Dissociations between spontaneous electroencephalographic features and the perturbational complexity index in the minimally conscious state.

The analysis of spontaneous electroencephalogram (EEG) is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Although preserved EEG patterns are highly suggestive of consciousness even in unresponsive patients, moderately or severely abnormal patterns are difficult to interpret. Indeed, growing evidence shows that consciousness can be present despite either large delta or reduced alpha activity in spontaneous EEG. Quantifying the complexity of EEG responses to direct cortical perturbations (perturbational complexity index [PCI]) may complement the observational approach and provide a reliable assessment of consciousness even when spontaneous EEG features are inconclusive. To seek empirical evidence of this hypothesis, we compared PCI with EEG spectral measures in the same population of minimally conscious state (MCS) patients (n = 40) hospitalized in rehabilitation facilities. We found a remarkable variability in spontaneous EEG features across MCS patients as compared with healthy controls: in particular, a pattern of predominant delta and highly reduced alpha power-more often observed in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients-was found in a non-negligible number of MCS patients. Conversely, PCI values invariably fell above an externally validated empirical cutoff for consciousness in all MCS patients, consistent with the presence of clearly discernible, albeit fleeting, behavioural signs of awareness. These results confirm that, in some MCS patients, spontaneous EEG rhythms may be inconclusive about the actual capacity for consciousness and suggest that a perturbational approach can effectively compensate for this pitfall with practical implications for the individual patient's stratification and tailored rehabilitation.

Non-Functional Jaw Muscular Activity in Patients with Disorders of Consciousness Revealed by A Long-Lasting Polygraphy.

The presence of involuntary, non-functional jaw muscle activity (NFJMA) has not yet been assessed in patients with disorders of consciousness (DOC), although the presence of bruxism and other forms of movement disorders involving facial muscles is probably more frequent than believed. In this work, we evaluated twenty-two prolonged or chronic DOC patients with a long-lasting polygraphic recording to verify NFJMA occurrence and assess its neurophysiological patterns in this group of patients. A total of 5 out of 22 patients showed the presence of significant NFJMA with electromyographic patterns similar to what can be observed in non-DOC patients with bruxism, thus suggesting a disinhibition of masticatory motor nuclei from the cortical control. On the other hand, in two DOC patients, electromyographic patterns advised for the presence of myorhythmia, thus suggesting a brainstem/diencephalic involvement. Functional, non-invasive tools such as long-lasting polygraphic recordings should be extended to a larger sample of patients, since they are increasingly important in revealing disorders potentially severe and impacting the quality of life of DOC patients.

Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study.

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.

Local sleep-like cortical reactivity in the awake brain after focal injury.

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods-reflecting transient suppressions of neuronal activity-in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

Cardio-respiratory autonomic responses to nociceptive stimuli in patients with disorders of consciousness.

The autonomic response to pain might discriminate among consciousness disorders. Therefore, aim of this study was to describe differences between minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients in their autonomic response to a nociceptive stimulus. ECG, respiration, finger blood pressure (BP) and total peripheral resistances (TPR) were continuously recorded before, during and after a standardized noxious stimulus in 20 adult brain-injured patients, 14 in UWS and 6 in MCS. Occurrence of fast autonomic responses synchronous with the stimulus was detected by visual inspection of the tracings; short-term (<20 s) and long-term (between 20s and 50 s from the stimulus) responses were evaluated by beat-by-beat quantitative analysis. The noxious stimulus elicited fast responses in both groups, but only MCS patients showed a significant short-term response in TPR and long-term response in HR. Thus, short- and long-term cardiovascular responses to pain might integrate neuro-behavioural assessments to discriminate between MCS and UWS.

Cardiac autonomic responses to nociceptive stimuli in patients with chronic disorders of consciousness.

OBJECTIVES: Patients with chronic disorders of consciousness (DOC) may show alterations of autonomic function; however, in this clinical population, no data are available on the specific effects of nociceptive stimuli on cardiac autonomic control. Thus, we aimed at investigating the effects of a noxious stimulation on heart rate variability (HRV) in a population of patients with chronic DOC, taking into account different states of consciousness (vegetative state/unresponsive wakefulness syndrome, VS/UWS and minimally conscious state, MCS). METHODS: We enrolled twenty-four DOC patients (VS/UWS, n = 12 and MCS, n = 12). ECG and respiration were recorded during baseline, immediately after the nociceptive stimulus and, finally, during the recovery period. Linear and nonlinear HRV measures were used to evaluate the cardiac autonomic control. RESULTS: In DOC patients, nonlinear HRV analysis showed that nociceptive stimuli are able to elicit a change of autonomic function characterized by an increased sympathetic and a reduced vagal modulation. A significant reduction of autonomic complexity has also been detected. More interestingly, VS/UWS patients showed a less complex dynamics compared to MCS patients. CONCLUSIONS: Cardiac autonomic responses are able to significantly differentiate the autonomic function between VS/UWS and MCS patients. SIGNIFICANCE: Nonlinear HRV analysis may represent a useful tool to characterize the cardiac autonomic responses to nociceptive stimuli in a chronic DOC population.

Evidence of altered pressure pain thresholds in persons with disorders of consciousness as measured by the Nociception Coma Scale-Italian version.

Pain assessment in patients with disorders of consciousness (DoC) is a controversial issue for clinicians, who require tools and standardised procedures for testing nociception in non-communicative patients. The aims of the present study were, first, to analyse the psychometric properties of the Italian version of the Nociception Coma Scale and, second, to evaluate pressure pain thresholds in a group of patients with DoC. The authors conducted a multi-centre study on 40 healthy participants and 60 DoC patients enrolled from six hospitals in Italy. For each group an electronic algometer was used to apply all nociceptive pressure stimuli. Our results show that the Italian version of the NCS retains the good psychometric properties of the original version and is therefore suitable for standardised pain assessment in clinical practice. In our study, pressure pain thresholds measured in a group of patients in vegetative and minimally conscious state were relatively lower than pain threshold values found in a group of healthy participants. Such findings motivate additional investigation on possible pain sensitisation in patients with severe brain injury and multiple co-morbidities, and on application of tailored therapeutic approaches useful for pain management in patients unable verbally to communicate their feelings.

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

OBJECTIVE: 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). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729.

Total, free and bound leptin and thyroid function in elderly women with different body weights.

OBJECTIVE: The present study was aimed at evaluating the relationship of total leptin, and its free leptin (FL) and bound leptin (BL) fractions with adipose mass in very old euthyroid women, in relationship to thyroid function. SUBJECTS AND METHODS: Twenty-five older women (age: 73-95 years) were studied. Subjects representing underweight, normal weight and overweight/obese conditions were included. Plasma leptin, TSH, free T(4) (FT(4)) and free T(3), (FT(3)) total and HDL cholesterol were measured. FL and BL were evaluated by Fast Protein Liquid Chromatography (FPLC) analysis. RESULTS: Plasma leptin concentration was positively correlated with body mass index (BMI) (r = 0.64, P = 0.0005) and tricipital skin-fold thickness (TF) (r = 0.46, P = 0.0187). Leptin was positively correlated with TSH (r = 0.50, P = 0.0116) and inversely with FT(3) (r = -0.40, P = 0.0477). TSH correlated with the adiposity indexes BMI (r = 0.40, P = 0.05) and TF (r = 0.42, P = 0.0336). Plasma FT(3) was positively correlated with FT(4) (r = 0.49, P = 0.012). FL and BL were evaluated in 8 out of 25 subjects. FL positively correlated with BMI (r = 0.81, P = 0.0218) and leptin (r = 0.83, P = 0.0004), whereas BL did not correlate with these parameters. CONCLUSIONS: The present results indicate that in very old women, plasma leptin concentrations reflect the extent of adipose mass and suggest that a complex regulatory interaction exists between leptin and thyroid function, possibly taking place at central (hypothalamus-pituitary) and peripheral (deiodinase activity) levels.