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BackgroundOver the past 30 years, there have been significant advances in the understanding of the mechanisms associated with loss and recovery of consciousness following severe brain injury. This work has provided a strong grounding for the development of novel restorative therapeutic interventions. Although all interventions are aimed at modulating and thereby restoring brain function, the landscape of existing interventions encompasses a very wide scope of techniques and protocols. Despite vigorous research efforts, few approaches have been assessed with rigorous, high-quality randomized controlled trials. As a growing number of exploratory interventions emerge, it is paramount to develop standardized approaches to reporting results. The successful evaluation of novel interventions depends on implementation of shared nomenclature and infrastructure. To address this gap, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups and charged them with developing common data elements (CDEs). Here, we report the work of the Therapeutic Interventions Working Group.MethodsThe working group reviewed existing CDEs relevant to therapeutic interventions within the National Institutes of Health National Institute of Neurological Disorders and Stroke database and reviewed the literature for assessing key areas of research in the intervention space. CDEs were then proposed, iteratively discussed and reviewed, classified, and organized in a case report form (CRF).ResultsWe developed a unified CRF, including CDEs and key design elements (i.e., methodological or protocol parameters), divided into five sections: (1) patient information, (2) general study information, (3) behavioral interventions, (4) pharmacological interventions, and (5) device interventions.ConclusionsThe newly created CRF enhances systematization of future work by proposing a portfolio of measures that should be collected in the development and implementation of studies assessing novel interventions intended to increase the level of consciousness or rate of recovery of consciousness in patients with disorders of consciousness.

ObjectiveMethodsResultConclusionDescribe the survival, sociodemographic and clinical characteristics of subjects with disorders of consciousness in a reference rehabilitation center, in a developing country.Patients with disorders of consciousness (DoC) caused by acquired neurological injuries, admitted between the years 2002–2018 in a neurorehabilitation center. Extracted data covered demographics, clinical details, survival time, and discharge information. Cox proportional hazard model and Kaplan-Meier analysis were used to reveal, associations with survival.Out of 5064 neurological cases, 159 patients were diagnosed with DoC. The demographic data showed a male dominance (65%), with an average injury age of 42 years. The most common causes were traumatic (41%), anoxic (36%), and vascular (10%), with traffic accidents accounting for 71% of traumatic injuries. The study found that 75% of patients remained in a vegetative state (VS), and 25% in a minimally conscious state (MCS), with an average survival of 2110 days.There were no significant differences in survival days between patients in MCS and VS. Patients with traumatic injuries showed a higher survival rate than those with non-traumatic injuries. Age and etiology were identified as factors associated with a higher risk of death. [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: 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]

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]

OBJECTIVES: For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries. DATA SOURCES: We reviewed salient medical literature regarding covert consciousness. STUDY SELECTION: We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness. DATA EXTRACTION AND DATA SYNTHESIS: We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries. CONCLUSIONS: Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited. [ABSTRACT FROM AUTHOR]

Abstract 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

BACKGROUND: Differential diagnosis of chronic disorders of consciousness remains one of the most difficult problems even for experienced clinicians. AIM: To evaluate the inter-expert consistency and capacity of the researcher-developed structural scale based on magnetic resonance imaging to differentiate chronic disorders of consciousness, named, DOC-MRIDS, on a larger sample of patients. MATERIALS AND METHODS: Sixty patients with a clinically stable status diagnosed with consciousness disorders (vegetative state, n=32; minimally conscious state, n=28) were enrolled. The revised coma recovery scale (CRS-R) was included in the clinical assessment. All patients underwent structural magnetic resonance imaging with 3.0-T Siemens scanners including T2 and T1 sequences. Structural changes were assessed using the DOC-MRIDS scale and included the following features: diffuse cortical atrophy, ventricular enlargement, gyri dilatation, leukoaraiosis, brainstem and/or thalamic degeneration, corpus callosum degeneration, and focal corpus callosum lesions. A total score was calculated. Magnetic resonance imaging data were analyzed by three neuroradiologists, and inter-observer agreement (Krippendorf’s alpha) was assessed. RESULTS: A high inter-examiner agreement of the DOC-MRIDS scale score was found, with α=0.806 (95% confidence interval 0.757–0.849). The vegetative state group had a higher DOC-MRIDS score than the minimally conscious state group (p 0.005). A negative correlation was obtained between CRS-R and DOC-MRIDS scale scores (ρ=–0.457, p 0.0001), individual clinical scale domains, and magnetic resonance imaging features. CONCLUSION: When assessing structural changes in patients with chronic consciousness disorders, the use of the DOC-MRIDS scale helps differentiate the type of such disorders with sufficient specificity, sensitivity, and inter-rater agreement. This scale can be used in clinical practice as an additional differential diagnostic tool.

Abstract 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.

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]

Clinical conversations surrounding the continuation or limitation of life-sustaining therapies (LLST) are both challenging and tragically necessary for patients with disorders of consciousness (DoC) following severe brain injury. Divergent cultural, philosophical and religious perspectives contribute to vast heterogeneity in clinical approaches to LLST—as reflected in regional differences and inter-clinician variability. Here we provide an ethical analysis of factors that inform LLST decisions among patients with DoC. We begin by introducing the clinical and ethical challenge and clarifying the distinction between withdrawing and withholding life-sustaining therapy. We then describe relevant factors that influence LLST decision-making including diagnostic and prognostic uncertainty, perception of pain, defining a 'good' outcome, and the role of clinicians. In concluding sections, we explore global variation in LLST practices as they pertain to patients with DoC and examine the impact of cultural and religious perspectives on approaches to LLST. Understanding and respecting the cultural and religious perspectives of patients and surrogates is essential to protecting patient autonomy and advancing goal-concordant care during critical moments of medical decision-making involving patients with DoC. [ABSTRACT FROM AUTHOR]

The advent of neurotechnologies including advanced functional magnetic resonance imaging and electroencephalography to detect states of awareness not detectable by traditional bedside neurobehavioral techniques (i.e., covert consciousness) promises to transform neuroscience research and clinical practice for patients with brain injury. As these interventions progress from research tools into actionable, guideline-endorsed clinical tests, ethical guidance for clinicians on how to responsibly communicate the sensitive results they yield is crucial yet remains underdeveloped. Drawing on insights from empirical and theoretical neuroethics research and our clinical experience with advanced neurotechnologies to detect consciousness in behaviorally unresponsive patients, we critically evaluate ethical promises and perils associated with disclosing the results of clinical covert consciousness assessments and describe a semistructured approach to responsible data sharing to mitigate potential risks. [ABSTRACT FROM AUTHOR]

Research on disorders of consciousness in children is scarce and includes disparate and barely comparable participants and assessment instruments and therefore provides inconclusive information on the clinical progress and recovery in this population. This study retrospectively investigated the neurobehavioral progress and the signs of transition between states of consciousness in a group of children admitted to a rehabilitation program either with an unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS). Systematic weekly assessments were conducted with the Coma Recovery Scale-Revised (CRS-R) until emergence from MCS, discharge, or death. Twenty-one children, nine admitted with a UWS and 12 admitted in an MCS, were included in the study. Four children with a UWS transitioned to an MCS with a CRS-R of 10 (9.2 to 12.2) by showing visual pursuit, visual fixation, or localization to noxious stimulation. Twelve children emerged from the MCS with a CRS-R of 20.5 (19 to 21.7). Children who emerged from the MCS had had a shorter time postinjury and higher CRS-R at admission, compared with those who did not emerge. Almost half of the children who were admitted with a UWS transitioned to an MCS, and almost all who were admitted in an MCS emerged from this state. Children who emerged had shorter times since injury and higher scores on the CRS-R at admission, compared with those who did not emerge. [ABSTRACT FROM AUTHOR]

Background: Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. Objective: This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). Methods: Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. Results: The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P

Medical comorbidities are frequent in patients with disorders of consciousness (DoC) and their impact on outcomes is under investigation. The aim of this study was to investigate patients with DoC in the acute stage and the influence of comorbidities. Patients admitted to intensive care units and neurological units with a diagnosis of coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) were investigated through the Glasgow Coma Scale (GCS), the Coma Recovery Scale ? Revised (CRS-R) and the Comorbidities Coma Scale (CoCos). Forty-three patients (21 men and 22 women; mean age at admission: 60.4???21.0) were included in the study. The most frequent diagnosis at admission was coma (72%) followed by VS/UWS (14%) and MCS (14%). The most frequent brain injury was subarachnoid hemorrhage (46%). At the 6-month follow-up, 19 patients had died (44%), 15 showed a full recovery of consciousness (35%), 7 were in a condition of emergence from MCS (16%), and 2 showed a persistent VS/UWS (5%). Forty-two (98%) patients showed at least one comorbidity: presence of life-support device (92.9%), anemia (76.2%), arterial hypertension (66,7%), hydrocephalus (45.3%), and respiratory infections (45.2%) were those most frequently reported. At the Multivariable Cox regression, the presence of renal disease (hazard ratio [HR] 33.37; p?=?0.033) and malnutrition (HR 14.52; p?=?0.001) were predictors of missed recovery of full consciousness. Although adverse outcomes are generally predicted by the severity of brain damage, the presence of medical comorbidities in an acute phase could influence outcomes and long-term prognosis.

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = −0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker. [ABSTRACT FROM AUTHOR]

Disorders of Consciousness are divided into two major categories such as vegetative and minimally conscious states. Objective measures that allow correct identification of patients with vegetative and minimally conscious state are needed. EEG microstate analysis is a promising approach that we believe has the potential to be effective in examining the resting state activities of the brain in different stages of consciousness by allowing the proper identification of vegetative and minimally conscious patients. As a result, we try to identify clinical evaluation scales and microstate characteristics with resting state EEGs from individuals with disorders of consciousness. Our prospective observational study included 28 individuals with a disorder of consciousness. Control group included 18 healthy subjects with proper EEG data. We made clinical evaluations using patient behavior scales. We also analyzed the EEGs using microstate analysis. In our study, microstate D coverage differed substantially between vegetative and minimally conscious state patients. Also, there was a strong connection between microstate D characteristics and clinical scale scores. Consequently, we have demonstrated that the most accurate parameter for representing consciousness level is microstate D. Microstate analysis appears to be a strong option for future use in the diagnosis, follow-up, and treatment response of patients with Disorders of Consciousness. [ABSTRACT FROM AUTHOR]

Brain imaging studies have recently provided some evidence in favor of covert cognitive processes that are ongoing in patients with disorders of consciousness (DoC) (e.g., a minimally conscious state and vegetative state/unresponsive wakefulness syndrome) when engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer's motor system maps others' actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, considering that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. The results indicate that some form of motor resonance is spared in a subset of patients with DoC, with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether diagnosed with VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and the difference between the resonance with biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials, following the stimulation of the median nerve at the wrist (i.e., the temporal marker signaling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters. [ABSTRACT FROM AUTHOR]

In disorders of consciousness, verticalization is considered an effective type of treatment to improve motor and cognitive recovery. Our purpose is to investigate neurophysiological effects of robotic verticalization training (RVT) in patients with minimally conscious state (MCS). Thirty subjects affected by MCS due to traumatic or vascular brain injury, attending the intensive Neurorehabilitation Unit of the IRCCS Neurolesi (Messina, Italy), were included in this retrospective study. They were equally divided into two groups: the control group (CG) received traditional verticalization with a static bed and the experimental group (EG) received advanced robotic verticalization using the Erigo device. Each patient was evaluated using both clinical scales, including Levels of Cognitive Functioning (LCF) and Functional Independence Measure (FIM), and quantitative EEG pre (T0) and post each treatment (T1). The treatment lasted for eight consecutive weeks, and sessions were held three times a week, in addition to standard neurorehabilitation. In addition to a notable improvement in clinical parameters, such as functional (FIM) (p < 0.01) and cognitive (LCF) (p < 0.01) outcomes, our findings showed a significant modification in alpha and beta bands post-intervention, underscoring the promising effect of the Erigo device to influence neural plasticity and indicating a noteworthy difference between pre-post intervention. This was not observed in the CG. The observed changes in alpha and beta bands underscore the potential of the Erigo device to induce neural plasticity. The device's custom features and programming, tailored to individual patient needs, may contribute to its unique impact on brain responses. [ABSTRACT FROM AUTHOR]

In rare cases, zolpidem administration has been found to paradoxically improve cognition in patients with brain injury in disorders of consciousness. Two minimally conscious plus (MCS+) patients at baseline, a 24-year-old woman 8 weeks post-traumatic brain injury (TBI) and 23-year-old man 6 weeks post-TBI, demonstrated behavioral improvements after off-label, single-dose administration of 10 mg of zolpidem. The patients demonstrated improved cognition on Coma Recovery Scale-Revised assessment after ingesting zolpidem. In particular, speech was substantially restored as one patient recovered functional communication and both demonstrated intelligible verbalizations for the first-time post-injuries following zolpidem. Overall, evidence is limited regarding the underlying mechanisms of various cognitive improvements in zolpidem response although studies incorporating neuroimaging are promising. The outcomes and similarities between these cases contribute to the current literature and highlight the need for rigorous studies in the future to guide zolpidem trials in patient care for those with DOC. [ABSTRACT FROM AUTHOR]

Eye tracking assessments are clinician dependent and can contribute to misclassification of coma. We investigated responsiveness to videos with and without audio in traumatic brain injury (TBI) subjects using video eye-tracking (VET). We recruited 20 healthy volunteers and 10 unresponsive TBI subjects. Clinicians were surveyed whether the subject was tracking on their bedside assessment. The Coma Recovery Scale-Revised (CRS-R) was also performed. Eye movements in response to three different 30-second videos with and without sound were recorded using VET. The videos consisted of moving characters (a dancer, a person skateboarding, and Spiderman). Tracking on VET was defined as visual fixation on the character and gaze movement in the same direction of the character on two separate occasions. Subjects were classified as "covert tracking" (tracking using VET only), "overt tracking" (VET and clinical exam by clinicians), and "no tracking". A k-nearest-neighbors model was also used to identify tracking computationally. Thalamocortical connectivity and structural integrity were evaluated with EEG and MRI. The ability to obey commands was evaluated at 6- and 12-month follow-up. The average age was 29 (± 17) years old. Three subjects demonstrated "covert tracking" (CRS-R of 6, 8, 7), two "overt tracking" (CRS-R 22, 11), and five subjects "no tracking" (CRS-R 8, 6, 5, 6, 7). Among the 84 tested trials in all subjects, 11 trials (13%) met the criteria for "covert tracking". Using the k-nearest approach, 14 trials (17%) were classified as "covert tracking". Subjects with "tracking" had higher thalamocortical connectivity, and had fewer structures injured in the eye-tracking network than those without tracking. At follow-up, 2 out of 3 "covert" and all "overt" subjects recovered consciousness versus only 2 subjects in the "no tracking" group. Immersive stimuli may serve as important objective tools to differentiate subtle tracking using VET. [ABSTRACT FROM AUTHOR]

The assessment of consciousness states, especially distinguishing minimally conscious states (MCS) from unresponsive wakefulness states (UWS), constitutes a pivotal role in clinical therapies. Despite that numerous neural signatures of consciousness have been proposed, the effectiveness and reliability of such signatures for clinical consciousness assessment still remains an intense debate. Through a comprehensive review of the literature, inconsistent findings are observed about the effectiveness of diverse neural signatures. Notably, the majority of existing studies have evaluated neural signatures on a limited number of subjects (usually below 30), which may result in uncertain conclusions due to small data bias. This study presents a systematic evaluation of neural signatures with large‐scale clinical resting‐state electroencephalography (EEG) signals containing 99 UWS, 129 MCS, 36 emergence from the minimally conscious state, and 32 healthy subjects (296 total) collected over 3 years. A total of 380 EEG‐based metrics for consciousness detection, including spectrum features, nonlinear measures, functional connectivity, and graph‐based measures, are summarized and evaluated. To further mitigate the effect of data bias, the evaluation is performed with bootstrap sampling so that reliable measures can be obtained. The results of this study suggest that relative power in alpha and delta serve as dependable indicators of consciousness. With the MCS group, there is a notable increase in the phase lag index‐related connectivity measures and enhanced functional connectivity between brain regions in comparison to the UWS group. A combination of features enables the development of an automatic detector of conscious states. [ABSTRACT FROM AUTHOR]

This study aimed to verify the reliability and validity of the Japanese version of the Coma Recovery Scale-Revised (CRS-R). Subjects included 59 patients with disorders of consciousness (DOC) due to acquired brain injury. To validate test-retest reliability, Evaluator A assessed the CRS-R twice on the same day (A1, A2). To examine inter-rater reliability, Evaluators A (A2) and B (B) assessed the CRS-R without a time interval. To test concurrent validity, Evaluator A (A1) assessed the CRS-R, Japan Coma Scale (JCS), and the Glasgow Coma Scale (GCS) consecutively. To validate diagnostic accuracy, we evaluated the degree of agreement between A1 and A2 and between A2 and B in their diagnosis of DOC by CRS-R. The test-retest (ρ = 0.92) and inter- (ρ = 0.98) reliability of CRS-R were excellent" and Concurrent validity of CRS-R with JCS (ρ = −0.82) and GCS (ρ = 0.92) were high. Results of DOC diagnosis were consistent for 48/59 cases (κ = 0.82) for A1 and A2 and for 54/59 cases (κ = 0.92) for A2 and B. The Japanese version of the CRS-R may be as reliable and valid as the original English and other language versions. [ABSTRACT FROM AUTHOR]

Detecting willful cognition in these patients is known to be challenging due to the patients' motor disabilities and high vigilance fluctuations but also due to the lack of expertise and use of adequate tools to assess these patients in specific settings. This review will discuss the main disorders of consciousness after severe brain injury, how to assess consciousness and cognition in these patients, as well as the challenges and tools available to overcome these challenges and reach an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Pediatric disorders of consciousness (PedDOC) encompass conditions that may occur following very severe traumatic or other forms of acquired brain injury sustained during childhood. As in adults, PedDOC is described as a disturbance of awareness and/or responsiveness. PedDOC is a complex condition that requires specialized care, infrastructures, and technologies. PedDOC poses many challenges to healthcare providers and caregivers during recovery and throughout development. In this commentary, we intend to highlight some considerations, controversies, and caveats on the diagnosis, prognosis and treatment of PedDOC. [ABSTRACT FROM AUTHOR]

Covert consciousness is a state of residual awareness following severe brain injury or neurological disorder that evades routine bedside behavioral detection. Patients with covert consciousness have preserved awareness but are incapable of self-expression through ordinary means of behavior or communication. Growing recognition of the limitations of bedside neurobehavioral examination in reliably detecting consciousness, along with advances in neurotechnologies capable of detecting brain states or subtle signs indicative of consciousness not discernible by routine examination, carry promise to transform approaches to classifying, diagnosing, prognosticating and treating disorders of consciousness. Here we describe and critically evaluate the evolving clinical category of covert consciousness, including approaches to its diagnosis through neuroimaging, electrophysiology, and novel behavioral tools, its prognostic relevance, and open questions pertaining to optimal clinical management of patients with covert consciousness recovering from severe brain injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Following a severe acquired brain injury, neuro-orthopaedic disorders are commonplace. While these disorders can impact patients' functional recovery and quality of life, little is known regarding the assessment, management and treatment of neuro-orthopaedic disorders in patients with disorders of consciousness (DoC). OBJECTIVE: To describe neuro-orthopaedic disorders in the context of DoC and provide insights on their management and treatment. METHODS: A review of the literature was conducted focusing on neuro-orthopaedic disorders in patients with prolonged DoC. RESULTS: Few studies have investigated the prevalence of spastic paresis in patients with prolonged DoC, which is extremely high, as well as its correlation with pain. Pilot studies exploring the effects of pharmacological treatments and physical therapy show encouraging results yet have limited efficacy. Other neuro-orthopaedic disorders, such as heterotopic ossification, are still poorly investigated. CONCLUSION: The literature of neuro-orthopaedic disorders in patients with prolonged DoC remains scarce, mainly focusing on spastic paresis. We recommend treating neuro-orthopaedic disorders in their early phases to prevent complications such as pain and improve patients' recovery. Additionally, this approach could enhance patients' ability to behaviourally demonstrate signs of consciousness, especially in the context of covert awareness. [ABSTRACT FROM AUTHOR]

The current classification scheme for severe disorders of consciousness (DoC) has several shortcomings. First, there is no consensus on how to incorporate patients with covert consciousness. Second, there is a mismatch between the definitions of severe DoC, based on consciousness, and the diagnosis of these same DoC, which is based on observable motoric responsiveness. Third, current categories are grouped into large heterogeneous syndromes which share phenotype, but do not incorporate underlying pathophysiology. Here we discuss several ethical issues pertaining to the current nosology of severe DoC. We conclude by proposing a revised nosology which addresses these shortcomings. [ABSTRACT FROM AUTHOR]

Diagnostic, prognostic, and therapeutic procedures for patients with prolonged disorders of consciousness (pDoCs) vary significantly across countries and clinical settings, likely due to organizational factors (e.g., research vs. non-academic hospitals), expertise and availability of resources (e.g., financial and human). Two international guidelines, one from the European Academy of Neurology (EAN) and one from the American Academy of Neurology (AAN) in collaboration with the American Congress of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), were developed to facilitate consistent practice among professionals working with this challenging patient population. While the recommendations of both guidelines agree in principle, it remains an open issue how to implement them into clinical practice in the care pathway for patients with pDoCs. We conducted an online survey to explore health professional clinical practices related to the management of patients with pDoCs, and compare said practices with selected recommendations from both the guidelines. The survey revealed that while some recommendations are being followed, others are not and/or may require more honing/specificity to enhance their clinical utility. Particular attention should be given to the implementation of a multimodal assessment of residual consciousness, to the detection and treatment of pain, and to the impact of restrictions imposed by COVID-19 pandemics on the involvement of patients' families/representatives. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potentially effective neuromodulation technique for addressing neurological disorders, including disorders of consciousness. Expanding upon our prior clinical study, which demonstrated the superior effectiveness of a 4-week taVNS treatment in patients with minimally conscious state (MCS) compared to those in a vegetative state/unresponsive wakefulness state, the aim of this investigation was to evaluate the safety and therapeutic efficacy of taVNS in individuals with MCS through a sham-controlled randomized double-blind clinical trial. Methods: A cohort of 50 adult patients (male = 33, female = 17) diagnosed with a MCS were randomly assigned to either the active taVNS (N = 25) or sham taVNS (N = 25) groups. The treatment period lasted for 4 weeks, followed by an 8-week follow-up period. The Coma Recovery Scale-Revised (CRS-R) and Glasgow Coma Scale (GCS) were administered at baseline and weekly during the initial 4 weeks. Additionally, the Disability Rating Scale (DRS) was used to assess the patients’ functional abilities via telephone at week 12. Furthermore, various neurophysiological measures, including electroencephalogram (EEG), upper-limb somatosensory evoked potentials (USEP), brainstem auditory evoked potentials (BAEP), and P300 event-related potentials (P300), were employed to monitor changes in brain activity and neural conduction pathways. Results: The scores for the active taVNS group in the CRS-R and GCS showed greater improvement over time compared to the sham taVNS group (CRS-R: 1-week, Z = −1.248, p = 0.212; 2-week, Z = −1.090, p = 0.276; 3-week, Z = −2.017, p = 0.044; 4-week, Z = −2.267, p = 0.023. GCS: 1-week, Z = −1.325, p = 0.185; 2-week, Z = −1.245, p = 0.213; 3-week, Z = −1.848, p = 0.065; 4-week, Z = −1.990, p = 0.047). Additionally, the EEG, USEP, BAEP, and P300 also demonstrated significant improvement in the active taVNS group compared to the sham taVNS group at week 4 (EEG, Z = −2.086, p = 0.037; USEP, Z = −2.014, p = 0.044; BAEP, Z = −2.298, p = 0.022; P300 amplitude, Z = −1.974, p = 0.049; P300 latency, t = 2.275, p = 0.027). Subgroup analysis revealed that patients with MCS derived greater benefits from receiving taVNS treatment earlier (CRS-R, Disease duration ≤ 1-month, mean difference = 8.50, 95% CI = [2.22, 14.78], p = 0.027; GCS, Disease duration ≤ 1-month, mean difference = 3.58, 95% CI = [0.14, 7.03], p = 0.044). By week 12, the active taVNS group exhibited lower Disability Rating Scale (DRS) scores compared to the sham taVNS group (Z = −2.105, p = 0.035), indicating a more favorable prognosis for MCS patients who underwent taVNS. Furthermore, no significant adverse events related to taVNS were observed during treatment. Conclusion: The findings of this study suggest that taVNS may serve as a potentially effective and safe intervention for facilitating the restoration of consciousness in individuals diagnosed with MCS. This therapeutic approach appears to enhance cerebral functioning and optimize neural conduction pathways. [ABSTRACT FROM AUTHOR]

In the last ten years, technological innovations have led to the development of new, advanced sensory stimulation (SS) tools, such as PC-based rehabilitative programs or virtual reality training. These are meant to stimulate residual cognitive abilities and, at the same time, assess cognition and awareness, also in patients with a minimally conscious state (MCS). Our purpose was to evaluate the clinical and neurophysiological effects of multi-sensory and emotional stimulation provided by Neurowave in patients with MCS, as compared to a conventional SS treatment. The psychological status of their caregivers was also monitored. In this retrospective study, we have included forty-two MCS patients and their caregivers. Each MCS subject was included in either the control group (CG), receiving a conventional SS, or the experimental group (EG), who was submitted to the experimental training with the Neurowave. They were assessed before (T0) and after the training (T1) through a specific clinical battery, including both motor and cognitive outcomes. Moreover, in the EG, we also monitored the brain electrophysiological activity (EEG and P300). In both study groups (EG and CG), the psychological caregiver's aspects, including anxiety levels, were measured using the Zung Self-Rating Anxiety Scale (SAS). The intra-group analysis (T0-T1) of the EG showed statistical significances in all patients' outcome measures, while in the CG, we found statistical significances in consciousness and awareness outcomes. The inter-group analysis between the EG and the CG showed no statistical differences, except for global communication skills. In conclusion, the multi-sensory stimulation approach through Neurowave was found to be an innovative rehabilitation treatment, also allowing the registration of brain activity during treatment. [ABSTRACT FROM AUTHOR]

The diagnosis of unresponsive wakefulness syndrome depends mostly on the motor response following verbal commands. However, there is a potential for misdiagnosis in patients who understand verbal commands (passive response) but cannot perform voluntary movements (active response). To evaluate passive and active responses in such patients, this study used an approach combining functional magnetic resonance imaging and passive listening tasks to evaluate the level of speech comprehension, with portable brain–computer interface modalities that were applied to elicit an active response to attentional modulation tasks at the bedside. We included ten patients who were clinically diagnosed as unresponsive wakefulness syndrome. Two of ten patients showed no significant activation, while limited activation in the auditory cortex was found in six patients. The remaining two patients showed significant activation in language areas, and were able to control the brain–computer interface with reliable accuracy. Using a combined passive/active approach, we identified unresponsive wakefulness syndrome patients who showed both active and passive neural responses. This suggests that some patients with unresponsive wakefulness syndrome diagnosed behaviourally are both wakeful and responsive, and the combined approach is useful for distinguishing a minimally conscious state from unresponsive wakefulness syndrome physiologically. • Passive auditory tasks in fMRI reveal the level of neuronal response. • SSVEP-BCI evokes active response from patients with disorder of consciousness. • The new approach physiologically distinguishes MCS from UWS. [ABSTRACT FROM AUTHOR]

Early neurorehabilitation and passive, upright mobilization strategies have been shown to be beneficial for individuals with disorders of consciousness (DOC). However, literature is limited in illustrating the use of an early, aggressive program with an added focus on dynamic and active upright mobilization. The purpose of this case report is to describe a two-week aggressive, upright standing and walking program with an individual with traumatic brain injury in an acute inpatient rehabilitation setting. The case investigates the association between aggressive mobilization with changes in level of consciousness and daily cognitive, motor and communicative behaviours. A 30-year-old male classified in DOC as minimally conscious state (MCS) participated in an early upright mobilization program. The two-week intervention consisted of aggressive static/passive and dynamic/active upright mobilization activities, involving a multidisciplinary rehabilitation team. Expressive communication, motor responses and current level of consciousness were monitored and assessed twice a day. Additionally, the patient's activation and arousal were subjectively monitored during daily therapy sessions. Following the dynamic/active mobilization activities, the patient demonstrated improved expressive communication, motor scores and increased activation and arousal during the mobilizations. After the two-week intervention, he emerged from DOC. This case report illustrates intense, more active/dynamic upright mobilization with the use of assisted technologies provides promise as an effective intervention for improving communication, motor responses, arousal and level of consciousness in a patient in MCS. Initiating upright, active activity sooner in the recovery process, may lead to improved outcomes and quicker emergence. Aggressive upright mobilization may be delivered safely to patients in DOC early in their rehabilitative care. Aggressive upright mobilization may be beneficial for patients in DOC. Higher intensity, more active/dynamic upright mobilization such as the use of Erigo®Pro + stepping and locomotor training on a treadmill with body weight support demonstrated positive outcomes with expressive communication, motor responses and arousal. Earlier initiation of aggressive mobilization may promote recovery. [ABSTRACT FROM AUTHOR]

Patients with prolonged disorders of consciousness (DOCs) longer than 28 days may continue to make significant gains and achieve functional recovery. Occasionally, this recovery trajectory may extend past 3 (for nontraumatic etiologies) and 12 months (for traumatic etiologies) into the chronic period. Prognosis is influenced by several factors including state of DOC, etiology, and demographics. There are several testing modalities that may aid prognostication under active investigation including electroencephalography, functional and anatomic magnetic resonance imaging, and event-related potentials. At this time, only one treatment (amantadine) has been routinely recommended to improve functional recovery in prolonged DOC. Given that some patients with prolonged or chronic DOC have the potential to recover both consciousness and functional status, it is important for neurologists experienced in prognostication to remain involved in their care. [ABSTRACT FROM AUTHOR]

Recent decades have seen significant expansion of the diagnosis of manifestations of awareness in patients with chronic disorders of consciousness (DOC) through the use of instrumented methods. Application of these methods has led to description of the "covert cognition" phenomenon. The present review addresses studies of the covert cognition in patients with DOC using functional magnetic resonance imaging. Most variants of the passive and active paradigms for this purpose are analyzed and systematized. Special attention is paid to integrated approaches using combinations of different paradigms and investigation methods. The importance of identifying the phenomenon of covert cognition for neurorehabilitation of patients with DOC is emphasized. [ABSTRACT FROM AUTHOR]

Supportive Palliative Care and Hospice professionals frequently attend to Minimally Conscious State (MCS) patients near the end of life and in so doing, face decisions over maintenance or withdrawal of artificial nutrition and hydration. Although both withholding and withdrawal of artificial nutrition and hydration (ANH) in such circumstances are considered by experts in ethics and law to be acceptable, not all families nor health care professionals agree. This paper will explore basic aspects of serious brain injuries, especially MCS, the psychological role of food in interpersonal relationships, and lessons from clinical ethics that can help in goals of care discussions about withdrawal of ANH. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the efficacy and safety of stimulating the vagus nerve in patients with disorders of consciousness (DOCs). Methods: A comprehensive systematic review was conducted, encompassing the search of databases such as PubMed, CENTRAL, EMBASE and PEDro from their inception until July 2023. Additionally, manual searches and exploration of grey literature were performed. The literature review was conducted independently by two reviewers for search strategy, selection of studies, data extraction, and judgment of evidence quality according to the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) Study Quality Scale. Results: A total of 1,269 articles were retrieved, and 10 studies met the inclusion criteria. Among these, there were three case reports, five case series, and only two randomized controlled trials (RCTs). Preliminary studies have suggested that stimulation of vagus nerve can enhance the levels of DOCs in both vegetative state/unresponsive wakefulness state (VS/UWS) and minimally conscious state (MCS). However, due to a lack of high-quality RCTs research and evidencebased medical evidence, no definitive conclusion can be drawn regarding the intervention's effectiveness on consciousness level. Additionally, there were no significant adverse effects observed following stimulation of vagus nerve. Conclusion: A definitive conclusion cannot be drawn from this systematic review as there was a limited number of eligible studies and low-quality evidence. The findings of this systematic review can serve as a roadmap for future research on the use of stimulation of vagus nerve to facilitate recovery from DOCs. [ABSTRACT FROM AUTHOR]

Background: The principal conditions differentiating disorders of consciousness (DOC) patients are the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS). Many individuals who suffer from sudden-onset severe brain injury move through stages of UWS/VS and MCS before regaining full awareness. In some patients, the DOC condition is protracted for years (PDOC). In this study, we observed PDOC patients for 6 months to assess possible changes in their level of consciousness. Methods: We enrolled 40 PDOC patients, 23 UWS/VS and 17 MCS hosted in a dedicated unit for long-term brain injury care. The time from injury was 472 ± 533 days for UWS/VS and 1090 ± 1079 days for MCS. The Wessex Head Injury Matrix (WHIM), Coma Recovery Scale-R (CRS-R), and Nociception Coma Scale were administered monthly for 6 months. Results: During the period of assessment, the percentage of UWS/VS shifted from 58 to 45%, while for the MCS, from 42 to 55%. A positive correlation was found for the UWS/VS patients between the months of observation with the CRS-R total score and WHIM total numbers of behaviors (TNB). In the UWS/VS group, the CRS-R auditive and visual subscales correlated positively with the observation time. During the whole period of observation, 8 patients had constant CRS-R total scores while the WHIM TNB changed in 7 of them. Conclusion: Our findings demonstrated that the monthly assessment of PDOC by means of the CRS-R and WHIM was able to detect also subtle changes in consciousness level. [ABSTRACT FROM AUTHOR]

The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective chart review was conducted to screen for patients diagnosed with MCS/UWS at our rehabilitation center between 2011 and 2020. Patients 18 years or older were included and underwent baseline VUDS after being diagnosed with MCS/UWS. We analyzed urodynamic parameters and subsequent changes in LUT management in this cohort. In total, 32 patients (7 females, 25 males, median age 37 years) with MCS/UWS were included for analysis. While at least one unfavorable VUDS finding (i.e., neurogenic detrusor overactivity [NDO], detrusor sphincter dyssynergia {DSD, high maximum detrusor pressure during storage phase [>40 cmH2O], low-compliance bladder [<20 mL/cmH2O], and vesico–uretero–renal reflux [VUR]) was found in each patient, NDO (78.1%, 25/32) and DSD (68.8%, 22/32) were the two most frequent unfavorable VUDS findings. Following baseline VUDS, new LUT treatment options were established in 56.3% (18/32) of all patients. In addition, bladder-emptying methods were changed in 46.9% (15/32) of all patients, resulting in fewer patients relying on indwelling catheters. Our retrospective exploratory study revealed a high prevalence of NDO and DSD in patients with MCS/UWS, illustrating the importance of VUDS to adapt LUT management in this cohort accordingly. [ABSTRACT FROM AUTHOR]

Abstract Background and objective Electroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients. Methods Resting-state EEG was recorded from twenty-five patients with DOC. Lempel–Ziv complexity (LZC) and permutation Lempel–Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients. Results PLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions. Conclusion Neural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

Abstract Background Decisions about appropriate treatment at the end of life are common in modern healthcare. Non-treatment decisions (NTDs), comprising both withdrawal and withholding of (potentially) life-prolonging treatment are in principle accepted in Norway. However, in practice they may give rise to significant moral problems for health professionals, patients and next of kin. Here, patient values must be considered. It is relevant to study the moral views and intuitions of the general population on NTDs and special areas of contention such as the role of next of kin in decision-making. Methods Electronic survey to members of a nationally representative panel of Norwegian adults. Respondents were presented with vignettes describing patients with disorders of consciousness, dementia, and cancer where patient preferences varied. Respondents answered ten questions about the acceptability of non-treatment decision making and the role of next of kin. Results We received 1035 complete responses (response rate 40.7%). A large majority, 88%, supported the right of competent patients to refuse treatment in general. When an NTD was in line with the patient’s previously expressed preferences, more respondents tended to find NTDs acceptable. More respondents would accept NTDs for themselves than for the vignette patients. In a scenario with an incompetent patient, clear majorities wanted the views of next of kin to be given some but not decisive weight, and more weight if concordant with the patient’s wishes. There were, however, large variations in the respondents’ views. Conclusion This survey of a representative sample of the Norwegian adult population indicates that attitudes to NTDs are often in line with national laws and guidelines. However, the high variance among the respondents and relatively large weight given to next of kin’s views, indicate a need for appropriate dialogue among all stakeholders to prevent conflicts and extra burdens. Furthermore, the emphasis given to previously expressed opinions indicates that advance care planning may increase the legitimacy of NTDs and prevent challenging decision-making processes.