Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception.     

Nutrition and hydration for the vegetative state and minimally conscious state patient

This paper presents nutritional issues particular to patients in the vegetative state (VS) or minimally conscious state (MCS). It assumes that such patients would be tube fed and it examines suitable ways of assessing and monitoring their nutrition. It covers problems frequently encountered such as undernourishment, high fluid requirements, bowel management, and vomiting. It also looks at the practicalities of long-term tube feeding. Once medical stability has been achieved, feeding these patients is almost always successful with the patient's body weight restored to being within normal limits.     

Deep brain stimulation improves electroencephalogram functional connectivity of patients with minimally conscious state

AimDeep brain stimulation (DBS) is a potential neuromodulatory therapy that enhances recovery from disorders of consciousness, especially minimally conscious state (MCS). This study measured the effects of DBS on the brain and explored the underlying mechanisms of DBS on MCS.MethodsNine patients with MCS were recruited for this study. The neuromodulation effects of 100 Hz DBS were explored via cross‐control experiments. Coma Recovery Scale‐Revised (CRS‐R) and EEG were recorded, and corresponding functional connectivity and network parameters were calculated.ResultsOur results showed that 100 Hz DBS could improve the functional connectivity of the whole, local and local–local brain regions, while no significant change in EEG functional connectivity was observed in sham DBS. The whole brain''s network parameters (clustering coefficient, path length, and small world characteristic) were significantly improved. In addition, a significant increase in the CRS‐R and functional connectivity of three MCS patients who received 100 Hz DBS for 6 months were observed.ConclusionThis study showed that DBS improved EEG functional connectivity and brain networks, indicating that the long‐term use of DBS could improve the level of consciousness of MCS patients.     

Resting-state EEG study of comatose patients: a connectivity and frequency analysis to find differences between vegetative and minimally conscious states

The aim of this study was to look for differences in the power spectra and in EEG connectivity measures between patients in the vegetative state (VS/UWS) and patients in the minimally conscious state (MCS). The EEG of 31 patients was recorded and analyzed. Power spectra were obtained using modern multitaper methods. Three connectivity measures (coherence, the imaginary part of coherency and the phase lag index) were computed. Of the 31 patients, 21 were diagnosed as MCS and 10 as VS/UWS using the Coma Recovery Scale-Revised (CRS-R). EEG power spectra revealed differences between the two conditions. The VS/UWS patients showed increased delta power but decreased alpha power compared with the MCS patients. Connectivity measures were correlated with the CRS-R diagnosis; patients in the VS/UWS had significantly lower connectivity than MCS patients in the theta and alpha bands. Standard EEG recorded in clinical conditions could be used as a tool to help the clinician in the diagnosis of disorders of consciousness.     

Information processing in severe disorders of consciousness: vegetative state and minimally conscious state.

OBJECTIVE: To study the presence of electrophysiological indicators of remaining cortical functions in patients with persistent vegetative state (PVS) and minimally conscious state (MCS). Previous electrophysiological and PET data indicated that some PVS patients have partially intact cortical processing functions. However, it remains unclear whether the reported patients were representative for PVS population or just some exceptional cases. Methods: Event-related brain responses to stimuli of different complexity levels, recorded in 98 patients with extremely severe diffuse brain injuries, 50 of which in PVS. Four main indicators of cortical functions were: (i) N1-P2 complex as an index of simple, undifferentiated cortical processing; (ii) mismatch negativity as an index of pre-attentive, probably unconscious, cortical orientation; (iii) P3 wave as an index of deep cortical analysis of physical stimuli, and (iv) brain responses to semantic stimuli. RESULTS: Cortical responses were found in all PVS patients with a background EEG activity > 4 Hz. All responses investigated, including those to semantic stimuli that indicated comprehension of meaning, occurred significantly above chance, though less frequently than in patients with severe brain injuries who were conscious. CONCLUSIONS: Cortical responses were lacking in most patients with severe EEG slowing (< 4 Hz). Follow-up data revealed that the presence of a mismatch negativity, a short disease duration, and the traumatic etiology were related to a better outcome. SIGNIFICANCE: The data show that in a subpopulation of PVS patients with preserved thalamocortical feedback connections, remaining cortical information processing is a consistent finding and may even involve semantic levels of processing.     

微意识状态与持续植物状态疗效的对比研究

目的 探讨微意识状态(MCS)与持续植物状态(PVS)患者疗效的差异. 方法 深圳市第三人民医院自2004年2月至2011年3月收治脑外伤、脑出血致持续昏迷状态患者56例,其中临床判定MCS状态23例,余PVS 33例,患者均采用最新的药物、一体化系统综合康复促醒治疗,比较2组患者治疗前、治疗1、3、5个疗程后PVS量表评分和疗效,评定不同年龄段MCS患者疗效的差异. 结果 治疗3疗程、5疗程后MCS组患者PVS评分均高于PVS组,差异有统计学意义(P＜0.05).MCS组患者治疗1、3、5疗程后,PVS组患者治疗3、5疗程后PVS评分均高于治疗前,2组患者治疗5疗程后PVS评分均高于治疗1疗程,差异均有统计学意义(P＜0.05);2组患者疗效的差异有统计学意义(P＜0.05),由平均秩次判断,MCS组疗效较好;不同年龄段MCS患者疗效的差异有统计学意义(P＜0.05),其中18～29岁MCS患者疗效最好,＞50岁最差. 结论 MCS患者的治疗疗效明显好于PVS患者,一体化的系统治疗对于MCS患者很重要,可使多数患者意识恢复.     

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.     

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.     

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.     

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.     

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.     

Automated EEG entropy measurements in coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state

Monitoring the level of consciousness in brain-injured patients with disorders of consciousness is crucial as it provides diagnostic and prognostic information. Behavioral assessment remains the gold standard for assessing consciousness but previous studies have shown a high rate of misdiagnosis. This study aimed to investigate the usefulness of electroencephalography (EEG) entropy measurements in differentiating unconscious (coma or vegetative) from minimally conscious patients. Left fronto-temporal EEG recordings (10-minute resting state epochs) were prospectively obtained in 56 patients and 16 age-matched healthy volunteers. Patients were assessed in the acute (≤1 month post-injury; n=29) or chronic (>1 month post-injury; n=27) stage. The etiology was traumatic in 23 patients. Automated online EEG entropy calculations (providing an arbitrary value ranging from 0 to 91) were compared with behavioral assessments (Coma Recovery Scale-Revised) and outcome. EEG entropy correlated with Coma Recovery Scale total scores (r=0.49). Mean EEG entropy values were higher in minimally conscious (73±19; mean and standard deviation) than in vegetative/unresponsive wakefulness syndrome patients (45±28). Receiver operating characteristic analysis revealed an entropy cut-off value of 52 differentiating acute unconscious from minimally conscious patients (sensitivity 89% and specificity 90%). In chronic patients, entropy measurements offered no reliable diagnostic information. EEG entropy measurements did not allow prediction of outcome. User-independent time-frequency balanced spectral EEG entropy measurements seem to constitute an interesting diagnostic - albeit not prognostic - tool for assessing neural network complexity in disorders of consciousness in the acute setting. Future studies are needed before using this tool in routine clinical practice, and these should seek to improve automated EEG quantification paradigms in order to reduce the remaining false negative and false positive findings.     

Brain response to one's own name in vegetative state, minimally conscious state, and locked-in syndrome

BACKGROUND: A major challenge in the management of severely brain-injured patients with altered states of consciousness is to estimate their residual perception of the environment. OBJECTIVE: To investigate the integrity of detection of one's own name in patients in a behaviorally well-documented vegetative state (VS), patients in a minimally conscious state (MCS), and patients with locked-in syndrome. DESIGN: We recorded the auditory evoked potentials to the patient's own name and to 7 other equiprobable first names in 15 brain-damaged patients. RESULTS: A P3 component was observed in response to the patient's name in all patients with locked-in syndrome, in all MCS patients, and in 3 of 5 patients in a VS. P3 latency was significantly (P<.05) delayed for MCS and VS patients compared with healthy volunteers. CONCLUSIONS: These results suggest that partially preserved semantic processing could be observed in noncommunicative brain-damaged patients, notably for the detection of salient stimuli, such as the subject's own name. This function seems delayed in MCS and (if present) in VS patients. More important, a P3 response does not necessarily reflect conscious perception and cannot be used to differentiate VS from MCS patients.     

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.     

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.