Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment

BACKGROUND: Previously published studies have reported that up to 43% of patients with disorders of consciousness are erroneously assigned a diagnosis of vegetative state (VS). However, no recent studies have investigated the accuracy of this grave clinical diagnosis. In this study, we compared consensus-based diagnoses of VS and MCS to those based on a well-established standardized neurobehavioral rating scale, the JFK Coma Recovery Scale-Revised (CRS-R). METHODS: We prospectively followed 103 patients (55 +/- 19 years) with mixed etiologies and compared the clinical consensus diagnosis provided by the physician on the basis of the medical staff's daily observations to diagnoses derived from CRS-R assessments performed by research staff. All patients were assigned a diagnosis of 'VS', 'MCS' or 'uncertain diagnosis.' RESULTS: Of the 44 patients diagnosed with VS based on the clinical consensus of the medical team, 18 (41%) were found to be in MCS following standardized assessment with the CRS-R. In the 41 patients with a consensus diagnosis of MCS, 4 (10%) had emerged from MCS, according to the CRS-R. We also found that the majority of patients assigned an uncertain diagnosis by clinical consensus (89%) were in MCS based on CRS-R findings. CONCLUSION: Despite the importance of diagnostic accuracy, the rate of misdiagnosis of VS has not substantially changed in the past 15 years. Standardized neurobehavioral assessment is a more sensitive means of establishing differential diagnosis in patients with disorders of consciousness when compared to diagnoses determined by clinical consensus

Visual fixation in the vegetative state: an observational case series PET study

BACKGROUND: Assessment of visual fixation is commonly used in the clinical examination of patients with disorders of consciousness. However, different international guidelines seem to disagree whether fixation is compatible with the diagnosis of the vegetative state (i.e., represents "automatic" subcortical processing) or is a sufficient sign of consciousness and higher order cortical processing. METHODS: We here studied cerebral metabolism in ten patients with chronic post-anoxic encephalopathy and 39 age-matched healthy controls. Five patients were in a vegetative state (without fixation) and five presented visual fixation but otherwise showed all criteria typical of the vegetative state. Patients were matched for age, etiology and time since insult and were followed by repeated Coma Recovery Scale-Revised (CRS-R) assessments for at least 1 year. Sustained visual fixation was considered as present when the eyes refixated a moving target for more than 2 seconds as defined by CRS-R criteria. RESULTS: Patients without fixation showed metabolic dysfunction in a widespread fronto-parietal cortical network (with only sparing of the brainstem and cerebellum) which was not different from the brain function seen in patients with visual fixation. Cortico-cortical functional connectivity with visual cortex showed no difference between both patient groups. Recovery rates did not differ between patients without or with fixation (none of the patients showed good outcome). CONCLUSIONS: Our findings suggest that sustained visual fixation in (non-traumatic) disorders of consciousness does not necessarily reflect consciousness and higher order cortical brain function

Disorders of Consciousness

Disorders of Consciousness are a big challenge for the entire process of rehabilitation: assessment, diagnosis, pharmacological, and rehabilitation programs, including conventional treatments and the use of new technologies

Single tDCS session of motor cortex in patients with disorders of consciousness: a pilot study

peer reviewedPrimary Objective: Patients with disorders of consciousness (DOC) face a lack of treatments and risk ofmisdiagnosis, potentially due to motor impairment. Transcranial direct current stimulation (tDCS)showed promising results over the prefrontal cortex in DOC and over the primary motor cortex (M1)in stroke. Tis pilot study aimed at evaluating the behavioral effects of M1 tDCS in patients with DOC.Research Design: In this randomized double-blind sham-controlled crossover trial, we included 10patients (49 ± 22 years, 7 ± 13 months since injury, 4 unresponsive wakefulness syndrome, 6 minimallyconscious state, 5 traumatic etiologies).Methods and Procedures: One session of tDCS (2 mA for 20 min) and one session of sham tDCS wereapplied over M1 in a randomized order with a washout period of minimum 24 h and behavioral effectswere assessed using the CRS-R. At the group level, no treatment effect was identified on the total score(p= .55) and on the motor subscale (p= .75). Two patients responded to tDCS by showing a new sign ofconsciousness (visual pursuit and object localization).Conclusions: One session of M1 tDCS failed to improve behavioral responsiveness in patients with DOC.Other application strategies should be tested

Detecting Awareness in the Vegetative State: Electroencephalographic Evidence for Attempted Movements to Command

Patients in the Vegetative State (VS) do not produce overt motor behavior to command and are therefore considered to be unaware of themselves and of their environments. However, we recently showed that high-density electroencephalography (EEG) can be used to detect covert command-following in some VS patients. Due to its portability and inexpensiveness, EEG assessments of awareness have the potential to contribute to a standard clinical protocol, thus improving diagnostic accuracy. However, this technique requires refinement and optimization if it is to be used widely as a clinical tool. We asked a patient who had been repeatedly diagnosed as VS for 12-years to try to move his left and right hands, between periods of rest, while EEG was recorded from four scalp electrodes. We identified appropriate and statistically reliable modulations of sensorimotor beta rhythms following commands to try to move, which could be significantly classified at a single-trial level. These reliable effects indicate that the patient attempted to follow the commands, and was therefore aware, but was unable to execute an overtly discernable action. The cognitive demands of this novel task are lower than those used previously and, crucially, allow for awareness to be determined on the basis of a 20-minute EEG recording made with only four electrodes. This approach makes EEG assessments of awareness clinically viable, and therefore has potential for inclusion in a standard assessment of awareness in the VS

Prediction of Global Functional Outcome and Post-Concussive Symptoms after Mild Traumatic Brain Injury: External Validation of Prognostic Models in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study

The majority of traumatic brain injuries (TBIs) are categorized as mild, according to a baseline Glasgow Coma Scale (GCS) score of 13-15. Prognostic models that were developed to predict functional outcome and persistent post-concussive symptoms (PPCS) after mild TBI have rarely been externally validated. We aimed to externally validate models predicting 3-12-month Glasgow Outcome Scale Extended (GOSE) or PPCS in adults with mild TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project, which included 2862 adults with mild TBI, with 6-month GOSE available for 2374 and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) results available for 1605 participants. Model performance was evaluated based on calibration (graphically and characterized by slope and intercept) and discrimination (C-index). We validated five published models for 6-month GOSE and three for 6-month PPCS scores. The models used different cutoffs for outcome and some included symptoms measured 2 weeks post-injury. Discriminative ability varied substantially (C-index between 0.58 and 0.79). The models developed in the Corticosteroid Randomisation After Significant Head Injury (CRASH) trial for prediction of GOSE </p

Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques

In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept - best left to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world, practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as 43%) - clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome). Based on the evidence to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation of residual function, formation of differential diagnoses, and estimation of prognosis

Attitudes Towards End-of-Life Decisions and the Subjective Concepts of Consciousness: An Empirical Analysis

Background: People have fought for their civil rights, primarily the right to live in dignity. At present, the development of technology in medicine and healthcare led to an apparent paradox: many people are fighting for the right to die. This study was aimed at testing whether different moral principles are associated with different attitudes towards end-of-life decisions for patients with a severe brain damage. Methodology: We focused on the ethical decisions about withdrawing life-sustaining treatments in patients with severe brain damage. 202 undergraduate students at the University of Padova were given one description drawn from four profiles describing different pathological states: the permanent vegetative state, the minimally conscious state, the locked-in syndrome, and the terminal illness. Participants were asked to evaluate how dead or how alive the patient was, and how appropriate it was to satisfy the patient's desire. Principal Findings: We found that the moral principles in which people believe affect not only people's judgments concerning the appropriateness of the withdrawal of life support, but also the perception of the death status of patients with severe brain injury. In particular, we found that the supporters of the Free Choice (FC) principle perceived the death status of the patients with different pathologies differently: the more people believe in the FC, the more they perceived patients as dead in pathologies where conscious awareness is severely impaired. By contrast, participants who agree with the Sanctity of Life (SL) principle did not show differences across pathologies. Conclusions: These results may shed light on the complex aspects of moral consensus for supporting or rejecting end-of-life decisions

Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition

Objective: To study the relationship between thalamic glucose metabolism and neurological outcome after severe traumatic brain injury (TBI). Methods: Forty-nine patients with severe and closed TBI and 10 healthy control subjects with 18F-FDG PET were studied. Patients were divided into three groups: MCS&VS group (n ¼ 17), patients in a vegetative or a minimally conscious state; In-PTA group (n ¼ 12), patients in a state of post-traumatic amnesia (PTA); and Out-PTA group (n ¼ 20), patients who had emerged from PTA. SPM5 software implemented in MATLAB 7 was used to determine the quantitative differences between patients and controls. FDG-PET images were spatially normalized and an automated thalamic ROI mask was generated. Group differences were analysed with two sample voxel-wise t-tests. Results: Thalamic hypometabolism was the most prominent in patients with low consciousness (MCS&VS group) and the thalamic hypometabolism in the In-PTA group was more prominent than that in the Out-PTA group. Healthy control subjects showed the greatest thalamic metabolism. These differences in metabolism were more pronounced in the internal regions of the thalamus. Conclusions: The results confirm the vulnerability of the thalamus to suffer the effect of the dynamic forces generated during a TBI. Patients with thalamic hypometabolism could represent a sub-set of subjects that are highly vulnerable to neurological disability after TBI.Lull Noguera, N.; Noé, E.; Lull Noguera, JJ.; Garcia Panach, J.; Chirivella, J.; Ferri, J.; López-Aznar, D.... (2010). Voxel-based statistical analysis of thalamic glucose metabolism in traumatic brain injury: relationship with consciousness and cognition. Brain Injury. 24(9):1098-1107. doi:10.3109/02699052.2010.494592S10981107249Gallagher, C. 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