Multiplexing Biosensor for the Detection of Extracellular Vesicles as Biomarkers of Tissue Damage and Recovery after Ischemic Stroke.

The inflammatory, reparative and regenerative mechanisms activated in ischemic stroke patients immediately after the event cooperate in the response to injury, in the restoration of functions and in brain remodeling even weeks after the event and can be sustained by the rehabilitation treatment. Nonetheless, patients' response to treatments is difficult to predict because of the lack of specific measurable markers of recovery, which could be complementary to clinical scales in the evaluation of patients. Considering that Extracellular Vesicles (EVs) are carriers of multiple molecules involved in the response to stroke injury, in the present study, we have identified a panel of EV-associated molecules that (i) confirm the crucial involvement of EVs in the processes that follow ischemic stroke, (ii) could possibly profile ischemic stroke patients at the beginning of the rehabilitation program, (iii) could be used in predicting patients' response to treatment. By means of a multiplexing Surface Plasmon Resonance imaging biosensor, subacute ischemic stroke patients were proven to have increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) and translocator protein (TSPO) on the surface of small EVs in blood. Besides, microglia EVs and endothelial EVs were shown to be significantly involved in the intercellular communications that occur more than 10 days after ischemic stroke, thus being potential tools for the profiling of patients in the subacute phase after ischemic stroke and in the prediction of their recovery.

Upper Limb Robotic Rehabilitation After Stroke: A Multicenter, Randomized Clinical Trial.

BACKGROUND AND PURPOSE: After stroke, only 12% of survivors obtain complete upper limb (UL) functional recovery, while in 30% to 60% UL deficits persist. Despite the complexity of the UL, prior robot-mediated therapy research has used only one robot in comparisons to conventional therapy. We evaluated the efficacy of robotic UL treatment using a set of 4 devices, compared with conventional therapy. METHODS: In a multicenter, randomized controlled trial, 247 subjects with subacute stroke were assigned either to robotic (using a set of 4 devices) or to conventional treatment, each consisting of 30 sessions. Subjects were evaluated before and after treatment, with follow-up assessment after 3 months. The primary outcome measure was change from baseline in the Fugl-Meyer Assessment (FMA) score. Secondary outcome measures were selected to assess motor function, activities, and participation. RESULTS: One hundred ninety subjects completed the posttreatment assessment, with a subset (n = 122) returning for follow-up evaluation. Mean FMA score improvement in the robotic group was 8.50 (confidence interval: 6.82 to 10.17), versus 8.57 (confidence interval: 6.97 to 10.18) in the conventional group, with no significant between-groups difference (adjusted mean difference -0.08, P = 0.948). Both groups also had similar change in secondary measures, except for the Motricity Index, with better results for the robotic group (adjusted mean difference 4.42, P = 0.037). At follow-up, subjects continued to improve with no between-groups differences. DISCUSSION AND CONCLUSIONS: Robotic treatment using a set of 4 devices significantly improved UL motor function, activities, and participation in subjects with subacute stroke to the same extent as a similar amount of conventional therapy. Video Abstract is available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A291).

Sensorimotor Perceptive Rehabilitation Integrated (SPRInt) program: exercises with augmented movement feedback associated to botulinum neurotoxin in idiopathic cervical dystonia-an observational study.

BACKGROUND: Idiopathic cervical dystonia (ICD) is a focal dystonia affecting neck muscles. Botulinum neurotoxin (BoNT) is the first-line treatment of ICD and different physical therapies (including exercise) are often proposed as adjunct treatments. However, the actual effectiveness of exercise in ICD is unclear. The aim of the current work is to assess the potential effectiveness of the Sensorimotor Perceptive Rehabilitation Integrated (SPRInt) exercise program as adjunct therapy for ICD. METHODS: Fifteen ICD patients received BoNT injections in the neck muscles and, 12 weeks later, received BoNT a second time and SPRInt started. SPRInt consists in 18 exercise sessions in which augmented feedback of movement (including visual and acoustic feedback) is extensively used. Dystonia burden was measured by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patients were evaluated immediately before, 6 and 12 weeks after each BoNT injection. RESULTS: Six weeks after the first BoNT injection (i.e., at BoNT peak effect), TWSTRS total score was better than baseline and remained improved at 12 weeks. TWSTRS disability domain slightly improved 6 weeks after the first BoNT injection, but after 6 more weeks returned to its baseline level. Disability improved more at SPRInt end (i.e., 6 weeks after the second BoNT injection), being even lower than after toxin alone. With a single-subject analysis, 4/10 patients who did not improve disability after BoNT improved after SPRInt plus BoNT. CONCLUSIONS: SPRInt plus BoNT can be more effective than BoNT alone in improving cervical dystonia patients' difficulties in the activities of daily living. TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT03247868 (https://register.clinicaltrials.gov).

Reliability, validity and discriminant ability of a robotic device for finger training in patients with subacute stroke.

BACKGROUND: The majority of stroke survivors experiences significant hand impairments, as weakness and spasticity, with a severe impact on the activity of daily living. To objectively evaluate hand deficits, quantitative measures are needed. The aim of this study is to assess the reliability, the validity and the discriminant ability of the instrumental measures provided by a robotic device for hand rehabilitation, in a sample of patients with subacute stroke. MATERIAL AND METHODS: In this study, 120 patients with stroke and 40 controls were enrolled. Clinical evaluation included finger flexion and extension strength (using the Medical Research Council, MRC), finger spasticity (using the Modified Ashworth Scale, MAS) and motor control and dexterity during ADL performance (by means of the Frenchay Arm Test, FAT). Robotic evaluations included finger flexion and extension strength, muscle tone at rest, and instrumented MAS and Modified Tardieu Scale. Subjects were evaluated twice, one day apart, to assess the test-retest reliability of the robotic measures, using the Intraclass Correlation Coefficient (ICC). To estimate the response stability, the standard errors of measurement and the minimum detectable change (MDC) were also calculated. Validity was assessed by analyzing the correlations between the robotic metrics and the clinical scales, using the Spearman's Correlation Coefficient (r). Finally, we investigated the ability of the robotic measures to distinguish between patients with stroke and healthy subjects, by means of Mann-Whitney U tests. RESULTS: All the investigated measures were able to discriminate patients with stroke from healthy subjects (p < 0.001). Test-retest reliability was found to be excellent for finger strength (in both flexion and extension) and muscle tone, with ICCs higher than 0.9. MDCs were equal to 10.6 N for finger flexion, 3.4 N for finger extension, and 14.3 N for muscle tone. Conversely, test-retest reliability of the spasticity measures was poor. Finally, finger strength (in both flexion and extension) was correlated with the clinical scales (r of about 0.7 with MRC, and about 0.5 with FAT). DISCUSSION: Finger strength (in both flexion and extension) and muscle tone, as provided by a robotic device for hand rehabilitation, are reliable and sensitive measures. Moreover, finger strength is strongly correlated with clinical scales. Changes higher than the obtained MDC in these robotic measures could be considered as clinically relevant and used to assess the effect of a rehabilitation treatment in patients with subacute stroke.

Effect of Impairment-Oriented and Function-Oriented Exercises on Mouth Function in Subjects with Systemic Sclerosis.

PURPOSE: The aim of this study was to develop an exercise protocol to improve maximal mouth opening (MMO), tongue protrusion (Tprot), tongue strength (Tstren), and lip strength (Lstren), and to assess its effects on subjects with scleroderma. METHODS: We performed four replicated single-system studies in a consecutive sample of subjects with scleroderma. An instrumented assessment measured MMO, Tprot, Tstren, and Lstren. Each day, subjects were assessed and performed orofacial exercises conducted by speech therapists. Treatments were first aimed at improving mouth physical characteristics by impairment-oriented exercises and then to improve skills with function-oriented exercises. RESULTS: The mean phase differences between assessment and treatment phases across subjects were from 0.88 to 9.56 mm in MMO, from 2.03 to 12.3 mm in Tprot, from -0.12 to 5.35 N in Tstren, and from -0.84 to 5.19 N in Lstren. After treatment, 3 subjects crossed the 5th percentile discriminating normal from abnormal performances for both Tstren and Tprot, while this occurred in 2 subjects for MMO and Lstren. CONCLUSIONS: The results of this study suggest that rehabilitation appears to be useful in reducing tongue and lip impairments and in improving oral functions in subjects with scleroderma.

Prediction of Falls in Subjects Suffering From Parkinson Disease, Multiple Sclerosis, and Stroke.

OBJECTIVE: To compare the risk of falls and fall predictors in patients with Parkinson disease (PD), multiple sclerosis (MS), and stroke using the same study design. DESIGN: Multicenter prospective cohort study. SETTING: Institutions for physical therapy and rehabilitation. PARTICIPANTS: Patients (N=299) with PD (n=94), MS (n=111), and stroke (n=94) seen for rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional scales were applied to investigate balance, disability, daily performance, self-confidence with balance, and social integration. Patients were followed for 6 months. Telephone interviews were organized at 2, 4, and 6 months to record falls and fall-related injuries. Incidence ratios, Kaplan-Meier survival curves, and Cox proportional hazards models were used. RESULTS: Of the 299 patients enrolled, 259 had complete follow-up. One hundred and twenty-two patients (47.1%) fell at least once; 82 (31.7%) were recurrent fallers and 44 (17.0%) suffered injuries; and 16%, 32%, and 40% fell at 2, 4, and 6 months. Risk of falls was associated with disease type (PD, MS, and stroke in decreasing order) and confidence with balance (Activities-specific Balance Confidence [ABC] scale). Recurrent fallers were 7%, 15%, and 24% at 2, 4, and 6 months. The risk of recurrent falls was associated with disease type, high educational level, and ABC score. Injured fallers were 3%, 8%, and 12% at 2, 4, and 6 months. The only predictor of falls with injuries was disease type (PD). CONCLUSIONS: PD, MS, and stroke carry a high risk of falls. Other predictors include perceived balance confidence and high educational level.

Minimal Clinically Important Difference of Berg Balance Scale in People With Multiple Sclerosis.

OBJECTIVE: To identify the minimal clinically important difference (MCID) to define clinically meaningful patient's improvement on the Berg Balance Scale (BBS) in people with multiple sclerosis (PwMS) in response to rehabilitation. DESIGN: Cohort study. SETTING: Neurorehabilitation institute. PARTICIPANTS: PwMS (N=110). INTERVENTIONS: This study comprised inpatients and outpatients who participated in research on balance and gait rehabilitation. All received 20 rehabilitation sessions with different intensities. Inpatients received daily treatments over a period of 4 weeks, while outpatients received 2 to 3 treatments per week for 10 weeks. MAIN OUTCOME MEASURES: An anchor-based approach using clinical global impression of improvement in balance (Activities-specific Balance Confidence [ABC] Scale) was used to determine the MCID of the BBS. The MCID was defined as the minimum change in the BBS total score (postintervention - preintervention) that was needed to perceive at least a 10% improvement on the ABC Scale. Receiver operating characteristic curves were used to define the cutoff of the optimal MCID of the BBS discriminating between improved and not improved subjects. RESULTS: The MCID for change on the BBS was 3 points for the whole sample, 3 points for the inpatients, and 2 points for the outpatients. The area under the curve was .65 for the whole sample, .64 for inpatients, and .68 for outpatients. CONCLUSIONS: The MCID for improvement in balance as measured by the BBS was 3 points, meaning that PwMS are likely to perceive that as a reproducible and clinically important change in their balance performance.

Wearable Sensor-Based Biofeedback Training for Balance and Gait in Parkinson Disease: A Pilot Randomized Controlled Trial.

OBJECTIVES: To analyze the feasibility and efficacy of a novel system (Gamepad [GAMing Experience in PArkinson's Disease]) for biofeedback rehabilitation of balance and gait in Parkinson disease (PD). DESIGN: Randomized controlled trial. SETTING: Clinical rehabilitation gym. PARTICIPANTS: Subjects with PD (N=42) were randomized into experimental and physiotherapy without biofeedback groups. INTERVENTIONS: Both groups underwent 20 sessions of training for balance and gait. The experimental group performed tailored functional tasks using Gamepad. The system, based on wearable inertial sensors, provided users with real-time visual and acoustic feedback about their movement during the exercises. The physiotherapy group underwent individually structured physiotherapy without feedback. MAIN OUTCOME MEASURES: Assessments were performed by a blinded examiner preintervention, postintervention, and at 1-month follow-up. Primary outcomes were the Berg Balance Scale (BBS) and 10-m walk test (10MWT). Secondary outcomes included instrumental stabilometric indexes and the Tele-healthcare Satisfaction Questionnaire. RESULTS: Gamepad was well accepted by participants. Statistically significant between-group differences in BBS scores suggested better balance performances of the experimental group compared with the physiotherapy without biofeedback group both posttraining (experimental group-physiotherapy without biofeedback group: mean, 2.3±3.4 points; P=.047) and at follow-up (experimental group-physiotherapy without biofeedback group: mean, 2.7±3.3 points; P=.018). Posttraining stabilometric indexes showed that mediolateral body sway during upright stance was significantly reduced in the experimental group compared with the physiotherapy without biofeedback group (experimental group-physiotherapy without biofeedback group: -1.6±1.5mm; P=.003). No significant between-group differences were found in the other outcomes. CONCLUSIONS: Gamepad-based training was feasible and superior to physiotherapy without feedback in improving BBS performance and retaining it for 1 month. After training, 10MWT data were comparable between groups. Further development of the system is warranted to allow the autonomous use of Gamepad outside clinical settings, to enhance gait improvements, and to increase transfer of training effects to real-life contexts.

Instrumented Assessment of Oral Motor Function in Healthy Subjects and People with Systemic Sclerosis.

The aim of the present study was to provide quantitative data of oral function in healthy subjects (HSs), validity of measurements and estimation of measurement bias, as well as quantify oral impairment in persons with scleroderma (SSc). 151 HSs and 12 subjects with SSc were recruited and assessed using instrumented tools, measuring maximal mouth opening; lip strength; and tongue strength, protrusion, retraction, and endurance. Twenty HSs were also retested 3-5 weeks later in order to assess the test-retest reliability of the measurements. Intraclass correlation coefficients proved to be satisfactory (>0.8) for both inter-rater and test-retest reliabilities of all measurements except for tongue retraction. In the HS group, maximal mouth opening and tongue and lips strength values were larger (P < 0.05) for males than females, while no significant differences were found for other variables. Older subjects had statistically significantly lower tongue retraction values and tongue endurance values than younger subjects. The SSc group showed a statistically significant decrease (P < 0.05) in almost all the measurements. Assessment procedures proved to be valid and reliable. Gender and height were predictors of mouth opening, lip and tongue strength, while age correlates with tongue retraction and endurance. Measurements highlighted the strong impact of SSc on oral functions and in particular on tongue protrusion, tongue strength, and endurance.

Relationship between quality of life and dysarthria in patients with multiple sclerosis.

OBJECTIVE: To evaluate dysarthria and dysarthria-related quality of life (QOL) and analyze its relations with duration of disease, severity, and general QOL in patients with multiple sclerosis (MS). DESIGN: Cross-sectional observational study. SETTING: Rehabilitation center. PARTICIPANTS: Consecutive patients with MS (N=163) were recruited (mean age, 52 ± 10.4 y; mean MS duration, 19 ± 10.4 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Presence of dysarthria; dysarthria characteristics; MS severity and duration; and dysarthria-related and generic QOL were evaluated by means of the therapy outcome measure scale; Robertson profile; Expanded Disability Status Scale (EDSS), years of disease; QOL of the dysarthric speaker questionnaire; and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), respectively. RESULTS: The mean EDSS score was 6.5 ± 1.3. Dysarthria affected 57 (35%) of the 163 patients. Dysarthria severity was mild in most of the 57 patients with dysarthria. Median Robertson profile scores were slightly but significantly higher in the nondysarthric group compared with the dysarthric group (P=.001). The QOL for the dysarthric speaker questionnaire was significantly more compromised in patients with dysarthria (P=.001). No difference on the SF-36 scores between patients with and without dysarthria was found, with the exception of the physical activity and physical pain subscales. The QOL for the dysarthric speaker questionnaire showed no correlation with MS duration and a weak correlation with EDSS score (r=.25). Correlations between the SF-36 and QOL for the dysarthric speaker scores were few and weak, with the exception of the role limitations because of emotions (r=-.428) and mental health subscales (r=-.383). CONCLUSIONS: Dysarthria-related QOL is compromised in patients with MS and dysarthria and might be used as a supplementary measure in clinical practice and research for patients who have MS.

Mobility and balance rehabilitation in multiple sclerosis: A systematic review and dose-response meta-analysis.

OBJECTIVE: To assess the benefits of neurological rehabilitation and the dose-response relationship for the treatment of mobility and balance in multiple sclerosis. METHODS: We included studies investigating the effects of neurological rehabilitation on mobility and balance with the following eligibility criteria for inclusion: Population, People with Multiple Sclerosis (PwMS); Intervention, method of rehabilitation interventions; Comparison, experimental (specific balance intervention) vs control (no intervention/no specific balance intervention); Outcome, balance clinical scales; Study Design, randomised controlled trials. We conducted a random effects dose-response meta-analysis to assess linear trend estimations and a one stage linear mixed effects meta-regression for estimating dose-response curves. RESULTS: We retrieved 196 studies from a list of 5020 for full text review and 71 studies (n subjects=3306) were included. One study was a cross-over and 70 studies were randomized controlled trials and the mean sample size per study was 46.5 ± 28.6 (mean±SD) with a mean age of 48.3 ± 7.8years, disease duration of 11.6 ± 6.1years, and EDSS of 4.4 ± 1.4points. Twenty-nine studies (40.8%) had the balance outcome as the primary outcome, while 42 studies (59.1%) had balance as secondary outcome or did not specify primary and secondary outcomes. Thirty-three trials (46.5%) had no active intervention as comparator and 38 trials (53.5%) had an active control group. Individual level data from 20 studies (n subjects=1016) were analyzed showing a medium pooled effect size for balance interventions (SMD=0.41; 95% CIs 0.22 to 0.59). Moreover, we analyzed 14 studies (n subjects=696) having balance as primary outcome and BBS as primary endpoint yielding a mean difference of 3.58 points (95% CIs 1.79 to 5.38, p<0.0001). Finally, we performed meta regression of the 20 studies showing an association between better outcome, log of intensity defined as minutes per session (ß=1.26; SEß=0.51; p = 0.02) and task-oriented intervention (ß=0.38; SEß=0.17; p = 0.05). CONCLUSION: Our analyses provide level 1 evidence on the effect of balance intervention to improve mobility. Furthermore, according to principles of neurological rehabilitation, high intensity and task-specific interventions are associated with better treatment outcomes.

Validity of 2 Fall Prevention Strategy Scales for People With Stroke, Parkinson's Disease, and Multiple Sclerosis.

BACKGROUND AND PURPOSE: Falls are a common and persistent concern among people with neurological disorders (PwND), as they frequently result in mobility deficits and may lead to loss of functional independence. This study investigated the ceiling and floor effects, internal consistency, and convergent validity of 2 patient-reported fall prevention strategy scales in PwND. METHODS: This is a prospective cohort study. Two-hundred and ninety-nine PwND (111 people with multiple sclerosis, 94 people with Parkinson's disease, and 94 people with stroke) were seen for rehabilitation and assessed. The number of retrospective and prospective falls, use of walking assistive devices, scores on the Fall Prevention Strategy Survey (FPSS), Falls Behavioural Scale (FaB), and balance and mobility scales (Berg Balance Scale, Dynamic Gait Index, Timed Up and Go, 10-m walking test, and Activities-specific Balance Confidence) were analyzed. RESULTS: Total score distributions showed negligible ceiling and floor effects for both the FPSS (ceiling: 0.3%, floor: 0.3%) and the FaB (ceiling: 0%, floor: 0%). The Cronbach α (CI) was of 0.87 (0.85-0.89) for the FPSS and 0.86 (0.84-0.88) for the FaB. In terms of convergent validity, the FPSS and FaB were moderately correlated (Spearman correlation coefficient = 0.65). Moreover, the correlations between the FPSS and FaB and balance and mobility scales ranged from 0.25 to 0.49 ( P < .01). Both scales are slightly better able to distinguish between retrospective fallers/nonfallers [area under the curve, AUC (95% CI): FPSS: 0.61 (0.5-0.7); FaB: 0.60 (0.5-0.6)] compared with prospective fallers/nonfallers [AUC (95% CI): FPSS: 0.56 (0.4-0.6); FaB: 0.57 (0.4-0.6)]. Both scales accurately identified individuals who typically required the use of a walking assistive device for daily ambulation [AUC (95% CI): FPSS: 0.74 (0.7-0.8); FaB: 0.69 (0.6-0.7)]. Multiple regression analysis showed that previous falls, use of an assistive device, and balance confidence significantly predicted participants' prevention strategies (FPSS: R2 = 0.31, F(8,159) = 10.5, P < .01; FaB: R2 = 0.31, F(8,164) = 10.89, P < .01). CONCLUSION: The FPSS and the FaB appear to be valid tools to assess fall prevention strategies in people with neurological disorders. Both scales provide unique and added value in providing information on individual behavior for fall prevention.

Functional profiles derived from the ICF Generic set and the responsiveness and validity of the Generic-6 set's Functioning score among persons after stroke.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) parsimonious Generic set can provide identification of functional profiles and recovery after rehabilitation in persons post stroke. AIM: To explore concurrent validity of the ICF Generic-6_Functioning score with the Barthel Index (BI) and responsiveness after rehabilitation in persons post stroke. Further, the feasibility of applying the ICF Brief Stroke Core set in routine rehabilitation recovery was evaluated. DESIGN: Prospective study. SETTING: Inpatient rehabilitation setting. POPULATION: Persons post stroke. METHODS: The study included 71 persons post stroke (mean age 66.8 [standard deviation 14.5], mean onset 199.3 [565.3] days, BI score improvement: 17/100), N.=44 acute stroke (<3 months, stroke subacute [SA]_group) and N.=27 chronic stroke (>3 months, Stroke chronic [SC]_group). The Brief Stroke core set, including the Generic set, was used for classification at admission and at discharge using the five grade qualifiers. The median value of the groups' qualifiers on the Generic set (excluding item 850) was used to form a Functioning score (Generic-6 FS). Responsiveness was assessed with effect sizes (ES) and confidence intervals (CI). The concurrent validity of the Generic-6 FS was explored with the BI as a gold standard using Spearman's correlation coefficient. P was set at 0.05. RESULTS: The Generic-6 FS proved responsive with ES being moderate for the Generic-6 FS and the BI for the whole group (0.48, CI 0.14-0.82 and 0.67, CI -1.02--0.32 respectively). ES of the Generic-6 FS was significant only for the SA_group (0.62, CI 0.27-0.96. Correlation between the Generic-6 FS and the BI at baseline and discharge were respectively r=-0.59 and r=0.60, while correlation between change values was lower (r=0.44). The Generic-6 FS did not distinguish between the SA_group and the SC_group. Classification with the ICF brief stroke core set was feasible with 89% of the persons being classified both at admission and discharge. CONCLUSIONS: ICF classification of persons post stroke during rehabilitation recovery was feasible. The Generic-6 FS detected changes in functioning and health in persons recovered for rehabilitation after stroke and distinguished between different recovery rates of persons in the acute and chronic phase after stroke.

Cross-Validation of Machine Learning Models for the Functional Outcome Prediction after Post-Stroke Robot-Assisted Rehabilitation.

The state of the art is still lacking an extensive analysis of which clinical characteristics are leading to better outcomes after robot-assisted rehabilitation on post-stroke patients. Prognostic machine learning-based models could promote the identification of predictive factors and be exploited as Clinical Decision Support Systems (CDSS). For this reason, the aim of this work was to set the first steps toward the development of a CDSS, by the development of machine learning models for the functional outcome prediction of post-stroke patients after upper-limb robotic rehabilitation. Four different regression algorithms were trained and cross-validated using a nested 5×10-fold cross-validation. The performances of each model on the test set were provided through the Median Average Error (MAE) and interquartile range. Additionally, interpretability analyses were performed, to evaluate the contribution of the features to the prediction. The results on the two best performing models showed a MAE of 13.6 [13.4] and 13.3 [14.8] on the Modified Barthel Index score (MBI). The interpretability analyses highlighted the Fugl-Meyer Assessment, MBI, and age as the most relevant features for the prediction of the outcome. This work showed promising results in terms of outcome prognosis after robot-assisted treatment. Further research should be planned for the development, validation and translation into clinical practice of CDSS in rehabilitation. Clinical relevance- This work establishes the premises for the development of data-driven tools able to support the clinical decision for the selection and optimisation of the robotic rehabilitation treatment.

Identification of modified dynamic gait index cutoff scores for assessing fall risk in people with Parkinson disease, stroke and multiple sclerosis.

BACKGROUND: Balance and gait impairments increase fall rate and injury in people with neurological disorders(PwND). The modified Dynamic Gait Index(mDGI) is a scale assessing dynamic balance during walking, however its ability in identifying Fallers and Recurrent Fallers has not been studied. RESEARCH QUESTION: To evaluate mDGI's ability in identifying retrospective Fallers and Recurrent Fallers establishing cut-off scores for its use in clinical practice. METHOD: In this cross-sectional study, the number of retrospective falls and mDGI scores were collected. PwND were categorised as Non-Fallers or Fallers (falls≥1) and as Recurrent Fallers(falls≥2) or Non-Recurrent/Non-Fallers(falls<2) according to their number of retrospective falls over two months. Two generalised linear logistic models were developed using a machine learning method to detect Fallers (Model 1) and Recurrent Fallers (Model 2) based on mDGI scores. ROC curves were used to identify mDGI cut-off scores to distinguish between different fall categories. RESULTS: 58 PwND (mean ± standard deviation age: 63.4 ± 12 years) including 28 people with Multiple Sclerosis, 15 people with Parkinson's disease and 15 people with Stroke were analysed. The mDGI score(median (IQR)) for Non-Fallers, Fallers, Recurrent Fallers and Non-Recurrent/Non-Fallers was respectively 50(22), 37(22), 26.5(20.25) and 46.5(20.5)points. The cut-off to identify Fallers from Non-Fallers was 49 points(sensitivity:100 %, specificity:50 %, post-test probability with mDGI ≤ cut-off: 53.2 %, post-test probability with mDGI > cut-off: 0%, AUC:0.68), while 29 points(sensitivity:60 %, specificity:79 %, post-test probability with mDGI ≤ cut-off:52.1 %, post-test probability with mDGI > cut-off:16.1 %, AUC:0.70) was the best cut-off to identify Recurrent Fallers. SIGNIFICANCE: People with mDGI score>49 points have low or minimal fall risk, while people with mDGI score≤49 points should be further investigated with other scales before starting a balance-focused rehabilitation intervention. People scoring ≤29 points on the mDGI scale may need a fall prevention intervention, regardless of the results of other balance clinical measures.

Design and implementation of a Stroke Rehabilitation Registry for the systematic assessment of processes and outcomes and the development of data-driven prediction models: The STRATEGY study protocol.

Background: Stroke represents the second preventable cause of death after cardiovascular disease and the third global cause of disability. In countries where national registries of the clinical quality of stroke care have been established, the publication and sharing of the collected data have led to an improvement in the quality of care and survival of patients. However, information on rehabilitation processes and outcomes is often lacking, and predictors of functional outcomes remain poorly explored. This paper describes a multicenter study protocol to implement a Stroke rehabilitation Registry, mainly based on a multidimensional assessment proposed by the Italian Society of Physical and Rehabilitation Medicine (PMIC2020), in a pilot Italian cohort of stroke survivors undergoing post-acute inpatient rehabilitation, to provide a systematic assessment of processes and outcomes and develop data-driven prediction models of functional outcomes. Methods: All patients with a diagnosis of ischemic or haemorrhagic stroke confirmed by clinical assessment, admitted to intensive rehabilitation units within 30 days from the acute event, aged 18+, and providing informed consent will be enrolled. Measures will be taken at admission (T0), at discharge (T1), and at follow-up, 3 months (T2) and 6 months (T3) after the stroke. Assessment variables include anamnestic data, clinical and nursing complexity information and measures of body structures and function, activity and participation (PMIC2020), rehabilitation interventions, adverse events and discharge data. The modified Barthel Index will be our primary outcome. In addition to classical biostatistical analysis, learning algorithms will be cross-validated to achieve data-driven prognosis prediction models. Conclusions: This study will test the feasibility of a stroke rehabilitation registry in the Italian health context and provide a systematic assessment of processes and outcomes for quality assessment and benchmarking. By the development of data-driven prediction models in stroke rehabilitation, this study will pave the way for the development of decision support tools for patient-oriented therapy planning and rehabilitation outcomes maximization. Clinical tial registration: The registration on ClinicalTrials.gov is ongoing and under review. The identification number will be provided when the review process will be completed.

Minimal clinically important difference of modified dynamic gait index in people with neurological disorders.

BACKGROUND: The minimal clinically important difference (MCID) of modified Dynamic Gait Index (mDGI) has not yet been determined for People with Neurological Disorders (PwND). RESEARCH QUESTION: To establish the MCID of the mDGI to determine clinically meaningful improvement in balance and gait in PwND. METHODS: In this longitudinal study from a randomised clinical trial, 55 participants both in and outpatients with neurological disorders, received fifteen 40-minute rehabilitation sessions. Inpatients received daily treatments over a period of three weeks while outpatients received three treatments/week over a period of five weeks. An anchor-based method using percentage rating of improvement in balance (Activities Balance Confidence scale, ABC) was used to determine the MCID of mDGI. The MCID was defined as the minimum change in mDGI total score (post - pre intervention) that was needed to perceive at least a 10 % improvement on the ABC scale. A Receiver Operating Characteristic curve was used to define the cut-off for the optimal MCID of the mDGI discriminating between improved and not improved participants. RESULTS: The MCID of the mDGI total score was 6 points and Area under the Curve was 0.64. For the mDGI time sub-scores the MCID was 2 points and Area under the Curve was 0.6. SIGNIFICANCE: The MCID of balance and gait improvement measured by mDGI was prudently establish at ≥7 points, meaning that this is the minimum improvement score PwND need to get to perceive a clinically relevant change in their balance and gait confidence. These reference values can be a tool incorporated into clinicians daily practice to interpret mDGI change scores helping to determine whether the intervention is effective; to develop clinical tailored intervention goals and to establish meaningful perceived change in PwND.

Age is negatively associated with upper limb recovery after conventional but not robotic rehabilitation in patients with stroke: a secondary analysis of a randomized-controlled trial.

BACKGROUND: There is consistent evidence that robotic rehabilitation is at least as effective as conventional physiotherapy for upper extremity (UE) recovery after stroke, suggesting to focus research on which subgroups of patients may better respond to either intervention. In this study, we evaluated which baseline variables are associated with the response after the two approaches. METHODS: This is a secondary analysis of a randomized-controlled trial comparing robotic and conventional treatment for the UE. After the assigned intervention, changes of the Fugl-Meyer Assessment UE score by ≥ 5 points classified patients as responders to treatment. Variables associated with the response were identified in a univariate analysis. Then, variables independently associated with recovery were investigated, in the whole group, and the two groups separately. RESULTS: A sample of 190 patients was evaluated after the treatment; 121 were responders. Age, baseline impairment, and neglect were significantly associated with worse response to the treatment. Age was the only independently associated variable (OR 0.967, p = 0.023). Considering separately the two interventions, age remained negatively associated with recovery (OR 0.948, p = 0.013) in the conventional group, while none of the variables previously identified were significantly associated with the response to treatment in the robotic group. CONCLUSIONS: We found that, in our sample, age is significantly associated with the outcome after conventional but not robotic UE rehabilitation. Possible explanations may include an enhanced positive attitude of the older patients towards technological training and reduced age-associated fatigue provided by robotic-assisted exercise. The possibly higher challenge proposed by robotic training, unbiased by the negative stereotypes concerning very old patients' expectations and chances to recover, may also explain our findings. TRIAL REGISTRATION NUMBER: NCT02879279.