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      Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool

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          Abstract

          Introduction

          Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction.

          Methods

          From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model.

          Results

          Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02).

          Discussion

          The association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation.

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          Most cited references38

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          The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility.

          To determine the measurement properties and diagnostic utility of the JFK Coma Recovery Scale-Revised (CRS-R). Analysis of interrater and test-retest reliability, internal consistency, concurrent validity, and diagnostic accuracy. Acute inpatient brain injury rehabilitation hospital. Convenience sample of 80 patients with severe acquired brain injury admitted to an inpatient Coma Intervention Program with a diagnosis of either vegetative state (VS) or minimally conscious state (MCS). Not applicable. The CRS-R, the JFK Coma Recovery Scale (CRS), and the Disability Rating Scale (DRS). Interrater and test-retest reliability were high for CRS-R total scores. Subscale analysis showed moderate to high interrater and test-retest agreement although systematic differences in scoring were noted on the visual and oromotor/verbal subscales. CRS-R total scores correlated significantly with total scores on the CRS and DRS indicating acceptable concurrent validity. The CRS-R was able to distinguish 10 patients in an MCS who were otherwise misclassified as in a VS by the DRS. The CRS-R can be administered reliably by trained examiners and repeated measurements yield stable estimates of patient status. CRS-R subscale scores demonstrated good agreement across raters and ratings but should be used cautiously because some scores were underrepresented in the current study. The CRS-R appears capable of differentiating patients in an MCS from those in a VS.
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            Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome

            Background Some patients awaken from coma (that is, open the eyes) but remain unresponsive (that is, only showing reflex movements without response to command). This syndrome has been coined vegetative state. We here present a new name for this challenging neurological condition: unresponsive wakefulness syndrome (abbreviated UWS). Discussion Many clinicians feel uncomfortable when referring to patients as vegetative. Indeed, to most of the lay public and media vegetative state has a pejorative connotation and seems inappropriately to refer to these patients as being vegetable-like. Some political and religious groups have hence felt the need to emphasize these vulnerable patients' rights as human beings. Moreover, since its first description over 35 years ago, an increasing number of functional neuroimaging and cognitive evoked potential studies have shown that physicians should be cautious to make strong claims about awareness in some patients without behavioral responses to command. Given these concerns regarding the negative associations intrinsic to the term vegetative state as well as the diagnostic errors and their potential effect on the treatment and care for these patients (who sometimes never recover behavioral signs of consciousness but often recover to what was recently coined a minimally conscious state) we here propose to replace the name. Conclusion Since after 35 years the medical community has been unsuccessful in changing the pejorative image associated with the words vegetative state, we think it would be better to change the term itself. We here offer physicians the possibility to refer to this condition as unresponsive wakefulness syndrome or UWS. As this neutral descriptive term indicates, it refers to patients showing a number of clinical signs (hence syndrome) of unresponsiveness (that is, without response to commands) in the presence of wakefulness (that is, eye opening).
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              Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment

              Background Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). Methods We prospectively followed 103 patients (55 ± 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' Results Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. Conclusion Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 June 2016
                2016
                : 11
                : 6
                : e0156882
                Affiliations
                [1 ]Acute Neurorehabilitation Unit, Department of Clinical Neurosciences, University Hospital of Lausanne, Lausanne, Switzerland
                [2 ]Department of Clinical Neurosciences, University Hospital of Lausanne, Lausanne, Switzerland
                [3 ]Faculty of Medicine, Lausanne University, Lausanne, Switzerland
                [4 ]Coma Science Group, University of Liege, Liege, Belgium
                [5 ]Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
                [6 ]Faculty of Medicine, University of Geneva, Geneva, Switzerland
                [7 ]Department of Neurology, SRH-Gesundheitszentrum, Bad Wimpfen, Germany
                University of Pennsylvania, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JMP EM CGK KD. Performed the experiments: EM CGK JMP KD. Analyzed the data: JMP DVDV MGP DEM. Contributed reagents/materials/analysis tools: JMP DVDV MGP JJ. Wrote the paper: JMP EM. Supervision of the experiment and critical revision of the manuscript: VH SL BD RF JJ.

                Article
                PONE-D-15-52941
                10.1371/journal.pone.0156882
                4928790
                27359335
                595e568c-23ed-4596-aef7-666f1a2f5851
                © 2016 Pignat et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 December 2015
                : 21 May 2016
                Page count
                Figures: 1, Tables: 6, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100006389, Université de Genève;
                Award Recipient :
                Funded by: Gianni Biaggi de Blasys Foundation
                Award Recipient :
                Funded by: Schumacher Foundation
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002661, Fonds De La Recherche Scientifique - FNRS;
                Award Recipient :
                Funded by: Foundation Parkinson Switzerland
                Award Recipient :
                Funded by: Foundation Synapsis
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001711, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung;
                Award Recipient :
                Funded by: Fondation Roger de Spoelberch
                Award Recipient :
                Funded by: Partridge Foundation
                Award Recipient :
                Funded by: Merz and Allergan
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001703, École Polytechnique Fédérale de Lausanne;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001703, École Polytechnique Fédérale de Lausanne;
                Award Recipient :
                V. Hömberg received funding from the German Research Foundation. S. Laureys received funding from National Fund for Scientific Research (NFSR). B. Draganski received funding from the Foundation Parkinson Switzerland, the Foundation Synapsis, the German Research Foundation and the Swiss National Science Foundation. R. Frackowiak received funding from the Fondation Roger de Spoelberch, the Partridge Foundation and for the LREN research neuroimaging platform. K. Diserens received funding from the Gianni Biaggi de Blasys Foundation and the Schumacher Foundation. K. Diserens received also funding from the companies Merz and Allergan for research on botulinum toxin treatment. This study was financially supported by the peer reviewed Gianni Biaggi de Blasys Foundation, which had no role in study design, in data collection, analysis and interpretation, nor in writing the final report. All the aforementioned institutions and companies had no role in study design, in data collection, analysis and interpretation, nor in writing the final report.
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