Assessment of White Matter Injury and Outcome in Severe Brain Trauma: A Prospective Multicenter Cohort
; ; et al
in Anesthesiology (2012), 117(6), 1300-1310
BACKGROUND:: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging ... [more ▼]
BACKGROUND:: Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). METHODS:: In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n = 38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. RESULTS:: Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75-0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54-0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. CONCLUSIONS:: White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score. [less ▲]Detailed reference viewed: 17 (2 ULg)
Connectivity graph analysis of the auditory resting state network in tinnitus.
MAUDOUX, Audrey ; Lefèbvre, Philippe ; et al
in Brain Research (2012), 1485
Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T magnetic resonance imaging (MRI) scanner during resting condition (i.e. eyes closed, no task performance ... [more ▼]
Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3T magnetic resonance imaging (MRI) scanner during resting condition (i.e. eyes closed, no task performance). The auditory resting-state component was selected using an automatic component selection approach. Functional connectivity (correlations/anti-correlations) in the extracted network was portrayed by integrating the independent component analysis (ICA) approach with a graph theory method. Tinnitus and control groups showed different graph connectivity patterns. In the control group, the connectivity graph was divided into two distinct anti-correlated networks. The first one encompassed the auditory cortices and the insula. The second one encompassed frontoparietal and anterior cingulate cortices, brainstem, amygdala, basal ganglia/nucleus accumbens and parahippocampal regions. In the tinnitus group, only one of the two previously described networks was observed, encompassing the auditory cortices and the insula. Direct group comparison showed, in the tinnitus group, an increased functional connectivity between auditory cortices and the left parahippocampal region surviving multiple comparisons. We investigated a possible correlation between four tinnitus relevant measures (tinnitus handicap inventory (THI) and tinnitus questionnaire (TQ) scores, tinnitus duration and tinnitus intensity during the scanning session) and the connectivity pattern in the tinnitus population. We observed a significant positive correlation between the beta values of the posterior cingulate/precuneus region and the THI score. Our results show a modified functional connectivity pattern in tinnitus sufferers and highlight the role of the parahippocampal region in tinnitus physiopathology. They also point out the importance of the activity and connectivity pattern of the posterior cingulate cortex/precuneus region to the development of the tinnitus associated distress. This article is part of a Special Issue entitled: Tinnitus Neuroscience. [less ▲]Detailed reference viewed: 59 (9 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: 26 (1 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: 278 (31 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: 307 (59 ULg)
Prognosis of patients with altered states of consciousness
Bruno, Marie-Aurélie ; ; Vanhaudenhuyse, Audrey et al
in Schnakers, Caroline; Laureys, Steven (Eds.) Coma and disorders of consciousness (2012)Detailed reference viewed: 103 (2 ULg)
Auditory resting-state network connectivity in tinnitus: a functional MRI study.
; Lefèbvre, Philippe ; et al
in PLoS ONE (2012), 7(5), 36222
The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test ... [more ▼]
The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI "resting-state" connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus. [less ▲]Detailed reference viewed: 23 (0 ULg)
Reduction in inter-hemispheric connectivity in disorders of consciousness.
; ; Soddu, Andrea et al
in PLoS ONE (2012), 7(5), 37238
Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC ... [more ▼]
Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC diagnosis may be offered by the analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured with functional magnetic resonance imaging (fMRI) during the resting-state. Previous work has shown reduced functional connectivity within the "default network", a subset of regions known to be deactivated during engaging tasks, which correlated with the degree of consciousness impairment. However, it remains unclear whether the breakdown of connectivity is restricted to the "default network", and to what degree changes in functional connectivity can be observed at the single subject level. Here, we analyzed resting-state inter-hemispheric connectivity in three homotopic regions of interest, which could reliably be identified based on distinct anatomical landmarks, and were part of the "Extrinsic" (externally oriented, task positive) network (pre- and postcentral gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a group of 11 healthy subjects and 8 DOC patients. At the group level, our results indicate decreased inter-hemispheric functional connectivity in subjects with impaired awareness as compared to subjects with intact awareness. Individual connectivity scores significantly correlated with the degree of consciousness. Furthermore, a single-case statistic indicated a significant deviation from the healthy sample in 5/8 patients. Importantly, of the three patients whose connectivity indices were comparable to the healthy sample, one was diagnosed as locked-in. Taken together, our results further highlight the clinical potential of resting-state connectivity analysis and might guide the way towards a connectivity measure complementing existing DOC diagnosis. [less ▲]Detailed reference viewed: 44 (2 ULg)
A role for the default mode network in the bases of disorders of consciousness.
; Soddu, Andrea ; et al
in Annals of Neurology (2012), 72(3), 335-43
OBJECTIVE: Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity ... [more ▼]
OBJECTIVE: Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity. Nevertheless, the integrity of the structural architecture supporting this network and its relation with the exhibited functional disconnections are very poorly understood. We investigated the structural connectivity and white matter integrity of the DMN in patients with disorders of consciousness of varying clinical severity. METHODS: Fifty-two patients--19 in a vegetative state (VS), 27 in a minimally conscious state (MCS), and 6 emerging from a minimally conscious state (EMCS)--and 23 healthy volunteers participated in the study. Structural connectivity was assessed by means of probabilistic tractography, and the integrity of the resulting fibers was characterized by their mean fractional anisotropy values. RESULTS: Patients showed significant impairments in all of the pathways connecting cortical regions within this network, as well as the pathway connecting the posterior cingulate cortex/precuneus with the thalamus, relative to the healthy volunteers. Moreover, the structural integrity of this pathway, as well as that of those connecting the posterior areas of the network, was correlated with the patients' behavioral signs for awareness, being higher in EMCS patients than those in the upper and lower ranges of the MCS patients, and lowest in VS patients. INTERPRETATION: These results provide a possible neural substrate for the functional disconnection previously described in these patients, and reinforce the importance of the DMN in the genesis of awareness and the neural bases of its disorders. [less ▲]Detailed reference viewed: 33 (2 ULg)
Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients.
Bruno, Marie-Aurélie ; Majerus, Steve ; Boly, Mélanie et al
in Journal of Neurology (2012), 259(6), 1087-98
Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this ... [more ▼]
Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 +/- 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 +/- 19 years; 4 traumatic; 21 +/- 23 months post injury) and 14 MCS+ (aged 43 +/- 19 years; 5 traumatic; 19 +/- 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto-temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression. [less ▲]Detailed reference viewed: 254 (10 ULg)
Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients.
; Gosseries, Olivia ; et al
in Brain : A Journal of Neurology (2012), 135(Pt 4), 1308-20
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing ... [more ▼]
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment. [less ▲]Detailed reference viewed: 185 (2 ULg)
Brain connectivity in disorders of consciousness.
Boly, Mélanie ; ; et al
in Brain connectivity (2012), 2(1), 1-10
The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest ... [more ▼]
The last 10 years witnessed a considerable increase in our knowledge of brain function in survivors to severe brain injuries with disorders of consciousness (DOC). At the same time, a growing interest developed for the use of functional neuroimaging as a new diagnostic tool in these patients. In this context, particular attention has been devoted to connectivity studies-as these, more than measures of brain metabolism, may be more appropriate to capture the dynamics of large populations of neurons. Here, we will review the pros and cons of various connectivity methods as potential diagnostic tools in brain-damaged patients with DOC. We will also discuss the relevance of the study of the level versus the contents of consciousness in this context. [less ▲]Detailed reference viewed: 50 (1 ULg)
Burnout in healthcare workers managing chronic patients with disorders of consciousness.
Gosseries, Olivia ; Demertzi, Athina ; et al
in Brain Injury (2012)
Objectives: The aim of this study was to assess the presence of burnout among professional caregivers managing patients with severe brain injury recovering from coma and working in neurorehabilitation ... [more ▼]
Objectives: The aim of this study was to assess the presence of burnout among professional caregivers managing patients with severe brain injury recovering from coma and working in neurorehabilitation centres or nursing homes. Methods: The Maslach Burnout Inventory was sent to 40 centres involved in the Belgian federal network for the care of vegetative and minimally conscious patients. The following demographic data were also collected: age, gender, profession, expertise in the field, amount of time spent with patients and working place. Results: Out of 1068 questionnaires sent, 568 were collected (53% response rate). Forty-five were excluded due to missing data. From the 523 healthcare workers, 18% (n = 93) presented a burnout, 33% (n = 171) showed emotional exhaustion and 36% (n = 186) had a depersonalization. Profession (i.e. nurse/nursing assistants), working place (i.e. nursing home) and the amount of time spent with patients were associated with burnout. The logistic regression showed that profession was nevertheless the strongest variable linked to burnout. Conclusions: According to this study, a significant percentage of professional caregivers and particularly nurses taking care of patients in a vegetative state and in a minimally conscious state suffered from burnout. Prevention of burnout symptoms among caregivers is crucial and is expected to promote more efficient medical care of these challenging patients. [less ▲]Detailed reference viewed: 47 (9 ULg)
Hierarchical clustering of brain activity during human nonrapid eye movement sleep.
Boly, Mélanie ; ; et al
in Proceedings of the National Academy of Sciences of the United States of America (2012)
Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM ... [more ▼]
Consciousness is reduced during nonrapid eye movement (NREM) sleep due to changes in brain function that are still poorly understood. Here, we tested the hypothesis that impaired consciousness during NREM sleep is associated with an increased modularity of brain activity. Cerebral connectivity was quantified in resting-state functional magnetic resonance imaging times series acquired in 13 healthy volunteers during wakefulness and NREM sleep. The analysis revealed a modification of the hierarchical organization of large-scale networks into smaller independent modules during NREM sleep, independently from EEG markers of the slow oscillation. Such modifications in brain connectivity, possibly driven by sleep ultraslow oscillations, could hinder the brain's ability to integrate information and account for decreased consciousness during NREM sleep. [less ▲]Detailed reference viewed: 75 (4 ULg)
Le Sommeil dans l'Etat Végétatif et de Conscience Minimale
Cologan, Victor ; ; et al
Poster (2011, November)
Présentation des résultats de l'étude du sommeil chez les patients cérébrolésés en état de conscience altéré.Detailed reference viewed: 14 (4 ULg)
Wachkoma: medizinische Grundlagen und neurowissenschaftliche Revolution
Demertzi, Athina ; ; et al
in Jox, R.; Borasio, G. D.; Kühlmeyer, K. (Eds.) Leben im Koma Interdisziplinäre Perspektiven auf das Problem des Wachkomas (2011)Detailed reference viewed: 171 (6 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: 102 (19 ULg)