Automated pupillometry to detect command following in neurological patients: A proof-of-concept study

Abstract

Background: Levels of consciousness in patients with acute and chronic brain injury are notoriously underestimated. Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis. Methods: To assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including 7 patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic. Results: Fourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%) neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥ 4 of 5 arithmetic tasks. None of the 5 sedated and unconscious ICU patients passed this threshold. Conclusions: Automated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury. We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown. If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal conscious awareness in unresponsive patients in whom standard investigations have failed to detect signs of covert consciousness.

European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness

“…There is a wealth of other clinical bedside markers that were excluded here due to lack of sufficient data but that nevertheless appear promising. These include searching for resistance to eye opening , command following using automated pupillometry , quantitative assessment of visual tracking , standardized rating of spontaneous motor behavior , possibility of oral feeding , evidence of circadian rhythms , exploitation of vegetative responses such as increased salivation with salient stimuli or modulations of the cardiac cycle , and sampling of observations made by nursing staff .…”

New Behavioral Signs of Consciousness in Patients with Severe Brain Injuries

“…Recent studies, beyond the scope of this article, suggest that electrophysiological findings, 63 64 65 66 67 68 69 70 71 72 73 neuroimaging findings, 16 43 74 pupil responses, 75 76 and autonomic nervous system correlates 77 78 might also reflect the level of consciousness in patients with DoC. Thus, we emphasize the need to further investigate and validate these parameters within the framework of a multimodal assessment (behavioral and neuroimaging) in DoC patients.…”

“…Regarding the diagnosis of DoC patients, some of the recommendations by the 2020 European Academy of Neurology guideline 27 are as follows: (1) passively opening patients' eyes who have no spontaneous or stimulation-triggered eye opening, and assess for both horizontal and vertical eye movements (patients with locked-in syndrome have preserved vertical eye movements) (strong recommendation); (2) using a mirror for visual pursuit, and if not elicited by a mirror, the use of pictures showing the patient's or relatives' faces or personal objects (strong recommendation); and (3) using repeated CRS-R (at least five times) assessments in the subacute–chronic setting and the Full Outline of UnResponsiveness scale in the acute setting instead of the GCS (strong recommendation). Also, the need for multicenter collaborations is highly stressed in this guideline, as well as the need for more studies investigating resistance to eye opening, 35 pupillary dilation assessment following mental arithmetic with automated pupillometry, 75 85 quantitative assessment of visual tracking, 86 87 standardized rating of spontaneous motor behavior, 58 the possibility of oral feeding, 53 evidence of circadian rhythms, 88 vegetative responses to salient stimuli, 89 and modulations of cardiac cycle (heart rate, heart rate variability, cardiac cycle phase shifts). 69 70…”

Language Assessment in Patients with Disorders of Consciousness

“…44 45 46 Note that other electrophysiological measures may be used, such as electromyography 47 or automated pupillometry. 48 These techniques, however, need to be further investigated to support their validity in the assessment of DoC patients.…”