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Disorders of consciousness represent altered mental status at its most severe, comprising a continuum between coma, the vegetative state/unresponsive wakefulness syndrome, the minimally conscious state, and emergence from the minimally conscious state. Patients often transition between these levels throughout their recovery, and determining a patient's current level can be challenging, particularly in the acute care setting. Although healthcare providers have classically relied on a bedside neurological exam or the Glasgow Coma Scale to aid with assessment of consciousness, studies have identified multiple limitations of doing so. Neurobehavioral assessment measures, such as the Coma Recovery Scale-Revised, have been developed to address these shortcomings. Each behavioral metric has strengths as well as weaknesses when applied in the acute care setting. In this review, we appraise common assessment approaches, outline alternative measures for fine-tuning these assessments in the acute care setting, and highlight strategies for implementing these practices in an interdisciplinary manner. [ABSTRACT FROM AUTHOR]

Cognitive motor dissociation (CMD) is characterized by a dissociation between volitional brain responses and motor control, detectable only through techniques such as electroencephalography (EEG) and functional magnetic resonance imaging. Hence, it has recently emerged as a major challenge in the assessment of patients with disorders of consciousness. Specifically, this review focuses on the prognostic implications of CMD detection during the acute stage of brain injury. CMD patients were identified in each diagnostic category (coma, unresponsive wakefulness syndrome/vegetative state, minimally conscious state minus) with a relatively similar prevalence of around 20%. Current knowledge tends to indicate that the diagnosis of CMD in the acute phase often predicts a more favorable clinical outcome compared with other unresponsive non-CMD patients. Nevertheless, the review underscores the limited research in this domain, probably at least partially explained by its nascent nature and the lack of uniformity in the nomenclature for CMD-related disorders, hindering the impact of the literature in the field. [ABSTRACT FROM AUTHOR]

The Curing Coma Campaign (CCC) and its contributing collaborators identified multiple key areas of knowledge and research gaps in coma and disorders of consciousness (DoC). This step was a crucial effort and essential to prioritize future educational and research efforts. These key areas include defining categories of DoC, assessing DoC using multimodal approach (e.g., behavioral assessment tools, advanced neuroimaging studies), discussing optimal clinical trials' design and exploring computational models to conduct clinical trials in patients with DoC, and establishing common data elements to standardize data collection. Other key areas focused on creating coma care registry and educating clinicians and patients and promoting awareness of DoC to improve care in patients with DoC. The ongoing efforts in these key areas are discussed. [ABSTRACT FROM AUTHOR]

Although research studies have begun to demonstrate relationships between disorders of consciousness and brain network biomarkers, there are limited data on the practical aspects of obtaining such network biomarkers to potentially guide care. As the state of knowledge continues to evolve, guidelines from professional societies such as the American and European Academies of Neurology and many experts have advocated that the risk–benefit ratio for the assessment of network biomarkers has begun to favor their application toward potentially detecting covert consciousness. Given the lack of detailed operationalization guidance and the context of the ethical implications, herein we offer a roadmap based on local institutional experience with the implementation of functional MRI in the neonatal, pediatric, and adult intensive care units of our local government-supported health system. We provide a case-based demonstrative approach intended to review the current literature and to assist with the initiation of such services at other facilities. [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]

Neuroprognostication following acute brain injury (ABI) is a complex process that involves integrating vast amounts of information to predict a patient's likely trajectory of neurologic recovery. In this setting, critically evaluating salient ethical questions is imperative, and the implications often inform high-stakes conversations about the continuation, limitation, or withdrawal of life-sustaining therapy. While neuroprognostication is central to these clinical "life-or-death" decisions, the ethical underpinnings of neuroprognostication itself have been underexplored for patients with ABI. In this article, we discuss the ethical challenges of individualized neuroprognostication including parsing and communicating its inherent uncertainty to surrogate decision-makers. We also explore the population-based ethical considerations that arise in the context of heterogenous prognostication practices. Finally, we examine the emergence of artificial intelligence-aided neuroprognostication, proposing an ethical framework relevant to both modern and longstanding prognostic tools. [ABSTRACT FROM AUTHOR]

Severe brain injury is associated with a period of impaired level of consciousness that can last from days to months and results in chronic impairment. Systematic assessment of level of function in patients with disorders of consciousness (DoC) is critical for diagnosis, prognostication, and evaluation of treatment efficacy. Approximately 40% of patients who are thought to be unconscious based on clinical bedside behavioral assessment demonstrate some signs of consciousness on standardized behavioral assessment. This finding, in addition to a growing body of literature demonstrating the advantages of standardized behavioral assessment of DoC, has led multiple professional societies and clinical guidelines to recommend standardized assessment over routine clinical evaluation of consciousness. Nevertheless, even standardized assessment is susceptible to biases and misdiagnosis, and examiners should consider factors, such as fluctuating arousal and aphasia, that may confound evaluation. We review approaches to behavioral assessment of consciousness, recent clinical guideline recommendations for use of specific measures to evaluate patients with DoC, and strategies for mitigating common biases that may confound the examination. [ABSTRACT FROM AUTHOR]

Therapeutic options for patients with disorders of consciousness (DoC) are still underexplored. Noninvasive brain stimulation (NIBS) techniques modulate neural activity of targeted brain areas and hold promise for the treatment of patients with DoC. In this review, we provide a summary of published research using NIBS as therapeutic intervention for DoC patients, with a focus on (but not limited to) randomized controlled trials (RCT). We aim to identify current challenges and knowledge gaps specific to NIBS research in DoC. Furthermore, we propose possible solutions and perspectives for this field. Thus far, the most studied technique remains transcranial electrical stimulation; however, its effect remains moderate. The identified key points that NIBS researchers should focus on in future studies are (1) the lack of large-scale RCTs; (2) the importance of identifying the endotypes of responders; and (3) the optimization of stimulation parameters to maximize the benefits of NIBS. [ABSTRACT FROM AUTHOR]

The assessment of residual language abilities in patients with disorders of consciousness (DoC) after severe brain injury is particularly challenging due to their limited behavioral repertoire. Moreover, associated language impairment such as receptive aphasia may lead to an underestimation of actual consciousness levels. In this review, we examine past research on the assessment of residual language processing in DoC patients, and we discuss currently available tools for identifying language-specific abilities and their prognostic value. We first highlight the need for validated and sensitive bedside behavioral assessment tools for residual language abilities in DoC patients. As regards neuroimaging and electrophysiological methods, the tasks involving higher level linguistic commands appear to be the most informative about level of consciousness and have the best prognostic value. Neuroimaging methods should be combined with the most appropriate behavioral tools in multimodal assessment protocols to assess receptive language abilities in DoC patients in the most complete and sensitive manner. [ABSTRACT FROM AUTHOR]

Pharmacologic interventions are commonly used to support rehabilitation efforts of patients with disorders of consciousness (DoC). The 2018 practice guidelines recommend amantadine in adults with traumatic DoC to promote functional recovery, though several other stimulants are used off-label in clinical practice and trials, such as methylphenidate, bromocriptine, levodopa, and zolpidem. Differences in the mechanisms of action, adverse effects, pharmacokinetics, and drug–drug interactions should be considered when selecting the best agent for each individual patient. Overall, pharmacologic stimulants may provide a safe and inexpensive pathway to increased functionality and participation in rehabilitation. This article provides a concise summary of scientific evidence supporting the use of pharmacologic therapies to stimulate recovery of consciousness in patients with DoC. [ABSTRACT FROM AUTHOR]

Prediction of recovery of consciousness after severe brain injury is difficult and limited by a lack of reliable, standardized biomarkers. Multiple approaches for analysis of clinical electroencephalography (EEG) that shed light on prognosis in acute severe brain injury have emerged in recent years. These approaches fall into two major categories: conventional characterization of EEG background and quantitative measurement of resting state or stimulus-induced EEG activity. Additionally, a small number of studies have associated the presence of electrophysiologic sleep features with prognosis in the acute phase of severe brain injury. In this review, we focus on approaches for the analysis of clinical EEG that have prognostic significance and that could be readily implemented with minimal additional equipment in clinical settings, such as intensive care and intensive rehabilitation units, for patients with acute disorders of consciousness. [ABSTRACT FROM AUTHOR]

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

This review provides an ethical analysis of disorders of consciousness (DoC) along the care continuum, from preinjury to injury, acute care to subacute care and early rehabilitation, and finally transitioning to chronic rehabilitation and societal reintegration. We provide an actionable, chronological assessment of ethical issues related to DoC care. This expands upon established ethics literature, which focuses almost exclusively on the clinical encounter for DoC. Our goal is to broaden the aperture of ethical analysis to address how social and environmental conditions predispose some persons to brain injury, and how such conditions might also pose barriers to meaningful societal reintegration after recovery. [ABSTRACT FROM AUTHOR]

The investigation of sleep in disorders of consciousness (DoC) has shown promising diagnostic and prognostic results. However, the methods employed in this field of research are diverse. This leads to confusion in the way forward for both scientific and clinical purposes. We review the literature that has investigated sleep in DoC patients and specifically outline the methodologies used next to the presented results. We highlight what knowledge we currently have and where increased efforts are needed before further clinical implementation. Specifically, the review shows that successful methods may employ a two-stage approach to sleep scoring, where one is the application of loosened standard criteria and the other a more general factor describing closeness of the electroencephalography to a healthy pattern, including a score that describes the extent to which sleep scoring criteria can be applied. This should be performed as part of a multimodal approach that also includes investigations of eye-opening/closure and that of circadian (24-hour) rhythmicity. Taken together, this puts the most promising methodologies in the field together for a comprehensive investigation. Large-scale approaches, incorporating multiple modalities and looking at individual variation, are now needed to advance our understanding of sleep in DoC and its role in diagnosis, treatment, and recovery. [ABSTRACT FROM AUTHOR]

Disorder of consciousness (DoC) after severe brain injury presents numerous challenges to clinicians, as the diagnosis, prognosis, and management are often uncertain. Magnetic resonance imaging (MRI) has long been used to evaluate brain structure in patients with DoC. More recently, advances in MRI technology have permitted more detailed investigations of the brain's structural integrity (via diffusion MRI) and function (via functional MRI). A growing literature has begun to show that these advanced forms of MRI may improve our understanding of DoC pathophysiology, facilitate the identification of patient consciousness, and improve the accuracy of clinical prognostication. Here we review the emerging evidence for the application of advanced MRI for patients with DoC. [ABSTRACT FROM AUTHOR]

In the last few years, functional neuroimaging and electroencephalography-based techniques have been used to address one of the most complex and challenging questions in clinical medicine, that of detecting covert awareness in behaviorally unresponsive patients who have survived severe brain injuries. This is a very diverse population with a wide range of etiologies and comorbidities, as well as variable cognitive and behavioral abilities, which render accurate diagnosis extremely challenging. These studies have shown that some chronic behaviorally unresponsive patients harbor not only covert consciousness but also highly preserved levels of mental life. Building on this work, although in its infancy, the investigation of covert consciousness in acutely brain-injured patients could have profound implications for patient prognosis, treatment, and decisions regarding withdrawal of care. The body of evidence on covert awareness presents a moral imperative to redouble our efforts for improving the quality of life and standard of care for all brain-injured patients with disorders of consciousness. [ABSTRACT FROM AUTHOR]

With the advent of advanced analytical methods applied to functional neuroimaging and neurophysiological data, cerebral conditions have been defined that challenge the established classification of disorders of consciousness. A subset of brain-damaged patients has been identified who cannot carry out motor commands, but who exhibit patterns of cerebral activation during mental imagery tasks that are indistinguishable from those in healthy controls. This condition, termed "cognitive motor dissociation," has overturned many assumptions regarding the detection, diagnosis, prognosis, and care of patients with brain injury. Three factors are likely to influence efforts to improve the classification of disorders of consciousness in the near future: the types of data that will become available to characterize brain states, the modeling paradigms utilized for data analysis, and the ability to implement classification schemes in the clinical setting. Here we review past achievements, present states, and future projections for the classification of impaired consciousness and responsiveness. [ABSTRACT FROM AUTHOR]

The accelerating integration of telehealth technologies in neurology practice has transformed traditional interactions between neurologists and patients, allied clinicians and society. Despite the irnmense promise of these technologies to irnprove systems of neurological care, the infusion of telehealth technologies into neurology practice introduces a host of unique ethical challenges. Proactive consideration of the ethical dimensions of teleneurologyand of the impactof these innovationson thefield of neurology more generally can help to ensure responsible development and deployment across stages of implementation. Toward these ends, this article explores key ethical dimensions of teleneurology practice and policy, presents a normative framework for their consideration, and calls attention to underexplored questions ripe for further study at this evolving nexus of teleneurology and neuroethics. To promote successful and ethically resilient development of teleneurology across diverse con- texts, clinicians, organizational leaders, and information technology specialists should work closely with neuroethicists with the common goal of identifying and rigorously assessing the trajectories and potential limits of teleneurology systems. [ABSTRACT FROM AUTHOR]

Consciousness defines our humanity more than any other biologic phenomena that a clinician might be called upon to examine, diagnose, or treat. When family comes to the bedside of a patient, they hope to find them talking, thinking, and feeling. The complexity of consciousness allows an expansive gradation of dysfunction such that we must consider numerous potential insults, possible interventions, and often an unknown likelihood of recovery. As value-laden questions are more often in the hands of surrogate decision makers, the neurologist is given the herculean task of not only diagnosing and treating alterations of consciousness but also predicting the likely course of the disease to empower surrogates to make a choice most consistent with the preferences of the patient. The degree of uncertainty in the diagnosis and prognosis demands that the clinician consider the ethics of the diagnosis, treatment, and prognostication of disorders of consciousness. Expectations of acute and chronic care, the extent of the formal neurological investigation, the potential of therapeutic trials, the self-fulfilling prophecy that can occur with prognostication, and the challenges of shared decision making are all subjects that we explore. [ABSTRACT FROM AUTHOR]

Graph: Brian L. Edlow, MD Graph: Olivia Gosseries, PhD The past two decades have been a time of rapid progress in detecting and predicting recovery of consciousness in patients with severe brain injuries. New behavioral, neuroimaging, and electrophysiological assessment techniques have begun to reveal signs of consciousness in patients previously believed to be unresponsive. Additional studies have revealed new behavioral signs of consciousness and evidence of language processing in patients with disorders of consciousness. [Extracted from the article]

I also take personal satisfaction in seeing Dr. Edlow, one of my former mentees, becoming such a world authority on this subject, and although I did not know Dr. Gosseries prior to this collaboration, I could not be more impressed with her vast knowledge and insights to the field. The Guest Editors of this issue of I Seminars in Neurology i are Drs. [Extracted from the article]