The Clinical Diagnostic Utility of Electrophysiological Techniques in Assessment of Patients With Disorders of Consciousness Following Acquired Brain Injury: A Systematic Review.

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

A study of the reliability of the Nociception Coma Scale.

OBJECTIVE: In this study, we investigated the reliability of the Nociception Coma Scale which has recently been developed to assess nociception in non-communicative, severely brain-injured patients. DESIGN: Prospective cross-sequential study. SETTING: Semi-intensive care unit and long-term brain injury care. SUBJECTS: Forty-four patients diagnosed as being in a vegetative state (n=26) or in a minimally conscious state (n=18). INTERVENTIONS: Patients were assessed by two experts (rater A and rater B) on two consecutive weeks to measure inter-rater agreement and test-retest reliability. MAIN MEASURES: Total scores and subscores of the Nociception Coma Scale. RESULTS: We performed a total of 176 assessments. The inter-rater agreement was moderate for the total scores (k = 0.57) and fair to substantial for the subscores (0.33 ≤ k ≤ 0.62) on week 2. The test-retest reliability was substantial for the total scores (k = 0.66) and moderate to almost perfect for the subscores (0.53 ≤ k ≤ 0.96) for rater A. The inter-rater agreement was weaker on week 1, whereas the test-retest reliability was lower for the least experienced rater (rater B). CONCLUSIONS: This study provides further evidence of the psychometric qualities of the Nociception Coma Scale. Future studies should assess the impact of practical experience and background on administration and scoring of the scale.

Burnout in healthcare workers managing chronic patients with disorders of consciousness.

OBJECTIVES: The aim of this study was to assess the presence of burnout among professional caregivers managing patients with severe brain injury recovering from coma and working in neurorehabilitation centres or nursing homes. METHODS: The Maslach Burnout Inventory was sent to 40 centres involved in the Belgian federal network for the care of vegetative and minimally conscious patients. The following demographic data were also collected: age, gender, profession, expertise in the field, amount of time spent with patients and working place. RESULTS: Out of 1068 questionnaires sent, 568 were collected (53% response rate). Forty-five were excluded due to missing data. From the 523 healthcare workers, 18% (n = 93) presented a burnout, 33% (n = 171) showed emotional exhaustion and 36% (n = 186) had a depersonalization. Profession (i.e. nurse/nursing assistants), working place (i.e. nursing home) and the amount of time spent with patients were associated with burnout. The logistic regression showed that profession was nevertheless the strongest variable linked to burnout. CONCLUSIONS: According to this study, a significant percentage of professional caregivers and particularly nurses taking care of patients in a vegetative state and in a minimally conscious state suffered from burnout. Prevention of burnout symptoms among caregivers is crucial and is expected to promote more efficient medical care of these challenging patients.

Clinical assessment of patients with disorders of consciousness.

The study of pathological impairments of consciousness, as they can appear in severely brain injured patients, can be particularly useful to better clarify cognitive processes and cerebral substrates which underlie consciousness. In this review, we will introduce the disorders of consciousness that can be presented by severely brain-injured patients and the behavioural scales that can be used to assess their level of consciousness. We will also discuss the difficulty to assess and detect remnant cognitive functioning in these patients.

[The Sensory Modality Assessment and Rehabilitation Technique (SMART): a behavioral assessment scale for disorders of consciousness]. / La Sensory Modality Assessment and Rehabilitation Technique (SMART) : une échelle comportementale d'évaluation et de revalidation pour des états altérés de conscience.

INTRODUCTION: Difficulties in detecting bedside signs of consciousness in non-communicative patients still lead to a high rate of misdiagnosis illustrating the need to employ standardized behavioral assessment scales. STATE OF ART: The Sensory Modality Assessment and Rehabilitation Technique (SMART) is a behavioral assessment scale of consciousness that assesses responses to multimodal sensory stimulation in disorders of consciousness. These stimulations can also be considered to have therapeutic value. PERSPECTIVES: We here review the different components and use of the SMART assessment and discuss its validity, reliability, and robustness in clinical practice. The scale has a high intra- and inter-observer reliability thanks to a detailed procedure description. However, in the absence of objective gold standards in the assessment of consciousness, it is currently difficult to make strong claims about its validity. A comparison between SMART and other standardized and validated coma-scales is proposed. CONCLUSION: In our view, SMART is an interesting tool for monitoring patients with altered states of consciousness subsequent to coma. Currently, we await studies on its concurrent validity as compared to other validated behavioral assessment scales and on the effect of SMART stimulations on patient outcome.

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.

Pain and non-pain processing during hypnosis: a thulium-YAG event-related fMRI study.

The neural mechanisms underlying the antinociceptive effects of hypnosis still remain unclear. Using a parametric single-trial thulium-YAG laser fMRI paradigm, we assessed changes in brain activation and connectivity related to the hypnotic state as compared to normal wakefulness in 13 healthy volunteers. Behaviorally, a difference in subjective ratings was found between normal wakefulness and hypnotic state for both non-painful and painful intensity-matched stimuli applied to the left hand. In normal wakefulness, non-painful range stimuli activated brainstem, contralateral primary somatosensory (S1) and bilateral insular cortices. Painful stimuli activated additional areas encompassing thalamus, bilateral striatum, anterior cingulate (ACC), premotor and dorsolateral prefrontal cortices. In hypnosis, intensity-matched stimuli in both the non-painful and painful range failed to elicit any cerebral activation. The interaction analysis identified that contralateral thalamus, bilateral striatum and ACC activated more in normal wakefulness compared to hypnosis during painful versus non-painful stimulation. Finally, we demonstrated hypnosis-related increases in functional connectivity between S1 and distant anterior insular and prefrontal cortices, possibly reflecting top-down modulation.

Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient.

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico-thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico-cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio-respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age-matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task-positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long-distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population.

Diagnostic and prognostic use of bispectral index in coma, vegetative state and related disorders.

PRIMARY OBJECTIVE: This study investigates (1) the utility of the bispectral index (BIS) to distinguish levels of consciousness in severely brain damaged patients and, particularly, disentangle vegetative state (VS) from minimally conscious state (MCS), as compared to other EEG parameters; (2) the prognostic value of BIS with regards to recovery after 1 year. RESEARCH DESIGN: Multi-centric prospective study. METHOD AND PROCEDURES: Unsedated patients recovering from coma were followed until death or transferal. Automated electrophysiological and standardized behavioural assessments were carried out twice a week. EEG recordings were categorized according to level of consciousness (coma, VS, MCS and Exit MCS). Outcome was assessed at 1 year post-insult. MAIN OUTCOMES AND RESULTS: One hundred and fifty-six EEG epochs obtained in 43 patients were included in the analyses. BIS showed a higher correlation with behavioural scales as compared to other EEG parameters. Moreover, BIS values differentiated levels of consciousness and distinguished VS from MCS while other EEG parameters did not. Finally, higher BIS values were found in patients who recovered at 1 year post-insult as compared to patients who did not recover. CONCLUSION: EEG-BIS recording is an interesting additional method to help in the diagnosis as well as in the prognosis of severely brain injured patients recovering from coma.

[Blink and you live: the locked-in syndrome]. / Le Locked-In Syndrome: la conscience emmurée.

INTRODUCTION: The Locked-In syndrome (LIS) is defined by: (i) the presence of sustained eye opening (bilateral ptosis should be ruled out as a complicating factor); (ii) preserved awareness; (iii) aphonia or hypophonia; (iv) quadriplegia or quadriparesis; and (v) a primary mode of communication that uses vertical or lateral eye movement or blinking. Acute ventral pontine lesions are its most common cause. Following such brainstem lesions patients may remain comatose for some time and then gradually awaken, remaining paralyzed and voiceless, superficially resembling the vegetative state. BACKGROUND: It has been shown that more than half of the time physicians fail to recognize early signs of awareness in LIS. Given appropriate medical care, life expectancy may be several decades but the chances of good motor recovery remain small. Eye-controlled computer technology now allows LIS patients to communicate and control their environment. Recent studies show that most LIS patients self-report meaningful quality of life and the demand for euthanasia is infrequent. CONCLUSION: Patients suffering from LIS should not be denied the right to die--and to die with dignity--but also they should not be denied the right to live--and to live with dignity and the best possible pain and symptom management and revalidation.

Revelations from the unconscious: studying residual brain function in coma and related states.

The purpose of our research is to contribute to a better understanding of the residual brain function of patients who survive an acute brain damage but remain in a coma, vegetative state, minimally conscious state or locked-in syndrome. The diagnosis, prognosis, therapy and medical management of these patients remain difficult. These studies are also of interest scientifically, as they help to elucidate the neural correlates of human consciousness. We here review our studies on bedside behavioral evaluation scales, electrophysiology and functional neuroimaging in these disorders of consciousness and conclude by discussing methodological and ethical issues and current concepts of the standards for care and quality of life in these challenging conditions.

[Near-death experiences: fact and fancy]. / Expériences de mort imminente: phénomènes paranormaux ou neurologiques?

Seeing a bright light at the end of a tunnel or having a sense of being out of the physical body are phenomena that some patients report after having been close to death. Some spiritual and psychological theories have been developed in order to explain these near-death-experiences. Clinical studies have aimed to determine their frequency and to assess their precipitating factors. Recent neuroimaging studies, however, have shown the involvement of the temporo-parietal cortex in the generation of out-of-body experiences and are offering a physiological, neurological account for the phenomenon, rebuffing dualistic, non-physical explanations.

[Hypnosis and pain perception]. / Hypnose et perception de la douleur.

Improvement in functional neuroimaging allows researchers to disentangle the brain mechanisms involved in the pain modulation encountered during hypnosis. It has been shown that the anterior cingulate and prefrontal cortices are important in the modulation of incoming sensory and noxious input. Moreover, clinical studies in certain types of surgery (eg thyroidectomy, mastectomy and plastic surgery) have demonstrated that hypnosis may avoid general anesthesia.

[Life with Locked-In syndrome]. / Quelle vie après le Locked-In syndrome?

The Locked-In Syndrome (LIS) is classically caused by an anterior pontine vascular lesion and characterized by quadriplegia and anarthria with preserved consciousness and intellectual functioning. We here review the definition, etiologies, diagnosis and prognosis of LIS patients and briefly discuss the few studies on their quality of life and the challenging end-of-life decisions that can be encountered. Some clinicians may consider that LIS is worse than being in a vegetative or in a minimally conscious state. However, preliminary data from chronic LIS survivors show a surprisingly preserved self-scored quality of life and requests of treatment withdrawal or euthanasia, though not absent, are infrequent.

[Pain assessment in non-communicative patients]. / Mesurer la douleur chez le patient non communicant.

Pain is a subjective experience. Its assessment is based on the subject's direct verbal report. This method of assessment is, however, impossible in patients who cannot communicate their feelings. In this context, indirect measurements such as behavioral observations or physiological measurements are needed. To facilitate the assessment of pain in non-communicative patients, numerous standardized behavioral scales have been developed. The aim of this review is to discuss the main validated pain scales employed in end-stage dementia, newborn and preverbal children, and severely brain damaged patients with a disorder of consciousness such as coma, the vegetative state or the minimally conscious state.

[Behavioural assessment and functional neuro-imaing in vegetative state patients]. / Evaluation comportementale et par neuroimagerie fonctionnelle des patients en état végétatif.

Currently, there remains a high rate of misdiagnosis of the vegetative state. This should incite clinicians to use the most sensitive "coma scales" to detect signs of consciousness in these patients. The gold standard remains the Glasgow Coma Scale (GCS, Teasdale and Jennet, 1974), with the Glasgow Liège Scale (GLS, Born, 1988) adding standardized assessment of brainstem reflexes. New sensible behavioral assessment tools for use in the acute neurocritical care setting include the Full Outline of UnResponsiveness (FOUR, Wijdicks et al., 2005). The Coma Recovery Scale-Revised (CRS-R, Giacino and Kalmar, 2004) specifically tests the diagnostic criteria differentiating vegetative from minimally conscious patients. Detecting signs of consciousness also depends on the employed methodology. We showed that for the assesment of the presence of visual pursuit, using a moving mirror is better suited than using a moving object or person. The clinical diagnosis can be confirmed by cerebral positron emission tomography studies objectively quantifying residual metabolic activity in vegetative and minimally conscious patients. Ongoing studies evaluate the prognostic value of functional magnetic resonance imaging studies in these challenging patient populations.

Spasticity in disorders of consciousness: a behavioral study.

BACKGROUND: Spasticity is a frequent complication after severe brain injury, which may impede the rehabilitation process and diminish the patients' quality of life. AIM: We here investigate the presence of spasticity in a population of non-communicative patients with disorders of consciousness. We also evaluate the correlation between spasticity and potential factors of co-morbidity, frequency of physical therapy, time since insult, presence of pain, presence of tendon retraction, etiology and diagnosis. DESIGN: Cross-sectional study. SETTING: University Hospital of Liège, Belgium. POPULATION: Sixty-five patients with chronic (>3 months post insult) disorders of consciousness were included (22 women; mean age: 44±14 y; 40 with traumatic etiology; 40 in a minimally conscious state; time since insult: 39±37 months). METHODS: Spasticity was measured with the Modified Ashworth Scale (MAS) and pain was assessed using the Nociception Coma Scale-Revised (NCS-R). RESULTS: Out of 65 patients, 58 demonstrated signs of spasticity (89%; MAS≥1), including 40 who showed severe spasticity (61.5%; MAS≥3). Patients with spasticity receiving anti-spastic medication were more spastic than unmedicated patients. A negative correlation was observed between the severity of spasticity and the frequency of physical therapy. MAS scores correlated positively with time since injury and NCS-R scores. We did not observe a difference of spasticity between the diagnoses. CONCLUSION: A large proportion of patients with disorders of consciousness develop severe spasticity, possibly affecting their functional recovery and their quality of life. The observed correlation between degrees of spasticity and pain scores highlights the importance of pain management in these patients with altered states of consciousness. Finally, the relationship between spasticity and treatment (i.e., pharmacological and physical therapy) should be further investigated in order to improve clinical care. CLINICAL REHABILITATION IMPACT: Managing spasticity at first signs could improve rehabilitation of patients with disorders of consciousness and maximize their chances of recovery. In addition, decreasing this trouble could allow a better quality of life for these non-communicative patients.