References of "Chatelle, Camille"
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See detailNociception Coma Scale Revised allows to identify patients with preserved neural basis for pain experience
Bonin, Estelle ULiege; Lejeune, Nicolas ULiege; Thibaut, Aurore ULiege et al

in Journal of Pain (in press)

The Nociception Coma Scale-Revised (NCS-R) was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute ... [more ▼]

The Nociception Coma Scale-Revised (NCS-R) was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute noxious stimuli. However, they failed to determine a reliable cut-off score that could be used to infer pain processing in these patients. This retrospective cross-sectional study aimed to determine a NCS-R cut-off score supporting preserved neural basis for pain experience, based on brain metabolism preservation as measured by fluorodeoxyglucose positron emission tomography (FDG-PET). We included patients in unresponsive wakefulness syndrome (UWS) confirmed by the FDG-PET and examined the NCS-R total scores. As the highest score was 4, we defined the cut-off to be 5 and compared the brain metabolism of these patients to matched patients with DOC and a NCS-R cut-off score ≥ 5 (i.e., potential pain), as well as healthy subjects. We found a higher global cerebral metabolism in healthy subjects compared to both patient groups and also in patients with potential pain compared with FDG-PET confirmed UWS. We observed a preserved metabolism in the left insula in patients with potential pain compared with FDG-PET confirmed UWS. [less ▲]

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See detailÉtats de conscience altérée: soins palliatifs et décisions de fin de vie
Lejeune, Nicolas ULiege; van Erp, Willemijn ULiege; Rohaut, Benjamin et al

in Jacquemin, Dominique; De Broucker, Didier (Eds.) Manuel de soins palliatifs (in press)

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See detailBrain metabolism but not grey matter volume underlies the presence of language function in the minimally conscious state
Aubinet, Charlène ULiege; Cassol, Helena ULiege; Gosseries, Olivia ULiege et al

in Neurorehabilitation and Neural Repair (2020), 34(2), 172-184

Background. The minimally conscious state (MCS) is subcategorized into MCS- and MCS+, depending on the absence or presence of high-level behavioral responses such as command following. Objective. We aim ... [more ▼]

Background. The minimally conscious state (MCS) is subcategorized into MCS- and MCS+, depending on the absence or presence of high-level behavioral responses such as command following. Objective. We aim to investigate the functional and structural neuroanatomy underlying the presence of these responses in MCS- and MCS+ patients. Methods. In this cross-sectional retrospective study, chronic MCS patients were diagnosed using repeated Coma Recovery Scale-Revised assessments. Fluorodeoxyglucose-positron emission tomography data were acquired on 57 patients (16 MCS-; 41 MCS+) and magnetic resonance imaging with voxel-based morphometry analysis was performed on 66 patients (17 MCS-; 49 MCS+). Brain glucose metabolism and grey matter integrity were compared between patient groups and control groups. A metabolic functional connectivity analysis testing the hypothesis of preserved language network in MCS+ compared to MCS- was also done. Results. Patients in MCS+ presented higher metabolism mainly in the left middle temporal cortex, known to be important for semantic processing, compared to the MCS- group. The left angular gyrus was also functionally disconnected from the left prefrontal cortex in MCS- compared to MCS+. No significant differences were found in grey matter volume between patient groups. Conclusions. The clinical sub-categorization of MCS is supported by differences in brain metabolism but not in grey matter structure, suggesting that brain function in the language network is the main support for recovery of command-following, intelligible verbalization and/or intentional communication in the MCS. Better characterizing the neural correlates of residual cognitive abilities of MCS patients contributes to reduce their misdiagnosis and to adapt therapeutic approaches. [less ▲]

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See detailEEG Correlates of Language Function in Traumatic Disorders of Consciousness
Chatelle, Camille ULiege; Rosenthal, E. S.; Bodien, Y. G. et al

in Neurocritical Care (2020)

Background/Objective: Behavioral examinations may fail to detect language function in patients with severe traumatic brain injury (TBI) due to confounds such as having an endotracheal tube. We ... [more ▼]

Background/Objective: Behavioral examinations may fail to detect language function in patients with severe traumatic brain injury (TBI) due to confounds such as having an endotracheal tube. We investigated whether resting and stimulus-evoked electroencephalography (EEG) methods detect the presence of language function in patients with severe TBI. Methods: Four EEG measures were assessed: (1) resting background (applying Forgacs’ criteria), (2) reactivity to speech, (3) background and reactivity (applying Synek’s criteria); and (4) an automated support vector machine (classifier for speech versus rest). Cohen’s kappa measured agreement between the four EEG measures and evidence of language function on a behavioral coma recovery scale-revised (CRS-R) and composite (CRS-R or functional MRI) reference standard. Sensitivity and specificity of each EEG measure were calculated against the reference standards. Results: We enrolled 17 adult patients with severe TBI (mean ± SD age 27.0 ± 7.0 years; median [range] 11.5 [2–1173] days post-injury) and 16 healthy subjects (age 28.5 ± 7.8 years). The classifier, followed by Forgacs’ criteria for resting background, demonstrated the highest agreement with the behavioral reference standard. Only Synek’s criteria for background and reactivity showed significant agreement with the composite reference standard. The classifier and resting background showed balanced sensitivity and specificity for behavioral (sensitivity = 84.6% and 80.8%; specificity = 57.1% for both) and composite reference standards (sensitivity = 79.3% and 75.9%, specificity = 50% for both). Conclusions: Methods applying an automated classifier, resting background, or resting background with reactivity may identify severe TBI patients with preserved language function. Automated classifier methods may enable unbiased and efficient assessment of larger populations or serial timepoints, while qualitative visual methods may be practical in community settings. © 2020, Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society. [less ▲]

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See detailCan the Nociception Coma Scale-Revised be used in patients with a tracheostomy?
Lejeune, Nicolas ULiege; Thibaut, Aurore ULiege; Martens, Géraldine ULiege et al

in Archives of Physical Medicine and Rehabilitation (2020)

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See detailÉvaluation clinique des états de conscience altérée: quelle échelle utiliser ?
Bonin, Estelle ULiege; Wolff, Audrey ULiege; Sanz, Leandro ULiege et al

in Lettre du Neurologue: le Courrier du Spécialiste (2019), XXIII(7), 253-254

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See detailGeneral Anesthesia: A Probe to Explore Consciousness
BONHOMME, Vincent ULiege; STAQUET, Cécile ULiege; Montupil, Javier ULiege et al

in Frontiers in Systems Neuroscience (2019)

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

in Brain Injury (2019), 33(11), 1409-1412

Objective: To obtain a CRS-R index suitable for diagnosis of patients with disorders of consciousness (DOC) and compare it to other CRS-R based scores to evaluate its potential for clinics and research ... [more ▼]

Objective: To obtain a CRS-R index suitable for diagnosis of patients with disorders of consciousness (DOC) and compare it to other CRS-R based scores to evaluate its potential for clinics and research. Design: We evaluated the diagnostic accuracy of several CRS-R-based scores in 124 patients with DOC. ROC analysis of the CRS-R total score, the Rasch-based CRS-R score, CRS-R-MS and the CRS-R index evaluated the diagnostic accuracy for patients with the Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS). Correlations were computed between the CRS-R-MS, CRS-R index, the Rasch-based score and the CRS-R total score. Results: Both the CRS-R-MS and CRS-R index ranged from 0 to 100, with a cut-off of 8.315 that perfectly distinguishes between patients with UWS and MCS. The CRS-R total score and Rasch-based score did not provide a cut-off score for patients with UWS and MCS. The proposed CRS-R index correlated with the CRS-R total score, Rasch-based score and the CRS-R-MS. Conclusion: The CRS-R index is reliable to diagnose patients with UWS and MCS and can be used in compliance with the CRS-R scoring guidelines. The obtained index offers the opportunity to improve the interpretation of clinical assessment and can be used in (longitudinal) research protocols. [less ▲]

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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

Conference (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 detailIs auditory localization a sign of consciousness? Evidence from neuroimaging and electrophysiology
Carrière, Manon ULiege; Cassol, Helena ULiege; Aubinet, Charlène ULiege et al

Conference (2019, March 16)

Background Auditory localization is often part of the clinical evaluation of patients recovering from coma. There is however no clear consensus whether it should be considered as a reflex or as a ... [more ▼]

Background Auditory localization is often part of the clinical evaluation of patients recovering from coma. There is however no clear consensus whether it should be considered as a reflex or as a conscious behavior. For example, auditory localisation corresponds to the diagnosis of unresponsive wakefulness syndrome (UWS) in the Coma Recovery Scale-Revised, while it is considered a sign of consciousness in other post-coma scales. This study aims to determine if auditory localization reflects conscious processing in patients with disorders of consciousness. Methods We first evaluated the proportion of patients with and without auditory localisation in 186 patients with severe brain injury, including 64 UWS, 28 minimally conscious minus (MCS-), 71 minimally conscious plus (MCS+), i.e., language relatively preserved) and 23 who emerged from MCS (EMCS). We then measured brain metabolism using fluorine-18 fluorodeoxyglucose positron emission tomography, functional connectivity using magnetic resonance imaging (MRI) and high-density electroencephalography (EEG) in patients in UWS with and without auditory localization. Findings Auditory localization was observed in 12% of patients in UWS, 46% of patients in MCS-, 62% of patients in MCS+ and 78% of patients in EMCS. Brain metabolism of patients in UWS without auditory localization was mostly restricted to primary areas, whereas a more widespread activity, including associative areas, was observed in patients in UWS with auditory localisation. Brain functional connectivity was also higher in patients in UWS with auditory localisation in the frontoparietal fMRI resting state network, along with higher EEG connectivity in alpha frequency band, compared to patients without auditory localization. Finally, differences were also found regarding the outcome, as the survival rate at two years appeared to be significantly higher in UWS patients with auditory localization as compared to those without auditory localization. Interpretation. Both clinical data in post-comatose patients and neuroimaging examinations in UWS patients with and without auditory localization support the idea that auditory localization should be considered as a sign of consciousness. [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 detailPupil diameter and Behavioral Responsiveness in Disorders of Consciousness
Mortaheb, Sepehr ULiege; Bonin, Estelle ULiege; Laureys, Steven ULiege et al

Poster (2019, March 15)

The clinical diagnosis of consciousness is mainly based on bedside observation of the patient's responses using standardized neurobehavioral scales. By definition, it is common to observe vigilance ... [more ▼]

The clinical diagnosis of consciousness is mainly based on bedside observation of the patient's responses using standardized neurobehavioral scales. By definition, it is common to observe vigilance fluctuation in patients in minimally conscious state (MCS) who would show reproducible but fluctuating signs of consciousness [1]. As the probability to detect voluntary responses depends on the patient's level of vigilance at the time of assessment, multiple assessments are needed in order to detect signs of consciousness and avoid misdiagnosis [2]. If this fluctuation is known in disorders of consciousness (DOC), it remains poorly understood and characterized. In this study, we investigated the relationship between pupil diameter (suggested as an objective physiological measure of alertness level in healthy subjects [3-6]) and behavioral responsiveness in DOC patients. To this end, five patients with chronic DOC (1 unresponsive wakefulness syndrome [UWS; ie, reflexive responses], 2 MCS- [ie, signs of consciousness but no signs of language preservation, 2 MCS+ [ie, signs of language preservation]; 3 males; age=47±15.16 (median ± SD), median TSI=284 days) were enrolled. For each patient, four behavioral assessments were performed in a single day using the Coma Recovery Scale-Revised. Before each assessment, pupil response was recorded for 10 minuttients (MCS-) was excluded from the analysis due to eye closure during whole recording period. Pupil diameter was recorded using Phasya Drowsimeter R100 glasses (eye images acquired at 120 Hz with a high-speed camera integrated into the glasses). Eye closure periods were marked manually. Several parameters were investigated: eye opening percentage (EOP), as well as median, variance, entropy, and Lempel-Ziv complexity of the pupil diameter. We here provide preliminary descriptive results for this small sample. We observed lower EOP and median pupil diameter when the patients were unresponsive (i.e., diagnosis of UWS) vs. when they were responsive at bedside (i.e., MCS; median EOP=74.78% vs 99.6%, median pupil diameter=21 vs 28). Variance did not show any specific pattern; however, complexity measures of entropy and Lempel-Ziv were also lower in the UWS (median entropy=9.83 vs 10.58 and median Lempel-Ziv complexity=121 vs 328). Median pupil diameter also seemed to be more sensitive to behavioural changes across different assessments. These preliminary data suggest that higher responsiveness is related to higher median and complexity of the pupillometry signal and eye opening percentage at rest, supporting that pupillometry markers could be used as potential predictor of behavioral responsiveness in DOC patients. [less ▲]

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See detailNociception Coma Scale Revised allows to identify patients with preserved neural basis for pain experience.
Bonin, Estelle ULiege; Lejeune, Nicolas ULiege; Thibaut, Aurore ULiege et al

Poster (2019, March 14)

The Nociception Coma Scale-Revised (NCS-R) was developed to help assessing pain in non-communicative patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing ... [more ▼]

The Nociception Coma Scale-Revised (NCS-R) was developed to help assessing pain in non-communicative patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing responses to acute noxious stimuli. However, they failed to determine a reliable cut-off score that could be used to infer pain processing in these patients. This retrospective cross-sectional study aimed to determine an NCS-R cut-off score supporting preserved neural basis for pain experience, based on brain metabolism as measured by fluorodeoxyglucose positron emission tomography (FDG-PET). We included FDG-PET confirmed patient with unresponsive wakefulness syndrome (UWS) (n=13) and looked at their highest NCS-R total scores. As the highest score was 4, we determined the cut-off of 5 and compared the brain metabolism of these patients with matched DOC patients with a cut-off score ≥ 5 (i.e., potential pain) and healthy controls. We found a higher global cerebral metabolism in healthy subjects compared with both patients’ groups and also in patients with potential pain compared with FDG-PET confirmed UWS. We observed a preserved metabolism in the left insula in patients with potential pain when compared with FDG-PET confirmed UWS. We also found a preservation of the connectivity between the left insula and the medial frontal gyrus in patients with potential pain compared with FDG-PET confirmed UWS. Our data suggest that using the cut-off score of 5 can be helpful to improve pain management in DOC patients. Future studies should focus on patients showing scores below this cut-off to better characterize their profile and improve cares. [less ▲]

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