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See detailDiagnostic accuracy of a CRS-R modified score in patients with disorders of consciousness.
Annen, Jitka ULiege; Filippini, Maria Maddalena ULiege; Bonin, Estelle ULiege et al

in Brain Injury (2019, March 16)

Introduction The Coma Recovery Scale-Revised (CRS-R) is the gold standard diagnostic tool for assessing patients with disorders of consciousness (DOC) after severe acquired brain injury (Giacino, Kalmar ... [more ▼]

Introduction The Coma Recovery Scale-Revised (CRS-R) is the gold standard diagnostic tool for assessing patients with disorders of consciousness (DOC) after severe acquired brain injury (Giacino, Kalmar and Whyte, 2004; Seel et al., 2010). Differential diagnosis of DOC includes the unresponsive wakefulness syndrome (UWS;(Laureys et al., 2010)), characterized by the recovery of eye-opening but no behavioral evidence of self or environmental awareness, and the minimally conscious state (MCS; (Giacino et al., 2002)) defined by clearly discernible but inconsistent behavioral signs of conscious awareness. The CRS-R assesses reflexes and cognitively mediated behavior in six domains, namely auditory (4 items), visual (5 items), motor (6 items), oromotor (3 items), communication (2 items) and arousal (3 items). Items in every subscale are hierarchically ordered (i.e. reflexive to cognitively-mediated behaviors; higher level behaviors correspond to higher level of neurologic functioning and ability to demonstrate lower-level behaviors or disappearance of pathological behaviors as sign of recovery) and can be used to infer the patient’s level of consciousness (La Porta et al., 2013; Gerrard, Zafonte and Giacino, 2014). Several studies on DOC investigating markers of consciousness, recovery and treatment used the CRS-R total score (i.e. addition of the highest scores reached for each subscale) as regressor in neuroimaging analyses (Bruno et al., 2012; Thibaut et al., 2012; Margetis et al., 2014; Bagnato et al., 2015). However, ignoring the hierarchy of the subscales in the CRS-R total score reduces the sensitivity for the diagnosis of MCS patients (i.e., 100% specificity for UWS but false negative diagnostic error of 22%, with a cut-off CRS-R total score of 10 (Bodien et al., 2016)). In addition, the ordinal nature of the CRS-R total score make it limited to use with parametric statistical tests (e.g., requiring normal distribution). A solution to this problem has been proposed by Sattin and colleagues (2015) who computed a CRS-R modified score (CRS-R MS1), by considering reflexes and cognitively mediated behaviors separately, reliably distinguishing between UWS and MCS patients. These authors also argue that the interpretation of the total CRS-R scores is limited due to “the underlying assumption that if a patient is able to show higher-level behaviors, he/she is also able to show lower-level responses”. Sattin et al. (2015) propose to account for the number of presented responses in every subscale (i.e., every items in a subscale should be assessed and scored). One major drawback to this approach is that according to the CRS-R guidelines, the assessor should start assessing the highest item and move to the next subscale once an item is scored, in line with the hierarchical organization of the scale. This means that, if the CRS-R is performed according to the guidelines (for which the CRS-R has been validated), the CRS-R modified score cannot be calculated. Even if assessing all items might be valid, it is unlikely to be done in many clinical and research settings as it would increase assessment time and fatigue the patient. We here propose to adapt the CRS-R MS1 by considering only the highest score reached on every subscale, respecting the CRS-R guidelines. Methods One-hundred twenty-four patients admitted to the University Hospital of Liège were assessed multiple times with the CRS-R, at least once including the assessment of all items. Patients for whom the CRS-R assessment including all items provided the same diagnosis as the patient’s final diagnosis were selected. The study was approved by the ethics committee of the University Hospital of Liège and the legal guardians of patients gave written informed consent for participation in the study, in accordance with the Declaration of Helsinki. The CRS-R total score and two CRS-R MS were calculated for every patient. The CRS-R MS combines scores for reflexes and cognitive behaviors of every CRS-R subscale which can be used to obtain the CSR-R MS from a transposition matrix. The CRS-R MS1 was calculated as previously described (Sattin et al., 2015), and the CRS-R MS2 only used the highest score in every subscale (i.e., assuming that lower items were successful). Statistics were performed in R (R Core team, 2012). We assessed group differences in age (two sample t-test), time since injury (two sample t-test) and etiology (χ2 test). Receiver Operating Characteristic were calculated to obtain the sensitivity and specificity at several classification thresholds (package pROC (Robin et al., 2011)). We calculated the correlation between the CRSR MS1 and CRSR MS2 using Pearson correlation, and both scores with the CRS-R total score using Spearman correlation. Finally, we used a Kolmogorov-Smirnoff test to evaluate whether CRSR MS1 and CRSR MS2 come from different distributions (i.e., if one approach provides additional information over the other). Results Eighty-five MCS patients (26 females; mean age 40.4 (SD±17.4) years old; 43 traumatic; mean time since injury 2.7 (SD±4.0) years) and 39 UWS patients (14 females; mean age 50.6 (SD±16.5) years old; 29 traumatic; mean time since injury 1.2 (SD±1.8) years) were included in the study. MCS patients were older (t(77.6)-3.15, p<0.002 95%CI[-16.7, -3.7]), were in a more chronic stage (t(121.9)=2.9, p = 0.005, 95%CI[974,427]), and suffered more often from a traumatic brain injury (χ2=6.8, p = 0.01) than UWS patients. The ROC analysis for both MS showed an AUC of 1 (cut-off:8.315, 100% specificity and sensitivity). The ROC analysis for the CRS-R total score showed an AUC of 0.94 (cut-off:9, sensitivity = 100%, specificity = 67%). A correlation was found between the CRSR total score and both the CRSR MS1 (r = 0.94, p < 0.0001, figure 1A) and CRSR MS2 (r = 0.96, p < 0.0001, figure 1B). The two CRS-R MS correlated (r = 0.96, p = 0.0001, figure 1C). CRSR MS1 and CRSR MS2 were drawn from the same distribution (D(124)= 0.13, p = 0.25). Discussion CRSR MS2 correlated strongly with the CRSR MS1, and perfectly discriminated UWS from MCS patients. As for accurate diagnosis the CRS-R should be repeated (preferably five times (Wannez et al., 2018)) short assessments are preferred, and possibly also reduce effects of fatigue. Second, the CRSR MS2 can be calculated with CRS-R assessments performed according to the CRS-R guidelines, facilitating its use in clinical environments, and in research settings where CRSR MS2 can be used pro- and retrospectively for research protocols. Furthermore, the results indicate that the two modified scores share the same distribution. This suggests that assessing all CRS-R items as proposed previously does not significantly contribute to the stratification of patients. The CRSR MS2 code is available via: Github A remaining limitation of the proposed score is that it does not allow to distinguish MCS minus (i.e. showing language independent signs of awareness, like visual pursuit) from MCS plus (i.e. showing language dependent signs of awareness) patients, or emergence from MCS. However, a clear consensus about the diagnostic criteria is needed before an updated modified score can be provided. In conclusion, the current analyses show that the calculation of the CRS-R modified score using the highest item in every subscale is valid for clinical diagnosis, and provides perspective for its use for research. Figure Figure 1. Correlation between the CRS-R total score and the CRS-R MS1 (1A), CRSR MS2 (1B), and between the two modified CRS-R scores (1C). MCS plus patients are here characterized by command following, intelligible verbalization and/or intentional communication. Acknowledgements This project has received funding from the University and University Hospital of Liege, the Belgian National Funds for Scientific Research (FRS-FNRS), the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2) the Luminous project (EU-H2020-fetopenga686764), the Center-TBI project (FP7-HEALTH- 602150), the Public Utility Foundation ‘Université Européenne du Travail’, “Fondazione Europea di Ricerca Biomedica”, the Bial Foundation, the Mind Science Foundation and the European Commission, the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 778234, European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) for their support in the framework of the PRODEX Programme. CC is a post-doctoral Marie Sklodowska-Curie fellow (H2020-MSCA-IF-2016-ADOC-752686), and SL is research director at FRS-FNRS. We are highly grateful to the members of the Liège Coma Science Group for their assistance in clinical evaluations, and we thank all the patients and their families and the Neurology department of the University hospital of Liège. [less ▲]

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See detailInternational validation of the Phone Outcome Questionnaire for patients with Disorders Of Consciousness
Wolff, Audrey ULiege; Estraneo, Anna; Noé, Quique et al

Poster (2019, March 15)

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the ... [more ▼]

Assessing the evolution of severely brain-injured patients with disorders of consciousness (DOC) with current tools like the Glasgow Outcome Scale-Extended (GOS-E) remains a challenge. At the bedside, the most reliable diagnostic tool is currently the Coma Recovery Scale-Revised. The CRS-R distinguishes patients with unresponsive wakefulness syndrome (UWS) from patients in minimally conscious state (MCS) and patients who have emerged from MCS (EMCS). This international multi-centric study aims to validate a phone outcome questionnaire (POQ) based on the CRS-R and compare it to the CRS-R performed at the bedside and to the GOS-E which evaluates the level of disability and assigns patient’s in outcomes categories. The POQ will allow clinicians to probe the evolution of patient’s state of consciousness based on caregivers feedback. This research project is part of the International Brain Injury Association, Disorders of Consciousness-Special Interest Group (DOCSIG) and DOCMA consortium. [less ▲]

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See detailA comparison of the P300 and PET in patients with disorders of consciousness in absence of response to command
Annen, Jitka ULiege; Wolff, Audrey ULiege; Blandiaux, Séverine ULiege et al

in European Journal of Neurology (2018, June), 25(S2),

Detection and interpretation of signs of "covert command following" in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in ... [more ▼]

Detection and interpretation of signs of "covert command following" in patients with disorders of consciousness (DOC) remains a challenge for clinicians. In this study, we used a tactile P3-based BCI in 12 patients without behavioral command following, attempting to establish "covert command following." These results were then confronted to cerebral metabolism preservation as measured with glucose PET (FDG-PET). One patient showed "covert command following" (i.e., above-threshold BCI performance) during the active tactile paradigm. This patient also showed a higher cerebral glucose metabolism within the language network (presumably required for command following) when compared with the other patients without "covert command-following" but having a cerebral glucose metabolism indicative of minimally conscious state. Our results suggest that the P3-based BCI might probe "covert command following" in patients without behavioral response to command and therefore could be a valuable addition in the clinical assessment of patients with DOC. [less ▲]

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See detailPCI & Auditory ERPs for the diagnosis of disorders of consciousness: a EEG-based methods comparison study
Blandiaux, Séverine ULiege; Raimondo, Federico ULiege; Wolff, Audrey ULiege et al

in European Journal of Neurology (2018, June), 25(S2),

INTRODUCTION Diagnosing the level of consciousness in patients suffering from severe brain lesions is still a major challenge. EEG-based systems can help discriminate conscious from unconscious patients ... [more ▼]

INTRODUCTION Diagnosing the level of consciousness in patients suffering from severe brain lesions is still a major challenge. EEG-based systems can help discriminate conscious from unconscious patients. This study aims to confront the results from two of the most reliable methods: the Perturbational Complexity Index (PCI) which is based on Transcranial Magnetic Stimulation (TMS-EEG), and a recent machine learning approach using EEG-extracted markers from a standardized oddball auditory stimulation paradigm (EEG-ERP). METHODS Patients presenting either an unresponsive wakefulness syndrome (UWS), a minimally conscious state (MCS) or an emergence of MCS (EMCS) underwent both TMS-EEG and EEG-ERP. We computed PCI value by compressing the spatiotemporal pattern of cortical responses to the perturbation of the cortex with TMS. For EEG-ERP, we extracted 60 markers corresponding to quantification of power spectrum and complexity in individual EEG sensors and information sharing between them. Using machine-learning, we predicted the individual probability of being (minimally) conscious. RESULTS PCI and EEG markers, when considered categorically (i.e. UWS vs MCS), were consistent for all UWS and EMCS patients, whereas the results for MCS patients showed less consistency. Nevertheless, we found a significant correlation between PCI values and the probability of being conscious with the multivariate classifier. CONCLUSION PCI correlated positively with the combination of EEG markers in severely brain-injured patients. These findings imply that EEG signatures of consciousness can be reliably extracted from different contexts and combined into coherent predictive models, encouraging future efforts in large-scale data-driven clinical neuroscience. [less ▲]

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See detailEvaluations comportementales chez les patients en état de conscience altérée
Wolff, Audrey ULiege; Blandiaux, Séverine ULiege; Cassol, Helena ULiege et al

in Jourdan, C; Pellas, F; Luauté, J (Eds.) et al Etats de conscience altérée - Actualités diagnostiques, pronostiques et thérapeutiques (2018)

A l’heure actuelle, l’évaluation de la conscience chez les patients sortant du coma reste un challenge car elle ne peut directement s’observer et être quantifiée, comme peuvent l’être par exemple le poids ... [more ▼]

A l’heure actuelle, l’évaluation de la conscience chez les patients sortant du coma reste un challenge car elle ne peut directement s’observer et être quantifiée, comme peuvent l’être par exemple le poids ou la taille. Le diagnostic des états de conscience altérés doit donc se baser une évaluation indirecte, et seulement sur ce qui est observable. Les évaluations comportementales restent encore à l’heure actuelle le gold standard pour les cliniciens et des études récentes ont mis en avant la nécessité d’utiliser des outils d’évaluation standardisés. Dans ce chapitre, nous aborderons brièvement quatre échelles utilisées régulièrement dans la pratique clinique en développant plus en profondeur la Coma Recovery Scale – Revised. Le but ici est de donner une vue globale des différentes échelles ainsi que d’apporter quelques recommandations pratiques quant à la réalisation des évaluations comportementales. [less ▲]

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See detailThe limits of consciousness
Wolff, Audrey ULiege

Scientific conference (2018, March 17)

Consciousness is essential for one’s normal functioning, including targeted interactions with the surrounding world and with other human beings. At present, many theories and definitions of consciousness ... [more ▼]

Consciousness is essential for one’s normal functioning, including targeted interactions with the surrounding world and with other human beings. At present, many theories and definitions of consciousness coexist, the focus of which can be on the philosophical discourse on consciousness, the clinical observation of consciousness, or the scientific understanding of consciousness through advanced imaging techniques. Discussions relating to whether consciousness is located in the brain, if it is created within certain neural networks or whether it transits throught he brain without being part of it are ongoing. Despite the variation in definitions and theories of consciousness, there is a wide consensus on the essentiality of wakefulness and awareness for consciousness. A lot of the patients in a coma will not survive, and the ones who recover will generally go through different altered states of consciousness. Some will fully regain consciousness; others will never come out of this state. Clinicians are facing every day the complex challenge of diagnosing those patients and help families to make choices about the future of the patient, notably concerning end of life decisions. The rate of misdiagnosis is still high for patients with disorders of consciousness and we still encounter misdiagnosed brain-dead patients. A number of ethical issues are raised by that non-communicative vulnerable population as for example the importance of a reliable diagnosis for the life sustaining treatments. Some patients having been considered as clinically dead or having lived close brushed with death will report perceptual experiences known as “Near-Death Experience” (NDE). There are only a few studies that describe that phenomenon, but most of the NDE experiencers describe it as a positive moment. NDEs are significantly changing NDE experiencers, their identity and their relationship to death. Death and consciousness are intertwined concepts that are hardly dissociable for clinicians in their practice. What are limits of consciousness and how those limits are linked to death. Anyway, the only life after death that we have proof of is the organ donation. [less ▲]

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See detailFluctuation in behavioral responsiveness in severely brain-injured patients
Chatelle, Camille ULiege; Thibaut, Aurore ULiege; Gosseries, Olivia ULiege et al

in European Journal of Neurology (2018), 25(2), 90276

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See detailConscience et états de conscience altérée
Cassol, Helena ULiege; Wolff, Audrey ULiege; Chatelle, Camille ULiege et al

in Jourdan, C; Pellas, F; Luauté, J (Eds.) et al Etats de conscience altérée (2018)

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See detailCircadian and ultradian rhythmicity in patients with disorders of consciousness
Camargo Fernandez Baca, Aldo ULiege; Blandiaux, Séverine ULiege; Piarulli, Andrea ULiege et al

in European Academy of Neurology (2018), 25(S2),

Background and aims: The Unresponsive Wakefulness Syndrome and Minimally Conscious State (UWS; MCS) are characterized by the absence or the presence but severe disordered signs of consciousness in spite ... [more ▼]

Background and aims: The Unresponsive Wakefulness Syndrome and Minimally Conscious State (UWS; MCS) are characterized by the absence or the presence but severe disordered signs of consciousness in spite of the presence of preserved sleep-wake cycles. Spectral entropy has used to find periodicity on EEG signals of DOC (disorders of consciousness) patients. Circadian and ultradian are fisiological rhythmits found in all living organisms. Methods: We used data from 126 patients (controls, EMCS, LIS, MCS, MCS+, MCS-, MCS*, and UWS). We recorded the movements on the wrist for 7 consecutive days, then we use average 5 complete days in 24 hours to compute the circadian rhythmicity and in 120 min to compute the ultradian rhythmicity. Spectral entropy is used to compute to find the signficant diffference inthe amplitude of the movements and its periodicity (spectral amplitude) is used to find the rhythmicity. Results: We have found a circadian rhythmicity in DOC patients within 18 hours in average and and ultradian rhythmicity between 40 to 80 min. Conclusion: The actigraphy can give useful information about the circadian and ultradian rhytmicity in DOC patients. [less ▲]

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See detailEvaluation de la douleur chez le patient cérébrolésé en état de conscience altérée
Martens, Géraldine ULiege; Blandiaux, Séverine ULiege; Wolff, Audrey ULiege et al

in Jourdan, C; Pellas, F; Luauté, J (Eds.) et al Etats de conscience altérée (2018)

La douleur se définit comme une “expérience sensorielle et émotionnelle désagréable associée à un dommage tissulaire potentiel ou réel” [1]. La douleur est donc une expérience subjective négative ... [more ▼]

La douleur se définit comme une “expérience sensorielle et émotionnelle désagréable associée à un dommage tissulaire potentiel ou réel” [1]. La douleur est donc une expérience subjective négative consciente. La nociception, quant à elle, correspond au “processus neuronal de codage des stimuli nociceptifs ( traduit et codé par les nocicepteurs)” et n’engendre pas nécessairement de la douleur. Certaines conditions, comme l’état de conscience altérée (ECA), peuvent entraver une évaluation optimale de la douleur. Néanmoins, l’évaluation de cette douleur est un élément important de la prise en charge clinique ainsi que du diagnostic, puisque le simple fait de ne pas pouvoir communiquer verbalement ne peut écarter la possibilité qu’un individu présente des douleurs [2]. De plus, de nombreuses situations en phase aigüe (mise en place d’un cathéter, polytraumatisme, etc.) ou chronique (présence de spasticité, d’escarres, etc.) peuvent être des sources potentielles de douleur pour les patients en ECA, celles-ci pouvant alors entraver la rééducation et diminuer leur qualité de vie [3]. Bien que nous ne puissions pas utiliser le compte rendu subjectif du patient non communicant, les outils dont nous disposons actuellement nous permettent malgré tout d’étudier ce qui se passe au niveau cérébral en réponse à des stimulations potentiellement douloureuses, ce qui nous permet de mieux comprendre et de tenter d’inférer la présence de douleur potentielle chez ces patients. Par ailleurs, nous pouvons également observer les réponses du patient à son chevet, comme pratiqué avec d’autres populations non communicantes telles que les patients déments et les nouveau-nés. Ce chapitre tentera d’apporter des clés permettant de mieux appréhender et gérer les signes de douleurs potentielles chez ces patients, sur la base des études de neuro-imagerie et des instruments cliniques disponibles. [less ▲]

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See detailThe challenges of research integrity
Wolff, Audrey ULiege

Scientific conference (2017, November 22)

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See detailEvaluation multimodale de patients en état de conscience altérée
Cassol, Helena ULiege; Wolff, Audrey ULiege

Conference (2017, November 09)

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