Search

Objective: We tested the preliminary effects of bilateral anodal transcranial direct current stimulation (tDCS) in patients with disorders of consciousness., Design: Open label pilot study., Subjects: Ten chronic (greater than 12 months) patients in a minimally conscious state (MCS) following severe traumatic brain injury., Methods: The patients received 10 sessions of bilateral M1 anodal tDCS. Behavioural changes were assessed with the Coma Recovery Scale-Revised (CRS-R) before stimulation (T-1, T0), after five sessions (T1), at the end of the stimulation (T2), after two weeks (T3) and after three months (T4). Moreover, an EEG assessment was conducted., Results: Eight out of 10 patients showed new clinical signs of consciousness; specifically, a 2-point CRS-R improvement was detected in the last follow-up (p = 0.004). EEG upper α bandwidth was greater in the parietal site at T1 (p < 0.034). In addition, we found a significant correlation between behavioral and EEG indices at T1 (r =  0.89; p =  0.001)., Conclusion: This preliminary study presents several limitations (small sample size and no control group). However, it provides important initial data that can be used to design randomized clinical trials testing this novel approach in MCS and to further explore EEG as a neural marker for the effects of tDCS.

Background: The prognosis value of early clinical diagnosis of consciousness impairment is documented by an extremely limited number of studies, whereas it may convey important information to guide medical decisions., Objective: We aimed at determining if patients diagnosed at an early stage (<90 days after brain injury) as being in the minimally conscious state (MCS) have a better prognosis than patients in the vegetative state/Unresponsive Wakefulness syndrome (VS/UWS), independent of care limitations or withdrawal decisions., Methods: Patients hospitalized in ICUs of the Pitié-Salpêtrière Hospital (Paris, France) from November 2008 to January 2011 were included and evaluated behaviourally with standardized assessment and with the Coma Recovery Scale-Revised as being either in the VS/UWS or in the MCS. They were then prospectively followed until 1July 2011 to evaluate their outcome with the GOSE. We compared survival function and outcomes of these two groups., Results: Both survival function and outcomes, including consciousness recovery, were significantly better in the MCS group. This difference of outcome still holds when considering only patients still alive at the end of the study., Conclusions: Early accurate clinical diagnosis of VS/UWS or MCS conveys a strong prognostic value of survival and of consciousness recovery.

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.

Objective: The Sensory Modality Assessment and Rehabilitation Technique (SMART) was developed to assess the levels of awareness, functional, sensory and communicative abilities of adults in vegetative (VS) or minimally-conscious states following severe brain injury. The current study seeks to ascertain if a total score can be derived from the individual assessments contained within SMART and to test the internal construct and predictive validity of that total score., Subjects: Persons in VS were recruited over a 3-year period and current status was determined after a 17-year follow-up., Design: Data were evaluated by fit to the Rasch model. Predictive validity for emergence from VS was ascertained through an Area-Under-the-Curve [AUC] analysis., Results: Sixty people in VS were assessed on several occasions. Average age on admission was 38.8 years; 30 had anoxic brain damage; 21 traumatic injury. The Rasch analysis indicated the raw score was a sufficient statistic for awareness. Over half [55%] failed to emerge from VS. For those with anoxic brain injury, a SMART cut point of 85 gave an AUC of 0.966 (95% CI = 0.910-1.00) for emergence, as did a cut point of 68 for those with traumatic brain injury., Discussion: The current analysis suggests that SMART may have important predictive attributes for emergence (or lack thereof). No change in status of those discharged in VS has been reported to this present day.

Objective: The aim of this study was to analyse immediate responses to individual dialogic music therapy (IDMT) of patients with unresponsive wakefulness syndrome (UWS) and individuals in a minimally conscious state (MCS) and to develop an assessment tool for IDMT., Methods: Seven patients were subjected to three conditions: (1) sounds and stimuli of the daily environment immediately before IDMT, (2) specific improvisational music therapy intended to establish a dialogue with the patient (IDMT) and (3) sounds and stimuli of the daily environment immediately after IDMT. Video recordings were analysed by six independent assessors using 'Music Therapy in a Vegetative or Minimally Conscious State (MUVES)', an assessment tool developed in this study. Diagnosis of UWS or MCS was established using the coma recovery scale-revised (CRS-R)., Results: During IDMT, MUVES total score was higher than during the other conditions (mean difference = 3.36; p = 0.02). During IDMT, there was no significant difference in MUVES total score between the UWS and MCS sub-groups (p = 0.29). Mean inter-rater-reliability of MUVES total score was 0.76., Conclusions: IDMT may induce immediate responses in patients in low awareness states, particularly also in patients with UWS. MUVES appears to be an acceptably reliable assessment tool for IDMT.

Aim: Recovery of consciousness and recovery of function among patients with prolonged disorders of consciousness rarely occur. Those patients who do regain consciousness typically remain with severe disability. The aim of this retrospective study is to suggest that continuing improvement is possible in a survivor of catastrophic brain injury after being in a prolonged state of disordered consciousness., Case Study: This retrospective single case study follows the progress of a 29 year old man, I.J, who sustained a severe traumatic brain injury following an assault in October 2011. He was in a vegetative state for 15 months and in a minimally conscious state for a further 4 months. This was followed by a slow and steady recovery of motor and cognitive functions. At 3 years post-injury I.J is considered to be moderately disabled. He is now living in the community with continuing outpatient support. On the disability rating scale his level of functioning is rated as mildly dependent., Conclusion: This study shows that continuing recovery to a level of moderate disability is possible, even after a prolonged disorder of consciousness. Intense multi-disciplinary long-term rehabilitation and cranioplasty may be contributing factors for such an unexpected recovery.

Primary Objective: To reveal covert abilities in a minimally conscious state (MCS) through an innovative activation paradigm based on olfactory imagery., Research Design: Case study., Methods and Procedures: A patient in MCS was asked to 'imagine an unpleasant odour' or to 'relax' in response to the appearance on a screen of a downward pointing arrow or a cross, respectively. Electrophysiological responses to stimuli were investigated by means of an 8-channel EEG equipment and analysed using a specific threshold algorithm. The protocol was repeated for 10 sessions separated from each other by 2 weeks. Accuracy, defined as the number of successes with respect to the total number of trials, was used to evaluate the number of times in which the classification strategy was successful., Main Outcomes and Results: Analyses of accuracy showed that the patient was able to activate and to relax himself purposefully and that he optimized his performances with the number of sessions, probably as a result of training-related improvements., Conclusions: Subtle signs of consciousness may be under-estimated and need to be revealed through specific activation tasks. This paradigm may be useful to detect covert signs of consciousness, especially when patients are precluded from carrying out more complex cognitive tasks.

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.

Objective: The aim of this study was to objectively evaluate the brain activity potential of patients with impaired consciousness in a chronic stage of diffuse brain injury (DBI) using functional MRI (fMRI) following music stimulation (MS)., Methods: Two patients in a minimally conscious state (MCS) and five patients in a vegetative state (VS) due to severe DBI were enrolled along with 21 healthy adults. This study examined the brain regions activated by music and assessed topographical differences of the MS-activated brain among healthy adults and these patients., Results: MS was shown to activate the bilateral superior temporal gyri (STG) of both healthy adults and patients in an MCS. In four of five patients in a VS, however, no significant activation in STG could be induced by the same MS. The remaining patient in a VS displayed the same MS-induced brain activation in STG as healthy adults and patients in an MCS and this patient's status also improved to an MCS 4 months after the study., Conclusions: The presence of STG activation by MS may predict a possible improvement of patients in a VS to MCS and fMRI employing MS may be a useful modality to objectively evaluate consciousness in these patients.

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.

Objective: The aim of the study was to validate the use of electromyography (EMG) for detecting responses to command in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS)., Methods: Thirty-eight patients were included in the study (23 traumatic, 25 patients >1 year post-onset), 10 diagnosed as being in VS/UWS, eight in MCS- (no response to command) and 20 in MCS+ (response to command). Eighteen age-matched controls participated in the experiment. The paradigm consisted of three commands (i.e. 'Move your hands', 'Move your legs' and 'Clench your teeth') and one control sentence (i.e. 'It is a sunny day') presented in random order. Each auditory stimulus was repeated 4 times within one block with a stimulus-onset asynchrony of 30 seconds., Results: Post-hoc analyses with Bonferroni correction revealed that EMG activity was higher solely for the target command in one patient in permanent VS/UWS and in three patients in MCS+., Conclusion: The use of EMG could help clinicians to detect conscious patients who do not show any volitional response during standard behavioural assessments. However, further investigations should determine the sensitivity of EMG as compared to neuroimaging and electrophysiological assessments.

Primary Objective: A comparison between unitary and non-unitary views on minimal consciousness., Research Design: First, unitary (all-or-none) and non-unitary (gradual or continuous) models of consciousness are defined as they have been developed in both philosophy and neurophysiology. Then, the implications of these ideas to the notion the minimally conscious state (MCS) are discussed., Methods and Procedures: Review and analysis of theoretical conceptions and empirical data., Main Outcome and Results: Both kinds of models are compatible with the actual definitions of MCS. Although unitary views may seem to contradict the description of the MCS in 'Neurology' 2002, the apparent contradiction can easily be solved. Most recent data, particularly those obtained using fMRI and concerning learning, emotional responsiveness and pain and suffering, speak for non-unitary models., Conclusions: Most evidence speaks for non-unitary models of minimal consciousness. If these models are correct, patients with MCS may have, in addition to temporal fluctuations, a lower level of consciousness compared with fully conscious individuals. A still lower level could characterize patients diagnosed as unresponsive wakefulness syndrome (UWS). From this point of view, therefore, the difference between UWS and MCS is gradual rather than qualitative. However, due to methodological limitations of the available studies, the evidence for non-unitary models cannot be regarded as definite.

Background: Functional neuroimaging studies have observed preserved neural activation to personally relevant stimuli in patients within the disorders of consciousness (DOC) spectrum. As the majority of studies have focused on adult DOC patients, little is known about preserved activation in the developing brain of children with impaired consciousness., Case Study: The aim of this study is to use fMRI to measure preserved neural activation to personally relevant stimuli (subject's own name and familiar voice) in a paediatric patient who sustained a traumatic brain injury and anoxic-ischaemia following a motor vehicle accident at 18 months of age rendering her probable for minimally conscious state. Contrasts revealed activation in the right middle frontal gyrus when hearing the subject's own name and the anterior supramarginal gyrus when hearing a familiar voice., Conclusion: This study provides preliminary support for fMRI as a method to measure preserved cognitive functioning in paediatric DOC patients.

Research Design: Analysis of inter-rater reliability and concurrent validity., Objective: To determine measurement properties of a Spanish version of The Coma Recovery Scale-Revised (CRS-R)., Methods and Procedures: A sample of 35 in-patients with severe acquired brain injury. To test concurrent validity of the translated scale, the Glasgow Coma Scale (GSC) and Disability Rating Scale (DRS) were also administered. Two experts in the field were recruited to assess inter-rater agreement., Results: Inter-rater reliability was good for total CRS-R scores (Cronbach α = 0.973, p = 0.001). Sub-scale analysis showed moderate-to-high inter-rater agreement. Total CRS-R scores correlated significantly (p < 0.05) with total GCS (r = 0.74) and DRS (r = 0.54) scores, indicating acceptable concurrent validity., Conclusions: The Spanish version of CRS-R can be administered reliably by trained and experienced examiners. CRS-R appears capable of differentiating patients in Emergence from Minimally Conscious State (EMCS) or in Minimally Conscious State (MCS) from those in a Vegetative State (VS).

Background: Functional neuroimaging of patients in the vegetative state has been shown to provide diagnostic and prognostic information beyond that which conventional behavioural assessments may allow. However, before these promising approaches may reach large numbers of patients through a standard clinical protocol, it is necessary to determine the utility of these assessments-i.e. the accuracy of their diagnoses., Methods and Results: This study demonstrated that, due to the nature of statistical testing and the absence of a 'ground truth' of consciousness, it is impossible to calculate the conventional measures of clinical utility-sensitivity and specificity-for diagnoses made on the basis of functional neuroimaging for command-following. Nevertheless, it is crucial for such measures to be determined in order for valuable clinical resources to be distributed wisely. Therefore, a number of alternative guidelines are offered for the estimation of clinical utility., Conclusions: By evaluating new and existing functional neuroimaging methods against the proposed guidelines, this study argues that it may be possible to achieve dramatically and efficiently improved diagnostic and prognostic accuracy for all vegetative state patients.

Introduction: Zolpidem is a non-benzodiazepine drug used for the therapy of insomnia, which has selectivity for stimulating the effect of GABA-A receptors. Recently, a paradoxical arousing effect of zolpidem in patients with severe brain damage has been repeatedly reported., Methods: A placebo-controlled magnetic resonance study was conducted to evaluate its effect on BOLD and metabolites spectral signals in a patient with severe brain injuries and an age-matched healthy volunteer. A multi-modal analysis was used to assess aspects in the pharmacologically-induced changes in the resting-state brain metabolism., Results: A significantly increased BOLD signal was transiently localized in the left frontal cortices, bilateral anterior cingulated areas, left thalamus and right head of the caudate nucleus. The healthy subject showed a deactivation of the frontal, parietal and temporal cortices. BOLD signal changes were found to significantly correlate with concentrations of extravascular metabolites in the left frontal cortex. It is discussed that, when zolpidem attaches to modified GABA receptors of neurodormant brain cells, brain activation is induced. This might explain the significant correlations of BOLD signal changes and proton-MRS metabolites in this patient after zolpidem., Conclusion: It was concluded that proton-MRS and BOLD signal assessment could be used to study zolpidem-induced metabolic modulation in a resting state.

Objective: To describes socio-demographic and clinical features of adults and children in vegetative state (VS) and minimally conscious state (MCS)., Design: Observational cross-sectional study., Methods: Demographic, aetiological and clinical data were collected, together with patients' management procedures. Mann-Whitney U-test was used for continuous variables and chi-squared test for categorical variables., Results: Six hundred patients (69.7% in VS; 6% children) were enrolled. No difference regarding age at enrolment, age at acute event and disease duration was observed between VS and MCS. Disease duration was superior to 10 years for 3.3% of the whole sample and 64.3-77% of cases had a non-traumatic aetiology. Mean number of drugs per adult patient was four and decreased consistently with increased disease duration., Discussion: Patients with VS and MCS were similar for age at acute event and at enrolment, both over 50 years, as well as for the frequency of non-traumatic aetiology. Disease duration was similar for both conditions and 2.6% of VS and 4.8% of MCS patients survived for more than 10 years. Finally care and treatment needs are similar and not related to diagnosis.

Introduction: Pain perception is currently an open question in patients suffering from prolonged disorders of consciousness. The aim of the present study was to examine nociceptive specific laser evoked responses (LEPs) in view of long-latency evoked potentials by non-painful electrical stimuli (SEPs) and auditory mismatch negativity (MM)., Methods: Three vegetative state (VS), four minimal Conscious State (MCS) patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, stimulating the dorsum of the right hand by noxious laser and innocuous electrical stimulus, according to normal controls subjective rating. An auditory paradigm for MM was also employed., Results: The MM was present in all patients. The LEP vertex complex was recognizable in all cases, with a significant latency increase of both N2 and P2 which displayed changes of topographic representation. Late SEPs were absent in all patients except in one MCS case, who showed a significant N2 and P2 latency increase., Discussion: The results may suggest that high relevant stimuli may be processed even in patients with severe brain damage. Larger series and multimodal approaches may contribute to confirm that cortical arousal toward pain salience may be a primary function for life persistence.

Primary Objective: Even in non-communicative disorders of consciousness such as vegetative and minimally conscious states, increasing the personal relevance and complexity of stimuli appears to enhance their activating effect in patients. It was hypothesized that enriched stimulation in an immersive environment could increase the number and/or the goal-directed quality of active movements., Methods, Research Design and Procedures: Twelve patients with severe disorders of consciousness in the post-acute phase underwent an experimental protocol of sensory stimulation based on biographically meaningful objects. Enriched stimulation was compared to both a pattern of stimulation without augmented context and to standard interactions in a clinical setting. An A-B-C-B-A paradigm was applied to minimize the confounding effects of clinical changes during the protocol. The motor behaviours were recorded using the Wessex Head Injury Matrix (WHIM) and analysed with standard parametric statistics., Results and Conclusions: The results show a difference in patient response as a function of stimulation context: familiar objects in an augmented environment elicited a greater range of behavioural responses. These results support the hypothesis that the emotional richness and complexity of environmental stimuli can play a key role in evoking active behaviours.

Objective: To evaluate microtubule-associated proteins (MAP-2), a dendritic marker of both acute damage and chronic neuronal regeneration after injury, in serum of survivors after severe TBI and examine the association with long-term outcome., Methods: Serum concentrations of MAP-2 were evaluated in 16 patients with severe TBI (Glasgow Coma Scale score [GCS] ≤ 8) 6 months post-injury and in 16 controls. Physical and cognitive outcomes were assessed, using the Glasgow Outcome Scale Extended (GOSE) and Levels of Cognitive Functioning Scale (LCFS), respectively., Results: Severe TBI patients had significantly higher serum MAP-2 concentrations than normal controls with no history of TBI (p = 0.008) at 6 months post-injury. MAP-2 levels correlated with the GOSE (r = 0.58, p = 0.02) and LCFS (r = 0.65, p = 0.007) at month 6. Significantly lower serum levels of MAP-2 were observed in patients in a vegetative state (VS) compared to non-VS patients (p < 0.05). A trend tracking the level of consciousness was observed., Conclusions: Severe TBI results in a chronic release of MAP-2 into the peripheral circulation in patients with higher levels of consciousness, suggesting that remodelling of synaptic junctions and neuroplasticity processes occur several months after injury. The data indicate MAP-2 as a potential marker for emergence to higher levels of cognitive function.

Background: The use of validated behavioural assessment scales in assessment of patients with Disorders of Consciousness (DOC) is well established. However, there is little evidence to guide decisions on total time spent in behavioural assessment., Objective: To assess whether brief behavioural assessment was as effective as extended behavioural assessment in detecting non-vegetative behaviours., Methods: Consecutive patients with suspected DOC were assessed with two standardized instruments: Coma Recovery Scale Revised (CRS-R) and Sensory Modality Assessment and Rehabilitation Technique (SMART). Assessors were blinded to results from the other scale at the point of assessment. Two administrations of CRS-R together took 50-60 minutes ('brief' assessment). One complete SMART assessment took 600 minutes ('extended' assessment). Patients were classified as being in a vegetative state (VS) or minimally conscious state (MCS)/emerged from minimally conscious state (EMCS), following brief and extended assessment., Results: Ten patients were assessed. Brief and extended assessment yielded the same diagnostic category (VS or MCS) for six patients and different categories for four, with extended assessment detecting higher level behaviours., Conclusions: Brief behavioural assessment was not as effective as extended assessment in detecting non-vegetative behaviours. Total time spent in behavioural assessment is likely important. Further studies and clearer clinical guidance are needed.

Research Design: Retrospective observational study., Objective: To compare motor variables between patients with severe traumatic brain injury who emerge and patients who do not emerge from vegetative state, in an attempt to identify early motor manifestations associated with consistent patient improvement., Methods and Procedures: Patients were divided into two groups: group 1, patients who emerged from vegetative state attaining at least a state of functional interactive communication and/or functional use of two different objects (n = 8); and group 2, patients who did not emerge (n = 7). Twenty-one motor variables were compared weekly between groups until the end of the treatment programme., Results: Significant differences were observed in head control (p = 0.051) and head turning (p = 0.002) variables, as well as in visual fixation and pursuit (p = 0.051) after a median of 41 days of therapy; and in head control and head turning; visual fixation and pursuit; phonation; pain localization, reach and grasp, and trunk movement (p ≤ 0.051) after a median of 212 days of programme duration., Conclusions: Head turning, together with or immediately followed by visual pursuit and fixation, proved to be clinically significant variables associated with recovery from vegetative state to higher states of consciousness beyond minimally conscious state.

Objective: This study tested the hypothesis of electroencephalographic reactivity (EEG-R) as a reliable tool for the prognostic evaluation of consciousness recovery in post-acute brain injury., Methods: EEG was recorded in 50 unconscious patients. All patients had a GCS ≤8 and LCF score ≤2. They suffered from traumatic brain injury, cerebrovascular disease or anoxia. EEG was classified according to Synek classification (1988) as benign, malignant and 'uncertain significance'. EEG-R to painful stimuli was tested., Results: Twenty per cent of patients fulfilled the criteria for benign prognosis, 38% for malignant prognosis, while 42% of them were included in the 'uncertain' category, preventing them from stating a prognosis. EEG-R was detected in 48% of patients classified 'uncertain' and 92% of them recovered consciousness within 5 months from EEG recording. Multivariable analysis indicates that an unconscious patient admitted to the Rehabilitation Unit within 2 months from brain injury, with a LCF score equal to 2 and the presence of EEG-R has a probability of recovery of consciousness higher than 97%., Conclusion: EEG-R is a good positive factor for the prognosis of recovery of consciousness in the post-acute phase of brain injury, with a high specificity (88.9%). Nevertheless, its absence is not invariably associated with a poor prognosis.

Background: Assessment of awareness in patients with severe brain injury remains subjective, although patients with even limited awareness (e.g. minimal conscious state, MCS) have different prognoses and treatment than those in vegetative state (VS). Recently, task appropriate differential regional activation in VS has been reported using fMRI during mental imagery., Primary Objective: Demonstration of conscious awareness in reproducible differential EEG source localization images in a VS patient reflecting requested mental imagery was performed., Methods: A VS patient (with re-test) and a normal control were requested to imagine singing and to mentally perform serial subtraction, while EEG was recorded. QEEG source localization was performed to identify regions of brain activation in response to tasks., Results: Replicable distinctive activation of brain areas appropriate for each task was seen in the VS patient and control. Frequency spectra shifted to beta, with significant source activation in regions including the bilateral anterior cingulate, insula, left caudate and dorsolateral pre-frontal cortex to singing and the putamen, insula, left pre-frontal cortex and right temporal gyrus to subtraction by 7's., Conclusions: Results from this single case suggests the potential utility of QEEG source localization images to detect awareness in patients clinically diagnosed as being in VS. This indicates the possibility that EEG may serve as an important adjunct to the assessment of awareness in patients with disorders of consciousness in the clinical setting.

Primary Objective: To explore the epidemiology of patients in a Vegetative State (VS) and Minimally Conscious State (MCS) that are cared for in long-term care facilities in Austria. The study was inspired by increasing evidence that the cognitive abilities of minimal behavioural patients with disorders of consciousness may be under-rated., Research Design: Since an unequivocal diagnostic code with which to follow-up these long-term patients after the acute event does not exist, a telephone survey was conducted., Methods and Procedures: A three-step telephone- and questionnaire-based inquiry was conducted between 2007 and 2009., Main Outcomes and Results: One hundred and fourteen out of 889 long-term care facilities and nursing homes cared for 269 patients in a VS and 120 patients in a MCS, indicating a prevalence of 3.36 patients per 100 000 for VS and 1.5 per 100 000 for MCS in long-term care facilities., Conclusions: The results are discussed in the light of differences in prevalence in other Western countries. Future studies should concentrate on these long-term patients since the results have implications regarding how to organize appropriate neurorehabilitative care that meets the needs of such patients.

Objective: Evaluating a learning assessment procedure for monitoring progress with two post-coma adults with a diagnosis of vegetative state., Method: ABABCBCB and ABABCB designs were used for the two participants, with A representing baseline, B intervention and C control conditions. Participants' activation of an optic microswitch by eyelid closure produced stimulation during B phases., Results: One participant increased responding during B phases and decreased it during the C condition, suggesting a non-reflective minimal level of consciousness. She showed P300 and mismatch negativity responses and scored at the vegetative level on the Coma Recovery Scale-Revised (CRS-R). The other participant increased responding during the initial B phases without decline during the first (viable) part of the C condition, suggesting a pre-conscious level. He showed indistinct P300 and mismatch negativity responses and vegetative-level scores on the CRS-R., Conclusion: Learning data seemed reconcilable with neurophysiological measures and more positive than CRS-R scores.

Background: Chronic disorders of consciousness are costly and challenging conditions to treat. Although recent studies that have tested pharmacological and electrical stimulation for these conditions are promising, the optimal intervention, mechanisms of action and side effects of these experimental therapies are unclear., Objective: To systematically review the clinical results of treatments for vegetative state (VS) and minimally conscious state (MCS) from the last 10 years., Methods: MEDLINE, LILACS and SCOPUS were searched as data sources. Because the potential bias when search is limited to databases of peer-reviewed journals, reference lists were examined and experts in the field were contacted for other relevant or unpublished articles (i.e. negative studies). No negative unpublished studies were found. Studies were included related to therapeutic interventions in adult MCS or VS patients at least 3 and 12 months after non-traumatic and traumatic injuries, respectively. Eight studies met the inclusion criteria. The following interventions were reviewed: levodopa, amantadine, zolpidem, baclofen, dorsal column stimulation and deep brain stimulation., Conclusions: The adverse effects that were associated with these treatments were typically mild. Most of the studies demonstrated considerable improvements with the interventions, but their low strength of evidence limit the generalizability of the findings.

Objective: The purpose of this study was to highlight a speech expression disorder considered as a mixed speech apraxia (SA) and dysarthria syndrome in patients with chronic severe diffuse brain injury (DBI) and to determine its correlation with anatomical localizations of brain lesions using neuroimaging., Methods: Among 140 patients with chronic severe DBI, eight showed this type of speech disorder. MRI (five patients) and FDG-PET (six patients) procedures were performed., Results: Affected patients could comprehend verbally, read words silently and express words using a word board. Compared with SA, the disorder is characterized by similarities in regards to reduced phonation and marked facio-oral apraxia, but by distinct differences in terms of an accompanying dysphagia and pyramidal/extra-pyramidal symptoms that are similar to symptoms associated with dysarthria due to pseudobulbar palsy. Diffuse regions of the white matter including the left arcuate fasciculus (AF) were significantly decreased in fractional anisotropy value. However, there was no significant cortical metabolic damage in FDG-PET., Conclusions: The observed speech disorder in these patients is a characteristic entity related to dysfunction of speech expression and may be attributable to damage of not only the AF but also a number of fibres that are related to dysarthria, cognitive and emotional impairments and pyramidal/extra-pyramidal symptoms.

Objectives: Vegetative State (VS) implies significant issues. The aim of the MORFEO study is to identify the most relevant complications in VS patients and to supply clinicians and policy-makers with data derived from the analysis of a cohort of patients treated in a dedicated long-term facility setting., Methods: A cohort of 22 VS patients treated between 2003 and 2007 were enrolled and followed up for 1 year. The information recorded were: Disability Rating Scale (DRS), Levels of Cognitive Functioning (LCF), pressure sores, nutritional status, neurological complications, articular complications (passive range of motion-ROM), deep-vein thrombosis and infections. The Kolmogorov-Smirnov test was used to verify the normal distribution of the variables. The indicators of complications were analysed with the Friedman test (continuous variables) and with the Cochran Q test (dichotomous variables)., Results: DRS and LCF values showed no significant variation. The number of pressure sores decreased. The nutritional status remained satisfying. The ROM worsened in lower limb joints; a trend (p = ns) towards an improved range was observed in shoulders and elbows. Fifteen infections were recorded., Conclusions: The data that proved significant suggest a minimum set of quality-of-care indicators in VS patients: pressure sores follow-up, nutritional status, ROM and incidence of infections.

Background: The prognosis of long-term severe disorders of consciousness due to traumatic brain injury is discouraging. There is little definitive evidence of the underlying mechanisms, but a deficiency of the dopaminergic system may be involved., Methods: In a prospective open-labelled clinical study, the feasibility, relative efficacy and safety of continuous subcutaneous (s.c.) administration of apomorphine in Vegetative State (VS) or Minimally Conscious State (MCS) patients due to severe traumatic brain injury (TBI) was tested. Apomorphine was administered to eight patients. Outcome measures were the Coma Near-Coma Scale (CNCS) and Disability Rating Scale (DRS)., Results: Drug management was implemented without any problems. There was improvement in the primary outcomes for all patients. Awakening was seen as rapidly as within the first 24 hours of drug administration and as late as 4 weeks. Seven of the patients had completely recovered consciousness. All improvements were sustained for at least 1 year, even after apomorphine was discontinued. Drug-related adverse events were all anticipated and resolved after the dose was reduced., Conclusion: Based on this open-label pilot study, continuous s.c. apomorphine infusion appears to be feasible, safe and potentially effective in improving consciousness in patients in VS and MCS due to severe TBI.

Background: Evoked potentials allow one to assess functional integrity of sensory pathways projecting to primary sensory cortices and event-related potentials assess higher order cortical functions associated with stimulus detection and decision-making. Evoked and event-related potentials have been used to predict emergence from coma. This study aimed to determine whether they can help prediction of consciousness recovery in post-traumatic vegetative state (VS)., Methods: Thirty-four patients in post-traumatic VS were assessed clinically and neurophysiologically at 2-3 months after injury and followed up to 1 year. Patients were assessed with the Disability Rating Scale (DRS) and with electroencephalogram (EEG), brainstem auditory (BAEP) and somatosensory evoked potentials (SEP) and P300. Demographic, clinical and neurophysiological measures were analysed by descriptive and logistic regression techniques., Results: At 1 year from injury, 26 patients (76%) had recovered consciousness and eight patients (24%) had not. In univariate analyses, a detectable P300, a reactive EEG and lower DRS scores were found at entry assessment more frequently (p < 0.05) in patients who later recovered consciousness than in those who did not. Logistic regression analysis revealed that P300 was the only factor contributing to prediction of conscious recovery with an area under the ROC curve of 0.94 (95% CI, 0.80-0.99)., Conclusions: P300 is a strong predictor of conscious recovery in VS.

Objective: To evaluate whether vegetative state patients maintain circadian rhythms., Research Design: An observational study of five single cases., Methods and Procedures: Five chronic vegetative state patients underwent clinical and neurological evaluations and 2-week continuous temperature measurements., Main Outcomes and Results: The two patients with traumatic brain injury showed well-formed circadian temperature rhythms and had more reflexive behaviours and relatively low cortical and sub-cortical atrophy, whereas the three patients from anoxic-hypoxic origin demonstrated no cycles or rhythmic behaviour., Conclusions: The presence of periods of wakefulness does not imply preserved sleep-wake cycling capacity, nor preserved circadian rhythms and it should not be taken as a distinguishing feature for the definition of the vegetative state.

Background: Traumatic brain injury (TBI) can induce long-term severe disorders of consciousness. Evidence suggests an underlying dopaminergic deficit. Dopamine agonists may therefore play an important role in recovery of consciousness., Objective: To explore the response to continuous subcutaneous administration of apomorphine in a patient who had remained in minimally conscious state for 104 days and to evaluate the anatomical substrate of the effect., Design: A prospective, open-label, daily treatment, dose-escalation single case clinical study, with retrospective diffusion tensor image (DTI) evaluation., Results: On the fist day of treatment, the patient was able to move his limbs on command and answer yes/no questions which had not been the case prior to apomorphine administration. Subsequently there was a full recovery of consciousness and substantial functional recovery that was sustained even after apomorphine discontinuation. At the highest dose, mild dyskinesias were observed. These resolved with a lowering of the dose. DTI demonstrated a decrease of thalamocortical and corticothalamic projections in this MCS patient compared to normal volunteers., Conclusion: Although this is an open-label single-patient case report, the data are consistent with the theory that a dopaminergic deficit underlies MCS and that it may be overcome with apomorphine administration.

Primary Objective: Detecting signs of learning in persons with a diagnosis of post-coma vegetative state and profound motor disabilities could modify their diagnostic label and provide new hopes. In this study, three adults with such a diagnosis were exposed to learning assessment to search for those signs. PROCEDURE AND DESIGN: The assessment procedure relied on participants' eye-blinking responses and microswitch-based technology. The technology consisted of an electronically regulated optic microswitch mounted on an eyeglasses' frame that the participants wore during the study and an electronic control system connected to stimulus sources. Each participant followed an ABABCB design, in which A represented baseline periods, B intervention periods with stimuli contingent on the responses and C a control condition with stimuli presented non-contingently., Main Outcomes and Results: The level of responding during the B phases was significantly higher than the levels observed during the A phases as well as the C phase for all participants (i.e. indicating clear signs of learning by them)., Conclusions: These findings may have important implications for (a) changing the participants' diagnostic label and offering them new programme opportunities and (b) including learning assessment within the evaluation package used for persons with post-coma profound multiple disabilities.

Aim: Late recovery of consciousness after 12 months in vegetative state is very rare and is almost invariably associated with severe disability. The aim of this study was to report that late recovery with moderate disability is possible, even after several months in vegetative state., Case Report: This study describes the case of a 22-year-old male student who recovered consciousness from vegetative state 19 months after a traumatic brain injury which had occurred in December 2000. A further slow recovery of motor and cognitive functions up to a moderate disability was observed over 7 years after the brain injury. The patient now lives in the community, speaks, walks and undertakes daily living as well as outdoor leisure activities independently, has resumed his previous university studies and has a part-time non-competitive job., Conclusions: This case demonstrates that attaining a condition of independent living is possible even after more than 1 year of post-traumatic vegetative state, with an improvement of motor and cognitive functions that can continue for years. Cranioplasty and long-term rehabilitation programmes may be among the variables potentially influencing this unexpected recovery.

Primary Objective: This study investigates (1) the utility of the bispectral index (BIS) to distinguish levels of consciousness in severely brain damaged patients and, particularly, disentangle vegetative state (VS) from minimally conscious state (MCS), as compared to other EEG parameters; (2) the prognostic value of BIS with regards to recovery after 1 year., Research Design: Multi-centric prospective study., Method and Procedures: Unsedated patients recovering from coma were followed until death or transferal. Automated electrophysiological and standardized behavioural assessments were carried out twice a week. EEG recordings were categorized according to level of consciousness (coma, VS, MCS and Exit MCS). Outcome was assessed at 1 year post-insult., Main Outcomes and Results: One hundred and fifty-six EEG epochs obtained in 43 patients were included in the analyses. BIS showed a higher correlation with behavioural scales as compared to other EEG parameters. Moreover, BIS values differentiated levels of consciousness and distinguished VS from MCS while other EEG parameters did not. Finally, higher BIS values were found in patients who recovered at 1 year post-insult as compared to patients who did not recover., Conclusion: EEG-BIS recording is an interesting additional method to help in the diagnosis as well as in the prognosis of severely brain injured patients recovering from coma.

Primary Objective: To study cerebral response in a functional magnetic resonance imaging (fMRI) task of speech perception in a sample of patients in vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury., Methods: Three patients in VS, four patients in MCS and 19 healthy volunteers were enrolled for the study. All subjects underwent an fMRI task of passive listening of narratives played forward and backward, alternated with periods of silence. This study analysed cerebral response to language and to complex sound processing in the healthy subjects' group and in each patient, using SPM5., Results: One patient in VS and one in MCS showed cerebral responses to language and to complex sound very similar to those shown by the healthy volunteers. Two more patients, one in VS and one in MCS, showed significant responses to complex sound only. Finally, one patient in VS and one patient in MCS failed to show significant activation in response to either stimulus., Conclusions: Some patients in VS and MCS can preserve cerebral responses to language and auditory stimuli. fMRI may be useful to identify these responses, which may pass unnoticed in a bedside examination.

Background and Purpose: Residual brain function has been documented in vegetative state patients, yet early prognosis remains difficult. The purpose of this study was to identify by artificial intelligence procedures (classification and regression trees, data-mining) the significant neurological signs correlated to and predictive of outcome., Methods: Three hundred and thirty-three patients in vegetative state of traumatic or non-traumatic aetiology referred to the S.Anna Institute were retrospectively studied. Twenty-two neurological signs were assessed according to criteria included in the UNI ENI ISO 9001 : 2000 quality standards at admission (Time(0)) and after 50, 100 or 180 days and entered into a CART (classification and regression tree) data-mining procedure with a decisional tree j48 (Weka software and 10-fold cross-validation). Outcome was conventionally rated by the Glasgow outcome scale., Results and Conclusions: Re-appearance with proper timing of spontaneous motility, eye tracking and oculo-cephalic reflex and disappearance of oral automatisms proved highly correlated to outcome and allowed early and reliable prognosis. These findings are consistent with the brain functional organization thought to sustain consciousness and warrant systematic investigation. Classification and regression trees and data-mining procedures proved applicable in neurology to sort out significant clinical signs also in clinical conditions characterized by paucity of signs such as the vegetative state. Extended application in clinical medicine is conceivable based on the approach peculiarities.

Primary Objective: This study evaluated the hypothesis that neural networks derangement in patients with a vegetative state (VS) may cause an alteration of heart rate (HR) non-linear pattern., Methods and Procedures: Fifteen consecutive patients with a persistent VS and 15 matched healthy control subjects were included in the study. A 6-hour continuous electrocardiographic recording was used for the time series analysis measuring the occurrence time of the intervals between consecutive normal sinus heart beats (RR' intervals). Parameters evaluating linear and non-linear HR variability were studied. Approximate Entropy (ApEn), a non-linear parameter that quantifies the unpredictability of fluctuations in an instantaneous HR time series, was calculated from the average values of time series with fixed input variables., Main Outcomes and Results: All linear parameters, with the only exception being the percentage of RR' intervals that were by at least 50 ms different from the previous interval (0.56, SD = 1.31 vs 10.35, SD = 12.58; p = 0.005) were similar in patients and in healthy control subjects. Mean ApEn values (0.68, SD = 0.24 vs 1.10, SD = 0.16; p = 0.0001) were lower in patients than in healthy control subjects., Conclusions: The findings support the hypothesis that derangement of neural networks may cause a reduction of non-linear behaviour in HR such as ApEn.

Primary Objective: Examining the evidence from contrasting epistemological sources a case is made for the use of music as an assessment medium with patients in low awareness states. Profound brain damage can result in long-term states of altered consciousness such as vegetative and minimally conscious states. Differential diagnosis with this population is immensely complex requiring diverse approaches. Neuroimaging alone is not, as yet, sufficient to establish diagnosis in this population and must be supplemented by repeated behavioural observation methods from a skilled and diverse treatment team, as there are enormous medico-legal and ethical implications. Evidence from research in neuroimaging and the behavioural health sciences indicates that auditory stimulation can reveal residual functioning and elicit optimal behaviours in such patients, particularly when the stimulation has emotional significance., Main Outcomes and Results: Behavioural assessment is complicated by limbic behaviours which can be misinterpreted as purposeful emotional responses. A case vignette using music therapy in a complex case illustrates such complications., Conclusions: Given the evidence for residual auditory functioning in patients in low awareness states, music is recommended as a medium for assessment. However, professionals involved in diagnosis must take caution against misinterpreting limbic responses and attributing greater meaning to such behaviours.

Primary Objective: The Rehabilitation Centre Leijpark in The Netherlands provides an Early Intensive Neurorehabilitation Programme (EINP) to children and young adults in a prolonged unconscious state after severe brain injury. In an extensive research project the effects of EINP were studied. This part of the project focused on the outcome in terms of level of consciousness (LOC) in relation to the specific characteristics of a retrospectively studied cohort., Research Design: This study was executed according to a one-group archived pre-test-post-test design., Subjects: Subjects were all consecutively admitted patients (n=145, 72% male) between December 1987-January 2001. Inclusion criteria were: age 0-25 years, within 6 months after injury, LOC at admission vegetative state (VS) or minimally conscious state (MCS). One hundred and four patients (72%) suffered a traumatic injury and 41 patients (28%) a non-traumatic injury., Methods and Procedures: All patients had received EINP until they reached consciousness or until it was concluded that no progress was achieved during 3 months after the start of EINP. Medical files were investigated to collect the patients' characteristics and injury data, to determine the LOC at admission and at discharge and to determine the discharge destination., Results: Almost two-thirds of the patients reached full consciousness. LOC at admission, aetiology and interval since injury were found to be significant prognostic factors. Traumatic patients had a much better outcome than non-traumatic patients. A comparison with earlier outcome studies showed a more favourable outcome than expected. It is argued that a multi-centre study is needed to confirm possible effects of EINP.

Primary Objective: To establish the reliability and validity of the Sensory Modality Assessment and Rehabilitation Technique (SMART) as a tool for discriminating awareness in patients with profound brain damage., Research Design: A comparative prospective study was conducted., Method and Procedures: Sixty subjects diagnosed in vegetative state (VS) on admission were assessed at 2-monthly intervals. Rancho level ratings derived from referring physicians, SMART and Western Neuro Sensory Stimulation Profile (WNSSP) scores were compared., Main Outcomes and Results: The intra-observer intra class correlation (ICC) was 0.97 and inter-observer ICC was 0.96, implying very little within and between observer scoring variations. A modest, although significant correlation was established between SMART and either physician or WNSSP scores. However, the correlation between the WNSSP and SMART was higher (r = 0.70) than that between WNSSP and physicians scores (r = 0.451) or between SMART and physicians (r= 0.474)., Conclusion: SMART is a valid and reliable assessment for discriminating awareness in VS and Minimally Conscious State (MCS).

A young woman was rendered tetraplegic and anarthric as a result of a traumatic brain injury in 1993. Two years later, she was considered to be in a minimally conscious state and became the subject of legal debate in the UK with regard to withdrawal of artificial feeding and hydration. Before injury, she made a verbal advanced directive that she would not wish to continue living if ever becoming severely disabled. Neuropsychological assessment found statistically significant evidence for sentience and expression of a wish to live and the application to Court was withdrawn. Further meaningful recovery occurred between 7-10 years after injury. She now lives in the community with 24 hour care. She speaks, initiates conversation and actions, expresses clear and consistent preferences and has a spontaneous sense of humour. She uses an electric wheelchair, eats solid food and drinks through a straw. Her mood is variable and sometimes low. This case demonstrates the need for careful consideration of advanced directives and for specialist neuropsychological assessment in people with severe cognitive and communication difficulties. It supports the view that routine assessment and follow-up of people thought to be in minimally conscious states is important. In addition, it shows that recovery with reduction in disability and significant implications for quality of life can continue for at least 10 years after extremely severe traumatic brain injury., (Copyright 2004 Taylor and Francis Ltd)

Primary Objective: To report the ability of 12 tracheostomized acute rehabilitation hospital inpatients with severely disordered consciousness post-traumatic brain injury (TBI) to participate in an objective swallowing assessment., Research Design: Post hoc analysis of data from a larger, prospective blinded comparison study., Methods and Procedures: Subjects completed a modified barium swallow (MBS) study. Food/drink and tracheostomy tube management recommendations were made., Main Outcomes and Results: All subjects participated successfully during an MBS. Post-MBS, 10 subjects began receiving small amounts of food and/or drink. Prior to hospital discharge, all subjects received some food and/or drink and were extubated. Subjects were deemed representative of this patient population and, from a swallowing perspective, other tracheostomized patient populations at the same facility., Conclusions: Clinicians should routinely consider tracheostomized, acute rehabilitation hospital inpatients with severely disordered consciousness post-TBI potential MBS candidates. Implications and continued research needs are discussed.

Since the recent diagnostic criteria for persistent vegetative state (PVS) require the presence of a sleep-wake cycle, certain patients in similar conditions should be excluded from PVS. Since the diagnosis of PVS might correlate with legal issues, an accurate definition is necessary. To clarify the clinical significance of a sleep-wake cycle, 12 patients in a state of permanent unconsciousness after brain damage were clinically and electrophysiologically reviewed. In addition to routine EEG, evoked potentials and MRI, the simultaneous recordings of EEG and patients by videotape were performed for 24 hours. Four patients who showed severe brain stem damage did not show a sleep-wake cycle. In the other eight patients, a sleep-wake cycle was observed. However, among these patients there was no obvious difference in their clinical status. Although these data suggest that the presence of a sleep-wake cycle might reflect the brain stem damage, it is considered that the presence of a sleep-wake cycle might be unnecessary for the diagnostic criteria for PVS. Further study of various forms of brain damage will provide better understanding of the significance of the presence of a sleep-wake cycle.