and electroencephalogram monitoring, behavioral, and neurophysiological signatures of MB were examined in 62 participants. MB exhibited a specific pattern of behavioral lapses, as well as decreased fast oscillatory activity and complexity over posterior electrodes compared to MW. Functional connectivity analyses revealed decreased long-range interareal connectivity during MB, compared to both ON and MW states. Event-related potentials with source reconstruction and temporal decoding techniques indicated a significant disruption in visual processing during MB, starting from 200 ms post stimulus and echoing into the late-stage of visual processing, suggesting a disruption of conscious access to sensory information during MB. Electroencephalogram-derived markers allowed the prediction of mental states at the trial level, offering a finer view of conscious dynamics than subjective reports alone. Overall, these findings challenge the notion of the wakeful conscious mind as inherently content-oriented, suggesting that MB reflects genuine gaps in the stream of conscious thoughts, arising from disruptions in the generation or accessibility of thought content.

Decision-making is a core cognitive function that enables adaptive behavior across diverse contexts. While extensively studied in wakefulness, its persistence and reconfiguration across sleep states remain poorly understood. Here, we use computational modeling to examine lexical decision-making across wakefulness, N1 sleep, and lucid REM sleep in both healthy participants (HP) and participants with narcolepsy (NP). Using facial electromyography (EMG) to capture real-time behavioral responses to spoken words and pseudowords, we quantify how decision-making strategies adapt under different sleep and consciousness states. Our findings reveal two key insights. First, decision-making mechanisms are dynamically reconfigured across sleep states. In N1 sleep, the advantage for word (vs. pseudoword) judgments is supported by faster sensory encoding and motor preparation, combined with efficient evidence accumulation. In contrast, in lucid REM sleep, the word advantage is driven exclusively by enhanced evidence accumulation, while sensory encoding and motor preparation remain unchanged. Second, cross-state comparisons reveal distinct patterns of preservation and impairment. In N1 sleep, word processing remains largely intact, whereas pseudoword processing is significantly impaired, characterized by prolonged stimulus encoding, delayed motor preparation, and reduced evidence accumulation. In contrast, lucid REM sleep is marked by a global reduction in processing efficiency, reflected in slower evidence accumulation and elevated decision thresholds for both words and pseudowords. These results demonstrate that rather than being uniformly degraded, decision-making is dynamically reconfigured across sleep stages, reflecting adaptive neurocognitive strategies that sustain cognition in altered states of consciousness. By identifying state-specific computational mechanisms, this study provides new insights into the brain's resilience and flexibility under changing cognitive and physiological conditions. ### Competing Interest Statement The authors have declared no competing interest.

We introduce here a general model of Functional Neurological Disorders based on the following hypothesis: a Functional Neurological Disorder could correspond to a consciously initiated voluntary top-down process causing involuntary lasting consequences that are consciously experienced and subjectively interpreted by the patient as involuntary. We develop this central hypothesis according to Global Neuronal Workspace theory of consciousness, that is particularly suited to describe interactions between conscious and non-conscious cognitive processes. We then present a list of predictions defining a research program aimed at empirically testing their validity. Finally, this general model leads us to reinterpret the long-debated links between hypnotic suggestion and functional neurological disorders. Driven by both scientific and therapeutic goals, this theoretical paper aims at bringing closer the psychiatric and neurological worlds of functional neurological disorders with the latest developments of cognitive neuroscience of consciousness.

Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness (DoC). This spectrum includes clinical categories such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioral assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to look for the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation - functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessment through interpretable machine learning (ML). The electrophysiological modalities included high-density electroencephalography (EEG) (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional magnetic resonance imaging (MRI), diffusion MRI, and 18F-fluoro-deoxy-glucose positron emission tomography (FDG PET). Our investigation reveals that specific modalities, such as functional assessments provide comprehensive insights into the currently evaluated state of consciousness - the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centers with different acquisition parameters. Importantly, we show that there is an improved model performance with the increase in the number of modalities. We observe a higher inter-modality disagreement for MCS patients and those patients who improve. Lastly, we observe a difference in feature importances in diagnosis and prognosis. This integrative multimodal and ML methodology presents a promising avenue for a more nuanced understanding of DoC, contributing to enhanced diagnostic precision and prognostic capabilities in clinical practice. ### Competing Interest Statement Jacobo D. Sitt and Lionel Naccache are scientific co-founders of NeuroMeters (have scientific advisory activity but no executive or management activity). ### Funding Statement This work was supported by the Ecole Doctorale Frontieres de l'Innovation en Recherche et Education-Programme Bettencourt (to D.M.). This project is part of the multicentric application for the EU ERAPerMed Joint Translational Call for Proposals for "Personalised Medicine: Multidisciplinary research towards implementation" (ERA PerMed JTC2019). It is funded by local funding agencies of the participating countries (for France it is the Agence Nationale de Recherche ANR, funding code: ANR-19-PERM-0002, for Germany the Federal Ministry of Education and Research BMBF, funding code: 01KU2003). This project is supported by the Human Brain Project (HBP) MODELDxConsciousness Consortium (Agence Nationale de Recherche ANR, funding code: S.1600.ANR.HBPR). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Pitie-Salpetriere Hospital (Comite de Protection des Personnes, Ile de France 1, Paris, France) under the French label of routine care research (protocol number 2013-A01385-40, code Recherche en soins courants, protocol number M-Neuro-DOC, CE SRLF 20-2). Medical Faculty of Ludwig-Maximilians-Universitat Munchen (Germany) (protocol numbers 20-634 and 20-635). IRCCS Fondazione Don Carlo Gnocchi (IRCCS Regione Lombardia, Italy) (protocol number 32/2021/CE_FdG/FC/SA). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data is not publicly available.

Probing cognition and consciousness in the absence of functional communication remains an extremely challenging task. In this perspective, we imagined a basic clinical procedure to explore pain anticipation at bedside. In a series of 61 patients with a disorder of consciousness, we tested the existence of a nociceptive anticipation response by pairing a somaesthetic stimulation with a noxious stimulation. We then explored how nociceptive anticipation response correlated with (i) clinical status inferred from Coma Recovery Scale-Revised scoring, (ii) with an EEG signature of stimulus anticipation-the contingent negative variation-and (iii) how nociceptive anticipation response could predict consciousness outcome at 6 months. Proportion of nociceptive anticipation response differed significantly according to the state of consciousness: nociceptive anticipation response was present in 5 of 5 emerging from minimally conscious state patients (100%), in 10 of 11 minimally conscious state plus patients (91%), but only in 8 of 17 minimally conscious state minus patients (47%), and only in 1 of 24 vegetative state/unresponsive wakefulness syndrome patients (4%) (chi(2 ) P < 0.0001). Nociceptive anticipation response correlated with the presence of a contingent negative variation, suggesting that patients with nociceptive anticipation response were more prone to actively expect and anticipate auditory stimuli (Fisher's exact test P = 0.05). However, nociceptive anticipation response presence did not predict consciousness recovery. Nociceptive anticipation response appears as a new additional behavioural sign that can be used to differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome patients. As most behavioural signs of minimally conscious state, the nociceptive anticipation response seems to reveal the existence of a cortically mediated state that does not necessarily reflect residual conscious processing.

Does being awake mean being conscious? This study investigates Mind Blanking (MB), characterized by an "emptiness of mind", comparing it with Mind Wandering (MW) and On-task (ON) states. Using a sustained attention task and electroencephalogram monitoring on 26 participants, behavioral and neurophysiological signatures of MB were examined. MB exhibited a specific pattern of behavioral lapses, as well as decreased fast oscillatory activity and complexity over posterior electrodes compared to MW. Functional connectivity analyses also revealed decreased frontal-posterior connectivity during MB and event-related potentials indicated a disruption in late-stage visual processing, suggesting a lack of conscious access to sensory information during MB. EEG-based neural features enabled trial-level prediction of mental states, furnishing estimates of the fine-grained dynamics of consciousness beyond subjective reports. Overall, these findings challenge the notion of continuous wake consciousness, suggesting that MB represents genuine gaps in our stream of thoughts.SIGNIFICANCE STATEMENT Employing cutting-edge neurophysiological techniques on high-density EEG recordings, our study unveils unique neurophysiological markers of mind blanking—a phenomenon characterized by lapses in conscious content amidst the flow of consciousness. Distinguished from task-oriented states and mind wandering, this signature sheds light on the elusive nature of mind blanking. Furthermore, we demonstrate the feasibility of decoding consciousness dynamics solely from EEG features, transcending the limitations of intermittent subjective reports. Our findings not only provide a novel framework for investigating the stream of consciousness but also challenge the conventional notion that wakefulness invariably signifies consciousness.### Competing Interest StatementThe authors have declared no competing interest.All data, code, and materials used in the analysis will be freely available upon publication.

Patients with bipolar disorder (BD) are at increased risk of dementia. The underlying mechanisms are debated. FDG-PET elucidates glucose metabolic reductions due to altered neuronal activity in the cerebral cortex, allowing detection and identification of neurodegenerative processes. This study aims to investigate cerebral glucose metabolism in cognitively impaired elderly patients with BD using FDG-PET imaging, to elucidate potential underlying mechanisms and improve diagnostic accuracy. We conducted a retrospective analysis of FDG-PET scans from 32 cognitively impaired elderly patients with BD (mean age 70.4 years). These were compared with scans from 35 non-degenerative controls (NDC) and patients diagnosed with Alzheimer’s disease (AD, n = 27), frontotemporal dementia (FTD, n = 26), and dementia with Lewy bodies (DLB, n = 18). Voxel-wise statistical analysis was performed using SPM software, adjusting for age and sex. No significant cortical hypometabolism was found in patients with BD compared to NDC. In contrast, typical patterns of hypometabolism were observed in the AD, FTD, and DLB groups. The findings suggest that late-life cognitive impairment in patients with BD is not due to a single common neurodegenerative process. The absence of abnormal cortical metabolism in cognitively impaired elderly patients with BD suggests that cognitive impairment in this population may not be driven by a common neurodegenerative pathway. Further studies using other biomarkers are needed to investigate the brain processes involved, which could lead to improved understanding and management of cognitive impairment in patients with BD.

ObjectiveAccording to a seminal hypothesis stated by Crick and Koch in 1995, one is not aware of neural activity in primary visual cortex (V1) because this region lacks reciprocal connections with prefrontal cortex (PFC).MethodsWe provide here a neuropsychological illustration of this hypothesis in a patient with a very rare form of cortical blindness: ventral and dorsal cortical pathways were lesioned bilaterally while V1 areas were partially preserved.ResultsVisual stimuli escaped conscious perception but still activated V1 regions that were functionally disconnected from PFC.InterpretationThese results are consistent with the hypothesis of a causal role of PFC in visual awareness.

Pupil dilation response (PDR) has been proposed as a physiological marker of conscious access to a stimulus or its attributes, such as novelty. In a previous study on healthy volunteers, we adapted the auditory “local global” paradigm and showed that violations of global regularity elicited a PDR. Notably without instructions, this global effect was present only in participants who could consciously report violations of global regularities. In the present study, we used a similar approach in 24 non-communicating patients affected with a Disorder of Consciousness (DoC) and compared PDR to ERPs regarding diagnostic and prognostic performance. At the group level, global effect could not be detected in DoC patients. At the individual level, the only patient with a PDR global effect was in a MCS and recovered consciousness at 6 months. Contrasting the most regular trials to the most irregular ones improved PDR’s diagnostic and prognostic power in DoC patients. Pupillometry is a promising tool but requires several methodological improvements to enhance the signal-to-noise ratio and make it more robust for probing consciousness and cognition in DoC patients.

Sleep has long been considered as a state of behavioral disconnection from the environment, without reactivity to external stimuli. Here we questioned this 'sleep disconnection' dogma by directly investigating behavioral responsiveness in 49 napping participants (27 with narcolepsy and 22 healthy volunteers) engaged in a lexical decision task. Participants were instructed to frown or smile depending on the stimulus type. We found accurate behavioral responses, visible via contractions of the corrugator or zygomatic muscles, in most sleep stages in both groups (except slow-wave sleep in healthy volunteers). Across sleep stages, responses occurred more frequently when stimuli were presented during high cognitive states than during low cognitive states, as indexed by prestimulus electroencephalography. Our findings suggest that transient windows of reactivity to external stimuli exist during bona fide sleep, even in healthy individuals. Such windows of reactivity could pave the way for real-time communication with sleepers to probe sleep-related mental and cognitive processes.

Hypnosis can be conceived as a unique opportunity to explore how top-down effects can influence various conscious and non-conscious processes. In the field of perception, such modulatory effects have been described in distinct sensory modalities. In the present study we focused on the auditory channel and aimed at creating a radical deafness to elementary sounds by a specific hypnotic suggestion. We report here a single case-study in a highly suggestible healthy volunteer who reported a total hypnotically suggested deafness. We recorded high-density scalp EEG during an auditory odd-ball paradigm before and after hypnotic deafness suggestion. While both early auditory event-related potentials to sounds (P1) and mismatch negativity component were not affected by hypnotic deafness, we observed a total disappearance of the late P3 complex component when the subject reported being deaf. Moreover, a centro-mesial positivity was present exclusively during the hypnotic condition prior to the P3 complex. Interestingly, source localization suggested an anterior cingulate cortex (ACC) origin of this neural event. Multivariate decoding analyses confirmed and specified these findings. Resting state analyses confirmed a similar level of conscious state in both conditions, and suggested a functional disconnection between auditory areas and other cortical areas. Taken together these results suggest the following plausible scenario: (i) preserved early processing of auditory information unaffected by hypnotic suggestion, (ii) conscious setting of an inhibitory process (ACC) preventing conscious access to sounds, (iii) functional disconnection between the modular and unconscious representations of sounds and global neuronal workspace. This single subject study presents several limits that are discussed and remains open to alternative interpretations. This original proof-of-concept paves the way to a larger study that will test the predictions stemming from our theoretical model and from this first report.

The clinical and fundamental exploration of patients suffering from disorders of consciousness (DoC) is commonly used by researchers both to test some of their key theoretical predictions and to serve as a unique source of empirical knowledge about possible dissociations between consciousness and cognitive and/or neural processes. For instance, the existence of states of vigilance free of any self-reportable subjective experience [e.g. "vegetative state (VS)" and "complex partial epileptic seizure"] originated from DoC and acted as a cornerstone for all theories by dissociating two concepts that were commonly equated and confused: vigilance and conscious state. In the present article, we first expose briefly the major achievements in the exploration and understanding of DoC. We then propose a synthetic taxonomy of DoC, and we finally highlight some current limits, caveats and questions that have to be addressed when using DoC to theorize consciousness. In particular, we show (i) that a purely behavioral approach of DoC is insufficient to characterize the conscious state of patients; (ii) that the comparison between patients in a minimally conscious state (MCS) and patients in a VS [also coined as unresponsive wakefulness syndrome (UWS)] does not correspond to a pure and minimal contrast between unconscious and conscious states and (iii) we emphasize, in the light of original resting-state positron emission tomography data, that behavioral MCS captures an important but misnamed clinical condition that rather corresponds to a cortically mediated state and that MCS does not necessarily imply the preservation of a conscious state.

Key Points Question Can electroencephalography (EEG), combined with clinical, biological, and magnetic resonance imaging (MRI) analyses, help to better characterize patients with neurologic coronavirus disease 2019 (COVID-19) and diagnose specific COVID-19–related encephalopathy? Findings Neurologic manifestations, biological findings, EEG findings, and brain MRI images were analyzed in a cohort study of 78 adult patients with COVID-19. Nine patients had no identified cause of brain injury, as revealed by biological and MRI findings; their injury was defined as COVID-19–related encephalopathy. Meaning This study suggests that, although neurologic manifestations, EEG findings, and MRI findings may appear heterogeneous and nonspecific, multimodal monitoring may better identify patients with COVID-19–related encephalopathy and guide treatment strategy.

Bipolar disorder is associated with an increased risk of dementia with aging. Little is known regarding this association, limiting appropriate diagnosis and management. We aimed to describe the characteristics of bipolar patients with late cognitive impairment for whom the hypothesis of an underlying neurodegenerative disease had been raised. We performed a retrospective multicenter study, recruiting bipolar patients over 50 years old from five French tertiary memory centers who had undergone cerebrospinal fluid (CSF) biomarker assessment for Alzheimer’s disease (AD). Clinical, neuropsychological, and paraclinical characteristics were analyzed and 78 patients were included. The mean age at the onset of cognitive impairment was 62.4 years (±9.2). The mean MMSE score was 22.8 (±4.5), the mean FAB was 11.7 (±3.9), and the mean FCRST was 15.8 (±7.4)/36.8 (±9.7) (free/total recall). A total of 48.6% of the patients displayed cognitive fluctuations, and 38.2% showed cognitive improvement during follow-ups; and 56.3% of the patients showed Parkinsonism, of which 12.7% had never received antipsychotics. Among patients who underwent DAT-scans, 35.3% displayed dopaminergic denervation; 10.3% of patients had CSF AD biological signature (“A+ T+” profile), while 56.4% had other abnormal CSF profiles. Thus, clinical presentation was dominated by executive dysfunction, episodic memory impairment, fluctuating cognition, and a high frequency of Parkinsonism. Specifically, high frequency of delusional episodes suggests limited tolerance of psychotropic drugs. Most patients had abnormal CSF biomarker profiles, but only a minority displayed AD’s specific biomarker signature. Therefore, while our results unveil shared common neurocognitive features in bipolar patients with cognitive impairment of suspected neurodegenerative origin they suggest a participation of various underlying pathologies rather than a common degenerative mechanism in the pathophysiology of this condition.

Les mutations IDH1/2 sont des anomalies moléculaires précoces dans la gliomagénèse, associées à un pronostic plus favorable. Leur perte au cours de la progression tumorale est exceptionnelle. Une femme de 58 ans, se présenta en novembre 2017 pour des troubles cognitifs conduisant à la découverte d'une lésion fronto-calleuse droite rehaussée de façon hétérogène. Une exérèse partielle de la lésion fut réalisée, permettant le diagnostic d'oligodendrogliome anaplasique avec mutation IDH1 et co-délétion 1p/19q. Une chimiothérapie par PCV fut administrée de janvier à juin 2018. En juillet 2019, une récidive tumorale a motivé la réalisation d'une deuxième exérèse. De façon surprenante, l'examen anatomopathologique montrait deux composantes tumorales distinctes : un secteur d'oligodendrogliome de grade II IDH1 muté, associé à des secteurs de glioblastome IDH1 sauvage. Un traitement par radio-chimiothérapie concomitante avec temozolomide fut débuté. Malheureusement, une progression rapide avec le développement de métastases sous-cutanées fut observée conduisant au décès un mois après la fin de la radiothérapie. La perte de mutation « driver » IDH1/2 est un évènement exceptionnel dans l'évolution des gliomes, jamais rapporté dans les oligodendrogliomes. Trois principales hypothèses sont envisagées : (i) la plus probable, perte de mutation IDH1 au sein d'un sous-clone conduisant à l'acquisition de résistance ; (ii) existence d'un clone fondateur IDH1/2 sauvage ayant évolué sous la forme de 2 contingents distincts ; (iii)développement chez la même patiente de 2 gliomes sans lien phylogénétique. L'évolution du profil moléculaire au cours de la progression d'une tumeur est à prendre en compte dans la compréhension des mécanismes de résistance aux traitements, et pour guider au mieux la prise en charge à l'aube de l'ère des thérapies ciblées