Factors Associated with Clinical Meaningful Recovery after Upper Limb Task-Oriented Training in People with Stroke: A Cohort Study Alberto Romano, Anna Di Meo, Maurizio Ferrarin, Rune Thorsen, Davide Cattaneo, Rita Bertoni, Johanna Jonsdottir Neurorehabilitation, 2025 Background Task-oriented training (TOT) is a commonly used intervention to improve upper extremity function after stroke. However, predictors of response to rehabilitation for performance and participation remain poorly understood. Aim To identify baseline predictors of clinically significant upper extremity (UE) recovery across impairment, performance, and participation in individuals post-stroke following TOT. Methods This is a retrospective study. Sixty-four individuals with stroke were enrolled and received five weeks of inpatient TOT for UE. Baseline characteristics and outcome measures were assessed using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) for impairment, the Action Research Arm Test (ARAT-15) for performance, and the QuickDASH-9 for participation. Participants were classified as responders and non-responders to the intervention, and binary logistic regression models were developed to predict responsiveness to impairment, performance, and participation measures. Results All outcome measures showed significant improvement post-intervention. The baseline FMA-UE score, chronicity, and dominance of the involved UE predicted responsiveness for impairment. The FMA-UE score was the main predictor of responsiveness in performance, while no predictors were identified for participation. Conclusions TOT improved UE impairment and performance in stroke patients, particularly those with moderate baseline impairment. Baseline UE function, chronicity, and dominance were key predictors of responsiveness in impairment and performance. This study highlights the importance of personalized TOT after a stroke. It demonstrates that baseline function, chronicity, and affected limb dominance predict impairment and performance responsiveness to TOT while emphasizing the need to incorporate strategies that facilitate real-world skill transfer and address personal and environmental factors to maximize participation.
Fatigue and Its Association with Upper Limb Function in People with Multiple Sclerosis Erica Grange, Davide Marengo, Rachele Di Giovanni, Giampaolo Brichetto, Margit Mueller, Andrea Tacchino, Rita Bertoni, Francesco Zagari, Angelo Pappalardo, Luca Prosperini, Rosalba Rosato, Davide Cattaneo, Claudio Solaro Neurology International, 2025 Background and Objectives: This cross-sectional study investigates the association between fatigue and upper limb (UL) function in people with Multiple Sclerosis (PwMS). Methods: Adult PwMS were recruited from five Italian MS centers. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS), while UL function was assessed through the Box and Block Test (BBT), Nine-Hole Peg Test (9HPT), and Hand-Grip Strength (HGS). Data analysis included Spearman rank correlations and Mann–Whitney U tests. Results: A total of 261 participants were involved. Significant correlations were found between fatigue severity, UL function, and patient-reported manual ability. Physical and cognitive aspects of fatigue were independently related to functional impairments. Participants with clinically relevant fatigue demonstrated lower subjective UL function, poorer BBT and HGS performance, and greater HGS asymmetry. Discussion: The study underscores the complex relationship between fatigue and functional impairments in MS. The findings suggest both strength and dexterity contribute to the perception of clinically relevant fatigue in PwMS, highlighting the importance of incorporating both domains to complement neurological assessment. Conclusion: Fatigue in PwMS is linked to both subjective and objective measures of UL function. Assessing strength and dexterity alongside fatigue may enhance clinical understanding and inform targeted rehabilitation strategies.
Efficacy of a Rehabilitation Treatment Using Action Observation Therapy Enhanced by Muscle Synergy-Derived Electrical Stimulation (OTHELLO) in Post-Stroke Patients: A RCT Study Protocol Monia Cabinio, Tiziana Lencioni, Arturo Nuara, Federica Rossetto, Valeria Blasi, Gaia Bailo, Rebecca Cardini, Rita Bertoni, Alessandro Viganò, Mariangela Bianco, Angela Comanducci, Pietro Avanzini, Maurizio Ferrarin, Luca Fornia, Francesca Baglio Journal of Central Nervous System Disease, 2025 Background: Action Observation Therapy (AOT) and Neuromuscular Electrical Stimulation (NMES) are widely adopted techniques for upper-limb rehabilitation in post-stroke patients. Although AOT and NMES are individually effective, studies investigating a potential synergistic effect on enhancing rehabilitative outcomes are lacking. Objectives: This study aims at comparing the effect of AOT and NMES applied together (AOT-NMES) on muscle synergies with respect to either AOT alone or a Motor Neutral Observation treatment alone (MNO, involving neither AOT nor NMES) on motor function recovery of upper limb. Design: Randomized Controlled Trial (RCT) with n = 60 post-stroke patients with resulting upper limb disability, randomly allocated (1:1:1 ratio) in three interventional arms: AOT-NMES (n = 20), AOT (n = 20) and MNO (n = 20). Methods and Analyses: All rehabilitation treatments will consist of n°15 60 min-long rehabilitative sessions. Primary outcome measure will be upper limb motor function, assessed using the Fugl-Meyer Assessment scale for upper limb (FM-UL), collected at the baseline (T0), post-intervention (T1) and at follow-up (T2, 6-months after T1). Other outcome measures will be collected through a multidimensional evaluation including assessing stroke-associated quality of life, neurophysiological data, biomechanical and MRI measures. The innovative protocol will also be evaluated for usability and safety. Discussion: We expect to determine the efficacy, usability and safety of the AOT-NMES rehabilitation approach for the recovery of upper limb motor function in post-stroke patients. The obtained results will also help reveal the neural underpinnings of motor recovery, as assessed by neurophysiological data, biomechanical and MRI measures.
Exploring the effectiveness of circuit training rehabilitation on balance, gait, and fatigue in multiple sclerosis: a systematic review and meta-analysis Rebecca Cardini, Chiara Corrini, Rita Bertoni, Denise Anastasi, Davide Cattaneo, Elisa Gervasoni Physiotherapy United Kingdom, 2024 BACKGROUND: People with Multiple Sclerosis (PwMS) often experience imbalance, gait dysfunction, and fatigue. Circuit Training (CT) can be viable for improving balance, gait, and fatigue in MS. To the author's knowledge, no studies have systematically reviewed the existing literature evaluating the effectiveness of CT in PwMS. OBJECTIVES: To investigate the effectiveness of CT in improving balance, gait, and reducing fatigue in PwMS and provide a quantitative and qualitative synthesis of Randomized Controlled Trials (RCTs). DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Google Scholar, and PEDro Database (Dec 2021 to May 2024). STUDY SELECTION: RCTs using CT in PwMS including balance, gait, or fatigue outcomes. DATA SYNTHESIS: Search inclusion criteria were: i) available full text, ii) CT rehabilitation, iii) balance, gait, or fatigue measured as outcomes, and iv) articles in English. Full text articles were analyzed by two screeners. If there was disagreement regarding inclusion, a further reviewer was consulted. No discrepancies were found. RESULTS: We identified 878 studies, 14 studies were eligible including 716 PwMS with a mean (standard deviation) age of 49.9 (10.9) years, disease duration of 10.8 (7.2) years, and Expanded Disability Status Scale score of 4.3 (0.9) points. RevMan 5.4.1 was used to run the meta-analysis. We found a significant overall effect on Berg Balance Scale (Mean Difference (MD) = 6.07 points, 95%CI:1.40,10.75; p = 0.01) and in Fatigue Severity Scale (MD = 0.98 points, 95%CI:0.30,1.66; p = 0.005) in favor of CT. We did not find a significant effect in Timed Up and Go (MD = 0.46 second, 95%CI:-0.04,0.96; p = 0.07), in Six-Minute Walk Test (MD = 17.46 m, 95%CI:-8.06,42.97; p = 0.18), and in Modified Fatigue Impact Scale (MD = 3.34 points, 95%CI:-0.41,7.09; p = 0.08) in favor of CT. We assessed methodological quality using RoB 2.0, and quality of evidence using GRADE. LIMITATIONS: Small number of studies, all identifying having some risk of bias. CONCLUSION: Circuit training can have positive effects on PwMS in terms of increasing balance, gait, and reducing fatigue. Further research is needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021286834. CONTRIBUTION OF THE PAPER.
Walk Longer! Using Wearable Inertial Sensors to Uncover Which Gait Aspects Should Be Treated to Increase Walking Endurance in People with Multiple Sclerosis Ilaria Carpinella, Rita Bertoni, Denise Anastasi, Rebecca Cardini, Tiziana Lencioni, Maurizio Ferrarin, Davide Cattaneo, Elisa Gervasoni Sensors, 2024 Reduced walking endurance is common in people with multiple sclerosis (PwMS), leading to reduced social participation and increased fall risk. This highlights the importance of identifying which gait aspects should be mostly targeted by rehabilitation to maintain/increase walking endurance in this population. A total of 56 PwMS and 24 healthy subjects (HSs) executed the 6 min walk test (6 MWT), a clinical measure of walking endurance, wearing three inertial sensors (IMUs) on their shanks and lower back. Five IMU-based digital metrics descriptive of different gait domains, i.e., double support duration, trunk sway, gait regularity, symmetry, and local dynamic instability, were computed. All metrics demonstrated moderate–high ability to discriminate between HSs and PwMS (AUC: 0.79–0.91) and were able to detect differences between PwMS at minimal (PwMSmFR) and moderate–high fall risk (PwMSFR). Compared to PwMSmFR, PwMSFR walked with a prolonged double support phase (+100%), larger trunk sway (+23%), lower stride regularity (−32%) and gait symmetry (−18%), and higher local dynamic instability (+24%). Normative cut-off values were provided for all metrics to help clinicians in detecting abnormal scores at an individual level. The five metrics, entered into a multiple linear regression model with 6 MWT distance as the dependent variable, showed that gait regularity and the three metrics most related to dynamic balance (i.e., double support duration, trunk sway, and local dynamic instability) were significant independent contributors to 6 MWT distance, while gait symmetry was not. While double support duration and local dynamic instability were independently associated with walking endurance in both PwMSmFR and PwMSFR, gait regularity and trunk sway significantly contributed to 6 MWT distance only in PwMSmFR and PwMSFR, respectively. Taken together, the present results allowed us to provide hints for tailored rehabilitation exercises aimed at specifically improving walking endurance in PwMS.
Machine learning based estimation of dynamic balance and gait adaptability in persons with neurological diseases using inertial sensors Piergiuseppe Liuzzi, Ilaria Carpinella, Denise Anastasi, Elisa Gervasoni, Tiziana Lencioni, Rita Bertoni, Maria Chiara Carrozza, Davide Cattaneo, Maurizio Ferrarin, Andrea Mannini Scientific Reports, 2023 Poor dynamic balance and impaired gait adaptation to different contexts are hallmarks of people with neurological disorders (PwND), leading to difficulties in daily life and increased fall risk. Frequent assessment of dynamic balance and gait adaptability is therefore essential for monitoring the evolution of these impairments and/or the long-term effects of rehabilitation. The modified dynamic gait index (mDGI) is a validated clinical test specifically devoted to evaluating gait facets in clinical settings under a physiotherapist’s supervision. The need of a clinical environment, consequently, limits the number of assessments. Wearable sensors are increasingly used to measure balance and locomotion in real-world contexts and may permit an increase in monitoring frequency. This study aims to provide a preliminary test of this opportunity by using nested cross-validated machine learning regressors to predict the mDGI scores of 95 PwND via inertial signals collected from short steady-state walking bouts derived from the 6-minute walk test. Four different models were compared, one for each pathology (multiple sclerosis, Parkinson’s disease, and stroke) and one for the pooled multipathological cohort. Model explanations were computed on the best-performing solution; the model trained on the multipathological cohort yielded a median (interquartile range) absolute test error of 3.58 (5.38) points. In total, 76% of the predictions were within the mDGI’s minimal detectable change of 5 points. These results confirm that steady-state walking measurements provide information about dynamic balance and gait adaptability and can help clinicians identify important features to improve upon during rehabilitation. Future developments will include training of the method using short steady-state walking bouts in real-world settings, analysing the feasibility of this solution to intensify performance monitoring, providing prompt detection of worsening/improvements, and complementing clinical assessments.
Correlation between patient-reported manual ability and three objective measures of upper limb function in people with multiple sclerosis Claudio Solaro, Rachele Di Giovanni, Erica Grange, Giampaolo Brichetto, Margit Mueller, Andrea Tacchino, Rita Bertoni, Francesco Patti, Angelo Pappalardo, Luca Prosperini, Letizia Castelli, Rosalba Rosato, Davide Cattaneo, Davide Marengo European Journal of Neurology, 2023 Background and purposeUpper limb (UL) function is often affected in people with multiple sclerosis (PwMS) and is typically assessed through objective measures, including the Nine Hole Peg Test (9‐HPT), Box and Block Test (BBT), and Hand Grip Strength (HGS). It is important to include the subjective perspective of PwMS in the assessment. This study aims to evaluate associations between Manual Ability Measure‐36 (MAM‐36) and 9‐HPT, BBT, and HGS in MS.MethodsThe cross‐sectional study included five Italian centers. Inclusion criteria were age ≥ 18 years, MS diagnosis, and stable disease course. Exclusion criteria were bilateral UL paralysis, and concomitant orthopedic or neurological diseases.ResultsA total of 199 PwMS were included: 128 female, mean age = 50.7 ± 13.0 years, 119 relapsing–remitting MS (RRMS), 31 primary and 49 secondary progressive MS, mean disease duration = 14.0 ± 10.4, years, mean Expanded Disability Status Scale (EDSS) = 4.6 ± 2.0.The MAM‐36 showed small correlations with 9‐HPT, BBT, and HGS. Correlations between MAM‐36 and 9‐HPT and BBT were highest among subjects with EDSS ≥ 6 and progressive MS. MAM‐36 and HGS showed the highest correlations in subjects with EDSS ≤ 5 and RRMS. Combining 9‐HPT and HGS provided the strongest predictive power over the MAM‐36.ConclusionsCorrelations between objective measures and MAM‐36 were small to moderate, meaning that objective measures do not match subjects' perception of UL function. The combination of 9‐HPT and HGS measures can help improve the assessment of UL function in activities of daily living.
