Améliorer le diagnostic des patients en état de conscience altérée: une approche comportementale

Le diagnostic des patients ayant survécu à de graves lésions cérébrales et se trouvant en état de conscience altérée est un véritable défi, pour diverses raisons éthiques et médicales. Pour situer le patient sur le continuum entre le coma et l’émergence de l’état de conscience minimale, le premier outil dont disposent cliniciens et chercheurs est l’évaluation clinique. Le but de la présente thèse est d’apporter des améliorations substantielles à ce niveau, et de fournir des recommandations pragmatiques pour les évaluations comportementales. Un premier volet concerne la Coma Recovery Scale-Revised, l’échelle la plus adaptée et largement recommandée pour évaluer les patients en état de conscience altérée. Nous avons mis en évidence que, comme suggéré dans la littérature, l’état des patients fluctuait, et que la répétition des évaluations était nécessaire. Cinq évaluations sur un court laps de temps (10 jours) permettaient d’obtenir un diagnostic fiable. Nous avons également montré que certains items de la Coma Recovery Scale-Revised étaient plus fréquemment observés, à savoir le mouvement sur demande, la poursuite visuelle, la fixation, la réaction motrice automatique et la localisation des stimulations nociceptives. Par ailleurs, une évaluation réduite aux cinq items les plus fréquents pouvait détecter 99% des patients en état de conscience minimale. Le deuxième volet de la thèse s’est concentré sur l’évaluation d’un de ces items fréquents : la poursuite visuelle. Nous avons défini des recommandations claires sur le stimulus à utiliser et les axes à évaluer : le miroir s’est indéniablement révélé être le plus efficace, comme déjà suggéré, mais aucune supériorité absolue d’un axe n’a été mise en évidence. Nous avons investigué la raison de l’efficacité du miroir, jusqu’alors considérée comme due à l’aspect autoréférentiel. Nous avons montré que l’utilisation d’unxiv Résuméstimulus purement autoréférentiel (photo du visage du patient) ne permettait pas d’atteindre la même efficacité que le miroir, suggérant que les caractéristiques physiques du miroir (brillance et dynamisme) intervenaient dans l’attirance pour le miroir. Cependant, un stimulus aussi brillant et dynamique mais sans reflet du propre visage ne se révélait pas parfaitement aussi efficace qu’un miroir. Ces résultats suggéraient que le miroir était efficace grâce à la combinaison de ces différents aspects, et non uniquement parce qu’il s’agissait du propre visage. De façon générale, les études sur la poursuite visuelle souffraient toujours d’un manque de mesures objectives, et nous avons cherché un moyen de pallier à cela. Après avoir enregistré les mouvements oculaires et le déplacement du miroir devant le visage du patient, nous avons entraîné une machine à correctement classer chaque mouvement comme étant suivi ou non. La référence était définie par trois experts qui avaient scoré les vidéos de poursuite visuelle. Nous avons également montré que l’évaluation au chevet du patient se révélait erronée pour environ 10% des patients, confirmant bien le besoin de mesures objectives de la poursuite visuelle

Resistance to eye opening in patients with disorders of consciousness

Introduction: Resistance to eye opening (REO) is a commonly encountered phenomenon in clinical practice. We aim to investigate whether REO is a sign of consciousness or a reflex in severely brain-injured patients. Methods: We recorded REO in chronic patients with disorders of consciousness during a multimodal diagnostic assessment. REO evaluations were performed daily in each patient and clinical diagnosis of unresponsive wakefulness syndrome (UWS), minimally conscious state with (MCS+) or without (MCS−) preserved language processing was made using the Coma Recovery Scale-Revised (CRS-R). Results: Out of 150 consecutive patients, 79 patients fit inclusion criteria. REO was seen in 19 patients (24.1%). At the group level, there was a significant relationship between the presence of REO and the level of consciousness. We also observed a difference in the repeatability of REO between patients in UWS, MCS− and MCS+. Out of 23 patients in UWS, six showed REO, in whom five showed atypical brain patterns activation. Conclusion: Our findings suggest a voluntary basis for REO and stress the need for multiple serial assessments of REO in these patients, especially since most patients show fluctuating levels of consciousness. © 2018 Springer-Verlag GmbH Germany, part of Springer Natur

Resting-state functional connectivity and cortical thickness characterization of a patient with Charles Bonnet syndrome

Charles Bonnet syndrome (CBS) is a rare condition characterized by visual impairment associated with complex visual hallucinations in elderly people. Although studies suggested that visual hallucinations may be caused by brain damage in the visual system in CBS patients, alterations in specific brain regions in the occipital cortex have not been studied. Functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI; without hallucinations) in CBS patients, has never been explored. We aimed to investigate brain structural and functional changes in a patient with CBS, as compared with late blind (LB) and normally sighted subjects. We employed voxel-based morphometry and cortical thickness analyses to investigate alterations in grey matter characteristics, and rs-fMRI to study changes in functional brain connectivity. Decreased grey matter volume was observed in the middle occipital gyrus and in the cuneus in the CBS patient and in the middle occipital gyrus and in the lingual gyrus within LB subjects, compared to their respective control groups. Reductions in cortical thickness in associative and multimodal cortices were observed in the CBS patient when comparing with LB subjects. The precuneus exhibited increased functional connectivity with the secondary visual cortex in the CBS patient compared to the controls. In contrast, LB patients showed decreased functional connectivity compared to sighted controls between the DMN and the temporo-occipital fusiform gyrus, a region known to support hallucinations. Our findings suggest a reorganization of the functional connectivity between regions involved in self-awareness and in visual and salience processing in CBS that may contribute to the appearance of visual hallucinations

Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness

peer reviewedRecent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behavioural consciousness with accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly with brain metabolism. Further, with classification analysis, we predict the behavioural diagnosis, brain metabolism and 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments of brain networks show robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of their brain network identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at the bedside in the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported in these patients. These metrics could also identify patients in whom further assessment is warranted using neuroimaging or conventional clinical evaluation. Finally, by providing objective characterization of states of consciousness, repeated assessments of network metrics could help track individual patients longitudinally, and also assess their neural responses to therapeutic and pharmacological interventions

Global structural integrity and effective connectivity in patients with disorders of consciousness

peer reviewedBackground Previous studies have separately reported impaired functional, structural, and effective connectivity in patients with disorders of consciousness (DOC). The perturbational complexity index (PCI) is a transcranial magnetic stimulation (TMS) derived marker of effective connectivity. The global fractional anisotropy (FA) is a marker of structural integrity. Little is known about how these parameters are related to each other. Objective We aimed at testing the relationship between structural integrity and effective connectivity. Methods We assessed 23 patients with severe brain injury more than 4 weeks post-onset, leading to DOC or locked-in syndrome, and 14 healthy subjects. We calculated PCI using repeated single pulse TMS coupled with high-density electroencephalography, and used it as a surrogate of effective connectivity. Structural integrity was measured using the global FA, derived from diffusion weighted imaging. We used linear regression modelling to test our hypothesis, and computed the correlation between PCI and FA in different groups. Results Global FA could predict 74% of PCI variance in the whole sample and 56% in the patients' group. No other predictors (age, gender, time since onset, behavioural score) improved the models. FA and PCI were correlated in the whole population (r = 0.86, p < 0.0001), the patients, and the healthy subjects subgroups. Conclusion We here demonstrated that effective connectivity correlates with structural integrity in brain-injured patients. Increased structural damage level decreases effective connectivity, which could prevent the emergence of consciousness