Co-designing an interactive artificial intelligent system with post-stroke patients and caregivers to augment the lost abilities and improve their quality of life: a human-centric approach.

Objectives: The motor disability due to stroke compromises the autonomy of patients and caregivers. To support autonomy and other personal and social needs, trustworthy, multifunctional, adaptive, and interactive assistive devices represent optimal solutions. To fulfill this aim, an artificial intelligence system named MAIA would aim to interpret users' intentions and translate them into actions performed by assistive devices. Analyzing their perspectives is essential to develop the MAIA system operating in harmony with patients' and caregivers' needs as much as possible. Methods: Post-stroke patients and caregivers were interviewed to explore the impact of motor disability on their lives, previous experiences with assistive technologies, opinions, and attitudes about MAIA and their needs. Interview transcripts were analyzed using inductive thematic analysis. Results: Sixteen interviews were conducted with 12 post-stroke patients and four caregivers. Three themes emerged: (1) Needs to be satisfied, (2) MAIA technology acceptance, and (3) Perceived trustfulness. Overall, patients are seeking rehabilitative technology, contrary to caregivers needing assistive technology to help them daily. An easy-to-use and ergonomic technology is preferable. However, a few participants trust a system based on artificial intelligence. Conclusion: An interactive artificial intelligence technology could help post-stroke patients and their caregivers to restore motor autonomy. The insights from participants to develop the system depends on their motor ability and the role of patients or caregiver. Although technology grows exponentially, more efforts are needed to strengthen people's trust in advanced technology.

Healthcare-associated infections and antimicrobial resistance in severe acquired brain injury: a retrospective multicenter study.

Background: Recent studies underscore that healthcare-associated infections (HAIs) and multidrug-resistant (MDR) HAIs affect rehabilitation outcomes and hospital length of stay (LOS) for severe acquired brain injury (sABI). Objective: This study aimed to estimate HAI incidence in different sABI rehabilitation settings and determine risk factors and HAI impact on neuromotor and cognitive recovery. Methods: We conducted a retrospective multicenter study in two semi-intensive units (SICUs), two high-specialty post-acute units (PAUs), and one long-term care (LTC) rehabilitation facility. Data extraction was performed by experienced clinicians, using a structured Excel file and they agreed upon criteria for case definitions of healthcare. The main outcome measures were the HAI and MDR HAI incidence and the LOS, the functional recovery was measured using the Level of Cognitive Functioning and Disability Rating Scale. Results: There were 134 sABI participants. The calculation of the probability level was adjusted for three pairwise comparisons among settings (0.05/3 = 0.017). The HAI and MDR HAI incidences were significantly higher in SICU (3.7 and 1.3 per 100 person-days) than in other settings (LTC: 1.9, p = 0.034 and 0.5, p = 0.026; PAU: 1.2, p < 0.001 and 0.3, p < 0.001). HAI and MDR HAI risk variables included older age, an increased number of devices, and carbapenemase-producing Enterobacteriaceae (CPE) colonization, while a high prealbumin plasma value seemed to have a protective effect. Conclusion: HAIs are related to longer LOS, and colonization is associated with poor prognosis and poor functional outcomes with reduced ability to achieve the cognitive capacity of self-care, employability, and independent living. The need to ensure the protection of non-colonized patients, especially those with severe disabilities on admission, is highlighted.

Hierarchical psychophysiological pathways subtend perceptual asymmetries in Neglect.

Stroke patients with left Hemispatial Neglect (LHN) show deficits in perceiving left contralesional stimuli with biased visuospatial perception towards the right hemifield. However, very little is known about the functional organization of the visuospatial perceptual neural network and how this can account for the profound reorganization of space representation in LHN. In the present work, we aimed at (1) identifying EEG measures that discriminate LHN patients against controls and (2) devise a causative neurophysiological model between the discriminative EEG measures. To these aims, EEG was recorded during exposure to lateralized visual stimuli which allowed for pre-and post-stimulus activity investigation across three groups: LHN patients, lesioned controls, and healthy individuals. Moreover, all participants performed a standard behavioral test assessing the perceptual asymmetry index in detecting lateralized stimuli. The between-groups discriminative EEG patterns were entered into a Structural Equation Model for the identification of causative hierarchical associations (i.e., pathways) between EEG measures and the perceptual asymmetry index. The model identified two pathways. A first pathway showed that the combined contribution of pre-stimulus frontoparietal connectivity and individual-alpha-frequency predicts post-stimulus processing, as measured by visual-evoked N100, which, in turn, predicts the perceptual asymmetry index. A second pathway directly links the inter-hemispheric distribution of alpha-amplitude with the perceptual asymmetry index. The two pathways can collectively explain 83.1% of the variance in the perceptual asymmetry index. Using causative modeling, the present study identified how psychophysiological correlates of visuospatial perception are organized and predict the degree of behavioral asymmetry in LHN patients and controls.

The Early Functional Abilities-revised may bridge the gap between the disorder of consciousness and the functional independence scales: evidence from Rasch analysis.

BACKGROUND: There is a tremendous clinical and research need to bridge the gap between disorder of consciousness and functional independence scales with a single unidimensional measure in people with acquired brain injury. AIM: To calibrate an essentially unidimensional subset of items from the Italian Early Functional Abilities (EFA), demonstrating internal construct validity and sufficient reliability for individual patient measurement. DESIGN: Multicenter observational cross-sectional study. SETTING: Inpatients from 11 different Italian Rehabilitation centers. POPULATION: Three hundred sixty-two adult patients with a disorder of consciousness due to an acquired brain injury. METHODS: The Italian version of EFA was administered to the sample and then submitted to Mokken analysis, Confirmatory Factor Analysis, Rasch analysis, Confirmatory Bifactor Analysis, and external construct validity. RESULTS: According to Mokken Analysis (all item scalability coefficients Hj positive; all item-pair scalability coefficients Hij >0.3; scale coefficient H=0.762), and Confirmatory Factor Analysis (RMSEA=0.081; SRMR=0.048; CFI=0.995; TLI=0.995), the Italian EFA showed a sufficient preliminary unidimensionality. Within Rasch Analysis, a final 12-item solution for the EFA (EFA-R) was calibrated. EFA-R is "essentially unidimensional" according to the following requirements: 1) analysis of residual correlations which supported item essential local independence; 2) a robust correlation between item subtests (rho=0.950); 3) only 2.1% of cases with significant difference between person parameter estimates by different subscales; 4) an explained common variance equal to 0.916 obtained from a final Confirmatory Bifactor Analysis. It also satisfied invariance requirement (unconditional χ220=9.81; P=0.457, conditional class-interval based χ235=33.1; P=0.557), and monotonicity. The reliability (Person Separation Index=0.887) was adequate for person measurements. A practical raw-score-to-measure conversion table based on the EFA-R calibration was devised. Finally, EFA-R strongly correlated with Coma Recovery Scale-Revised (rho=0.922) and motor FIM™ (rho=0.808). CONCLUSIONS: EFA-R is an essentially unidimensional subset of 12 items with adequate internal construct validity and sufficient reliability for individual patient measurement under the Rasch Model Theory framework. CLINICAL REHABILITATION IMPACT: EFA-R has the potential to measure people's functional abilities whose consciousness is improving despite ongoing severe motor-functional impairments during the early stages of rehabilitation. It provides "a measurement bridge" between the disorder of consciousness and the functional independence scales in patients with severe acquired brain injury.

Accuracy of EEG Biomarkers in the Detection of Clinical Outcome in Disorders of Consciousness after Severe Acquired Brain Injury: Preliminary Results of a Pilot Study Using a Machine Learning Approach.

Accurate outcome detection in neuro-rehabilitative settings is crucial for appropriate long-term rehabilitative decisions in patients with disorders of consciousness (DoC). EEG measures derived from high-density EEG can provide helpful information regarding diagnosis and recovery in DoC patients. However, the accuracy rate of EEG biomarkers to predict the clinical outcome in DoC patients is largely unknown. This study investigated the accuracy of psychophysiological biomarkers based on clinical EEG in predicting clinical outcomes in DoC patients. To this aim, we extracted a set of EEG biomarkers in 33 DoC patients with traumatic and nontraumatic etiologies and estimated their accuracy to discriminate patients' etiologies and predict clinical outcomes 6 months after the injury. Machine learning reached an accuracy of 83.3% (sensitivity = 92.3%, specificity = 60%) with EEG-based functional connectivity predicting clinical outcome in nontraumatic patients. Furthermore, the combination of functional connectivity and dominant frequency in EEG activity best predicted clinical outcomes in traumatic patients with an accuracy of 80% (sensitivity = 85.7%, specificity = 71.4%). These results highlight the importance of functional connectivity in predicting recovery in DoC patients. Moreover, this study shows the high translational value of EEG biomarkers both in terms of feasibility and accuracy for the assessment of DoC.

A Multifunctional Adaptive and Interactive AI system to support people living with stroke, acquired brain or spinal cord injuries: A study protocol.

BACKGROUND: Acquired brain injury and spinal cord injury are leading causes of severe motor disabilities impacting a person's autonomy and social life. Enhancing neurological recovery driven by neurogenesis and neuronal plasticity could represent future solutions; however, at present, recovery of activities employing assistive technologies integrating artificial intelligence is worthy of examining. MAIA (Multifunctional, adaptive, and interactive AI system for Acting in multiple contexts) is a human-centered AI aiming to allow end-users to control assistive devices naturally and efficiently by using continuous bidirectional exchanges among multiple sensorimotor information. METHODS: Aimed at exploring the acceptability of MAIA, semi-structured interviews (both individual interviews and focus groups) are used to prompt possible end-users (both patients and caregivers) to express their opinions about expected functionalities, outfits, and the services that MAIA should embed, once developed, to fit end-users needs. DISCUSSION: End-user indications are expected to interest MAIA technical, health-related, and setting components. Moreover, psycho-social issues are expected to align with the technology acceptance model. In particular, they are likely to involve intrinsic motivational and extrinsic social aspects, aspects concerning the usefulness of the MAIA system, and the related ease to use. At last, we expect individual factors to impact MAIA: gender, fragility levels, psychological aspects involved in the mental representation of body image, personal endurance, and tolerance toward AT-related burden might be the aspects end-users rise in evaluating the MAIA project.

[Is it time to implement Cardiac Arrest Centers in Italy? The integrated experience in the decade 2009-2019 between metropolitan area and Maggiore Hospital of Bologna]. / È il momento per implementare i Centri per l'Arresto Cardiaco in Italia? L'esperienza integrata nel decennio 2009-2019 tra area metropolitana ed Ospedale Maggiore di Bologna.

Cardiac arrest (CA) is the third cause of death in Europe. This paper highlights the various treatments for the prevention and early management of CA and provides an overview of available evidence on the CA center concept. The experience of Maggiore Hospital of Bologna, Italy over the last 11 years is also outlined along with the treatments applied to patients with CA and their impact on improving outcomes. The new concept of the "Systems Saving Lives" approach is presented as a potential way for implementing Italian healthcare systems involved in the management of CA patients. Finally, the future perspective of implementation of CA centers in Italy is also described encouraging the healthcare professionals involved in the treatment of CA patients to consider a multidisciplinary approach (including a cardiologist, emergency physician, neurologist, physiatrist, radiologist, and intensivist).

Efficacy of Repetitive Transcranial Magnetic Stimulation Combined With Visual Scanning Treatment on Cognitive-Behavioral Symptoms of Unilateral Spatial Neglect in Patients With Traumatic Brain Injury: Study Protocol for a Randomized Controlled Trial.

Left hemispatial neglect (LHSN) is a frequent and disabling condition affecting patients who suffered from traumatic brain injury (TBI). LHSN is a neuropsychological syndrome characterized clinically by difficulties in attending, responding, and consciously representing the right side of space. Despite its frequency, scientific evidence on effective treatments for this condition in TBI patients is still low. According to existing literature, we hypothesize that in TBI, LHSN is caused by an imbalance in inter-hemispheric activity due to hyperactivity of the left hemisphere, as observed in LHSN after right strokes. Thus, by inhibiting this left hyperactivity, repetitive Transcranial Magnetic Stimulation (rTMS) would have a rebalancing effect, reducing LHSN symptoms in TBI patients. We plan to test this hypothesis within a single-blind, randomized SHAM controlled trial in which TBI patients will receive inhibitory i-rTMS followed by cognitive treatment for 15 days. Neurophysiological and clinical measures will be collected before, afterward, and in the follow-up. This study will give the first empirical evidence about the efficacy of a novel approach to treating LHSN in TBI patients. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04573413?cond=Neglect%2C+Hemispatial&cntry=IT&city=Bologna&draw=2&rank=2, identifier: NCT04573413.

Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive and behavioral symptoms of left hemispatial neglect in right hemispheric stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Left hemispatial neglect (LHN) is a neuropsychological syndrome often associated with right hemispheric stroke. Patients with LHN have difficulties in attending, responding, and consciously representing the right side of space. Various rehabilitation protocols have been proposed to reduce clinical symptoms related to LHN, using cognitive treatments, or on non-invasive brain stimulation. However, evidence of their benefit is still lacking; in particular, only a few studies focused on the efficacy of combining different approaches in the same patient. METHODS: In the present study, we present the SMART ATLAS trial (Stimolazione MAgnetica Ripetitiva Transcranica nell'ATtenzione LAteralizzata dopo Stroke), a multicenter, randomized, controlled trial with pre-test (baseline), post-test, and 12 weeks follow-up assessments based on a novel rehabilitation protocol based on the combination of brain stimulation and standard cognitive treatment. In particular, we will compare the efficacy of inhibitory repetitive-transcranial magnetic stimulation (r-TMS), applied over the left intact parietal cortex of LHN patients, followed by visual scanning treatment, in comparison with a placebo stimulation (SHAM control) followed by the same visual scanning treatment, on visuospatial symptoms and neurophysiological parameters of LHN in a population of stroke patients. DISCUSSION: Our trial results may provide scientific evidence of a new, relatively low-cost rehabilitation protocol for the treatment of LHN. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080999 . Registered on September 2019.

Behavioural and electrophysiological effects of tDCS to prefrontal cortex in patients with disorders of consciousness.

OBJECTIVES: Left dorsolateral prefrontal cortex anodal transcranial direct current stimulation (tDCS) was applied in a group of patients with disorders of consciousness to determine the effects of modulation of spontaneous oscillatory brain activity. METHODS: 12 patients in an unresponsive wakefulness syndrome (UWS) and 12 in a minimally conscious state (MCS) underwent 2-weeks active and 2-weeks sham tDCS. Neurophysiological assessment was performed with EEG power spectra and coherence analysis directly before and after each session. RESULTS: An increase of power and coherence of the frontal and parietal alpha and beta frequency bands and significant clinical improvements were seen after the active tDCS in MCS patients. In contrast, UWS patients showed some local frontal changes in the slow frequencies. No treatment effect was observed after sham. CONCLUSIONS: tDCS could induce changes in cortical EEG oscillations, modulating the travel of alpha and beta waves between anterior and posterior brain areas when some cognitive functions were preserved. This plays an important role in consciousness by integrating cognitive-emotional processing with the state of arousal. In unresponsive people, brain integration seems to be lost. SIGNIFICANCE: Our results further support the critical role of long-range fronto-parietal connections in consciousness and show the potential therapeutic utility of tDCS.

Risk of Exclusion From Stroke Rehabilitation in the Oldest Old.

OBJECTIVE: To investigate whether oldest-old age (≥85y) is an independent predictor of exclusion from stroke rehabilitation. DESIGN: Retrospective cohort study. SETTING: Stroke unit (SU) of a tertiary hospital. PARTICIPANTS: Elderly patients (N=1055; aged 65-74y, n=230; aged 75-84y, n=432; aged ≥85y, n=393) who, between 2009 and 2012, were admitted to the SU with acute stroke and evaluated by a multiprofessional team for access to rehabilitation. The study excluded patients for whom rehabilitation was unnecessary or inappropriate. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Access to an early mobilization (EM) protocol during SU stay and subsequent access to postacute rehabilitation after SU discharge. Analyses were adjusted for prestroke and stroke-related characteristics. RESULTS: 32.2% of patients were excluded from EM. Multivariable-adjusted odds ratios (ORs) of EM exclusion were 1.30 (95% confidence interval [CI], .76-2.21) for ages 75 to 84 years and 2.07 (95% CI, 1.19-3.59) for ages ≥85 years compared with ages 65 to 74 years. Of 656 patients admitted to EM and who, at SU discharge, had not yet fully recovered their prestroke functional status, 18.4% were excluded from postacute rehabilitation. For patients able to walk unassisted at SU discharge, the probability of exclusion did not change across age groups. For patients unable to walk unassisted at SU discharge, ORs of exclusion from postacute rehabilitation were 3.74 (95% CI, 1.26-11.13) for ages 75 to 84 years and 9.15 (95% CI, 3.05-27.46) for ages ≥85 years compared with ages 65 to 74 years. CONCLUSIONS: Oldest-old age is an independent predictor of exclusion from stroke rehabilitation.

Care pathways models and clinical outcomes in Disorders of consciousness.

OBJECTIVE: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients' clinical outcomes. MATERIALS AND METHODS: A multicenter observational pilot study was realized. Clinicians collected data on the care pathways of patients with Disorder of consciousness by asking 90 patients' caregivers to complete an ad hoc questionnaire through a structured phone interview. Questionnaire consisted of three sections: sociodemographic data, description of the care pathway done by the patient, and caregiver evaluation of health services and information received. RESULTS: Seventy-three patients were analyzed. Length of hospital stay was different across the health care models and it was associated with improvement in clinical diagnosis. In long-term care units, the diagnosis at admission and the number of caregivers available for each patient (median value = 3) showed an indirect relationship with worsening probability in clinical outcome. Caregivers reported that communication with professionals (42%) and the answer to the need of information were the most critical points in the acute phase, whereas presence of Non-Governmental Organizations (25%) and availability of psychologists for caregivers (21%) were often missing during long-term care. The 65% of caregivers reported they did not know the UN Convention on the Rights of Persons with Disabilities. CONCLUSION: This study highlights relevant differences in analyzed models, despite a recommended national pathway of care. Future public health considerations and actions are needed to guarantee equity and standardization of the care process in all European countries.

Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury.

Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that the over-production of cytokines and the alteration of the redox homeostasis in the post-acute phase might adversely affect the neurological and functional recovery. Inflammatory and antioxidant activity markers might offer a feasible way to highlight some of the processes opposing recovery after a severe TBI.

Neuropsychological changes and cranioplasty: A group analysis.

BACKGROUND: Cranioplasty is the surgical answer to cranial defect due to decompressive craniectomy in order to increase patient's safety and for cosmetic reasons. Two main neurological sequelae of skull breaches have been described and cranioplasty has been suggested as a way to treat these neurological symptoms, but its effects on cognitive and motor functions are still unclear. MATERIALS AND METHODS: In order to better elucidate if and to what extent the cranioplasty affects the whole array of cognitive functions or just some specific domains, 29 patients were studied pre- and post-cranioplasty, with structured assessments of memory, attention, language and executive functioning performed ~ 4 months and 1 month before cranioplasty and 1 month and 6 months after surgery. RESULTS AND CONCLUSION: Cranioplasty affects the cognitive profile with a non-specific pattern of change. Timing of the cranioplasty plays a key role to enucleate cognitive improvement, indeed greater cognitive changes were seen in patients who had cranioplasty within 6 months following the injury. Thus, cranioplasty must be considered a key factor in neuropsychological recovery and should be performed as soon as possible following the injury in order to take advantage of the window of opportunity for rehabilitation.

Traumatic brain injury and NADPH oxidase: a deep relationship.

Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI.

Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients with Disorders of Consciousness.

Evaluation of consciousness needs to be supported by the evidence of brain activation during external stimulation in patients with unresponsive wakefulness syndrome (UWS). Assessment of patients should include techniques that do not depend on overt motor responses and allow an objective investigation of the spontaneous patterns of brain activity. In particular, electroencephalography (EEG) coherence allows to easily measure functional relationships between pairs of neocortical regions and seems to be closely correlated with cognitive or behavioral measures. Here, we show the contribution of higher order associative cortices of patients with disorder of consciousness (N = 26) in response to simple sensory stimuli, such as visual, auditory and noxious stimulation. In all stimulus modalities an increase of short-range parietal and long-range fronto-parietal coherences in gamma frequencies were seen in the controls and minimally conscious patients. By contrast, UWS patients showed no significant modifications in the EEG patterns after stimulation. Our results suggest that UWS patients can not activate associative cortical networks, suggesting a lack of information integration. In fact, fronto-parietal circuits result to be connectively disrupted, conversely to patients that exhibit some form of consciousness. In the light of this, EEG coherence can be considered a powerful tool to quantify the involvement of cognitive processing giving information about the integrity of fronto-parietal network. This measure can represent a new neurophysiological marker of unconsciousness and help in determining an accurate diagnosis and rehabilitative intervention in each patient.

Nocturnal melatonin regulation in post-traumatic vegetative state: a possible role for melatonin supplementation?

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.

Can we scientifically and reliably measure the level of consciousness in vegetative and minimally conscious States? Rasch analysis of the coma recovery scale-revised.

OBJECTIVES: (1) To appraise, by the means of Rasch analysis, the internal validity and reliability of the Coma Recovery Scale-Revised (CRS-R) in a sample of patients with disorder of consciousness (DOC); and (2) to provide information about the comparability of CRS-R scores across persons with DOC across different settings and groups, including different etiologies. DESIGN: Multicenter observational prospective study. SETTING: Two rehabilitation wards, 1 intermediate care facility, and 2 nursing homes in Italy. PARTICIPANTS: Consecutively admitted patients (N=129) for which assessments at 2 different time points were available, giving a total sample of 258 observations. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: CRS-R. RESULTS: After controlling for any possible dependency between persons' measures collected at different time points, and for uniform differential item functioning by etiology showed by the visual subscale, Rasch analysis demonstrated adequate satisfaction of all the model's requirements, including adequate ordering of scoring categories, unidimensionality, local independence, invariance (χ(2)21=27.798, P=.146), and absence of differential item functioning across patients' sex, age, time, and setting. The reliability (person separation index=.896) was adequate for individual person measurement. We devised a practical raw score to measure conversion tables based on the CRS-R calibrations. CONCLUSIONS: The CRS-R is a psychometrically sound and robust measurement tool. The linear measures of ability derived from the CRS-R total scores do satisfy all the principles of scientific measurement and are sufficiently reliable for high stakes assessments, such as the diagnosis of the level of consciousness in individual patients. Future studies are needed to directly explore the capabilities of the CRS-R measures to reduce the risk of vegetative state misdiagnosis.

Self-reported gait unsteadiness in mildly impaired neurological patients: an objective assessment through statistical gait analysis.

BACKGROUND: Self-reported gait unsteadiness is often a problem in neurological patients without any clinical evidence of ataxia, because it leads to reduced activity and limitations in function. However, in the literature there are only a few papers that address this disorder. The aim of this study is to identify objectively subclinical abnormal gait strategies in these patients. METHODS: Eleven patients affected by self-reported unsteadiness during gait (4 TBI and 7 MS) and ten healthy subjects underwent gait analysis while walking back and forth on a 15-m long corridor. Time-distance parameters, ankle sagittal motion, and muscular activity during gait were acquired by a wearable gait analysis system (Step32, DemItalia, Italy) on a high number of successive strides in the same walk and statistically processed. Both self-selected gait speed and high speed were tested under relatively unconstrained conditions. Non-parametric statistical analysis (Mann-Whitney, Wilcoxon tests) was carried out on the means of the data of the two examined groups. RESULTS: The main findings, with data adjusted for velocity of progression, show that increased double support and reduced velocity of progression are the main parameters to discriminate patients with self-reported unsteadiness from healthy controls. Muscular intervals of activation showed a significant increase in the activity duration of the Rectus Femoris and Tibialis Anterior in patients with respect to the control group at high speed. CONCLUSIONS: Patients with a subjective sensation of instability, not clinically documented, walk with altered strategies, especially at high gait speed. This is thought to depend on the mechanisms of postural control and coordination. The gait anomalies detected might explain the symptoms reported by the patients and allow for a more focused treatment design. The wearable gait analysis system used for long distance statistical walking assessment was able to detect subtle differences in functional performance monitoring, otherwise not detectable by common clinical examinations.

Unexpected neuropsychological improvement after cranioplasty: a case series study.

OBJECTIVE: Decompressive craniectomy is often emergently performed in an effort to reduce intracranial hypertension. After this urgent intervention, brain-injured patients often start rehabilitation programs but are left with a skull defect. Cranioplasty is often performed in these situations in order to repair this defect, mainly for cosmetic reasons and/or the patient's safety. The possible effects of this breach on the patients' neurological recovery are poorly understood and have been scarcely evaluated until now. The effect of cranioplasty on cognitive and motor functions in severely brain-injured individuals remains controversial. METHODS AND PROCEDURES: In order to further support evidence of the beneficial effects of cranioplasty on motor and cognitive function in severely brain-injured individuals, we discuss four cases, retrospectively selected among a cohort of several patients who underwent decompressive craniectomy after severe brain injury. The selected patients presented a biphasic pattern of recovery of cognitive and motor performance consisting of an initial improvement, followed by a progressive worsening of neurological signs and symptoms, and, ultimately, an unexpected recovery of function following cranioplasty. MAIN OUTCOMES AND RESULTS: In all four cases, we found a deterioration of motor and neuropsychological deficits prior to cranioplasty and a subsequent unexpected improvement in performance on a neuropsychological battery and a series of motor function tests immediately after cranioplasty. CONCLUSIONS: Results give clear evidence that a subset of patients are negatively affected by the persistence of a breach in skull integrity during the rehabilitation phase of brain injury. Moreover, they show that the repair of the cranial defect can trigger relevant neurological improvement in both motor and cognitive domains. This possibility should serve as a reminder to rehabilitation clinicians to give serious consideration to prompt performance of cranioplasty during the time allotted for the rehabilitation of these patients.