Disorders Of Consciousness Patients Research Articles

Long-term outcome of patients with disorders of consciousness with and without epileptiform activity and seizures: a prospective single centre cohort study.

Brain-injured patients can experience epileptic seizures beyond 1week from injury (unprovoked remote symptomatic epileptic seizures). In our longitudinal observational study, we analysed occurrence of unprovoked remote epileptic seizures and interictal epileptiform activity in 130 traumatic, vascular or anoxic inpatientswith disorders of consciousness (DOC), with a clinical diagnosis of vegetative state (n=97) or minimally conscious state (n=33). We also investigated impact of epileptic seizures and epileptiform activity on clinical outcome (30months post-onset). Epileptic seizures occurred in 35/130 patients (26.9%), epileptiform activity in 61/130 (46.9%) patients, without significant differences related to clinical diagnosis or aetiology. Among patients with epileptiform activity, only 26/61 (42.6%) developed clinically evident seizures. Mortality at 30months was not significantly influenced by the presence of seizures or epileptiform activity. The proportion of patients who recovered at long-term follow-up was higher in patients without than in patients with epileptic seizures, but was similar in patients with or without epileptiform activity. The presence of epileptic seizures but not of epileptiform activity, significantly affected the level of responsiveness at final outcome. In conclusion, seizures were detected in about one third of the whole sample, and in about a half of patients with epileptiform activity, regardless of clinical diagnosis or aetiology. Although epileptic seizures or epileptiform activity did not significantly affect mortality rate, we demonstrated that epileptic seizures could hamper recovery of consciousness. Epileptic seizures thus qualify as one of the factors largely undetermined at the moment which can influence prognosis in DOC patients.

Towards a method to differentiate chronic disorder of consciousness patients' awareness: The Low-Resolution Brain Electromagnetic Tomography Analysis

Assessing residual signs of awareness in patients suffering from chronic disorders of consciousness (DOC) is a challenging issue. DOC patient behavioral assessment is often doubtful since some individuals may retain covert traces of awareness; thus, some Unresponsive Wakefulness Syndrome (UWS) patients may be misdiagnosed. The aim of our study was to explore possible differences between the source powers within poly-modal cortices to differentiate Minimally Conscious State (MCS) from UWS. To this end, we recorded an electroencephalogram (EEG) during awake resting state and performed a Low-Resolution Brain Electromagnetic Tomography (LORETA), which is a 3D source localization method allowing the visualization of the most probable neuroanatomical generators of EEG differences. MCS and UWS patients showed significant variations concerning the frontal source power of delta-band, frontal and parietal of theta, parietal and occipital of alpha, central of beta, and parietal of gamma, in correlation with the Coma Recovery Scale-Revised (CRS-R) score. The alpha-band was the most significant LORETA data correlating with the consciousness level. In addition, we observed a significant correlation between central beta-peaks and the motor abilities and a dissociation between theta and gamma bands within parietal regions. Our findings suggest that LORETA analysis may be useful in DOC differential diagnosis since distinct neurophysiological correlates in some UWS patients could be used to assess deeper the residual cerebral activity of brain areas responsible for covert awareness.

Neurotechnological assessment of consciousness disorders: five ethical imperatives

Disorders of consciousness (DOCs) cause great human suffering and material costs for society. Understanding of these disorders has advanced remarkably in recent years, but uncertainty remains with respect to the diagnostic criteria and standards of care. One of the most serious problems concerns misdiagnoses, their impact on medical decision-making, and on patients' well-being. Recent studies use neurotechnology to assess residual consciousness in DOC patients that traditional behavioral diagnostic criteria are unable to detect. The results show an urgent need to strengthen the development of new diagnostic tools and more refined diagnostic criteria. If residual consciousness may be inferred from robust and reproducible results from neurotechnological communication with DOC patients, this also raises ethical challenges. With reference to the moral notions of beneficence and fundamental rights, five ethical imperatives are here suggested in terms of diagnosis, communication, interpretation of subjective states, adaptation of living conditions, and care.

Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool.

IntroductionAttaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction.MethodsFrom the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model.ResultsFifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02).DiscussionThe association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation.

Can self-relevant stimuli help assessing patients with disorders of consciousness?

Emotional and self-relevant stimuli are able to automatically attract attention and their use in patients suffering from disorders of consciousness (DOC) might help detecting otherwise hidden signs of cognition. We here recorded EEG in three Locked-in syndrome (LIS) and four Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) patients while they listened to the voice of a family member or an unfamiliar voice during a passive. Data indicate that, in a passive listening condition, the familiar voice induces stronger alpha desynchronization than the unfamiliar one. In an active condition, the target evoked stronger alpha desynchronization in controls, two LIS patients and one VS/UWS patient. Results suggest that self-relevant familiar voice stimuli can engage additional attentional resources and might allow the detection of otherwise hidden signs of instruction-following and thus residual awareness. Further studies are necessary to find sensitive paradigms that are suited to find subtle signs of cognition and awareness in DOC patients.

Unravelling motor networks in patients with chronic disorders of consciousness: A promising minimally invasive approach

Behavioral responsiveness and awareness levels correlate with the degree of functional connectivity within cortical-thalamocortical networks, whose breakdown accounts for chronic disorders of consciousness (DOC). Our study was aimed at assessing the role of the primary motor area (M1) and premotor-M1 circuitry dysfunction in motor output deterioration in minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients. As a control group, we included a healthy subject (HC) sample in the study. We evaluated the effects of different types of transcranial magnetic stimuli over M1 by recording post-stimulus time histogram (PSTH), which includes a series of peaks of unit firing activity that match with D and I-waves, characterizing the descending corticospinal volleys evoked by transcranial magnetic stimuli. As compared to HC, DOC patients showed a dysfunction of intra-M1 and premotor-M1 circuits, which correlated with the Coma Recovery Scale-Revised scorings. Nonetheless, one UWS patient showed a partially preserved premotor-M1 circuitry, paralleled by a severe intra-M1 circuitry dysfunction. Our data suggest that motor unresponsiveness in some DOC patients may be due to a pure motor output failure, as in the functional locked-in syndrome (fLIS), rather than to a premotor-motor connectivity impairment, which instead characterizes MCS and UWS.

The Minimal Energetic Requirement of Sustained Awareness after Brain Injury

Differentiation of the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS) is a persistent clinical challenge [1]. Based on positron emission tomography (PET) studies with [(18)F]-fluorodeoxyglucose (FDG) during sleep and anesthesia, the global cerebral metabolic rate of glucose has been proposed as an indicator of consciousness [2, 3]. Likewise, FDG-PET may contribute to the clinical diagnosis of disorders of consciousness (DOCs) [4, 5]. However, current methods are non-quantitative and have important drawbacks deriving from visually guided assessment of relative changes in brain metabolism [4]. We here used FDG-PET to measure resting state brain glucose metabolism in 131 DOC patients to identify objective quantitative metabolic indicators and predictors of awareness. Quantitation of images was performed by normalizing to extracerebral tissue. We show that 42% of normal cortical activity represents the minimal energetic requirement for the presence of conscious awareness. Overall, the cerebral metabolic rate accounted for the current level, or imminent return, of awareness in 94% of the patient population, suggesting a global energetic threshold effect, associated with the reemergence of consciousness after brain injury. Our data further revealed that regional variations relative to the global resting metabolic level reflect preservation of specific cognitive or sensory modules, such as vision and language comprehension. These findings provide a simple and objective metabolic marker of consciousness, which can readily be implemented clinically. The direct correlation between brain metabolism and behavior further suggests that DOCs can fundamentally be understood as pathological neuroenergetic conditions and provide a unifying physiological basis for these syndromes.

Long-Term (Six Years) Clinical Outcome Discrimination of Patients in the Vegetative State Could be Achieved Based on the Operational Architectonics EEG Analysis: A Pilot Feasibility Study.

Electroencephalogram (EEG) recordings are increasingly used to evaluate patients with disorders of consciousness (DOC) or assess their prognosis outcome in the short-term perspective. However, there is a lack of information concerning the effectiveness of EEG in classifying long-term (many years) outcome in chronic DOC patients. Here we tested whether EEG operational architectonics parameters (geared towards consciousness phenomenon detection rather than neurophysiological processes) could be useful for distinguishing a very long-term (6 years) clinical outcome of DOC patients whose EEGs were registered within 3 months post-injury. The obtained results suggest that EEG recorded at third month after sustaining brain damage, may contain useful information on the long-term outcome of patients in vegetative state: it could discriminate patients who remain in a persistent vegetative state from patients who reach a minimally conscious state or even recover a full consciousness in a long-term perspective (6 years) post-injury. These findings, if confirmed in further studies, may be pivotal for long-term planning of clinical care, rehabilitative programs, medical-legal decisions concerning the patients, and policy makers.

Transcranial Alternating Current Stimulation in Patients with Chronic Disorder of Consciousness: A Possible Way to Cut the Diagnostic Gordian Knot?

Unresponsive wakefulness syndrome (UWS) is a chronic disorder of consciousness (DOC) characterized by a lack of awareness and purposeful motor behaviors, owing to an extensive brain connectivity impairment. Nevertheless, some UWS patients may retain residual brain connectivity patterns, which may sustain a covert awareness, namely functional locked-in syndrome (fLIS). We evaluated the possibility of bringing to light such residual neural networks using a non-invasive neurostimulation protocol. To this end, we enrolled 15 healthy individuals and 26 DOC patients (minimally conscious state-MCS- and UWS), who underwent a γ-band transcranial alternating current stimulation (tACS) over the right dorsolateral prefrontal cortex. We measured the effects of tACS on power and partial-directed coherence within local and long-range cortical networks, before and after the protocol application. tACS was able to specifically modulate large-scale cortical effective connectivity and excitability in all the MCS participants and some UWS patients, who could be, therefore, considered as suffering from fLIS. Hence, tACS could be a useful approach in supporting a DOC differential diagnosis, depending on the level of preservation of the cortical large-scale effective connectivity.

End-Of-Life Decisions in Chronic Disorders of Consciousness: Sacrality and Dignity as Factors

The management of patients suffering from chronic disorders of consciousness (DOC) inevitably raises important ethical questions about the end of life decisions. Some ethical positions claim respect of human life sacredness and the use of good medical practices require allowing DOC patients to live as long as possible, since no one can arbitrarily end either his/her or others’ life. On the other hand, some currents of thought claim respect of human life dignity, patients’ wishes, and the right of free choice entail allowing the withdrawal of life sustaining therapy. This could happen when patients (or surrogates) believe their own life to be not worth living, or if therapy is not very beneficial, excessively burdensome, or even futile. Indeed, the decision to withdraw therapies in a DOC patient should be guided by reliable information about DOC diagnosis and prognosis and on how the patient would wish to be treated in such a condition. Taking into account such issues, it would be possible to make the decision that more adequately fits a DOC patient’s best interest. This review aims to overview the range of ethical issues referring to end-of-life decisions in DOC patients, with regard to the thorny debate on the sacredness and dignity of human life.

Could autonomic system assessment be helpful in disorders of consciousness diagnosis? A neurophysiological study

Although patients with chronic disorders of consciousness (DOC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), show a limited repertoire of awareness signs, owing to a large-scale cortico-thalamo-cortical functional disconnectivity, an activation of some cortical areas in response to relevant stimuli has been described by means of electrophysiological and functional neuroimaging approaches. In addition, cognitive processes associated with autonomic nervous system (ANS) responses elicited by nociceptive stimuli have been identified in some DOC patients. In an attempt to identify ANS functionality markers that could be useful in differentiating UWS and MCS individuals, we measured the amplitude, latency and γ-band power (γPOW) of ultra-late laser-evoked potentials (CLEPs) and skin reflex (SR), which both express some aspects of cognitive processes related to ANS functionality, besides other ANS parameters either during a 24(hh)-polygraphy or following a solid-state laser repetitive nociceptive stimulation. MCS showed physiological modification of vital signs (O2 saturation, hearth rate, hearth rate variability) throughout the night and a preservation of SR-γPOW, whereas UWS did not show significant variations. Following repetitive nociceptive stimulation, MCS patients had a significant increase in CLEP-γPOW, O2 saturation, hearth rate, and hearth rate variability, whereas UWS individuals did not show any significant change (but two patients, who reached high Coma Recovery Scale-Revised scores). Hence, our work suggests that a wide-spectrum electrophysiological evaluation of ANS functionality may support DOC differential diagnosis. Interestingly, the two above-mentioned UWS patients showed MCS-like vital sign modifications and electrophysiological pain responsiveness. It is therefore hypothesizable that our approach could be helpful in identifying residual aware autonomic system-related cognitive processes even in some UWS patients. Such issue draws the attention to either DOC clinical diagnosis or adequate pain treatment in DOC patients.

86. Diagnostic value of standard EEG in prolonged Disorders of Consciousness

Assessment of responsiveness is critical for definition of treatment and prognosis of Disorders of Consciousness (DOC), but is very challenging. In the present cross-sectional study we analyzed the background predominant EEG activity (in terms of frequency and voltage) and reactivity to eye closing and to tactile, acoustic, noxiceptive stimuli and Intermittent Photic Stimulation (IPS) in 63 prolonged traumatic, vascular and anoxic DOC patients (30 F; mean age 55.4 yrs.), with a clinical diagnosis of vegetative state (VS, n = 33) or minimally conscious state (MCS, n = 30). The distribution of specific patterns of background EEG activity was significantly different between the two diagnosis (p = .001) and across the three etiologies (p = .003). Reactivity to several stimuli was significantly more frequent in MCS than in VS: such difference was significant for IPS (p = .004), whereas it only approached the significance level for eye closing (p = .06) and acoustic stimuli (p = .06). Presence of at least one reactivity, including or excluding IPS reactivity, was significantly more frequent in MCS than in VS (p < .006), and had good sensibility but low specificity for diagnosis of MCS. Presence of at least 3 kinds of reactivity had the highest specificity (.83). Qualitative analysis of standard EEG can provide additional elements for diagnosis of DOC.

ID 368 – Regional changes in detrend fluctuation analysis exponent values in healthy subjects

Objective Detrended Fluctuation Analysis (DFA) was applied to EEGs recorded in healthy subjects as part of a study aimed at establishing the EEG in the bedside assessment of patients with disorder of consciousness (DOC). Analysis of normal human EEG indicates complex brain dynamics conforming to power laws statistics, with the suggestion of disrupted brain dynamics in DOC patients. Methods EEG recordings in healthy subjects ( n = 20),aged 24–59 years (mean 39.5, ± 10.11 years) were filtered between 0.5–70 Hz and sampled at 256 Hz. Artefact rejection was achieved by using independent component analysis (ICA). DFA Exponents were calculated for alpha (8–13 Hz), theta (4–7 Hz), beta (14–30 Hz) and delta (0.5–4 Hz) frequencies. Results Summarising exponent values across subjects indicates alpha DFA exponents were predictive for beta and theta DFA exponents values ( R 2 = 0.97 and 0. 93 respectively) and influenced by region. Conclusion Alpha DFA exponents were predictive for beta and theta exponent values suggesting an interaction between regions underpinning fluctuations of alpha, beta and theta oscillations. Applying this analysis to EEGs recorded in DOC patients could facilitate behavioural assessment and predict improved outcomes in the absence of unequivocal clinical signs of higher awareness. Key Message DFA exponents derived from EEG signals could facilitate characterization of patients with disorder of consciousness and equivocal clinical signs.

Quantitative research into the deconditioning of hemodynamic to disorder of consciousness carried out using transcranial Doppler ultrasonography and photoplethysmography obtained via finger-transmissive absorption.

In this study, transcranial Doppler ultrasonography (TCD) and photoplethysmography (PPG) have been utilized, through the observation of peripheral and cerebrovascular hemodynamic changes of the disorder of consciousness (DOC) patients, measured on clinical behavior scale of Coma Recovery Score-Revised (CRS-R) to obesrve their diagnostic value in evaluation of DOC patients. TCD ultrasound was used to evaluate the flow velocity and waveform patterns of middle cerebral artery (MCA), while PPG infrared signals were utilized to assess the peripheral circulation as a mean of measuring cardiovascular activities. The research was carried out on a sample of 36 individuals, of which 16 met the DOC criteria and 20 were healthy individuals. Each person in the patients groups was assessed by the CRS-R. The velocity of middle cerebral artery in tested patients in a whole cardiac cycle, detected by TCD, decreased comparing with normal values. The values of pulsatility index (PI) of the MCA increased in patients groups comparing with normal. Through binary variables correlation analysis, we found that the PI of the left MCA of TCD of the patients significantly inversely correlated with their motor subscore, included in their CRS-R in the level of α = 0.05 (Pearson’s product-moment correlation coefficient = −0.556, p = 0.025). The values of photoplethysmographic augmentation index (PAI) that were detected by PPG increased comparing with normal. Finally, using binary variables correlation analysis we found the significant inverse correlation between the PAI of PPG and the mean velocity of the left MCA of the TCD in the level of α = 0.05 (Pearson’s product-moment correlation coefficient = −0.377, p = 0.022) in all the groups. The results of this study revealed a specific relationship between PI and PAI in the DOC patients. That relationship can potentially be exploited to enhance the capabilities in early assessment of the deconditioning of the DOC patients’ cardiovascular system and its influence on their cerebral vascular system. Ultimately, the dependency discovered can assist in predicting the tendency of the prognosis of the DOC patients in clinic.

A Short Commentary on Non-invasive Brain Stimulation in Chronic Disorder of Consciousness Differential Diagnosis

The diagnosis and awareness assessments in chronic disorders of consciousness (DOC) are biased, owing to their reliance on clinical behavioral measures. Indeed, objective tools should be employed with the goal of more precise awareness detection in these patients. To this end, brain stimulation techniques have been developed to demonstrate residual cortical-thalamocortical connectivity patterns sustaining fragment of awareness. This short commentary aims at illustrating the Non-Invasive Brain Stimulation (NIBS) techniques applied to DOC patients. NIBS are promising in helping clinicians to differentiate among DOC patients and to identify residual fragments of awareness within Vegetative State individuals, namely Functional Locked-In Syndrome.

Cortical Responsiveness to Nociceptive Stimuli in Patients with Chronic Disorders of Consciousness: Do C-Fiber Laser Evoked Potentials Have a Role?

It has been shown that the presence of Aδ-fiber laser evoked potentials (Aδ-LEP) in patients suffering from chronic disorders of consciousness (DOC), such as vegetative state (VS) and minimally conscious state (MCS), may be the expression of a residual cortical pain arousal. Interestingly, the study of C-fiber LEP (C-LEP) could be useful in the assessment of cortical pain arousal in the DOC individuals who lack of Aδ-LEP. To this end, we enrolled 38 DOC patients following post-anoxic or post-traumatic brain injury, who met the international criteria for VS and MCS diagnosis. Each subject was clinically evaluated, through the coma recovery scale-revised (CRS-R) and the nociceptive coma scale-revised (NCS-R), and electrophysiologically tested by means of a solid-state laser for Aδ-LEP and C-LEP. VS individuals showed increased latencies and reduced amplitudes of both the Aδ-LEP and C-LEP components in comparison to MCS patients. Although nearly all of the patients had both the LEP components, some VS individuals showed only the C-LEP ones. Notably, such patients had a similar NCS-R score to those having both the LEP components. Hence, we could hypothesize that C-LEP generators may be rearranged or partially spared in order to still guarantee cortical pain arousal when Aδ-LEP generators are damaged. Therefore, the residual presence of C-LEP should be assessed when Aδ-LEP are missing, since a potential pain experience should be still present in some patients, so to properly initiate, or adapt, the most appropriate pain treatment.

How Can Music Influence the Autonomic Nervous System Response in Patients with Severe Disorder of Consciousness?

Activations to pleasant and unpleasant musical stimuli were observed within an extensive neuronal network and different brain structures, as well as in the processing of the syntactic and semantic aspects of the music. Previous studies evidenced a correlation between autonomic activity and emotion evoked by music listening in patients with Disorders of Consciousness (DoC). In this study, we analyzed retrospectively the autonomic response to musical stimuli by mean of normalized units of Low Frequency (nuLF) and Sample Entropy (SampEn) of Heart Rate Variability (HRV) parameters, and their possible correlation to the different complexity of four musical samples (i.e., Mussorgsky, Tchaikovsky, Grieg, and Boccherini) in Healthy subjects and Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) patients. The complexity of musical sample was based on Formal Complexity and General Dynamics parameters defined by Imberty's semiology studies. The results showed a significant difference between the two groups for SampEn during the listening of Mussorgsky's music and for nuLF during the listening of Boccherini and Mussorgsky's music. Moreover, the VS/UWS group showed a reduction of nuLF as well as SampEn comparing music of increasing Formal Complexity and General Dynamics. These results put in evidence how the internal structure of the music can change the autonomic response in patients with DoC. Further investigations are required to better comprehend how musical stimulation can modify the autonomic response in DoC patients, in order to administer the stimuli in a more effective way.

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized, Controlled Trial.

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients’ arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718

Central olfactory processing in patients with disorders of consciousness.

Previous studies have demonstrated that individuals suffering from disorder of consciousness (DOC) maintain some minor neural processing of percepts mediated by senses that early in their pathway intersect the thalamus, a key dysfunctional area in DOC patients. Here the degree of sensory preservation within the olfactory system, a system that lacks an obligatory thalamic relay, and its relationship to the consciousness level in DOC patients of various etiologies was assessed. Clinical Coma Recovery Scale - Revised (CRS-R) as well as cerebral responses to odors by means of functional magnetic resonance were obtained in a group of vegetative state/unresponsive wakefulness syndrome (n = 26) patients, minimally conscious state (n = 7) patients and healthy controls (n = 25). A majority of vegetative state/unresponsive wakefulness syndrome patients (58%) and 100% of minimally conscious state patients demonstrated a significant preservation of olfactory neural processing, manifested by activation within the piriform cortex, an area considered as a primary olfactory region. Degree of preservation of olfactory processing differed linearly in line with the patients' etiologies where groups demonstrating greater conscious awareness demonstrated more significant processing. Viewed over all DOC patients, there was a significant negative association between odor-related activity in the orbitofrontal cortex and CRS-R scores. It is demonstrated that DOC patients exhibit a significant preservation of olfactory neural processing with a clear relationship to etiopathologies and clinical measures even years after of chronification of DOC.

Brain default mode network study of consciousness disorder patients with diffuse axonal injury

Objective To investigate the early abnormal functional connectivity of brain default mode network (DMN) and its evaluation for consciousness level after injury in consciousness disorder patients with diffuse axonal injury. Methods A total of 15 patients with consciousness disorder diagnosed as diffuse axonal injury at Department of Neurosurgery, Wuhan General Hospital of Guangzhou Military Command from April 2013 to March 2014 were selected. The resting-state functional magnetic resonance data of the 15 consciousness disorder patients with diffuse axonal injury and 15 healthy volunteers were collected. The independent component analysis was used to extract the DMN ingredient in each subject. The two-sample t-test was performed between the groups in order to obtain the different brain areas, and the correlation analysis of the Glasgow coma scale (GCS) and the coma recovery scale-revised (CRS-R) at 6 months after injury were performed at the different brain areas and the magnetic resonance data were collected on the same day. Results The functional connectivity degree of the precuneus/posterior cingulate, bilateral inferior parietal lobule, ventromedial prefrontal cortex, and left temporal lobe in brain DMN in patients with diffuse axonal injury were significantly lower than those of control group (P<0.01). The functional connectivity of the precuneus/posterior cingulated and GCS showed significant power correlation (P<0.05), and it also showed significant power correlation with CRS-R (P<0.01). Conclusions The early brain DMN functional connectivity has abnormality in consciousness disorder patients with diffuse axonal injury. The abnormal functional connectivity of the precuneus/posterior cingulate may become an indicator for assessing the degree of consciousness disorder and the prognosis of consciousness disorder. Key words: Diffuse axonal injury; Consciousness disorders; Prognosis; Magnetic resonance imaging; Default mode network