Despite evidence from neuroimaging research, diagnosis and early prognosis in the vegetative (VS/UWS) and minimally conscious (MCS) states still depend on the observation of clinical signs of responsiveness. Multiple testing has documented a systematic variability during the day in the incidence of established signs of responsiveness. Spontaneous fluctuations of the Coma Recovery Scale-revised (CRS-r) scores are conceivable. We retrospectively analyzed the CRS-r repeatedly administered to 7 VS/UWS and 12 MCS subjects undergoing systematic observation during a conventional 13 weeks. rehabilitation plan. The CRS-r global, visual and auditory scores were found higher in the morning than at the afternoon administration in both VS/UWS and MCS subgroups over the entire period of observation. The probability for a VS/UWS subject of being classified as MCS at the morning testing at least once during the 13 weeks. observation was as high as 30 %, i.e., compatible with the reported misdiagnosis rate between the two clinical conditions. Multiple CRS-r testing is advisable to minimize the risk of misclassification; estimates of spontaneous variability could be used to characterize with greater accuracy patients with disorder of consciousness and possibly help optimize the rehabilitation plan.

Visual pursuit marks substantial recuperation from a vegetative state and evolution into a minimally-conscious state, but its incidence in different studies suggests some unreliability in contrast with its established prognostic relevance. Subjects in vegetative ( n =9) or minimally-conscious ( n =13) states were tested for visual pursuit 6 times/day (9:30, 10:30, and 11:30 am , and 2:00, 3:00, and 4.00 pm , for a total of 132 determinations). Visual pursuit was observed at all testing times in 8 minimally-conscious patients, and never in 5 subjects in a vegetative state. Its incidence per subject ranged from 50–100% of testing times in the minimally-conscious state (83±23%), and 0–33% in a vegetative state (7%±12), with spontaneous fluctuations during the day and maximal levels at 10.30 am and 3.00 pm , and was never observed at the post-prandial time point (2:00 pm ). The overall chance of observing visual tracking at least once during the day was ∼33% in the vegetative state, whereas that of not observing it in the minimally-conscious state was ∼38%. These percentages are congruent with the reported misdiagnosis rate between the two conditions, and document spontaneous variability possibly related to circadian rhythms.

Objectives: Considering sensory stimulation programs (SSP) as a treatment for disorders of consciousness is still debated today. Previous studies investigating its efficacy were affected by various biases among which small sample size and spontaneous recovery. In this study, treatment-related changes were assessed using time-series design in patients with disorders of consciousness (i.e., vegetative state—VS and minimally conscious state—MCS). Methods: A withdrawal design (ABAB) was used. During B phases, patients underwent a SSP (3 days a week, including auditory, visual, tactile, olfactory, and gustatory stimulation). The program was not applied during A phases. To assess behavioral changes, the Coma Recovery Scale-Revised (CRS-R) was administered by an independent rater on a weekly basis, across all phases. Each phase lasted 4 weeks. In a subset of patients, resting state functional magnetic resonance imaging (fMRI) data were collected at the end of each phase. Results: Twenty nine patients (48 ± 19 years old; 15 traumatic; 21 > a year post-injury; 11 VS and 18 MCS) were included in our study. Higher CRS-R total scores (medium effect size) as well as higher arousal and oromotor subscores were observed in the B phases (treatment) as compared to A phases (no treatment), in the MCS group but not in the VS group. In the three patients who underwent fMRI analyses, a modulation of metabolic activity related to treatment was observed in middle frontal gyrus, superior temporal gyrus as well as ventro-anterior thalamic nucleus. Conclusion: Our results suggest that SSP may not be sufficient to restore consciousness. SSP might nevertheless lead to improved behavioral responsiveness in MCS patients. Our results show higher CRS-R total scores when treatment is applied, and more exactly, increased arousal and oromotor functions.

Background Disorders of consciousness are challenging to diagnose, with inconsistent behavioural responses, motor and cognitive disabilities, leading to approximately 40% misdiagnoses. Heart rate variability (HRV) reflects the complexity of the heart-brain two-way dynamic interactions. HRV entropy analysis quantifies the unpredictability and complexity of the heart rate beats intervals. We here investigate the complexity index (CI), a score of HRV complexity by aggregating the non-linear multi-scale entropies over a range of time scales, and its discriminative power in chronic patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), and its relation to brain functional connectivity. Methods We investigated the CI in short (CIs) and long (CIl) time scales in 14 UWS and 16 MCS sedated. CI for MCS and UWS groups were compared using a Mann-Whitney exact test. Spearman’s correlation tests were conducted between the Coma Recovery Scale-revised (CRS-R) and both CI. Discriminative power of both CI was assessed with One-R machine learning model. Correlation between CI and brain connectivity (detected with functional magnetic resonance imagery using seed-based and hypothesis-free intrinsic connectivity) was investigated using a linear regression in a subgroup of 10 UWS and 11 MCS patients with sufficient image quality. Results Higher CIs and CIl values were observed in MCS compared to UWS. Positive correlations were found between CRS-R and both CI. The One-R classifier selected CIl as the best discriminator between UWS and MCS with 90% accuracy, 7% false positive and 13% false negative rates after a 10-fold cross-validation test. Positive correlations were observed between both CI and the recovery of functional connectivity of brain areas belonging to the central autonomic networks (CAN). Conclusion CI of MCS compared to UWS patients has high discriminative power and low false negative rate at one third of the estimated human assessors’ misdiagnosis, providing an easy, inexpensive and non-invasive diagnostic tool. CI reflects functional connectivity changes in the CAN, suggesting that CI can provide an indirect way to screen and monitor connectivity changes in this neural system. Future studies should assess the extent of CI’s predictive power in a larger cohort of patients and prognostic power in acute patients.

The physiological role and relevance of the mechanisms sustaining circadian rhythms have been acknowledged. Abnormalities of the circadian and/or sleep-wakefulness cycles can result in major metabolic disorders or behavioral/professional inadequacies and stand as independent risk factors for metabolic, psychiatric, and cerebrovascular disorders and early markers of disease. Neuroimaging and clinical evidence have documented functional interactions between autonomic (ANS) and CNS structures that are described by a concept model (Central Autonomic Network) based on the brain-heart two-way interplay. The circadian rhythms of autonomic function, ANS-mediated processes, and ANS/CNS interaction appear to be sources of variability adding to a variety of environmental factors, and may become crucial when considering the ANS major role in internal environment constancy and adaptation that are fundamental to homeostasis. The CNS/ANS interaction has not yet obtained full attention and systematic investigation remains overdue.