Re-awakening the brain: Forcing transitions in disorders of consciousness by external in silico perturbation.

A fundamental challenge in neuroscience is accurately defining brain states and predicting how and where to perturb the brain to force a transition. Here, we investigated resting-state fMRI data of patients suffering from disorders of consciousness (DoC) after coma (minimally conscious and unresponsive wakefulness states) and healthy controls. We applied model-free and model-based approaches to help elucidate the underlying brain mechanisms of patients with DoC. The model-free approach allowed us to characterize brain states in DoC and healthy controls as a probabilistic metastable substate (PMS) space. The PMS of each group was defined by a repertoire of unique patterns (i.e., metastable substates) with different probabilities of occurrence. In the model-based approach, we adjusted the PMS of each DoC group to a causal whole-brain model. This allowed us to explore optimal strategies for promoting transitions by applying off-line in silico probing. Furthermore, this approach enabled us to evaluate the impact of local perturbations in terms of their global effects and sensitivity to stimulation, which is a model-based biomarker providing a deeper understanding of the mechanisms underlying DoC. Our results show that transitions were obtained in a synchronous protocol, in which the somatomotor network, thalamus, precuneus and insula were the most sensitive areas to perturbation. This motivates further work to continue understanding brain function and treatments of disorders of consciousness.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

Musical and electrical stimulation as intervention in disorder of consciousness (DOC) patients: A randomised cross-over trial.

BACKGROUND: Disorders of consciousness (DOC), i.e., unresponsive wakefulness syndrome (UWS) or vegetative state (VS) and minimally conscious state (MCS), are conditions that can arise from severe brain injury, inducing widespread functional changes. Given the damaging implications resulting from these conditions, there is an increasing need for rehabilitation treatments aimed at enhancing the level of consciousness, the quality of life, and creating new recovery perspectives for the patients. Music may represent an additional rehabilitative tool in contexts where cognition and language are severely compromised, such as among DOC patients. A further type of rehabilitation strategies for DOC patients consists of Non-Invasive Brain Stimulation techniques (NIBS), including transcranial electrical stimulation (tES), affecting neural excitability and promoting brain plasticity. OBJECTIVE: We here propose a novel rehabilitation protocol for DOC patients that combines music-based intervention and NIBS in neurological patients. The main objectives are (i) to assess the residual neuroplastic processes in DOC patients exposed to music, (ii) to determine the putative neural modulation and the clinical outcome in DOC patients of non-pharmacological strategies, i.e., tES(control condition), and music stimulation, and (iii) to evaluate the putative positive impact of this intervention on caregiver's burden and psychological distress. METHODS: This is a randomised cross-over trial in which a total of 30 participants will be randomly allocated to one of three different combinations of conditions: (i) Music only, (ii) tES only (control condition), (iii) Music + tES. The music intervention will consist of listening to an individually tailored playlist including familiar and self-relevant music together with fixed songs; concerning NIBS, tES will be applied for 20 minutes every day, 5 times a week, for two weeks. After these stimulations two weeks of placebo treatments will follow, with sham stimulation combined with noise for other two weeks. The primary outcomes will be clinical, i.e., based on the differences in the scores obtained on the neuropsychological tests, such as Coma Recovery Scale-Revised, and neurophysiological measures as EEG, collected pre-intervention, post-intervention and post-placebo. DISCUSSION: This study proposes a novel rehabilitation protocol for patients with DOC including a combined intervention of music and NIBS. Considering the need for rigorous longitudinal randomised controlled trials for people with severe brain injury disease, the results of this study will be highly informative for highlighting and implementing the putative beneficial role of music and NIBS in rehabilitation treatments. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05706831, registered on January 30, 2023.

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.

Verbal Glasgow Coma Scale as predictor of persistent disorder of consciousness: Insights for improving accuracy and reliability in clinical practice.

This brief report discusses the relationship between verbal function, disorders of consciousness, and neurological follow-up after acute brain injury. It provides valuable insights for improving the accuracy and reliability of Verbal Glasgow Coma Scale scoring in clinical practice. The report addresses the need for standardized training and underlines the importance of physiological stabilization before assessment. Clarity in communication, recognition of non-verbal cues, and serial assessments are emphasized as critical factors to reduce the Verbal Glasgow Coma Scale inconsistencies. It also promotes interdisciplinary collaboration and cultural sensitivity to refine the Verbal Glasgow Coma Scale evaluation, improving the prediction of long-term neurological outcomes after acute brain injury and optimizing effective rehabilitation programs. Possible strategies to implement in the routine clinical practice the provided tips are discussed.

Global Field Time-Frequency Representation-Based Discriminative Similarity Analysis of Passive Auditory ERPs for Diagnosis of Disorders of Consciousness.

Behavioural diagnosis of patients with disorders of consciousness (DOC) is challenging and prone to inaccuracies. Consequently, there have been increased efforts to develop bedside assessment based on EEG and event-related potentials (ERPs) that are more sensitive to the neural factors supporting conscious awareness. However, individual detection of residual consciousness using these techniques is less established. Here, we hypothesize that the cross-state similarity (defined as the similarity between healthy and impaired conscious states) of passive brain responses to auditory stimuli can index the level of awareness in individual DOC patients. To this end, we introduce the global field time-frequency representation-based discriminative similarity analysis (GFTFR-DSA). This method quantifies the average cross-state similarity index between an individual patient and our constructed healthy templates using the GFTFR as an EEG feature. We demonstrate that the proposed GFTFR feature exhibits superior within-group consistency in 34 healthy controls over traditional EEG features such as temporal waveforms. Second, we observed the GFTFR-based similarity index was significantly higher in patients with a minimally conscious state (MCS, 40 patients) than those with unresponsive wakefulness syndrome (UWS, 54 patients), supporting our hypothesis. Finally, applying a linear support vector machine classifier for individual MCS/UWS classification, the model achieved a balanced accuracy and F1 score of 0.77. Overall, our findings indicate that combining discriminative and interpretable markers, along with automatic machine learning algorithms, is effective for the differential diagnosis in patients with DOC. Importantly, this approach can, in principle, be transferred into any ERP of interest to better inform DOC diagnoses.

Cortical responses to auditory stimulation predict the prognosis of patients with disorders of consciousness.

OBJECTIVE: This study aimed to assess the prognosis of patients with disorders of consciousness (DoC) using auditory stimulation with electroencephalogram (EEG) recordings. METHODS: We enrolled 72 patients with DoC in the study, which involved subjecting patients to auditory stimulation while EEG responses were recorded. Coma Recovery Scale-Revised (CRS-R) scores and Glasgow Outcome Scale (GOS) were determined for each patient and followed up for three months. A frequency spectrum analysis was performed on the EEG recordings. Finally, the power spectral density (PSD) index was used to predict the prognosis of patients with DoC based on a support vector machine (SVM) model. RESULTS: Power spectral analyses revealed that the cortical response to auditory stimulation showed a decreasing trend with decreasing consciousness levels. Auditory stimulation-induced changes in absolute PSD at the delta and theta bands were positively correlated with the CRS-R and GOS scores. Furthermore, these cortical responses to auditory stimulation had a good ability to discriminate between good and poor prognoses of patients with DoC. CONCLUSIONS: Auditory stimulation-induced changes in the PSD were highly predictive of DoC outcomes. SIGNIFICANCE: Our findings showed that cortical responses to auditory stimulation may be an important electrophysiological indicator of prognosis in patients with DoC.

Spatio-temporal analysis of EEG features during consciousness recovery in patients with disorders of consciousness.

OBJECTIVE: As consciousness recovery is not only dynamic but also involves interactions between various brain regions, elucidating the mechanism of recovery requires tracking cortical activity in spatio-temporal dimensions. METHODS: We tracked the cortical activities of 40 patients (mean age: 54.38 years; 28 males; 21 patients with minimally conscious states) with disorders of consciousness, and collected a total of 156 electroencephalographic signals. We investigated the longitudinal changes in EEG nonlinear dynamic features (i.e., approximate entropy, sample entropy, and Lempel-Ziv complexity) and relative wavelet energy along with consciousness recovery. RESULTS: Global EEG features showed a non-monotonic trend during consciousness recovery (P < 0.05). When the level of consciousness of patients was transferred to a minimally conscious state from an unresponsive wakefulness syndrome/ vegetative state, an inflection point appeared in the EEG features. The EEG feature change trends between the injured and uninjured areas were dissimilar (P < 0.05). Importantly, the degree of dissimilarity increased non-monotonically across the levels of consciousness (P < 0.05). CONCLUSIONS: EEG recovery was non-monotonic and dissimilar in spatio-temporal dimensions, with an inflection point. SIGNIFICANCE: These findings further clarify the process of consciousness recovery and provide assistance in exploring the mechanism of consciousness recovery.

Brain Responses to Propofol in Advance of Recovery from Coma and Disorders of Consciousness: A Preliminary Study.

Rationale: Predicting recovery of consciousness in unresponsive, brain-injured individuals has crucial implications for clinical decision-making. Propofol induces distinctive brain network reconfiguration in the healthy brain as it loses consciousness. In patients with disorders of consciousness, the brain network's reconfiguration to propofol may reveal the patient's underlying capacity for consciousness. Objectives: To design and test a new metric for the prognostication of consciousness recovery in disorders of consciousness. Methods: Using a within-subject design, we conducted an anesthetic protocol with concomitant high-density EEG in 12 patients with a disorder of consciousness after a brain injury. We quantified the reconfiguration of EEG network hubs and directed functional connectivity before, during, and after propofol exposure and obtained an index of propofol-induced network reconfiguration: the adaptive reconfiguration index. We compared the index of patients who recovered consciousness 3 months after EEG (n = 3) to that of patients who did not recover or remained in a chronic disorder of consciousness (n = 7) and conducted a logistic regression to assess prognostic accuracy. Measurements and Main Results: The adaptive reconfiguration index was significantly higher in patients who later recovered full consciousness (U value = 21, P = 0.008) and able to discriminate with 100% accuracy whether the patient recovered consciousness. Conclusions: The adaptive reconfiguration index of patients who recovered from a disorder of consciousness at 3-month follow-up was linearly separable from that of patients who did not recover or remained in a chronic disorder of consciousness on the single-subject level. EEG and propofol can be administered at the bedside with few contraindications, affording the adaptive reconfiguration index tremendous translational potential as a prognostic measure of consciousness recovery in acute clinical settings.

Structural and functional connectivity of the ascending arousal network for prediction of outcome in patients with acute disorders of consciousness.

To determine the role of early acquisition of blood oxygen level-dependent (BOLD) signals and diffusion tensor imaging (DTI) for analysis of the connectivity of the ascending arousal network (AAN) in predicting neurological outcomes after acute traumatic brain injury (TBI), cardiopulmonary arrest (CPA), or stroke. A prospective analysis of 50 comatose patients was performed during their ICU stay. Image processing was conducted to assess structural and functional connectivity of the AAN. Outcomes were evaluated after 3 and 6 months. Nineteen patients (38%) had stroke, 18 (36%) CPA, and 13 (26%) TBI. Twenty-three patients were comatose (44%), 11 were in a minimally conscious state (20%), and 16 had unresponsive wakefulness syndrome (32%). Univariate analysis demonstrated that measurements of diffusivity, functional connectivity, and numbers of fibers in the gray matter, white matter, whole brain, midbrain reticular formation, and pontis oralis nucleus may serve as predictive biomarkers of outcome depending on the diagnosis. Multivariate analysis demonstrated a correlation of the predicted value and the real outcome for each separate diagnosis and for all the etiologies together. Findings suggest that the above imaging biomarkers may have a predictive role for the outcome of comatose patients after acute TBI, CPA, or stroke.

Spontaneous transient brain states in EEG source space in disorders of consciousness.

Spontaneous transient states were recently identified by functional magnetic resonance imaging and magnetoencephalography in healthy subjects. They organize and coordinate neural activity in brain networks. How spontaneous transient states are altered in abnormal brain conditions is unknown. Here, we conducted a transient state analysis on resting-state electroencephalography (EEG) source space and developed a state transfer analysis to patients with disorders of consciousness (DOC). They uncovered different neural coordination patterns, including spatial power patterns, temporal dynamics, spectral shifts, and connectivity construction varies at potentially very fast (millisecond) time scales, in groups with different consciousness levels: healthy subjects, patients in minimally conscious state (MCS), and patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Machine learning based on transient state features reveal high classification accuracy between MCS and VS/UWS. This study developed methodology of transient states analysis on EEG source space and abnormal brain conditions. Findings correlate spontaneous transient states with human consciousness and suggest potential roles of transient states in brain disease assessment.

Virtually spatialized sounds enhance auditory processing in healthy participants and patients with a disorder of consciousness.

Neuroscientific and clinical studies on auditory perception often use headphones to limit sound interference. In these conditions, sounds are perceived as internalized because they lack the sound-attributes that normally occur with a sound produced from a point in space around the listener. Without the spatial attention mechanisms that occur with localized sounds, auditory functional assessments could thus be underestimated. We hypothesize that adding virtually externalization and localization cues to sounds through headphones enhance sound discrimination in both healthy participants and patients with a disorder of consciousness (DOC). Hd-EEG was analyzed in 14 healthy participants and 18 patients while they listened to self-relevant and irrelevant stimuli in two forms: diotic (classic sound presentation with an "internalized" feeling) and convolved with a binaural room impulse response (to create an "externalized" feeling). Convolution enhanced the brains' discriminative response as well as the processing of irrelevant sounds itself, in both healthy participants and DOC patients. For the healthy participants, these effects could be associated with enhanced activation of both the dorsal (where/how) and ventral (what) auditory streams, suggesting that spatial attributes support speech discrimination. Thus, virtually spatialized sounds might "call attention to the outside world" and improve the sensitivity of assessment of brain function in DOC patients.

Prognostic Impact of Branch Vessel Involvement on Computed Tomography versus Clinical Presentation of Malperfusion in Patients With Type a Acute Aortic Dissection.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.

Asymmetric neural dynamics characterize loss and recovery of consciousness.

Anesthetics are known to disrupt neural interactions in cortical and subcortical brain circuits. While the effect of anesthetic drugs on consciousness is reversible, the neural mechanism mediating induction and recovery may be different. Insight into these distinct mechanisms can be gained from a systematic comparison of neural dynamics during slow induction of and emergence from anesthesia. To this end, we used functional magnetic resonance imaging (fMRI) data obtained in healthy volunteers before, during, and after the administration of propofol at incrementally adjusted target concentrations. We analyzed functional connectivity of corticocortical and subcorticocortical networks and the temporal autocorrelation of fMRI signal as an index of neural processing timescales. We found that en route to unconsciousness, temporal autocorrelation across the entire brain gradually increased, whereas functional connectivity gradually decreased. In contrast, regaining consciousness was associated with an abrupt restoration of cortical but not subcortical temporal autocorrelation and an abrupt boost of subcorticocortical functional connectivity. Pharmacokinetic effects could not account for the difference in neural dynamics between induction and emergence. We conclude that the induction and recovery phases of anesthesia follow asymmetric neural dynamics. A rapid increase in the speed of cortical neural processing and subcorticocortical neural interactions may be a mechanism that reboots consciousness.

Very Long-Term Outcomes in Children Admitted in a Disorder of Consciousness After Severe Traumatic Brain Injury.

OBJECTIVES: To investigate functional outcomes and state of consciousness at 1 year and ≥2 years postinjury in children who sustained a traumatic brain injury and were in a disorder of consciousness (DOC), either vegetative state (VS) or minimally conscious state (MCS), upon admission to inpatient rehabilitation. DESIGN: Retrospective chart review. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Children aged 2-18 years (N=37) who were admitted to inpatient rehabilitation with admission scores <30 on the Cognitive and Linguistic Scale (CALS). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Glasgow Outcome Scale- Extended, Pediatric Revision (GOS-E Peds), and state of consciousness based on previously established guidelines. RESULTS: At admission, 16 children were in VS (43.2%) and 21 (56.8%) were in MCS. Children admitted in VS had a significantly longer time from injury to inpatient rehabilitation admission, lower CALS admission scores, were more likely to be in a DOC ≥28 days, and had greater disability at both follow-up time points. At the 1-year follow-up, 3 patients were in VS, 7 were in MCS, and 27 had emerged from MCS. By the time of the most recent follow-up (≥2y), 2 more patients had emerged from MCS. Across the cohort, GOS-E Peds scores at 1 year ranged from VS (GOS-E Peds, 7) to upper moderate disability (GOS-E Peds, 3). Most patients were functioning in the lower severe disability category (GOS-E Peds, 6) at 1 year (43.2%) and at the time of the most recent follow-up (43.2%). Twenty-seven patients (73.0%) showed stable GOS-E Peds scores between the 2 time points, 6 (16.2%) improved, and 4 (10.8%) were deceased. CONCLUSIONS: Although a majority of patients emerged from a DOC by 1 year postinjury, most continued to demonstrate notable functional impairment at the 1-year follow-up that persisted to the most recent follow-up. A small subset demonstrated important improvements between 1 year and the most recent follow-up (2 patients emerged, 6 patients showed improvement in GOS-E Peds scores).

Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality. METHODS: A total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death. RESULTS: A total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04-1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age- and severity-matched controls. CONCLUSIONS: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies.

Substantial progress has been made over the past two decades in detecting, predicting and promoting recovery of consciousness in patients with disorders of consciousness (DoC) caused by severe brain injuries. Advanced neuroimaging and electrophysiological techniques have revealed new insights into the biological mechanisms underlying recovery of consciousness and have enabled the identification of preserved brain networks in patients who seem unresponsive, thus raising hope for more accurate diagnosis and prognosis. Emerging evidence suggests that covert consciousness, or cognitive motor dissociation (CMD), is present in up to 15-20% of patients with DoC and that detection of CMD in the intensive care unit can predict functional recovery at 1 year post injury. Although fundamental questions remain about which patients with DoC have the potential for recovery, novel pharmacological and electrophysiological therapies have shown the potential to reactivate injured neural networks and promote re-emergence of consciousness. In this Review, we focus on mechanisms of recovery from DoC in the acute and subacute-to-chronic stages, and we discuss recent progress in detecting and predicting recovery of consciousness. We also describe the developments in pharmacological and electrophysiological therapies that are creating new opportunities to improve the lives of patients with DoC.

Predicting Outcome of Acquired Brain Injury by the Evolution of Paroxysmal Sympathetic Hyperactivity Signs.

In this multi-center study, we provide a systematic evaluation of the clinical variability associated with paroxysmal sympathetic hyperactivity (PSH) in patients with acquired brain injury (ABI) to determine how these signs can impact outcomes. A total of 156 ABI patients with a disorder of consciousness (DoC) were admitted to neurorehabilitation subacute units (intensive rehabilitation unit; IRU) and evaluated at baseline (T0), after 4 months from event (T1), and at discharge (T2). The outcome measure was the Glasgow Outcome Scale-Extended, whereas age, sex, etiology, Coma Recovery Scale-Revised (CRS-r), Rancho Los Amigos Scale (RLAS), Early Rehabilitation Barthel Index (ERBI), PSH-Assessment Measure (PSH-AM) scores and other clinical features were considered as predictive factors. A machine learning (ML) approach was used to identify the best predictive model of clinical outcomes. The etiology was predominantly vascular (50.8%), followed by traumatic (36.2%). At admission, prevalence of PSH was 31.3%, which decreased to 16.6% and 4.4% at T1 and T2, respectively. At T2, 2.8% were dead and 61.1% had a full recovery of consciousness, whereas 36.1% remained in VS or MCS. A support vector machine (SVM)-based ML approach provides the best model with 82% accuracy in predicting outcomes. Analysis of variable importance shows that the most important clinical factors influencing the outcome are the PSH-AM scores measured at T0 and T1, together with neurological diagnosis, CRS-r, and RLAS scores measured at T0. This joint multi-center effort provides a comprehensive picture of the clinical impact of PSH signs in ABI patients, demonstrating its predictive value in comparison with other well-known clinical measurements.