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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)

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 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)

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 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 detailNeuroimaging in Disorders of Consciousness
Bodart, Olivier ULg; Charland-Verville, Vanessa ULg; Laureys, Steven ULg et al

in Filippi, M. (Ed.) Oxford Textbook of Clinical Neurology (2014)

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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 detailBrain dead yet mind alive: A positron emission tomography case study of brain metabolism in Cotard’s syndrome
Charland-Verville, Vanessa ULg; Bruno, Marie-Aurélie ULg; Bahri, Mohamed Ali ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2013), 49(7), 1997-1999

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See detailCharacteristics of Near-Death Experiences Memories as Compared to Real and Imagined Events Memories
Thonnard, Marie ULg; Charland-Verville, Vanessa ULg; Brédart, Serge ULg et al

in PLoS ONE (2013), 8(3),

Since the dawn of time, Near-Death Experiences (NDEs) have intrigued and, nowadays, are still not fully explained. Since reports of NDEs are proposed to be imagined events, and since memories of imagined ... [more ▼]

Since the dawn of time, Near-Death Experiences (NDEs) have intrigued and, nowadays, are still not fully explained. Since reports of NDEs are proposed to be imagined events, and since memories of imagined event have, on average, fewer phenomenological characteristics than real events memories, we here compared phenomenological characteristics of NDEs reports with memories of imagined and real events. We included three groups of coma survivors (8 patients with NDE as defined by the Greyson NDE scale, 6 patients without NDE but with memory of their coma, 7 patients without memories of their coma) and a group of 18 age-matched healthy volunteers. Five types of memories were assessed using Memory Characteristics Questionnaire (MCQ – Johnson et al., 1988): target memory (NDE for NDE memory group, coma memory for coma memory group, and first childhood memory for no memory and control groups), old and recent real event memories and old and recent imagined event memories. Since NDEs are known to have high emotional content, participants were requested to choose the most emotionally salient memories for both real and imagined recent and old event memories. Results showed that, in NDE memories group, NDE memories have more characteristics than memories of imagined and real events (p<0.02). NDE memories contain more self-referential and emotional information and have better clarity than memories of coma (all p<0.02). The present study showed that NDE memories contain more characteristics than real event memories and coma memories. Thus, this suggests that they cannot be considered as imagined event memories. On the contrary, their physiological origins could lead them to be really perceived although not lived in the reality. Further work is needed to better understand this phenomenon. [less ▲]

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See detailMemories of Near-Death experiences are they memories of imagined events?
Thonnard, Marie ULg; Charland-Verville, Vanessa ULg; Brédart, Serge ULg et al

Poster (2012, October 27)

Background: The phenomenon of Near-Death Experiences (NDEs) has always intrigued but is still not fully explained despite numerous theories and studies. Since reports of NDEs are proposed to be imagined ... [more ▼]

Background: The phenomenon of Near-Death Experiences (NDEs) has always intrigued but is still not fully explained despite numerous theories and studies. Since reports of NDEs are proposed to be imagined events (French, 2001), and since memories of imagined events have, on average, fewer phenomenological characteristics than real event memories (e.g. Johnson et al., 1988), we here compared phenomenological characteristics of NDEs reports with memories of imagined and real events. Methods: We included 3 groups of coma survivors (8 patients with NDE as defined by the Greyson NDE scale – the “NDE memory group”- , 6 patients without NDE but with memory of their coma – the “coma memory group” – and 7 patients without memories of their coma – the “no memory group”) and a group of 18 age-matched healthy volunteers. Five memories were assessed using Memory Characteristics Questionnaire (MCQ – Johnson et al., 1988): target memory (NDE for NDE memory group, coma memory for coma memory group, and first childhood memory for no memory and control groups), old and recent real event memories and old and recent imagined event memories. Results: In NDE group, NDE memories showd more characteristics than memories of imagined and real events (p<0.02). These memories contain more self-referential and emotional information and have better clarity than memories of coma (all p<0.02). Conclusion: The present study showed that NDE memories contain more characteristics than real event memories and coma memories. Thus, they cannot be considered as classic imagined event memories. On the contrary, their physiological origins could lead them to be really perceived although not lived in the reality. Further work is needed to better understand this phenomenon [less ▲]

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See detailDétection de signes de conscience chez des patients sévèrement cérébro- lésés avec le contrôle volontaire de la respiration.
Charland-Verville, Vanessa ULg

Master's dissertation (2012)

Suite à un accident cérébral grave, les patients peuvent évoluer d’un coma (patient non-éveillable et inconscient), vers un état végétatif/syndrome d’éveil non-répondant (patient éveillé mais inconscient ... [more ▼]

Suite à un accident cérébral grave, les patients peuvent évoluer d’un coma (patient non-éveillable et inconscient), vers un état végétatif/syndrome d’éveil non-répondant (patient éveillé mais inconscient), vers un état de conscience minimale (patient éveillé et conscient, mais non-communiquant), ou un locked-in syndrome (patient éveillé, conscient, mais ne pouvant exprimer sa conscience que par le biais de mouvements oculaires). L’attribution d’un diagnostic différentiel suite aux évaluations cliniques à l’aide d’échelles comportementales peut se révéler extrêmement complexe avec un taux d’erreurs diagnostiques pouvant toucher plus de 4 patients sur 10 (Childs, Mercer, & Childs, 1993; Schnakers, Vanhaudenhuyse, Giacino, Ventura, Boly et al., 2009c). Ce diagnostic aura un impact tant au niveau éthique que clinique, influant sur les décisions de fins de vie comme sur les soins et traitements prodigués au patient (Demertzi, Schnakers, Ledoux, Chatelle, Bruno et al., 2009; Johnson, 2011). Afin d’affiner le diagnostic des états de conscience altérée, un vaste champ de recherche s’est créé ayant pour but le développement d’outils objectifs complémentaires à l’examen comportemental clinique. Le but de ce travail s’inscrit donc dans le cadre de la mise au point de techniques permettant de détecter des signes de conscience chez ces patients incapables de communiquer et d’exprimer leur conscience par les voies classiques. En effet, nous avons proposé l’utilisation du sniff controller, une toute nouvelle technique permettant de répondre à la commande par la respiration. Notre paradigme, utilisé pour la première fois auprès de patients atteints de trouble de la conscience, avait pour but de demander aux patients de moduler volontairement leur respiration afin de dépasser un seuil prédéfini. Selon les résultats obtenus, il semble que le sniff controller, moyennant plus d’essais et certaines modifications à apporter au système et au paradigme, pourrait se révéler être un outil complémentaire dans l’évaluation para-clinique de ces patients. En effet, l’utilisation de ce système pourrait se révéler comme plus sensible à la détection de réponse à la commande que les évaluations comportementales. De plus, il s’agit d’une interface peu dispendieuse, relativement simple d’utilisation, transportable au chevet du patient et tout à fait non-invasive. Par ailleurs, en ne reposant pas directement sur l’activité cérébrale, cette technique n’est pas sensible aux artéfacts cérébraux inhérents aux lésions cérébrales rencontrées chez les patients. [less ▲]

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See detailOlfaction in athletes with concussion
Charland-Verville, Vanessa ULg; Lassonde, Maryse; Frasnelli, Johannes

in American journal of rhinology & allergy (2012), 26(3), 222-226

BACKGROUND: Moderate to severe traumatic brain injuries (TBIs) commonly lead to olfactory dysfunction; it is, however, unclear whether and to what degree mild TBI such as concussions, which are common ... [more ▼]

BACKGROUND: Moderate to severe traumatic brain injuries (TBIs) commonly lead to olfactory dysfunction; it is, however, unclear whether and to what degree mild TBI such as concussions, which are common sports injuries, affect olfactory function. We therefore aimed to evaluate smell function in athletes who sustained one or more sport concussions in a cross-sectional design. METHODS: Twenty-two University-level football players with one or multiple concussions and 13 control athletes without a history of concussion participated. We measured olfactory function by using the Sniffin' Sticks test to assess subjects' ability to discriminate and identify odors as well as their detection thresholds. In addition, we assessed odor intensity and pleasantness. RESULTS: We used number of concussions and time since the last concussion as independent variables and measure of olfactory function as dependent variables. Although we did not observe any significant effect of the number of concussions, athletes with a longer delay from time of concussion scored significantly weaker than more recently concussed subjects on the odor identification test and on an aggregate olfactory score. Accordingly, we observed a significant negative linear correlation between the odor identification score and the time elapsed since the last concussion. CONCLUSION: These findings suggest a possible degenerative effect of concussions on olfactory function. [less ▲]

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See detailResting state networks and consciousness Alterations of multiple resting state network connectivity in physiological, pharmacological and pathological consciousness states
Heine, Lizette ULg; Soddu, Andrea ULg; Gomez Jaramillo, Francisco Albeiro ULg et al

in Frontiers in Psychology [=FPSYG] (2012)

In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in fMRI functional connectivity under physiological ... [more ▼]

In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in fMRI functional connectivity under physiological (sleep), pharmacological (anesthesia) and pathological altered states of consciousness, such as brain death, coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. The reviewed RSNs were the DMN, left and right executive control, salience, sensorimotor, auditory and visual networks. We highlight some methodological issues concerning resting state analyses in severely injured brains mainly in terms of hypothesis-driven seed-based correlation analysis and data-driven independent components analysis approaches. Finally, we attempt to contextualize our discussion within theoretical frameworks of conscious processes. We think that this “lesion” approach allows us to better determine the necessary conditions under which normal conscious cognition takes place. At the clinical level, we acknowledge the technical merits of the resting state paradigm. Indeed, fast and easy acquisitions are preferable to activation paradigms in clinical populations. Finally, we emphasize the need to validate the diagnostic and prognostic value of fMRI resting state measurements in non-communicating brain damaged patients. [less ▲]

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See detailComa and related disorders
Charland-Verville, Vanessa ULg; Habbal, Dina; Laureys, Steven ULg et al

in Swiss Archives of Neurology and Psychiatry (2012), 163(8), 265-272

Disorders of consciousness represent a major challenge in clinical practice. The last decade of neuroscience research brought new insights about brain function and neural correlates of these pathological ... [more ▼]

Disorders of consciousness represent a major challenge in clinical practice. The last decade of neuroscience research brought new insights about brain function and neural correlates of these pathological states of consciousness. Although behavioural evaluation still remains the gold standard, conscious behaviours are too often missed, leading to unwanted grey zones between conscious and unconscious patients. In order to increase the chances of detecting the signs of consciousness, scientists now focus on the development and validation of neuroimaging and electrophysiological paradigms in noncommunicative patients. Recent insights in this field also raise new questions of medical ethics. Indeed, for conscious patients, legal questions will occur about treatment plans, rehabilitation and communication strategies while for the unconscious patients, end-of-life decisions will take place after the patients’ condition is stated as “permanent” or “irreversible”. [less ▲]

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See detailThe ethics of managing disorders of consciousness
Demertzi, Athina ULg; Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg et al

in Schnakers, Caroline; Laureys, Steven (Eds.) Coma and disorders of consciousness (2012)

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See detailFunctional imaging and impaired consciousness
Vanhaudenhuyse, Audrey ULg; Boly, Mélanie ULg; Bruno, Marie-Aurélie ULg et al

in Schnakers, Caroline; Laureys, Steven (Eds.) Coma and disorders of consciousness (2012)

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See detailResting state networks and consciousness: alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness States.
Heine, Lizette ULg; Soddu, Andrea ULg; Gomez, Francisco et al

in Frontiers in Psychology [=FPSYG] (2012), 3

In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in functional magnetic resonance imaging (fMRI ... [more ▼]

In order to better understand the functional contribution of resting state activity to conscious cognition, we aimed to review increases and decreases in functional magnetic resonance imaging (fMRI) functional connectivity under physiological (sleep), pharmacological (anesthesia), and pathological altered states of consciousness, such as brain death, coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. The reviewed resting state networks were the DMN, left and right executive control, salience, sensorimotor, auditory, and visual networks. We highlight some methodological issues concerning resting state analyses in severely injured brains mainly in terms of hypothesis-driven seed-based correlation analysis and data-driven independent components analysis approaches. Finally, we attempt to contextualize our discussion within theoretical frameworks of conscious processes. We think that this "lesion" approach allows us to better determine the necessary conditions under which normal conscious cognition takes place. At the clinical level, we acknowledge the technical merits of the resting state paradigm. Indeed, fast and easy acquisitions are preferable to activation paradigms in clinical populations. Finally, we emphasize the need to validate the diagnostic and prognostic value of fMRI resting state measurements in non-communicating brain damaged patients. [less ▲]

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See detailDésordres de la conscience : aspects éthiques.
Demertzi, Athina ULg; Gosseries, Olivia ULg; Bruno, Marie-Aurélie ULg et al

in Schnakers, Caroline; LAUREYS, Steven (Eds.) Comas et états de conscience altérée (2011)

L’apparition de la ventilation mécanique dans les années cinquante et le développement des soins intensifs dans les années soixante ont permis à de nombreux patients de survivre à de graves lésions ... [more ▼]

L’apparition de la ventilation mécanique dans les années cinquante et le développement des soins intensifs dans les années soixante ont permis à de nombreux patients de survivre à de graves lésions cérébrales. Bien que ces avancées technologiques soient étonnantes, de nombreux patients vont alors se retrouver dans des états cliniques critiques peu rencontrés auparavant (1). L’impact éthique de ces états d’inconscience se reflète lors de la rédaction des premiers comités de bioéthique et lors de l’apparition du concept d’acharnement thérapeutique. En 1968, le comité spécial de l’école médicale de Harvard a publié un article essentiel redéfinissant la mort comme étant un coma irréversible et une perte permanente de toutes les fonctions cérébrales (2). Le comité, composé de dix médecins, d’un théologien, d’un avocat et d’un historien des sciences, a débattu des questions médicales, juridiques et sociétales quant à la prise en charge des patients en mort cérébrale. Nous donnerons ici un bref aperçu des principales questions éthiques liées à la notion de conscience et à la prise en charge médicale des patients atteints de troubles de la conscience (TDC) tels que le coma, l’état végétatif et l’état de conscience minimale. Nous mettrons également l’accent sur le problème de la gestion de la douleur et des prises de décision en fin de vie. [less ▲]

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