Clinical subcategorization of minimally conscious state according to resting functional connectivity.

Patients in minimally conscious state (MCS) have been subcategorized in MCS plus and MCS minus, based on command-following, intelligible verbalization or intentional communication. We here aimed to better characterize the functional neuroanatomy of MCS based on this clinical subcategorization by means of resting state functional magnetic resonance imaging (fMRI). Resting state fMRI was acquired in 292 MCS patients and a seed-based analysis was conducted on a convenience sample of 10 MCS plus patients, 9 MCS minus patients and 35 healthy subjects. We investigated the left and right frontoparietal networks (FPN), auditory network, default mode network (DMN), thalamocortical connectivity and DMN between-network anticorrelations. We also employed an analysis based on regions of interest (ROI) to examine interhemispheric connectivity and investigated intergroup differences in gray/white matter volume by means of voxel-based morphometry. We found a higher connectivity in MCS plus as compared to MCS minus in the left FPN, specifically between the left dorso-lateral prefrontal cortex and left temporo-occipital fusiform cortex. No differences between patient groups were observed in the auditory network, right FPN, DMN, thalamocortical and interhemispheric connectivity, between-network anticorrelations and gray/white matter volume. Our preliminary group-level results suggest that the clinical subcategorization of MCS may involve functional connectivity differences in a language-related executive control network. MCS plus and minus patients are seemingly not differentiated by networks associated to auditory processing, perception of surroundings and internal awareness/self-mentation, nor by interhemispheric integration and structural brain damage.

The Coma Recovery Scale Modified Score: a new scoring system for the Coma Recovery Scale-revised for assessment of patients with disorders of consciousness.

The differential diagnosis between vegetative state and minimally conscious state is still complex and the development of an evaluation systems is one of the challenging tasks for researchers and professionals. The Coma Recovery Scale-revised is considered the gold standard for clinical/behavioral assessment and for the differential diagnosis of patients with disorder of consciousness. However, the scale presents some limitations in that (i) scores may partially overlap between different diagnoses and (ii) there is an underlying assumption that if a patient is able to show higher-level behaviors, he/she is also able to show lower-level responses. In the present study, a procedure to calculate a modified Coma Recovery Scale-revised score is presented that attempts to avoid these problems. To exemplify this new scoring approach, 60 patients with disorder of consciousness were studied and the results showed the usefulness of the Modified Score.

Coma recovery scale-r: variability in the disorder of consciousness.

BACKGROUND: Despite evidence from neuroimaging research, diagnosis and early prognosis in the vegetative (VS/UWS) and minimally conscious (MCS) states still depend on the observation of clinical signs of responsiveness. Multiple testing has documented a systematic variability during the day in the incidence of established signs of responsiveness. Spontaneous fluctuations of the Coma Recovery Scale-revised (CRS-r) scores are conceivable. METHODS: We retrospectively analyzed the CRS-r repeatedly administered to 7 VS/UWS and 12 MCS subjects undergoing systematic observation during a conventional 13 weeks. rehabilitation plan. RESULTS: The CRS-r global, visual and auditory scores were found higher in the morning than at the afternoon administration in both VS/UWS and MCS subgroups over the entire period of observation. The probability for a VS/UWS subject of being classified as MCS at the morning testing at least once during the 13 weeks. observation was as high as 30%, i.e., compatible with the reported misdiagnosis rate between the two clinical conditions. CONCLUSIONS: Multiple CRS-r testing is advisable to minimize the risk of misclassification; estimates of spontaneous variability could be used to characterize with greater accuracy patients with disorder of consciousness and possibly help optimize the rehabilitation plan.

What kind of consciousness is minimal?

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.

Predicting outcome from subacute unresponsive wakefulness syndrome or vegetative state.

Predicting recovery of consciousness in patients who survive their coma but evolve to a vegetative state (recently coined unresponsive wakefulness syndrome) remains a challenge. Most previous prognostic studies have focused on the acute coma phase. A novel outcome scale (combining behavioural, aetiology, electroencephalographic, sleep electroencephalographic and somatosensory evoked potential data) has been proposed for patients in subacute unresponsive wakefulness syndrome. The scale's clinical application awaits validation in a larger population.

A diagnostic illusory? The case of distinguishing between "vegetative" and "minimally conscious" states.

Throughout affluent societies there are growing numbers of people who survive severe brain injuries only to be left with long-term chronic disorders of consciousness. This patient group who exist betwixt and between life and death are variously diagnosed as in 'comatose', 'vegetative', and, more recently, 'minimally conscious' states. Drawing on a nascent body of sociological work in this field and developments in the sociology of diagnosis in concert with Bauman's thesis of 'ambivalence' and Turner's work on 'liminality', this article proposes a concept we label as diagnostic illusory in order to capture the ambiguities, nuanced complexities and tensions that the biomedical imperative to name and classify these patients give rise to. Our concept emerged through a reading of debates within medical journals alongside an analysis of qualitative data generated by way of a study of accounts of those close to patients: primarily relatives (N = 51); neurologists (N = 4); lawyers (N = 2); and others (N = 5) involved in their health care in the UK.

Large scale screening of neural signatures of consciousness in patients in a vegetative or minimally conscious state.

In recent years, numerous electrophysiological signatures of consciousness have been proposed. Here, we perform a systematic analysis of these electroencephalography markers by quantifying their efficiency in differentiating patients in a vegetative state from those in a minimally conscious or conscious state. Capitalizing on a review of previous experiments and current theories, we identify a series of measures that can be organized into four dimensions: (i) event-related potentials versus ongoing electroencephalography activity; (ii) local dynamics versus inter-electrode information exchange; (iii) spectral patterns versus information complexity; and (iv) average versus fluctuations over the recording session. We analysed a large set of 181 high-density electroencephalography recordings acquired in a 30 minutes protocol. We show that low-frequency power, electroencephalography complexity, and information exchange constitute the most reliable signatures of the conscious state. When combined, these measures synergize to allow an automatic classification of patients' state of consciousness.

Psychometric properties of the disorders of consciousness scale.

OBJECTIVE: To provide evidence for psychometric properties of the Disorders of Consciousness Scale (DOCS). DESIGN: Prospective observational cohort. SETTINGS: Seven rehabilitation facilities. PARTICIPANTS: Patients (N=174) with severe brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE DOCS RESULTS: Initial analyses suggested eliminating 6 items to maximize psychometrics, resulting in the DOCS-25. The 25 items form a unidimensional hierarchy, rating scale categories are ordered, there are no misfitting items, and differential item functioning was not found according to sex, type of brain injury, veteran status, and days from onset. Person separation reliability (.91) indicates that the DOCS-25 is appropriate for individual patient measurement. Items are well targeted to the sample, with the difference between mean person and item calibrations less than 1 logit. DOCS-25 Rasch measures result in a 62% gain in relative precision over total raw scores. Internal consistency is very good (Cronbach α=.86); interrater agreement is excellent (intracIass correlation coefficient=.90) for both the DOCS-25 and the sensory subscales. The DOCS-25 total measure, but not subscale measures, correlates with the Glasgow Coma Scale and the Coma/Near-Coma Scales and distinguishes significantly between vegetative and minimally conscious states, indicating concurrent validity. CONCLUSIONS: The DOCS-25 is psychometrically strong. It has excellent measurement precision and captures a broad range of patient function, which is critical for capturing recovery of consciousness. The sensory subscales are clinically informative but should not be reported as separate measures. The Keyform synthesizes clinical observations to visualize response patterns with potential for informing clinical decision-making. Future studies should determine sensitivity to change, examine issues of rater severity, and explore the usefulness of the Keyform in clinical practice.

Development of a simple score to predict outcome for unresponsive wakefulness syndrome.

INTRODUCTION: Accurate assessment of prognosis for patients with unresponsive wakefulness syndrome (UWS; formerly vegetative state) may help clinicians and families guide the type and intensity of therapy; however, there is no suitable and accurate means to predict the outcome so far. We aimed to develop a simple bedside scoring system to predict the likelihood of awareness recovery in patients with UWS. METHODS: We prospectively enrolled 56 patients (age range 10 to 73 years) with UWS 3 to 12 weeks post-onset. We collected demographic data and performed neurological, serological and neurophysiological tests at study entry. Each patient received a one year follow-up, during which awareness recovery was assessed by experienced physicians on the basis of clinical criteria. Univariate and multivariable analyses were employed to assess the relationships between predictors and awareness recovery. RESULTS: A total of 56 participants were included in the study; of these, 24 patients recovered awareness, 3 with moderate disabilities, 8 with severe disabilities, 12 were in a minimally conscious state, and 1 died after recovery. During the study, 23 patients remained in UWS and 9 died in UWS. Motor response, type of brain injury, electroencephalogram reactivity, sleep spindles and N20 were shown to be independent predictors for awareness recovery. Based on their coefficients in the model, we assigned these predictors with 1 point each and created a 5-point score for prediction of awareness recovery. The resulting score showed good predictive accuracy in the derivation cohort. The area under the receiver operating characteristic curve for the score was 0.918 with 87.50% sensitivity. CONCLUSION: This simple bedside prognostic score can be used to predict the probability of awareness recovery in UWS, thus provide families and clinicians with useful outcome information.

ICF-DOC: the ICF dedicated checklist for evaluating functioning and disability in people with disorders of consciousness.

Clinicians need a comprehensive description of patients' functioning state to capture the complex interaction between symptoms and environmental factors, and to determine the actual level of functioning in patients in a vegetative state or a minimally conscious state. The aim of this study is to develop an International Classification of Functioning, Disability, and Health (ICF) checklist for patients with disorders of consciousness (DOC) so as to capture and describe, with a tailored list of categories, the most common health, disability, and functioning issues of adult patients with DOC. The WHO ICF checklist was used as a basis for collecting data. This was an observational, cross-sectional, multicenter study conducted in 69 Italian centers. Specific methodological procedures were used to identify the most appropriate categories for DOC patients to be added to or deleted from the ICF checklist so as to develop the ICF-DOC checklist. A total of 566 adult patients were enrolled: 398 in a vegetative state and 168 in a minimally conscious state. A total of 127 ICF categories reached the threshold of 20% concerning the presence of a problem: 37 categories from the body functions chapter, 13 from the body structures chapter, 46 from the activities and participations chapter, and 31 from the environmental factors chapter. ICF categories identified in this study can be useful guidelines for clinicians and researchers to collect data on functioning and disability of adult patients with DOC. The new ICF-DOC checklist allows monitoring of the effects of interventions on functional areas and possible changes in each patient in follow-up studies.

Should we continue treatment for M? The benefits of living.

Wilkinson and Savulescu did not agree with the court's decision to continue M's treatment and suggested in their recent commentary that the magnitude of benefits of being alive for M is small compared with the potential use of health resources for other patients. We argue that the benefits of being sensate to the surroundings for an otherwise unconscious person are not necessarily small. One cannot assess on behalf of another person the magnitude of benefits of being alive according to the intensity or the duration of negative experiences. Denying life-sustaining treatment to patients in a minimally conscious state solely on the grounds that they are less capable of enjoying the benefits represents grave discrimination against disabled persons. For patients in a minimally conscious state who have not delegated a surrogate or made any advance decision about their medical treatment, the duty of doctors is to preserve their right to self-determination and maximise their capacity to enjoy their life. M should live on, and life-sustaining treatment should not be withdrawn.

Clinical differentiation and outcome evaluation in vegetative and minimally conscious state patients:the neurophysiological approach.

The neurophysiological approach to patients with disorders of consciousness allows recording of both central and peripheral nervous system electrical activities and provides a functional assessment. Data obtained using this approach can supplement information from clinical neurological examination, but also from the use of morphological neuroimaging techniques: computed tomography and magnetic resonance imaging. Neuro-physiological techniques, such as electroencephalography (EEG), evoked potentials, transcranial magnetic stimulation, and EEG in association with functional magnetic resonance imaging, allow monitoring of clinical conditions and can help in the formulation of a prognosis. The aim of this review is to describe the main neurophysiological techniques used in disorders of consciousness to evaluate residual cerebral function, to provide information on the neuronal dysfunction for outcome evaluation, and to differentiate clinically between the vegetative and minimally conscious states.

Is there a cartesian renaissance of the mind or is it time for a new taxonomy for low responsive states?

The mass media have recently pointed out the likelihood of diagnostic errors in post-coma patients. Late recoveries of consciousness, even after 20 years, might indicate hidden misdiagnoses that are not corrected over a long period of time. The rate of misdiagnoses of patients in a vegetative state is very high when based on behavioral assessment strategies alone. An extremely restrictive motor repertoire, as occurs in locked-in patients, seems to be the major factor responsible for diagnostic confusion. Functional neuroimaging techniques are regarded as promising tools in unearthing covert awareness in behaviorally unresponsive patients who are unable to produce any motor output. However, unless we believe that these patients persistently live in an unconvincing Cartesian-like state, in which thinking and acting are mutually dissociated, we have to admit that a new taxonomy for low responsive states is called for. This taxonomy should take into account the possible syndromic overlap between disorders of consciousness and locked-in syndrome. We should suspect a "locked-in state" in behaviorally unresponsive patients unless we reach strong evidence that such is not the case; this is the only way to avoid dramatic misdiagnoses.

[Ethical aspects of dealing with coma patients]. / Ethische Aspekte im Umgang mit Komapatienten.

The number of patients who survive severe brain injury increased due to progress in neurosurgery and intensive care. To establish a proper prognosis on the coma stage and the possible potential of remission is difficult in many cases. The treatment of patients in chronic coma leads to economic and ethical problems. Progress in functional radiology may help to obtain a proper prognosis in future. While numerous issues deal with ethical aspects in case of brain death only few do so with treatment decisions in chronic coma patients.

Brain damage and the moral significance of consciousness.

Neuroimaging studies of brain-damaged patients diagnosed as in the vegetative state suggest that the patients might be conscious. This might seem to raise no new ethical questions given that in related disputes both sides agree that evidence for consciousness gives strong reason to preserve life. We question this assumption. We clarify the widely held but obscure principle that consciousness is morally significant. It is hard to apply this principle to difficult cases given that philosophers of mind distinguish between a range of notions of consciousness and that is unclear which of these is assumed by the principle. We suggest that the morally relevant notion is that of phenomenal consciousness and then use our analysis to interpret cases of brain damage. We argue that enjoyment of consciousness might actually give stronger moral reasons not to preserve a patient's life and, indeed, that these might be stronger when patients retain significant cognitive function.