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Background: Large hemispheric infarction (LHI) is an ischemic stroke affecting at least two-thirds of the middle cerebral artery territory, with or without involvement of the anterior cerebral artery or posterior cerebral artery, and approximately 77% of LHI patients have early consciousness disorder (ECD). We constructed a functional brain network for LHI patients with an acute consciousness disorder to identify new diagnostic markers related to ECDs by analyzing brain network characteristics and mechanisms., Methods: Between August 1, 2017, and September 30, 2018, patients with acute (< 1 month) LHI were admitted to the neurocritical care unit at Xuanwu Hospital of Capital Medical University. Electroencephalography (EEG) data were recorded, and the MATLAB platform (2017b) was used to calculate spectral power, entropy, coherence and phase synchronization. The quantitative EEG and brain network characteristics of different consciousness states and different frequency bands were analyzed (α = 0.05). EEG data were recorded 38 times in 30 patients, 25 of whom were in the ECD group, while 13 patients were in the conscious group., Results: (1) Spectral power analysis: The conscious group had higher beta relative spectral power across the whole brain, higher alpha spectral power in the frontal-parietal lobe on the infarction contralateral side, and lower theta and delta spectral power in the central-occipital lobe on the infarction contralateral side than the ECD group. (2) Entropy analysis: The conscious group had higher approximate entropy (ApEn) and permutation entropy (PeEn) across the whole brain than the ECD group. (3) Coherence: The conscious group had higher alpha coherence in nearly the whole brain and higher beta coherence in the bilateral frontal-parietal and parietal-occipital lobes than the ECD group. (4) Phase synchronization: The conscious group had higher alpha and beta synchronization in nearly the whole brain, particularly in the frontal-parietal and parietal-occipital lobes, than the ECD group. (5) Graph theory: The conscious group had higher small-worldness in each frequency band than the ECD group., Conclusion: In patients with LHI, higher levels of consciousness were associated with more alpha and beta oscillations and fewer delta and theta oscillations. Higher ApEn, PeEn, total brain connectivity, and small-worldness and a wider signal distribution range corresponded to a higher consciousness level.

Background/objective: Behavioral examinations may fail to detect language function in patients with severe traumatic brain injury (TBI) due to confounds such as having an endotracheal tube. We investigated whether resting and stimulus-evoked electroencephalography (EEG) methods detect the presence of language function in patients with severe TBI., Methods: Four EEG measures were assessed: (1) resting background (applying Forgacs' criteria), (2) reactivity to speech, (3) background and reactivity (applying Synek's criteria); and (4) an automated support vector machine (classifier for speech versus rest). Cohen's kappa measured agreement between the four EEG measures and evidence of language function on a behavioral coma recovery scale-revised (CRS-R) and composite (CRS-R or functional MRI) reference standard. Sensitivity and specificity of each EEG measure were calculated against the reference standards., Results: We enrolled 17 adult patients with severe TBI (mean ± SD age 27.0 ± 7.0 years; median [range] 11.5 [2-1173] days post-injury) and 16 healthy subjects (age 28.5 ± 7.8 years). The classifier, followed by Forgacs' criteria for resting background, demonstrated the highest agreement with the behavioral reference standard. Only Synek's criteria for background and reactivity showed significant agreement with the composite reference standard. The classifier and resting background showed balanced sensitivity and specificity for behavioral (sensitivity = 84.6% and 80.8%; specificity = 57.1% for both) and composite reference standards (sensitivity = 79.3% and 75.9%, specificity = 50% for both)., Conclusions: Methods applying an automated classifier, resting background, or resting background with reactivity may identify severe TBI patients with preserved language function. Automated classifier methods may enable unbiased and efficient assessment of larger populations or serial timepoints, while qualitative visual methods may be practical in community settings.

Introduction: New guidelines regarding the diagnosis of disorders of consciousness (DOC) (such as vegetative state and minimally conscious state) have recently been published by the American Academy of Neurology and the European Academy of Neurology. This follows an impressive number of prospective studies performed on DOC and recent multi-centric studies with larger sample size, which have gathered precious information on the recovery of cohort of patients through years and which now call for a better management of patients with DOC., Areas Covered: This review will discuss recent updates on the clinical entities of DOC, the challenges for an accurate diagnosis and the last developments in diagnostic tools., Expert Opinion: The authors will also discuss the impact of the new guidelines on their way of diagnosing patients and how diagnosis will most likely change in a near future.

Objective: This international multicenter, prospective, observational study aimed at identifying predictors of short-term clinical outcome in patients with prolonged disorders of consciousness (DoC) due to acquired severe brain injury., Methods: Patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS) were enrolled within 3 months from their brain injury in 12 specialized medical institutions. Demographic, anamnestic, clinical, and neurophysiologic data were collected at study entry. Patients were then followed up for assessing the primary outcome, that is, clinical diagnosis according to standardized criteria at 6 months postinjury., Results: We enrolled 147 patients (44 women; mean age 49.4 [95% confidence interval 46.1-52.6] years; VS/UWS 71, MCS 76; traumatic 55, vascular 56, anoxic 36; mean time postinjury 59.6 [55.4-63.6] days). The 6-month follow-up was complete for 143 patients (VS/UWS 70; MCS 73). With respect to study entry, the clinical diagnosis improved in 72 patients (VS/UWS 27; MCS 45). Younger age, shorter time postinjury, higher Coma Recovery Scale-Revised total score, and presence of EEG reactivity to eye opening at study entry predicted better outcome, whereas etiology, clinical diagnosis, Disability Rating Scale score, EEG background activity, acoustic reactivity, and P300 on event-related potentials were not associated with outcome., Conclusions: Multimodal assessment could identify patients with higher likelihood of clinical improvement in order to help clinicians, families, and funding sources with various aspects of decision-making. This multicenter, international study aims to stimulate further research that drives international consensus regarding standardization of prognostic procedures for patients with DoC., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Previous studies have shown that a single Coma-Recovery Scale-Revision (CRS-R) assessment can identify high rates of misdiagnosis by clinical consensus. The aim of this study was to investigate the proportion of misdiagnosis by clinical consensus compared to repeated behavior-scale assessments in patients with prolonged disorders of consciousness (DOC)., Methods: Patients with prolonged DOC during hospitalization were screened by clinicians, and the clinicians formed a clinical-consensus diagnosis. Trained professionals used the CRS-R to evaluate the consciousness levels of the enrolled patients repeatedly (≥5 times) within a week. Based on the repeated evaluation results, the enrolled patients with prolonged DOC were divided into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and emergence from MCS (EMCS). Finally, the relationship between the results of the CRS-R and the clinical consensus were analyzed., Results: In this study, 137 patients with a clinical-consensus diagnosis of prolonged DOC were enrolled. It was found that 24.7% of patients with clinical UWS were actually in MCS after a single CRS-R behavior evaluation, while the repeated CRS-R evaluation results showed that the proportion of misdiagnosis of MCS was 38.2%. A total of 16.7% of EMCS patients were misdiagnosed with clinical MCS, and 1.1% of EMCS patients were misdiagnosed with clinical UWS., Conclusions: The rate of the misdiagnosis by clinical consensus is still relatively high. Therefore, clinicians should be aware of the importance of the bedside CRS-R behavior assessment and should apply the CRS-R tool in daily procedures., Trial Registration: ClinicalTrials.gov ID: NCT04139239 ; Registered 24 October 2019 - Retrospectively registered.

Background: The complexity of neurophysiological brain responses to direct cortical stimulation, referred to as the perturbational complexity index (PCI), has been shown able to discriminate between consciousness and unconsciousness in patients surviving severe brain injury as well as several other conditions (e.g., wake, dreamless sleep, sleep and ketamine dreaming, anesthesia)., Objective: This study asks whether, in patients with a disorder of consciousness (DOC), the complexity of the neurophysiological response to cortical stimulation is preferentially associated with atrophy within specific brain structures., Methods: We perform a retrospective analysis of 40 DOC patients and correlate their maximal PCI to MR-based measurements of cortical thinning and subcortical atrophy., Results: PCI was systematically and inversely associated with the degree of local atrophy within the globus pallidus, a region previously linked to electrocortical and behavioral arousal. Conversely, we fail to detect any association between variance in cortical ribbon thickness and PCI., Conclusion: These findings corroborate the previously reported association between pallidal atrophy and low behavioral arousal and suggest that this region's role in maintaining the overall balance of excitation and inhibition may critically affect the emergence of complex cortical interactions in chronic disorders of consciousness. This finding thus also suggests a target for potential neuromodulatory intervention in DOC patients., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: According to electroencephalogram (EEG) descriptors included in the American Clinical Neurophysiology Society (ACNS) terminology, we generated a score, and we compared it to the EEG scores previously proposed in order to identify the one with the best prognostic power for neurological outcome at post-acute stages in patients with severe disorders of consciousness (DoC)., Materials and Methods: Patients included in the analysis were clinically evaluated with the Coma Recovery Scale-Revised (CRS-R). An EEG was performed within the first week after admission to Intensive Rehabilitation Unit (IRU). EEGs were classified according to the ACNS terminology and to the scores of Bagnato and Estraneo., Results: A total of 260 patients admitted to the IRU were analysed. A total of 160 patients (61%) improved their consciousness level during IRU stay. EEG score based on the ANCS terminology showed higher overall performance (receiver-operating area under the curve = 0.79) and greater sensitivity (65%), at comparable specificities (80%), for clinical improvement as compared to both CRS-R admission score and other EEG scores. Combining our EEG score with CRS-R score at admission, the cumulative sensitivity increased to 76% when at least one good prognostic index test was present in the same patient, whereas specificity increased up to 93% if both the good prognostic patterns of clinical and instrumental parameters were simultaneously present., Conclusion: The EEG scored according to the ACNS terminology is the best among those looked at for the prediction of short-term clinical improvement in patients with DoC and represents a useful instrumental test, complementary to clinical evaluation at admission, to be added in post-acute neurological prognostication methods., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In 2018, the American Academy of Neurology, the American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research published a systematic evidence-based review and an associated practice guideline for improved assessment, treatment, and rehabilitation of patients with disorders of consciousness. Patients with disorders of consciousness include individuals in the vegetative and minimally conscious states, as well as others with covert consciousness and cognitive motor dissociation. These landmark publications (concurrently published in Neurology and Archives of Physical Medicine and Rehabilitation) supplant the 1994 New England Journal of Medicine Multi-Society Task Force report on the vegetative state and the 2002 criteria establishing minimally conscious states. The guideline re-designates the permanent vegetative state as chronic. In our article, we consider the legal and ethical implications of the practice guideline for clinical practice and explain the vulnerability of these patients who suffer from high rates of misdiagnosis, inadequate medical surveillance, undertreatment of pain, inadequate rehabilitation, and segregation in chronic care. We argue that these deficiencies in medical care are inconsistent with our growing appreciation of the dynamic nature of these brain states and an emerging standard of care as articulated by the national guideline. These deficiencies also violate domestic and international disability law. To substantiate this latter claim, we apply disability law to this population, focusing on key Americans with Disabilities Act mandates, the relevance of the 1999 Supreme Court, Olmstead v. L.C., and the utility of Olmstead enforcement actions to integrate the care of these individuals into the medical mainstream., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: Growing evidence have linked disorders of consciousness (DOC) with the changes in frequency-specific functional networks. However, the alteration of inter-frequency dynamics in brain networks remain largely unknown. In this study, we investigated the network integration and segregation across frequency bands in a multiplex network framework., Approach: Resting-state EEG data were recorded and analysed from 19 patients in minimally conscious state, 35 patients in unresponsive wakefulness syndrome (UWS) and 23 healthy controls. Frequency-based multiplex (cross-frequency) networks were reconstructed by integrating the five frequency-specific networks. Multiplex graph metrics, named multiplex participation coefficient and multiplex clustering coefficient, were employed to assess the network topology of subjects with different levels of consciousness., Main Results: Results revealed DOC networks, compared to those of healthy controls, may work at a less optimal point (closer to complete disorder) with increased integration and decreased segregation considering inter-frequency dynamics. Both metrics show increased spatial and temporal variability with the consciousness levels. Moreover, significant correlation can be found between the alteration of cross-frequency networks in DOC patients and their behavioural performance at both local and global scales., Significance: These findings may contribute to the development of EEG network study and benefit our understanding of the processes of consciousness and their pathophysiology for DOC.

We provide here the first systematic review on the studies dealing with repetitive transcranial magnetic stimulation (rTMS) for traumatic brain injury (TBI) in animals and humans. Several experimental studies in animal models have explored with promising results the use of rTMS to enhance neuroprotection and recovery after TBI. However, there are surprisingly few studies that have obtained substantial evidence regarding effects of rTMS in humans with TBI, many of them are case reports investigating the heterogeneous conditions linked to TBI. The most studies have investigated the effects of rTMS in subjects with post-traumatic depression and variable effects have been observed. rTMS has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC), but in subjects with TBI therapeutic effects on DOC have also been variously documented. Beneficial effects have been reported in subjects with cognitive/emotional disturbances and auditory dysfunction (tinnitus and hallucinations), although the results are somewhat conflicting. rTMS applied over the left prefrontal cortex may relieve, at least transiently, post-traumatic headache. Isolated rTMS studies have been performed in TBI patients with motor impairment, chronic dizziness or pain. Especially whether provided in combination, rTMS and neurorehabilitation may be synergistic in the potential to translate experimental findings in the clinical practice. In order to reach definitive conclusions, well-designed randomized controlled studies with larger patient samples, improved design and optimized rTMS setup, are warranted to verify and corroborate the initial promising findings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We investigated the clinical course of patients with prolonged disorders of consciousness (PDoC), predictors of emergence from PDoC (EDoC), and the temporal dynamics of six neurobehavior domains based on the JFK Coma Recovery Scale-Revised (CRS-R) during the recovery., Methods: A total of 50 traumatic and non-traumatic patients with PDoC were enrolled between October 2014 and February 2017. A retrospective analysis of the clinical findings and neurobehavioral signs was conducted using standardized methodology such as CRS-R. The findings were used to investigate the incidence and predictors of EDoC and determine the cumulative pattern of neurobehavioral recovery at 6 months, 1 year, and 2 years post-injury., Results: The results showed that 46% of the subjects emerged from PDoC after 200 median days (64-1197 days) of injury onset. The significant predictors of EDoC included minimally conscious state (MCS) (vs. vegetative state), higher auditory, communication, arousal, total CRS-R scores, shorter lag time post-injury, and the absence of intra-axial lesions. In terms of cumulative recovery of motor and communication signs in patients who emerged from PDoC, 39 and 32% showed EDoC at 6 months post-injury, and 88 and 93% exhibited EDoC at 2 years post-injury, respectively., Conclusions: Nearly half of the patients with PDoC recovered consciousness during inpatient rehabilitation. MCS, shorter lag time, the absence of intra-axial lesions, higher auditory, communication, arousal, and total CRS-R scores were important predictors for EDoC. Motor scores in the early stage of recovery and communication scores after prolonged intervals contributed to the higher levels of cumulative EDoC.

Background and Purpose: Patients with acquired brain injury and acute or prolonged disorders of consciousness (DoC) are challenging. Evidence to support diagnostic decisions on coma and other DoC is limited but accumulating. This guideline provides the state-of-the-art evidence regarding the diagnosis of DoC, summarizing data from bedside examination techniques, functional neuroimaging and electroencephalography (EEG)., Methods: Sixteen members of the European Academy of Neurology (EAN) Scientific Panel on Coma and Chronic Disorders of Consciousness, representing 10 European countries, reviewed the scientific evidence for the evaluation of coma and other DoC using standard bibliographic measures. Recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The guideline was endorsed by the EAN., Results: Besides a comprehensive neurological examination, the following suggestions are made: probe for voluntary eye movements using a mirror; repeat clinical assessments in the subacute and chronic setting, using the Coma Recovery Scale - Revised; use the Full Outline of Unresponsiveness score instead of the Glasgow Coma Scale in the acute setting; obtain clinical standard EEG; search for sleep patterns on EEG, particularly rapid eye movement sleep and slow-wave sleep; and, whenever feasible, consider positron emission tomography, resting state functional magnetic resonance imaging (fMRI), active fMRI or EEG paradigms and quantitative analysis of high-density EEG to complement behavioral assessment in patients without command following at the bedside., Conclusions: Standardized clinical evaluation, EEG-based techniques and functional neuroimaging should be integrated for multimodal evaluation of patients with DoC. The state of consciousness should be classified according to the highest level revealed by any of these three approaches., (© 2020 European Academy of Neurology.)

Objective: To understand the clinical characteristics, prognoses, and prognostic factors of vegetative state (VS) and minimal consciousness state (MCS) patients hospitalized for comprehensive rehabilitation., Materials and Methods: The data of VS and MCS patients admitted in the past six years were retrospectively analyzed. Age of onset, etiology, course of disease, complications, and retention of tracheal intubation, gastric tube, and urethral catheter were recorded. All patients were followed for one year after onset, and their Glasgow Outcome Scale (GOS) scores were assessed. Long-term prognostic factors were analyzed using logistic regression., Results: The proportion of patients with traumatic brain injuries in the MCS group was higher than in the VS group (p<0.05), while hypoxic-ischemic encephalopathy accounted for a higher proportion in the VS group; the differences were statistically significant between the two groups. The occurrence of infection was the highest in both groups, followed by spasticity and epilepsy. The occurrence of other complications was slightly different between the two groups but did not reach statistical significance (p>0.05). Age, etiology, and consciousness at admission had a significant impact on the long-term prognoses of VS or MCS patients (p<0.05), and the age of onset was the most important factor (the highest OR)., Conclusions: Infection, spasticity, and epilepsy are common complications in both VS and MCS patients. Recovery of consciousness after one year was shown to be affected by age, etiology, and consciousness at admission.

Introduction : Some neurologic conditions that can quickly and with low costs be recognized, classified and treated thanks to the availability of an EEG recording in an emergency setting. However, although considered a cheap, not invasive, highly accurate diagnostic investigation, still today, an EEG recording in emergency, in real time during the event paroxysmal ictal phase, is not yet been become a routine. Areas covered : This review will cover the role and utility of EEG recording in the emergency setting, both in emergency department and intensive care unit, in adult and pediatric age, in people admitted for status epilepticus (convulsive or non-convulsive), paroxysmal non-epileptic events, or other conditions/diseases presenting with mental status changes. Expert opinion : The prompt recognition of some specific EEG-patterns can permit an immediate and appropriate therapeutic choice with the resolution of dramatic clinical pictures, which, if not recognized, sometimes could result in severe prognostic events with high mortality or neuropsychiatric disability. It is important in the next future, to improve the availability of these EEG digital continuous monitoring, which should be widely used in emergency settings, developing moreover tools and techniques permitting also review, analysis and EEG-reporting by experts who can work away from the hospital.

The Nociception Coma Scale-Revised (NCS-R) was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute noxious stimuli. However, they failed to determine a reliable cut-off score that could be used to infer pain processing in these patients. This retrospective cross-sectional study aimed to determine a NCS-R cut-off score supporting preserved neural basis for pain experience, based on brain metabolism preservation as measured by fluorodeoxyglucose positron emission tomography (FDG-PET). We included patients in unresponsive wakefulness syndrome (UWS) confirmed by the FDG-PET and examined the NCS-R total scores. As the highest score was 4, we defined the cut-off to be 5 and compared the brain metabolism of these patients to matched patients with DOC and a NCS-R cut-off score ≥5 (ie, potential pain), as well as healthy subjects. We found a higher global cerebral metabolism in healthy subjects compared to both patient groups and also in patients with potential pain compared with FDG-PET confirmed UWS. We observed a preserved metabolism in the left insula in patients with potential pain compared with FDG-PET confirmed UWS. PERSPECTIVES: Our data suggest that using the cut-off score of 5 could be helpful to improve pain management in patients with DOC. Future studies should focus on patients showing scores below this cut-off to better characterize their profile and improve care., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To generate foundational knowledge in the creation of a quality-of-life instrument for patients who are clinically diagnosed as being in a vegetative or minimally conscious state but are able to communicate by modulating their brain activity (i.e., behaviourally nonresponsive and covertly aware). The study aimed to identify a short list of key domains that could be used to formulate questions for an instrument that determines their self-reported quality of life., Methods: A novel two-pronged strategy was employed: (i) a scoping review of quality-of-life instruments created for patient populations sharing some characteristics with patients who are behaviourally nonresponsive and covertly aware was done to compile a set of potentially relevant domains of quality of life; and (ii) a three-round Delphi consensus process with a multidisciplinary panel of experts was done to determine which of the identified domains of quality of life are most important to those who are behaviourally nonresponsive and covertly aware. Five expert groups were recruited for this study including healthcare workers, neuroscientists, bioethicists, quality-of-life methodologists, and patient advocates., Results: Thirty-five individuals participated in the study with an average response rate of 95% per round. Over the three rounds, experts reached consensus on 34 of 44 domains (42 domains were identified in the scoping review and two new domains were added based on suggestions by experts). 22 domains were rated as being important for inclusion in a quality-of-life instrument and 12 domains were deemed to be of less importance. Participants agreed that domains related to physical pain, communication, and personal relationships were of primary importance. Based on subgroup analyses, there was a high degree of consistency among expert groups., Conclusions: Quality of life should be a central patient-reported outcome in all patient populations regardless of patients' ability to communicate. It remains to be determined how covertly aware patients perceive their circumstances and quality of life after suffering a life-altering injury. Nonetheless, it is important that any further dialogue on what constitutes a life worth living should not occur without direct patient input.

Objective: Recent works have shown that flexible information processing is closely related to the reconfiguration of human brain networks underlying brain functions. However, the role of network switching for consciousness is poorly explored and whether such transition can indicate the behavioral performance of patients with disorders of consciousness (DOC) remains unknown. Here, we investigate the relationship between the switching of brain networks (states) over time and the consciousness levels., Approach: By applying multilayer network methods, we calculated time-resolved functional connectivity from source-level EEG data in different frequency bands. At various time scales, we explored how the human brain changes its community structure and traverses across defined network states (integrated and segregated states) in subjects with different consciousness levels., Main Results: Network switching in the human brain is decreased with increasing time scale opposite to that in random systems. Transitions of community assignment (denoted by flexibility) are negatively correlated with the consciousness levels (particularly in the alpha band) at short time scales. At long time scales, the opposite trend is found. Compared to healthy controls, patients show a new balance between dynamic segregation and integration, with decreased proportion and mean duration of segregated state (contrary to those of integrated state) at small scales., Significance: These findings may contribute to the development of EEG-based network analysis and shed new light on the pathological mechanisms of neurological disorders like DOC.

Various diseases cause consciousness disturbance, many of which are directly related to life and functional prognosis. As they often affect the respiratory and circulatory functions, differential diagnosis must be considered while stabilizing the patients. Although appropriate treatment should be started promptly after differential diagnosis, preconceptions could lead to misdiagnosis. A detailed medical interview cannot be conducted directly with the patient, which is a significant disadvantage faced by medical professionals in consciousness disturbance cases compared to other neurological disorders. Therefore, careful physical examination and diagnosis are important. At the same time, differential diagnosis may change over time, and follow-up examinations are necessary. Here, we would like to report three emergency cases of consciousness disturbance.

Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients' behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

In our previous study, a Paediatric Early Warning Score could be calculated for only one-fifth of 102,993 children transported by ambulance to hospital, as components other than supplemental oxygen were not reliably measured: respiratory rate 90,358 (88%); Glasgow Coma Score 83,648 (81%); heart rate 83,330 (81%); time to capillary reperfusion 81,685 (79%); oxygen saturation 71,372 (69%); temperature 60,402 (59%); systolic blood pressure 37,088 (36%). We tested 12 abbreviated scores with 3-5 components. The discrimination of these 12 scores for the primary outcome (30-day mortality or admission to paediatric intensive care), as measured by the area under the receiving operator characteristic curve, ranged from 0.69 to 0.80. Scores could be calculated for at most 74,508 (72%) children when heart rate, conscious level and respiratory rate were measured, with or without supplemental oxygen: the discrimination of these two versions was 0.75 and 0.77, respectively. Optimal threshold scores of 3 and 2 for these two abbreviated versions discriminated an outcome rate of 2-3% in about one third of children from the other children who had < 1% rate of outcome., (© 2019 Association of Anaesthetists.)

This study explored the utility of the Coma Recovery Scale-Revised (CRS-R) in predicting emergence from a disorder of consciousness, using a sample of veterans who were treated at one of the five Veterans Affairs (VA) polytrauma rehabilitation centre sites in an Emerging Consciousness programme. Participants ( N  = 70) included both combat and non-combat active duty military personnel and veterans who sustained either a severe traumatic brain injury, or anoxic brain injury and were considered to have a disorder of consciousness at the time of admission. Patient information was retrospectively collected from electronic medical records from one of the VA polytrauma rehabilitation centre sites. Receiver Operator Characteristic models were utilised to explore "cut-off scores" for predicting emergence using the CRS-R. Results showed that week-three scores on the CRS-R were more accurate in determining whether a veteran would emerge from a disorder of consciousness. Limitations, including a limited sample size are explored, along with implications and recommendations for future research and clinical practice.

Background : Clinical outcome of patients with disorders of consciousness (DOC) is seen as generally very poor. Here, we specify individual outcome chances for patients with DOC on the basis of clinical and event-related-potentials (ERPs) data and identify subgroups, who vary substantially regarding their outcome chances. Methods : We employed data from 102 patients and used standard clinical protocol data (age, etiology, diagnosis, gender), sensory (N100, Mismatch-Negativity) and cognitive (P300, N400) ERPs to predict patients' recovery rates. Results : Two significant prediction models emerged: In both, subgroups of patients with good (51%, tree 1) to very good recovery chances (97%, tree 2) could be identified. The first model was obtained from standard clinical data. The second model included cognitive ERPs and resulted in considerably better patient classification. Moreover, when taking cognitive ERPs into account, the standard protocol data did not add further significant information, neither did sensory ERPs. Conclusion : The presented information about outcome chances of individual patients with DOC will be vital for these patients and critical for clinical professionals who have to direct specialized treatments and council relatives. Legal guardians and families, in turn, need to know what to expect in the future in order to prepare for the challenges ahead.

Background: The Full Outline of Un-Responsiveness Score (FOURs) is a scale for clinical assessment of consciousness that was introduced to overcome disadvantages of the widely accepted Glasgow Coma Scale (GCS)., Objective: To carry out a systematic review and critical analysis of the available literature on the clinical application of FOURs and perform a comparison to GCS, in terms of reliability and predictive value., Methods: Initial search retrieved a total of 147 papers. After applying strict inclusion criteria and further article selection to overcome data heterogeneity, a statistical comparison of inter-rater reliability, in-hospital mortality and long-term outcome prediction between the two scales in the adult and pediatric population was done., Results: Even though FOURs is more complicated than GCS, its application remains quite simple. Its reliability, validity and predictive value have been supported by an increasing number of studies, especially in critical care. A statistically significant difference (p = .034) in predicting in-hospital mortality in adults, in favor of FOURs when compared to GCS, was found. However, whether it poses a clinically significant advantage in detecting patients' deterioration and outcome prediction, compared to other scaling systems, remains unclear., Conclusions: Further studies are needed to discern the FOURs' clinical usefulness, especially in patients in non-critical condition, with milder disorders of consciousness., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The assessment of awareness in patients with chronic Disorders of Consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. The level of awareness impairment may depend on the degree of deterioration of the large-scale cortical-thalamo-cortical networks induced by brain injury. Electrophysiological approaches may shed light on awareness presence in patients with DoC by estimating cortical functions related to the cortical-thalamo-cortical networks including, for example, the cortico-subcortical processes generating motor responses to the perturbation of the peri-personal space (PPS). We measured the amplitude, latency, and duration of the hand-blink reflex (HBR) responses by recording electromyography (EMG) signals from both the orbicularis oculi muscles while electrically stimulating the median nerve at the wrist. Such a BR is thought to be mediated by a neural circuit at the brainstem level. Despite its defensive-response nature, HBR can be modulated by the distance between the stimulated hand and the face. This suggests a functional top-down control of HBR as reflected by HBR features changes (latency, amplitude, and magnitude). We therefore estimated HBR responses in a sample of patients with DoC (8 MCS and 12 UWS, compared to 15 healthy controls -HC) while performing a motor task targeting the PPS. This consisted of passive movements in which the hand of the subject was positioned at different distances from the participant's face. We aimed at demonstrating a residual top-down modulation of HBR properties, which could be useful to differentiate patients with DoC and, potentially, demonstrate awareness preservation. We found a decrease in latency, and an increase in duration and magnitude of HBR responses, which were all inversely related to the hand-to-face distance in HC and patients with MCS, but not in individuals with UWS. Our data suggest that only patients with MCS have preserved, residual, top-down modulation of the processes related to the PPS from higher-order cortical areas to sensory-motor integration network. Although the sample size was relatively small, being thus our data preliminary, HBR assessment seems a rapid, easy, and first-level tool to differentiate patients with MCS from those with UWS. We may also hypothesize that such a HBR modulation suggests awareness preservation.

Objective: Constructing a framework to evaluate consciousness is an important issue in neuroscience research and clinical practice. However, there is still no systematic framework for quantifying altered consciousness along the dimensions of both level and content. This study builds a framework to differentiate the following states: coma, general anesthesia, minimally conscious state (MCS), and normal wakefulness., Methods: This study analyzed electroencephalography (EEG) recorded from frontal channels in patients with disorders of consciousness (either coma or MCS), patients under general anesthesia, and healthy participants in normal waking consciousness (NWC). Four non-linear methods-permutation entropy (PE), sample entropy (SampEn), permutation Lempel-Ziv complexity (PLZC), and detrended fluctuation analysis (DFA)-as well as relative power (RP), extracted features from the EEG recordings. A genetic algorithm-based support vector machine (GA-SVM) classified the states of consciousness based on the extracted features. A multivariable linear regression model then built EEG indices for level and content of consciousness., Results: The PE differentiated all four states of consciousness (p<0.001). Altered contents of consciousness for NWC, MCS, coma, and general anesthesia were best differentiated by the SampEn, and PLZC. In contrast, the levels of consciousness for these four states were best differentiated by RP of Gamma and PE. A multi-dimensional index, combined with the GA-SVM, showed that the integration of PE, PLZC, SampEn, and DFA had the highest classification accuracy (92.3%). The GA-SVM was better than random forest and neural networks at differentiating these four states. The 'coordinate value' in the dimensions of level and content were constructed by the multivariable linear regression model and the non-linear measures PE, PLZC, SampEn, and DFA., Conclusions: Multi-dimensional measurements, especially the PE, SampEn, PLZC, and DFA, when combined with GA-SVM, are promising methods for constructing a framework to quantify consciousness.

Cerebral thrombophlebitis is a rare but severe disease whose underestimated frequency is increasingly recognized among children and, unlike adults, management is controversial. We report the case of a 12-year old child bitten by a friend at the level of the scalp, in the frontotemporal region of the head. This bite evolved due to the occurrence of a swelling evoking a frontotemporoparietal cellulitis complicated by cerebral thrombophlebitis, diagnosed based on the clinical feature and imaging. The patient was admitted in our hospital in a state of conscience disorder. Anticoagulant and etiological treatments enabled good clinical evolution., Competing Interests: Les auteurs ne déclarent aucun conflit d’interêts., (© Soufiane Badsi et al.)

Patients with disorders of consciousness (DOC) suffer from awareness deficits. Comorbidities such as motor disabilities or visual problems hamper clinical assessments, which can lead to misdiagnosis of the level of consciousness and render the patient unable to communicate. Objective measures of consciousness can reduce the risk of misdiagnosis and could enable patients to communicate by voluntarily modulating their brain activity. This chapter gives an overview of the literature regarding brain-computer interface (BCI) research in DOC patients. Different auditory, visual, and motor imagery paradigms are discussed, alongside their corresponding advantages and disadvantages. At this point, the use of BCIs for DOC patients in clinical applications is still preliminary. However, perspectives on the improvements in BCIs for DOC patients seem positive, and implementation during rehabilitation shows promise., (© 2020 Elsevier B.V. All rights reserved.)

Aim: Systemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics., Material and Method: Among the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded., Results: In total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up., Conclusions: SLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose of Review: Diagnostic classification of patients with disorders of consciousness (DoC) is based on clinician's observation of volitional behaviours. However, patients' caregivers often report higher levels of responsiveness with respect to those observed during the clinical assessment. Thus, increasing efforts have been aimed at comprehending the effects of self-referential and emotional stimuli on patients' responsiveness. Here we systematically reviewed the original experimental studies that compared behavioural and electrophysiological responses with salient vs. neutral material in patients in vegetative state/unresponsive wakefulness syndrome or in minimally conscious state., Recent Findings: Most of the reviewed studies showed that salient stimuli (i.e. patient's own or familiar faces, patient's own name, and familiar voices) seem to elicit a higher amount of behavioural or electrophysiological responses with respect to neutral pictures or sounds. Importantly, a quite high percentage of patients seem to respond to salient stimuli only. The present review could foster use of personally salient stimuli in assessing DoC. However, the low overall quality of evidence and some limitations in the general reviewing process might induce caution in transferring these suggestions into clinical practice.

A 26-year-old man presented at the emergency department with confusion and decreased consciousness after several days of vomiting. In the preceding 6 months, he had used a 2-litre tank of nitrous oxide (N 2 O) weekly. His metabolic encephalopathy was caused by hyperammonaemia which probably resulted from interference of N 2 O-induced vitamin B 12 deficiency with ammonia degradation. A catabolic state might have contributed to the hyperammonaemia in this case. After treatment with vitamin B 12 and lactulose, both his consciousness and hyperammonaemia improved. He reported no residual complaints after 3 months of follow-up. Since N 2 O is increasingly used as a recreational drug, we recommend considering hyperammonaemia as a cause of metabolic encephalopathy in cases of N 2 O use and altered mental status., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Disorders of consciousness (DOC) after traumatic brain injury (TBI) raise the mortality of patients, restrict the rehabilitation of patients with TBI, and increase the physical and economic burden that TBI imposes on patients and their families. Thus, treatment to promote early awakening in DOC after TBI is of vital importance. Various treatments have been reported, but there is no advanced evidence base to support them. Transcranial direct current stimulation (tDCS) has shown great potential in promoting neuroelectrochemical effects. This protocol is for a double-blind, randomized, controlled, clinical trial aiming to research the effects and safety of conventional rehabilitation combined with tDCS therapy in patients with DOC after TBI., Methods/design: Eighty patients with DOC after TBI will be randomized into one of two groups receiving conventional rehabilitation combined with sham tDCS or conventional rehabilitation combined with active tDCS. The intervention period in each of the two groups will last 4 weeks (20 min per day, 6 days per week). Primary outcomes (Glasgow Outcome Scale (GOS)) will be measured at baseline and the end of every week from the first to the fourth week. Secondary outcomes will be measured at baseline and the end of the fourth week. Adverse events and untoward effects will be measured during each treatment., Discussion: Patients with central nervous system lesions have received tDCS as a painless, non-invasive, easily applied and effective therapy for several decades, and there has been some evidence in recent years showing partial improvement on the level of consciousness of partial patients with DOC. However, reports mainly focus on the patients in a minimally conscious state (MCS), and there is a lack of large-sample clinical trials. This protocol presents an objective design for a randomized controlled trial that aims to study the effectiveness of conventional rehabilitation combined with tDCS therapy for DOC after TBI, to evaluate its safety, and to explore effective and economical therapeutic methods., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800014808 . Registered on 7 February 2018.

Objective: Ethanol intake can increase the sedative effects of gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), although the real clinical impact is unknown. We studied the clinical impact of the co-ingestion of ethanol in patients presenting to the Emergency Department (ED) with acute toxicity related to GHB/GBL use., Method: We performed a secondary analysis of the Euro-DEN Plus Registry (14 countries, 22 EDs) which includes 17,371 consecutive patients presenting to the ED with acute recreational drug toxicity over 39 consecutive months (October 2013 - December 2016). We compared the epidemiological and clinical characteristics and ED management of patients identified as presenting with acute toxicity related to lone GHB/GBL (Group A) or GHB/GBL combined with ethanol (Group B) without other concomitant drugs., Results: A total of 609 patients were included (age 32 (8) years; 116 women (19%); Group A: 183 patients and Group B: 426). The most common features were reduction in consciousness (defined as Glasgow Coma Score <13 points: 56.1%) and agitation/aggressiveness (33.6%). Those with ethanol co-ingestion were younger patients (Group A/B: 31.5/33.1 years, p = 0.029) and ethanol co-ingestion was associated with a lower frequency of bradycardia (23.5%/15.7%, p = 0.027) and more frequent arrival at the ED by ambulance (68.3/86.6%; p < 0.001), reduction in consciousness (58.9%/49.1%; p = 0.031), need for treatment in the ED (49.2%/60.4%; p = 0.011), use of sedatives (20.1%/12.8%; p = 0.034), admission to critical care units (22.4%/55.3%; p < 0.001), and longer hospital stay (stay longer than 6 h: 16.9%/28.4%; p = 0.003)., Conclusions: Co-ingestion of ethanol increases the adverse effects of patients intoxicated by GHB/GBL, leading to greater depression of consciousness, need for treatment, admission to the ICU and longer hospital stay., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethanol intoxication of infants and young children can be a challenging diagnosis in the pediatric emergency department, and features of the poisoning may differ in comparison with adolescents. The sources of ethanol exposures in this age are varied and include unintentional, malicious, and iatrogenic etiologies. Young children exposed to ethanol often present with mixed clinical signs and symptoms that may not fit the traditional ethanol or sedative-hypnotic toxidrome. Pediatric ethanol intoxications are often managed supportively, and recovery is usually rapid. The purpose of this review is to describe the sources of ethanol poisoning among children 6 years and younger, highlight presenting symptoms and pharmacokinetic considerations unique to this age group, and review management strategies. In addition, published cases of ethanol poisoning due to ingestion among young infants are compiled for presentation.

Background: Generalized tonic-clonic seizures (GTCS), syncope, and psychogenic nonepileptic seizures (PNES) are common emergent neurological conditions that cause transient disturbances of consciousness; however, it is sometimes difficult to distinguish them., Objective: This study aimed to explore the value of serum uric acid levels in differentiating among GTCS, syncope, and PNES by analyzing serum uric acid levels in patients with GTCS, syncope, and PNES., Methods: A total of 391 patients were retrospectively analyzed. Venous blood was drawn from the patients within 20 min of their arrival to the emergency department; serum uric acid levels were measured using the uricase method., Results: Serum uric acid levels and the percentage of patients with elevated uric acid (elevation percentage) were significantly higher in the group with GTCS (n = 179) than in the groups with syncope (n = 156) (p < 0.001) and PNES (n = 56) (p < 0.001). The result remained the same when the serum uric acid level of male or female patients in the group with GTCS were compared separately with that in the other two groups (all p < 0.001). In the group with GTCS, both the serum uric acid level (p < 0.001) and elevation percentage (p < 0.05) were significantly higher in males than in females. The receiver operating characteristics (ROC) analysis in male patients yielded a serum uric acid value of 428.50 μmol/L with a sensitivity of 0.78 and a specificity of 0.99 as the optimal cutoff value to distinguish GTCS from other events. In female patients, a cutoff value of 338.00 μmol/L had a sensitivity of 0.69 and a specificity of 0.91 to distinguish GTCS from other events. For the group with GTCS, the period of time between the onset of seizure and serum uric acid levels dropping to normal were analyzed in 40 patients. The duration was 44.56 ± 11.46 h for males (n = 23) and 40.37 ± 9.78 h for females (n = 17) with no significant difference (p = 0.325)., Conclusion: Serum uric acid levels provided certain clinical value for the differentiation of GTCS, syncope, and PNES; however, this requires verification in prospective studies with larger sample sizes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Full Outline of UnResponsiveness (FOUR) score assessment of consciousness replaces the Glasgow Coma Scale (GCS) verbal component with assessment of brainstem reflexes. A comprehensive overview studying the relationship between a patient's FOUR score and outcome is lacking. We aim to systematically review published literature reporting the relationship of FOUR score to outcome in adult patients with impaired consciousness. We systematically searched for records of relevant studies: CENTRAL, MEDLINE, EMBASE, Scopus, Web of Science, ClinicalTrials.gov, and OpenGrey. Prospective, observational studies of patients with impaired consciousness were included where consciousness was assessed using FOUR score, and where the outcome in mortality or validated functional outcome scores was reported. Consensus-based screening and quality appraisal were performed. Outcome prognostication was synthesized narratively. Forty records (37 studies) were identified, with overall low ( n  = 2), moderate ( n  = 25), or high ( n  = 13) risk of bias. There was significant heterogeneity in patient characteristics. FOUR score showed good to excellent prognostication of in-hospital mortality in most studies (area under curve [AUC], >0.80). It was good at predicting poor functional outcome (AUC, 0.80-0.90). There was some evidence that motor and eye components (also GCS components) had better prognostic ability than brainstem components. Overall, FOUR score relates closely to in-hospital mortality and poor functional outcome. More studies with standardized design are needed to better characterize it in different patient groups, confirm the differences between its four components, and compare it with the performance of GCS and its recently described derivative, the GCS-Pupils, which includes pupil response as a fourth component.

Objective: To evaluate whether electroencephalographic (EEG) features recorded during the post-acute stage in patients with severe disorders of consciousness (DoC) after acute brain injury (ABI), contribute to neurological outcome prediction of these patients at discharge from the intensive rehabilitation unit (IRU)., Methods: We retrospectively evaluated all patients consecutively admitted to the IRU from August 2012 to December 2016. Inclusion criteria were: 1) age >18years, 2) patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS), and 3) EEG and a coma recovery scale-revised (CRS-R) score available within the first week after admission. Clinical evaluation was performed using the Italian version of the CRS-R score. EEGs were classified according to American Clinical Neurophysiology Society (ACNS) terminology. Clinical state at final discharge was evaluated using the CRS-R score., Results: In total, 102 patients were included in the analysis. After a mean of five months of IRU stay, among the 61 UWS subjects, 19 transitioned to MCS and 11 recovered to exit-MCS (E-MCS); twenty-three of the 41 subjects in MCS progressed to E-MCS. Using logistic regression, consciousness level (UWS/MCS-OR=13.4), CRS-R score at admission (OR=1.33) and use of activating drugs (OR=4.7) were significant predictors of clinical improvement. Multivariable analysis showed that specific EEG patterns were independent predictors of improved consciousness at discharge in UWS patients., Discussion: EEG performed within the first week after IRU admission, classified according to ACNS-terminology in patients with UWS at admission, can provide useful prognostic contribution., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Introduction: Children with disorders of consciousness (DOC) represent the highest end of the acquired brain injury (ABI) severity spectrum for survivors and experience a multitude of functional impairments. Current clinical management in DOC uses behavioural evaluation measures and interventions that fail to (1) describe the physiological consequences of ABI and (2) elicit functional gains. In paediatric DOC, there is a critical need to develop evidence-based interventions to promote recovery of basic responses to improve rehabilitation and aid decision-making for medical teams and caregivers. The purpose of this investigation is to examine the safety, tolerability and feasibility of transcranial direct current stimulation (tDCS) in children with DOC., Methods and Analysis: This study is an open-label dose escalation trial evaluating the safety, tolerability and feasibility of tDCS in 10 children (5-17 years) receiving inpatient rehabilitation for DOC. This study will follow a modified rule-based design, allowing for intrapatient escalation, where a cohort of patients will be assigned to an initial tDCS current of 0.5 or 1 mA based on participant's head circumference and according to the safety data available in other paediatric populations. The subsequent assignment of increased current (1 or 2 mA) according to the prespecified rules will be based on the clinical observation of adverse events in the patients. The study will include up to three, 20 min sessions of anodal tDCS (sham, 0.5 or 1 mA, 1 or 2 mA) applied over the dorsolateral prefrontal cortex. The primary outcomes are adverse events, pain associated with tDCS and intolerable disruption of inpatient care. Secondary outcomes are changes in electroencephalography (EEG) phase-locking and event-related potential components and the Coma Recovery Scale-Revised total score from prestimulation to poststimulation., Ethics and Dissemination: The Johns Hopkins IRB (#IRB00174966) approved this study. Trial results will be disseminated through journals and conferences., Registration Number: NCT03618849., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Full Outline of UnResponsivness (FOUR) score is a neurological assessment score. Its theoretical benefit over preexisting scores is its evaluation of brainstem reflexes and respiratory pattern which may allow better assessment of patients with severe neurologic impairment., Objective: Our goal was to perform a scoping systematic review on the available literature for FOUR score and outcome prediction in critically ill patients. The primary outcome of interest was patient global outcome, as assessed by any of: mortality, modified Rankin Score, Glasgow Outcome Score, or any other functional or neuropsychiatric outcome. Information on interobserver reliability was also extracted., Methods: MEDLINE and five other databases were searched. Inclusion criteria were: humans, adults, and children; prospective randomized controlled trial; prospective cohort, cohort/control, case series, prospective, and retrospective studies. Two reviewers independently screened the results. Full texts for citations passing this initial screen were obtained. Inclusion and exclusion criteria were applied to each article to obtain final articles for review. Results on adult populations are presented here. Data are reported following the preferred reporting items for systematic reviews and meta-analyses guidelines., Results: The initial search yielded 1709 citations. Of those used, 49 were based on adult and 6 on pediatric populations. All but 8 retrospective adult studies were performed prospectively. Patient categories included traumatic brain injury, intraventricular hemorrhage, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke, general/combined neurology and neurosurgery, post-cardiac arrest, medicine/general critical illness, and patients in the emergency department. A total of 9092 adult patients were studied. Fourteen studies demonstrated good interobserver reliability of the FOUR score. Nine studies demonstrated prognostic value of the FOUR score in predicting mortality and functional outcomes. Thirty-two studies demonstrated equivalency or superiority of the FOUR score compared to Glasgow Coma Score in prediction of mortality and functional outcomes., Conclusions: The FOUR score has been shown to be a useful outcome predictor in many patients with depressed level of consciousness. It displays good inter-rater reliability among physicians and nurses.

Objective: The objective of this study was to explore the role for quadratic phase coupling within electroencephalography (EEG) oscillations in the diagnosis of consciousness and consciousness restoration for disorders of consciousness (DOC)., Methods: Fifty-one DOC patients were enrolled in this study. For each patient, a Coma Recovery Scale-Revised (CRS-R) score and 20-min resting-state EEG were recorded. Consciousness recovery was assessed with a CRS-R score at a three-month follow-up. Twenty healthy subjects were included as controls. General harmonic wavelet transform-based bicoherence was used to quantify the quadratic phase coupling characteristics of the EEG oscillations., Results: Quadratic phase self-coupling (QPSC) at the delta (QPSC&#95;delta), theta (QPSC&#95;theta) and alpha (QPSC&#95;alpha) bands were closely correlated with patient CRS-R scores. Particularly, the QPSC&#95;theta value could significantly differentiate between vegetative state (VS) patients, minimally conscious state (MCS) patients and healthy control subjects. As compared to VS patients, patients with MCS had a lower QPSC&#95;theta value on the left as well as a higher QPSC&#95;alpha value in right frontal regions. The frontal QPSC&#95;theta value showed significant differences between recovered and unrecovered patients., Conclusion: QPSC characteristics could differentiate between consciousness states and show a predictive ability for the recovery of consciousness in DOC patients., Significance: Changes in QPSC accompany consciousness injury and restoration in DOC patients. A QPSC assessment is helpful in the diagnosis and prognosis of DOC patients., (Copyright © 2019. Published by Elsevier B.V.)

Background: The identification of salient stimuli useful for rehabilitation purposes is important in patients with disorders of consciousness (DOC): among these, olfactory stimuli might play an important role due to the functional coupling between olfactory and emotional processing. However, a high percentage of post brain injury patients present anosmia., Aims of the Study: The aim of this pilot research is to present an innovative approach to test olfactory functions at the bedside using four selected odors in patients with DOC., Methods: Sixteen patients with DOC were tested with two assessment techniques the new olfactory discrimination protocol (ODP) and a functional magnetic resonance imaging paradigm to evaluate olfactory neural process. The Frequentist and Bayesian methods were used to analyze reliability properties of the new tool., Results: Analysis showed a good agreement between assessment techniques and a substantial test-retest reliability of the ODP. Cohen's Ks were equal to 0.814 (95% CI = 0.471, 1) and 0.607 (0.118; 1) respectively, using the Frequentist approach, while they were 0.762 (95% HPD = 0.470; 0.966) and 0.650 (0.320; 0.913) with the Bayesian approach in the 11 patients analyzed., Conclusions: Despite the limits of this preliminary research, the ODP can be useful for clinicians for the preliminary assessment of the olfactory discrimination in patients with DOC., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease presenting with various manifestations including dementia, weakness, transient impaired consciousness, encephalitis-like episodes and also epileptic seizures. However, the nature of epileptic seizures, focal or generalized onset, remains unclear. A man at age 76 was admitted to a local hospital due to febrile impaired consciousness lasting several days. During the hospital stay, a generalized convulsion occurred, and afterward he remained obtunded. He was transferred to our hospital for further treatment. One additional seizure occurred while on an ambulance to our hospital and two additional seizures shortly after the arrival, which indicated convulsive status epilepticus (SE). The ictal EEG showed low amplitude fast activity arising from the left centro-parietal area with an evolutionary pattern. The clinical concomitant was the contralateral versive seizure evolving to a bilateral convulsion. Inter-ictal epileptiform abnormalities seen on the tracings taken on later days consisted of brief potentially ictal rhythmic discharges (B(I)RDs) and frequent sharp waves recorded from both frontal areas. These findings along with the ictal discharges would indicate a multifocal epileptic disorder in this patient. Diffusion weighted images (DWIs) of this patient showed hyperintensity signals in the cortico-medullary junctions in the bilateral frontal and the left parietal regions. Skin biopsy revealed characteristic intranuclear inclusions, and hence the diagnosis of NIID was made. The regions of epileptic foci on EEG corresponded well to the hyperintensity areas in DWIs, which suggests the cerebral cortices near the DWI hyperintensity could be more hyperactive than other regions. This case report suggests that some of the prolonged impaired consciousness and the encephalitis-like episodes in NIID could be related to epileptic seizures and even non-convulsive SE or a post-ictal twilight state after an unwitnessed convulsion. This issue should be further studied for the appropriate treatment of episodic encephalopathy and epileptic seizures in NIID.

Cerebral diseases such as epileptic seizures, cerebral hemorrhages or meningoencephalitis are the primary cause of approximately 50 % of non-traumatic acute disorders of consciousness. For the differential diagnosis, history and other symptoms are important such as hemiplegia, signs of brain stem dysfunction, meningism or headache. Metabolic, endocrinologic, toxicologic or electrolytic causes of coma usually can be diagnosed by laboratory examinations. Anamnestic informations, body inspection, clinical neurological examination as well as laboratory and imaging findings have to be added and categorized by a multilevel composition to establish a conclusive diagnosis. Simultaneously therapeutic measures for suspected primary cerebral diseases must be initiated, for example a rapid antibiotic treatment in case of a possible bacterial meningitis. A fast and structured diagnostic approach is crucial for ensuring a good prognosis and helps to miss relevant diagnostic steps. Potential diagnostic and therapeutic pitfalls must be kept in mind., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)