Development and validation of a nomogram for tracheotomy decannulation in individuals in a persistent vegetative state: A multicentre study.

BACKGROUND: Decannulation for people in a persistent vegetative state (PVS) is challenging and relevant predictors of successful decannulation have yet to be identified. OBJECTIVE: This study aimed to explore the predictors of tracheostomy decannulation outcomes in individuals in PVS and to develop a nomogram. METHOD: In 2022, 872 people with tracheostomy in PVS were retrospectively enrolled and their data was randomly divided into a training set and a validation set in a 7:3 ratio. Univariate and multivariate regression analyses were performed on the training set to explore the influencing factors for decannulation and nomogram development. Internal validation was performed using 5-fold cross-validation. External validation was performed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) on both the training and validation sets. RESULT: Data from 610 to 262 individuals were used for the training and validation sets, respectively. The multivariate regression analysis found that duration of tracheostomy tube placement≥30 days (Odds Ratio [OR] 0.216, 95 % CI 0.151-0.310), pulmonary infection (OR 0.528, 95 %CI 0.366-0.761), hypoproteinemia (OR 0.669, 95 % CI 0.463-0.967), no passive standing training (OR 0.372, 95 % CI 0.253-0.547), abnormal swallowing reflex (OR 0.276, 95 % CI 0.116-0.656), mechanical ventilation (OR 0.658, 95 % CI 0.461-0.940), intensive care unit (ICU) duration>4 weeks (OR 0.517, 95 % CI 0.332-0.805), duration of endotracheal tube (OR 0.855, 95 % CI 0.803-0.907), older age (OR 0.981, 95 % CI 0.966-0.996) were risk factors for decannulation failure. Conversely, peroral feeding (OR 1.684, 95 % CI 1.178-2.406), passive standing training≥60 min (OR 1.687, 95 % CI 1.072-2.656), private caregiver (OR 1.944, 95 % CI 1.350-2.799) and ICU duration<2 weeks (OR 1.758, 95 % CI 1.173-2.634) were protective factors conducive to successful decannulation. The 5-fold cross-validation revealed a mean area under the curve of 0.744. The ROC curve C-indexes for the training and validation sets were 0.784 and 0.768, respectively, and the model exhibited good stability and accuracy. The DCA revealed a net benefit when the risk threshold was between 0 and 0.4. CONCLUSION: The nomogram can help adjust the treatment and reduce decannulation failure. REGISTRATION: Clinical registration is not mandatory for retrospective studies.

[Neuromodulatory pharmacotherapy individualization in prolonged and chronic consciousness disorders after severe traumatic brain injury]. / K probleme individualizatsii neiromodulyatornoi farmakoterapii pri prolongirovannykh i khronicheskikh narusheniyakh soznaniya vsledstvie tyazheloi cherepno-mozgovoi travmy.

One of the most probable causes of effective therapy for post-comatose disorders of consciousness is the lack of individualization of drug prescriptions. In this observational study, we analyzed 48 courses of neuromodulatory therapy in 28 patients with prolonged and chronic disorders of consciousness following severe traumatic brain injury. Comparison of 24 effective and 24 ineffective courses demonstrated higher effectiveness of pharmacotherapy through its individualization, i.e. the choice of a drug whose neuromodulatory spectrum would correspond to neurological syndromes of neurotransmitter dysfunction. In this approach, 74% of therapy courses were effective while opposite management resulted only 34% of effective courses.

Task-based EEG and fMRI paradigms in a multimodal clinical diagnostic framework for disorders of consciousness.

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

Single session of intermittent theta burst stimulation alters brain activity of patients in vegetative state.

BACKGROUND: Non-invasive brain stimulation is considered as a promising technology for treating patients with disorders of consciousness (DOC). Various approaches and protocols have been proposed; however, few of them have shown potential effects on patients with vegetative state (VS). This study aimed to explore the neuro-modulation effects of intermittent theta burst stimulation (iTBS) on the brains of patients with VS and to provide a pilot investigation into its possible role in treating such patients. METHODS: We conducted a sham-controlled crossover study, a real and a sham session of iTBS were delivered over the left dorsolateral prefrontal cortex of such patients. A measurement of an electroencephalography (EEG) and a behavioral assessment of the Coma Recovery Scale-Revised (CRS-R) were applied to evaluate the modulation effects of iTBS before and after stimulation. RESULTS: No meaningful changes of CRS-R were found. The iTBS altered the spectrum, complexity and functional connectivity of the patients. The real stimulation induced a trend of decreasing of delta power at T1 and T2 in the frontal region, significant increasing of permutation entropy at the T2 in the left frontal region. In addition, brain functional connectivity, particularly inter-hemispheric connectivity, was strengthened between the electrodes of the frontal region. The sham stimulation, however, did not induce any significant changes of the brain activity. CONCLUSIONS: One session of iTBS significantly altered the oscillation power, complexity and functional connectivity of brain activity of VS patients. It may be a valuable tool on modulating the brain activities of patients with VS.

Modulation of Corticospinal Excitability during Action Observation in Patients with Disorders of Consciousness.

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.

Neurobehavioral Progress and Signs of Transition in Children With Prolonged Disorders of Consciousness: A Retrospective Longitudinal Study With the Coma Recovery Scale-Revised.

BACKGROUND: 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). METHODS: Systematic weekly assessments were conducted with the Coma Recovery Scale-Revised (CRS-R) until emergence from MCS, discharge, or death. RESULTS: 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. CONCLUSIONS: 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.

Assessment of Frequency and Predictive Value of Comorbidities in Patients With Disorders of Consciousness in the Acute Setting.

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.

Limitation of life sustaining therapy in disorders of consciousness: ethics and practice.

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.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Covert cortical processing: a diagnosis in search of a definition.

Historically, clinical evaluation of unresponsive patients following brain injury has relied principally on serial behavioral examination to search for emerging signs of consciousness and track recovery. Advances in neuroimaging and electrophysiologic techniques now enable clinicians to peer into residual brain functions even in the absence of overt behavioral signs. These advances have expanded clinicians' ability to sub-stratify behaviorally unresponsive and seemingly unaware patients following brain injury by querying and classifying covert brain activity made evident through active or passive neuroimaging or electrophysiologic techniques, including functional MRI, electroencephalography (EEG), transcranial magnetic stimulation-EEG, and positron emission tomography. Clinical research has thus reciprocally influenced clinical practice, giving rise to new diagnostic categories including cognitive-motor dissociation (i.e. 'covert consciousness') and covert cortical processing (CCP). While covert consciousness has received extensive attention and study, CCP is relatively less understood. We describe that CCP is an emerging and clinically relevant state of consciousness marked by the presence of intact association cortex responses to environmental stimuli in the absence of behavioral evidence of stimulus processing. CCP is not a monotonic state but rather encapsulates a spectrum of possible association cortex responses from rudimentary to complex and to a range of possible stimuli. In constructing a roadmap for this evolving field, we emphasize that efforts to inform clinicians, philosophers, and researchers of this condition are crucial. Along with strategies to sensitize diagnostic criteria and disorders of consciousness nosology to these vital discoveries, democratizing access to the resources necessary for clinical identification of CCP is an emerging clinical and ethical imperative.

Disclosing Results of Tests for Covert Consciousness: A Framework for Ethical Translation.

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.

Neuro-orthopaedic assessment and management in patients with prolonged disorders of consciousness: A review.

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.

Covert consciousness.

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.

Brain injury, medical progress, and the disability paradox: Towards an Americans with Abilities Act.

It is helpful to think about the needs of patients with moderate to severe brain injury through the lens of disability law. However, there are limitations to current disability law that contribute to ongoing segregation and marginalization of individuals with severe brain injury. Indeed, one of the paradoxes of American jurisprudence is that more clear constitutional protections accrue to those who have definitively immutable conditions. Thus, as neuroscience brings new therapies to those with brain injury, they may become less protected by the constitutional elements of disability law because their conditions have changed and become mutable. This is the clinical progress that brain injury professionals all seek to achieve, but ironically these advances could potentially degrade the legal protections of patients who benefit from emerging treatments. In this paper, we will critically examine this paradox at the interface of medicine and the law and suggest that the Americans with Disabilities Act (ADA) could be nicely complemented by legislation we have named the Americans with Abilities Act (AWAA). Instead of focusing on disabilities that need protection, the AWAA seeks to sustain and foster newfound abilities made possible by the fruits of medicine and neuroscience.

Ethical issues of nosology in disorders of consciousness.

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.

Pediatric disorders of consciousness: Considerations, controversies, and caveats.

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.

Assessing consciousness and cognition in disorders of consciousness.

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.

EEG Microstate Analysis in Patients with Disorders of Consciousness and Its Clinical Significance.

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.

Cognitive Motor Dissociation: Gap Analysis and Future Directions.

BACKGROUND: Patients with disorders of consciousness who are behaviorally unresponsive may demonstrate volitional brain responses to motor imagery or motor commands detectable on functional magnetic resonance imaging or electroencephalography. This state of cognitive motor dissociation (CMD) may have prognostic significance. METHODS: The Neurocritical Care Society's Curing Coma Campaign identified an international group of experts who convened in a series of monthly online meetings between September 2021 and April 2023 to examine the science of CMD and identify key knowledge gaps and unmet needs. RESULTS: The group identified major knowledge gaps in CMD research: (1) lack of information about patient experiences and caregiver accounts of CMD, (2) limited epidemiological data on CMD, (3) uncertainty about underlying mechanisms of CMD, (4) methodological variability that limits testing of CMD as a biomarker for prognostication and treatment trials, (5) educational gaps for health care personnel about the incidence and potential prognostic relevance of CMD, and (6) challenges related to identification of patients with CMD who may be able to communicate using brain-computer interfaces. CONCLUSIONS: To improve the management of patients with disorders of consciousness, research efforts should address these mechanistic, epidemiological, bioengineering, and educational gaps to enable large-scale implementation of CMD assessment in clinical practice.

Common Data Element for Disorders of Consciousness: Recommendations from the Working Group on Therapeutic Interventions.

BACKGROUND: Over 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. METHODS: The 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). RESULTS: We 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. CONCLUSIONS: The 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.