Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study
; Gosseries, Olivia ; Bruno, Marie-Aurélie 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 ▲]Detailed reference viewed: 12 (1 ULg)
Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study.
Thonnard, Marie ; Gosseries, Olivia ; Demertzi, Athina 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 ▲]Detailed reference viewed: 17 (1 ULg)
Electroencephalographic profiles for differentiation of disorders of consciousness.
; Chatelle, Camille ; Bruno, Marie-Aurélie et al
in BioMedical Engineering OnLine (2013), 12
BACKGROUND: Electroencephalography (EEG) is best suited for long-term monitoring of brain functions in patients with disorders of consciousness (DOC). Mathematical tools are needed to facilitate efficient ... [more ▼]
BACKGROUND: Electroencephalography (EEG) is best suited for long-term monitoring of brain functions in patients with disorders of consciousness (DOC). Mathematical tools are needed to facilitate efficient interpretation of long-duration sleep-wake EEG recordings. METHODS: Starting with matching pursuit (MP) decomposition, we automatically detect and parametrize sleep spindles, slow wave activity, K-complexes and alpha, beta and theta waves present in EEG recordings, and automatically construct profiles of their time evolution, relevant to the assessment of residual brain function in patients with DOC. RESULTS: Above proposed EEG profiles were computed for 32 patients diagnosed as minimally conscious state (MCS, 20 patients), vegetative state/unresponsive wakefulness syndrome (VS/UWS, 11 patients) and Locked-in Syndrome (LiS, 1 patient). Their interpretation revealed significant correlations between patients' behavioral diagnosis and: (a) occurrence of sleep EEG patterns including sleep spindles, slow wave activity and light/deep sleep cycles, (b) appearance and variability across time of alpha, beta, and theta rhythms. Discrimination between MCS and VS/UWS based upon prominent features of these profiles classified correctly 87 % of cases. CONCLUSIONS: Proposed EEG profiles offer user-independent, repeatable, comprehensive and continuous representation of relevant EEG characteristics, intended as an aid in differentiation between VS/UWS and MCS states and diagnostic prognosis. To enable further development of this methodology into clinically usable tests, we share user-friendly software for MP decomposition of EEG (http://braintech.pl/svarog) and scripts used for creation of the presented profiles (attached to this article). [less ▲]Detailed reference viewed: 26 (6 ULg)
A Comparison of Two Spelling Brain-Computer Interfaces Based on Visual P3 and SSVEP in Locked-In Syndrome
; Chatelle, Camille ; et al
in PLoS ONE (2013), 8(9), 73691
Objectives: We study the applicability of a visual P3-based and a Steady State Visually Evoked Potentials (SSVEP)-based Brain-Computer Interfaces (BCIs) for mental text spelling on a cohort of patients ... [more ▼]
Objectives: We study the applicability of a visual P3-based and a Steady State Visually Evoked Potentials (SSVEP)-based Brain-Computer Interfaces (BCIs) for mental text spelling on a cohort of patients with incomplete Locked-In Syndrome (LIS). Methods: Seven patients performed repeated sessions with each BCI. We assessed BCI performance, mental workload and overall satisfaction for both systems. We also investigated the effect of the quality of life and level of motor impairment on the performance. Results: All seven patients were able to achieve an accuracy of 70% or more with the SSVEP-based BCI, compared to 3 patients with the P3-based BCI, showing a better performance with the SSVEP BCI than with the P3 BCI in the studied cohort. Moreover, the better performance of the SSVEP-based BCI was accompanied by a lower mental workload and a higher overall satisfaction. No relationship was found between BCI performance and level of motor impairment or quality of life. Conclusion:Our results show a better usability of the SSVEP-based BCI than the P3-based one for the sessions performed by the tested population of locked-in patients with respect to all the criteria considered. The study shows the advantage of developing alternative BCIs with respect to the traditional matrix-based P3 speller using different designs and signal modalities such as SSVEPs to build a faster, more accurate, less mentally demanding and more satisfying BCI by testing both types of BCIs on a convenience sample of LIS patients. [less ▲]Detailed reference viewed: 43 (7 ULg)
Brain dead yet mind alive: A positron emission tomography case study of brain metabolism in Cotard’s syndrome
Charland-Verville, Vanessa ; Bruno, Marie-Aurélie ; Bahri, Mohamed Ali et al
in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2013), 49(7), 1997-1999Detailed reference viewed: 39 (9 ULg)
La stimulation transcranienne a courant continu : un nouvel outil de neurostimulation.
Thibaut, Aurore ; Chatelle, Camille ; Gosseries, Olivia et al
in Revue Neurologique (2013), 169
Transcranial direct current stimulation (tDCS) is a safe method to modulate cortical excitability. Anodal stimulation can improve the stimulated area's functions whereas cathodal stimulation reduces them ... [more ▼]
Transcranial direct current stimulation (tDCS) is a safe method to modulate cortical excitability. Anodal stimulation can improve the stimulated area's functions whereas cathodal stimulation reduces them. Currently, a lot of clinical trials have been conducted to study the effect of tDCS on post-stroke motor and language deficits, in depression, chronic pain, memory impairment and tinnitus in order to decrease symptoms. Results showed that, if an effect is observed with tDCS, it does not persist over time. Current studies suggest that direct current stimulation is a promising technique that helps to improve rehabilitation after stroke, to enhance cognitive deficiencies, to reduce depression and to relieve chronic pain. Moreover, it is a safe, simple and cheap device that could be easily integrated in a rehabilitation program. [less ▲]Detailed reference viewed: 17 (2 ULg)
Spasticity after stroke: Physiology, assessment and treatment
Thibaut, Aurore ; Chatelle, Camille ; Ziegler, Erik et al
in Brain Injury (2013), 27(10), 1093-1105
Spasticity following a stroke occurs in about 30% of patients. The mechanisms underlying this disorder, however, are not well understood. This review aims to define spasticity, describe hypotheses ... [more ▼]
Spasticity following a stroke occurs in about 30% of patients. The mechanisms underlying this disorder, however, are not well understood. This review aims to define spasticity, describe hypotheses explaining its development after a stroke, give an overview of related neuroimaging studies as well as a description of the most common scales used to quantify the degree of spasticity and finally explore which treatments are currently being used to treat this disorder. The lack of consensus is highlighted on the basis of spasticity and the associated absence of guidelines for treatment, use of drugs and rehabilitation programmes. Future studies require controlled protocols to determine the efficiency of pharmacological and non-pharmacological treatments for spasticity. Neuroimaging may help predict the occurrence of spasticity and could provide insight into its neurological basis. [less ▲]Detailed reference viewed: 142 (15 ULg)
Probing command following in patients with disorders of consciousness using a brain-computer interface.
; Noirhomme, Quentin ; et al
in Clinical Neurophysiology (2013), 124(1), 101-6
OBJECTIVE: To determine if brain-computer interfaces (BCIs) could serve as supportive tools for detecting consciousness in patients with disorders of consciousness by detecting response to command and ... [more ▼]
OBJECTIVE: To determine if brain-computer interfaces (BCIs) could serve as supportive tools for detecting consciousness in patients with disorders of consciousness by detecting response to command and communication. METHODS: We tested a 4-choice auditory oddball EEG-BCI paradigm on 16 healthy subjects and 18 patients in a vegetative state/unresponsive wakefulness syndrome, in a minimally conscious state (MCS), and in locked-in syndrome (LIS). Subjects were exposed to 4 training trials and 10 -12 questions. RESULTS: Thirteen healthy subjects and one LIS patient were able to communicate using the BCI. Four of those did not present with a P3. One MCS patient showed command following with the BCI while no behavioral response could be detected at bedside. All other patients did not show any response to command and could not communicate with the BCI. CONCLUSION: The present study provides evidence that EEG based BCI can detect command following in patients with altered states of consciousness and functional communication in patients with locked-in syndrome. However, BCI approaches have to be simplified to increase sensitivity. SIGNIFICANCE: For some patients without any clinical sign of consciousness, a BCI might bear the potential to employ a "yes-no" spelling device offering the hope of functional interactive communication. [less ▲]Detailed reference viewed: 143 (18 ULg)
Detecting Consciousness with a Brain-computer Interface
Noirhomme, Quentin ; Lesenfants, Damien ; Lehembre, Remy et al
in Pons, J. L.; Torricelli, D.; Pajaro, M. (Eds.) Converging Clinical and Engineering Research on Neurorehabilitation (2012, November)
Recent electrophysiological and neuroimaging studies showed command-specific changes in EEG or fMRI signals of unresponsive patients providing motor-independent evidence of conscious thoughts. These ... [more ▼]
Recent electrophysiological and neuroimaging studies showed command-specific changes in EEG or fMRI signals of unresponsive patients providing motor-independent evidence of conscious thoughts. These promising results have paved the way for a new application for Brain-computer Interface (BCI): detecting consciousness in patients with disorders of consciousness (DOC). In the present abstract, we review the first results obtained by BCI-like applications in patients with DOC and discuss the challenges facing BCI research. We believe that patients with DOC may benefit from BCI based diagnosis. BCIs may detect changes in the signal in response to command and, in some cases, may permit communication. [less ▲]Detailed reference viewed: 109 (18 ULg)
Brain-computer interfacing in disorders of consciousness.
Chatelle, Camille ; ; Noirhomme, Quentin et al
in Brain Injury (2012), 26(12), 1510-22
Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential ... [more ▼]
Background: Recent neuroimaging research has strikingly demonstrated the existence of covert awareness in some patients with disorders of consciousness (DoC). These findings have highlighted the potential for the development of simple brain-computer interfaces (BCI) as a diagnosis in behaviourally unresponsive patients. Objectives: This study here reviews current EEG-based BCIs that hold potential for assessing and eventually assisting patients with DoC. It highlights key areas for further development that might eventually make their application feasible in this challenging patient group. Methods: The major types of BCIs proposed in the literature are considered, namely those based on the P3 potential, sensorimotor rhythms, steady state oscillations and slow cortical potentials. In each case, a brief overview of the relevant literature is provided and then their relative merits for BCI applications in DoC are considered. Results: A range of BCI designs have been proposed and tested for enabling communication in fully conscious, paralysed patients. Although many of these have potential applicability for patients with DoC, they share some key challenges that need to be overcome, including limitations of stimulation modality, feedback, user training and consistency. Conclusion: Future work will need to address the technical and practical challenges facing reliable implementation at the patient's bedside. [less ▲]Detailed reference viewed: 7 (0 ULg)
A sensitive scale to assess nociceptive pain in patients with disorders of consciousness.
Chatelle, Camille ; Majerus, Steve ; et al
in Journal of Neurology, Neurosurgery & Psychiatry (2012), 83(12), 1233-7
OBJECTIVE: To determine the sensitivity of the Nociception Coma Scale (NCS), the first scale developed to assess nociceptive pain in vegetative state and minimally conscious state patients, in comparing ... [more ▼]
OBJECTIVE: To determine the sensitivity of the Nociception Coma Scale (NCS), the first scale developed to assess nociceptive pain in vegetative state and minimally conscious state patients, in comparing behavioural changes in response to noxious versus non-noxious stimulation. METHODS: The NCS was administered to assess patients' responses in three conditions: (1) baseline (observation of spontaneous behaviours), (2) non-noxious/tactile stimulation (taps on the patient's shoulder), and (3) noxious stimulation (pressure on the nail bed). RESULTS: We included 64 patients (27 vegetative state and 37 minimally conscious state; age range 20-82 years; 22 traumatic brain injury; 21 in the acute stage). The NCS total scores and subscores (motor, verbal and facial) were higher for the noxious versus the non-noxious stimulation conditions. We did not observe a difference between the non-noxious and the noxious stimulation conditions for the visual subscale. We also found a NCS cut-off value of 4 differentiating the patients receiving a noxious stimulation from patients receiving a non-noxious stimulation. The exclusion of the visual subscale increased the cut-off sensitivity (from 46% to 73%; specificity of 97% and accuracy of 85%). CONCLUSION: We propose a new version of the NCS excluding the visual subscale, the NCS-R, which constitutes a highly sensitive tool to assess responses to nociceptive pain in severely brain injured patients. [less ▲]Detailed reference viewed: 18 (1 ULg)
Electrophysiological investigations of brain function in coma, vegetative and minimally conscious patients.
Lehembre, Remy ; Gosseries, Olivia ; et al
in Archives Italiennes de Biologie (2012), 150(2-3), 122-39
Electroencephalographic activity in the context of disorders of consciousness is a swiss knife like tool that can evaluate different aspects of cognitive residual function, detect consciousness and ... [more ▼]
Electroencephalographic activity in the context of disorders of consciousness is a swiss knife like tool that can evaluate different aspects of cognitive residual function, detect consciousness and provide a mean to communicate with the outside world without using muscular channels. Standard recordings in the neurological department offer a first global view of the electrogenesis of a patient and can spot abnormal epileptiform activity and therefore guide treatment. Although visual patterns have a prognosis value, they are not sufficient to provide a diagnosis between vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) patients. Quantitative electroencephalography (qEEG) processes the data and retrieves features, not visible on the raw traces, which can then be classified. Current results using qEEG show that MCS can be differentiated from VS/UWS patients at the group level. Event Related Potentials (ERP) are triggered by varying stimuli and reflect the time course of information processing related to the stimuli from low-level peripheral receptive structures to high-order associative cortices. It is hence possible to assess auditory, visual, or emotive pathways. Different stimuli elicit positive or negative components with different time signatures. The presence of these components when observed in passive paradigms is usually a sign of good prognosis but it cannot differentiate VS/UWS and MCS patients. Recently, researchers have developed active paradigms showing that the amplitude of the component is modulated when the subject's attention is focused on a task during stimulus presentation. Hence significant differences between ERPs of a patient in a passive compared to an active paradigm can be a proof of consciousness. An EEG-based brain-computer interface (BCI) can then be tested to provide the patient with a communication tool. BCIs have considerably improved the past two decades. However they are not easily adaptable to comatose patients as they can have visual or auditory impairments or different lesions affecting their EEG signal. Future progress will require large databases of resting state-EEG and ERPs experiment of patients of different etiologies. This will allow the identification of specific patterns related to the diagnostic of consciousness. Standardized procedures in the use of BCIs will also be needed to find the most suited technique for each individual patient. [less ▲]Detailed reference viewed: 96 (3 ULg)
Resting-state EEG study of comatose patients: a connectivity and frequency analysis to find differences between vegetative and minimally conscious states.
Lehembre, Remy ; Bruno, Marie-Aurélie ; Vanhaudenhuyse, Audrey et al
in Functional Neurology (2012), 27(1), 41-47
The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS ... [more ▼]
The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS). The EEG of 31 patients was recorded and analyzed. Power spectra were obtained using modern multitaper methods. Three connectivity measures (coherence, the imaginary part of coherency and the phase lag index) were computed. Of the 31 patients, 21 were diagnosed as MCS and 10 as VS/UWS using the Coma Recovery Scale-Revised (CRS-R). EEG power spectra revealed differences between the two conditions. The VS/UWS patients showed increased delta power but decreased alpha power compared with the MCS patients. Connectivity measures were correlated with the CRS-R diagnosis; patients in the VS/UWS had significantly lower connectivity than MCS patients in the theta and alpha bands. Standard EEG recorded in clinical conditions could be used as a tool to help the clinician in the diagnosis of disorders of consciousness. [less ▲]Detailed reference viewed: 179 (30 ULg)
Metabolic activity in external and internal awareness networks in severely brain-damaged patients.
Thibaut, Aurore ; Bruno, Marie-Aurélie ; Chatelle, Camille et al
in Journal of Rehabilitation Medicine (2012), 44(6), 487-94
OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been ... [more ▼]
OBJECTIVE: An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. DESIGN: Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. SUBJECTS: Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). RESULTS: A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. CONCLUSION: Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside. [less ▲]Detailed reference viewed: 199 (52 ULg)
Désordres de la conscience : aspects éthiques.
Demertzi, Athina ; Gosseries, Olivia ; Bruno, Marie-Aurélie 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 ▲]Detailed reference viewed: 80 (17 ULg)
Interface cerveau-ordinateur : une aide à la communication ?
Chatelle, Camille ; ; Noirhomme, Quentin et al
in Schnakers, Caroline; Laureys, Steven (Eds.) Coma et états de conscience altérée (2011)Detailed reference viewed: 16 (0 ULg)
La neuro-imagerie: un outil diagnostique des etats de conscience alteree.
Thonnard, Marie ; Boly, Mélanie ; et al
in Medecine Sciences : M/S (2011), 27(1), 77-81
Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of ... [more ▼]
Vegetative and minimally conscious states diagnosis remained a major clinical challenge. New paradigms such as measurement of the global cerebral metabolism, the structural and functional integrity of fronto-parietal network, or the spontaneous activity in resting state have been shown to be helpful to disentangle vegetative from minimally conscious patients. Active neuroimagery paradigms also allow detecting voluntary and conscious activity in non-communicative patients. The implementation of these methods in clinical routine could permit to reduce the current high rate of misdiagnosis (40%). [less ▲]Detailed reference viewed: 18 (5 ULg)