Eleonora Diella

Background: Natural history data are crucial for supporting clinical trial readiness in muscular dystrophies. Multisystemic and slowly progressive diseases, such as myotonic dystrophy type 1 (DM1), require significant efforts to define the different aspects of evolution across multiple systems. Methods: Our study aimed to model the progression of different functions (namely, muscular, motor, and respiratory) over more than 20 years in 3 different DM1 subtypes (congenital, childhood, and adult forms) related to disease duration. Results: We defined disease progression curves of different functions (muscular assessed through MRC scale during 565 visits, motor assessed through MFM scale during 409 visits, and respiratory assessed through spirometry and nocturnal saturation during 533 visits) in 9 congenital, 25 childhood, and 45 adult form, related to disease duration through a linear mixed model. The shape and slope of the progression curves differ across phenotypes, with some functional domains showing earlier and steeper declines. Conclusion: The progression curves confirm some clinical observations: (1) the decline of the upper limbs’ strength is more evident in the distal portion; (2) the decline of the lower limbs is due to ankle muscles; (3) the lung restriction and nocturnal oxygen desaturation parallel obesity onset. In addition, they show that the D1 sub- scale of the MFM scale is the most affected functional motor parameter, with a trend of decline similar to the ankle strength and the 6-minute walking test. Taken together, our data provide important guidance for the design of future clinical studies in DM1.

Evidence-based guidelines for motor rehabilitation in Hereditary Spastic Paraplegia (HSP) are still lacking but robotic gait training may offer benefits for motor function and walking. The aim of this study is to evaluate the effects of a robot-assisted gait training (RAGT) combined with traditional treatment (TT) on gait pattern, motor skills and quality of life in subjects affected by HSP. 40 patients (33 pure; 20 pediatric) underwent an intensive program with RAGT and TT daily (five-times a week for three consecutive weeks). Patients were evaluated pre and post intervention with gait analysis, gross-motor and timed walking tests and quality of life questionnaires. A three-month follow-up was conducted. A statistically significant improvement was observed in the Six-Minute Walk Test (6MWT). Enhancements have been obtained also in the Ten-Meter Walk Test (10mWT), the Berg Balance Scale (BBS) and the GMFM-88. The Spastic Paraplegia Rating Scale (SPRS) suggested reduction in disease severity. Quality of life's questionnaires showed improved perceived physical health. Gait analysis data did not show significant changes. Intensive treatment with a combination of RAGT and TT improves functional skills and quality of life in HSP. These new findings could guide clinical management and development of future rehabilitation studies.

Background: Cerebral palsy (CP) is the most common cause of disability in developmental age, affecting motor and postural skills. With growth, lower-limb orthopedic surgery often becomes necessary. Post-surgical walking rehabilitation programs generally involve conventional therapy with only limited evidence on the use of robot-assisted gait training (RAGT). The aim of the present pilot study is to assess the feasibility and the preliminary functional outcomes of an intensive 3-week rehabilitation of 15 sessions with Lokomat combined with 15 sessions of conventional physiotherapy. Methods: In total, 27 patients with diplegic cerebral palsy who underwent orthopedic surgery were recruited. Outcomes collected: the 6 min walking test (primary outcome), the Gross Motor Function Measure-88, the Gillette Functional Assessment Questionnaire, 3D gait analysis, and spasticity and force metrics of the lower limbs. Paired statistical tests were used to assess pre–post changes. Results: A pre–post statistically significant improvement was observed in gait endurance in the 6MWT (Δ = 28.56 ± 34.28 m; p < 0.001) and in gross motor functional skills. Gait parameters showed some functional and structural improvements, and joint stiffness was reduced in some measures. Conclusions: This combined rehabilitative approach seems to be promising in postoperative patients with CP. Future studies, involving a control group and larger sample size, are needed to generalize our results.

This paper describes the development, fabrication and testing of Playcuff, a wearable device designed to act as a videogame controller for children with motor disabilities, which also provides an orthotic action to improve the control of the upper limb. The aim of this device is to empower children with motor impairment and enable them to access and enjoy gaming despite their disabilities. The videogame controller function was achieved through on-board gesture classification using a two-tiered Fine Tree machine learning algorithm integrated into the device’s firmware. Based on features extracted from two inertial sensors present on the device, the classifier was trained to identify in real time 22 classes representing different postures and movements of forearm and wrist, showing an accuracy higher than 94%. A cohort of children ( n = 19, aged 9.01 ± 1.95 years old) with neuromotor impairment involving the upper limb were enrolled to test the device. The acceptability and effectiveness of the device were evaluated through a specific questionnaire: the resulting answers were heavily skewed towards appreciation (80.5%) rather than criticism. The methods of classification were found to be simple and effective in controlling the game. In conclusion, Playcuff was shown to be a versatile and well-received orthotic controller, which could be used in future also for videogame-based rehabilitation.

Objectives: To examine the emotional, cognitive and dispositional experience of children and adolescents undergoing Lokomat rehabilitation by integrating self-evaluation, therapist observations and physiological metrics across repeated sessions, with the aim of characterising how patient experience evolves throughout paediatric robot-assisted gait training. Design: Prospective observational study using a multidimensional assessment approach combining self-report, therapist ratings and physiological measures. Setting: Inpatients undergoing robot-assisted gait training (RAGT) with the Lokomat at the Scientific Institute Eugenio Medea in Bosisio Parini (Italy). Participants: 42 children and adolescents (N=42; mean age 11.66±5.59 years) undergoing RAGT. Interventions: Robot-assisted gait therapy with the Lokomat. Participants underwent 30-minute therapy sessions as per routine rehabilitation protocols, with treatment durations ranging from 15 to 20 sessions, as prescribed by their referring clinician. Primary and secondary outcome measures: Participants completed ad-hoc questionnaires about emotional, cognitive and dispositional factors before and after therapy; therapists provided structured assessments of patient engagement and psychological states. Physiological data, such as heart rate variability (HRV) and electrodermal activity (EDA), were recorded using wearable sensors to capture physiological correlates of emotional and cognitive engagement. Results: The results showed that by the end of Lokomat therapy, patients displayed increased cognitive engagement and better emotional regulation, along with higher vagal activity (normalised high-frequency) and increased phasic EDA responses. According to the therapists, patients appeared more confident, calm and cooperative. Sympathetic activation observed during satisfaction ratings reflected the involvement of the autonomic nervous system in positive emotional experiences. Conclusions: This study, therefore, emphasises a multidimensional approach to rehabilitation, which involves subjective patient self-assessments, therapist observations and physiological signals in an effort to capture a more comprehensive patient experience. The findings highlight the importance of personalised, patient-centred approaches and contribute new evidence on the psychological and physiological effects of RAGT in paediatric populations. Further research is warranted to confirm these results and explore their clinical implications. Trial registration number: NCT05767268 .

Children with neuromotor disorders often experience hand impairments that limit independence in daily tasks as well as the acquisition of new skills. Robotic aids like hand exoskeletons can improve function, but many designs fail to meet user needs, reducing adoption. This study collected parental feedback to guide the development of user-centered hand exoskeletons. An anonymous online survey was distributed to the parents of children with neurological disorders and previously treated at IRCCS E. Medea - Associazione "La Nostra Famiglia" in Bosisio Parini, Italy. Only parents of children with upper limb impairments were invited to answer. The survey explored their perceptions of hand exoskeletons, focusing on functional needs, user-friendliness, and training expectations. A total of forty-six surveys were completed, of which three were incomplete and therefore excluded. Of the forty-three considered, 76.3% expressed interest in a hand exoskeleton for their child, identifying dressing, hygiene, and eating as key activities to address. Key issues in the development of an exoskeleton for the parents were weight, comfort, associated aesthetics and trust. User feedback emphasizes the need for comfortable, lightweight designs with aesthetic appeal to reduce stigma. Parents prioritized functional benefits for daily activities over recreational use.

Background: Telerehabilitation is a promising solution to provide continuity of care. Most existing telerehabilitation platforms focus on rehabilitating upper limbs, balance, and cognitive training, but exercises improving cardiovascular fitness are often neglected. Objective: The objective of this study is to evaluate the acceptability and feasibility of a telerehabilitation intervention combining cognitive and aerobic exercises. Methods: A virtual reality–based dual-task exercise exploiting a cycle ergometer was designed, developed, and integrated with a commercially available telerehabilitation platform. Patients with different conditions were enrolled and administered subjective questionnaires investigating attitudes toward technology, usability, technology acceptance, and subjective workload. Their therapists were interviewed, and adherence and performance data were analyzed. Results: In total, 26 patients with neurological or post-COVID symptoms were included. Their attitude toward technology (range: 0‐5) did not change after the training period (pre: 3.44 [IQR 0.63]; post: 3.50 [IQR 0.48]); the platform was rated usable and acceptable. Frustration and physical and mental workload were present, especially among younger participants. The adherence was moderate, but individual differences were present (0.59 [IQR 0.54]). The therapists highlighted the potential of remote rehabilitation programs but also identified some limitations. Conclusions: This study proved the feasibility and acceptability of a customized virtual reality–based telerehabilitation program allowing for the safe implementation of aerobic cycling-based dual-task training. The solution was judged meaningful for dehospitalized patients, although some environmental and technical barriers should be overcome to implement telerehabilitation more effectively.

Background/Objectives: Rett syndrome is a rare neurodevelopmental disorder that can severely affect motor functioning, particularly walking. Previous training programs proposed treadmills as tools to increase walking endurance of patients with Rett syndrome, but these trainings did not include virtual reality (VR). The aim of this study was to assess the feasibility of a short treadmill training coupled to VR in girls with Rett syndrome. Methods: Nine patients with Rett syndrome underwent a 3-day treadmill walking program performed in semi-immersive VR. During the training, the happiness index and performance metrics were collected. At the end of the training parents filled out the Suitability Evaluation Questionnaire (SEQ) and, when feasible, patients underwent a gait assessment. Results: All the subjects recruited performed the three GRAIL sessions and parents showed a good satisfaction and considered the integration of treadmill and VR a good possibility for future rehabilitative programs. Participants showed greater satisfaction in environments requiring walking and their attention increased during training sessions, hypothesizing the feasibility of longer trainings with treadmill and VR. Data collected from gait analysis provided insights, although preliminary, concerning differences in gait pattern amongst the recruited subjects. Conclusions: Despite the small sample size and limited training duration, the paper suggests that a walking training with a treadmill combined with VR can represent a new strategy for Rett rehabilitation.

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.