Neurophysiological patterns of vegetative and minimally conscious states

This paper reviews the possible usefulness of electroencephalogram (EEG) and evoked potential (EP) recording in vegetative and poorly-responsive patients. There is a marked inter-individual EEG and EP variability, which reflects the state heterogeneity. Four clinical applications are described: (1) the identification of primary midbrain dysfunction--and, therefore, a possible reversibility--in post-traumatic states; (2) the identification of the permeability of sensory channels; (3) quantitative follow-up; and (4) individual assessment of cognitive functions and/or consciousness. Regarding this last issue, the loss of primary cortical EPs, although rarely observed, constitutes one major argument against consciousness. Conversely, cognitive EPs definitely proved the persistence of cognitive functions in several vegetative patients. Whether these cognitive functions are conscious or not remains a matter of debate.     

Neurophysiological correlates of persistent vegetative and minimally conscious states

The evaluation of patients after severe brain injury is a complex process for the clinician, even with the information provided by a detailed neurological examination. The clinical examination often does not provide sufficient information to fully evaluate these patients due to several factors. Limited and inconsistent motor responses may obscure expression of greater cognitive capacities. More importantly, evaluation of the functional integrity of the cerebral cortical, thalamic and basal ganglia system is poorly indicated by the clinical examination in many patients. Neurophysiological studies provide a complementary set of objective data for evaluating brain-injured patients, as well as predicting and following the course of their recovery. This additional information can be of great importance since vegetative patients may be difficult to distinguish clinically from those in the minimally conscious state. This is important because the latter category of patients may have a significantly better prognosis for recovery in the initial phase of injury. Electrodiagnostic and imaging studies can help the practitioner to determine the degree of preserved and recovering neurological function. In this review we will assess the various neurophysiological studies currently at our disposal to evaluate and follow the clinical course of patients who have suffered severe brain injuries.     

Incidence and prevalence of the vegetative and minimally conscious states

The methodological difficulties of obtaining accurate epidemiological data for vegetative state (VS) and minimally conscious state (MCS) are considered, and prompt the conclusion that published data are of uncertain validity, partly due to variation in the criteria for diagnosis. On the basis of these data, incidence of VS continuing for at least six months arises at a rate of between 5 and 25 per million population (PMP). The prevalence of VS in adults in the US is between 40 and 168 PMP, and may be lower in the UK, but precise figures are not available. The incidence and prevalence of MCS have yet to be established.     

Residual cognitive function in comatose, vegetative and minimally conscious states

PURPOSE OF REVIEW: The clinical evaluation of cognition in non-communicative severely brain-damaged patients is inherently difficult. In addition to novel behavioural 'consciousness-scales', the role of para-clinical markers of consciousness, such as event related potentials and functional neuroimaging is reviewed. RECENT FINDINGS: New behavioural scales for vegetative and minimally conscious patients have been shown to reduce diagnostic error but regrettably remain underused in clinical routine. Electrophysiological studies have confirmed their role in estimating outcome and possibly cognition. Several recent functional neuroimaging studies have shown residual cortical function in undeniably vegetative patients. This cortical activation, however, seems limited to primary 'low-level' areas and does not imply 'higher-order' integration, considered necessary for conscious perception. Minimally conscious patients show large-scale high-order cerebral activation, apparently dependent upon the emotional relevance of the stimulation. SUMMARY: Careful clinical assessment of putative 'conscious behaviour' in vegetative and minimally conscious patients is the first requirement for their proper diagnosis and management. Complementary functional neuroimaging and electrophysiological studies will have a major impact on future clinical decision making and may guide selective therapeutic options. At present, more experimental evidence and the elucidation of methodological and ethical controversies are awaited prior to their routine clinical use.     

The neurological assessment of patients in vegetative and minimally conscious states

Patients with serious central nervous system (CNS) injuries can enter a chronic state in which there is impaired awareness, but the presence of preserved basic vegetative functions. Such cases present formidable challenges to the medical practitioner in terms of clinical assessment and thus management. This paper presents the neurological approach to such patients highlighting the clinical clues that need to be sought to decide whether the patient is in a persistent vegetative or minimally conscious state (i.e., showing any responsiveness to external stimuli), or alternatively suffering from a locked-in syndrome. This neurological clinical formulation is then assimilated with other tests and assessments from a range of medical specialities, and by so doing helps confirm the clinical impression. This multidisciplinary approach is vital in the assessment of such patients and ideally should also include neurophysiological and functional imaging paradigms.     

Diagnostic and prognostic guidelines for the vegetative and minimally conscious states

Many individuals who sustain severe brain injury experience prolonged or permanent disorders of consciousness. While these disorders may appear homogeneous, important distinctions exist in prognosis and clinical management. Studies suggest, however, that the incidence of diagnostic inaccuracy is high in both acute care and rehabilitation settings. In this paper, we review consensus-based diagnostic and prognostic criteria for the vegetative and minimally conscious states. We also discuss recent developments and future directions for research in this area.     

Levodopa treatment for patients in persistent vegetative or minimally conscious states

The persistent vegetative state (PVS) and the minimally conscious state (MCS) are conditions of altered consciousness after severe brain damage due to a variety of pathologies. However, the specific pathophysiological mechanisms and a therapeutic strategy for intervention have not as yet been established. We review previous reports of levodopa treatment for patients in PVS, MCS, or other mental disorders, and have focused on five representative cases: four of PVS and one of MCS after severe brain injury. In summary, our review suggests the effectiveness of levodopa treatment is probably dependent upon the following criteria: (1) Diagnosis of PVS or MCS as distinct from other related conditions, (2) Concomitant symptoms of parkinsonism, and (3) Concomitant neuroradiological findings of high intensity lesions in the dopaminergic pathway on T2 weighted MRI. The apparent success of levodopa in the five cases described may reflect a specific subgroup of PVS and MCS patients, where the administration of levodopa is effective. However, we should not regard PVS or MCS as a single entity, since levodopa is unlikely to be effective in all cases. Therapeutic strategies should aim to identify the key pathophysiological mechanism for each patient and target interventions accordingly.     

Neurometabolic coupling in the vegetative and minimally conscious states: preliminary findings

The objective of this study was to determine the integrity of the homoeostatic coupling relationship between neuronal electrical function and cerebral metabolism in the vegetative and minimally conscious states. Ten patients who met recognised diagnostic criteria (six in the vegetative state and four minimally conscious) were investigated using simultaneous electroencephalography and positron emission tomography. It was found that the coupling between neuronal electrical activity and regional glucose metabolism was preserved in all the minimally conscious patients but was absent in all the vegetative state patients. Our preliminary results suggest patients in the vegetative state may endure an impaired coupling relation between neuronal electrical function and cerebral energy metabolism.     

The vegetative and minimally conscious states: diagnosis, prognosis and treatment

Severe acquired brain injury has profound impact on alertness, cognition, and behavior. Among those who survive the initial injury, a significant minority fail to fully recover self and environmental awareness, and go on to experience prolonged disorders of consciousness (DOC) that can last a lifetime. Although there are no standards of care to guide clinical management, a growing body of empirical evidence is beginning to accrue to inform clinical decision making. In this article, we review the state of the science as it pertains to diagnosis, prognosis, and treatment of patients with DOC.     

Risk factors for mortality in 600 patients in vegetative and minimally conscious states

A significant proportion of patients who survive traumatic or nontraumatic severe acquired brain injuries experiences disorders of consciousness. The vegetative state and the minimally conscious state may have different prognoses, and while some patients regain awareness, others have negative outcomes and die. The aim of this work is to identify age-related, medical and behavioural risk factors for mortality in those patients. Participants were enrolled from June 2009 to March 2012 in 107 Italian health care institutions. Univariate and multivariate Cox proportional hazard models were adopted to screen and test candidate risk factors. The study enrolled 600 subjects in vegetative and minimally conscious states for an overall mortality rate of 180.1 per 1,000 person-years. The following traits were associated with a significantly lower chance of survival: age at the acute event higher than 51 years, disease duration less than 1 year, post-anoxic aetiology, absence of visual fixation, and the presence of endocrine, nutritional, and metabolic diseases, and immunity disorders. Clinical history, behavioural assessment, and age-related factors provide important prognostic information on negative outcomes that helps clinicians and researchers to predict patients who are at higher risk of mortality. This knowledge has important clinical, managerial, and ethical implications.     

The vegetative and minimally conscious states: consensus-based criteria for establishing diagnosis and prognosis

Disorders of consciousness continue to be the subject of hot debate in healthcare settings, research consortiums, bioethics departments and media forums. There are no standards of care to guide assessment and treatment decisions resulting in wide disparities in daily practice. In response to this problem, expert panels in neurology and neurorehabilitation were convened and charged with developing consensus-based definitions and diagnostic criteria for disorders of consciousness. The Multi-Society Task Force Report on the persistent vegetative state and the Aspen Workgroup statement on the minimally conscious state represent two such initiatives. This paper summarizes the practice recommendations proposed by these groups and discusses their implications for existing and future interventions.     

Oscillatory brain activity in vegetative and minimally conscious state during a sentence comprehension task

Patients with altered states of consciousness continue to constitute a major challenge in terms of clinical assessment, treatment and daily management. Furthermore, the exploration of brain function in severely brain-damaged patients represents a unique lesional approach to the scientific study of consciousness. Electroencephalography is one means of identifying covert behaviour in the absence of motor activity in these critically ill patients. Here we focus on a language processing task which assesses whether vegetative (n=10) and minimally conscious state patients (n=4) (vs control subjects, n=14) understand semantic information on a sentence level ("The opposite of black is... white/yellow/nice"). Results indicate that only MCS but not VS patients show differential processing of unrelated ("nice") and antonym ("white") words in the form of parietal alpha (10-12Hz) event-related synchronization and desynchronization (ERS/ERD), respectively. Controls show a more typical pattern, characterized by alpha ERD in response to unrelated words and alpha ERS in response to antonyms.     

Spontaneous blinking behaviour in persistent vegetative and minimally conscious states: relationships with evolution and outcome

There is evidence that spontaneous blinking correlates with cognitive functions. This arises from the observation that blinking rate (BR) is modulated by arousal levels, basic cognitive processes (e.g., attention, information processing, memory, etc.) and more complex cognitive functions (e.g., reading, speaking, etc.). The aim of this work was to test the role of BR evaluation in the assessment of cognitive network functioning in awake patients with consciousness deficits. Thirteen patients were recruited for the study, and were assessed by the Glasgow coma scale (GCS) and Glasgow outcome scale (GOS) on admittance and discharge, respectively. A level of cognitive functioning scale (LCFS) score was assigned at every change in awareness or at least every 2 weeks. At the same time as the clinical tests, the BR was observed for a 5-min period. Ten healthy subjects, observed throughout three non-consecutive days, formed the control group. The BR underwent a different temporal behaviour in the two diagnostic categories. In the persistent vegetative state (PVS) group it remained stable throughout time and linked with the clinical conditions of the patients; whereas in the non-persistent vegetative state (NPVS) group it decreased over time as the cognitive conditions improved. Moreover, a strong inverse correlation was found between overall BR values and LCFS scores. We have concluded that the blinking behaviour changes manifested in PVS and NPVS patients reflect different evolution phases of a cholinergic-dopaminergic imbalance, and that a reduced BR characterizes the early stages of consciousness recovery.     

Rehabilitation interventions for vegetative and minimally conscious patients

Brain injury rehabilitation is a complex and challenging task for all members of the multidisciplinary team. Medical advances have allowed more severely impaired patients to survive and consequently the number of patients in the vegetative and minimally conscious states have proportionately increased. Thus, the need for evidence-based practice and further research demonstrating the effects of specific rehabilitation interventions is required. This article reviews the current research and consensus on rehabilitation for patients in the vegetative and minimally conscious states.     

Event-related potentials (MMN and novelty P3) in permanent vegetative or minimally conscious states

ObjectiveTo assess markers of cognition, if any, in patients in a permanent vegetative state (PVS).MethodsEvent-related potential (ERP) mapping was performed on 27 patients in permanent (4–261 months after coma onset) vegetative (PVS, n = 16) or minimally conscious states (MCS, n = 11) due to anoxia (n = 18) or other aetiologies (n = 9). Mismatch negativity (MMN) to duration-deviant tones and novelty P3 (nP3) to the subject’s own name were recorded according to a paradigm previously validated in healthy volunteers and comatose patients. SEPs, MLAEPs and BAEPs were also recorded.ResultsMMN was present in 5/27 and nP3 in 7/27 patients. ERPs were not related to the time from coma onset and not different in MCS and in PVS. Normal SEPs and MLAEPs, and present nP3s were less frequent in anoxia than in other aetiologies.ConclusionsIrrespective of their clinical assessment, a few patients are likely to process sound deviance (MMN) or novelty (nP3), mainly when their state is not due to anoxia.SignificanceSome PVS patients may be able to put certain awareness marker processes to work. The diagnostic criteria for PVS or MCS, currently based on mere behaviour, should also include functional brain investigations, such as ERPs, related to the aetiology.