References of "Demertzi, Athina"
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See detailBeyond the gaze: Communicating in chronic locked-in syndrome
Lugo, Z.R; Bruno, Marie-Aurelie; Gosseries, Olivia ULg et al

in Brain Injury (2015), 29

OBJECTIVE Locked-in syndrome (LIS) usually follows a brainstem stroke and is characterized by paralysis of all voluntary muscles (except eyes' movements or blinking) and lack of speech with preserved ... [more ▼]

OBJECTIVE Locked-in syndrome (LIS) usually follows a brainstem stroke and is characterized by paralysis of all voluntary muscles (except eyes' movements or blinking) and lack of speech with preserved consciousness. Several tools have been developed to promote communication with these patients. The aim of the study was to evaluate the current status regarding communication in a cohort of LIS patients. DESIGN A survey was conducted in collaboration with the French Association of Locked-in syndrome (ALIS). SUBJECTS AND METHODS Two hundred and four patients, members of ALIS, were invited to fill in a questionnaire on communication issues and clinical evolution (recovery of verbal language and movements, presence of visual and/or auditory deficits). RESULTS Eighty-eight responses were processed. All respondents (35% female, mean age = 52 ± 12 years, mean time in LIS = 10 ± 6 years) reported using a yes/no communication code using mainly eyes' movements and 62% used assisting technology; 49% could communicate through verbal language and 73% have recovered some functional movements within the years. CONCLUSION The results highlight the possibility to recover non-eye dependent communication, speech production and some functional movement in the majority of chronic LIS patients. [less ▲]

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See detailConsciousness: And Disorders of Consciousness
Heine, Lizette ULg; Demertzi, Athina ULg; Laureys, Steven ULg et al

in Toga, Arthur W (Ed.) Brain mapping : an encyclopedic reference (2015)

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See detailDetecting Levels of Consciousness
Demertzi, Athina ULg; Laureys, Steven ULg

in Levy, N; Clausen, J (Eds.) Handbook of Neuroethics (2015)

Patients with disordered consciousness due to brain injury pose medical and ethical challenges. Rates of clinical misdiagnosis of “vegetative”/unresponsive, minimally conscious and locked-in syndrome ... [more ▼]

Patients with disordered consciousness due to brain injury pose medical and ethical challenges. Rates of clinical misdiagnosis of “vegetative”/unresponsive, minimally conscious and locked-in syndrome states remain challengingly high. Clinical misdiagnosis raises profound ethical concerns in terms of medical management, treatment of pain, and end-of-life decisions. Therefore, valid diagnosis is of utmost importance in clinical settings. A number of neuroimaging and electrophysiology studies now suggest that some behaviorally “vegetative state” patients may nevertheless show atypical cortical activation during resting state conditions; in some cases, they are able to follow commands or even communicate through willfully modified brain activity. Advances in investigating disorders of consciousness with neuroimaging techniques promise to lead to a more accurate understanding of individual patients’ cognitive abilities and to shed light on the gray zones of these clinical conditions. The formulation of an ethical framework which will strike a balance between the protection of these patients and further research on disorders of consciousness is an ethical, clinical, and scientific demand. [less ▲]

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See detailImaging correlation in non-communicating patients
Heine, Lizette ULg; Di Perri, Carol ULg; Soddu, Andrea ULg et al

in Rossetti, A.O; Laureys, Steven (Eds.) Clinical Neurophysiology in Disorders of Consciousness-Brain Function Monitoring in the ICU and beyond (2015)

The diagnosis and medical management of patients with acute or chronic disorders of consciousness (DOC) are challenging. Motor-independent functional neuroimaging technologies are increasingly employed to ... [more ▼]

The diagnosis and medical management of patients with acute or chronic disorders of consciousness (DOC) are challenging. Motor-independent functional neuroimaging technologies are increasingly employed to study covert cognitive processes in the absence of behavioural reports. Studies with functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) performed in this patient population have utilized active, passive and restingstate paradigms. Active paradigms refer to mental imagery tasks that measure wilful modulation of brain signal in specific brain areas, aiming to detect command-following. Passive paradigms are used to measure brain responses to external sensory stimulation (e.g. auditory, somatosensory and visual). Alternatively, in resting-state paradigms, spontaneous brain function is assessed while subjects receive no external stimulation and are instructed to let their mind wander. Independently from each other, these methods have shown differences between healthy controls and patients, as well as among patients with DOC. However, these techniques cannot yet be used in clinical settings before robust information at the single-subject level will be provided: it is expected that multimodal research will improve the single-patient diagnosis, shed light on the prognostic biomarkers, and eventually promote the medical management of patients with consciousness alterations. [less ▲]

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See detailThinking on patients’ behalf: attitudes of healthcare providers towards medico-ethical issues in non-communicating patients
Demertzi, Athina ULg; Laureys, Steven ULg

in Sturma, D; Honnefelder, L; Fuchs, M (Eds.) Yearbook for Science and Ethics (2015)

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See detailTutorial on novel techniques for assessing patients with disorders of consciousness
Chatelle, Camille ULg; Sitt, Jacobo; Goldfine, Andrew et al

Conference (2015)

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See detailUnresponsive wakefulness & translational neurorehabilitation.
Charland-Verville, Vanessa ULg; Thibaut, Aurore ULg; Wannez, Sarah ULg et al

Scientific conference (2014, April 10)

The past 15years 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 15years 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 come 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 detailEffect of zolpidem in chronic disorders of consciousness: a prospective open-label study.
Thonnard, Marie ULg; Gosseries, Olivia ULg; Demertzi, Athina ULg et al

in Functional Neurology (2014), 28(4), 259-64

Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty ... [more ▼]

Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-blind placebo-controlled trial was performed in order to better specify the effects of zolpidem, but the patient, on this trial, failed to show any clinical improvements. The present open-label study therefore failed to show any clinically significant improvement (i.e., change of Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study diagnosis) in any of the 60 studied chronic DOC patients. [less ▲]

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See detailSelf in the vegetative state
VANHAUDENHUYSE, Audrey ULg; Demertzi, Athina ULg; Brédart, Serge ULg et al

in Mishara, A; Corlett, P; Fletcher, P (Eds.) et al Phenomenological Neuropsychiatry: Bridging the Clinic with Clinical Neuroscience (2014)

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See detailPositron emission tomography imaging in altered states of consciousness: Coma, sleep and hypnosis
Thibaut, Aurore ULg; Chatelle, Camille ULg; Stender, Johan et al

in Dierckx, Rudi; Otte, Andreas; Vries, Erik (Eds.) et al PET and SPECT in Neurology (2014)

Positron emission tomography (PET) allows studies of cerebral metabolism and blood flow and has been widely used to investigate physiological mechanisms underlying altered states of consciousness. The aim ... [more ▼]

Positron emission tomography (PET) allows studies of cerebral metabolism and blood flow and has been widely used to investigate physiological mechanisms underlying altered states of consciousness. The aim of this chapter is to review the current literature on brain metabolism during physiological or pathological loss of consciousness including studies on disorders of consciousness arising from severe brain injury (vegetative/unresponsive or minimally conscious states), and related non-pathological conditions such as sleep and hypnotic states. Identifying brain areas specifically involved in conscious processing, these studies have contributed to our understanding of the underlying physiology of consciousness. The precuneal and cingulate cortices, for example, seem to be key areas for maintaining consciousness awareness. Other areas such as hypothalamus, amygdala or the temporo-occipital cortex seem to play a role in different states of unconsciousness such as rapid eye movement sleep and hypnosis. PET studies permit a better comprehension of the loss of consciousness, and focus the implication of specific neural areas and networks in pathologically (vegetative/unresponsive or minimally conscious states), physiologically (sleep), and hypnotically altered states of consciousness. [less ▲]

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See detailChanges in cerebral metabolism in patients with a minimally conscious state responding to zolpidem.
Chatelle, Camille ULg; Thibaut, Aurore ULg; Gosseries, Olivia ULg et al

in Frontiers in Neuroscience (2014), 8

BACKGROUND: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of ... [more ▼]

BACKGROUND: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS). METHODS: [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8). RESULTS: Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration. CONCLUSION: Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS. [less ▲]

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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 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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