Toward an interventional science of recovery after coma.

Recovery of consciousness after coma remains one of the most challenging areas for accurate diagnosis and effective therapeutic engagement in the clinical neurosciences. Recovery depends on preservation of neuronal integrity and evolving changes in network function that re-establish environmental responsiveness. It typically occurs in defined steps: it begins with eye opening and unresponsiveness in a vegetative state, then limited recovery of responsiveness characterizes the minimally conscious state, and this is followed by recovery of reliable communication. This review considers several points for novel interventions, for example, in persons with cognitive motor dissociation in whom a hidden cognitive reserve is revealed. Circuit mechanisms underlying restoration of behavioral responsiveness and communication are discussed. An emerging theme is the possibility to rescue latent capacities in partially damaged human networks across time. These opportunities should be exploited for therapeutic engagement to achieve individualized solutions for restoration of communication and environmental interaction across varying levels of recovery.

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.

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.

A nomogram based on quantitative EEG to predict the prognosis of nontraumatic coma patients in the neuro-intensive care unit.

OBJECTIVE: We aimed to establish a quantitative electroencephalography-based prognostic prediction model specifically tailored for nontraumatic coma patients to guide clinical work. METHODS: This retrospective study included 126 patients with nontraumatic coma admitted to the First Affiliated Hospital of Chongqing Medical University from December 2020 to December 2022. Six in-hospital deaths were excluded. The Glasgow Outcome Scale assessed the prognosis at 3 months after discharge. The least absolute shrinkage and selection operator regression analysis and stepwise regression method were applied to select the most relevant predictors. We developed a predictive model using binary logistic regression and then presented it as a nomogram. We assessed the predictive effectiveness and clinical utility of the model. RESULTS: After excluding six deaths that occurred within the hospital, a total of 120 patients were included in this study. Three predictor variables were identified, including APACHE II score [39.129 (1.4244-1074.9000)], sleep cycle [OR: 0.006 (0.0002-0.1808)], and RAV [0.068 (0.0049-0.9500)]. The prognostic prediction model showed exceptional discriminative ability, with an AUC of 0.939 (95 % CI: 0.899-0.979). CONCLUSION: A lack of sleep cycles, smaller relative alpha variants, and higher APACHE II scores were associated with a poor prognosis of nontraumatic coma patients in the neurointensive care unit at 3 months after discharge. CLINICAL IMPLICATION: This study presents a novel methodology for the prognostic assessment of nontraumatic coma patients and is anticipated to play a significant role in clinical practice.

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.

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited. METHODS: In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months. RESULTS: A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups. CONCLUSIONS: Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Neuroprognostication Under ECMO After Cardiac Arrest: Are Classical Tools Still Performant?

BACKGROUND: According to international guidelines, neuroprognostication in comatose patients after cardiac arrest (CA) is performed using a multimodal approach. However, patients undergoing extracorporeal membrane oxygenation (ECMO) may have longer pharmacological sedation and show alteration in biological markers, potentially challenging prognostication. Here, we aimed to assess whether routinely used predictors of poor neurological outcome also exert an acceptable performance in patients undergoing ECMO after CA. METHODS: This observational retrospective study of our registry includes consecutive comatose adults after CA. Patients deceased within 36 h and not undergoing prognostic tests were excluded. Veno-arterial ECMO was initiated in patients < 80 years old presenting a refractory CA, with a no flow < 5 min and a low flow ≤ 60 min on admission. Neuroprognostication test performance (including pupillary reflex, electroencephalogram, somatosensory-evoked potentials, neuron-specific enolase) toward mortality and poor functional outcome (Cerebral Performance Categories [CPC] score 3-5) was compared between patients undergoing ECMO and those without ECMO. RESULTS: We analyzed 397 patients without ECMO and 50 undergoing ECMO. The median age was 65 (interquartile range 54-74), and 69.8% of patients were men. Most had a cardiac etiology (67.6%); 52% of the patients had a shockable rhythm, and the median time to return of an effective circulation was 20 (interquartile range 10-28) minutes. Compared with those without ECMO, patients receiving ECMO had worse functional outcome (74% with CPC scores 3-5 vs. 59%, p = 0.040) and a nonsignificant higher mortality (60% vs. 47%, p = 0.080). Apart from the neuron-specific enolase level (higher in patients with ECMO, p < 0.001), the presence of prognostic items (pupillary reflex, electroencephalogram background and reactivity, somatosensory-evoked potentials, and myoclonus) related to unfavorable outcome (CPC score 3-5) in both groups was similar, as was the prevalence of at least any two such items concomitantly. The specificity of each these variables toward poor outcome was between 92 and 100% in both groups, and of the combination of at least two items, it was 99.3% in patients without ECMO and 100% in those with ECMO. The predictive performance (receiver operating characteristic curve) of their combination toward poor outcome was 0.822 (patients without ECMO) and 0.681 (patients with ECMO) (p = 0.134). CONCLUSIONS: Pending a prospective assessment on a larger cohort, in comatose patients after CA, the performance of prognostic factors seems comparable in patients with ECMO and those without ECMO. In particular, the combination of at least two poor outcome criteria appears valid across these two groups.

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain. METHODS: We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation. RESULTS: We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group. CONCLUSIONS: In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).

Characteristics of circulatory failure after out-of-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Circulatory failure after out-of-hospital cardiac arrest (OHCA) as part of the postcardiac arrest syndrome (PCAS) is believed to be caused by an initial myocardial depression that later subsides into a superimposed vasodilatation. However, the relative contribution of myocardial dysfunction and systemic inflammation has not been established. Our objective was to describe the macrocirculatory and microcirculatory failure in PCAS in more detail. METHODS: We included 42 comatose patients after OHCA where circulatory variables were invasively monitored from admission until day 5. We measured the development in cardiac power output (CPO), stroke work (SW), aortic elastance, microcirculatory metabolism, inflammatory and cardiac biomarkers and need for vasoactive medications. We used survival analysis and Cox regression to assess time to norepinephrine discontinuation and negative fluid balance, stratified by inflammatory and cardiac biomarkers. RESULTS: CPO, SW and oxygen delivery increased during the first 48 hours. Although the estimated afterload fell, the blood pressure was kept above 65 mmHg with a diminishing need for norepinephrine, indicating a gradually re-established macrocirculatory homoeostasis. Time to norepinephrine discontinuation was longer for patients with higher pro-brain natriuretic peptide concentration (HR 0.45, 95% CI 0.21 to 0.96), while inflammatory biomarkers and other cardiac biomarkers did not predict the duration of vasoactive pressure support. Markers of microcirculatory distress, such as lactate and venous-to-arterial carbon dioxide difference, were normalised within 24 hours. CONCLUSION: The circulatory failure was initially characterised by reduced CPO and SW, however, microcirculatory and macrocirculatory homoeostasis was restored within 48 hours. We found that biomarkers indicating acute heart failure, and not inflammation, predicted longer circulatory support with norepinephrine. Taken together, this indicates an early and resolving, rather than a late and emerging vasodilatation. TRIAL REGISTRATION: NCT02648061.

A method to assess the default EEG macrostate and its reactivity to stimulation.

OBJECTIVE: The default mode network (DMN) is deactivated by stimulation. We aimed to assess the DMN reactivity impairment by routine EEG recordings in stroke patients with impaired consciousness. METHODS: Binocular light flashes were delivered at 1 Hz in 1-minute epochs, following a 1-minute baseline (PRE). The EEG was decomposed in a series of binary oscillatory macrostates by topographic spectral clustering. The most deactivated macrostate was labeled the default EEG macrostate (DEM). Its reactivity (DER) was quantified as the decrease in DEM occurrence probability during stimulation. A normalized DER index (DERI) was calculated as DER/PRE. The measures were compared between 14 healthy controls and 32 comatose patients under EEG monitoring following an acute stroke. RESULTS: The DEM was mapped to the posterior DMN hubs. In the patients, these DEM source dipoles were 3-4 times less frequent and were associated with an increased theta activity. Even in a reduced 6-channel montage, a DER below 6.26% corresponding to a DERI below 0.25 could discriminate the patients with sensitivity and specificity well above 80%. CONCLUSION: The method detected the DMN impairment in post-stroke coma patients. SIGNIFICANCE: The DEM and its reactivity to stimulation could be useful to monitor the DMN function at bedside.

It's not what you say, it's how you say it: A retrospective study of the impact of prosody on own-name P300 in comatose patients.

OBJECTIVE: The acoustic characteristics of stimuli influence the characteristics of the corresponding evoked potentials in healthy subjects. Own-name stimuli are used in clinical practice to assess the level of consciousness in intensive care units. The influence of the acoustic variability of these stimuli has never been evaluated. Here, we explored the influence of this variability on the characteristics of the subject's own name (SON) P300. METHODS: We retrospectively analyzed 251 disorders of consciousness patients from Lyon and Paris Hospitals who underwent an "own-name protocol". A reverse correlation analysis was performed to test for an association between acoustic properties of own-names stimuli used and the characteristics of the P300 wave observed. RESULTS: Own-names pronounced with increasing pitch prosody showed P300 responses 66 ms earlier than own-names that had a decreasing prosody [IC95% = 6.36; 125.9 ms]. CONCLUSIONS: Speech prosody of the stimuli in the "own name protocol" is associated with latencies differences of the P300 response among patients for whom these responses were observed. Further investigations are needed to confirm these results. SIGNIFICANCE: Speech prosody of the stimuli in the "own name protocol" is a non-negligible parameter, associated with P300 latency differences. Speech prosody should be standardized in SON P300 studies.

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.

Heart rate complexity: An early prognostic marker of patient outcome after cardiac arrest.

OBJECTIVE: Early prognostication in comatose patients after cardiac arrest (CA) is difficult but essential to inform relatives and optimize treatment. Here we investigate the predictive value of heart-rate variability captured by multiscale entropy (MSE) for long-term outcomes in comatose patients during the first 24 hours after CA. METHODS: In this retrospective analysis of prospective multi-centric cohort, we analyzed MSE of the heart rate in 79 comatose patients after CA while undergoing targeted temperature management and sedation during the first day of coma. From the MSE, two complexity indices were derived by summing values over short and long time scales (CIs and CIl). We splitted the data in training and test datasets for analysing the predictive value for patient outcomes (defined as best cerebral performance category within 3 months) of CIs and CIl. RESULTS: Across the whole dataset, CIl provided the best sensitivity, specificity, and accuracy (88%, 75%, and 82%, respectively). Positive and negative predictive power were 81% and 84%. CONCLUSIONS: Characterizing the complexity of the ECG in patients after CA provides an accurate prediction of both favorable and unfavorable outcomes. SIGNIFICANCE: The analysis of heartrate variability by means of MSE provides accurate outcome prediction on the first day of coma.

ICU delirium burden predicts functional neurologic outcomes.

BACKGROUND: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness. METHODS: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016. Altogether, patients were assessed daily for delirium 2941days using the Confusion Assessment Method for the ICU (CAM-ICU). Hospitalization delirium burden (DB) was quantified as number of hospital days with delirium divided by total days at risk. Survival status up to 2.5 years and neurologic outcomes using the Glasgow Outcome Scale were recorded at discharge 3, 6, and 12 months post-discharge. RESULTS: Of 178 patients, 19 (10.7%) were excluded from outcome analyses due to persistent coma. Among the remaining 159, 123 (77.4%) experienced delirium. DB was independently associated with >4-fold increased mortality at 2.5 years following ICU admission (adjusted hazard ratio [aHR], 4.77; 95% CI, 2.10-10.83; P < .001), and worse neurologic outcome at discharge (adjusted odds ratio [aOR], 0.02; 0.01-0.09; P < .001), 3 (aOR, 0.11; 0.04-0.31; P < .001), 6 (aOR, 0.10; 0.04-0.29; P < .001), and 12 months (aOR, 0.19; 0.07-0.52; P = .001). DB in the ICU alone was not associated with mortality (HR, 1.79; 0.93-3.44; P = .082) and predicted neurologic outcome less strongly than entire hospital stay DB. Similarly, the number of delirium days in the ICU and for whole hospitalization were not associated with mortality (HR, 1.00; 0.93-1.08; P = .917 and HR, 0.98; 0.94-1.03, P = .535) nor with neurological outcomes, except for the association between ICU delirium days and neurological outcome at discharge (OR, 0.90; 0.81-0.99, P = .038). CONCLUSIONS: Delirium burden throughout hospitalization independently predicts long term neurologic outcomes and death up to 2.5 years after critical illness, and is more predictive than delirium burden in the ICU alone and number of delirium days.

Background frequency can enhance the prognostication power of EEG patterns categories in comatose cardiac arrest survivors: a prospective, multicenter, observational cohort study.

BACKGROUND: We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns ("highly malignant," "malignant," and "benign") according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest. METHODS: This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3-5) at 1 month. RESULTS: Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the "highly malignant" pattern (40.7%) was most prevalent, followed by the "benign" (33.9%) and "malignant" (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with "malignant" patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of "highly malignant" or "malignant" EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%. CONCLUSIONS: The "highly malignant" patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422 . Registered 11 September 2016-Retrospectively registered.

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.

Complementary roles of neural synchrony and complexity for indexing consciousness and chances of surviving in acute coma.

An open challenge in consciousness research is understanding how neural functions are altered by pathological loss of consciousness. To maintain consciousness, the brain needs synchronized communication of information across brain regions, and sufficient complexity in neural activity. Coordination of brain activity, typically indexed through measures of neural synchrony, has been shown to decrease when consciousness is lost and to reflect the clinical state of patients with disorders of consciousness. Moreover, when consciousness is lost, neural activity loses complexity, while the levels of neural noise, indexed by the slope of the electroencephalography (EEG) spectral exponent decrease. Although these properties have been well investigated in resting state activity, it remains unknown whether the sensory processing network, which has been shown to be preserved in coma, suffers from a loss of synchronization or information content. Here, we focused on acute coma and hypothesized that neural synchrony in response to auditory stimuli would reflect coma severity, while complexity, or neural noise, would reflect the presence or loss of consciousness. Results showed that neural synchrony of EEG signals was stronger for survivors than non-survivors and predictive of patients' outcome, but indistinguishable between survivors and healthy controls. Measures of neural complexity and neural noise were not informative of patients' outcome and had high or low values for patients compared to controls. Our results suggest different roles for neural synchrony and complexity in acute coma. Synchrony represents a precondition for consciousness, while complexity needs an equilibrium between high or low values to support conscious cognition.

Sudden coma at the onset of severe refractory thrombotic thrombocytopenic purpura with successful treatment.

Most patients develop coma several days after the onset of thrombotic thrombocytopenic purpura (TTP) caused by microvascular occlusion. However, aggravated coma as the first symptom of TTP has rarely been reported. Although plasma exchange (PEX) and steroids have reduced mortality, the prognosis of patients with TTP is still poor. We reported a patient with refractory TTP presenting with aggravated coma on admission. After days of successful PEX, rituximab, and glucocorticoid therapy for clinical remission, the patient regained consciousness and returned to his normal life with a good outcome. Our case highlights that TTP should be considered when coma occurs as the first symptom.

Clinical significance of mismatch negativity in predicting the awakening of comatose patients after severe brain injury.

We assessed the clinical significance of mismatch negativity (MMN) in predicting the awakening of comatose patients with severe brain injury. The clinical data of patients with severe brain injury, admitted to the neurosurgical intensive care unit of Xiangya Hospital of Central South University from July 2018 to March 2020, who underwent auditory MMN examinations within 28 days after coma onset, were reviewed. Correlations between clinical factors and prognosis [Glasgow Outcome Scale (GCS) for 3 mo] were analyzed. Fifty-three patients were included; 37 (69.8%) had favorable outcomes. A univariate analysis revealed the Glasgow Coma Scale (GCS) and absolute MMN amplitudes at electrodes Fz and Cz were significantly correlated with prognosis. Only GCS scores and MMN amplitude at Fz were independent predictors in multivariate logistic regression analysis (area under the curve 0.744 vs. 0.753, respectively); both combined, improved accuracy to 84.6%. MMN amplitudes at Fz were dichotomized at a value of 1.08 µV with a sensitivity and specificity of 81.1% and 68.7%, respectively, for predicting comatose patients' awakening. In conclusion, MMN amplitude at Fz is a reliable prognostic indicator for comatose patients with severe brain injury; the prediction value improved when combined with GCS. Thus, an event-related potential component with a clear site and cutoff value may support prognostication in severe brain injury.NEW & NOTEWORTHY Mismatch negativity (MMN) can assess the prognosis of comatose patients after severe brain injury, especially for MMN amplitude. In addition, MMN analysis at electrode Fz best predicts recovery of consciousness in patients with severe brain injury. Importantly, a quantitative approach (cutoff value of 1.08 µV) may improve the use of MMN for prognostication.