Joseph T. Giacino

The minimally conscious state: Definition and diagnostic criteria

ObjectiveTo establish consensus recommendations among health care specialties for defining and establishing diagnostic criteria for the minimally conscious state (MCS). BackgroundThere is a subgroup of patients with severe alteration in consciousness who do not meet diagnostic criteria for coma or the vegetative state (VS). These patients demonstrate inconsistent but discernible evidence of consciousness. It is important to distinguish patients in MCS from those in coma and VS because preliminary findings suggest that there are meaningful differences in outcome. MethodsAn evidence-based literature review of disorders of consciousness was completed to define MCS, develop diagnostic criteria for entry into MCS, and identify markers for emergence to higher levels of cognitive function. ResultsThere were insufficient data to establish evidence-based guidelines for diagnosis, prognosis, and management of MCS. Therefore, a consensus-based case definition with behaviorally referenced diagnostic criteria was formulated to facilitate future empirical investigation. ConclusionsMCS is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from coma and VS by documenting the presence of specific behavioral features not found in either of these conditions. Patients may evolve to MCS from coma or VS after acute brain injury. MCS may also result from degenerative or congenital nervous system disorders. This condition is often transient but may also exist as a permanent outcome. Defining MCS should promote further research on its epidemiology, neuropathology, natural history, and management.

Behavioural improvements with thalamic stimulation after severe traumatic brain injury

Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS), a condition that is characterized by intermittent evidence of awareness of self or the environment. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions.

fMRI reveals large-scale network activation in minimally conscious patients

Background: The minimally conscious state (MCS) resulting from severe brain damage refers to a subset of patients who demonstrate unequivocal, but intermittent, behavioral evidence of awareness of self or their environment. Although clinical examination may suggest residual cognitive function, neurobiological correlates of putative cognition in MCS have not been demonstrated. Objective: To test the hypothesis that MCS patients retain active cerebral networks that underlie cognitive function even though command following and communication abilities are inconsistent. Methods: fMRI was employed to investigate cortical responses to passive language and tactile stimulation in two male adults with severe brain injuries leading to MCS and in seven healthy volunteers. Results: In the case of the patient language-related tasks, auditory stimulation with personalized narratives elicited cortical activity in the superior and middle temporal gyrus. The healthy volunteers imaged during comparable passive language stimulation demonstrated responses similar to the patients’ responses. However, when the narratives were presented as a time-reversed signal, and therefore without linguistic content, the MCS patients demonstrated markedly reduced responses as compared with volunteer subjects, suggesting reduced engagement for “linguistically” meaningless stimuli. Conclusions: The first fMRI maps of cortical activity associated with language processing and tactile stimulation of patients in the minimally conscious state (MCS) are presented. These findings of active cortical networks that serve language functions suggest that some MCS patients may retain widely distributed cortical systems with potential for cognitive and sensory function despite their inability to follow simple instructions or communicate reliably.

Possible axonal regrowth in late recovery from the minimally conscious state

We used diffusion tensor imaging (DTI) to study 2 patients with traumatic brain injury. The first patient recovered reliable expressive language after 19 years in a minimally conscious state (MCS); the second had remained in MCS for 6 years. Comparison of white matter integrity in the patients and 20 normal subjects using histograms of apparent diffusion constants and diffusion anisotropy identified widespread altered diffusivity and decreased anisotropy in the damaged white matter. These findings remained unchanged over an 18-month interval between 2 studies in the first patient. In addition, in this patient, we identified large, bilateral regions of posterior white matter with significantly increased anisotropy that reduced over 18 months. In contrast, notable increases in anisotropy within the midline cerebellar white matter in the second study correlated with marked clinical improvements in motor functions. This finding was further correlated with an increase in resting metabolism measured by PET in this subregion. Aberrant white matter structures were evident in the second patients DTI images but were not clinically correlated. We propose that axonal regrowth may underlie these findings and provide a biological mechanism for late recovery. Our results are discussed in the context of recent experimental studies that support this inference.

Assessment Scales for Disorders of Consciousness: Evidence-Based Recommendations for Clinical Practice and Research

OBJECTIVES To conduct a systematic review of behavioral assessment scales for disorders of consciousness (DOC); provide evidence-based recommendations for clinical use based on their content validity, reliability, diagnostic validity, and ability to predict functional outcomes; and provide research recommendations on DOC scale development and validation. DATA SOURCES Articles published through March 31, 2009, using MEDLINE, CINAHL, Psychology and Behavioral Sciences Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Biomedical Reference Collection, and PsycINFO. Thirteen primary terms that defined DOC were paired with 30 secondary terms that defined aspects of measurement. Scale names, abbreviations, and authors were also used as search terms. Task force members identified additional articles by using personal knowledge and examination of references in reviewed articles. STUDY SELECTION Primary criteria included the following: (1) provided reliability, diagnostic validity, and/or prognostic validity data; (2) examined a cohort, case control, or case series sample of persons with DOC who were age older than or equal to 18 years; and (3) assessed in an acute care or rehabilitation setting. Articles were excluded if peer review was not conducted, original data were not reported, or an English language article was not available. The initial search yielded 580 articles. After paired rater review of study abstracts, guideline development was based on 37 articles representing 13 DOC scales. DATA EXTRACTION Rater pairs classified studies addressing diagnostic and prognostic validity by using the American Academy of Neurology 4-tier level of evidence scheme, and reliability by using a task force-developed 3-tier evidence scheme. An independent quality review of ratings was conducted, and corrections were made. DATA SYNTHESIS The Coma Recovery Scale-Revised (CRS-R), Sensory Stimulation Assessment Measure (SSAM), Wessex Head Injury Matrix (WHIM), Western Neuro Sensory Stimulation Profile (WNSSP), Sensory Modality Assessment Technique (SMART), Disorders of Consciousness Scale (DOCS), and Coma/Near-Coma Scale (CNC) have acceptable standardized administration and scoring procedures. The CRS-R has excellent content validity and is the only scale to address all Aspen Workgroup criteria. The SMART, SSAM, WHIM, and WNSSP demonstrate good content validity, containing items that could distinguish persons who are in a vegetative state, are in a minimally conscious state (MCS), or have emerged from MCS. The Full Outline of UnResponsiveness Score (FOUR), WNSSP, CRS-R, Comprehensive Levels of Consciousness Scale (CLOCS), and Innsbruck Coma Scale (INNS) showed substantial evidence of internal consistency. The FOUR and the CRS-R showed substantial evidence of good interrater reliability. Evidence of diagnostic validity and prognostic validity in brain injury survivor samples had very high levels of potential bias because of methodologic issues such as lack of rater masking. CONCLUSIONS The CRS-R may be used to assess DOC with minor reservations, and the SMART, WNSSP, SSAM, WHIM, and DOCS may be used to assess DOC with moderate reservations. The CNC may be used to assess DOC with major reservations. The FOUR, INNS, Glasgow-Liege Coma Scale, Swedish Reaction Level Scale-1985, Loewenstein Communication Scale, and CLOCS are not recommended at this time for bedside behavioral assessment of DOC because of a lack of content validity, lack of standardization, and/or unproven reliability.

Disorders of consciousness after acquired brain injury: The state of the science

The concept of consciousness continues to defy definition and elude the grasp of philosophical and scientific efforts to formulate a testable construct that maps to human experience. Severe acquired brain injury results in the dissolution of consciousness, providing a natural model from which key insights about consciousness may be drawn. In the clinical setting, neurologists and neurorehabilitation specialists are called on to discern the level of consciousness in patients who are unable to communicate through word or gesture, and to project outcomes and recommend approaches to treatment. Standards of care are not available to guide clinical decision-making for this population, often leading to inconsistent, inaccurate and inappropriate care. In this Review, we describe the state of the science with regard to clinical management of patients with prolonged disorders of consciousness. We review consciousness-altering pathophysiological mechanisms, specific clinical syndromes, and novel diagnostic and prognostic applications of advanced neuroimaging and electrophysiological procedures. We conclude with a provocative discussion of bioethical and medicolegal issues that are unique to this population and have a profound impact on care, as well as raising questions of broad societal interest.

The vegetative and minimally conscious states: A comparison of clinical features and functional outcome

Objective:To compare the vegetative (VS) and minimally conscious states (MCS) with regard to the incidence of specific clinical features and differences in functional outcome across the first year post injury. It was hypothesized that patients diagnosed with MCS on admission to rehabilitation would have more favorable outcomes at 1 year post injury relative to patients diagnosed with VS and that this difference would be more pronounced for traumatic (TBI) versus nontraumatic brain injury (NTB1). Design: Retrospective analysis of clinical findings collected using a standardized methodology (ie, Coma Recovery Scale). Findings were utilized to determine diagnosis and functional outcome at 1, 3, 6, and 12 months post injury. Setting: Acute and extended care brain injury rehabilitation hospital. Patients: 104 patients (62 male, 42 female; mean age = 37 years; mean weeks post injury to admission = 10) with severe TBI or NTB1 (VS = 55; MCS = 49) admitted to a rehabilitation-based coma intervention program. Results: Functional outcome at 3,6, and 12 months post Injury was significantly more favorable for patients diagnosed with MCS relative to those with an admitting diagnosis of VS, and this difference was greatest for patients in MCS following TBI. Visual tracking and motor agitation were found to occur in VS but were of low frequency in comparison to MCS. Conclusions: In patients with severe disorders of consciousness, those diagnosed with MCS show more continuous improvement and attain significantly more favorable outcomes by 1 year post injury than those diagnosed with VS. The presence of specific clinical features, particularly visual tracking, may contribute additional information to differential diagnosis in patients whose level of behavioral responsiveness is severely diminished.

The JFK coma recovery scale—revised

The JFK Coma Recovery Scale (CRS) was developed to help characterise and monitor patients functioning at Rancho Levels I–IV and has been used widely in both clinical and research settings within the US and Europe. The CRS was recently revised to address a number of concerns emanating from our own clinical experience with the scale, feedback from users and researchers as well as the results of Rasch analyses. Additionally, the CRS did not include all of the behavioural criteria necessary to diagnose the minimally conscious state (MCS), thereby limiting diagnostic utility. The revised JFK Coma Recovery Scale (CRS-R) includes addition of new items, merging of items found to be statistically similar, deletion or modification of items showing poor fit with the scales underlying construct, renaming of items, more stringent scoring criteria, and quantification of elicited behaviours to improve accuracy of rating. Psychometric properties of the CRS-R appear to meet standards for measurement and evaluation tools for use in clinical and research settings, and diagnostic application suggests that the scale is capable of discriminating patients in the minimally conscious state from those in the vegetative state. Individuals interested in obtaining a copy of the JFK CRS-R and administration and scoring procedures are referred to the authors.

Monitoring rate of recovery to predict outcome in minimally responsive patients

Existing methods of assessing neurobehavioral responsiveness in severely brain-injured patients are limited by their inability to recognize subtle clinical changes over time. This study evaluates the Coma Recovery Scale (CRS), developed for use during acute rehabilitation. The CRS was designed to detect subtle changes in neurobehavioral status and to predict outcome in patients with sever alterations of consciousness. Acceptable levels of concurrent validity were established with the Disability Rating Scale ([DRS], r = -.93) and the Glasgow Coma Scale ([GCS], r = .90). The CRS was also found to have adequate interrater reliability (kappa = .83). Twenty-eight minimally responsive patients, unable to communicate or follow commands reliably, were evaluated on the CRS, the DRS, and the GCS. Although initial scores on all three scales were significantly correlated with outcome at discharge, change scores were more predictive of outcome. In addition, CRS change scores correlated higher with outcome (r = -.78, p less than .01) than DRS and GCS change scores. These findings indicate that the CRS is a sensitive measure of neurobehavioral responsiveness and suggest that rate of change during acute rehabilitation may be an important outcome predictor.

The Vegetative and Minimally Conscious States: Current Knowledge and Remaining Questions

In the last 2 decades, the minimally conscious state has been distinguished conceptually from the vegetative state and operational criteria for these diagnoses have been published. Standardized and individualized assessment tools have been developed to assist with the diagnosis of severe disorders of consciousness and the measurement of clinical improvement. The natural course of recovery and the importance of key prognostic predictors have been elucidated. Important advances have also been made in defining the similarities and differences in the pathophysiology of these two states, and functional imaging modalities have begun to explicate the neural substrate underlying the behavioral features of these disorders. Research on the efficacy of treatments for severe disorders of consciousness lags behind, due to the practical and ethical difficulties in executing large rigorously controlled clinical trials. The past and future scientific developments in this area provide an important background for continuing discussions of the ethical controversies surrounding end-of-life decision making and resource allocation.