Perception of diagnosis by family caregivers in severe brain injury patients in China.

OBJECTIVES: Surrogate decision-making by family caregivers for patients with severe brain injury is influenced by the availability and understanding of relevant information and expectations for future rehabilitation. We aimed to compare the consistency of family caregivers' perceptions with clinical diagnoses and to inform their expectation of prognosis in the future. METHODS: The Coma Recovery Scale-Revised was used to assess the diagnosis of inpatients with severe brain injury between February 2019 and February 2020. A main family caregiver was included per patient. The family caregiver's perception of the patient's consciousness and expectations of future recovery were collected through questionnaires and compared consistently with the clinical diagnosis. RESULTS: The final sample included 101 main family caregivers of patients (57 UWS, unresponsive wakefulness syndrome, 37 MCS, minimally conscious state, 7 EMCS, emergence from MCS) with severe brain injury. Only 57 family caregivers correctly assessed the level of consciousness as indicated by the CRS-R, showing weak consistency (Kappa = 0.217, P = 0.002). Family caregivers' demographic characteristics and CRS-R diagnosis influenced the consistency between perception and clinical diagnosis. Family caregivers who provided hands-on care to patients showed higher levels of consistent perception (AOR = 12.24, 95% CI = 2.06-73.00, P = 0.006). Compared to UWS, the family caregivers of MCS patients were more likely to have a correct perception (OR = 7.68, 95% CI = 1.34-44.06). Family caregivers had positive expectations for patients' recovery in terms of both communication and returning to normal life. CONCLUSION: Nearly half of family caregivers have inadequate understanding of their relative's level of consciousness, and most of them report overly optimistic expectations that do not align with clinical diagnosis. Providing more medical information to family caregivers to support their surrogate decision-making process is essential.

Mood assessments of family caregivers of patients with severe brain injury in China.

OBJECTIVES: Long-term care of severe brain injury patients places a significant mental burden on family caregivers, yet few studies have reported the situation in China. We aimed to describe the mood states of family caregivers of patients with severe brain injury and examine the influencing factors that affect caregivers' moods. METHODS: Cross-sectional survey was used to assess the mood profiles of Chinese family caregivers between February 2019 and February 2020. Demographic data of caregivers and patients, the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7) were used to assess the level of depressive and anxiety symptoms. The quality of life score was also assessed by a visual analog scale, and the Coma Recovery Scale-Revised was used to assess the patient's consciousness. RESULT: One hundred and one patients with severe brain injury (57 unresponsive wakefulness syndrome, UWS) between the age of 14 and 70 and their main family caregivers were enrolled in the study. Most caregivers displayed depressive (n = 62) and anxiety symptoms (n = 65), with 17 and 20 of these family caregivers reporting (moderately) severe depressive symptom and severe anxiety symptom, respectively. The caregiver's depressive symptom level significantly decreased as the patient's injury lasted longer (r = - 0.208, P = 0.037). Moreover, the age of the patient negatively related to the levels of depressive (r = - 0.310, P = 0.002) and anxiety symptoms (r = - 0.289, P = 0.003) in caregivers. There was a significant positive correlation between anxiety and depressive symptoms scores in family caregivers (r = 0.838, P < 0.001). The higher the level of anxiety (r = - 0.273, P = 0.006) and depressive symptoms (r = - 0.265, P = 0.007), the worse the quality of life. CONCLUSION: Many family caregivers of patients with severe brain injury experience various levels of anxiety and depressive symptoms in China. Tailor-made psychological help seems imperative. Researchers and doctors can provide information about patient's conditions to assist family members in discussing rehabilitation options for patients in different states of consciousness will help to ease anxiety of family caregivers.

The visual stimulation in disorders of consciousness.

Severe brain damage usually leads to disorders of consciousness (DOC), which include coma, unresponsive wakefulness syndrome (UWS) and a minimally conscious state (MCS). Visual stimulation is widely used, especially in the diagnosis and treatment and treatment of DOC. Researchers have indicated that tests based on visual stimulation including visual pursuit, when used in conjunction with the Coma Recovery Scale-Revised, are able to differentiate between UWS from an MCS. Recently, targeting patients' circadian rhythms has been proposed to be a possible treatment target for DOC. Indeed, light therapy has been applied in some other fields, including treating seasonal affective disorder, sleep problems, and Parkinson's disease. However, at present, although visual stimulation and light therapy are frequently used in DOC, there is still no international unified standard. Therefore, we recommend the development of an international consensus in regard to the definitions, operational criteria and assessment procedures of visual stimulation and light therapy. This review combines visual stimulation, circadian rhythm recovery, and light therapy in DOC patients and presents the mechanisms and current advances in applications related to light therapy and visual stimulation in an attempt to provide additional ideas for future research and treatment of DOC.

Clinical application of neuromodulation therapy in patients with disorder of consciousness: A pooled analysis of 544 participants.

BACKGROUND: The number of patients with disorders of consciousness (DoC) has increased dramatically with the advancement of intensive care and emergency medicine, which brings tremendous economic burdens and even ethical issues to families and society. OBJECTIVE: To evaluate the effectiveness of neuromodulation therapy for patients with DoC. METHODS: First, we conducted a literature review of individual patient data (IPD) on PubMed, EMBASE, and Cochrane-controlled trials following PRISMA guidelines. Then, we collected neuromodulation cases from our institution. Finally, we conducted a pooled analysis using the participants from the medical literature (n = 522) and our local institutions (n = 22). RESULTS: In this pooled analysis of 544 patients with DoC with a mean age of 46.33 years, our results revealed that patients have improved CRS-R scores [1.0 points (95% CI, 0.57-1.42)] after neuromodulation. Among them, patients have better effectiveness in traumatic than non-traumatic etiology (P < 0.05). The effectiveness of consciousness improvement could be affected by the age, baseline consciousness state, and duration of stimulation. Compared with non-invasive intervention, an invasive intervention can bring more behavioral improvement (P < 0.0001) to MCS rather than UWS/VS patients. Importantly, neuromodulation is a valuable therapy even years after the onset of DoC. CONCLUSION: This pooled analysis spotlights that the application of neuromodulation can improve the behavioral performance of patients with DoC. A preliminary trend is that age, etiology, baseline consciousness state, and stimulation duration could impact its effectiveness.

Randomized trial of transcutaneous auricular vagus nerve stimulation on patients with disorders of consciousness: A study protocol.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has recently been explored for the treatment of Disorders of consciousness (DoC) caused by traumatic brain injury. The evidence of taVNS during the consciousness recovery has been recently reported. However, the mechanism of taVNS in the recovery of consciousness is not clear. This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), Electrophysiology (EEG), and Single-molecular array (Simoa). Methods/design: Nighty patients with DoC acquired brain injury are randomized into one of three groups receiving sham taVNS or active taVNS (just left and left or right), respectively. Each of the three groups will experience a 40 days cycle (every 10 days for a small period, baseline 2 weeks, intervention 2 weeks, 40 min per day, 5 days per week, then no intervention for 2 weeks, intervention 2 weeks, 40 min per day, and 5 days per week). Primary outcomes (CRS-R) will be recorded five times during every period. Secondary outcomes will be recorded at the first and at the last period [MRI, EEG, Phosphorylated tau (P-tau), and Neurofilament light chain (NFL)]. We will take notes the adverse events and untoward effects during all cycles. Discussion: Transcutaneous auricular vagus nerve stimulation as a painless, non-invasive, easily applied, and effective therapy was applied for treatment of patients with depression and epilepsy several decades ago. Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS on brain activity. Therefore, we will design a randomized controlled trial to evaluate the effectiveness and safety of taVNS therapy for DoC, and explore neural anatomy correlated to taVNS during the consciousness recovery. Finally, this protocol also tests some biomarkers along with the recovery of consciousness. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2100045161. Registered on 9 April 2021.

Study protocol: Developing telephone follow-up scale for patients with disorders of consciousness.

Background: The significant lack of rehabilitation prognostic data is the main reason that affects the treatment decision-making and ethical issues of patients with disorders of consciousness (DoC). Currently, the clinic's consciousness assessment tools cannot satisfy DoC patients' follow-up needs. Objective: The purpose of this study is to construct a sensitive, professional, and simple telephone follow-up scale for DoC patients to follow up on the prognosis, especially the recovery of consciousness, of prolonged DoC patients transferred to community hospitals or at home. Methods: This study is to adopt expert consultation to construct and to verify the validity and feasibility of the scale on-site. Conclusion: At present, there is a strong demand for portable, accurate, and easily operated scales. It is helpful to improve the rehabilitation data of prolonged DoC patients and provide more basis for their treatment and rehabilitation.

Chinese translation and validation of the Near-Death Experience Content scale.

Introduction: In recent years, a growing number of near-death experience (NDE) testimonies have been collected worldwide due to an increasing interest in research on this phenomenon. China has many patients who survive life-threatening situations, leaving over much data on NDEs to be collected for research. In the historical context of Eastern civilization, many mentally controlled practices in China can also lead to "NDEs-like" (e.g., meditation). This study aimed (1) to translate and validate the recently developed Near-Death Experience Content (NDE-C) scale into Chinese and (2) to quantify and identify NDEs and NDEs-like in China with this new Chinese version of the NDE-C scale. Methods: Here, we presented the work that had been performed to translate the NDE-C scale into Chinese and validated this version on 79 NDE testimonies. Results: Brislin's back-translation model was performed to translate a Chinese version of the NDE-C scale and internal consistency (the Cronbach's α value for the total group = 0.846) as well as the confirmatory factor analysis was conducted. Discussion: Currently, the Chinese version of the NDE-C scale is ready for use in research practice in the context of Eastern culture, to screen people who have experienced an NDEs(-like) and to quantify their subjective experience, promoting further NDEs-related research in China.

Brain-Computer Interfaces for Awareness Detection, Auxiliary Diagnosis, Prognosis, and Rehabilitation in Patients with Disorders of Consciousness.

In recent years, neuroimaging studies have remarkably demonstrated the presence of cognitive motor dissociation in patients with disorders of consciousness (DoC). These findings accelerated the development of brain-computer interfaces (BCIs) as clinical tools for behaviorally unresponsive patients. This article reviews the recent progress of BCIs in patients with DoC and discusses the open challenges. In view of the practical application of BCIs in patients with DoC, four aspects of the relevant literature are introduced: consciousness detection, auxiliary diagnosis, prognosis, and rehabilitation. For each aspect, the paradigm design, brain signal processing methods, and experimental results of representative BCI systems are analyzed. Furthermore, this article provides guidance for BCI design for patients with DoC and discusses practical challenges for future research.

Olfactory Stimulation and the Diagnosis of Patients With Disorders of Consciousness: A Double-Blind, Randomized Clinical Trial.

OBJECTIVES: The aim of this study was to determine whether behavioral responses elicited by olfactory stimulation are a predictor of conscious behavioral response and prognosis of patients with disorders of consciousness (DOC). METHODS: Twenty-three DOC patients (8 unresponsive wakefulness syndrome [UWS]; 15 minimally conscious state [MCS]) were recruited for this study in which 1-Octen-3-ol (familiar neutral odor) and pyridine were used to test odor behavioral responses, and water was used as an odorless stimulus. One rater presented the three odors in front of each patient's nose randomly, and another one videotaped all behavioral responses (e.g., pouting, wrinkling nose, slightly shaking head, frowning, etc.). Two independent raters, blind to the stimuli and the patient's diagnosis, gave the behavioral results according to the recorded videos. One-, 3-, and 6-month follow-up evaluations were conducted to obtain a good prognostic value. RESULTS: All MCS patients showed behavioral responses to the 1-Octen-3-ol stimulus; nine MCS and one UWS showed olfactory emotional responses to the pyridine, and two MCS showed olfactory emotional responses to the water stimulus. The incidence of behavioral response was significantly higher using 1-Octen-3-ol than it was for water by McNemar test (p < 0.001), significantly higher using pyridine than it was for water (p < 0.01). The χ2 test results indicated that there were significant differences between MCS and UWS to 1-Octen-3-ol (p < 0.001). For MCS patients, the incidence of behavioral response was no different between using 1-Octen-3-ol and pyridine (p > 0.05). There was no significant relationship between the olfactory behavioral response and the improvement of consciousness based on the χ2 test analysis (p > 0.05). CONCLUSION: Olfactory stimuli, especially for the familiar neutral odor, might be effective for eliciting a conscious behavioral response and estimating the clinical diagnosis of DOC patients. CLINICAL TRIAL REGISTRATION: [https://clinicaltrials.gov/ct2/show/NCT03732092], [identifier NCT03732092].

Corrigendum: Estimating the Minimal Number of Repeated Examinations for Random Responsiveness With the Coma Recovery Scale-Revised as an Example.

[This corrects the article DOI: 10.3389/fnint.2021.685627.].

Estimating the Minimal Number of Repeated Examinations for Random Responsiveness With the Coma Recovery Scale-Revised as an Example.

Objective: The aim of this study was to develop a general method to estimate the minimal number of repeated examinations needed to detect patients with random responsiveness, given a limited rate of missed diagnosis. Methods: Basic statistical theory was applied to develop the method. As an application, 100 patients with disorders of consciousness (DOC) were assessed with the Coma Recovery Scale-Revised (CRS-R). DOC patients were supposed to be examined for 13 times over 20 days, while anyone who was diagnosed as a minimally conscious state (MCS) in a round would no longer be examined in the subsequent rounds. To test the validation of this method, a series of the stochastic simulation was completed by computer software under all the conditions of possible combinations of three kinds of distributions for p, five values of p, and four sizes of the sample and repeated for 100 times. Results: A series of formula was developed to estimate the probability of a positive response to a single examination given by a patient and the minimal number of successive examinations needed based on the numbers of patients detected in the first i (i =1, 2,.) rounds of repeated examinations. As applied to the DOC patients assessed with the CRS-R, with a rate of missed diagnosis < 0.0001, the estimate of the minimal number of examinations was six in traumatic brain injury patients and five in non-traumatic brain injury patients. The outcome of the simulation showed that this method performed well under various conditions possibly occurring in practice. Interpretation: The method developed in this paper holds in theory and works well in application and stochastic simulation. It could be applied to any other kind of examinations for random responsiveness, not limited to CRS-R for detecting MCS; this should be validated in further research.

Spontaneous transient brain states in EEG source space in disorders of consciousness.

Spontaneous transient states were recently identified by functional magnetic resonance imaging and magnetoencephalography in healthy subjects. They organize and coordinate neural activity in brain networks. How spontaneous transient states are altered in abnormal brain conditions is unknown. Here, we conducted a transient state analysis on resting-state electroencephalography (EEG) source space and developed a state transfer analysis to patients with disorders of consciousness (DOC). They uncovered different neural coordination patterns, including spatial power patterns, temporal dynamics, spectral shifts, and connectivity construction varies at potentially very fast (millisecond) time scales, in groups with different consciousness levels: healthy subjects, patients in minimally conscious state (MCS), and patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Machine learning based on transient state features reveal high classification accuracy between MCS and VS/UWS. This study developed methodology of transient states analysis on EEG source space and abnormal brain conditions. Findings correlate spontaneous transient states with human consciousness and suggest potential roles of transient states in brain disease assessment.

Non-invasive brain intervention techniques used in patients with disorders of consciousness.

Aim of the study: With the development of emergency medicine and intensive care technology, the number of people who survive with disorders of consciousness (DOC) has dramatically increased. The diagnosis and treatment of such patients have attracted much attention from the medical community. From the latest evidence-based guidelines, non-invasive brain intervention (NIBI) techniques may be valuable and promising in the diagnosis and conscious rehabilitation of DOC patients.Methods: This work reviews the studies on NIBI techniques for the assessment and intervention of DOC patients.Results: A large number of studies have explored the application of NIBI techniques in DOC patients. The NIBI techniques include transcranial magnetic stimulation, transcranial electric stimulation, music stimulation, near-infrared laser stimulation, focused shock wave therapy, low-intensity focused ultrasound pulsation and transcutaneous auricular vagus nerve stimulation.Conclusions: NIBI techniques present numerous advantages such as being painless, safe and inexpensive; having adjustable parameters and targets; and having broad development prospects in treating DOC patients.

The misdiagnosis of prolonged disorders of consciousness by a clinical consensus compared with repeated coma-recovery scale-revised assessment.

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.

Burnout syndrome in healthcare professionals who care for patients with prolonged disorders of consciousness: a cross-sectional survey.

BACKGROUND: Burnout is more common among healthcare professionals, that is an important problem of professional distress that can seriously affect healthcare professionals' emotional state, health, medical quality and doctor-patient relationship. However, only few studies researched the burnout status of healthcare professionals who care for patients with prolonged disorders of consciousness. The aim of this study was to evaluate the level of burnout and related contributing personal and environment factors in healthcare professionals managing these patients. METHODS: Institution-based cross-sectional study. Maslach Burnout Inventory-Human Services Survey was used to evaluate burnout in professionals who specially care for patients with prolonged disorders of consciousness in the neurorehabilitation department. RESULTS: A total of 200 questionnaires were distributed, 121 were collected, among them 93 questionnaires could be used for further analysis. In this study, 61 participants (65.6%) showed burnout (55.2% physicians and 82.9% nurses). For the risks and Maslach Burnout Inventory scores, emotional exhaustion and depersonalization were correlated with age, gender, occupation, marital status, years of practice, and education level. Reduced personal accomplishment was correlated with marital status. The variables of age (< 29 years old), occupation (nurses), marital status (unmarried), years of practice (< 5 years), and educational level (≤ Undergraduate) were associated with high levels of burnout. CONCLUSIONS: Healthcare professionals who care for patients with disorders of consciousness experienced high levels of burnout. Especially those who were younger, nurse, unmarried, less practice experience or lower educational levels were more likely to experience high burnout.

A study of the reliability and validity of the Chinese version of the Nociception Coma Scale-Revised.

OBJECTIVE: The aim of the study was to check on the reliability and validity of the translated version of Nociception Coma Scale-Revised. DESIGN: Prospective psychometric study. SETTING: Rehabilitation and neurology unit in hospital. SUBJECTS: Patients with prolonged disorders of consciousness. INTERVENTIONS: None. MAIN MEASURES: The original English version of the Nociception Coma Scale-Revised was translated into Chinese. The reliability and validity were undertaken by trained raters. Intraclass correlation coefficients were used to assess inter-rater reliability and test-retest reliability. Cronbach's alpha test was used to investigate internal consistency. Spearman's correlation was used to calculate concurrent validity. The Coma Recovery Scale-revised was used to assess the consciousness of patients. RESULTS: Eighty-four patients were enrolled in the study. Inter-rater reliability of the Chinese version of Nociception Coma Scale-Revised was high for total scores and motor and verbal subscores and good for facial subscores. Test-retest reliability was high for total score and for all subscores. Analysis revealed a moderate internal consistency for subscores. For the concurrent validity, a strong correlation was found between the Nociception Coma Scale-Revised and the Face, Legs, Activity, Cry, and Consolability behavioral scale for all patients. A moderate correlation was found between the Nociception Coma Scale-Revised and the Coma Recovery Scale-revised scores for all patients. CONCLUSION: The Chinese version of Nociception Coma Scale-Revised has good reliability and validity data for assessing responses to pain in patients with prolonged disorders of consciousness.

Clinical application of Chinese Nanjing persistent vegetative state scale.

BACKGROUND: It is a challenge to characterize the consciousness level of patients with severe disturbance of consciousness and predict their prognosis effectively for Chinese doctors. We aimed to investigate the psychometric property and the diagnostic practicality of severe disturbance of consciousness by Chinese Nanjing persistent vegetative state scale (CNPVSS) which was first set up in 1996 and modified in 2001 and 2011. METHODS: The concurrent validity, inter-rater consistency and diagnostic accuracy of CNPVSS and Chinese version of coma recovery scale-revised (CRS-R) were investigated by assessment of 380 patients with severe disorders of consciousness. RESULTS: Total scores of the CNPVSS were correlated significantly with that of the CRS-R, indicating acceptable concurrent validity. Sub-scale analysis showed moderate to high inter-rater reliability and test-retest reliability. CNPVSS was superior to CRS-R on the diagnosis sensitivity. The CNPVSS was able to distinguish 65 patients in emergence from minimal consciousness state who were misclassified as in minimal consciousness state (MCS) by the CRS-R, and it could also distinguish two patients in MCS who were misclassified as in vegetative state by the CRS-R. CONCLUSION: The CNPVSS is an appropriate measurement and is sensitive to distinguish the MCS patients from the VS patients.

Ethics of life-sustaining treatment in locked-in syndrome: A Chinese survey.

BACKGROUND: Locked-in syndrome (LIS) characterizes individuals who have experienced pontine lesions, who have limited motor output but with preserved cognitive abilities. Despite their severe physical impairment, individuals with LIS self-profess a higher quality of life than generally expected. Such third-person expectations about LIS are shaped by personal and cultural factors in western countries. OBJECTIVE: We sought to investigate whether such opinions are further influenced by the cultural background in East Asia. We surveyed attitudes about the ethics of life-sustaining treatment in LIS in a cohort of medical and non-medical Chinese participants. RESULTS: The final study sample included 1545 respondents: medical professionals (n=597, 39%), neurologists (n=303, 20%), legal professionals (n=276, 18%) and other professionals (n=369, 24%), including 180 family members of individuals with LIS. Most of the participants (70%), especially neurologists, thought that life-sustaining treatment could not be stopped in individuals with LIS. It might be unnecessary to withdraw life-sustaining treatment, because the condition involved is not terminal and irreversible, and physical treatment can be beneficial for the patient. A significant proportion (59%) of respondents would like to be kept alive if they were in that condition; however, older people thought the opposite. Families experience the stress of caring for individuals with LIS. The mean (SD) quality of life score for relatives was 0.73 (2.889) (on a -5, +5 scale), which was significantly lower than that of non-relatives, 1.75 (1.969) (P<0.001). CONCLUSIONS: Differences in opinions about end of life in LIS are affected by personal characteristics. The current survey did not identify a dissociation between personal preferences and general opinions, potentially because of a social uniformity in China where individualism is less pronounced. Future open-ended surveys could identify specific needs of caregivers so that strategic interventions to reduce ethical debasement are designed.