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Objective: Brain-injured patients who are unresponsive at the bedside (ie, vegetative state/unresponsive wakefulness syndrome - VS/UWS) may present brain activity similar to patients in minimally conscious state (MCS). This peculiar condition has been termed "non-behavioural MCS" or "MCS*". In the present study we aimed to investigate the proportion and underlying brain characteristics of patients in MCS*., Methods: Brain 18 F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) was acquired on 135 brain-injured patients diagnosed in prolonged VS/UWS (n = 48) or MCS (n = 87). From an existing database, relative metabolic preservation in the fronto-parietal network (measured with standardized uptake value) was visually inspected by three experts. Patients with hypometabolism of the fronto-parietal network were labelled "VS/UWS", while its (partial) preservation either confirmed the behavioural diagnosis of "MCS" or, in absence of behavioural signs of consciousness, suggested a diagnosis of "MCS*". Clinical outcome at 1-year follow-up, functional connectivity, grey matter atrophy, and regional brain metabolic patterns were investigated in the three groups (VS/UWS, MCS* and MCS)., Results: 67% of behavioural VS/UWS presented a partial preservation of brain metabolism (ie, MCS*). Compared to VS/UWS patients, MCS* patients demonstrated a better outcome, global functional connectivity and grey matter preservation more compatible with the diagnosis of MCS. MCS* patients presented lower brain metabolism mostly in the posterior brain regions compared to MCS patients., Interpretation: MCS* is a frequent phenomenon that is associated with better outcome and better brain preservation than the diagnosis of VS/UWS. Complementary exams should be provided to all unresponsive patients before taking medical decisions. ANN NEUROL 2021;90:89-100., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Patients with chronic disorders of consciousness face a significant lack of treatment options., Objective: We aimed at investigating the feasibility and the behavioral effects of home-based transcranial direct current stimulation (tDCS), applied by relatives or caregivers, in chronic patients in minimally conscious state (MCS)., Methods: Each participant received, in a randomized order, 20 sessions of active and 20 sessions of sham tDCS applied over the prefrontal cortex for 4 weeks; separated by 8 weeks of washout. Level of consciousness was assessed using the Coma Recovery Scale-Revised before the first stimulation (baseline), at the end of the 20 tDCS sessions (direct effects) and 8 weeks after the end of each stimulation period (long-term effects). Reported adverse events and data relative to the adherence (i.e., amount of sessions effectively received) were collected as well., Results: Twenty-seven patients completed the study and 22 patients received at least 80% of the stimulation sessions. All patients tolerated tDCS well, no severe adverse events were noticed after real stimulation and the overall adherence (i.e., total duration of stimulation) was good. A moderate effect size (0.47 and 0.53, for modified intention to treat and per protocol analysis, respectively) was observed at the end of the 4 weeks of tDCS in favor of the active treatment., Conclusions: We demonstrated that home-based tDCS can be used adequately outside a research facility or hospital by patients' relatives or caregivers. In addition, 4 weeks of tDCS moderately improved the recovery of signs of consciousness in chronic MCS patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of the study is to explore the possibility of oral feeding in unresponsive wakefulness syndrome/vegetative state (UWS/VS) patients., Method: We reviewed the clinical information of 68 UWS/VS patients (mean age 45 ± 11; range 16-79 years) searching for mention of oral feeding. UWS/VS diagnosis was made after repeated behavioural assessments using the Coma Recovery Scale-Revised. Patients also had complementary neuroimaging evaluations (positron emission tomography, functional magnetic resonance imaging and electroencephalography and diffusion tensor imaging)., Results: Out of the 68 UWS/VS patients, only two could resume oral feeding (3%). The first patient had oral feeding (only liquid and semi liquid) in addition to gastrostomy feeding and the second one could achieve full oral feeding (liquid and mixed solid food). Clinical assessments concluded that they fulfilled the criteria for a diagnosis of UWS/VS. Results from neuroimaging and neurophysiology were typical for the first patient with regard to the diagnosis of UWS/VS but atypical for the second patient., Conclusion: Oral feeding that implies a full and complex oral phase could probably be considered as a sign of consciousness. However, we actually do not know which components are necessary to consider the swallowing conscious as compared to reflex. We also discussed the importance of swallowing assessment and management in all patients with altered state of consciousness.

Objective: Visual pursuit should be tested with a mirror in patients with disorders of consciousness. This stimulus was indeed more efficient than a person or an object, and the auto-referential aspect was supposed to be the key feature. The present study tested the hypothesis that the mirror was more efficient because of its self-aspect., Methods: The mirror was compared (1) to the patient's picture and to the picture of a famous face, in 22 patients in minimally conscious state and (2) to the patient's picture and a fake mirror, which had dynamical and bright aspects of the mirror, without reflecting the face, in 26 other patients in minimally conscious state., Results: The mirror was more efficient than the patient's picture, which was not statistically different from the famous face. The second part of the study confirmed the statistical difference between the mirror and the picture. However, the fake mirror was neither statistically different from the mirror nor from the picture., Conclusions: Although our results suggest that the hypothesis proposed by previous studies was partly wrong, they confirm that the mirror is the best stimulus to use when assessing visual pursuit.

Objectives: To assess the effects of repeated transcranial direct current stimulation (tDCS) sessions on the level of consciousness in chronic patients in minimally conscious state (MCS)., Methods: In this randomized double-blind sham-controlled crossover study, we enrolled 16 patients in chronic MCS. For 5 consecutive days, each patient received active or sham tDCS over the left prefrontal cortex (2 mA during 20 min). Consciousness was assessed with the Coma Recovery Scale-Revised (CRS-R) before the first stimulation (baseline), after each stimulation (day 1-day 5) and 1 week after the end of each session (day 12)., Results: A treatment effect (p = 0.013; effect size = 0.43) was observed at the end of the active tDCS session (day 5) as well as 1 week after the end of the active tDCS session (day 12; p = 0.002; effect size = 0.57). A longitudinal increase of the CRS-R total scores was identified for the active tDCS session (p < 0.001), while no change was found for the sham session (p = 0.64). Nine patients were identified as responders (56%)., Conclusion: Our results suggest that repeated (5 days) left prefrontal tDCS improves the recovery of consciousness in some chronic patients in MCS, up to 1 week after the end of the stimulations.

Background: Between pathologically impaired consciousness and normal consciousness exists a scarcely researched transition zone, referred to as emergence from minimally conscious state, in which patients regain the capacity for functional communication, object use, or both. We investigated neural correlates of consciousness in these patients compared with patients with disorders of consciousness and healthy controls, by multimodal imaging., Methods: In this cross-sectional, multimodal imaging study, patients with unresponsive wakefulness syndrome, patients in a minimally conscious state, and patients who had emerged from a minimally conscious state, diagnosed with the Coma Recovery Scale-Revised, were recruited from the neurology department of the Centre Hospitalier Universitaire de Liège, Belgium. Key exclusion criteria were neuroimaging examination in an acute state, sedation or anaesthesia during scanning, large focal brain damage, motion parameters of more than 3 mm in translation and 3° in rotation, and suboptimal segmentation and normalisation. We acquired resting state functional and structural MRI data and (18)F-fluorodeoxyglucose (FDG) PET data; we used seed-based functional MRI (fMRI) analysis to investigate positive default mode network connectivity (within-network correlations) and negative default mode network connectivity (between-network anticorrelations). We correlated FDG-PET brain metabolism with fMRI connectivity. We used voxel-based morphometry to test the effect of anatomical deformations on functional connectivity., Findings: We recruited a convenience sample of 58 patients (21 [36%] with unresponsive wakefulness syndrome, 24 [41%] in a minimally conscious state, and 13 [22%] who had emerged from a minimally conscious state) and 35 healthy controls between Oct 1, 2009, and Oct 31, 2014. We detected consciousness-level-dependent increases (from unresponsive wakefulness syndrome, minimally conscious state, emergence from minimally conscious state, to healthy controls) for positive and negative default mode network connectivity, brain metabolism, and grey matter volume (p<0·05 false discovery rate corrected for multiple comparisons). Positive default mode network connectivity differed between patients and controls but not among patient groups (F test p<0·0001). Negative default mode network connectivity was only detected in healthy controls and in those who had emerged from a minimally conscious state; patients with unresponsive wakefulness syndrome or in a minimally conscious state showed pathological between-network positive connectivity (hyperconnectivity; F test p<0·0001). Brain metabolism correlated with positive default mode network connectivity (Spearman's r=0·50 [95% CI 0·26 to 0·61]; p<0·0001) and negative default mode network connectivity (Spearman's r=-0·52 [-0·35 to -0·67); p<0·0001). Grey matter volume did not differ between the studied groups (F test p=0·06)., Interpretation: Partial preservation of between-network anticorrelations, which are seemingly of neuronal origin and cannot be solely explained by morphological deformations, characterise patients who have emerged from a minimally conscious state. Conversely, patients with disorders of consciousness show pathological between-network correlations. Apart from a deeper understanding of the neural correlates of consciousness, these findings have clinical implications and might be particularly relevant for outcome prediction and could inspire new therapeutic options., Funding: Belgian National Funds for Scientific Research (FNRS), European Commission, Natural Sciences and Engineering Research Council of Canada, James McDonnell Foundation, European Space Agency, Mind Science Foundation, French Speaking Community Concerted Research Action, Fondazione Europea di Ricerca Biomedica, University and University Hospital of Liège (Liège, Belgium), and University of Western Ontario (London, ON, Canada)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it remains unclear why clinical improvement is only observed in a subgroup of patients., Objectives: In this retrospective study, we investigated the relationship between tDCS responsiveness and neuroimaging data from MCS patients., Methods: Structural Magnetic Resonance Imaging (MRI), Fluorodeoxyglucose Positron emission tomography (FDG-PET) and clinical electroencephalography (EEG) were acquired in 21 sub-acute and chronic MCS patients (8 tDCS responders) who subsequently (<48 h) received left dorsolateral prefrontal (DLPF) tDCS in a double-blind randomized cross-over trial. The behavioral data have been published elsewhere (Thibaut et al., Neurology, 2014)., Results: Grey matter atrophy was observed in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the cingulate cortex, the hippocampi, part of the rolandic regions, and the left thalamus. FDG-PET showed hypometabolism in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the precuneus, and the thalamus. EEG did not show any difference between the two groups., Conclusion: Our findings suggest that the transient increase of signs of consciousness following left DLPF tDCS in patients in MCS require grey matter preservation and residual metabolic activity in cortical and subcortical brain areas known to be involved in attention and working memory. These results further underline the critical role of long-range cortico-thalamic connections in consciousness recovery, providing important information for guidelines on the use of tDCS in disorders of consciousness., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Spasticity is a frequent complication after severe brain injury, which may impede the rehabilitation process and diminish the patients' quality of life., Aim: We here investigate the presence of spasticity in a population of non-communicative patients with disorders of consciousness. We also evaluate the correlation between spasticity and potential factors of co-morbidity, frequency of physical therapy, time since insult, presence of pain, presence of tendon retraction, etiology and diagnosis., Design: Cross-sectional study., Setting: University Hospital of Liège, Belgium., Population: Sixty-five patients with chronic (>3 months post insult) disorders of consciousness were included (22 women; mean age: 44±14 y; 40 with traumatic etiology; 40 in a minimally conscious state; time since insult: 39±37 months)., Methods: Spasticity was measured with the Modified Ashworth Scale (MAS) and pain was assessed using the Nociception Coma Scale-Revised (NCS-R)., Results: Out of 65 patients, 58 demonstrated signs of spasticity (89%; MAS≥1), including 40 who showed severe spasticity (61.5%; MAS≥3). Patients with spasticity receiving anti-spastic medication were more spastic than unmedicated patients. A negative correlation was observed between the severity of spasticity and the frequency of physical therapy. MAS scores correlated positively with time since injury and NCS-R scores. We did not observe a difference of spasticity between the diagnoses., Conclusion: A large proportion of patients with disorders of consciousness develop severe spasticity, possibly affecting their functional recovery and their quality of life. The observed correlation between degrees of spasticity and pain scores highlights the importance of pain management in these patients with altered states of consciousness. Finally, the relationship between spasticity and treatment (i.e., pharmacological and physical therapy) should be further investigated in order to improve clinical care., Clinical Rehabilitation Impact: Managing spasticity at first signs could improve rehabilitation of patients with disorders of consciousness and maximize their chances of recovery. In addition, decreasing this trouble could allow a better quality of life for these non-communicative patients.

Objective: To assess the effectiveness of soft splints on spasticity and hand opening in chronic patients with upper limb spasticity and disorders of consciousness (vegetative state/unresponsive wakefulness syndrome-VS/UWS and minimally conscious state-MCS)., Methods: In this prospective single-blind controlled trial, a blind evaluator assessed spasticity (Modified Ashworth Scale and Modified Tardieu Scale), range of motion (ROM) at the metacarpophalangeal, wrist and elbow joints and the patients' hand opening before and after soft splinting, manual stretching and a control condition (i.e. no treatment), as well as 60 minutes later., Subjects: Seventeen patients with chronic (>3 months) disorders of consciousness were included (five VS/UWS; seven women; mean age = 42 ± 12 years; time since insult = 35 ± 31 months). Patients received either passive splinting, manual stretching treatment or no treatment., Results: Thirty minutes of soft splinting or 30 minutes of manual stretching both improved spasticity of the finger flexors. An increase of hand opening ability was observed after 30 minutes of soft splinting., Conclusion: Thirty minutes of soft splint application reduces spasticity and improves hand opening of patients with chronic disorders of consciousness. Soft splinting is well tolerated and does not require supervision.

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

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.

BACKGROUND: Spasticity is a frequent complication after severe brain injury, which may prevent the rehabilitation process and worsen the patients' quality of life. OBJECTIVES: In this study, we investigated the correlation between spasticity, muscle contracture, and the frequency of physical therapy (PT) in subacute and chronic patients with disorders of consciousness (DOC). METHODS: 109 patients with subacute and chronic disorders of consciousness (Vegetative state/Unresponsive wakefulness syndrome – VS/UWS; minimally conscious state – MCS and patients who emerged from MCS – EMCS) were included in the study (39 female; mean age: 40±13.5y; 60 with traumatic etiology; 35 VS/UWS, 68 MCS, 6 EMCS; time since insult: 38±42months). The number of PT sessions (i.e., 20 to 30 minutes of conventional stretching of the four limbs) was collected based on patients' medical record and varied between 0 to 6 times per week (low PT = 0–3 and high PT = 4–6 sessions per week). Spasticity was measured with the Modified Ashworth Scale (MAS) on every segment for both upper (UL) and lower limbs (LL). The presence of muscle contracture was assessed in every joint. We tested the relationship between spasticity and muscle contracture with the frequency of PT as well as other potential confounders such as time since injury or anti-spastic medication intake. RESULTS: We identified a negative correlation between the frequency of PT and MAS scores as well as the presence of muscle contracture. We also identified that patients who received less than four sessions per week were more likely to be spastic and suffer from muscle contracture than patients receiving 4 sessions or more. When separating subacute (3 to 12 months post-insult) and chronic (>12months post-insult) patients, these negative correlations were only observed in chronic patients. A logit regression model showed that frequency of PT influenced spasticity, whereas neither time since insult nor medication had a significant impact on the presence of spasticity. On the other hand, PT, time since injury and medication seemed to be associated with the presence of muscle contracture. CONCLUSION: Our results suggest that, in subacute and chronic patients with DOC, PT could have an impact on patients' spasticity and muscles contractures. Beside PT, other factors such as time since onset and medication seem to influence the development of muscle contractures. These findings support the need for frequent PT sessions and regular re-evaluation of the overall spastic treatment for patients with DOC. [ABSTRACT FROM AUTHOR]