[Functional coma: case report and systematic review]. / Functioneel coma: casusbeschrijving en systematisch literatuuroverzicht.

We describe a case of a patient with a functional coma ,and give a systemic review of literature. Functional coma is an extremely rare disorder with only 21 described cases in the literature. The disease is linked to a conversion disorder or a dissociative disorder and is predominantly found in females. Predisposing factors are a history of sexual or physical abuse, psychiatric disorders, previous episodes of functional coma, and recent surgery with general anesthesia. Several clinical signs are suggestive for the diagnosis, however none of them is sufficiently sensitive or specific. Therefore, functional coma remains an exclusion diagnosis. Vital signs must be normal, just as a routine blood examination, an electroencephalogram and imaging of the central nervous system. The most important differential diagnosis are catatonia, factitious disorder, and malingering. Spontaneous recovery can be expected after a duration of about 45 minutes to 4 days.

Psychogenic coma after general anesthesia with remimazolam and remifentanil -a case report.

BACKGROUND: Delayed emergence from general anesthesia is associated with life-threatening conditions with pharmacological, neurological, metabolic, and rarely, psychiatric causes. This case report was presented to report psychogenic coma after recovery from anesthesia with remimazolam and remifentanil. CASE: An elderly woman was unresponsive after recovery from anesthesia with remimazolam and remifentanil. Physical examination, laboratory testing, and radiographic imaging did not reveal any obvious organic causes. Pharmacological or metabolic abnormalities were not found. Absence of those causes strongly suggests that prolonged unconsciousness is related to psychiatric origin. The patient spontaneously regained consciousness after 48 h without any neurological complications. CONCLUSIONS: Anesthesiologists should be aware of the possibility of psychogenic coma for patients with unexplained delay in emergence from anesthesia after the exclusion of other causes.

Wakefulness-Promoting Effects of Lateral Hypothalamic Area-Deep Brain Stimulation in Traumatic Brain Injury-Induced Comatose Rats: Upregulation of α1-Adrenoceptor Subtypes and Downregulation of Gamma-Aminobutyric Acid ß Receptor Expression Via the Orexins Pathway.

OBJECTIVE: Previous studies have shown that deep brain stimulation (DBS) can improve the level of consciousness of comatose patients with traumatic brain injuries (TBIs). However, the most suitable targets for DBS are unknown, and the mechanisms underlying recovery remain to be determined. The aim of the present study was to assess the effects of lateral hypothalamic area-DBS (LHA-DBS) in comatose rats with TBIs. METHODS: A total of 55 Sprague-Dawley rats were randomly assigned to 5 groups: the control group, TBI group, stimulated (TBI+LHA-DBS) group, antagonist (TBI+SB334867+LHA-DBS) group, and antagonist control (TBI+saline+LHA-DBS) group. The rats in the control group had undergone a sham operation and anesthesia, without coma induction. Coma was induced using a free-fall drop method. The rats in the stimulated group received bilateral LHA stimulation (frequency, 200 Hz; voltage, 2-4 V; pulse width, 0.1 ms) for 1 hour, with 5-minute intervals between subsequent stimulations, which were applied alternately to the left and right sides of the lateral hypothalamus. The comatose rats in the antagonist group received an intracerebroventricular injection with an orexins receptor type 1 (OX1R) antagonist (SB334867) and then received LHA-DBS. A I-VI consciousness scale and electroencephalography were used to assess the level of consciousness in each group of rats after LHA-DBS. Western blotting and immunofluorescence were used to detect OX1R expression in the LHA and α1-adrenoceptor (α1-AR) subtype and gamma-aminobutyric acid ß receptor (GABABR) expression in the prefrontal cortex. RESULTS: In the TBI, stimulated, antagonist, and antagonist control groups, 5, 10, 6, and 9 rats were awakened. The electroencephalographic readings indicated that the proportion of δ waves was lower in the stimulated group than in the TBI and antagonist groups (P < 0.05). Western blotting and immunofluorescence analysis showed that OX1R expression was greater in the stimulated group than in the TBI group (P < 0.05). The expression of α1-AR was also greater in the stimulated group than in the TBI and antagonist groups (P < 0.05). In contrast, the GABABR levels in the stimulated group were lower than those in the TBI and antagonist groups (P < 0.05). A statistically significant difference was found between the antagonist and antagonist control groups. CONCLUSIONS: Taken together, these results suggest that LHA-DBS promotes the recovery of consciousness in comatose rats with TBIs. Upregulation of α1-AR expression and downregulation of GABABR expression in the prefrontal cortex via the orexins and OX1R pathways might be involved in the wakefulness-promoting effects of LHA-DBS.

The neural basis of consciousness.

Consciousness has evolved and is a feature of all animals with sufficiently complex nervous systems. It is, therefore, primarily a problem for biology, rather than physics. In this review, I will consider three aspects of consciousness: level of consciousness, whether we are awake or in a coma; the contents of consciousness, what determines how a small amount of sensory information is associated with subjective experience, while the rest is not; and meta-consciousness, the ability to reflect upon our subjective experiences and, importantly, to share them with others. I will discuss and compare current theories of the neural and cognitive mechanisms involved in producing these three aspects of consciousness and conclude that the research in this area is flourishing and has already succeeded to delineate these mechanisms in surprising detail.

Preliminary validation of the coma recovery scale for pediatrics in typically developing young children.

Objective: To examine the basic psychometric features of a modified version of the Coma Recovery Scale-Revised (CRS-R) for use in young children with disorders of consciousness (DoC).Method: The CRS-R was modified to create the Coma Recovery Scale for Pediatrics (CRS-P) and administered to 33 typically developing children (8-59 months). Total scores, subtest scores, and inter-rater reliability were evaluated. Performance on the two items representing emergence to conscious state (CS) - functional object use (FOU) and functional communication (FC) was examined across the age range.Results: Inter-rater reliability of CRS-P subscale scores was adequate (Kw = .87-1.00). All 4-year-olds, 75% of 3-year-olds, 10% of 2-year-olds, and 0% <2 years scored at the CRS-P ceiling. Total and subtest scores were strongly correlated with age as were the two behaviors representing emergence to CS (FOU, FC) - all children >12 months and none <12 months of age met criteria for FOU; all children ≥3 years, 20% between 2 and <3 years, and none <2 years met criteria for FC.Conclusions: The CRS-P is appropriate for use in children as young as 12 months of age, with a strong association between performance and age at administration. The CRS-P also captures emergence to CS, a key clinical milestone.

Between being healthy and becoming comatose: the neuropsychiatric landscape of critical illness with a focus on delirium, DSM-5 and ICD-11.

BACKGROUND: One of the most important questions remaining in matters of critical illness in the year 2019 is arguably how to address the diverse neuropsychiatric complications of critical illness. MAIN TEXT: The ICD-11 and DSM-5, two of the world's leading classification systems, disagree regarding important aspects of delirium; moreover, they do not mention critical illness and its neuropsychiatric complications at all. CONCLUSIONS: It would have been desirable for the committees revising the DSM-IV-TR and ICD-10 to have joined forces in order to generate classification systems that complement each other and, moreover, that address the "The Neuro-Psychiatry of Critical Illness".

Real and illusory perceptions of patients in induced coma.

OBJECTIVE: To identify, in the scientific literature, real and illusory perceptions of adult patients in induced coma. METHODS: This is an integrative review of 15 primary studies from the Medline, Web of Science, LILACS, CINAHL and SCOPUS databases. RESULTS: The main memories reported after induced coma were thirst, cold, and pain. In some studies, patients reported they were unable to tell whether they were awake or dreaming, whether it was real or unreal. Satisfactory memories were reported by patients related to the care received and the use of bedside journals. CONCLUSION: Evidence showed a number of studies aiming to identify delirium, but without a focus on analyzing real or illusory perceptions of patients after induced coma. Thus, this integrative review identified scientific evidence of memories related to perceptions of sedated patients in the intensive care unit.

Nonverbal communication of trauma patients in a state of minimal consciousness.

INTRODUCTION: In spite of the rapid development in various communication-support technologies for those waking up from a coma, studies describing the sole process of reconstructing communication in this group of patients are scarce. OBJECTIVE: The aim of this study was to analyze communication reactions in a minimal state of consciousness and describe the nonverbal behaviours characteristic for each stages significant for the therapy of communication. MATERIAL AND METHODS: 18 severely brain-injured patients in a minimal state of consciousness participated in the half-year observation study, which included people experiencing at least 4 weeks of consciousness disorder/coma. Age of patients 25±5 years. Psychological assessment included: observation of various attempts of communications undertaken by patients, caregivers and family interview, the Glasgow Coma Scale (GCS) and Individual Communication Sheet. RESULTS: Data analysis showed a significant increase in preverbal communication, both in primal and sensory areas when compared between Stage II (GCS=6-8 points) and Stage III (GCS=9-12 points). After a time, primary communication reached a high level. Patients produced communication attempts from the behaviour organization level, and an increase in the nonverbal communication level was noted. Based on observations, nonverbal communication profiles for each stage of waking up from a coma were introduced. CONCLUSIONS: It was found that in the process of waking up from a coma the patients communicate with the use of the preverbal level of primal communication, the sensory and behaviour organization activities. The characteristics of the communication reactions show that in Stage III there is a significant increase in two preverbal communication areas: primal and sensory acts, when compared with Stage II.

Real and illusory perceptions of patients in induced coma / Percepciones reales e ilusorias de pacientes en coma inducido / Percepções reais e ilusórias de pacientes em coma induzido

ABSTRACT Objective: To identify, in the scientific literature, real and illusory perceptions of adult patients in induced coma. Methods: This is an integrative review of 15 primary studies from the Medline, Web of Science, LILACS, CINAHL and SCOPUS databases. Results: The main memories reported after induced coma were thirst, cold, and pain. In some studies, patients reported they were unable to tell whether they were awake or dreaming, whether it was real or unreal. Satisfactory memories were reported by patients related to the care received and the use of bedside journals. Conclusion: Evidence showed a number of studies aiming to identify delirium, but without a focus on analyzing real or illusory perceptions of patients after induced coma. Thus, this integrative review identified scientific evidence of memories related to perceptions of sedated patients in the intensive care unit.

RESUMEN Objetivo: Identificar, a partir de la literatura científica, percepciones reales e ilusorias de pacientes adultos en coma inducido. Método: Revisión integrativa de 15 estudios primarios alojados en las bases de datos Medline, Web of Science, LILACS, CINAHL y SCOPUS. Resultados: Los recuerdos más reportados luego del coma inducido son sed, frío y dolor. Existen estudios en los que los pacientes afirmaron no distinguir si estaban despiertos o soñando, si era real o irreal. Se identificaron relatos de recuerdos satisfactorios relacionados al cuidado recibido y al uso diario de cabecera. Conclusión: Las evidencias mostraron un abanico de estudios cuyo objetivo era identificar el delirium, aunque con menor enfoque en la identificación real o ilusoria del paciente luego del coma inducido. Así, esta revisión integrativa consiguió identificar evidencias científicas acerca de los recuerdos relativos a la percepción del paciente sedado e internado en la Unidad de Terapia Intensiva.

RESUMO Objetivo: Identificar, a partir da literatura científica, percepções reais e ilusórias de pacientes adultos em coma induzido. Método: Revisão integrativa de 15 estudos primários localizados nas bases de dados Medline, Web of Science, LILACS, CINAHL e SCOPUS. Resultados: As principais memórias relatadas após o coma induzido são sede, frio e dor. Há estudos em que os pacientes afirmaram não distinguir se estavam acordados ou sonhando, se o que acontecia era real ou irreal. Identificaram-se relatos de memórias satisfatórias relacionadas ao cuidado recebido e ao uso de diários de cabeceira. Conclusão: As evidências mostraram um leque de estudos direcionados a identificar o delirium, porém com menor foco na identificação da percepção real ou ilusória do paciente após coma induzido. Desse modo, esta revisão integrativa proporcionou a identificação de evidências científicas sobre as memórias relativas à percepção do paciente sedado e em estadia na Unidade de Terapia Intensiva.

Comparison of Single and Combined Effects of Nature Sounds and Foot Sole Reflexology Massage on the Level of Consciousness in Traumatic Comatose Patients: A Randomized Controlled Clinical Trial.

Consciousness disturbances are the most common posttraumatic complications. The purpose of this study was to compare the single and combined effects of nature sounds and foot sole reflexology massage on level of consciousness in traumatic comatose patients. This randomized controlled clinical trial was conducted in 2 teaching hospitals in an urban area of Iran. Samples were 120 traumatic comatose patients who were randomly assigned into control, nature sounds, foot reflexology massage, and nature sounds plus foot sole reflexology massage groups. Patients in all groups received routine care. Interventions were performed twice a day for 2 weeks, each time for 30 minutes. The patients' level of consciousness was assessed using the Glasgow Coma Scale before, 1 week, and 2 weeks after the intervention. The groups had no significant differences in the mean scores of the consciousness level before, 1 week after, and the last day of the intervention. Also, there was a significant difference in the number of patients who regained full consciousness (P = .001) in the intervention groups compared with the control group. Significant differences in the number of days of consciousness were reported in at least one of the groups compared with other groups (P = .001). This difference was significant in the control group compared with the foot reflexology massage group (P = .032), as well as the nature sounds plus foot sole reflexology massage group (P = .001). Single or combined interventions can increase the level of consciousness in comatose patients and reduce the duration of coma.

Outcome of Frail Do-Not-Intubate Subjects With End-Stage Chronic Respiratory Failure and Their Opinion of Noninvasive Ventilation to Reverse Hypercapnic Coma.

BACKGROUND: The use of noninvasive ventilation (NIV) in the emergency setting to reverse hypercapnic coma in frail patients with end-stage chronic respiratory failure and do-not-intubate orders remains a questionable issue given the poor outcome of this vulnerable population. We aimed to answer this issue by assessing not only subjects' outcome with NIV but also subjects' point of view regarding NIV for this indication. METHODS: A prospective observational case-control study was conducted in 3 French tertiary care hospitals during a 2-y period. Forty-three individuals who were comatose (with pH < 7.25 and PaCO2 > 100 mm Hg at admission) were compared with 43 subjects who were not comatose and who were treated with NIV for acute hypercapnic respiratory failure. NIV was applied by using the same protocol in both groups. They all had a do-not-intubate order and were considered vulnerable individuals with end-stage chronic respiratory failure according to well-validated scores. RESULTS: NIV yielded similar outcomes in the 2 groups regarding in-hospital mortality (n = 12 [28%] vs n = 12 [28%] in the noncomatose controls, P > .99) and 6-month survival (n = 28 [65%] vs n = 22 [51%] in the noncomatose controls, P = .31). Despite poor quality of life scores (21.5 ± 10 vs 31 ± 6 in the awakened controls, P = .056) as assessed by using the VQ11 questionnaire 6 months to 1 y after hospital discharge, a large majority of the survivors (n = 23 [85%]) would be willing to receive NIV again if a new episode of acute hypercapnic respiratory failure occurs. CONCLUSIONS: In the frailest subjects with supposed end-stage chronic respiratory failure that justifies treatment limitation decisions, it is worth trying NIV when acute hypercapnic respiratory failure occurs, even in the case of extreme respiratory acidosis with hypercapnic coma at admission.

EEG of patients in coma after traumatic brain injury reflects physical parameters of auditory stimulation but not its emotional content.

PRIMARY OBJECTIVE: We aimed to investigate the origin of EEG response of patients in coma and after moderate TBI to emotional stimulation, whether they distinguish emotional content or only react to the physical features of an audio signal. RESEARCH DESIGN: We registered EEG during continuous pleasant and unpleasant non-verbal stimulation and in rest. A total of 69 subjects participated in our study: healthy adults, conscious patients after moderate TBI and patients in coma after severe TBI. We analysed the distances between the stimuli according to EEG data and applied correlation analysis to the distances, acoustic parameters of stimuli, subjects' emotional assessment of the stimuli, GCS score and Doppler ultrasound data. MAIN OUTCOMES AND RESULTS: The EEG response to the stimulation in patients in coma mostly reflects the physical parameters of the stimuli, and correlated with Doppler ultrasound data. The EEG of healthy adults reflects their psychological assessment of the stimuli. Patients after moderate TBI differentiate unpleasant stimuli well and pleasant stimuli poorly, they mainly consider pitch to cope with this task like healthy adults do. CONCLUSIONS: The reactivity to the acoustic features of emotional stimulation in patients in coma should be investigated further as a marker of patients' recovery. ABBREVIATIONS: TBI: traumatic brain injurym; TBI: moderate TBI; MCA: middle cerebral artery; GCS: Glasgow Coma Scale; M: mean; SD: standard deviation.

Beecher Dépassé: Fifty Years of Determining Death, Legally.

Five decades ago, Henry Knowles Beecher, a renowned professor of research anesthesiology, sought to solve a problem created by modern medicine. The solution proposed by Beecher and his colleagues on the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death proved very influential.1 Indeed, other contemporaneous medical developments magnified its significance yet also made the solution it offered somewhat problematic. As we mark this fiftieth anniversary, at a time when concerns about the conceptual model on which its recommendations rested are being voiced by critics from medicine as well as philosophy, it is worthwhile to view the committee's report in relation to the problem that prompted its existence as well as the one to which it was quickly applied.

A Path Not Taken: Beecher, Brain Death, and the Aims of Medicine.

It has been fifty years since a report by an ad hoc committee of Harvard Medical School ushered in the widespread adoption of brain death as a definition of death. Yet brain death remains disputed as an acceptable definition within bioethics. The continuous debate among bioethicists has had three key recurring features: first and foremost, argument over alleged flaws in the conceptual logic and consistency of the "whole-brain" approach as a description of the meaning of death; second, efforts to fix perceived limitations of brain death-based practices to optimize transplantation, especially given that transplantation was the presumed original intended purpose of the definition; and third, a basic unease provoked by the experience of using the criteria and managing a body in this state of "irreversible coma." The third feature is the one I find the most compelling, though it is less explored, and it persists because of the failures of the prior two. Brain death remains strange-to medical personnel, families, philosophers. That is not because it hasn't yet been logically argued well enough or conceptually framed adequately, but because those things don't matter as much to resolving this strangeness as the bioethical approach to brain death over the last fifty years has assumed it does. It is necessary to look to other things that can anchor the aims of medicine in the midst of this strangeness.

The effectiveness of non-invasive brain stimulation on arousal and alertness in patients in coma or persistent vegetative state after traumatic brain injury: Protocol of systematic review and network meta-analysis.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability worldwide. The survivors usually suffer from disorders of consciousness, especially coma state and persistent vegetative state. For these patients, there is no standard treatment for them, but non-invasive brain stimulations are considered as relatively more acceptable treatments. However, the knowledge regarding the relative effectiveness and the rank of the effectiveness of the non-invasive brain stimulations is limited. Thus, in this study, we aim to conduct a systematic review and network meta-analysis to evaluate the effect of non-invasive train stimulations on arousal and alertness in patients in a coma or persistent vegetative state after traumatic brain injury. METHODS AND ANALYSIS: A comprehensive search strategy will be performed in the relevant databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wan Fang Data). The random or quasi-random controlled trails focusing on the effectiveness of the non-invasive brain stimulations will be included. The risk of bias for the included studies will be appraised using the Cochrane collaboration tool for assessing risk of bias. The standard pairwise meta-analysis and a Bayesian network meta-analysis will be conducted. ETHICS AND DISSEMINATION: This research is a systematic review and network meta-analysis. Thus, there is no requirement of ethical approval and patient informed consent. PROSPERO REGISTRATION NUMBER: CRD42018104945.

Psychogenic coma after dental surgery under general anaesthesia.

Delayed awakening after general anaesthesia due to psychogenic coma is a phenomenon that rarely presents to the oral and maxillofacial surgeon. A case of psychogenic coma following general anaesthesia for dental extractions is presented here. It is recommended that patients at risk of conversion disorder should be counselled about the risks of psychogenic coma. Early diagnosis of this condition could lead to better patient management.

Assessment of Visual Pursuit in Patients With Disorders of Consciousness Based on a Brain-Computer Interface.

Visual pursuit assessment is extensively applied in the behavioral scale-based clinical examination of patients with disorders of consciousness (DOC). However, this assessment is challenging because it relies on behavioral markers, and these patients severely lack behavioral responses. Brain-computer interfaces (BCIs) may provide a potential solution to detect brain responses to external stimuli without requiring behavioral expressions. A BCI system was designed to simulate visual pursuit detection in the coma recovery scale-revised (CRS-R). The graphical user interface included four buttons, one that moved on the screen and three that did not. These buttons flashed in a random order. The patients were prompted to follow the moving button. Based on the collected electroencephalography data, the algorithm determined whether the patient focused on the moving target. Among the 14 DOC patients who participated in the assessments based on the BCI system and the CRS-R, four patients exhibited visual pursuit, and three were nonresponsive in both assessments. More importantly, seven patients who did not exhibit visual pursuit in CRS-R were detected to be responsive to the moving target stimuli in the BCI assessment. Furthermore, five out of seven recovered consciousness to some degree and showed visual pursuit in the second CRS-R assessment. The proposed BCI system is better able to detect visual pursuit than the behavioral scale-based assessment and thus can assist in clinically evaluating the challenging population of DOC patients.

Neurologic outcomes in pediatric cardiac arrest survivors enrolled in the THAPCA trials.

OBJECTIVE: To implement a standardized approach to characterize neurologic outcomes among 12-month survivors in the Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trials. METHODS: Two multicenter trials enrolled children age 48 hours to 18 years who remained comatose after cardiac arrest (CA) occurring out-of-hospital (THAPCA-OH, NCT00878644) or in-hospital (THAPCA-IH, NCT00880087); patients were randomized to therapeutic hypothermia or therapeutic normothermia. The primary outcome, survival with favorable 12-month neurobehavioral outcome (Vineland Adaptive Behavior Scales [VABS-II]), did not differ between treatment groups in either trial. Neurologists examined 181 12-month survivors, described findings using the novel semi-quantitative Pediatric Resuscitation after Cardiac Arrest (PRCA) form, and rated findings in 6 domains; scores ranged from 0 (no deficits) to 21 (maximal deficits). PRCA scores were compared with 12-month VABS-II scores and cognitive scores. RESULTS: Neurologic outcome PRCA scores were classified as no/minimal impairment, PRCA 0-3, 81/179 (45%); mild impairment, PRCA 4-7, 24/179 (13%); moderate impairment, PRCA 8-11, 15/179 (8%); severe impairment, PRCA 12-16, 20/179 (11%); profound impairment, PRCA 17-21, 39/179 (21%) (2/181 incomplete). VABS-II scores correlated strongly with PRCA category (r = -0.88, p < 0.0001, Pearson correlation coefficient) and cognitive scores (r = -0.72, p < 0.0001). Factors associated with poor outcomes included out-of-hospital CA, seizure recognition in the early postarrest period, and poor neurologic status at hospital discharge. CONCLUSION: The PRCA provides a robust method for depicting neurologic outcomes after acute encephalopathy caused by CA in children. It provides a global semiquantitative rating of neurologic impairment and domain-specific impairment. The strong correlation with well-established neurobehavioral outcome measures supports its validity over a broad age range and wide spectrum of outcomes.

False memory susceptibility in coma survivors with and without a near-death experience.

It has been postulated that memories of near-death experiences (NDEs) could be (at least in part) reconstructions based on experiencers' (NDErs) previous knowledge and could be built as a result of the individual's attempt to interpret the confusing experience. From the point of view of the experiencer, NDE memories are perceived as being unrivalled memories due to its associated rich phenomenology. However, the scientific literature devoted to the cognitive functioning of NDErs in general, and their memory performance in particular, is rather limited. This study examined NDErs' susceptibility to false memories using the Deese-Roediger-McDermott (DRM) paradigm. We included 20 NDErs who reported having had their experience in the context of a life-threatening event (Greyson NDE scale total score ≥7/32) and 20 volunteers (matched for age, gender, education level, and time since brain insult) who reported a life-threatening event but without a NDE. Both groups were presented with DRM lists for a recall task during which they were asked to assign "Remember/Know/Guess" judgements to any recalled response. In addition, they were later asked to complete a post-recall test designed to obtain estimates of activation and monitoring of critical lures. Results demonstrated that NDErs and volunteers were equally likely to produce false memories, but that NDErs recalled them more frequently associated with compelling illusory recollection. Of particular interest, analyses of activation and monitoring estimates suggest that NDErs and volunteers groups were equally likely to think of critical lures, but source monitoring was less successful in NDErs compared to volunteers.