Periodic Reporting for period 1 - ADOC (Characterization and monitoring of vigilance fluctuation in disorders of consciousness)
Reporting period: 2017-08-01 to 2019-07-31
The clinical diagnosis of consciousness in patients with severe brain injury is mainly based on bedside observation of the patient's responses to the environment using standardized neurobehavioral scales. However, they are not all reliable and studies have revealed that about 40% of the patients are clinically misdiagnosed as being unconscious. In addition, as the probability to detect voluntary responses depends on the patient's level of vigilance at the time of assessment, multiple assessments are needed to detect signs of consciousness and, consequently, to avoid misdiagnoses. Misdiagnoses can lead to critical ethical consequences, especially in terms of end-of-life decision-making and pain treatment. In this project, we aimed at better characterize vigilance fluctuation (as defined by a change in behavioral responsiveness during the day) in patients with severe brain injury using neurophysiological parameters (i.e. eye responses, electroencephalography, actigraphy).
We acquired data using eye and electroencephalography (EEG) recordings in 16 severely brain-injured patients. Patients were seen 4 times in one day at fixed time-points (i.e. 9h30 – 11h30 – 13h30 – 15h30). During each session, the patients’ level of responsiveness was assessed with the Coma Recovery-Scale-Revised (CRS-R) by a trained examiner. EEG and eye responses were also recorded 10 minutes before and after each assessment.
Preliminary analyses suggested that higher responsiveness was related to higher median and complexity of the pupillometry signal and eye opening percentage, at rest, supporting that pupillometry markers could be used as potential predictor of behavioral responsiveness in these patients.
In parallel, we collected retrospective data acquired in 24 severely brain-injured patients over a short period of time (7 days). Patients were included if they had at least four assessments, performed twice in the morning and twice in the afternoon.
All patients but one showed variability in responsiveness (i.e. CRS-R scores) across the four assessments and there was no difference between mean scores obtained in the morning or in the afternoon. About 50% of the patients showed diagnostic changes across the four assessments. Nineteen of these patients also had actigraphy recorded. Seventeen out of 19 (89%) showed significant rhythms on actigraphy, suggesting circadian rhythm. In these patients, we could not report a correlation between CRSR scores and motor activity.
Preliminary analyses suggested that higher responsiveness was related to higher median and complexity of the pupillometry signal and eye opening percentage, at rest, supporting that pupillometry markers could be used as potential predictor of behavioral responsiveness in these patients.
In parallel, we collected retrospective data acquired in 24 severely brain-injured patients over a short period of time (7 days). Patients were included if they had at least four assessments, performed twice in the morning and twice in the afternoon.
All patients but one showed variability in responsiveness (i.e. CRS-R scores) across the four assessments and there was no difference between mean scores obtained in the morning or in the afternoon. About 50% of the patients showed diagnostic changes across the four assessments. Nineteen of these patients also had actigraphy recorded. Seventeen out of 19 (89%) showed significant rhythms on actigraphy, suggesting circadian rhythm. In these patients, we could not report a correlation between CRSR scores and motor activity.
The preliminary analyses of neurophysiological data support the interest of eye parameters, such as eye opening and pupil diameter, to be used as potential predictors of behavioral responsiveness in this population, as already shown in healthy population.
Although a previous study suggested that there could be a common trend in vigilance fluctuation in severely brain-injured patients (better responsiveness in the morning than in the afternoon), our data collected over a short period of time (7 days) rather underline a high heterogeneity in daytime behavioral fluctuation in these patients. It also supports previous literature highlighting the necessity to use multiple assessments within a short time-period to get a reliable diagnosis.
In the future, this could help to develop objective tools for vigilance monitoring and therefore increase the chance to detect signs of consciousness and improve care for severely brain-injured patients.
Although a previous study suggested that there could be a common trend in vigilance fluctuation in severely brain-injured patients (better responsiveness in the morning than in the afternoon), our data collected over a short period of time (7 days) rather underline a high heterogeneity in daytime behavioral fluctuation in these patients. It also supports previous literature highlighting the necessity to use multiple assessments within a short time-period to get a reliable diagnosis.
In the future, this could help to develop objective tools for vigilance monitoring and therefore increase the chance to detect signs of consciousness and improve care for severely brain-injured patients.