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Background: Sleep plays a crucial role in neuroplasticity and recovery from brain injury, particularly in disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Traditional sleep monitoring methods like polysomnography (PSG) are complex and often impractical for longterm use in clinical settings. Target: This study aimed to explore the utility of the Bispectral Index (BIS) as a more practical alternative for monitoring sleep patterns in DoC patients. Methods: We conducted simultaneous PSG and BIS monitoring on 38 DoC patients (19 UWS and 19 MCS). The study focused on analyzing sleep timing distribution, the effectiveness of BIS in differentiating sleep stages, and its correlation with consciousness levels. Results: Our findings revealed that DoC patients exhibited irregular and fragmented sleep patterns, necessitating extended monitoring periods. The BIS effectively differentiated various sleep stages, with significant differences in BIS values observed across these stages. However, BIS values did not show significant differences between UWS and MCS patients, indicating that BIS primarily indicates wakefulness rather than cognitive awareness. DoC patients have disturbed sleep-wake cycles that require prolonged monitoring. BIS can well distinguish sleep stages in DoC patients, and the distribution of values is similar to that of normal subjects. However, BIS could not distinguish the level of consciousness of DoC patients. Conclusion: The study demonstrates the potential of BIS as a practical tool for long-term sleep monitoring in DoC patients, offering a less intrusive alternative to traditional methods. [ABSTRACT FROM AUTHOR]

Background and purpose: Stroke can lead to significant after-effects, including motor function impairments, language impairments (aphasia), disorders of consciousness (DoC), and cognitive deficits. Computer-aided analysis of EEG connectivity matrices and microstates from bedside EEG monitoring can replace traditional clinical observation methods, offering an automatic approach to monitoring the progression of these after-effects. This EEG-based method also enables quicker and more efficient assessments for medical practitioners. Methods: In this study, we employed Functional Connectivity features that extract spatial representation and Microstate features that focus on the time domain representation to monitor the after-effects of ischemic stroke patients. As the dataset from stroke patients is heavily imbalanced across various clinical after-effects conditions, we designed an ensemble classifier, RSBagging, to address the issue of classifiers often favoring the majority classes in the classification of imbalanced datasets. Results: The experimental results demonstrate that different connectivity matrices are effective for three classification tasks: consciousness level, motor disturbance, and stroke location. Using our RSBagging model, all three tasks achieve over 98% accuracy, sensitivity, specificity, and F1-score, significantly outperforming the existing classifiers SVM, XGBoost, and Random Forest. Conclusion: Therefore, the RSBagging classifier based on connectivity matrices offers an effective method for monitoring the after-effects in stroke patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Developments in eye-tracking technology are opening up new possibilities for diagnosing patients in a state of minimal consciousness because they can provide information on visual behavior, and the movements of the eyeballs are correlated with the patients' level of consciousness. The purpose of this study was to provide validation of a tool, based on eye tracking by comparing the results obtained with the assessment obtained using the Coma Recovery Scale-Revised (CRS-R). Methods: The mul-ti-center clinical trial was conducted in Poland in 2022–2023. The results of 46 patients who were not able to communicate verbally due to severe brain injury were analyzed in this study. The state of consciousness of patients was assessed using the Minimally Conscious State Detection test (MCSD), installed on an eye tracker and compared to CRS-R. The examinations consisted of performing the MCSD test on patients five times (T1–T5) within 14 days. Collected data were processed based on the FDA and GCP's regulatory requirements. Depending on the nature of the data, the mean and standard deviation, median and lower and upper quartiles, and maximum and minimum values were calculated. Passing–Bablok regression analysis was used to assess the measurement equiva-lence of the methods used. Results: There was no difference between the MCSD and CRS-R in the raw change between T5 and T1 time points, as well as in the total % of points from all time points. The MCSD results from each time point show that at least the first two measurements serve to famil-iarize and adapt the patient to the measurement process, and the third and next measurement should be considered reliable. Conclusions: The results indicated a significant relationship be-tween the scores obtained with MCSD and CRS-R. The results suggest that it seems reasonable to introduce an assessment of the patient's state of consciousness based on eye-tracking technology. The use of modern technology to assess a patient's state of consciousness opens up the opportunity for greater objectivity, as well as a reduction in the workload of qualified personnel. [ABSTRACT FROM AUTHOR]

Diagnostic and prognostic decision-making in patients with Disorders of Consciousness (DoC) is challenging. It has been suggested that spontaneous eye blink rate is an index of patients’ level of consciousness easy to detect in clinical practice. Further blinking features (i.e., amplitude, duration, variability in intervals between blinks) may change as a function of cognitive load, but have not been investigated in patients with DoC.This multicentre, longitudinal study aims at exploring the diagnostic and prognostic value of spontaneous eye blinking features in DoC.Eight European medical institutions will enrol consecutively admitted adult patients with DoC. Within two weeks from study entry demographic, anamnestic and clinical data will be collected. Moreover, patients will undergo two 20-minute EEG-EOG recordings at rest, to collect blinking features and EEG activity. A clinical follow-up will be performed after 6 months. A group of healthy individuals will be enrolled for reference.Possible differences in blink features between patients and the reference group, differences across diagnostic sub-groups, and correlations between blinking features and clinical outcome will be investigated.The results of this study might help clinicians to reduce misdiagnosis rate in DoC and provide useful information for prognostication and care pathway plan. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of and life-sustaining treatment (LST) for patients with disorders of consciousness (DoC) and locked-in syndrome (LIS) have been the subject of intense debate. Objective: We aim to investigate the application of diagnostic knowledge, opinions about the administration of LST, and ethical challenges related to DoC and LIS. Design: A cross-sectional study. Methods: A survey was conducted among Chinese neurologists. Questionnaires included three vignettes (unresponsive wakefulness syndrome (UWS); minimally conscious state (MCS), and LIS). They were randomly distributed among neurologists from August 2018 to December 2019. Results: A sample of 360 questionnaires was included (response rate: 78%). Overall, 63% of the participants chose the correct diagnostic category. The neurologists who received the MCS case chose the category more accurately than the neurologists with the UWS (p < 0.001) and LIS case (p = 0.002). Most neurologists preferred never to limit LST for their patients (47%, 63%, and 67% in UWS, MCS, and LIS groups, p = 0.052). A large group of neurologists believed UWS patients could feel pain (73%), with no difference from MCS and LIS patients (p > 0.05). Deciding for patients in the absence of surrogates was rated extremely challenging. Conclusion: A large proportion of Chinese neurologists in our study didn't apply the accurate diagnostic categories to the description of DoC and LIS patients. This calls for more education and training. Most Chinese neurologists were reluctant to limit LST for patients. This may indicate that there may be a need to emphasize the allocation of more resources toward long-term care in China. Plain language summary: Clinical and ethical challenges The diagnosis of and life-sustaining treatment (LST) for patients with disorders of consciousness (DoC) and Locked-in syndrome (LIS) have been the subject of intense debate. To describe the knowledge and attitudes of physicians regarding patients with some DoC and LIS in Eastern countries we conducted a vignette-based survey among Chinese neurologists. This study reveals significant differences from previous studies, namely, lower diagnostic accuracy and less limitation of life-sustaining treatment. This may be closely related to policies, cultures, economies, and laws among countries. A deeper understanding of neurologists' moral beliefs and attitudes can inform healthcare policy and might point to areas of research and healthcare practice that need further regulatory attention. A normative orientation through institutional, regional, or national policies for decision-making can increase the likelihood of reaching consistent and transparent decisions about the care of patients with severe brain injury across different regions and cities. [ABSTRACT FROM AUTHOR]

Background: This review focuses on the prognostic role of resting-state functional magnetic resonance imaging (fMRI) in disorders of consciousness (DOCs). Several studies were conducted to determine the diagnostic accuracy in DOC patients to identify prognostic markers and to understand the neural correlates of consciousness. A correct diagnosis of consciousness in unresponsive or minimally responsive patients is important for prognostic and therapeutic management. Functional connectivity is considered as an important tool for the formulation of cerebral networks; it takes into account the primary sensorimotor, language, visual and central executive areas, where fMRI studies show damage in brain connectivity in the areas of frontoparietal networks in DOC patients. Methods: The integration of neuroimaging or neurophysiological methods could improve our knowledge of the neural correlates of clinical response after an acquired brain injury. The use of MRI is widely reported in the literature in different neurological diseases. In particular, fMRI is the most widely used brain-imaging technique to investigate the neural mechanisms underlying cognition and motor function. We carried out a detailed literature search following the relevant guidelines (PRISMA), where we collected data and results on patients with disorders of consciousness from the studies performed. Results: In this review, 12 studies were selected, which showed the importance of the prognostic role of fMRI for DOCs. Conclusions: Currently there are still few studies on this topic. Future studies using fMRI are to be considered an added value for the prognosis and management of DOCs. [ABSTRACT FROM AUTHOR]

Background: The establishment of a resuscitation room management for nontraumatic critically ill children appears to make sense. This study collected data of pediatric patients suffering from nontraumatic critically ill conditions treated in a resuscitation room. Methods: The retrospective OBSERvE-DUS-PED study (November 2019–October 2022) recorded pediatric patients (age < 18 years) who were admitted to the emergency department (ED) for resuscitation room care. The routinely documented data on treatment were taken from the hospital information system MEDICO® and the patient data management system COPRA® in accordance with the OBSERvE dataset. The study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University (2023-2377). Results: The study included 52 pediatric resuscitation room patients. Adolescents aged 14–17 years were the most frequent in the cohort representing 37% of the total and neonates/infants (0–1 year) were lowest at 8%. The most common symptoms categorized according to ABCDE problems were disturbance of consciousness (D) at 61%, cardiovascular failure (C) at 25%, respiratory insufficiency (B) at 6%, airway obstruction (A) and exposure/environment (E) problems each at 4%. The out-of-hospital and in-hospital emergency procedures were performed with the following frequencies: venous (58% vs. 65%), intraosseous (14% vs. 2%) and central venous access (0% vs. 12%), invasive airway management (35% vs. 8%), cardiopulmonary resuscitation (21% vs. 10%), vasopressors (15% vs. 17%), and intra-arterial pressure measurement (0% vs. 17%). The mean duration of resuscitation room management was 70 ± 43 min. The 30-day mortality was 17%. Conclusion: The OBSERvE-DUS-PED study demonstrates the major challenges in the care of critically ill nontraumatic pediatric patients, both in out-of-hospital and in-hospital management. The variety and complexity of the referral diagnoses as well as the immediate vital threat to the patients make it appear sensible to treat such patients primarily in a resuscitation room of the ED due to the available material, infrastructural and personnel resources. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cranioplasty (CP) is the main surgical procedure aiming to repair a morphological defect in the skull. It has been shown that early CP is useful for patients with traumatic brain injury (TBI) to achieve functional recovery, whereas few studies have investigated the clinical effects of ultra-late CP on TBI outcomes. Methods: Here, we describe the clinical course over 2 years of a TBI patient who underwent CP 19 months after fronto-parietal decompressive craniectomy (DC) of a limited size. Results: We found that after ultra-late CP, a meaningful functional recovery (cognitive and motor), with emergence from a minimally conscious state and recovery of functional communication, was revealed. Conclusions: Our preliminary findings contribute to the actual debate on the timing of CP for this neurosurgical procedure's therapeutic success, as early CP has already been shown. [ABSTRACT FROM AUTHOR]

Functional neuroimaging and electrophysiological assessments can identify evidence of residual consciousness and cognition in patients with prolonged disorders of consciousness (PDOC) who are otherwise behaviourally unresponsive. These functional neurodiagnostics are increasingly available in clinical settings and are recommended by international clinical guidelines to reduce diagnostic and prognostic uncertainty, and thereby assist family caregivers in their best-interests decision-making. Nevertheless, little is known about how family caregivers make sense of the results of these state-of-the-art functional neurodiagnostics. By applying Interpretative Phenomenological Analysis (IPA) to interviews with family caregivers of patients with diagnoses of PDOC who had received a functional neurodiagnostic assessment, we identify three primary themes of sense-making: The special significance of "brain scans"; A dynamic sense-making process; Holding on to hope and holding on to the person. These themes highlight the challenges of helping family caregivers to balance the relative importance of functional neurodiagnostic results with other clinical assessments and identify an ability of family caregivers to hold a contradiction in which they hope for recovery but simultaneously express a rational understanding of evidence to the contrary. We offer several recommendations for the ways in which family caregivers can be better supported to make sense of the results of functional neurodiagnostics. [ABSTRACT FROM AUTHOR]

Background: Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs. Methods: The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms. Results: Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children. Conclusions: The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges. [ABSTRACT FROM AUTHOR]

People with disorders of consciousness (DoC) are characteristically unable to synchronously participate in decision-making about clinical care or research. The inability to self-advocate exacerbates preexisting socioeconomic and geographic disparities, which include the wide variability observed across individuals, hospitals, and countries in access to acute care, expertise, and sophisticated diagnostic, prognostic, and therapeutic interventions. Concerns about equity for people with DoC are particularly notable when they lack a surrogate decision-maker (legally referred to as "unrepresented" or "unbefriended"). Decisions about both short-term and long-term life-sustaining treatment typically rely on neuroprognostication and individual patient preferences that carry additional ethical considerations for people with DoC, as even individuals with well thought out advance directives cannot anticipate every possible situation to guide such decisions. Further challenges exist with the inclusion of people with DoC in research because consent must be completed (in most circumstances) through a surrogate, which excludes those who are unrepresented and may discourage investigators from exploring questions related to this population. In this article, the Curing Coma Campaign Ethics Working Group reviews equity considerations in clinical care and research involving persons with DoC in the following domains: (1) access to acute care and expertise, (2) access to diagnostics and therapeutics, (3) neuroprognostication, (4) medical decision-making for unrepresented people, (5) end-of-life decision-making, (6) access to postacute rehabilitative care, (7) access to research, (8) inclusion of unrepresented people in research, and (9) remuneration and reciprocity for research participation. The goal of this discussion is to advance equitable, harmonized, guideline-directed, and goal-concordant care for people with DoC of all backgrounds worldwide, prioritizing the ethical standards of respect for autonomy, beneficence, and justice. Although the focus of this evaluation is on people with DoC, much of the discussion can be extrapolated to other critically ill persons worldwide. [ABSTRACT FROM AUTHOR]

Approximately 5 to 10% of patients in the emergency department have altered mental status, which is considered as a significant sign of the illness. Elderly patients and patients with concomitant medical conditions, especially those affecting the central nervous system, have an increased risk. Because altered mental status is a symptom of various conditions and diseases, differential diagnosis is challenging for physicians. Using the fundamental emergency care principles of emergency medicine and the ABCDE approach, the cause of the altered mental status can be suspected during the patient’s first encounter. Initial stabilization and clinical assessment are prioritized to direct the physician towards more target therapy of the underlying cause. These clinical guidelines aim to facilitate and enhance the recognition and initial management of patients with altered mental status. [ABSTRACT FROM AUTHOR]

Objective: To estimate rates and time to reach emergence of consciousness from vegetative state/unresponsive wakefulness syndrome (VS/UWS), and explore factors associated with improved recovery in children and adolescents with disorders of consciousness (DoC) following severe traumatic and non-traumatic brain injury. Methods: Analytical, retrospective, cohort study. Clinical records of consecutively referred patients admitted in VS/UWS to a neurological rehabilitation institute in Argentina, between 2005 and 2021 were reviewed. Seventy children and adolescents were included in the analysis. A specialized 12-week rehabilitation program was administered, and emergence was defined by scores ≥44 points on the Western Neuro Sensory Stimulation Profile (WNSSP), sustained for at least 3 weeks on consecutive weekly evaluations. Results: Emergence from VS/UWS to consciousness occurred within 5.4 (SD 2.6) weeks in almost one-third of patients. Multivariate Cox regression analysis showed emergence was significantly lower in patients with hypoxic ischemic encephalopathy compared to patients with other non-traumatic etiologies [HRadj 0.23 (95% CI 0.06–0.89); p = 0.03)]. Conclusions: Our findings reinforce growing evidence on the impact of etiology on DoC recovery in pediatric populations, ultimately influencing treatment and family-related decisions in child neurorehabilitation. [ABSTRACT FROM AUTHOR]

We aimed to investigate the electrocardiogram (ECG) features in persons with chronic disorders of consciousness (DOC, ≥ 29 days since injury, DSI) resulted from the most severe brain damages. The ECG data from 30 patients with chronic DOC and 18 healthy controls (HCs) were recorded during resting wakefulness state for about five minutes. The patients were classified into vegetative state (VS) and minimally conscious state (MCS). Eight ECG metrics were extracted for comparisons between the subject subgroups, and regression analysis of the metrics were conducted on the DSI (29–593 days). The DOC patients exhibit a significantly higher heart rate (HR, p = 0.009) and lower values for SDNN (p = 0.001), CVRR (p = 0.009), and T-wave amplitude (p < 0.001) compared to the HCs. However, there're no significant differences in QRS, QT, QTc, or ST amplitude between the two groups (p > 0.05). Three ECG metrics of the DOC patients—HR, SDNN, and CVRR—are significantly correlated with the DSI. The ECG abnormalities persist in chronic DOC patients. The abnormalities are mainly manifested in the rhythm features HR, SDNN and CVRR, but not the waveform features such as QRS width, QT, QTc, ST and T-wave amplitudes. The abnormal cardiac rhythmic features (heart rate, HR, and heart rate variability, HRV) are found to persist in long-term (measured after 29 ~ 593 days since injury, DSI) in patients with disorders of consciousness (DOC). HR and HRV are respectively negatively and positively related to DSI. These findings have important implications on DOC patient management. [ABSTRACT FROM AUTHOR]

Background and Objectives: Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method that modulates cortical excitability and shows promising results for treating disorders of consciousness (DoCs). Robotic verticalization training (RVT) has been shown to enhance motor and cognitive recovery. This study evaluates the effects of an innovative approach combining RVT with tDCS in individuals with DoCs. Methods: Twenty-four subjects with DoCs, particularly those with chronic minimally conscious state (MCS) due to vascular or traumatic brain injury, participated in a quasi-randomized study at the Neurorehabilitation Unit, IRCCS Neurolesi (Messina, Italy). Participants were divided into either a control group (CG) receiving RVT alone or an experimental group (EG) receiving combined tDCS and RVT. Both groups underwent treatments five times weekly for four weeks, with tDCS/sham sessions over the dorsolateral prefrontal cortex (DLPFC) lasting 20 min before Erigo training sessions, which lasted 45 min. Results: The findings indicate that combining tDCS with Erigo® Pro RTT could lead to greater improvements in cognitive functioning and P300 latency compared to the CG. Conclusions: These results suggest that the integrated approach of tDCS with RVT could offer significant benefits for patients with MCS, highlighting its potential to enhance cognitive recovery, such as reducing P300 latency. [ABSTRACT FROM AUTHOR]

Disorders of consciousness (DoC) are generally diagnosed by clinical assessment, which is a predominantly motor-driven process and accounts for up to 40 % of non-communication being misdiagnosed as unresponsive wakefulness syndrome (UWS) (previously known as prolonged/persistent vegetative state). Given the consequences of misdiagnosis, a more reliable and objective multimodal protocol to diagnosing DoC is needed, but has not been produced due to concerns regarding their interpretation and reliability. Of the techniques commonly used to detect consciousness in DoC, task-based paradigms (active paradigms) produce the most unequivocal result when findings are positive. It is well-established that command following (CF) reliably reflects preserved consciousness. Task-based electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can detect motor-independent CF and reveal preserved covert consciousness in up to 14 % of UWS patients. Accordingly, to improve the diagnostic accuracy of DoC, we propose a practical multimodal clinical decision framework centered on task-based EEG and fMRI, and complemented by measures like transcranial magnetic stimulation (TMS-EEG). [ABSTRACT FROM AUTHOR]

Background: Disorders of consciousness (DoC) are frequently encountered in both, acute and chronic brain injuries. In many countries, early withdrawal of life-sustaining treatments is common practice for these patients even though the accuracy of predicting recovery is debated and delayed recovery can be seen. In this review, we will discuss theoretical concepts of consciousness and pathophysiology, explore effective strategies for management, and discuss the accurate prediction of long-term clinical outcomes. We will also address research challenges. Main text: DoC are characterized by alterations in arousal and/or content, being classified as coma, unresponsive wakefulness syndrome/vegetative state, minimally conscious state, and confusional state. Patients with willful modulation of brain activity detectable by functional MRI or EEG but not by behavioral examination is a state also known as covert consciousness or cognitive motor dissociation. This state may be as common as every 4th or 5th patient without behavioral evidence of verbal command following and has been identified as an independent predictor of long-term functional recovery. Underlying mechanisms are uncertain but intact arousal and thalamocortical projections maybe be essential. Insights into the mechanisms underlying DoC will be of major importance as these will provide a framework to conceptualize treatment approaches, including medical, mechanical, or electoral brain stimulation. Conclusions: We are beginning to gain insights into the underlying mechanisms of DoC, identifying novel advanced prognostication tools to improve the accuracy of recovery predictions, and are starting to conceptualize targeted treatments to support the recovery of DoC patients. It is essential to determine how these advancements can be implemented and benefit DoC patients across a range of clinical settings and global societal systems. The Curing Coma Campaign has highlighted major gaps knowledge and provides a roadmap to advance the field of coma science with the goal to support the recovery of patients with DoC. [ABSTRACT FROM AUTHOR]

Objective: Unresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state (MCS) are considered different clinical entities, but their differential diagnosis remains challenging. As a potential clinical tool, functional magnetic resonance imaging (fMRI) could detect residual awareness without the need for the patients' actual motor responses. This study aimed to investigate the diagnostic value of fMRI for distinguishing between UWS/VS and MCS through a meta-analysis of the existing studies. Methods: We conducted a comprehensive search (from the database creation date to November. 2023) for relevant English articles on fMRI for the differential diagnosis of UWS/VS and MCS. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of fMRI in distinguishing between UWS/VS and MCS. The statistical I2 test was used to assess heterogeneity, and the source of heterogeneity was investigated by performing a meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test. Results: Ten studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.71 (95% CI 0.62-0.79) and 0.71 (95% CI 0.54-0.84), respectively. The fMRI for the differential diagnosis of UWS/VS and MCS has a moderate positive likelihood ratio (2.5) and a relatively low negative likelihood ratio (0.40). Additionally, SROC curves showed that the AUC was 0.76 (95% CI 0.72-0.80). Conclusion: Functional magnetic resonance imaging has a good performance in the differential diagnosis of UWS/VS and MCS, and may provide a potential tool for evaluating the prognosis and guiding the rehabilitation therapy in patients with disorders of consciousness. [ABSTRACT FROM AUTHOR]

Background: Disorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies. Methods: Twenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated. Results: One-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031). Conclusions: Applying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy. Trial registration: www.ClinicalTrials.gov, identifier: NCT05187000. [ABSTRACT FROM AUTHOR]

Background: Acupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients. Methods: A single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day's rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively. Discussion: This trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches. [ABSTRACT FROM AUTHOR]

Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale—Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management. [ABSTRACT FROM AUTHOR]

Stretch syncope (SS) is a benign, uncommon, distinct condition described mainly in adolescent males. It is responsible for paroxysmal events started by stereotyped stretching actions with neck hyperextension, culminating in alteration of consciousness. Motor manifestations are often present and may be associated with a generalized slowing of the electroencephalographic activity, challenging the diagnosis. Despite a few cases reported in the literature, different mechanisms have been implied in the pathogenesis, involving both local and systemic hemodynamic phenomena. Here, we report on an 8-year-old girl with self-induced SS, providing new insights into the related neurophysiological profile and discussing the possible etiology. Our evidence of transient and dynamic vascular impairment supports the hypothesis of SS as a multifactorial disorder. [ABSTRACT FROM AUTHOR]

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical characteristics, short‐ and long‐term functional outcomes, and risk factors for antibody‐related autoimmune encephalitis (AE) in patients with disorders of consciousness (DoC). Methods: Clinical data were collected from AE patients admitted to Xuanwu Hospital of Capital Medical University from January 2012 to December 2021, and patients were followed up for up to 24 months after immunotherapy. Results: A total of 312 patients with AE were included: 197 (63.1%) with anti‐NMDAR encephalitis, 71 (22.8%) with anti‐LGI1 encephalitis, 20 (6.4%) with anti‐GABAbR encephalitis, 10 (3.2%) with anti‐CASPR2 encephalitis, 10 (3.2%) with anti‐GAD65 encephalitis, and 4 (1.3%) with anti‐AMPAR2 encephalitis. Among these patients, 32.4% (101/312) presented with DoC, and the median (interquartile range, IQR) time to DoC was 16 (7.5, 32) days. DoC patients had higher rates of various clinical features of AE (p <.05). DoC was associated with elevated lumbar puncture cerebrospinal fluid (CSF) pressure, CSF leukocyte count, and specific antibody titer (p <.05). A high percentage of patients in the DoC group had a poor prognosis at discharge and at 6 months after immunotherapy (p <.001), but no significant difference in prognosis was noted between the DoC group and the non‐DoC group at 12 and 24 months after immunotherapy. Dyskinesia (OR = 3.266, 95% CI: 1.550–6.925, p =.002), autonomic dysfunction (OR = 5.871, 95% CI: 2.574–14.096, and p <.001), increased CSF pressure (OR = 1.007, 95% CI: 1.001–1.014, p =.046), and modified Rankin scale (mRS) score ≥3 at the initiation of immunotherapy (OR = 7.457, 95% CI: 3.225–18.839, p <.001) were independent risk factors for DoC in AE patients. Conclusion: DoC is a relatively common clinical symptom in patients with AE, especially critically ill patients. Despite requiring longer hospitalization, DoC mostly improves with treatment of the primary disease and has a good long‐term prognosis after aggressive life support and combination immunotherapy. [ABSTRACT FROM AUTHOR]

For patients who may lack capacity, the Mental Capacity Act 2005 requires capacity to be assessed for each decision at the time that treatment is offered, but this is not practical for every element of basic care and intervention delivered to patients undergoing rehabilitation following acquired brain injury, especially if their needs are changing. In this quality improvement project, we introduced a system for screening Mental Capacity and documentation to identify patients with a) largely intact cognition for whom capacity may be reasonably be presumed, and b) those in prolonged disorders of consciousness who clearly lacked capacity for all decisions. This enabled the multidisciplinary team to concentrate on evaluation of capacity in the third group who had more nuanced ability and required detailed assessment or support for decision-making. Two rounds of audit demonstrated that implementation improved the consistency of assessment and documentation. Multicentre roll-out of this approach is now required. [ABSTRACT FROM AUTHOR]

Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment. Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes (n = 177) between the ages of 27 and 85 (M = 54.1, SD = 14.7). Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms. Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p = 0.08). Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC. [ABSTRACT FROM AUTHOR]

To observe whether maintaining the appropriate depth of anesthesia with Bispectral Index (BIS) can improve the prognosis of Spinal Cord stimulation (SCS) implantation in patients with chronic Disorders of consciousness (DoC). Methods: 103 patients with DoC undergoing SCS implantation were reviewed, and 83 patients with DoC were included according to the standard of inclusion and exclusion Criteria. Patients were divided into a BIS group (n =45) and a non-BIS group (n =38) according to whether BIS monitoring was used during the operation. The depth of anesthesia in the BIS group was maintained between 40– 60. The anesthesiologist adjusted the depth of anesthesia in the non-BIS group according to clinical experience. Relevant information such as disease course, cause, anesthesia time, and operation time were collected. Preoperative CRS-R(preoperative) score, postoperative CRS-R(24h), and postoperative CRS-R(3m) changes were collected. Results: The CRS-R(3m) score in the BIS group was higher than that in the non-BIS group (preoperative), and the difference was statistically significant (P < 0.05). In CRS-R (24h), the BIS group was higher than the non-BIS group, and the difference was statistically significant (X2=8.787, P =0.004). The improvement of consciousness was included in the multivariate Logistic regression analysis model, and it was found that the thalamus was an independent factor affecting the improvement of consciousness (P < 0.05). During follow-up, 1 patient in the BIS group had a decrease in consciousness from MCS− to VS/ UWS and 2 patients in the non-BIS group died during follow-up. Conclusion: Patients can be benefit in hearing in CRS-R (24h). We recommend the use of BIS to monitor the depth of anesthesia in patients with DoC to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The aim of this prospective, observational cohort study was to investigate and assess diverse neuroimaging biomarkers to predict patients' neurological recovery after coma. 32 patients (18–76 years, M = 44.8, SD = 17.7) with disorders of consciousness participated in the study. Multimodal neuroimaging data acquired during the patient's hospitalization were used to derive cortical glucose metabolism (18F-fluorodeoxyglucose positron emission tomography/computed tomography), and structural (diffusion-weighted imaging) and functional connectivity (resting-state functional MRI) indices. The recovery outcome was defined as a continuous composite score constructed from a multivariate neurobehavioral recovery assessment administered upon the discharge from the hospital. Fractional anisotropy-based white matter integrity in the anterior forebrain mesocircuit (r = 0.72, p <.001, 95% CI: 0.87, 0.45), and the functional connectivity between the antagonistic default mode and dorsal attention resting-state networks (r = − 0.74, p < 0.001, 95% CI: − 0.46, − 0.88) strongly correlated with the recovery outcome. The association between the posterior glucose metabolism and the recovery outcome was moderate (r = 0.38, p = 0.040, 95% CI: 0.66, 0.02). Structural (adjusted R2 = 0.84, p = 0.003) or functional connectivity biomarker (adjusted R2 = 0.85, p = 0.001), but not their combination, significantly improved the model fit to predict the recovery compared solely to bedside neurobehavioral evaluation (adjusted R2 = 0.75). The present study elucidates an important role of specific MRI-derived structural and functional connectivity biomarkers in diagnosis and prognosis of recovery after coma and has implications for clinical care of patients with severe brain injury. [ABSTRACT FROM AUTHOR]

• A link between consciousness state and decannulation has been suggested. • 144 patients with prolonged disorders of consciousness after severe acquired brain injury. • Almost all decannulated patients improved their consciousness before decannulation. • No decannulated patient had unresponsive wakefulness syndrome. • Consciousness may influence swallowing skills involved in decannulation. To prospectively investigate the evolution of the consciousness state and the cannula-weaning progression in patients with prolonged disorders of consciousness. Nonconcurrent cohort study. A rehabilitation unit. Adult patients (N=144) with prolonged disorders of consciousness after a severe acquired brain injury admitted between June 2020 and September 2022. Not applicable. Consciousness state was assessed by repeated Coma Recovery Scale-Revised (CRS-R) questionnaire administration at admission and weekly afterward. The dates of the first improvement of consciousness state and the achievement of decannulation were recorded. Decannulation followed an internal protocol of multiprofessional rehabilitation. One hundred forty-four patients were included: age, 69 years; 64 (44.4%) with hemorrhagic etiology; time post onset, 40 days, CRS-R score at admission, 9, median length of stay, 90 days. Seventy-three (50.7%) patients were decannulated. They showed a significantly higher CRS-R (P <.001) and states of consciousness (P <.001) at admission, at the first improvement of the consciousness state (P =.003), and at discharge (P <.001); a lower severity in the Cumulative Illness Rating Scale at admission (P =.01); and a lower rate of pulmonary infections with recurrence (P =.021), compared with nondecannulated patients. Almost all decannulated patients (97.3%) improved their consciousness before decannulation. Consciousness states at decannulation were as follows: unresponsive wakefulness syndrome, 0 (0%); minimally conscious state (MCS) minus, 4 (5.5%); MCS plus, 7 (9.6%); and emergence from MCS, 62 (84.9%). Kaplan-Meier analysis showed a significant divergence between the curves with a higher probability of decannulation in patients who improved consciousness (P <.001). This study showed that the presence of signs of consciousness, even subtle, is a necessary condition for decannulation, suggesting that consciousness may influence some of the components implied in the decannulation process. [ABSTRACT FROM AUTHOR]

Background: Studies that have shown neurological improvement following cranioplasty (CP) after decompressive craniectomy (DC) in patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) did not include control groups. The aim of this study was to assess the justification of CP for these patients. Methods: Data were collected from medical records of inpatients with UWS and MCS admitted between 2002 and 2018. Results: Of the 144 participants (mean age 40 years, 76% males, 75% in UWS), 37% had CP following DC. The Loewenstein Communication Scale (LCS) gain was 12 ± 17 and 16 ± 17 for the control and study patients, respectively. The corresponding consciousness recovery rate (based on Coma Recovery Scale-Revised scores) was 51% and 53%, respectively. One-year survival rates were 0.80 and 0.93, and 5-year survival rates were 0.67 and 0.73, respectively. Mean outcome values were higher for the study group, but the differences between the groups did not reach statistical significance. Conclusions: The study did not demonstrate that CP increases brain recovery or survival. Nevertheless, it showed that CP did not decrease them either, and it did not increase complications rate. The findings, therefore, support offering CP to patients with UWS and MCS as CP does not increase risks and can achieve additional goals for these patients. Certain patients with reduced consciousness undergo an operation to remove a portion of the skull to relieve intracranial pressure. This study compared the outcomes of such patients with those of similar patients who later underwent an additional operation to repair the skull. The second operation, which restores cosmesis and has other advantages, did not decrease consciousness recovery or survival and did not increase the risk of complications; therefore, we concluded that it can be offered to these patients. [ABSTRACT FROM AUTHOR]

Accurate prediction of the recovery of Disorders of Consciousness (DoC) is of paramount significance for clinicians and families. Serum total bilirubin (TBIL) formed by activation of heme oxygenase 2, is associated with incidence and prognosis of cardiovascular and cerebrovascular diseases. However, studies that based TBIL and DoC are limited. The study attempted to examine the association between serum TBIL levels and prognosis in patients with DoC. One hundred and sixty-eight patients with DoC in the Second hospital of Shandong University from June 2021 to June 2023 were recruited. The clinical characteristics and venous blood samples were collected within 24 h after admission. The diagnosis of DoC was determined by two skilled investigators employing various behavioral evaluations along the coma recovery scale-revised (CRS-R) and the investigators conducted follow-up assessments of diagnosis at 1, 3, and 6 months after admission. For statistical analysis, we categorized patients with an improvement in clinical diagnosis from study entry as having a "good outcome". In total, 139 individuals enrolled in the study. The median TBIL level was 8.2 μmol/L. Good recovery of DoC at 1, 3, and 6 months occurred in 25 (18.0%), 41 (29.5%), and 56 (40.3%) patients, respectively. After full adjustment, a significant association was found between TBIL levels and the prognosis of DoC at 1, 3, and 6 months. When TBIL levels were analyzed as categorical variables, an increasing trend in the tertiles of TBIL levels demonstrated a significant positive association with the recovery of DoC at 1, 3, and 6 months. Stratified analysis revealed that the association between serum TBIL levels and the recovery of DoC remained consistent across different sub-populations. A high serum TBIL level is associated with an improved likelihood of recovery of DoC. Additional research is required to elucidate the underlying pathophysiological causal association between TBIL levels and DoC. [ABSTRACT FROM AUTHOR]

Background: The mesocircuit model describes a complex network that includes the prefrontal cortical-striatopallidal-thalamo-cortical loop systems and is involved in the mechanism underlying consciousness in patients with disorders of consciousness (DoC). Inhibitory signals to the thalamus become hyperactive in DoC patients, leading to a loss of consciousness. Reactivating this mesocircuit system is important for recovering consciousness in these patients. We investigated how the residual integrity of the thalamo-dorsolateral prefrontal cortex tract (TDLPFCT) influences consciousness in patients with DoC. Methods: This retrospective case-control study included three groups: prolonged DoC (n = 20), stroke without DoC (n = 20), and healthy controls (n = 20). Diffusion tensor imaging (DTI) was performed at least 4 weeks after the onset. Thalamo-DLPFC tracts were reconstructed using diffusion tensor tractography, and fractional anisotropy (FA) and tract volume (TV) were measured for each hemisphere. Consciousness was assessed using the revised coma recovery scale (CRS-R) within a week of brain imaging. Results: Significant differences in DLPFCT TV were observed across all three groups, in both affected and less-affected lobes, with the DoC group showing the greatest reduction. A significant correlation was found between the TV of the less-affected TDLPFCT and CRS-R score. Conclusion: The integrity of the TDLPFCT, particularly in the less affected hemisphere, is associated with consciousness levels in patients with prolonged DoC. This finding suggests its potential importance in assessing prognosis and further developing therapeutic strategies for patients with DoC. [ABSTRACT FROM AUTHOR]

Objectives: We performed the current research to describe healthcare providers' perspectives toward withdrawal of life-sustaining treatment (WLST) and advanced directive (AD) of patients with unresponsive wakefulness syndrome (UWS) and to identify influencing factors of their perspectives. Methods: Healthcare providers were recruited during a professional conference on disorders of consciousness (DoC). Participants completed self-administered questionnaires which included demographics, personal perspectives regarding WLST and the perception of ADs. Results: A total of 230 Chinese healthcare providers (female: 69.7%) were included. Only a small proportion reported positive attitudes toward withdrawing artificial nutrition and hydration (35.2%), antibiotics (30.9%), and do-not-resuscitation orders (23.5%) in UWS patients. As for predictors' identification, religion was significantly associated with the positive attitude toward DNR order (p = 0.004). Moreover, although 47.4% of the participants had never heard of ADs before of conference, almost all of them would consider ADs (95.7%) thereafter, especially for non-neurologists (p = 0.033). Conclusion: The propensity to WLST for UWS in China is low and perspective on WLST is significantly associated with individual characteristics. The attitudes of healthcare providers toward integrating ADs in the decisional process are positive. Future research regarding ADs and their predictors should be carried out to improve the quality of end-of-life care of UWS in China. [ABSTRACT FROM AUTHOR]

BACKGROUND Patients with brain injury who are Unresponsive to Commands may perform Cognigrees, tive tasks that are detected on functional magnetic resonance imaging (fMILI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale--Revised (CRS-R). RESULTS Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 3Z9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25°6 of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (259/0) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38°/0) with an observable response to verbal commands. CONCLUSIONS Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others. [ABSTRACT FROM AUTHOR]

Severe traumatic brain injuries typically result in loss of consciousness or coma. In deeply comatose patients with traumatic brain injury, cortical dynamics become simple, repetitive, and predictable. We review evidence that this low-complexity, high-predictability state results from a passive cortical state, represented by a stable repetitive attractor, that hinders the flexible formation of neuronal ensembles necessary for conscious experience. Our data and those from other groups support the hypothesis that this cortical passive state is because of the loss of thalamocortical input. We identify the unpredictability and complexity of cortical dynamics captured by local field potential as a sign of recovery from this passive coma attractor. In this Perspective article, we discuss how these electrophysiological biomarkers of the recovery of consciousness could inform the design of closed-loop stimulation paradigms to treat disorders of consciousness. [ABSTRACT FROM AUTHOR]

Background: There is no diagnostic assessment procedure with moderate or strong evidence of use, and evidence for current means of treating prolonged disorders of consciousness (pDOC) is sparse. This may be related to the fact that the mechanisms of pDOC have not been studied deeply enough and are not clear enough. Therefore, the aim of this study was to explore the mechanism of pDOC using functional near‐infrared spectroscopy (fNIRS) to provide a basis for the treatment of pDOC, as well as to explore preclinical markers for determining the arousal of pDOC patients. Methods: Five minutes resting‐state data were collected from 10 pDOC patients and 13healthy adults using fNIRS. Based on the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the time series, the resting‐state cortical brain functional connectivity strengths of the two groups were calculated, and the functional connectivity strengths of homologous and heterologous brain networks were compared at the sensorimotor network (SEN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), and visual network (VIS) levels. Univariate binary logistic regression analyses were performed on brain networks with statistically significant differences to identify brain networks associated with arousal in pDOC patients. The receiver operating characteristic (ROC) curves were further analyzed to determine the cut‐off value of the relevant brain networks to provide clinical biomarkers for the prediction of arousal in pDOC patients. Results: The results showed that the functional connectivity strengths of oxyhemoglobin (HbO)‐based SEN∼SEN, VIS∼VIS, DAN∼DAN, DMN∼DMN, SEN∼VIS, SEN∼FPN, SEN∼DAN, SEN∼DMN, VIS∼FPN, VIS∼DAN, VIS∼DMN, HbR‐based SEN∼SEN, and SEN∼DAN were significantly reduced in the pDOC group and were factors that could reflect the participants' state of consciousness. The cut‐off value of resting‐state functional connectivity strength calculated by ROC curve analysis can be used as a potential preclinical marker for predicting the arousal state of subjects. Conclusion: Resting‐state functional connectivity strength of cortical networks is significantly reduced in pDOC patients. The cut‐off values of resting‐state functional connectivity strength are potential preclinical markers for predicting arousal in pDOC patients. [ABSTRACT FROM AUTHOR]

Unconsciousness in severe acquired brain injury (sABI) patients occurs with different cognitive and neural profiles. Perturbational approaches, which enable the estimation of proxies for brain reorganization, have added a new avenue for investigating the non‐behavioural diagnosis of consciousness. In this prospective observational study, we conducted a comparative analysis of the topological patterns of heartbeat‐evoked potentials (HEP) between patients experiencing a prolonged disorder of consciousness (pDoC) and patients emerging from a minimally consciousness state (eMCS). A total of 219 sABI patients were enrolled, each undergoing a synchronous EEG‐ECG resting‐state recording, together with a standardized consciousness diagnosis. A number of graph metrics were computed before/after the HEP (Before/After) using the R‐peak on the ECG signal. The peak value of the global field power of the HEP was found to be significantly higher in eMCS patients with no difference in latency. Power spectrum was not able to discriminate consciousness neither Before nor After. Node assortativity and global efficiency were found to vary with different trends at unconsciousness. Lastly, the Perturbational Complexity Index of the HEP was found to be significantly higher in eMCS patients compared with pDoC. Given that cortical elaboration of peripheral inputs may serve as a non‐behavioural determinant of consciousness, we have devised a low‐cost and translatable technique capable of estimating causal proxies of brain functionality with an endogenous, non‐invasive stimulus. Thus, we present an effective means to enhance consciousness assessment by incorporating the interaction between the autonomic nervous system (ANS) and central nervous system (CNS) into the loop. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics and death -related risk factors of patients with acute ethylene glycol (EG) poisoning in order to guide clinical diagnosis and prognosis evaluation. Methods A retrospective analysis was done on the clinical data of 43 patients with acute EG poisoning admitted to the Emergency Department and ICU in 3 hospitals in Xinjiang from January 2010 to December 2022. The patients were divided into survival and death groups based on their in -hospital survival status. The differences in various indicators between the two groups were compared. Binary logistic regression analysis was used to determine independent risk factors affecting prognosis, and the receiver operating curve characteristic (ROC) curve was used to analyze the predictive ability of relevant indicators for the prognosis of acute EG poisoning patients. Results Among 43 patients, 31 were male (72.09% ), and 32 cases were accidental ingestion (74.42%). There were 9 cases of death (20.93%) and 41 cases (95.35%) of acute kidney injury. The patients had varying degrees of consciousness disorders [GCS score (9.767 ± 1.900) points]. The values of lactate, potassium ions, anion gap (AG), osmolar gap (OG), and blood creatinine were higher than the normal reference range. Results of the binary logistic regression analysis indicated that a higher AG was associated with an increased risk of mortality (OR = 1.424, P < 0.05); higher GCS scores were associated with a decreased risk of mortality (OR = 0.161, P < 0.05); and patients treated with ethanol had a reduced risk of mortality compared to those without ethanol treatment (OR = 0.003, P < 0.05). ROC analysis showed that the area under the curve (AUC) for the combination of AG and GCS scores was 0.918 (95% CI: 0.836 to 1), which was higher than the AUC for AG alone (0.886, 95% CI: 0.771 to 1) and the AUC of GCS score (0.842, 95% CI: 0.718 to 0.965). Conclusions Acute ethylene glycol (EG) poisoning was characterized by high AG metabolic acidosis with elevated OG or altered consciousness, often leading to acute kidney injury. High AG, low GCS scores, and a lack of ethanol treatment were independent risk factors for mortality. The prediction accuracy of the patient’s prognosis could be improved with the combination of AG and GCS scores. [ABSTRACT FROM AUTHOR]

The purpose of this study was to differentiate clinically meaningful improvement or deterioration from normal fluctuations in patients with disorders of consciousness (DoC) following severe brain injury. We computed indices of responsiveness for the Coma Recovery Scale-Revised (CRS-R) using data from a clinical trial of 180 participants with DoC. We used CRS-R scores from baseline (enrollment in a clinical trial) and a 4-week follow-up assessment period for these calculations. To improve precision, we transformed ordinal CRS-R total scores (0–23 points) to equal-interval measures on a 0–100 unit scale using Rasch Measurement theory. Using the 0–100 unit total Rasch measures, we calculated distribution-based 0.5 standard deviation (SD) minimal clinically important difference, minimal detectable change using 95% confidence intervals, and conditional minimal detectable change using 95% confidence intervals. The distribution-based minimal clinically important difference evaluates group-level changes, whereas the minimal detectable change values evaluate individual-level changes. The minimal clinically important difference and minimal detectable change are derived using the overall variability across total measures at baseline and 4 weeks. The conditional minimal detectable change is generated for each possible pair of CRS-R Rasch person measures and accounts for variation in standard error across the scale. We applied these indices to determine the proportions of participants who made a change beyond measurement error within each of the two subgroups, based on treatment arm (amantadine hydrochloride or placebo) or categorization of baseline Rasch person measure to states of consciousness (i.e., unresponsive wakefulness syndrome and minimally conscious state). We compared the proportion of participants in each treatment arm who made a change according to the minimal detectable change and determined whether they also changed to another state of consciousness. CRS-R indices of responsiveness (using the 0–100 transformed scale) were as follows: 0.5SD minimal clinically important difference = 9 units, minimal detectable change = 11 units, and the conditional minimal detectable change ranged from 11 to 42 units. For the amantadine and placebo groups, 70% and 58% of participants showed change beyond measurement error using the minimal detectable change, respectively. For the unresponsive wakefulness syndrome and minimally conscious state groups, 54% and 69% of participants changed beyond measurement error using the minimal detectable change, respectively. Among 115 participants (64% of the total sample) who made a change beyond measurement error, 29 participants (25%) did not change state of consciousness. CRS-R indices of responsiveness can support clinicians and researchers in discerning when behavioral changes in patients with DoC exceed measurement error. Notably, the minimal detectable change can support the detection of patients who make a "true" change within or across states of consciousness. Our findings highlight that the continued use of ordinal scores may result in incorrect inferences about the degree and relevance of a change score. [ABSTRACT FROM AUTHOR]

The potential influence of pituitary-related hormones (including both pituitary gland and target gland hormones) on functional recovery after traumatic brain injury has been observed. However, the relationship between these hormones and the recovery of consciousness in patients with disorders of consciousness (DOC) remains unclear. In this retrospective and observational study, 208 patients with DOC were recruited. According to the Glasgow Outcome Scale (GOS) scores after 6 months, patients with DOC were categorized into two subgroups: a favorable prognosis subgroup (n = 38) comprising those who regained consciousness (GOS score ≥3), and a poor prognosis subgroup (n = 156) comprising those who remained in DOC (GOS score <3). Comparative analyses of pituitary-related hormone levels between the two subgroups were conducted. Further, a binary logistic regression analysis was conducted to assess the predictive value of pituitary-related hormones for the patients' prognosis. The favorable prognosis subgroup showed a significant increase in adrenocorticotropic hormone (ACTH) levels (p = 0.036). Moreover, higher ACTH levels and shorter days since injury were significantly associated with a better prognosis, with odds ratios (ORs) of 0.928 (95% confidence interval [CI] = 0.873-0.985, p = 0.014) and 1.015 (95% CI = 1.005-1.026, p = 0.005), respectively. A subsequent receiver operating characteristic (ROC) analysis demonstrated the potential to predict patients' prognosis with an area under the curve value of 0.78, an overall accuracy of 75.5%, a sensitivity of 77.5%, and a specificity of 66.7%. Our findings indicate that ACTH levels could serve as a clinically valuable and convenient predictor for patients' prognosis. [ABSTRACT FROM AUTHOR]

Background: Identifying covert consciousness in intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can detect residual consciousness in ICU patients with DoC. Methods: We prospectively enrolled clinically low-response or unresponsive patients with traumatic or nontraumatic DoC from ICUs of a tertiary referral center. Age-matched and sex-matched healthy volunteers served as controls. Patients were categorized into clinically unresponsive (coma or unresponsive wakefulness syndrome) or clinically low-responsive (minimally conscious state or better). Using automated pupillometry, we recorded pupillary dilation to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with task-specific success criteria (e.g., ≥ 3 of 5 pupillary dilations on five consecutive mental arithmetic tasks). Results: We obtained 699 pupillometry recordings at 178 time points from 91 ICU patients with brain injury (mean age 60 ± 13.8 years, 31% women, and 49.5% nontraumatic brain injuries). Recordings were also obtained from 26 matched controls (59 ± 14.8 years, 38% women). Passive paradigms yielded limited distinctions between patients and controls. However, active paradigms enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥ 3 pupillary dilations were seen in 17.8% of clinically unresponsive patients and 50.0% of clinically low-responsive patients (odds ratio 4.56, 95% confidence interval 2.09–10.10; p < 0.001). In comparison, 76.9% healthy controls responded with ≥ 3 pupillary dilations (p = 0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman's rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho = 1, p = 0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior 2 weeks before overt signs of awareness, suggesting prolonged cognitive motor dissociation. Conclusions: Automated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence covert consciousness, in ICU patients with acute DoC. [ABSTRACT FROM AUTHOR]

Background: We developed a gap analysis that examines the role of brain–computer interfaces (BCI) in patients with disorders of consciousness (DoC), focusing on their assessment, establishment of communication, and engagement with their environment. Methods: The Curing Coma Campaign convened a Coma Science work group that included 16 clinicians and neuroscientists with expertise in DoC. The work group met online biweekly and performed a gap analysis of the primary question. Results: We outline a roadmap for assessing BCI readiness in patients with DoC and for advancing the use of BCI devices in patients with DoC. Additionally, we discuss preliminary studies that inform development of BCI solutions for communication and assessment of readiness for use of BCIs in DoC study participants. Special emphasis is placed on the challenges posed by the complex pathophysiologies caused by heterogeneous brain injuries and their impact on neuronal signaling. The differences between one-way and two-way communication are specifically considered. Possible implanted and noninvasive BCI solutions for acute and chronic DoC in adult and pediatric populations are also addressed. Conclusions: We identify clinical and technical gaps hindering the use of BCI in patients with DoC in each of these contexts and provide a roadmap for research aimed at improving communication for adults and children with DoC, spanning the clinical spectrum from intensive care unit to chronic care. [ABSTRACT FROM AUTHOR]

The article discusses several research on mind-body medicine and technology. A study examined machine learning applied to functional magnetic resonance imaging data to analyze states of consciousness shift induced by pharmacologic and nonpharmacologic methods. Another explored the use of machine learning to understand how body movement and posture encode acute psychosocial stress. Investigators evaluated mindfulness-based stress reduction using a virtual human, chatbot and live human being.

People with disorders of consciousness, either as a consequence of an acquired brain injury or a traumatic brain injury, may pose serious challenges to medical and/or rehabilitative centers with an increased burden on caregivers and families. The objectives of this study were as follows: to explore the use of extended reality as a critical means of rehabilitative support in people with disorders of consciousness and brain injuries; to evaluate its impact on recovery processes; to assess the improvements in the participants' quality of life, and to reduce the burden on families and caregivers by using extended reality and artificial-intelligence-based programs. A selective review of the newest empirical studies on the use of extended reality and artificial-intelligence-based interventions in patients with brain injuries and disorders of consciousness was conducted over the last decade. The potential for bias in this selective review is acknowledged. A conceptual framework was detailed. The data showed that extended reality and artificial-intelligence-based programs successfully enhanced the adaptive responding of the participants involved, and improved their quality of life. The burden on caregivers and families was reduced accordingly. Extended reality and artificial intelligence may be viewed as crucial means of recovery in people with disorders of consciousness and brain injuries. [ABSTRACT FROM AUTHOR]

Introduction: We present a relationship‐centred shared‐decision‐making (RCSDM) process model to explicate factors that shape decision‐making processes during physical medicine and rehabilitation (PMR) encounters among patients, their care partners and practitioners. Existing shared decision‐making (SDM) models fall short in addressing the everyday decisions routinely made regarding persons with chronic disabilities who require high levels of support, their care partners and rehabilitation practitioners. In PMR, these everyday decisions are small scale, immediate and in service to a larger therapeutic goal. They can be thought of as micro‐decisions and involve multiple practitioners, care partners and patients. How micro‐decisions are made in this context is contingent on multiple roles and relationships among these relevant parties. Our model centres on micro‐decisions among patients, their care partners and practitioners based on our disorders of consciousness (DoC) research. Methods: To develop our model, we examined peer‐reviewed literature in SDM in PMR, chronic disability and person‐centeredness; formed collaborations and co‐created our constructs with rehabilitation practitioners and with care partners who have lived experience of caring for persons with DoC; analysed emerging empirical data and vetted early versions with expert scientific and clinical audiences. Our model builds from the core tenets of relational autonomy, and scholarship and activism of disability advocates. Findings: Our model conceptualizes four non‐hierarchical levels of analysis to understand the process of micro‐decision‐making in chronic disability and medical rehabilitation: social forces (historical and sociological); roles and relationships (multiple and intersecting); relational dimensions (interactional and contextual) and micro‐decision moments (initiation, response and closure). Discussion: Relationships among patients, their care partners and practitioners are the intersubjective milieu within which decisions are made. Our conceptual model explicates the process of micro‐decision‐making in PMR. Patient or Public Contribution: Care partners (or caregivers) and rehabilitation practitioners are active members of our team. We work together to develop research projects, collect, analyse and disseminate data. The conceptual model we present in this manuscript was co‐created—input from care partners and practitioners on previously collected data became the impetus to develop the RCSDM process model and share co‐authorship in this manuscript. [ABSTRACT FROM AUTHOR]

Consciousness is a multidisciplinary phenomenon that intensively reaches many areas of neuroscience. This review presents the latest theories of consciousness with the focus on quantum theories and actual neuronal correlates of consciousness (neuroanatomy of consciousness), divided into cortical and subcortical regions. We also mention major depressive disorder and schizophrenia as disorders of consciousness and try to look at them form a different perspective. It is widely accepted that consciousness, or mental activity, is somehow correlated with the activity and function of the "material" brain. Since quantum theory is the fundamental theory of matter currently available, it remains a legitimate question whether quantum theory can help us gain a deeper understanding of consciousness. However, to better understand the concept of consciousness, more detailed and deeper neurobiological research is necessary. A more accurate assessment of level of consciousness can help to build awareness and provide new ideas for patients with impaired consciousness. [ABSTRACT FROM AUTHOR]

Objective: To investigate if eye tracking can support detection of covert voluntary eye movements and to compare these findings with a simultaneously performed clinical assessment according to the Coma Recovery Scale manual regarding visual stimuli. Design: Observational case series. Subjects: Twelve outpatients with prolonged disorders of consciousness recruited from the rehabilitation clinic of a regional rehabilitation unit. Method: Eye movements were recorded with a wearable eye tracker while performing 4 test items from the Coma Recovery Scale Revised. The clinical assessment and recorded eye movement responses were analysed for agreement. Results: Response data was obtained from 238 out of 288 trials. Eye-tracking data were obtained in median 89.6% of the trials (37.5–100%). The eye tracking assessment judged a significantly higher percentage of trials as a response (46.2%) compared with the clinical assessment (18.1%), mainly in test items “visual pursuit” and “visual fixation”. Conclusion: Eye tracking showed potential to be more effective in the detection of putative voluntary eye movements compared with conventional examination. Based on the findings in this and previous studies, eye tracking may serve as a useful complementary tool when examining patients with prolonged disorders of consciousness.