Disorders of Consciousness

Non-invasive neuromodulation (NIN) techniques have been widely utilized in treating patients with disorders of consciousness (DoC), but their therapeutic effects have been inconsistent. Given the reliance of NIN techniques on synaptic plasticity, and the potential impairment of synaptic plasticity (particularly homeostatic plasticity) resulting from severe brain injury, it is possible that the variation in therapeutic effects is due to alterations in homeostatic plasticity in patients with DoC. Therefore, this study will use preconditioning TMS to examine the retention of homeostatic plasticity in patients with DoC. We will enroll 30 patients with DoC and 15 healthy controls and randomize the order of their sessions. According to the priming protocol, the trial was divided into three different sessions with a 2-day break between each session. The session will involve a 10-min duration of transcranial direct current stimulation (tDCS) priming, followed by a 192-s period of transcranial magnetic stimulation (TMS) test. Transcranial stimulation will be specifically targeted toward the left primary motor cortex. Measurements of motor evoked potentials will be taken at several time points: baseline, after tDCS, and after TMS. Coma Recovery Scale-Revised will be conducted both baseline and after TMS. Studying whether homeostatic plasticity is preserved in patients with DoC is beneficial for gaining a better understanding of their brain condition. If the homeostatic plasticity of patients with DoC is impaired, then NIN, which are based on altering synaptic plasticity in healthy individuals to achieve stimulating effects, may not be directly translatable to the therapeutic interventions for patients with DoC. Instead, the homeostatic plasticity of patients should be restored before implementing the intervention.

The characteristics of disorders of consciousness (DOC) are changes in arousal and/or awareness caused by severe brain injuries. To date, the management of DOC patients remains a complex and challenging task, and neuromodulation techniques offer a promising solution. However, a bibliometric analysis focusing on neuromodulation techniques in DOC is currently absent. The aim of this study is to provide a bibliometric visualization analysis to investigate the research hotspots and frontiers in the field of neuromodulation techniques in DOC from 2012 to 2022. The publications were collected and retrieved from the Web of Science (WoS) from 2012 to 2022. CiteSpace and Microsoft Excel were utilized perform the first global bibliographic analysis of the literature related to neuromodulation techniques for DOC. The analysis included a total of 338 publications. From 2012 to 2022, a consistent yet irregular increase in the number of articles published on neuromodulation techniques in DOC was observed. Frontiers in Neurology published the highest number of papers (n = 16). Neurosciences represented the main research hotspot category (n = 170). The most prolific country, institution, and author were the USA (n = 105), the University of Liege (n = 41), and Laureys Steven (n = 38), respectively. An analysis of keywords revealed that UWS/VS, MCS, and TMS constituted the primary research trends and focal points within this domain. This bibliometric study sheds light on the current progress and emerging trends of neuromodulation techniques in DOC from 2012 to 2022. The focal topics in this domain encompass the precise diagnosis of consciousness levels in patients suffering from DOC and the pursuit of efficacious neuromodulation-based evaluation and treatment protocols for such patients.

Objective To investigate the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with disorders of consciousness. Design and Setting We performed a randomized, double-blinded, sham-controlled trial. Participants Patients (N = 40) with disorders of consciousness. Interventions Forty patients with disorders of consciousness (time since onset of the disorder 49.0 ± 24.6 days) were enrolled and randomized to groups receiving either active-rTMS or sham-rTMS. The active-TMS protocol had a frequency of 20 Hz, was delivered over the left dorsolateral prefrontal cortex and had a 100% rest motor threshold. The sham-rTMS protocol was the same as the active protocol without magnetic stimulation over the cortex. Main Outcome Measures Consciousness was evaluated by the Coma Recovery Scale-Revised (CRS-R) before and after the four-week intervention. The ratio of patients that awakened from disorders of consciousness was followed up at discharge. Results Before rTMS sessions, there were no significant differences in consciousness scores between groups. Compared to sham-rTMS (6.25 ± 1.29), patients with disorders of consciousness treated by active rTMS showed strikingly improved consciousness (8.45 ± 3.55). In-depth analysis revealed that only some patients showed obvious increases in consciousness scores induced by active rTMS. Furthermore, rTMS did not significantly enhance the awakening ratio. Conclusions rTMS showed therapeutic efficacy for improving consciousness in some, but not all, patients with disorders of consciousness. It is essential to discern the potential patients whose consciousness can be improved by rTMS.

The presence or absence of consciousness is the linchpin of taxonomy for disorders of consciousness (DOCs), as well as a focal point for end-of-life decision making for patients with DOCs. Focus on consciousness in this latter context has been criticized for a number of reasons, including the uncertainty of the diagnostic criteria for consciousness, the irrelevance of some forms of consciousness for determining a patient’s interests, and the ambiguous distinction between consciousness and unconsciousness. As a result, there have been recent suggestions that perhaps consciousness ought not to play the focal role that it does in decision making for persons with DOCs, and that other considerations, such as patient and family values, ought to take center stage. In this article, I take a step back and reexamine the meaning of consciousness in the DOC taxonomy. I propose that, while consciousness in DOC taxonomy is defined as “wakeful awareness,” this definition, while clinically expedient, occasions ethical misunderstanding. Using resources from non-Western philosophy of mind, I argue that the form of consciousness that is ethically relevant in DOCs is intransitive, or pure. I contrast this pure experience with transitive consciousness to highlight why ethical conclusions ought not define consciousness solely as “wakeful awareness,” even if clinical criteria do.

The objective of this study was to investigate the value of mismatch negativity (MMN) and P300 event-related potentials for discriminating the consciousness state and predicting improvement of consciousness at 6months in patients with coma and other disorders of consciousness (DOC). We performed MMN and P300 on 42 patients with DOC with a mean onset time of 40.21 ± 19.43days. These patients with DOC were categorized into coma, unresponsive wakefulness syndrome (UWS), minimal consciousness minus (MCS-), and minimal consciousness plus (MCS +) groups according to neurobehavioral assessment and the Coma Recovery Scale-Revised score. The primary outcome was the improvement of consciousness at 6months in patients with DOC. We assessed the efficacy of MMN and P300 in quantitatively predicting the prognosis at 6months and the capability of MMN and P300 parameters to differentiate between DOC. At least one significant difference in either MMN or P300 parameters was displayed among the DOC groups, but not between the MCS- and MCS+ groups (significance level: 0.05). Both MMN and P300 amplitudes showed desirable predictive accuracy at 6months, with areas under the curve (AUCs) of 0.859 and 0.856, respectively. The optimal thresholds for MMN and P300 amplitudes were 2.044 and 1.095μV. However, the combined MMN-P300 amplitude showed better 6-month predictive accuracy (AUC 0.934, 95% confidence interval 0.860-1.000), with a sensitivity of 85% and a specificity of 90.9%. MMN and P300 may help discriminate among coma, UWS, and MCS, but not between patients with MCS- and patients with MCS+ . The MMN amplitude, P300 amplitude, and especially combined MMN-P300 amplitude at 6months may be interesting predictors of consciousness improvement at 6months in patients with DOC. Chinese Clinical Trial Registry identifier ChiCTR2400083798.

Deep brain stimulation (DBS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DoC). DBS is hypothesized to modulate brain activity in local and widespread functional networks by delivering electrical impulses to deep brain nuclei, thereby promoting arousal. This individual patient data meta-analysis aimed to evaluate the therapeutic impact of DBS on improving conscious awareness in patients with DoC and to identify potential predictors of treatment responsiveness. Nine studies comprising 81 patients with DoC who underwent DBS were included. The primary outcome measure across all studies was the Coma Recovery Scale-Revised (CRS-R). Subgroup analyses were performed based on age, duration of DoC, etiology, and DBS target. Study-level data were pooled using random-effects meta-analytic models. The pooled mean CRS-R improvement post-DBS was 2.15 (95% CI: 1.06-3.23), indicating a modest treatment effect. Only 39.5% of patients achieved the minimum clinically important difference of ≥three CRS-R points, and 30.9% transitioned to a higher DoC category. Younger patients with shorter DoC durations tended to show greater improvements. Etiology was largely nonpredictive, although patients with hypoxic-ischemic encephalopathy exhibited marginally better responses. Considerable heterogeneity was observed across studies (I2 = 76.5%). Adverse effects, including infections and seizures, were reported. DBS may confer modest improvements in conscious awareness for selected patients with DoC, but therapeutic benefits remain limited and risks substantial. Rigorous patient selection frameworks and standardized protocols are essential to guide clinical decision-making and future trials.

The management of patients suffering from chronic disorders of consciousness (DOC) inevitably raises important ethical questions about the end of life decisions. Some ethical positions claim respect of human life sacredness and the use of good medical practices require allowing DOC patients to live as long as possible, since no one can arbitrarily end either his/her or others’ life. On the other hand, some currents of thought claim respect of human life dignity, patients’ wishes, and the right of free choice entail allowing the withdrawal of life sustaining therapy. This could happen when patients (or surrogates) believe their own life to be not worth living, or if therapy is not very beneficial, excessively burdensome, or even futile. Indeed, the decision to withdraw therapies in a DOC patient should be guided by reliable information about DOC diagnosis and prognosis and on how the patient would wish to be treated in such a condition. Taking into account such issues, it would be possible to make the decision that more adequately fits a DOC patient’s best interest. This review aims to overview the range of ethical issues referring to end-of-life decisions in DOC patients, with regard to the thorny debate on the sacredness and dignity of human life.

PurposeA potential involvement of thyrotropic axis in influencing the state of consciousness could be hypothesized. We aimed at investigating thyroid function tests as predictors of disorders of consciousness (DoC) and relating recovery in a large cohort of patients with DoC secondary to acquired brain injury (ABI).MethodsThis retrospective, multicenter, cohort study included 151 patients with DoC following ABI, consecutively admitted for a 6-month neurorehabilitation program. Data on etiology of brain injury, evolution of DoC, disability and rehabilitation assessments, and death during rehabilitation were collected at baseline and on discharge. Thyroid function tests (serum TSH, fT4 and fT3 levels) were assessed on admission in all patients and at final discharge in 50 patients.ResultsLower baseline TSH levels and greater TSH increments (ΔTSH) after neurorehabilitation predicted a favorable change in DoC independent of age, sex, BMI, etiology of brain injury and initial DoC subtype (TSH: OR=0.712, CI 95% 0.533-0.951, p=0.01; ΔTSH: OR=2.878, CI 95% 1.147-7.223, p=0.02). On the other hand, neither fT4 nor fT3 or their variations appeared to play any role on DoC changes after 6-months inpatient neurorehabilitation. A lower magnitude of ΔfT4 acted as a strong predictor of improved functional disability level (β=0.655, p=0.002) and cognitive functions (β=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes.ConclusionsSerum TSH levels assessed in the subacute post-ABI phase and its variation during neurorehabilitation could represent a potential biomarker of DoC evolution, while variations in fT4 levels seem to be associated with rehabilitation and cognitive functions. Further studies are needed to investigate the mechanisms underlying these associations.

People with disorders of consciousness (DoC) are characteristically unable to synchronously participate in decision-making about clinical care or research. The inability to self-advocate exacerbates preexisting socioeconomic and geographic disparities, which include the wide variability observed across individuals, hospitals, and countries in access to acute care, expertise, and sophisticated diagnostic, prognostic, and therapeutic interventions. Concerns about equity for people with DoC are particularly notable when they lack a surrogate decision-maker (legally referred to as "unrepresented" or "unbefriended"). Decisions about both short-term and long-term life-sustaining treatment typically rely on neuroprognostication and individual patient preferences that carry additional ethical considerations for people with DoC, as even individuals with well thought out advance directives cannot anticipate every possible situation to guide such decisions. Further challenges exist with the inclusion of people with DoC in research because consent must be completed (in most circumstances) through a surrogate, which excludes those who are unrepresented and may discourage investigators from exploring questions related to this population. In this article, the Curing Coma Campaign Ethics Working Group reviews equity considerations in clinical care and research involving persons with DoC in the following domains: (1) access to acute care and expertise, (2) access to diagnostics and therapeutics, (3) neuroprognostication, (4) medical decision-making for unrepresented people, (5) end-of-life decision-making, (6) access to postacute rehabilitative care, (7) access to research, (8) inclusion of unrepresented people in research, and (9) remuneration and reciprocity for research participation. The goal of this discussion is to advance equitable, harmonized, guideline-directed, and goal-concordant care for people with DoC of all backgrounds worldwide, prioritizing the ethical standards of respect for autonomy, beneficence, and justice. Although the focus of this evaluation is on people with DoC, much of the discussion can be extrapolated to other critically ill persons worldwide.

Neuroimaging biomarkers for the diagnosis and prognosis of patients with disorders of consciousness

To explore the factors that affect the recovery of consciousness in patients with disorders of consciousness following brain trauma. We analyzed the data of 114 patients with disorders of consciousness following brain trauma admitted for rehabilitation. Bilateral logistic regression analysis was used to explore the factors that affected the recovery of the patients' consciousness. A logistic regression model was established and the ROC curve was drawn to obtain the optimal threshold of the prognostic model. Univariate analysis showed that vegetative state duration (P<0.001), CRS-R scores (P<0.001), hydrocephalus (P=0.037), hypertonia (P=0.034), central fever (P=0.035), paroxysmal sympathetic hyperactivity (PSH) (P=0.004), and epilepsy seizures were correlated with the recovery of consciousness. Logistic multivariate analysis showed that central fever (OR=3.493, P=0.044), vegetative state duration (OR=1.016, P=0.008), PSH (OR=4.223, P=0.034) and CRS-R scores (OR=0.640, P=0.002) all significantly affected the recovery of consciousness. The χ2 value of the Hosmer-Lemeshow test was 10.214 (P=0.250), and the goodness of fit of this model indicated an outstanding fitting (c=0.91). The presence of PSH is the one of the most important factor followed by centric fever to affect the outcome of patients with disorders of consciousness. A lower CRS-R score and a longer duration of vegetative state also predict a poor recovery of consciousness in these patients.

Disorders of consciousness are powerful predictors of outcomes including mortality among critically ill patients. Encephalopathy, delirium, and coma are disorders of consciousness frequently encountered by critical care nurses but often classified incorrectly. To provide a greater understanding of disorders of consciousness and to provide standardized assessments and nursing interventions for these disorders. A literature search was conducted by using the terms consciousness, mental status, awareness, arousal, wakefulness, assessment, disorders of consciousness, delirium, encephalopathy, coma, vegetative state, and minimal consciousness. Articles were published in the past 10 years in CINAHL and PubMed. Articles were excluded if they were not in English or directly related to caring for patients with a disorder of consciousness. The remaining 142 articles were evaluated for inclusion; 81 articles received full review. A disorder of consciousness signifies that the threshold for compensation has been surpassed with potentially irreversible damage. Altered thalamocortical interactions and reduced cortical activity impair communication networks across the various parts of the brain, causing a disturbance in consciousness. The cue-response theory is a model that describes the process and impact of nursing care on recovery from acute brain injury. Appropriate standardized assessments and interventions must be used to manage altered levels of consciousness in critically ill patients. Paying close attention to neurological changes and monitoring them with standardized assessments are critical to implementing early measures to prevent complications.

Death or prolonged disorders of consciousness (DOC) of a loved one are both considered relational-losses that severely disrupt attachment-bonds. Grief in both conditions was compared by exploring the impact of familial-role and attachment-orientation. In DOC, caregivers’ grief was found significantly intensified relative to Death. Familial-role impacted grief in both conditions alike, with partners' heightened grief in DOC reflecting the complexity of their stagnant bonds. In Death, avoidance-attachment mitigated grief, while in DOC anxiety-attachment accentuated grief, we suggest that while physical-separation in death facilitates the modification of continuing attachment-schema, in DOC, modification may be required while the patient is still alive.

To investigate the diagnostic utility of electrophysiological recordings during active cognitive tasks in detecting residual cognitive capacities in patients with disorders of consciousness (DoC) after severe acquired brain injury. Systematic review of empirical research in MEDLINE, Embase, PsycINFO, and Cochrane from January 2002 to March 2016. Data extracted included sample size, type of electrophysiological technique and task design, rate of cognitive responders, false negatives and positives, and excluded subjects from the study analysis. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality appraisal of the retrieved literature. Twenty-four studies examining electrophysiological signs of command-following in patients with DoC were identified. Sensitivity rates in healthy controls demonstrated variable accuracy across the studies, ranging from 71% to 100%. In patients with DoC, specificity and sensitivity rates varied in the included studies, ranging from 0% to 100%. Pronounced heterogeneity was found between studies regarding methodological approaches, task design, and procedures of analysis, rendering comparison between studies challenging. We are still far from establishing precise recommendations for standardized electrophysiological diagnostic procedures in DoC, but electrophysiological methods may add supplemental diagnostic information of covert cognition in some patients with DoC.

Disorders of consciousness include coma (cannot be aroused, eye remain closed), vegetative state-VS (can appear to be awake, but unable to purposefully interact) and minimally conscious state-MCS (minimal but definite awareness). The objective of this study is to assess the impact of the SARS-CoV-2 infection on the Disorder of Consciousness (DOC) Rehabilitation Unit. This is a retrospective, longitudinal, descriptive, observational, pilot study. We consecutively enrolled 18 patients (age range: 40-72 years, 9 females and 9 males), from three to five months after a brain injury. They were grouped into VS (n = 8) and MCS (n = 10). A confirmed case of COVID-19 was defined as a positive result on high-throughput sequencing or real-time reverse-transcription polymerase chain reaction analysis of throat swab specimens. We collected data of lung Computed Tomography (CT) and laboratory exams. DOC patients who were positive for SARS-CoV-2 were classified into severe and no severe infected group, according to the American Thoracic Society guidelines. A total of 18 hospitalized patients with (16) and without confirmed (2) SARS-CoV-2 infection were included in the analysis. After one month, a follow-up clinical evaluation reported that one patient died, one patient was transferred from Covid Unit to Emergency Unit and 3 patients were resulted negative to double swab and they returned to Rehabilitative Unit. Significant differences were reported about hypertension, cardiac disease and respiratory problems between the patients with severe infection and patients without severe infection (P< 0.001). The laboratory findings, such as blood cell counts (P < 0.001), C-reactive protein, D-dimer, potassium and vitamin D levels, seemed to be considered as useful prognostic predictors. To our knowledge, this is the first longitudinal study on a sample of chronic DOC patients affected by SARS-CoV-2. This study may offer important new clinical information on COVID-19 for management of DOC patients. Our findings showed that for the subjects with severe infection due to COVID-19, rapid clinical deterioration or worsening could be associated with clinical and laboratory findings, which could contribute to high mortality rate. During the COVID-19 epidemic period, the clinicians should consider all the reported risk factors to avoid delayed diagnosis or misdiagnosis and to prevent the infection transmission in DOC Rehabilitation Unit.