The Curing Coma Campaign: Framing Initial Scientific Challenges-Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting.

Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the "grand challenge" of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the "curing coma community" to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.

Nociception Coma Scale-Revised: Nurses' Experience in Clinical Practice.

BACKGROUND: The Nociception Coma Scale-Revised (NCS-R) is a rating scale developed and validated for measurement of nociception and pain among patients with brain injuries in unresponsive wakefulness syndrome or minimally conscious state. However, little is known about its use in daily clinical practice. AIMS: The aim of this study was to explore clinical experience with the NCS-R by means of focus group interviews with nurses and nurse assistants in a subacute rehabilitation ward for patients with severe brain injuries. DESIGN: Qualitative focus group interview study. SETTINGS: Department for highly specialized neurorehabilitation for patients with severe brain injuries. PARTICIPANTS/SUBJECTS: Nurses and nurse assistants. METHODS: In total, 12 experienced registered nurses and nurse assistants participated in two recorded focus group interviews. The participants were selected from the subacute neurorehabilitation ward on the following criteria: Employed at the ward for at least 11 months and being introduced to and having experience with using the NCS-R in own patients for a minimum period of 6 months. An inductive qualitative analysis was conducted by reading the interview text through several times, and meaning units were defined first separately and later jointly between the authors. Then meaning units were coded and categorized into subthemes and themes. RESULTS: We found three themes, general relevance of the NCS-R, NCS-R versus level of consciousness, and overall assessment of pain in patients with disorders of consciousness, with a total of eight subthemes. CONCLUSIONS: The content and subscales of the NCS-R are relevant for pain assessment in patients with severe brain injury in subacute rehabilitation. However, with the present cutoff value at 4 points, challenges are associated with using NCS-R, especially in patients with unresponsive wakefulness syndrome because they are at risk of not being assessed with respect to pain.

Intrinsic network reactivity differentiates levels of consciousness in comatose patients.

OBJECTIVE: We devise a data-driven framework to assess the level of consciousness in etiologically heterogeneous comatose patients using intrinsic dynamical changes of resting-state Electroencephalogram (EEG) signals. METHODS: EEG signals were collected from 54 comatose patients (GCS ⩽ 8) and 20 control patients (GCS > 8). We analyzed the EEG signals using a new technique, termed Intrinsic Network Reactivity Index (INRI), that aims to assess the overall lability of brain dynamics without the use of extrinsic stimulation. The proposed technique uses three sigma EEG events as a trigger for ensuing changes to the directional derivative of signals across the EEG montage. RESULTS: The INRI had a positive relationship with GCS and was significantly different between various levels of consciousness. In comparison, classical band-limited power analysis did not show any specific patterns correlated to GCS. CONCLUSIONS: These findings suggest that reaching low variance EEG activation patterns becomes progressively harder as the level of consciousness of patients deteriorate, and provide a quantitative index based on passive measurements that characterize this change. SIGNIFICANCE: Our results emphasize the role of intrinsic brain dynamics in assessing the level of consciousness in coma patients and the possibility of employing simple electrophysiological measures to recognize the severity of disorders of consciousness (DOC).

[The Russian version of Coma Recovery Scale-revised - a standardized method for assessment of patients with disorders of consciousness]. / Russkoiazychnaia versiia peresmotrennoi shkaly vosstanovleniia posle komy - standartizirovannyi metod otsenki patsientov s khronicheskimi narusheniiami soznaniia.

The authors officially present for the first time the Russian version of Coma Recovery Scale-Revised (CRS-R). Today CRS-R is the only validated scale in Russian for assessment of patients with chronic disorders of consciousness (DOC). The study showed high consistency for different researchers, high sensitivity in the evaluation of patients over time as well as high concurrent validity. This article contains the text of the scale and recommendations how to use CRS-R and interpret the data. Presented version of the CRS-R is recommended for use in DOC patients. Russian version of the CRS-R is a standardized, comprehensive and systematic approach to the examination and assessment of patients with chronic DOS. It ensures the standard approach to examination and assessment that warrants the accuracy and homogeneity of the obtained results.

Reliability of Glasgow Coma Score in pediatric trauma patients.

BACKGROUND: Discordant assessments of Glasgow Coma Score (GCS) following trauma can result in inappropriate triage. This study sought to determine the reliability of prehospital GCS compared to emergency department (ED) GCS. METHODS: We conducted a retrospective review of traumas from 01/2000 to 12/2015 at a Level-1 pediatric trauma center. We evaluated reliability between field and ED GCS using Pearson's correlation. We ascertained the difference between prehospital and ED GCS (delta-GCS). Associations between patient characteristics and delta-GCS were modeled using Poisson and linear regression, adjusting for demographic and clinical covariates. RESULTS: We identified 5306 patients. Pearson's correlation for GCS measurements was 0.57 for ages 0-3, and 0.67-0.77 for other age groups. Mean delta-GCS was highest for age<3years (0.95, SD=2.4). Poisson regression demonstrated that compared to children 0-3years, higher age was associated with lower delta-GCS (RR 0.65 95% CI 0.56-0.74). Linear regression showed that in those with a delta-GCS, more severe injury (higher ISS, worse ED disposition) and older age were associated with a negative change, signifying decline in score. CONCLUSIONS: GCS is generally unreliable in pediatric trauma patients aged 0-3years, particularly the verbal score component. This may impact accuracy of triage priority for pediatric trauma patients. LEVEL OF EVIDENCE: III, Prognostic.

A Comparison Between the Effectiveness of Full Outline of Unresponsiveness and Glasgow Coma Score at Neurosurgical Intensive Care Unit Patients.

AIM: To evaluate the effectiveness and the use of Glasgow Coma Score (GCS) and Full Outline of Unresponsiveness (FOUR) score by nurses in the follow-up and evaluation of patients admitted to the neurosurgical intensive care unit for cranial surgery or head trauma. MATERIAL and METHODS: The study was performed at a neurosurgical intensive care unit. Sample size was determined as 47 patients (a= 0.05, power= 0.95). The correlation coefficient less than 0.5 was accepted as weak. In the first 24 hours, Karnofsky Performance Scale was applied and the Acute Physiology and Chronic Health Evaluation II (APACHE II) Score calculated for patients who were admitted to the intensive care unit for cranial surgery or head trauma. Also FOUR and GCS were applied by two different nurses twice a day. Intraclass Correlation Coefficient, Pearson Correlation and Cronbach?s Alpha Security Index analyses were used to evaluate the data. RESULTS: Concordance was above 0.810 and correlation was above 0.837 between GCS and FOUR score evaluation results of nurses. Correlation of two different evaluation at every shift for GCS was 0.887, and for FOUR was 0.827 and above. Karnofsky Performance Scale correlation with FOUR and GCS scores of patients at admission and discharge from the intensive care unit was 0.709 and above. The correlation between APACHE II and FOUR was 0.851; between APACHE II and GCS 0.853. There was no difference between the evaluations of two scores and two nurses statistically. CONCLUSION: Concordance between nurses was found high both for GCS and FOUR. The FOUR score is as effective as GCS on the follow-up of patients who are managed in the neurosurgical intensive care units.

Postanoxic alpha, theta or alpha-theta coma: Clinical setting and neurological outcome.

AIM: The aim of this study was to determine the prognosis of 26 consecutive adults with alpha coma (AC), theta coma (TC) or alpha-theta coma (ATC) following CRA and to describe the clinical setting and EEG features of these patients. METHODS: We retrospective analyzed a prospectively collected cohort of adult patients diagnosed as having AC, TC or ATC after CRA between January 2008 and June 2016. None of patients included in this analysis underwent therapeutic hypothermia (TH). Neurological outcome was expressed as the best score 6 months after CRA using the five-point Glasgow-Pisttsburgh Cerebral Performance Categories (CPC) RESULTS: Twenty-six patients were identified with a diagnosis of postanoxic AC, TC or ATC coma. There were 20 (77%) men and 6 (23%) women. The mean age was 63 ±â€¯16 years. The most frequent EEG pattern was TC (21 patients, 80%), followed by AC (3 patients, 12%) and ATC (2 patients, 8%). The cardiac rhythm as primary origin of the CRA was ventricular fibrillation (VF) in 16 patients (61.5%), asystole in 8 patients (34.6%) and ventricular tachycardia (VT) in one patient (3.8%). The presence of EEG reactivity was present in 8 patients (30%). The mortality rate was 85%. Of the 4 surviving patients, two (3.8%) had moderate disability (CPC 2), one (3.8%) had severe disability (CPC 3) and one (3.8%) reached a good recovery. The age was significantly lower in survivors 46.2 ±â€¯10.8 versus nonsurvivors 63.3 ±â€¯15.5 (p = 0.04). There was increased association of EEG reactivity with survival (p = 0.07). CONCLUSION: Hypoxic-ischemic AC, TC and ATC are associated with a poor prognosis and a high rate of mortality. In younger patients with AC, TC and ATC and incomplete forms showing reactivity on the EEG, there is a greater probability of clinical recovery.

[Severity assessment strategies based on administrative data using stroke as an example]. / Möglichkeiten zur Einschätzung des Schweregrades einer Erkrankung auf der Basis von Routinedaten am Beispiel des Schlaganfalls.

BACKGROUND AND OBJECTIVES: Information on disease severity is relevant for many studies with claims data in health service research, but only limited information is available in routine data. Stroke serves as an example to analyse whether the combination of different information in claims data can provide insight into the severity of a disease. METHOD: As a first step, a literature search was conducted. Strategies to assess the severity of a disease by means of routine data were examined with regard to approval and applicability to German sickness fund data. In order to apply and extend the identified procedures, the statutory health insurance sample AOK Hessen/KV Hessen (VSH) served as data source. It is an 18.75 % random sample of persons insured by the AOK Hessen, with 2013 being the most recent year. Stroke patients were identified by the ICD-10 GM code I63 and I64. Patients with said diagnoses being coded as a hospital discharge diagnosis in 2012 were included due to an acute event in 2012 (n=944). The follow-up time was one year. RESULTS: Ten studies covering seven different methods to assess stroke severity were identified. Codes for coma (4.2 % of stroke patients in the SHI sample) as well as coma and/or the application of a PEG tube (9.8 % of the stroke patients) were applied as a proxy for disease severity of acute cases. Taking age, sex and comorbidity into consideration, patients in a coma show a significantly increased risk of mortality compared to those without coma. Three operationalisations were chosen as possible proxies for disease severity of stroke in the further course of disease: i) sequelae (hemiplegia, neurological neglect), ii) duration of the index inpatient stay, and iii) nursing care/ care level 3 for the first time after stroke. The latter proxy has the highest explanatory value for SHI costs. CONCLUSION: The studies identified use many variables mainly based on hospital information in order to describe disease severity. With the exception of coma, these proxies were neither validated nor did the authors provide more detailed grounds for their use. An identified score for stroke severity could not be applied to SHI data. To develop a comparable score requires a linkage of clinical and administrative data. Since routine data include information from all sectors of care, it should be explored whether these data (for example, the patients' care needs) are suitable to assess disease severity. For validation, separate databases and, optimally, primary patient data are necessary.

Predictive value of EEG in postanoxic encephalopathy: A quantitative model-based approach.

INTRODUCTION: The majority of comatose patients after cardiac arrest do not regain consciousness due to severe postanoxic encephalopathy. Early and accurate outcome prediction is therefore essential in determining further therapeutic interventions. The electroencephalogram is a standardized and commonly available tool used to estimate prognosis in postanoxic patients. The identification of pathological EEG patterns with poor prognosis relies however primarily on visual EEG scoring by experts. We introduced a model-based approach of EEG analysis (state space model) that allows for an objective and quantitative description of spectral EEG variability. METHODS: We retrospectively analyzed standard EEG recordings in 83 comatose patients after cardiac arrest between 2005 and 2013 in the intensive care unit of the University Hospital Zürich. Neurological outcome was assessed one month after cardiac arrest using the Cerebral Performance Category. For a dynamic and quantitative EEG analysis, we implemented a model-based approach (state space analysis) to quantify EEG background variability independent from visual scoring of EEG epochs. Spectral variability was compared between groups and correlated with clinical outcome parameters and visual EEG patterns. RESULTS: Quantitative assessment of spectral EEG variability (state space velocity) revealed significant differences between patients with poor and good outcome after cardiac arrest: Lower mean velocity in temporal electrodes (T4 and T5) was significantly associated with poor prognostic outcome (p<0.005) and correlated with independently identified visual EEG patterns such as generalized periodic discharges (p<0.02). Receiver operating characteristic (ROC) analysis confirmed the predictive value of lower state space velocity for poor clinical outcome after cardiac arrest (AUC 80.8, 70% sensitivity, 15% false positive rate). CONCLUSION: Model-based quantitative EEG analysis (state space analysis) provides a novel, complementary marker for prognosis in postanoxic encephalopathy.

[Unconsciousness and clouded awareness]. / Bewusstseinsstörung oder -trübung.

Stupor and coma are clinical states in which patients have impaired responsiveness or are unresponsive to external stimulation and are either difficult to arouse or are unarousable. The term stupor refer to states between alertness and coma. An alteration in arousal represents an acute life-threatening emergency, requiring prompt intervention for preservation of life and brain function.

Representing the Glasgow Coma Scale in IT: Proper Specification is Required for Assessment Scales.

In healthcare a huge amount of assessment scales and score systems are in use to abbreviate and summarize the results of clinical observations to interpret a patient's condition in a valid and reliable manner. It is challenging to convey the information in a semantic interoperable form to other systems. A bad approach would be to invent individual models for each of them. Within this paper we would like to demonstrate that a generic model is sufficient by demonstrating the realization with the Glasgow Coma Scale.

Prognostic value of EEG indexes for the Glasgow outcome scale of comatose patients in the acute phase.

The purpose of this work is the estimation of the Glasgow outcome scale (GOS) from a single continuous electroencephalogram (c-EEG) routinely recorded to monitor comatose patients in the neurosurgical intensive care unit. c-EEG was recorded from 13 patients in the acute phase: five with GOS = 5, four with GOS = 3 and four with GOS = 1. Different indexes were extracted from epochs of c-EEG (classical: amplitude and spectral estimators; non classical: from recurrence quantification analysis-RQA-and approximate entropy). Descriptors of different indexes (temporal variation and mean, standard deviation, skewness of the distribution across epochs) were used to train support vector machines to identify the correct GOS. We found classifiers allowing correct classification of the patients. Spectral indexes allowed to get optimal performances in classifying GOS 1 and 3. Nonlinear indexes (especially determinism from RQA) were optimal for identifying GOS = 5. Thus, the integration of information from classical/linear and nonlinear c-EEG descriptors in a multi-index classifier is important for GOS estimation.

EEG in connection with coma.

BACKGROUND: Coma is a dynamic condition that may have various causes. Important changes may take place rapidly, often with consequences for treatment. The purpose of this article is to provide a brief overview of EEG patterns in comas with various causes, and indicate how EEG contributes in an assessment of the prognosis for coma patients. METHOD: The article is based on many years of clinical and research-based experience of EEG used for patients in coma. A self-built reference database was supplemented by searches for relevant articles in PubMed. RESULTS: EEG reveals immediate changes in coma, and can provide early information on cause and prognosis. It is the only diagnostic tool for detecting a non-convulsive epileptic status. Locked-in- syndrome may be overseen without EEG. Repeated EEG scans increase diagnostic certainty and make it possible to monitor the development of coma. INTERPRETATION: EEG reflects brain function continuously and therefore holds a key place in the assessment and treatment of coma.

Practical use of the Glasgow Coma Scale; a comprehensive narrative review of GCS methodology.

OBJECTIVE: Narrative review of Glasgow Coma Scale (GCS) methodology. DESIGN: Narrative review of published papers describing methodological aspects of the GCS, from Premedline, Medline, EMBASE, CINAHL and Ovid Nursing databases from 1950 to May 2012. RESULTS: Examination of 18,851 references limited to descriptions of GCS development, pathophysiological correlations, examination techniques, complications or clinician agreement gave a final set of 33, which were summarised in this review. CONCLUSION: The GCS was designed for the objective measurement of level of consciousness, assessment of trend, and to facilitate accurate and valid communication between clinicians. Concerns have been raised about the potential for misleading levels of precision engendered by the use of the GCS, and the use of simpler scales suggested. This review discusses the GCS and conditions affecting calculation of domain and summary scores, and recommends a method of implementation and interpretation.

Metabolic vs structural coma in the ED--an observational study.

BACKGROUND: Patients presenting unconscious may reasonably be categorized as suffering from a metabolic or structural condition. STUDY OBJECTIVE: The objective was to investigate if some routinely recorded clinical features may help to distinguish between these 2 main forms of coma in the emergency department (ED). METHODS: Adults admitted to an ED in Stockholm between February 2003 and May 2005 with a Glasgow Coma Scale (GCS) score less than 11 were enrolled prospectively. The GCS score was entered into a protocol that was complemented with available data within 1 month. RESULTS: The study population of 875 patients was classified into 2 main groups: one with a metabolic (n = 633; 72%) and one with a structural disorder (n = 242; 28%). Among the clinical features recorded in the ED, 3 were found to be strongly associated with a metabolic disorder, namely, young age, low or normal blood pressure, and absence of focal signs in the neurological examination. Patients younger than 51 years with a systolic blood pressure less than 151 mm Hg who did not display signs of focal pathology had a probability of 96% for having a metabolic coma. The mean GCS score on admission was identical in the groups. Hospital mortality was 14% in the metabolic and 56% in the structural group. CONCLUSIONS: These findings indicate that unconscious young adults who present without a traumatic incident with a low or normal blood pressure and without signs of focal pathology most probably suffer from a metabolic disorder, wherefore computed tomography of the brain may be postponed and often avoided.

A multicenter prospective study of interobserver agreement using the Full Outline of Unresponsiveness score coma scale in the intensive care unit.

OBJECTIVE: The classification of the comatose patient has been greatly improved with the use of coma scales. The Full Outline of Unresponsiveness score has emerged as an alternative to the Glasgow Coma Scale in that it incorporates essential information needed to assess the depth of coma. One set of patients for which the Full Outline of Unresponsiveness score could be particularly beneficial is those admitted to an intensive care unit, where approximately 30%-35% of all patients are intubated or ventilated. This manuscript reports on a study that examined the inter-rater reliability of the Full Outline of Unresponsiveness score in five intensive care units. SETTING: Seven intensive care units at five U.S. hospitals partici-pated. SUBJECTS: Patients admitted during parts of 2010 and 2011 had their Full Outline of Unresponsiveness score assessed independently by two nurses within 1 hr of admission. DESIGN: We evaluated the weighted kappa statistic of the Full Outline of Unresponsiveness score over all patients and stratified by mechanical ventilation status. Finally, we looked for evidence of heterogeneity in Full Outline of Unresponsiveness score agreement across hospitals. MEASUREMENTS AND MAIN RESULTS: A total of 907 adult critically ill patients had Full Outline of Unresponsiveness score assessments by two evaluators. The overall weighted kappa statistic was 0.92, and this did not differ by whether or not a patient was on a ventilator. Among hospitals there was modest heterogeneity for the weighted kappa; however, all of the values were >0.80. CONCLUSIONS: The Full Outline of Unresponsiveness score showed excellent inter-rater agreement overall and at each of the five hospitals. This demonstrates that the Full Outline of Unresponsiveness score can be utilized reliably in critically ill patients.

[The first 24 hours - the unconscious patient from the neurologist's viewpoint]. / Die ersten 24 Stunden - Der Patient mit Bewusstseinsstörung aus neurologischer Sicht.

About 50 % of non-traumatic impairments of consciousness are caused by primary cerebral diseases such as epilepsy, intracerebral hemorrhage or meningoencephalitis. In addition to primary cerebral conditions, internal diseases can also lead to focal neurological symptoms or neuroimaging abnormalities. Anamnestic informations, body inspection, clinical neurological examination as well as laboratory and imaging findings have to be added and categorized by a multilevel composition to establish a conclusive diagnosis. Simultaneously therapeutic measures for suspected primary cerebral diseases must be initiated, for example a rapid antibiotic treatment in case of a possible bacterial meningitis. A fast and structured diagnostic approach is crucial for ensuring a good prognosis and helps to miss relevant diagnostic steps. Potential diagnostic and therapeutic pitfalls must be kept in mind.