Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness.

Objective: This study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors. Methods: This study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model. Result: The results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets. Conclusion: This study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.

Analysis of Factors Related to the Efficacy of Consciousness-Regaining Therapy for Prolonged Disorder of Consciousness: A Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to the efficacy of consciousness-regaining therapy (CRT) for prolonged disorder of consciousness. METHODS: A retrospective analysis was conducted on the case data of 114 patients with prolonged disorder of consciousness (pDOC) admitted to the Department of Functional Neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022 to explore the relevant factors that affect the efficacy of CRT for pDOC. Next, basic information on the cases, data on pDOC disease assessment, CRT methods, and efficacy evaluation were collected. RESULTS: These 114 patients were grouped, and a comparative analysis was done based on the efficacy at the end of treatment. Of these, 61 cases were allotted to the ineffective group and 53 cases to the effective group. There was a lack of statistical difference (P > 0.05) between the 2 groups based on gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of CRT, and CRT duration (P > 0.05). However, secondary hydrocephalus, CRT methods, JFK Coma Recovery Scale-Revised grading before treatment, and extended Glasgow Outcome Scale score at six months after treatment were found to be statistically different. The results of binary logistic regression analysis showed that the type of therapy (OR = 0.169, 95% CI: 0.057-0.508) affected the efficacy of CRT (P < 0.05). CONCLUSIONS: Personalized awakening therapy using various invasive CRT methods could improve the efficacy of therapy for pDOC compared with noninvasive therapy.

Brain microstate spatio-temporal dynamics as a candidate endotype of consciousness.

Consciousness can be defined as a phenomenological experience continuously evolving. Current research showed how conscious mental activity can be subdivided into a series of atomic brain states converging to a discrete spatiotemporal pattern of global neuronal firing. Using the high temporal resolution of EEG recordings in patients with a severe Acquired Brain Injury (sABI) admitted to an Intensive Rehabilitation Unit (IRU), we detected a novel endotype of consciousness from the spatiotemporal brain dynamics identified via microstate analysis. Also, we investigated whether microstate features were associated with common neurophysiological alterations. Finally, the prognostic information comprised in such descriptors was analysed in a sub-cohort of patients with prolonged Disorder of Consciousness (pDoC). Occurrence of frontally-oriented microstates (C microstate), likelihood of maintaining such brain state or transitioning to the C topography and complexity were found to be indicators of consciousness presence and levels. Features of left-right asymmetric microstates and transitions toward them were found to be negatively correlated with antero-posterior brain reorganization and EEG symmetry. Substantial differences in microstates' sequence complexity and presence of C topography were found between groups of patients with alpha dominant background, cortical reactivity and antero-posterior gradient. Also, transitioning from left-right to antero-posterior microstates was found to be an independent predictor of consciousness recovery, stronger than consciousness levels at IRU's admission. In conclusions, global brain dynamics measured with scale-free estimators can be considered an indicator of consciousness presence and a candidate marker of short-term recovery in patients with a pDoC.

EEG fractal dimensions predict high-level behavioral responses in minimally conscious patients.

Objective.Brain-injured patients may enter a state of minimal or inconsistent awareness termed minimally conscious state (MCS). Such patient may (MCS+) or may not (MCS-) exhibit high-level behavioral responses, and the two groups retain two inherently different rehabilitative paths and expected outcomes. We hypothesized that brain complexity may be treated as a proxy of high-level cognition and thus could be used as a neural correlate of consciousness.Approach.In this prospective observational study, 68 MCS patients (MCS-: 30; women: 31) were included (median [IQR] age 69 [20]; time post-onset 83 [28]). At admission to intensive rehabilitation, 30 min resting-state closed-eyes recordings were performed together with consciousness diagnosis following international guidelines. The width of the multifractal singularity spectrum (MSS) was computed for each channel time series and entered nested cross-validated interpretable machine learning models targeting the differential diagnosis of MCS±.Main results.Frontal MSS widths (p< 0.05), as well as the ones deriving from the left centro-temporal network (C3:p= 0.018, T3:p= 0.017; T5:p= 0.003) were found to be significantly higher in the MCS+ cohort. The best performing solution was found to be the K-nearest neighbor model with an aggregated test accuracy of 75.5% (median [IQR] AuROC for 100 executions 0.88 [0.02]). Coherently, the electrodes with highest Shapley values were found to be Fz and Cz, with four out the first five ranked features belonging to the fronto-central network.Significance.MCS+ is a frequent condition associated with a notably better prognosis than the MCS-. High fractality in the left centro-temporal network results coherent with neurological networks involved in the language function, proper of MCS+ patients. Using EEG-based interpretable algorithm to complement differential diagnosis of consciousness may improve rehabilitation pathways and communications with caregivers.

Treatments for prolonged disorder of consciousness in recent five years: a visualized analysis / 中国康复理论与实践

ObjectiveTo investigate the current landscape and hotspots on researches about treatment of prolonged disorder of consciousness (pDOC) in the recent five years, and forecast the trends. MethodsLiterature about treatment of pDOC was retrieved from the Web of Science Core Collection database, from January 1st, 2019, to June 7th, 2023. The data were analyzed with CiteSpace 5.8.R3 to create knowledge maps for authors, countries, institutions, keywords, references, co-cited authors and co-cited literature. ResultsA total of 411 articles were included. Aurore Thibaut was the most influential author, Belgium was the most influential country, and Harvard Medical School was the institution with the most publications. The researches focused on neuromodulation, prognostic assessment and care, and management of swallowing function. The neuromodulation techniques mainly included transcranial direct current stimulation, repetitive transcranial magnetic stimulation, deep brain stimulation and transcutaneous auricular vague nerve stimulation. In the coming years, the researches trended to explore neuromodulation and mechanisms of consciousness recovery, and the main neuromodulation techniques might be deep brain stimulation and transcutaneous auricular vague nerve stimulation. ConclusionThe researches about treatment of pDOC are increasing, mainly focusing on neuromodulation, prognostic evaluation, nursing care, and training for swallowing function. More researches would focus on neuromodulation and mechanisms for restoring consciousness.

Effect of repetitive transcranial magnetic stimulation combined with median nerve electrical stimulation on patients with prolonged disorders of consciousness in different age / 中国康复理论与实践

ObjectiveTo investigate the effect of combination with repetitive transcranial magnetic stimulation (rTMS) and median nerve electrical stimulation (MNS) on patients with prolonged disorders of consciousness (pDOC) in different age. MethodsFrom January, 2021 to May, 2023, 93 patients with pDOC in the First Affiliated Hospital of Nanchang University were divided into young group (≤ 45 years old), middle-aged group (46 to 60 years old) and elderly group (> 60 years old). All the groups were treated with rTMS and MNS for four weeks. The Coma Recovery Scale-Revised (CRS-R), Glasgow Coma Scale (GCS), and Full Outline of Unresponsiveness Scale (FOUR) were used to evaluate the efficiency of awakening after treatment and the awakening ratios were compared among three groups weekly. Four weeks after treatment, regional cerebral blood flow (rCBF) was measured with CT perfusion imaging. The score of Glasgow Outcome Scale Extended (GOS-E) was compared six months after treatment. ResultsFrom three weeks after treatment, the scores of CRS-R, GCS and FOUR increased in all groups (P < 0.05). After weekly treatment, there was no significant difference in the composition ratio of consciousness level and the awakening ratio among three groups (χ2 < 11.057, P > 0.05). After four weeks of treatment, rCBF improved in three groups (|t| > 2.495, P < 0.05), however, there was no difference among three groups (F < 1.887, P > 0.05). There was no difference in the score of GOS-E at six months after treatment (F = 3.083, P = 0.055). ConclusionrTMS combined with MNS is effective on pDOC patients in different ages, and elderly patients could also benefit from it.

Modulation of cerebral cortex activity by acupuncture in patients with prolonged disorder of consciousness: An fNIRS study.

Background and objective: Acupuncture is a promising non-pharmacological therapy for patients with prolonged disorder of consciousness (PDOC); however, its underlying mechanism remains uncertain. This study aimed to reveal the modulatory effects of acupuncture on the cerebral cortex activity among patients with PDOC. Materials and methods: Twenty-eight PDOC patients were randomly assigned to the treatment (n = 14) or control (n = 14) group. The treatment group received one session of acupuncture, while the control group received one session of sham acupuncture. All patients underwent evaluation of the functional connectivity and activation response of the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1) via functional near-infrared spectroscopy. We further explored the potential correlation of the consciousness level and activation response/functional connectivity with acupuncture. Results: Compared to the control group, a single session of acupuncture significantly tended to enhance resting-state functional connectivity (rsFC) in DLPFC-M1, DLPFC-M1, and S1-S1. And the activation level of the DLPFC (both sides) in the acupuncture group is significantly higher than those in sham acupuncture group. However, no significant correlation was found between the consciousness level and activation response/functional connectivity. Conclusion: One session of acupuncture has a significant modulation of rsFC and activation in the DLPFC, M1, and S1 with PDOC patients. Acupuncture-evoked effect may have some functional significance in PDOC patients. This is an important step toward exploring the acupuncture effects on PDOC patients.

Establishment and evaluation of a prediction model for acute gastrointestinal injury in patients with prolonged disorder of consciousness.

OBJECTIVE: To establish a prediction model for acute gastrointestinal injury (AGI) in patients with prolonged disorder of consciousness (pDOC) and to evaluate and apply the prediction model.  METHODS: The clinical data of 165 patients with pDOC admitted to the hyperbaric oxygen department from January 2021 to December 2021 were retrospectively reviewed, and the patients were divided into an AGI group (n = 91) and an N-AGI group (n = 74) according to whether AGI occurred. A prediction model was built by fitting multiple independent influencing factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model, the Hosmer-Lemeshow (H-L) test was used to evaluate the goodness-of-fit of the model, and the ROC curve and calibration curve were drawn to evaluate the predictive performance. A nomogram was plotted to visualize the prediction model. RESULTS: According to the multivariate logistic regression analysis results, the prediction model was finally constructed with the CRS-R score, DAO, PCT, ALB, and I-FABP, and a nomogram was generated. The area under the ROC curve (AUC) of the prediction model was 0.931, the sensitivity was 83.5%, and the specificity was 93.2%. The data were divided into 5 groups for the H-L test (χ2 = 2.54, P = 0.468 > 0.05) and into 10 groups for the H-L test (χ2 = 9.98, P = 0.267 > 0.05). A calibration curve was drawn based on the test results, indicating that the prediction model has a good goodness-of-fit and good prediction stability. CONCLUSION: The prediction model for AGI in pDOC patients constructed in this study can be used in clinical practice and is helpful to predict the occurrence of AGI in pDOC patients.

Effectiveness of transcranial direct current stimulation over dorsolateral prefrontal cortex in patients with prolonged disorders of consciousness: A systematic review and meta-analysis.

Background: Transcranial direct current stimulation (tDCS) has been widely studied for treatment of patients with prolonged disorders of consciousness (PDOC). The dorsolateral prefrontal cortex (DLPFC) is a hot target for intervention, but some controversies remain. Purpose: This review aimed to systematically investigate the therapeutic effects of DLPFC-anodal-tDCS for patients with PDOC through a meta-analysis approach. Data sources: Searches for relevant articles available in English were conducted using EMBASE, Medline, Web of Science, EBSCO, and Cochrane Central Register of Controlled Trials from inception until March 26, 2022. Study selection: All randomized parallel or cross-over controlled trials comparing the effect of intervention with active-tDCS and Sham-tDCS on Coma Recovery Scale Revised (CRS-R) score in individuals with PDOC were included. Data extraction: Two authors independently extracted data, assessed the methodological quality, and rated each study. Data synthesis: Ten randomized parallel or cross-over controlled trials were eligible for systematic review, and eight of the studies involving 165 individuals were identified as eligible for meta-analysis. Compared with Sham-tDCS, the use of anode-tDCS over DLPFC improved the CRS-R score (SMD = 0.71; 95% CI: 0.47-0.95, I 2 = 10%). Patients with PDOC classified as MCS and clinically diagnosed as CVA or TBI may benefit from anode-tDCS. Limitations: Failure to evaluate the long-term effects and lack of quantitative analysis of neurological examination are the main limitations for the application of anode-tDCS. Conclusions: Anodal-tDCS over the left DLPFC may be advantageous to the recovery of patients with MCS and clinically diagnosed with CVA or TBI. There is a lack of evidence to support the duration of the disease course will limit the performance of the treatment. Further studies are needed to explore the diversity of stimulation targets and help to improve the mesocircuit model. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=279391, identifier: CRD42022279391.

Recent advance in event-related potentials in assessment of prolonged disorders of consciousness / 中华神经医学杂志

Event-related potentials (ERPs), especially N100, mismatch negative, P300 and N400, play important roles in the evaluation of consciousness and prognoses of patients with prolonged disorders of consciousness (pDOC). The improvement of ERPs experimental paradigm, analysis of brain origin and brain network of ERPs components, and combination of ERPs with other techniques are the research hotspots in pDOC evaluation. This article reviews the recent advance in the above directions as follows, in order to provide reference for subsequent clinical research.

Peripheral inflammatory markers in patients with prolonged disorder of consciousness after severe traumatic brain injury.

BACKGROUND: Inflammatory processes are known to be the key secondary effects of severe traumatic brain injury (sTBI). The aim of the present study was to assess the value of peripheral inflammatory markers in the chronic unconscious phase after sTBI. METHODS: This was a prospective cohort study. A total of 101 patients with prolonged disorder of consciousness (DoC) and 22 healthy controls (HC) were enrolled in the study. Serum levels of interleukin (IL)-1ß, -4, -6, -10, -13, and tumor necrosis factor-α (TNF-α) were investigated in patients with prolonged DoC after sTBI. In addition, the Coma Recovery Scale-revised (CRS-R) was used to quantify the consciousness level, and clinical outcomes at 12 months were determined using the Glasgow Outcome Scale (GOS). Predictive logistic model was built based on the demographic characteristics and cytokine levels. RESULTS: At baseline, IL-6, -10, -13, and TNF-α levels were significantly higher in patients with prolonged DoC compared with controls, while no differences in cytokine levels were observed between patients in a vegetative state (VS) and those in a minimally conscious state (MCS). IL-13 and TNF-α were found to be correlated with behavioral scores in patients with prolonged DoC, and were associated with recovery 12 months later. CONCLUSIONS: The results of the study provide information about long-term inflammatory responses in the chronic unconscious phase after brain trauma. Further larger studies are required to validate the value of these inflammatory markers.

Assessing emergence from a prolonged disorder of consciousness: Current opinion and practice in the UK.

BACKGROUND: A patient in PDOC must demonstrate functional object use or functional communication to confirm they have emerged from this state. A range of tasks and stimuli are used and patients must achieve 100% accuracy. As consciousness occurs along a continuum, determining emergence is not straightforward. OBJECTIVE: To establish the opinions of expert clinicians on how emergence is determined in practice. METHODS: An online survey was completed by clinicians working in specialist rehabilitation settings across the UK. Questions were asked about diagnosis and confidence, informal assessment, formal assessment, and family involvement. Descriptive statistics were used to analyse responses to closed questions. Responses to open questions were analysed using thematic analysis. RESULTS: Seventy-five surveys were analysed. Approximately a third (30.4 %) used tasks other than those recommended to determine emergence. A lack of confidence in tasks to detect the return of functional communication was reported by 46.4%. The majority (78.6%) reported they worked with patients who they felt had emerged, but could not demonstrate it based on the current criteria. A range of stimuli were employed, but 30.6% of respondents were not confident they could choose stimuli appropriately. Respondents reported a range of benefits and challenges when involving family in assessment.

How do we build a picture of a patient in prolonged disorder of consciousness?

Accurate diagnosis of prolonged disorders of consciousness can be challenging and requires the input of a specialist interdisciplinary team who are experienced in informal assessment as well as the administration of formal validated observational assessment tools. There is limited guidance on the selection of these assessment tools. This study examines the factors involved in a team's choice making and how choice of assessment helps build a picture of a patient. Twelve clinicians working within a specialist prolonged disorders of consciousness unit participated in the study. Five took part in an individual structured interview and seven took part in a focus group. Data were evaluated using thematic analysis. The results show that there was a range of factors which influenced decisions over choice of assessment tools. No one assessment tool is perfect and therefore participants favour combining the characteristics of two assessment tools in order to achieve a higher-quality assessment. The use of two assessment tools rather than one, is thought to be key in helping to build an overall picture of the patient. The findings of this study may be useful in the training of clinicians working with this specialist caseload, in the future development of tools themselves and in guiding further research into using a combination of assessment tools for best outcome in this patient group.

An NHS Trust and others v Y and another [2018] UKSC 46: Reducing the Role of the Courts in Treatment Withdrawal.

In An NHS Trust and others v Y and another, the Supreme Court was asked to address the question of whether a court order must always be obtained before clinically assisted nutrition and hydration (CANH), which is keeping alive a person with a prolonged disorder of consciousness (PDOC). This case note explores the Court's decision to dispense with the need for such a court order and analyses that important change in approach from the perspective of the right to life protected in Article 2 European Convention on Human Rights (ECHR) as well as in the broader context of end of life decision-making.

How many patients in a prolonged disorder of consciousness might need a best interests meeting about starting or continuing gastrostomy feeding?

OBJECTIVE:: To estimate the number of people in a prolonged disorder of consciousness (PDOC) who may need a formal best interests decision-making process to consider starting and/or continuing life-sustaining treatment each year in the population of a developed country. METHOD:: Identification of studies on people with a PDOC giving information about incidence, and/or prevalence, and/or cause, and/or location of long-term care. Sources included systematic reviews, a new search of MEDLINE (April 2018), and a personal collection of papers. Validating information was sought from existing data on services. RESULTS:: There are few epidemiologically sound studies, most having bias and/or missing information. The best estimate of incidence of PDOC due to acute onset disease is 2.6/100,000/year; the best estimate of prevalence is between 2.0 and 5.0/100,000. There is evidence that prevalence in the Netherlands is about 10% of that in other countries. The commonest documented causes are cerebral hypoxia, stroke, traumatic brain injury, and tumours. There is some evidence suggesting that dementia is a common cause, but PDOC due to progressive disorders has not been studied systematically. Most people receive long-term care in nursing homes, but a significant proportion (10%-15%) may be cared for at home. CONCLUSION:: Each year, about 5/100,000 people will enter a prolonged state of unconsciousness from acute onset and progressive brain damage; and at any one time, there may be 5/100,000 people in that state. However, the evidence is very limited in quality and quantity. The numbers may be greater.

How often is the diagnosis of the permanent vegetative state incorrect? A review of the evidence.

Some research suggests that 40% of people in the vegetative state are misdiagnosed. This review investigates the frequency, nature and causes of reported misdiagnosis of patients in the vegetative state, focusing on the nature of the error. It is a systematic review of all relevant literature, using references from key papers identified. The data are summarized in tables. Five clinical studies of the rate of misdiagnosis in practice were identified, encompassing 236 patients in the vegetative state of whom 80 (34%) were reclassified as having some awareness, often minimal. The studies often included patients in the recovery phase after acute injury, and were poorly reported. Five systematic reviews of signs and technologically based neurophysiological tests were identified, and they showed that most studies were small, lacked accurate or important details, and were subject to bias. Studies were not replicated. Many signs and tests did not differ between people in the vegetative state and in the minimally conscious state, and those that did were unable to diagnose an individual patient. The few single case reports suggest that failure to ensure an accurate diagnosis of the underlying neurological damage and dysfunction could, rarely, lead to significant misdiagnosis usually in patients who had brain-stem damage with little thalamic or cortical damage. Significant misdiagnosis of awareness, with an apparently 'vegetative' patient having good awareness, is rare. Careful neurological assessment of the cause and routine measurement of awareness using the Coma Recovery Scale - Revised should further reduce mistakes.