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See detailMultiple fMRI system-level baseline connectivity is disrupted in patients with consciousness alterations
Demertzi, Athina ULg; Gomez, Francisco; Crone, Julia-Sophia et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 52

Introduction: In healthy conditions, group-level fMRI resting state analyses identify ten resting state networks (RSNs) of cognitive relevance. Here, we aim to assess the tennetwork model in severely ... [more ▼]

Introduction: In healthy conditions, group-level fMRI resting state analyses identify ten resting state networks (RSNs) of cognitive relevance. Here, we aim to assess the tennetwork model in severely brain-injured patients suffering from disorders of consciousness and to identify those networks which will be most relevant to discriminate between patients and healthy subjects. Methods: 300 fMRI volumes were obtained in 27 healthy controls and 53 patients in minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/ UWS) and coma. Independent component analysis (ICA) reduced data dimensionality. The ten networks were identified by means of a multiple template-matching procedure and were tested on neuronality properties (neuronal vs non-neuronal) in a data-driven way. Univariate analyses detected between-group differences in networks’ neuronal properties and estimated voxel-wise functional connectivity in the networks, which were significantly less identifiable in patients. A nearest-neighbor “clinical” classifier was used to determine the networks with high between-group discriminative accuracy. Results: Healthy controls were characterized by more neuronal components compared to patients in VS/UWS and in coma. Compared to healthy controls, fewer patients in MCS and VS/UWS showed components of neuronal origin for the left executive control network, default mode network (DMN), auditory, and right executive control network. The “clinical” classifier indicated the DMN and auditory network with the highest accuracy (85.3%) in discriminating patients from healthy subjects. [less ▲]

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See detailDiagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study
Stender, Johan; Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg et al

in Lancet Neurology (2014), 384(9942), 514-522

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness ... [more ▼]

Background: Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI). Methods: For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale—Revised (CRS—R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS—R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale—Extended. Findings: We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). 18F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85—98) and high congruence (85%, 77—90) with behavioural CRS—R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30—61) and had lower overall congruence with behavioural scores (63%, 51—73) than PET imaging. 18F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64—81), and fMRI in 36 of 65 patients (56%, 43—67). 13 of 42 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS—R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. Interpretation: Cerebral 18F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate. Funding: The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège. [less ▲]

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See detailMeasuring consciousness in coma and related states
Di Perri, Carol; Thibaut, Aurore ULg; Soddu, Andrea ULg et al

in World Journal of Radiology (2014), 6(8), 589-597

Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of consciousness (DOC) provide a model from which ... [more ▼]

Consciousness is a prismatic and ambiguous concept that still eludes any universal definition. Severe acquired brain injuries resulting in a disorder of consciousness (DOC) provide a model from which insights into consciousness can be drawn. A number of recent studies highlight the difficulty in making a diagnosis in patients with DOC based only on behavioral assessments. Here we aim to provide an overview of how neuroimaging techniques can help assess patients with DOC. Such techniques are expected to facilitate a more accurate understanding of brain function in states of unconsciousness and to improve the evaluation of the patient’s cognitive abilities by providing both diagnostic and prognostic indicators. [less ▲]

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See detailTechnology-based assessment in patients with disorders of consciousness
Di Perri, Carol ULg; Heine, Lizette ULg; Amico, Enrico ULg et al

in Annali dell'Istituto Superiore di Sanita (2014), 50(3), 209-220

INTRODUCTION A number of studies highlight the difficulty in forming a diagnosis for patients with disorders of consciousness when this is established merely on behavioral assessments. BACKGROUND Positron ... [more ▼]

INTRODUCTION A number of studies highlight the difficulty in forming a diagnosis for patients with disorders of consciousness when this is established merely on behavioral assessments. BACKGROUND Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and electroencephalography combined with transcranial magnetic stimulation (TMS-EEG) techniques are promoting the clinical characterization of this challenging population. With such technology-based "objective" tools, patients are also differentially able to follow simple commands and in some cases even communicate through modified brain activity. Consequently, the vegetative state and minimally conscious state have been revised and new nosologies have been proposed, namely the unresponsive wakefulness syndrome, the minimally conscious state plus and minus, and the functional locked-in syndrome. AIM To our mind, an integration of different technical modalities is important to gain a holistic vision of the underlying pathophysiology of disorders of consciousness in general and to promote single-patient medical management in particular. [less ▲]

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See detailConsciousness alterations after severe brain injury
Demertzi, Athina ULg; Laureys, Steven ULg

in Mangun, G.R.; Gazzaniga, M.S. (Eds.) The Cognitive Neurosciences (2014)

The past fifteen years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of consciousness in the human brain following severe brain damage. Highlighted ... [more ▼]

The past fifteen years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities. These first scientific demonstrations support the possibility that some severely brain-injured patients in long-standing conditions of limited behavioral responsiveness may nonetheless retain latent capacities for awareness. Such capacities include the human functions of language and higher-level cognition that, either spontaneously or by thought-directed interventions, may reemerge even at long time intervals or can remain unrecognized. Functional neuroimaging, such as positron emission tomography and functional magnetic resonance imaging, as well as electroencephalography and evoked potential studies, have offered the possibility to objectively approach covert cognitive processes in patients who are otherwise incapable of intelligible or sustained behavioral expression. Such studies have used experimental protocols to assess brain function during resting-state conditions and after external stimulation. These technologies have further permitted the detection of nonverbal command-following and even established muscle- independent means of communication with some behaviorally unresponsive patients. Such advances are expected to shed light on the gray zones between the clinical entities of consciousness and help resolve medical and ethical controversies around the management of such challenging situations. [less ▲]

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See detailBrain Computer Interfaces and diagnosis
Chatelle, Camille ULg; LAUREYS, Steven ULg; Noirhomme, Quentin ULg

in Grübler, Gerd; Hildt, Elisabeth (Eds.) Brain-Computer-Interfaces in their ethical, social and cultural contexts (2014)

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See detailMind-matter interactions in severe brain injury and coma
Charland-Verville, Vanessa ULg; Laureys, Steven ULg

in Fundacao Bial (Ed.) Behind and Beyond the Brain (2014)

The past fifteen years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage ... [more ▼]

The past fifteen years have provided an unprecedented collection of discoveries that bear upon our scientific understanding of recovery of consciousness in the human brain following severe brain damage. Highlighted among these discoveries are unique demonstrations that patients with little or no behavioral evidence of conscious awareness may retain critical cognitive capacities and the first scientific demonstrations that some patients, with severely injured brains and very longstanding conditions of limited behavioral responsiveness, may nonetheless harbor latent capacities for recovery. Included among such capacities are particularly human functions of language and higher-level cognition that either spontaneously or through direct interventions may reemerge even at long time intervals or remain unrecognized. When patients in “persistent vegetative state” (recently also coined unresponsive wakefulness syndrome) show minimal signs of consciousness but are unable to reliably communicate the term minimally responsive or minimally conscious state (MCS) is used. MCS was recently subcategorized based on the complexity of patients' behaviors: MCS+ describes high-level behavioral responses (i.e., command following, intelligible verbalizations or non-functional communication) and MCS- describes low-level behavioral responses (i.e., visual pursuit, localization of noxious stimulation or contingent behavior such as appropriate smiling or crying to emotional stimuli). Patients who show non-behavioral evidence of consciousness or communication only measurable via ancillary testing (i.e., functional MRI, positron emission tomography, EEG or evoked potentials) can be considered to be in a functional locked-in syndrome. An improved assessment of brain function in coma and related states is not only changing nosology and medical care but also offers a better-documented diagnosis and prognosis and helps to further identify the neural correlates of human consciousness. Taken together, recent studies show that awareness is an emergent property of the collective behavior of frontoparietal top-down connectivity. Within this network, external (sensory) awareness depends on lateral prefrontal/parietal cortices while internal (self) awareness correlates with precuneal/mesiofrontal midline activity. Of clinical importance, this knowledge now permits to improve the diagnosis, prognosis and treatment of patients with disorders of consciousness, which currently remains very challenging. New technological advances now also permit to show command-specific changes in fMRI, EEG or eye-pupil measurements providing motor-independent evidence of conscious thoughts and in some cases even of communication. We will conclude by discussing related ethical issues and the challenge of improving our clinical care and quality of life in these challenging patients with disorders of consciousness. [less ▲]

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See detailAmantadine, Apomorphine and Zolpidem in the Treatment of Disorders of Consciousness
Gosseries, Olivia ULg; Charland-Verville, Vanessa ULg; Thonnard, Marie ULg et al

in Current Pharmaceutical Design (2014), 20

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to ... [more ▼]

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to enhance our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition. [less ▲]

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See detailDetection of visual pursuit in patients in minimally conscious state: a matter of stimuli and visual plane?
Thonnard, Marie; Wannez, Sarah ULg; Keen, Shannan et al

in Brain injury (2014), 28(9), 1164-70

OBJECTIVES: The aim of this study was to determine whether the assessment of pursuit eye movements in patients in minimally conscious state (MCS) is influenced by the choice of the visual stimulus (study ... [more ▼]

OBJECTIVES: The aim of this study was to determine whether the assessment of pursuit eye movements in patients in minimally conscious state (MCS) is influenced by the choice of the visual stimulus (study 1) and by the moving plane (study 2). METHODS: Patients with MCS (MCS- and MCS+) in the acute (<1 month post-injury) or chronic (>1 month) setting were assessed. The Coma Recovery Scale-Revised (CRS-R) procedure was used to test visual pursuit of a moving mirror, object and person (study 1, n = 88) and to test vertical and horizontal visual tracking (study 2, n = 94). RESULTS: Study 1: Patients with visual pursuit tracked preferentially the moving mirror over the moving person or object. Study 2: Patients displaying visual pursuit, especially in MCS- and in chronic setting, preferentially tracked on the horizontal rather than the vertical plane. CONCLUSION: The findings confirm the importance of using a mirror to assess visual pursuit in patients in MCS and of initiating testing using the horizontal plane, specifically in patients in MCS- and those in chronic setting. Assessment should then be done on the vertical plane if visual pursuit is not detected on the horizontal plane. [less ▲]

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See detailAssessing dynamical correlations between functional and structural brain connectivity
Liegeois, Raphaël ULg; Ziegler, Erik; Phillips, Christophe ULg et al

Poster (2014)

The link between resting­‐state functional connectivity (FC), measured by the correlations of the fMRI BOLD time courses, and structural connectivity (SC) has been repeatedly investigated recently ... [more ▼]

The link between resting­‐state functional connectivity (FC), measured by the correlations of the fMRI BOLD time courses, and structural connectivity (SC) has been repeatedly investigated recently. Meanwhile, the importance of considering the dynamics of neuronal processes has also been highlighted. In this work we show how the classical static (i.e. considered as constant) relationship between SC and FC could be enriched when the FC dynamics are taken into account. We use a sliding window approach to explore these dynamics and show that the window width should be chosen in a particular range in order to unveil statistically significant (i.e. not due to noise) fluctuations of the FC-­‐SC correlation. [less ▲]

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See detailA European survey on attitudes towards pain and end-of-life issues in locked-in syndrome
Demertzi, Athina ULg; Jox, Ralf J; Racine, Eric et al

in Brain Injury (2014), 28(9), 12091215

Objectives: Patients with locked-in syndrome often self-report a higher quality of life than generally expected. This study reports third-person attitudes towards several salient issues on locked-in ... [more ▼]

Objectives: Patients with locked-in syndrome often self-report a higher quality of life than generally expected. This study reports third-person attitudes towards several salient issues on locked-in syndrome. Methods: Close-ended survey among conference attendees from 33 European countries. Analysis included chi-square tests and logistic regressions. Results: From the 3332 respondents (33% physicians, 18% other clinicians, 49% other professions; 47% religious), 90% agreed that patients with locked-in syndrome can feel pain. The majority (75%) disagreed with treatment withdrawal, but 56% did not wish to be kept alive if they imagined themselves in this condition (p<0.001). Religious and southern Europeans opposed to treatment withdrawal more often than non-religious (p<0.001) and participants from the North (p=0.001). When the locked-in syndrome was compared to disorders of consciousness, more respondents endorsed that being in a chronic locked-in syndrome was worse than being in a vegetative state or minimally conscious state for patients (59%) than they thought for families (40%, p<0.001). Conclusions: Personal characteristics mediate opinions about locked-in syndrome. The dissociation between personal preferences and general opinions underlie the difference in perspective in disability. Ethical responses to dilemmas involving patients with locked-in syndrome should consider the diverging ethical attitudes of stakeholders. [less ▲]

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See detailHow electroencephalography serves the anesthesiologist.
Marchant, Nicolas ULg; Sanders, Robert; Sleigh, Jamie et al

in Clinical EEG and neuroscience (2014), 45(1), 22-32

Major clinical endpoints of general anesthesia, such as the alteration of consciousness, are achieved through effects of anesthetic agents on the central nervous system, and, more precisely, on the brain ... [more ▼]

Major clinical endpoints of general anesthesia, such as the alteration of consciousness, are achieved through effects of anesthetic agents on the central nervous system, and, more precisely, on the brain. Historically, clinicians and researchers have always been interested in quantifying and characterizing those effects through recordings of surface brain electrical activity, namely electroencephalography (EEG). Over decades of research, the complex signal has been dissected to extract its core substance, with significant advances in the interpretation of the information it may contain. Methodological, engineering, statistical, mathematical, and computer progress now furnishes advanced tools that not only allow quantification of the effects of anesthesia, but also shed light on some aspects of anesthetic mechanisms. In this article, we will review how advanced EEG serves the anesthesiologist in that respect, but will not review other intraoperative utilities that have no direct relationship with consciousness, such as monitoring of brain and spinal cord integrity. We will start with a reminder of anesthestic effects on raw EEG and its time and frequency domain components, as well as a summary of the EEG analysis techniques of use for the anesthesiologist. This will introduce the description of the use of EEG to assess the depth of the hypnotic and anti-nociceptive components of anesthesia, and its clinical utility. The last part will describe the use of EEG for the understanding of mechanisms of anesthesia-induced alteration of consciousness. We will see how, eventually in association with transcranial magnetic stimulation, it allows exploring functional cerebral networks during anesthesia. We will also see how EEG recordings during anesthesia, and their sophisticated analysis, may help corroborate current theories of mental content generation. [less ▲]

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See detailFunctional neuroanatomy of disorders of consciousness
Di Perri, Carol; Stender, Johan; Laureys, Steven ULg et al

in CAVANNA, Andrea (Ed.) Epilepsy and behavior Alteration of Counsciousness in Epilepsy (2014)

Our understanding of the mechanisms of loss and recovery of consciousness, following severe brain injury or during anesthesia, is changing rapidly. Recent neuroimaging studies have shown that patients ... [more ▼]

Our understanding of the mechanisms of loss and recovery of consciousness, following severe brain injury or during anesthesia, is changing rapidly. Recent neuroimaging studies have shown that patients with chronic disorders of consciousness and subjects undergoing general anesthesia present a complex dysfunctionality in the architecture of brain connectivity. At present, the global hallmark of impaired consciousness appears to be amultifaceted dysfunctional connectivity pattern with both within-network loss of connectivity in awidespread frontoparietal network and between-network hyperconnectivity involving other regions such as the insula and ventral tegmental area. Despite ongoing efforts, the mechanisms underlying the emergence of consciousness after severe brain injury are not thoroughly understood. Important questions remain unanswered:What triggers the connectivity impairment leading to disorders of consciousness? Why do some patients recover from coma, while others with apparently similar brain injuries do not? Understanding these mechanisms could lead to a better comprehension of brain function and, hopefully, lead to new therapeutic strategies in this challenging patient population. [less ▲]

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See detailPreserved Covert Cognition in Noncommunicative Patients With Severe Brain Injury?
schnakers, caroline; Giacino, Joseph T; Løvstad, Marianne et al

in Neurorehabilitation and Neural Repair (2014)

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See detailNociception coma scale-revised scores correlate with metabolism in the anterior cingulate cortex.
Chatelle, Camille ULg; Thibaut, Aurore ULg; Bruno, Marie-Aurelie et al

in Neurorehabilitation and neural repair (2014), 28(2), 149-52

BACKGROUND: . The Nociception Coma Scale-Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. OBJECTIVE: . To identify correlations ... [more ▼]

BACKGROUND: . The Nociception Coma Scale-Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. OBJECTIVE: . To identify correlations between cerebral glucose metabolism and NCS-R total scores. METHODS: . [18F]-fluorodeoxyglucose positron emission tomography, NCS-R, and Coma Recovery Scale-Revised assessments were performed in 49 patients with disorders of consciousness. RESULTS: . We identified a significant positive correlation between NCS-R total scores and metabolism in the posterior part of the anterior cingulate cortex, known to be involved in pain processing. No other cluster reached significance. No significant effect of clinical diagnosis (vegetative/unresponsive vs minimally conscious states), etiology or interval since insult was observed. CONCLUSIONS: . Our data support the hypothesis that the NCS-R total scores are related to cortical processing of nociception and may constitute an appropriate behavioral tool to assess, monitor, and treat possible pain in brain-damaged noncommunicative patients with disorders of consciousness. Future studies using event-related functional magnetic resonance imaging should investigate the correlation between NCS-R scores and brain activation in response to noxious stimulation at the single-subject level. [less ▲]

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See detailAssessment of visual fixatio in vegetative and minimally conscious states
Di, Haibo; Nie, Yunzhi; Hu, Xiaohu et al

in BMC Neurology (2014), 14(147),

Background: Visual fixation plays a key role in the differentiation between vegetative state/unresponsive wakefulness (VS/UWS) syndrome and minimally conscious state (MCS). However, the use of different ... [more ▼]

Background: Visual fixation plays a key role in the differentiation between vegetative state/unresponsive wakefulness (VS/UWS) syndrome and minimally conscious state (MCS). However, the use of different stimuli changes the frequency of visual fixation occured in patients, thereby possibly affecting the accuracy of the diagnosis. In order to establish a standardized assessment of visual fixation in patients in disorders of consciousness (DOC), we compared the frequency of visual fixation elicited by mirror,a ball and a light. Method: Visual fixation was assessed in eighty-one post-comatose patients diagnosed with a MCS or VS/UWS. Occurrence of fixation to different stimuli was analysis used Chi-square testing. Result: 40 (49%) out of the 81 patients showed fixation to visual stimuli. Among those, significantly more patients (39, 48%) had visual fixation elicited by mirror compared to a ball (23, 28%) and mirror compared to a light (20, 25%).Conclusion: The use of a mirror during the assessment of visual fixation showed higher positive response rate, compared to other stimuli in eliciting a visual fixating response. Therefore, fixation elicited by a mirror can be a very sensitive and accurate test to differentiate the two disorders of consciousness. [less ▲]

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See detailPain issues in disorders of consciousness
Chatelle, Camille ULg; Thibaut, Aurore ULg; Wythe, John et al

in Brain Injury (2014), 28(9), 1202-1208

Background: The assessment of pain and nociception in non-communicative patients with disorders of consciousness (DOC) is a real challenge for clinicians. It is, therefore, important to develop sensitive ... [more ▼]

Background: The assessment of pain and nociception in non-communicative patients with disorders of consciousness (DOC) is a real challenge for clinicians. It is, therefore, important to develop sensitive standardized tools usable at the bedside. Objectives: This review aims to provide an overview of the current knowledge about pain processing and assessment in patients with DOC. Methods: A search was performed on PubMed using MeSH terms including vegetative state, unresponsive wakefulness syndrome, minimally conscious state, consciousness disorders, pain, nociception, neuroimaging and pain assessment. Results: Neuroimaging studies investigating pain processing in patients with DOC and their implication for clinicians are reviewed. Current works on the development of standardized and sensitive tools for assessing nociception are described. Conclusion: The suggested pain perception capacity highlighted by neuroimaging studies in patients in a MCS and in some patients in a VS/UWS supports the idea that these patients need analgesic treatment and monitoring. The first tool which has been developed to assess nociception and pain in patients with DOC is the NCS. Its revised version represents a rapid, standardized and sensitive scale which can be easily implemented in a clinical setting. Complementary pain assessments are also under validation in order to offer more options to clinicians. [less ▲]

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See detailQuantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients
Stender, Johan; Kupers, Ron; Rodell, Anders et al

in Journal of Cerebral Blood Flow & Metabolism (2014)

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc ... [more ▼]

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n = 14), MCS (n = 21) or emergence from MCS (EMCS, n = 6), and healthy volunteers (n = 29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients. [less ▲]

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