seconds-administration-guidelines-fast-tool-to-assess-consciousness

SECONDs Administration Guidelines: A Fast Tool to Assess Consciousness in Brain-injured Patients

Establishing an accurate diagnosis is crucial for patients with disorders of consciousness (DoC) following a severe brain injury. The Coma Recovery ...

University of Liège

University Hospital of Liège

Recently, neuroscientists and clinicians have seen the rapid evolution of diagnoses in disorders of consciousness. The unresponsive wakefulness syndrome-vegetative state, the minimally conscious state plus and minus, and the functional locked-in syndrome have been defined using new neuroimaging techniques. Diffusion tensor imaging, positron emission tomography, functional magnetic resonance imaging, electroencephalography, and transcranial magnetic stimulation techniques have all promoted important discoveries in the field of disorders of consciousness. This has led to a better understanding of these patients' condition and to the development of new prognosis, therapeutic, and communication tools. However, low sensitivity and artifacts problems need to be solved to bring these new technologies to the single-patient level; they also need to be studied in larger scale and randomized control trials. In addition, new ethics questions have arisen and need to be investigated. 

Coma and disorders of consciousness: scientific advances and practical considerations for clinicians.

Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes of the patients' neurological status, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to improve our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition. 

Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness.

Predicting recovery of consciousness in patients who survive their coma but evolve to a vegetative state (recently coined unresponsive wakefulness syndrome) remains a challenge. Most previous prognostic studies have focused on the acute coma phase. A novel outcome scale (combining behavioural, aetiology, electroencephalographic, sleep electroencephalographic and somatosensory evoked potential data) has been proposed for patients in subacute unresponsive wakefulness syndrome. The scale's clinical application awaits validation in a larger population. 

Predicting outcome from subacute unresponsive wakefulness syndrome or vegetative state.

Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs).

Stratification of unresponsive patients by an independently validated index of brain complexity.

Visual pursuit is a key marker of residual consciousness in patients with disorders of consciousness (DOC). Currently, its assessment relies on subjective clinical decisions. In this study, we explore the variability of such clinical assessments, and present an easy-to-use device composed of cameras and video processing algorithms that could help the clinician to improve the detection of visual pursuit in a clinical context. Visual pursuit was assessed by an experienced research neuropsychologist on 31 patients with DOC and on 23 healthy subjects, while the device was used to simultaneously record videos of both one eye and the mirror. These videos were then scored by three researchers: the experienced research neuropsychologist who did the clinical assessment, another experienced research neuropsychologist, and a neurologist. For each video, a consensus was decided between the three persons, and used as the gold standard of the presence or absence of visual pursuit. Almost 10% of the patients were misclassified at the bedside according to their consensus. An automatic classifier analyzed eye and mirror trajectories, and was able to identify patients and healthy subjects with visual pursuit, in total agreement with the consensus on video. In conclusion, our device can be used easily in patients with DOC while respecting the current guidelines of visual pursuit assessment. Our results suggest that our material and our classification method can identify patients with visual pursuit, as well as the three researchers based on video recordings can.

Objective assessment of visual pursuit in patients with disorders of consciousness: an exploratory study.

Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefulness syndrome from patients in minimally conscious state (MCS). The Coma Recovery Scale-Revised (CRS-R) is the most sensitive scale to differentiate the different altered states of consciousness and eleven items detect the MCS. The aim of this study is to document the prevalence of these items. We analysed behavioural assessments of 282 patients diagnosed in MCS based on the CRS-R. Results showed that some items are particularly frequent among patients in MCS, namely fixation, visual pursuit, and reproducible movement to command, which were observed in more than 50% of patients. These responses were also the most probably observed items when the patients only showed one sign of consciousness. On the other hand, some items were rarely or never observed alone, e.g., object localisation (reaching), object manipulation, intelligible verbalisation, and object recognition. The results also showed that limiting the CRS-R assessment to the five most frequently observed items (i.e., fixation, visual pursuit, reproducible movement to command, automatic motor response and localisation to noxious stimulation) detected 99% of the patients in MCS. If clinicians have only limited time to assess patients with disorders of consciousness, we suggest to evaluate at least these five items of the CRS-R.

Prevalence of coma-recovery scale-revised signs of consciousness in patients in minimally conscious state.

Resistance to eye opening (REO) is a commonly encountered phenomenon in clinical practice. We aim to investigate whether REO is a sign of consciousness or a reflex in severely brain-injured patients.

Resistance to eye opening in patients with disorders of consciousness.

Meditation-induced modulation of brain response to transcranial magnetic stimulation.

The Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain-injured patients, PCI depends on elaborate experimental setups and offline processing, and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings.

A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations.

General anesthesia reversibly alters consciousness, without shutting down the brain globally. Depending on the anesthetic agent and dose, it may produce different consciousness states including a complete absence of subjective experience (unconsciousness), a conscious experience without perception of the environment (disconnected consciousness, like during dreaming), or episodes of oriented consciousness with awareness of the environment (connected consciousness). Each consciousness state may potentially be followed by explicit or implicit memories after the procedure. In this respect, anesthesia can be considered as a proxy to explore consciousness. During the recent years, progress in the exploration of brain function has allowed a better understanding of the neural correlates of consciousness, and of their alterations during anesthesia. Several changes in functional and effective between-region brain connectivity, consciousness network topology, and spatio-temporal dynamics of between-region interactions have been evidenced during anesthesia. Despite a set of effects that are common to many anesthetic agents, it is still uneasy to draw a comprehensive picture of the precise cascades during general anesthesia. Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the detection of specific consciousness states in unresponsive patients and their associated memory processes, the processing of sensory information during anesthesia, the pharmacodynamic interactions between anesthetic agents, the direction-dependent hysteresis phenomenon during the transitions between consciousness states, the mechanisms of cognitive alterations that follow an anesthetic procedure, the identification of an eventual unitary mechanism of anesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical or sleep-wake cycle targets of anesthetic agents, as well as the vast between-studies variations in dose and administration mode, leading to difficulties in between-studies comparisons. In this narrative review, we draw the picture of the current state of knowledge in anesthesia-induced unconsciousness, from insights gathered on propofol, halogenated vapors, ketamine, dexmedetomidine, benzodiazepines and xenon. We also describe how anesthesia can help understanding consciousness, we develop the above-mentioned unresolved questions, and propose tracks for future research.

General Anesthesia: A Probe to Explore Consciousness.

The Coma Recovery Scale-Revised (CRS-R) is the gold standard to assess severely brain-injured patients with prolonged disorders of consciousness (DoC). However, the amount of time needed to complete this examination may limit its use in clinical settings.

Simplified Evaluation of CONsciousness Disorders (SECONDs) in individuals with severe brain injury: a validation study.

Due to life-saving medical advances, the diagnosis and treatment of disorders of consciousness (DOC) has become a more commonly occurring clinical issue. One recently developed intervention option has been non-invasive transcranial direct current stimulation. This dichotomy of patient responders may be better understood by investigating the mechanism behind the transcranial direct current stimulation (tDCS) intervention. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) has been an important diagnostic tool in DOC patients. We therefore examined the neural response using TMS-EEG both before and after tDCS in seven DOC patients (four diagnosed as in a minimally conscious state and three with unresponsive wakefulness syndrome). tDCS was applied over the dorsolateral prefrontal cortex, while TMS pulses were applied to the premotor cortex. None of the seven patients showed relevant behavioral change after tDCS. We did, however, find that the overall evoked slow activity was reduced following tDCS intervention. We also found a positive correlation between the strength of the slow activity and the amount of high-frequency suppression. However, there was no significant pre-post tDCS difference in high frequencies. In the resting-state EEG, we observed that both the incidence of slow waves and the positive slope of the wave were affected by tDCS. Taken together, these results suggest that the tDCS intervention can reduce the slow-wave activity component of bistability, but this may not directly affect high-frequency activity. We hypothesize that while reduced slow activity may be necessary for the recovery of neural function, especially consciousness, this alone is insufficient.

Article	Year
Coma and disorders of consciousness: scientific advances and practical considerations for clinicians. Seminars in neurology\| PubMed ID: 23888393	2013
Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness. Current pharmaceutical design\| PubMed ID: 24025057	2014
Predicting outcome from subacute unresponsive wakefulness syndrome or vegetative state. Critical care (London, England)\| PubMed ID: 25029668	2014
Stratification of unresponsive patients by an independently validated index of brain complexity. Annals of neurology\| PubMed ID: 27717082	2016
Objective assessment of visual pursuit in patients with disorders of consciousness: an exploratory study. Journal of neurology\| PubMed ID: 28364295	2017
Prevalence of coma-recovery scale-revised signs of consciousness in patients in minimally conscious state. Neuropsychological rehabilitation\| PubMed ID: 28399715	2018
Resistance to eye opening in patients with disorders of consciousness. Journal of neurology\| PubMed ID: 29623396	2018
Meditation-induced modulation of brain response to transcranial magnetic stimulation. Brain stimulation\| PubMed ID: 30205950	2018
A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations. Brain stimulation\| PubMed ID: 31133480	2019
General Anesthesia: A Probe to Explore Consciousness. Frontiers in systems neuroscience\| PubMed ID: 31474839	2019
Simplified Evaluation of CONsciousness Disorders (SECONDs) in individuals with severe brain injury: a validation study. Annals of physical and rehabilitation medicine\| PubMed ID: 32992025	2020
Decreased Evoked Slow-Activity After tDCS in Disorders of Consciousness. Frontiers in systems neuroscience\| PubMed ID: 33100977	2020

Olivier Bodart

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