User-centred assistive SystEm for arm Functions in neUromuscuLar subjects (USEFUL): a randomized controlled study.

BACKGROUND: Upper limb assistive devices can compensate for muscular weakness and empower the user in the execution of daily activities. Multiple devices have been recently proposed but there is still a lack in the scientific comparison of their efficacy. METHODS: We conducted a cross-over multi-centric randomized controlled trial to assess the functional improvement at the upper limb level of two arms supports on 36 patients with muscular dystrophy. Participants tested a passive device (i.e., Wrex by Jaeco) and a semi-active solution for gravity compensation (i.e., Armon Ayura). We evaluated devices' effectiveness with an externally-assessed scale (i.e., Performance of the Upper Limb-PUL-module), a self-perceived scale (i.e., Abilhand questionnaire), and a usability scale (i.e., System Usability Scale). Friedman's test was used to assess significant functional gain for PUL module and Abilhand questionnaire. Moreover, PUL changes were compared by means of the Friedman's test. RESULTS: Most of the patients improved upper limb function with the use of arm supports (median PUL scores increase of 1-3 points). However, the effectiveness of each device was related to the level of residual ability of the end-user. Slightly impaired patients maintained the same independence without and with assistive devices, even if they reported reduced muscular fatigue for both devices. Moderately impaired patients enhanced their arm functionality with both devices, and they obtained higher improvements with the semi-active one (median PUL scores increase of 9 points). Finally, severely impaired subjects benefited only from the semi-active device (median PUL scores increase of 12 points). Inadequate strength was recognized as a barrier to passive devices. The usability, measured by the System Usability Scale, was evaluated by end-users "good" (70/100 points) for the passive, and "excellent" (80/100 points) for the semi-active device. CONCLUSIONS: This study demonstrated that assistive devices can improve the quality of life of people suffering from muscular dystrophy. The use of passive devices, despite being low cost and easy to use, shows limitations in the efficacy of the assistance to daily tasks, limiting the assistance to a predefined horizontal plane. The addition of one active degree of freedom improves efficacy and usability especially for medium to severe patients. Further investigations are needed to increase the evidence on the effect of arm supports on quality of life and diseases' progression in subjects with degenerative disorders. Trial registration clinicaltrials.gov, NCT03127241, Registered 25th April 2017. The clinical trial was also registered as a post-market study at the Italian Ministry of Health.

Validation of the Italian version of a patient-reported outcome measure for Hereditary Spastic Paraplegia.

BACKGROUND AND AIM: Patient-reported outcome measures (PROMs) are recognized as valuable measures in the clinical setting. In 2018 we developed the Italian version of the "Hereditary Spastic Paraplegia-Self Notion and Perception Questionnaire" (HSP-SNAP), a disease-specific questionnaire that collects personal perception on motor symptoms related to HSP such as stiffness, weakness, imbalance, reduced endurance, fatigue and pain. In this study our primary aim was to assess the questionnaire validity and reliability. Our secondary aim was to characterize the symptoms "perceived" by patients with HSP and compare them with those "perceived" by age-matched healthy subjects. METHODS: The 12-item HSP-SNAP questionnaire was submitted to 20 external judges for comprehensibility and to 15 external judges for content validity assessment. We recruited 40 subjects with HSP and asked them to fill the questionnaire twice for test-retest procedure. They also completed the Medical Outcome Survey Short Form (SF-36) and were evaluated by the Spastic Paraplegia Rating Scale and the Six-Minute Walk Test. We also recruited 44 healthy subjects who completed the HSP-SNAP once to test score variability. RESULTS: The HSP-SNAP content validity index was high (0.8±0.1) and the test-retest analysis showed high reliability (ICC = 0.94). The mean HSP-SNAP score (score range 0-48) of the HSP group was 22.2±7.8, which was significantly lower than healthy subjects (43.1±6.3). The most commonly perceived symptom was stiffness, followed by weakness and imbalance. CONCLUSION: Although HSP-SNAP does not investigate non-motor symptoms and we validated only its Italian version, it showed good validity and reliability and it could be used in combination with other objective outcome measures for clinical purposes or as endpoints for future clinical rehabilitation studies. TRIAL REGISTRATION: Trial Registration: ClinicalTrial.gov, NCT04256681. Registered 3 February 2020.

The Effect of a New Generation of Ankle Foot Orthoses on Sloped Walking in Children with Hemiplegia Using the Gait Real Time Analysis Interactive Lab (GRAIL).

Cerebral palsy poses challenges in walking, necessitating ankle foot orthoses (AFOs) for stability. Gait analysis, particularly on slopes, is crucial for effective AFO assessment. The study aimed to compare the performance of commercially available AFOs with a new sports-specific AFO in children with hemiplegic cerebral palsy and to assess the effects of varying slopes on gait. Eighteen participants, aged 6-11, with hemiplegia, underwent gait analysis using GRAIL technology. Two AFO types were tested on slopes (uphill +10 deg, downhill -5 deg, level-ground). Kinematic, kinetic, and spatiotemporal parameters were analyzed. The new AFO contributed to significant changes in ankle dorsi-plantar-flexion, foot progression, and trunk and hip rotation during downhill walking. Additionally, the new AFO had varied effects on spatiotemporal gait parameters, with an increased stride length during downhill walking. Slope variations significantly influenced the kinematics and kinetics. This study provides valuable insights into AFO effectiveness and the impact of slopes on gait in hemiplegic cerebral palsy. The findings underscore the need for personalized interventions, considering environmental factors, and enhancing clinical and research approaches for improving mobility in cerebral palsy.

Is Social Training Delivered with a Head-Mounted Display Suitable for Patients with Hereditary Ataxia?

Social cognition is fundamental in everyday life to understand "others' behavior", which is a key feature of social abilities. Previous studies demonstrated the efficacy of a rehabilitative intervention in semi-immersive virtual reality (VR) controlled by whole-body motion to improve the ability of patients with cerebellar disorders to predict others' intentions (VR-SPIRIT). Patients with severe ataxia that have difficulties at multiple levels of social processing could benefit from this intervention in terms of improving their social prediction skills, but they may have difficulties in controlling VR with whole-body movements. Therefore, we implemented VR-SPIRIT on a wearable, affordable, and easy-to-use technology, such as the Oculus Quest, a head-mounted display. The aim of this work was to evaluate the usability and tolerability of this VR application. We recruited 10 patients (37.7 ± 14.8 years old, seven males) with different types of hereditary ataxia who performed a single VR-SPIRIT session using the Oculus Quest viewer. After the session, patients answered a series of questionnaires to investigate the overall usability of the system and its potential effects in terms of cyber sickness. The preliminary results demonstrated system usability and tolerability. Indeed, only three patients did not complete the session due to different problems (dizziness, nausea, and boredom). In future studies, more patients will be enrolled to assess the effectiveness of the application, paving the way for the implementation of social training that can also be delivered at home.

Context expectation influences the gait pattern biomechanics.

Beyond classical aspects related to locomotion (biomechanics), it has been hypothesized that walking pattern is influenced by a combination of distinct computations including online sensory/perceptual sampling and the processing of expectations (neuromechanics). Here, we aimed to explore the potential impact of contrasting scenarios ("risky and potentially dangerous" scenario; "safe and comfortable" scenario) on walking pattern in a group of healthy young adults. Firstly, and consistently with previous literature, we confirmed that the scenario influences gait pattern when it is recalled concurrently to participants' walking activity (motor interference). More intriguingly, our main result showed that participants' gait pattern is also influenced by the contextual scenario when it is evoked only before the start of walking activity (motor expectation). This condition was designed to test the impact of expectations (risky scenario vs. safe scenario) on gait pattern, and the stimulation that preceded walking activity served as prior. Noteworthy, we combined statistical and machine learning (Support-Vector Machine classifier) approaches to stratify distinct levels of analyses that explored the multi-facets architecture of walking. In a nutshell, our combined statistical and machine learning analyses converge in suggesting that walking before steps is not just a paradox.

The Performance of Upper Limb (PUL) module in limb-girdle muscular dystrophy.

Limb-girdle muscular dystrophy (LGMD) is a genetic muscle disorder causing weakness and wasting of the proximal limb musculature. When ambulation is lost, the attention must be shifted to the upper limb muscles' function. We studied the upper limb muscle strength and the corresponding function in 15 LGMDR1/LGMD2A and 13 LGMDR2/LGMD2B, through the Performance of Upper Limb scale and the MRC score of upper limbs. The proximal item K and the distal items N and R were lower in LGMD2B/R2. The mean MRC score of all the muscles involved linearly correlated (r2 = 0.922) for item K in LGMD2B/R2. The functional worsening paralleled the muscles weakness in LGMD2B/R2. By contrast, at proximal level the function of LGMD2A/R1 was preserved despite muscle weakness was present, presumably due to compensatory strategies. Sometimes the combination of parameters might be more informative than considering them separately. PUL scale and MRC might be interesting outcome measures in non-ambulant patients.

Could an Immersive Virtual Reality Training Improve Navigation Skills in Children with Cerebral Palsy? A Pilot Controlled Study.

Children with cerebral palsy (CP) suffer deficits in their motor, sensory, and cognitive abilities, as well as in their visuospatial competences. In the last years, several authors have tried to correlate the visuospatial abilities with the navigational ones. Given their importance in everyday functions, navigation skills have been deeply studied using increasingly cutting-edge techniques such as virtual reality (VR). However, to our knowledge, there are no studies focused on training using immersive VR (IVR) in children with movement disorders. For this reason, we proposed an IVR training to 35 young participants with CP and conceived to improve their navigation skills in a "simil-real" environment while playing on a dynamic platform. A subgroup performed a part of the training which was specifically dedicated to the use of the allocentric strategy (i.e., looking for landmarks) to navigate the virtual environment. We then compared the children's navigation and spatial skills pre- and post-intervention. All the children improved their visual-spatial abilities; particularly, if the IVR activities specifically trained their ability to look for landmarks and use them to navigate. The results of this work highlight the potential of an IVR training program to increase the navigation abilities of patients with CPs.

Genetic modifiers of upper limb function in Duchenne muscular dystrophy.

Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations.

Over three decades of natural history of limb girdle muscular dystrophy type R1/2A and R2/2B: Mathematical modelling of a multifactorial study.

We aimed to describe the natural history of Limb Girdle Muscular Dystrophy type 2A and 2B over more than three decades by considering muscular strength, motor, cardiac and respiratory function. 428 visits of nineteen 2A and twenty 2B patients were retrospectively analysed through a regression model to create the curves of evolution with disease duration of muscle strength (through Medical Research Council grading), motor function measure scale (D1, D2 and D3 domains) and cardio-pulmonary function tests. Clinically relevant muscular and motor function alterations occurred after the first decade of disease, while mild respiratory function alterations started after the second, with preserved cardiac function. Although type 2A showed relatively stronger distal lower limb muscles, while type 2B started with relatively stronger upper limb muscles, the corresponding motor functions were similar, becoming severely compromised after 25 years of disease. This was the longest retrospective study in types 2A and 2B. It defined curves of disease evolution not only from a neuromuscular, but also from functional, cardiac, and respiratory points of view, to be used to evaluate how the natural progression is changed by therapies. Due to slow disease progression, it was not possible to identify time sensitive endpoints.

Test-retest reliability of the Performance of Upper Limb (PUL) module for muscular dystrophy patients.

The Performance of the Upper Limb (PUL) module is an externally-assessed clinical scale, initially designed for the Duchenne muscular dystrophy population. It provides an upper extremity functional score suitable for both weaker ambulatory and non-ambulatory phases up to the severely impaired patients. It is capable of characterizing overall progression and severity of disease and of tracking the stereotypical proximal-to-distal progressive loss of upper limb function in muscular dystrophy. Since the PUL module has been validated only with Duchenne patients, its use also for Becker and Limb-Girdle muscular dystrophy patients has been here evaluated, to verify its reliability and extend its use. In particular, two different assessors performed this scale on 32 dystrophic subjects in two consecutive days. The results showed that the PUL module has high reliability, both absolute and relative, based on the calculation of Pearson's r (0.9942), Intraclass Correlation Coefficient (0.9943), Standard Error of Measurement (1.36), Minimum Detectable Change (3.77), and Coefficient of Variation (3%). The Minimum Detectable Change, in particular, can be used in clinical trials to perform a comprehensive longitudinal evaluation of the effects of interventions with the lapse of time. According to this analysis, an intervention is effective if the difference in the PUL score between subsequent evaluation points is equal or higher than 4 points; otherwise, the observed effect is not relevant. Inter-rater reliability with ten different assessors was evaluated, and it has been demonstrated that deviation from the mean is lower than calculated Minimum Detectable Change. The present work provides evidence that the PUL module is a reliable and valid instrument for measuring upper limb ability in people with different forms of muscular dystrophy. Therefore, the PUL module might be extended to other pathologies and reliably used in multicenter settings.

Sensitivity of Neuroimaging Indicators in Monitoring the Effects of Interferon Gamma Treatment in Friedreich's Ataxia.

The identification of efficient markers of disease progression and response to possibly effective treatments is a key priority for slowly progressive, rare and neurodegenerative diseases, such as Friedreich's ataxia. Various imaging modalities have documented specific abnormalities in Friedreich's ataxia that could be tracked to provide useful indicators of efficacy in clinical trials. Advanced MRI imaging (diffusion tensor imaging, DTI; functional MRI, fMRI; and resting-state fMRI, rs-fMRI) and retinal imaging (optical coherence tomography, OCT) were tested longitudinally in a small group of Friedreich's ataxia patients participating in an open-label clinical trial testing the safety and the efficacy of 6-month treatment with interferon gamma. While the DTI indices documented the slow progression of fractional anisotropy loss, fMRI and rs-fMRI were significantly modified during and after treatment. The fMRI changes significantly correlated with the Scale for the Assessment and Rating of Ataxia, which is used to monitor clinical response. OCT documented the known thickness reduction of the retinal nerve fiber layer thickness, but there was no change over time. This pilot study provides indications for the potential utility of fMRI and rs-fMRI as ancillary measures in clinical trials for Friedreich's ataxia.

Immersive Virtual Reality to Improve Walking Abilities in Cerebral Palsy: A Pilot Study.

Immersive virtual reality (IVR) offers new possibilities to perform treatments in an ecological and interactive environment with multimodal online feedbacks. Sixteen school-aged children (mean age 11 ± 2.4 years) with Bilateral CP-diplegia, attending mainstream schools were recruited for a pilot study in a pre-post treatment experimental design. The intervention was focused on walking competences and endurance and performed by the Gait Real-time Analysis Interactive Lab (GRAIL), an innovative treadmill platform based on IVR. The participants underwent eighteen therapy sessions in 4 weeks. Functional evaluations, instrumental measures including GAIT analysis and parental questionnaire were utilized to assess the treatment effects. Walking pattern (stride length left and right side, respectively p = 0.001 and 0.003; walking speed p = 0.001), endurance (6MWT, p = 0.026), gross motor abilities (GMFM-88, p = 0.041) and most kinematic and kinetic parameters significantly improved after the intervention. The changes were mainly predicted by age and cognitive abilities. The effect could have been due to the possibility of IVR to foster integration of motor/perceptual competences beyond the training of the walking ability, giving a chance of improvement also to older and already treated children.