Maria Cristina Mauro

Background: Cerebral palsy (CP) is the most common neuromotor disability in children and often results in spastic diplegia, which can lead to crouch gait. This gait pattern, resulting from weakness predominantly in the extensor muscles and spasticity mainly affecting the flexors, is characterized by excessive knee flexion, insufficient hip extension, and excessive ankle dorsiflexion, which together can progressively impair walking. The Agilik powered knee-ankle-foot orthosis is designed to enhance knee extension and potentially improve gait in children with CP. Here we present the protocol of a study that aims to evaluate the clinical effectiveness of Agilik in a domiciliary setting. Methods: According to this protocol, the multicentre randomized controlled trial will enrol 40 children with CP (aged 5–17 years) exhibiting crouch gait. Participants will be randomly assigned to either the Intervention Group, which will receive training with the Agilik device, or the Control Group, which will maintain their standard routines and therapies. All participants will undergo physical examination and baseline assessments. Then, while the Control Group continues the usual care, the Intervention Group will begin the Agilik program, including three device fitting visits, 4/5 weeks of hospital training, and two months of home-based sessions. Both groups will be evaluated at three time points: baseline, after the intervention, and at a one-month follow-up. Primary endpoints include the 6-Minute Walking Test and Knee Extension in Mid-Stance computed during gait analysis. Secondary endpoints assess gross-motor abilities, gait speed, 3D gait analysis with electromyography, joint range of motion, muscle length, self-perceived performance, spasticity, and balance. Additionally, the Intervention Group will provide feedback on the usability and acceptability of the device, and on cognitive, behavioural and affective engagement. Discussion: This trial will provide valuable insights into the effectiveness of the Agilik device in children with CP and crouch gait. It will help emphasizing the potential benefits of the device on daily living activities and gait performance. The findings could influence clinical practice and guide future interventions for managing crouch gait in CP, potentially leading to enhanced quality of life for these children. Trial registration: The trial has been registered the 30 ^th September 2024 on ClinicalTrials.gov with the identifier NCT06622655.

Introduction: Stroke-related brain changes have traditionally been studied through oscillatory electroencephalographic (EEG) activity, but recent evidence highlights the value of aperiodic components. This pilot randomized controlled trial aimed to assess stroke-related aperiodic EEG changes following virtual reality-based robotic rehabilitation using the Spectral Exponent Index (SEI).Methods: Nineteen patients with subacute stroke were randomized to unilateral (n = 9) or bilateral (n = 10) upper limb training with a robotic exoskeleton (30 sessions). EEG was recorded at rest before (T0), after (T1), and at 1-week follow-up (T2). SEI was computed for hemispheric and sensorimotor clusters, in affected (AH) and unaffected (UH) hemispheres. Clinical evaluation was performed at T0 and T1 with validated clinical scales.Results: At T0, the SEI in the sensorimotor cluster of the AH was significantly lower than in the UH. At T1, the SEI in the AH increased together with clinical improvements in upper limb motor function. At T2, the SEI in the AH decreased again and was lower than in the UH. No differences were found between unilateral and bilateral groups.Discussion: Robotic rehabilitation modulated the aperiodic EEG background in the affected hemisphere of patients with stroke, particularly in sensorimotor areas. These SEI changes mirrored motor recovery, suggesting that it may represent a useful biomarker to track localized neural mechanisms of functional improvement after stroke. No differences between unilateral and bilateral training likely reflect the pilot sample size or shared cortical mechanisms of action activated by both rehabilitation approaches.Clinical Trial Registration: ClinicalTrials.gov registration number: NCT05176600.

Background: Rehabilitation after stroke often employs Robots and Allied Digital Technologies (RADTs). However, evidence of their effectiveness remains inconclusive due to study heterogeneity and limited sample sizes. Methods: This is a protocol of a pragmatic multicentre, multimodal, randomised, controlled, parallel-group (1:1) interventional study with blinded assessors aimed at assessing the effectiveness and sustainability of RADT-mediated rehabilitation compared to traditional rehabilitation. The trial will recruit 596 adult subacute post-stroke patients. Participants will be randomised into either the experimental group (using RADTs and two therapists supervising four to six patients) or the control group (individual traditional rehabilitation). Patients in both groups will undergo a comprehensive rehabilitation treatment, targeting (a) upper limb sensorimotor abilities; (b) lower limb sensorimotor abilities and gait; (c) balance; and (d) cognitive abilities. Patients will undergo 25 sessions, each lasting 45 min, with a frequency of 5 (inpatients) or 3 (outpatients) times a week. The primary endpoint is the non-inferiority of RADTs in the recovery of the activities of daily living (ADL) using the modified Barthel Index. If non-inferiority is established, the study will evaluate the superiority. Secondary endpoints will analyse the improvements in the aforementioned domains, as well as changes in neural plasticity and biochemical aspects. Upper limb dexterity and gait recovery rates during treatment will be monitored. The study will also evaluate ADL and quality of life during a six-month follow-up period. Acceptability and usability of integrated RADTs-based rehabilitation for patients, families, and healthcare providers, along with economic and organisational sustainability for patients, payers, and society, will also be assessed. Conclusions: This study aims to establish stronger evidence on the effectiveness of RADTs in post-stroke patients. Trial registration number: NCT06547827.

Background/Objectives: Robotic rehabilitation holds great potential for improving patient outcomes, but the integration of these technologies into clinical practice is hindered by a lack of comprehensive tools for assessing patients’ needs. This systematic review aimed to identify gaps in the current literature, with a focus on methodologies and tools for evaluating such needs, particularly those based on the International Classification of Functioning, Disability, and Health (ICF) framework. Methods: A systematic review of qualitative studies published between 2021 and 2023 was conducted, updating a previous (2020) review. Studies were identified through PubMed, Scopus, and Web of Science using inclusion criteria focused on qualitative methods capturing patients’ experiences with robotic and technological rehabilitation devices. Results: The review analyzed 19 new studies and 20 from the prior review, revealing a reliance on semi-structured interviews targeting small, heterogeneous populations. No studies employed standardized ICF-based tools, and gaps were noted in the exploration of conditions such as Parkinson’s disease, frailty, or conditions that allowed for multi-device experiences. Conclusions: The findings emphasize the necessity for tailored surveys grounded in the ICF framework to completely evaluate the needs of patients suffering from sensory, motor, and/or cognitive disorders caused by different health conditions. This work lays the foundation for more inclusive, effective, and patient-centered robotic rehabilitation strategies.

Background/Objectives: Finding innovative digital solutions is fundamental to ensure prompt and continuous care for patients with chronic neurological disorders, whose demand for rehabilitation also in home-based settings is steadily increasing. The aim is to verify the safety and the effectiveness of two telerehabilitation (TR) models in improving recovery from subacute upper limb (UL) disability after stroke, with and without a robotic device. Methods: One hundred nineteen subjects with subacute post-stroke UL disability were assessed for eligibility. Of them, 30 patients were enrolled in the study and randomly assigned to either the Robotic Group (RG), undergoing a 20-session TR program, using a robotic device, or the Non-Robotic Group (NRG), undergoing a 20-session TR program without robotics. Clinical evaluations were measured at baseline (T0) and post-intervention (T1, 5 weeks after baseline), and included assessments of quality of life, motor skills, and clinical/functional status. The primary outcome measure was the World Health Organization Disability Assessment Schedule 2.0, evaluating the change in perceived disability. Results: Statistical analysis shows that patients of both groups improved significantly over time in all domains analyzed (mean decrease from baseline in the WHODAS 2.0 of 6.09 ± 2.62% for the NRG, and of 0.76 ± 2.21% for the RG), with a greater improvement of patients in the NRG in motor (Fugl-Meyer Assessment Upper Extremity—motor function, Box and Block Test) and cognitive skills (Trail Making Test-A). Conclusions: This study highlights the potential of TR programs to transform stroke rehabilitation by enhancing accessibility and patient-centered care, promoting autonomy, improving adherence, and leading to better outcomes and quality of life for stroke survivors.

Bilateral robotic rehabilitation has proven helpful in the recovery of upper limb motor function in patients with stroke, but its effects on the cortical reorganization mechanisms underlying recovery are still unclear. This pilot Randomized Controlled Trial (RCT) aimed to evaluate the effects on the interhemispheric balance of unilateral or bilateral robotic treatments in patients with subacute stroke, using Quantitative Electroencephalography (qEEG). 19 patients with ischemic stroke underwent a 30-session upper limb neurorehabilitation intervention using a bilateral upper limb exoskeleton. Each patient was randomly assigned to the bilateral (BG, n=10) or unilateral treatment group (UG, n=9). EEG evaluations were performed before (T0) and right after (T0+) the first treatment session, after 30 treatment sessions (T1), and at 1-week follow-up (T2), in both eyes open and eyes closed conditions. From the acquired EEG data, the pairwise-derived Brain Symmetry Index (pdBSI) was computed. In addition, clinical evaluation was performed at T0 and T1 with validated clinical scales. After the treatment, a significant improvement in clinical and EEG evaluations was observed for both groups, but only the BG showed reduced pdBSI in delta and theta bands. In the cluster of sensorimotor channels, there was no significant difference between groups. The observed changes were not maintained at follow-up. No significant changes were observed in the pdBSI after a single rehabilitation session. Results suggest that balancing of interhemispheric symmetry comes along with a clinical improvement in the upper extremity and that the pdBSI can be used to investigate the mechanisms of neuronal plasticity involved in robotic rehabilitation after stroke.

Introduction Rehabilitation after stroke often employs Robots and Allied Digital Technologies (RADTs). However, evidence of their effectiveness remains inconclusive due to study heterogeneity and limited sample sizes. Here, we describe a protocol for a multicentre randomized controlled pragmatic trial aimed at comprehensively and accurately assessing the effectiveness and sustainability of RADT-mediated rehabilitation, compared to traditional rehabilitation. Methods and analysis This is a pragmatic multicentre, multimodal, randomised, controlled, parallel-group (1:1) interventional study with blinded assessors. The trial will recruit 596 adult post-stroke patients in the subacute phase (less than 6 months post-stroke). Patients will be recruited from thirteen rehabilitation centres participating in a national research initiative, encompassing both outpatient and inpatient clinical settings. Participants will be randomized into either the experimental group, or the control group. The experimental group will receive rehabilitation using RADTs within a new organizational model, where two physical therapists supervise four to six patients; patients will undergo a comprehensive rehabilitation treatment, targeting the following domains: a) upper limb sensorimotor abilities; b) lower limb sensorimotor abilities and gait; c) balance; d) cognitive abilities. In the control group, patients will undergo individual traditional rehabilitation, maintaining a 1:1 patient-to-therapist ratio, targeting the same domains. Patients will undergo a total of 25 sessions, each lasting 45 minutes, with a frequency of 5 times a week, for inpatients; and 3 times a week, for outpatients. The primary endpoint is to demonstrate non-inferiority in the recovery of the activities of daily living as measured by the modified Barthel Index. If non-inferiority is established, the study will then evaluate the superiority of RADTs in the recovery of the activities of daily living. Secondary endpoints include improvements in upper and lower limb function, balance, cognitive function, and, according to the ICF, in the body functions, activities, and participation domains. Additional analyses will cover neurophysiological assessments of neural plasticity, as well as biochemical, and genetic evaluations. Upper limb dexterity and gait recovery rates during treatment will be monitored. The study will also evaluate daily activities and quality of life during a six-month follow-up period post-treatment. Acceptability and usability of integrated RADTs-based rehabilitation for patients, families, and healthcare providers, along with economic and organizational sustainability for patients, payers, and society, will also be assessed. Outcomes will be measured and analysed by blinded assessors. Ethics and dissemination This study was reviewed and approved by National Ethics Committee for clinical trials of Public Research Bodies (EPR) and other National Public Institutions (CEN). The results will be disseminated through scientific articles in peer-reviewed journals and presentations at both national and international conferences. Trial registration number NCT06547827 • The effectiveness of robotics and allied technologies will be evaluated using a novel approach involving a multimodal intervention. This approach addresses all impaired functions to holistically enhance activities of daily living, which represent the patient’s most important needs. • In addition to clinical scales, neurophysiological and biochemical data will be considered for a deeper understanding of the mechanisms underlying motor recovery. • Detailed patient profiling will enable the creation of predictive models to identify subjects who may respond better to treatment integrated with robotics and allied technologies. • The economic analysis will allow us to assess the sustainability of a new organizational model based on the use of robotics and allied technologies, where two physiotherapists supervise a group of patients simultaneously. • A study limitation is the use of different technologies across research centres. However, this reflects real-world conditions. To address the inevitable variability, we clearly defined the functional domains for treatment with robotic or technological systems, focusing on the lower limbs, balance, upper limb segments, and cognitive functions. Moreover, to manage other possible sources of variability due to the number of centres involved, a consensus was reached about clear protocols for clinical evaluation and therapy administration to be shared in clinical practice by all the participating centres.