Neurophysiological and Clinical Effects of Upper Limb Robot-Assisted Rehabilitation on Motor Recovery in Patients with Subacute Stroke: A Multicenter Randomized Controlled Trial Study Protocol.

BACKGROUND: The efficacy of upper limb (UL) robot-assisted therapy (RAT) on functional improvement after stroke remains unclear. However, recently published randomized controlled trials have supported its potential benefits in enhancing the activities of daily living, arm and hand function, and muscle strength. Task-specific and high-intensity exercises are key points in facilitating motor re-learning in neurorehabilitation since RAT can provide an assisted-as-needed approach. This study aims to investigate the clinical effects of an exoskeleton robotic system for UL rehabilitation compared with conventional therapy (CT) in people with subacute stroke. As a secondary aim, we seek to identify patients' characteristics, which can predict better recovery after UL-RAT and detects whether it could elicit greater brain stimulation. METHODS: A total of 84 subacute stroke patients will be recruited from 7 Italian rehabilitation centers over 3 years. The patients will be randomly allocated to either CT (control group, CG) or CT plus UL-RT through an Armeo®Power (Hocoma AG, CH, Volketswil, Switzerland) exoskeleton (experimental group, EG). A sample stratification based on distance since onset, DSO (DSO ≤ 30; DSO > 30), and Fugl-Meyer Assessment (FM)-UL (FM-UL ≤ 22; 22 < FM-UL ≤ 44) will be considered for the randomization. The outcomes will be recorded at baseline (T0), after 25 + 3 sessions of intervention (T1), and at 6 months post-stroke (T2). The motor functioning assessed by the FM-UL (0-66) will be considered the primary outcome. The clinical assessments will be set based on the International Classification of Function, Disability and Health (ICF). A patient satisfaction questionnaire will be evaluated in the EG at T1. A subgroup of patients will be evaluated at T0 and T1 via electroencephalography. Their brain electrical activity will be recorded during rest conditions with their eyes closed and open (5 min each). CONCLUSION: The results of this trial will provide an in-depth understanding of the efficacy of early UL-RAT through a whole arm exoskeleton and how it may relate to the neural plasticity process. The trial was registered at ClinicalTrial.gov with the registration identifier NCT04697368.

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs. Clinical trial identifier: NCT04673240.

Long-Term Spasticity Management in Post-Stroke Patients: Issues and Possible Actions-A Systematic Review with an Italian Expert Opinion.

Spasticity is a well-known motor dysfunction occurring after a stroke. A group of Italian physicians' experts in treating post-stroke spasticity (PSS) reviewed the current scientific evidence concerning the state-of-the-art clinical management of PSS management and the appropriate use of botulinum toxin, aiming to identify issues, possible actions, and effective management of the patient affected by spasticity. The participants were clinicians specifically selected to cover the range of multidisciplinary clinical and research expertise needed to diagnose and manage PSS. When evidence was not available, the panel discussed and agreed on the best way to manage and treat PSS. To address the barriers identified, the panel provides a series of consensus recommendations. This systematic review provides a focused guide in the evaluation and management of patients with PSS and its complications. The recommendations reached by this panel of experts should be used by less-experienced doctors in real life and should be used as a guide on how to best use botulinum toxin injection in treating spasticity after a stroke.

Application of an Artificial Neural Network to Identify the Factors Influencing Neurorehabilitation Outcomes of Patients with Ischemic Stroke Treated with Thrombolysis.

The administration of thrombolysis usually reduces the risk of death and the consequences of stroke in the acute phase. However, having received thrombolysis administration is not a prognostic factor for neurorehabilitation outcome in the subacute phase of stroke. It is conceivably due to the complex intertwining of many clinical factors. An artificial neural network (ANN) analysis could be helpful in identifying the prognostic factors of neurorehabilitation outcomes and assigning a weight to each of the factors considered. This study hypothesizes that the prognostic factors could be different between patients who received and those who did not receive thrombolytic treatment, even if thrombolysis is not a prognostic factor per se. In a sample of 862 patients with ischemic stroke, the tested ANN identified some common factors (such as disability at admission, age, unilateral spatial neglect), some factors with higher weight in patients who received thrombolysis (hypertension, epilepsy, aphasia, obesity), and some other factors with higher weight in the other patients (dysphagia, malnutrition, total arterial circulatory infarction). Despite the fact that thrombolysis is not an independent prognostic factor for neurorehabilitation, it seems to modify the relative importance of other clinical factors in predicting which patients will better respond to neurorehabilitation.

May Dual Transcranial Direct Current Stimulation Enhance the Efficacy of Robot-Assisted Therapy for Promoting Upper Limb Recovery in Chronic Stroke?

OBJECTIVE: To assess whether dual transcranial direct current stimulation (tDCS) may enhance the efficacy of exoskeleton robotic training on upper limb motor functions in patients with chronic stroke. METHODS: A prospective, bi-center, double-blind, randomized clinical trial study was performed. Patients with moderate-to-severe stroke (according to The National Institute of Health Stroke Scale) were randomly assigned to receive dual or sham tDCS immediately before robotic therapy (10 sessions, 2 weeks). The primary outcome was the Fugl-Meyer for Upper Extremity, assessed before, after, and at the 12-week follow-up. Neurophysiological evaluation of corticospinal projections to upper limb muscles was performed by recording motor evoked potentials (MEPs). ClinicalTrials.gov-NCT03026712. RESULTS: Two hundred and sixty individuals were tested for eligibility, of which 80 were enrolled and agreed to participate. Excluding 14 dropouts, 66 patients were randomly assigned into the 2 groups. Results showed that chronic patients were stable before treatment and significantly improved after that. The records within subject improvements were not significantly different between the 2 groups. However, a post-hoc analysis subdividing patients in 2 subgroups based on the presence or absence of MEPs at the baseline showed a significantly higher effect of real tDCS in patients without MEPs when compared to patients with MEPs (F = 4.6, P = .007). CONCLUSION: The adjunction of dual tDCS to robotic arm training did not further enhance recovery in the treated sample of patients with chronic stroke. However, a significant improvement in the subgroup of patients with a severe corticospinal dysfunction (as suggested by the absence of MEPs) suggests that they could benefit from such a treatment combination.

Inside the Michelangelo effect: The role of art and aesthetic attractiveness on perceived fatigue and hand kinematics in virtual painting.

It has recently been discovered that during a virtual reality task of painting, if the subjects have the illusion of recreating an artistic masterpiece, they improve their performances and perceive less fatigue compared to simply coloring a virtual canvas. This phenomenon has been called the Michelangelo effect. However, it was unclear if this effect was related to the aesthetic experience of beauty or if it was specific to artistic stimuli. To clarify this point, 26 healthy subjects performed the virtual task of erasing a blank sheet on the canvas, revealing an image that could be a painting or a photo, classified as beautiful or not. Beautiful paintings were famous artistic portraits, non-beautiful paintings were rough reproductions of them. Photos of popular people were matched with paintings according to their similarity for somatic traits, posture, and clothes. Beautiful and non-beautiful photos were classified according to whether the pictured person was famous or not for their beauty. For each stimulus the objective beauty, subjective beauty, and effort to complete the task perceived by the subject were self-assessed on a numerical rating scale, recorded and analyzed. Furthermore, the hand kinematic trajectory was instrumentally recorded and its spatiotemporal parameters were computed. Less fatigue was perceived for the paintings than for the photos (p = .020), but not for beautiful versus non-beautiful stimuli (p = .325). Only in the artistic stimuli, subjective beauty was found to be negatively correlated with perceived fatigue (p = .030) and performed errors (p = .005). The kinematic parameters were found to be affected by the interactions between the gender of the participant and that of the person in the photo. These results supported the idea that the Michelangelo effect was stronger when subjects interacted with artefacts, modulated by the perceived beauty of the artistic stimulus.

Combining Robot-Assisted Gait Training and Non-Invasive Brain Stimulation in Chronic Stroke Patients: A Systematic Review.

Gait impairment is one of the most common disorders of patients with chronic stroke, which hugely affects the ability to carry out the activities of daily living and the quality of life. Recently, traditional rehabilitation techniques have been associated with non-invasive brain stimulation (NIBS) techniques, which enhance brain plasticity, with the aim of promoting recovery in patients with chronic stroke. NIBS effectiveness in improving gait parameters in patients with chronic stroke has been in several studies evaluated. Robotic devices are emerging as promising tools for the treatment of stroke-related disabilities by performing repetitive, intensive, and task-specific treatments and have been proved to be effective for the enhancement of motor recovery in patients with chronic stroke. To date, several studies have examined the combination of NIBS with robotic-assisted gait training, but the effectiveness of this approach is not yet well established. The main purpose of this systematic review is to clarify whether the combination of NIBS and robot-assisted gait training may improve walking function in patients with chronic stroke. Our systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Studies eligible for review were identified through PubMed/MEDLINE, Embase, Scopus, and PEDro from inception to March 15, 2021, and the outcomes considered were gait assessments. Seven studies were included in the qualitative analysis of this systematic review, with a total population of 186 patients with chronic stroke. All studies specified technical characteristics of robotic devices and NIBS used, with high heterogeneity of protocols. Methodological studies have shown a significantly greater improvement in walking capacity recorded with 6MWT. Finally, research studies have highlighted a positive effect on walking recovery by combination of robot-assisted gait training with non-invasive brain stimulation. Furthermore, future studies should identify the best characteristics of the combined therapeutic protocols. Systematic Review Registration: CRD42021244869.

Identification of Determinants of Biofeedback Treatment's Efficacy in Treating Migraine and Oxidative Stress by ARIANNA (ARtificial Intelligent Assistant for Neural Network Analysis).

Migraines are a public health problem that impose severe socioeconomic burdens and causes related disabilities. Among the non-pharmacological therapeutic approaches, behavioral treatments such as biofeedback have proven effective for both adults and children. Oxidative stress is undoubtedly involved in the pathophysiology of migraines. Evidence shows a complex relationship between nitric oxide (NO) and superoxide anions, and their modification could lead to an effective treatment. Conventional analyses may fail in highlighting the complex, nonlinear relationship among factors and outcomes. The aim of the present study was to verify if an artificial neural network (ANN) named ARIANNA could verify if the serum levels of the decomposition products of NO-nitrite and nitrate (NOx)-the superoxide dismutase (SOD) serum levels, and the Migraine Disability Assessment Scores (MIDAS) could constitute prognostic variables predicting biofeedback's efficacy in migraine treatment. Twenty women affected by chronic migraine were enrolled and underwent an EMG-biofeedback treatment. The results show an accuracy for the ANN of 75% in predicting the post-treatment MIDAS score, highlighting a statistically significant correlation (R = -0.675, p = 0.011) between NOx (nitrite and nitrate) and MIDAS only when the peroxide levels in the serum were within a specific range. In conclusion, the ANN was proven to be an innovative methodology for interpreting the complex biological phenomena and biofeedback treatment in migraines.

The Effects of Sternocleidomastoid Muscle Taping on Postural Control in Healthy Young Adults: A Pilot Crossover Study.

BACKGROUND: Postural control is a complex ability, also controlled by the somatosensory connection of the neck muscles with the vestibular nuclei. This circuit seems to be interested in maintaining head stabilization during movements. The sternocleidomastoid (SCM) muscle is the dominant source of the vestibular afferents as confirmed by neurophysiological acquisition. The aim of this study is to evaluate whether the application of kinesio-tape on the SCM muscle can induce a perturbation of the standing postural control by altering the somatosensory system of the neck muscles. METHODS: Thirteen healthy participants (age: 24.46 ± 3.04 yrs; 9 female) were enrolled, and the four kinesio-tape (KT) conditions were performed in a random order: without KT application (Ctrl); right KT application (R-SCM); left KT application (L-SCM); and bilateral KT application (B-SCM). All conditions were performed three times with open eyes and closed eyes. RESULTS: There was a significant increase in the length of the centre of pressure (CoP), in the maximal oscillation, and in the anteroposterior root mean square between the three tape application conditions with respect to the Ctrl condition with open eyes. The same parameters were statistically different when the participants were blindfolded in the B-SCM condition with respect to the Ctrl condition. A statistical decrease in the difference in weight distribution between the two feet was observed in the B-SCM group with respect to the Ctrl group in both open and closed eyes conditions. CONCLUSIONS: Our results suggest that KT on the SCM muscles may involve some space-time parameters of postural control. Bilateral KT improved the weight distribution between the feet but showed a parallel increase in anteroposterior oscillations and in the length of the CoP with respect to the Ctrl condition. The perturbation seems to be greater in the somatosensory system when it is working coupled with visual afferences during an upright position.

Rehabilitation outcomes in Huntington disease patients with low body mass index.

OBJECTIVES: A catabolic state and a progressive body weight loss are a well-documented hallmark of Huntington Disease (HD). No study is still available on the effectiveness of intensive in-hospital rehabilitation in HD patients with low body mass index (BMI). METHODS: Twenty HD patients with low BMI value were enrolled in this study. Disease severity was assessed before and after rehabilitation by the Barthel Index, the Total Functional Capacity Scale, and the Physical Performance Test. RESULTS: BMI-scores correlated with clinical measures before and after rehabilitation. All patients showed an improvement in outcome measures (p<0.001), and an increase in BMI values (p<0.001) after rehabilitation. Effectiveness of rehabilitation correlated with the values of BMI assessed before reheducational programs (p=0.024) and with BMI values observed in each patient in the three months before admission to hospital (p=0.002). CONCLUSIONS: Findings of the current study show that the effectiveness of the rehabilitation is positively correlated with the BMI values and confirm the efficacy of in-hospital intensive rehabilitation as a valid strategy finalized to improve neuromotor performances and global functional recovery even in HD patients with low BMI and at risk of malnutrition.

Artificial Neural Network Detects Hip Muscle Forces as Determinant for Harmonic Walking in People after Stroke.

Many recent studies have highlighted that the harmony of physiological walking is based on a specific proportion between the durations of the phases of the gait cycle. When this proportion is close to the so-called golden ratio (about 1.618), the gait cycle assumes an autosimilar fractal structure. In stroke patients this harmony is altered, but it is unclear which factor is associated with the ratios between gait phases because these relationships are probably not linear. We used an artificial neural network to determine the weights associable to each factor for determining the ratio between gait phases and hence the harmony of walking. As expected, the gait ratio obtained as the ratio between stride duration and stance duration was found to be associated with walking speed and stride length, but also with hip muscle forces. These muscles could be important for exploiting the recovery of energy typical of the pendular mechanism of walking. Our study also highlighted that the results of an artificial neural network should be associated with a reliability analysis, being a non-deterministic approach. A good level of reliability was found for the findings of our study.

The golden ratio as an ecological affordance leading to aesthetic attractiveness.

The golden ratio (GR) is an irrational number (close to 1.618) that repeatedly occurs in nature as well as in masterpieces of art. The GR has been considered a proportion perfectly representing beauty since ancient times, and it was investigated in several scientific fields, but with conflicting results. This study aims at investigating if this proportion is associated with a judgment of beauty independently of the type of the stimulus, and the factors that may affect this aesthetic preference. In Experiment 1, an online psychophysical questionnaire was administered to 256 volunteers asked to choose among three possible proportions between the parts of the same stimulus (GR, 1.5, and 1.8). In Experiment 2, we recorded eye movements in 15 participants who had to express an aesthetic judgment on the same stimuli of Experiment 1. The results revealed a slight overall preference for GR (53%, p < .001), with higher preferences for stimuli representing humans, anthropomorphic sculptures, and paintings, regardless of the cultural level. In Experiment 2, a shorter dwell time was significantly associated with a better aesthetic judgment (p = .005), suggesting the possibility that GR could be associated with easier visual processing, and it could be hence considered as a visual affordance.

Motor imagery and gait control in Parkinson's disease: techniques and new perspectives in neurorehabilitation.

INTRODUCTION: Motor imagery (MI), defined as the ability to mentally represent an action without actual movement, has been used to improve motor function in athletes and, more recently, in neurological disorders such as Parkinson's disease (PD). Several studies have investigated the neural correlates of motor imagery, which change also depending on the action imagined. AREAS COVERED: This review focuses on locomotion, which is a crucial activity in everyday life and is often impaired by neurological conditions. After a general discussion on the neural correlates of motor imagery and locomotion, we review the evidence highlighting the abnormalities in gait control and gait imagery in PD patients. Next, new perspectives and techniques for PD patients' rehabilitation are discussed, namely Brain Computer Interfaces (BCIs), neurofeedback, and virtual reality (VR). EXPERT OPINION: Despite the few studies, the literature review supports the potential beneficial effects of motor imagery interventions in PD focused on locomotion. The development of new technologies could empower the administration of training based on motor imagery locomotor tasks, and their application could lead to new rehabilitation protocols aimed at improving walking ability in patients with PD.

Validation of SuPerSense, a Sensorized Surface for the Evaluation of Posture Perception in Supine Position.

This study aimed to validate a sensorized version of a perceptive surface that may be used for the early assessment of misperception of body midline representation in subjects with right stroke, even when they are not yet able to stand in an upright posture. This device, called SuPerSense, allows testing of the load distribution of the body weight on the back in a supine position. The device was tested in 15 patients with stroke, 15 age-matched healthy subjects, and 15 young healthy adults, assessing three parameters analogous to those conventionally extracted by a baropodometric platform in a standing posture. Subjects were hence tested on SuPerSense in a supine position and on a baropodometric platform in an upright posture in two different conditions: with open eyes and with closed eyes. Significant correlations were found between the lengths of the center of pressure path with the two devices in the open-eyes condition (R = 0.44, p = 0.002). The parameters extracted by SuPerSense were significantly different among groups only when patients were divided into those with right versus left brain damage. This last result is conceivably related to the role of the right hemisphere of the brain in the analysis of spatial information.

Robot-Assisted Training for Upper Limb in Stroke (ROBOTAS): An Observational, Multicenter Study to Identify Determinants of Efficacy.

BACKGROUND: The loss of arm function is a common and disabling outcome after stroke. Robot-assisted upper limb (UL) training may improve outcomes. The aim of this study was to explore the effect of robot-assisted training using end-effector and exoskeleton robots on UL function following a stroke in real-life clinical practice. METHODS: A total of 105 patients affected by a first-ever supratentorial stroke were enrolled in 18 neurorehabilitation centers and treated with electromechanically assisted arm training as an add-on to conventional therapy. Both interventions provided either an exoskeleton or an end-effector device (as per clinical practice) and consisted of 20 sessions (3/5 times per week; 6-8 weeks). Patients were assessed by validated UL scales at baseline (T0), post-treatment (T1), and at three-month follow-up (T2). The primary outcome was the Fugl-Meyer Assessment for the upper extremity (FMA-UE). RESULTS: FMA-UE improved at T1 by 6 points on average in the end-effector group and 11 points on average in the exoskeleton group (p < 0.0001). Exoskeletons were more effective in the subacute phase, whereas the end-effectors were more effective in the chronic phase (p < 0.0001). CONCLUSIONS: robot-assisted training might help improve UL function in stroke patients as an add-on treatment in both subacute and chronic stages. Pragmatic and highmethodological studies are needed to confirm the showed effectiveness of the exoskeleton and end-effector devices.

Effects of a posture shirt with back active correction keeper on static and dynamic balance in Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) suffer from postural disorders. This study aims at investigating the short- and medium-term effects of a shirt with appropriate tie-rods that allows to correct the posture of the trunk. METHODS: This is a longitudinal clinical study in which a pressure platform was used to assess the static and dynamic baropodometry and the static stabilometry of 20 patients with PD (70.95 ± 8.39 years old; 13 males, time from the onset of symptoms: 6.95 ± 4.04 years, Unified Parkinson's Disease Rating Scale score: UPDRS = 7.25 ± 6.26) without and with a shirt, specifically designed for improving posture, at baseline and after one month of wearing. RESULTS: The results showed a significant improvement in symmetry of loads (p = 0.015) and an enlargement of the foot contact surface (p = 0.038). A significant correlation was found between the change in forefoot load and time spent daily in wearing the shirt (R = 0.575, p = 0.008), with an optimal value identified at 8 h per day. CONCLUSION: The use of a postural shirt in patients with PD symmetrized the postural load and enlarged the foot contact surface improving their balance.

Effects of cognitive workload on heart and locomotor rhythms coupling.

Different physiological signals could be coupled under specific conditions, in some cases related to pathologies or reductions in system complexity. Cardiac-locomotor synchronization (CLS) has been one of the most investigating coupling. The influence of a cognitive task on walking was investigated in dual-task experiments, but how different cognitive tasks may influence CLS has poorly been investigated. Twenty healthy subjects performed a dual-task walking (coupled with verbal fluency vs calculation) on a treadmill at three different speeds (comfortable speed CS; fast-speed: CS + 2 km/h; slow-speed: CS-2 km/h) while cardiac and walking rhythms were recorded using surface electrodes and a triaxial accelerometer, respectively. According to previous studies, we found a cognitive-motor interference for which cognitive performance was affected by motor exercise, but not vice-versa. We found a CLS at the baseline condition, at fast speed in both cognitive tasks, while at comfortable speed only for the verbal fluency task. In conclusion, the cardiac and locomotor rhythms were not coupled at slow speed and at comfortable speed during subtraction task. Cognitive performances generally increased at faster speed, when cardiac locomotor coupling was stronger.

Italian Version of the Pittsburgh Rehabilitation Participation Scale: Psychometric Analysis of Validity and Reliability.

Patient's active participation in therapy is a key component of successful rehabilitation. In fact, low participation has been shown to be a prognostic factor of poor outcome; however, participation is rarely assessed in clinical settings. The Pittsburgh Rehabilitation Participation Scale (PRPS) is a validated, quick, and accurate measure of participation, relying on clinicians' observation, and not requiring any self-report by patients. The aim of this study was to validate an Italian version of the PRPS. Following forward and back-translation of PRPS into Italian, the translated version was validated in a total of 640 therapy sessions, related to a cohort of 32 patients admitted to an Italian hospital. It was tested for concurrent validity, finding significant correlations with Barthel Index (R > 0.58, p < 0.001) and SF-36 Physical and Mental Health (R > 0.4, p < 0.02), for predictive validity, finding significant correlation with the effectiveness of rehabilitation (R = 0.358, p = 0.045), and for inter-rater and intra-rater reliability, computing an Intra-class correlation coefficient (ICC = 0.926 and 0.756, respectively). These psychometric properties results were similar to those of the original version of this scale. The proposed PRPS can be helpful for Italian clinicians in the assessment of patient's participation during rehabilitation.

Artificial Neural Network Analyzing Wearable Device Gait Data for Identifying Patients With Stroke Unable to Return to Work.

A potential dramatic effect of long-term disability due to stroke is the inability to return to work. An accurate prognosis and the identification of the parameters inflating the possibility of return to work after neurorehabilitation are crucial. Many factors may influence it, such as mobility and, in particular, walking ability. In this pilot study, two emerging technologies have been combined with the aim of developing a prognostic tool for identifying patients able to return to work: a wearable inertial measurement unit for gait analysis and an artificial neural network (ANN). Compared with more conventional statistics, the ANN showed a higher accuracy in identifying patients with respect to healthy subjects (90.9 vs. 75.8%) and also in identifying the subjects unable to return to work (93.9 vs. 81.8%). In this last analysis, the duration of double support phase resulted the most important input of the ANN. The potentiality of the ANN, developed also in other fields such as marketing on social networks, could allow a powerful support for clinicians that today should manage a large amount of instrumentally recorded parameters in patients with stroke.