Abstract
The assessment of the consciousness level of Unresponsive Wakefulness Syndrome (UWS) patients often depends on a subjective interpretation of the observed spontaneous and volitional behavior. To date, the misdiagnosis level is around 30%. The aim of this study was to observe the behavior of UWS patients, during the administration of noxious stimulation by a Trace Conditioning protocol, assessed by the Galvanic Skin Response (GSR) and Heart Rate Variability (HRV) entropy. We recruited 13 Healthy Control (HC) and 30 UWS patients at 31 ± 9 days from the acute event evaluated by Coma Recovery Scale–Revised (CRS-R) and Nociception Coma Scale (NCS). Two different stimuli [musical stimulus (MUS) and nociceptive stimulus (NOC)], preceded, respectively by two different tones, were administered following the sequences (A) MUS1 – NOC1 – MUS2 – MUS3 – NOC2 – MUS4 – NOC3 – NOC*, and (B) MUS1*, NOC1*, NOC2*, MUS2*, NOC3*, MUS3*, NOC4*, MUS4*. All the (*) indicate the only tones administration. CRS-R and NCS assessments were repeated for three consecutive weeks. MUS4, NOC3, and NOC* were compared for GSR wave peak magnitude, time to reach the peak, and time of wave's decay by Wilcoxon's test to assess the Conditioned Response (CR). The Sample Entropy (SampEn) was recorded in baseline and both sequences. Machine Learning approach was used to identify a rule to discriminate the CR. The GSR magnitude of CR was higher comparing music stimulus (p < 0.0001) and CR extinction (p < 0.002) in nine patients and in HC. Patients with CR showed a higher SampEn in sequence A compared to patients without CR. Within the third and fourth weeks from protocol administration, eight of the nine patients (88.9%) evolved into MCS. The Machine-learning showed a high performance to differentiate presence/absence of CR (≥95%). The possibility to observe the CR to the noxious stimulus, by means of the GSR and SampEn, can represent a potential method to reduce the misdiagnosis in UWS patients.
Highlights
Disorders of Consciousness (DOC) are a spectrum of pathologies affecting one’s ability to interact with the external world
We explored the possibility to observe the autonomic response related to a Trace Conditioning learning experiment, by means of a nociceptive stimulus in Unresponsive Wakefulness Syndrome (UWS) patients, and if such learning may have a significance in the recovery of the consciousness
MCS, Minimally Conscious State; UWS, Unresponsive Wakefulness Syndrome; UWS*, patients without Conditioned Response (CR) that change the level of consciousness after 6 months from the onset; HEM, Hemorrhagic; TBI, Traumatic Brain Injury; ANOX, Anoxic; CR, Conditional Response (0 = absent; 1 = present); CRS-R, Coma Recovery Scale–Revised; NCS, Nociception Coma Scale; Week (I-IV), Successive weeks during which the patients were assessed by CRS-R and NCS
Summary
Disorders of Consciousness (DOC) are a spectrum of pathologies affecting one’s ability to interact with the external world They are increasingly becoming a worldwide health concern, whether due to a traumatic (Meaney et al, 2014; Roebuck-Spencer and Cernich, 2014) or non-traumatic cause (Gitler et al, 2017; Erkkinen et al, 2018), with its share of ethically challenging questions (Fins, 2005; Demertzi et al, 2011; Riganello et al, 2016), including life and death decisions. The MCS patients exhibit minimal but discernible signs of non-reflex behaviors which occur reproducibly (yet inconsistently) as a response to visual, auditory, tactile, or noxious stimuli; UWS (Laureys et al, 2010) condition is characterized by a spontaneous opening of the eyes and no sign of consciousness, but reflexive responses to external stimuli (Jennett, 2002; Dolce et al, 2010)
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