Traditional versus progressive robot-assisted gait training in people with multiple sclerosis and severe gait disability: study protocol for the PROGR-EX randomised controlled trial.

Gait disorders are the most frequent symptoms associated to multiple sclerosis (MS). Robot-assisted gait training (RAGT) in people with MS (PwMS) has been proposed as a possible effective treatment option for severe motor disability without significant superiority when compared to intensive overground gait training (OGT). Furthermore, RAGT at high intensity may enhance fatigue and spasticity. This study aims to evaluate the effects of a low-intensity RAGT at progressively increasing intensity compared to conventional RAGT and OGT in PwMS and moderate to severe walking impairment. 24 PwMS will be recruited and assigned to one of the three treatment groups: low-intensity RAGT at progressively increasing intensity, conventional RAGT and OGT. All participants will receive 3-weekly treatment sessions of 3 hours each for 4 weeks. In the first 2 hours of treatment, all participants will receive a rehabilitation programme based on stretching exercises, muscle strengthening and educational interventions. During the last hour, subjects will undergo specific gait training according to the assignment group. Outcomes will be assessed before and after treatment and at 3-month follow-up. The primary outcome is walking speed. Secondary outcomes include mobility and balance, psychological measures, muscle oxygen consumption, electrical and haemodynamic brain activity, urinary biomarkers, usability, and acceptability of robotic devices for motor rehabilitation. The results of this study will provide a safe, affordable and non-operator-dependent, intervention for PwMS. Results in terms of functional, psychological, neurophysiological and biological outcomes will confirm our hypothesis. The study's trial registration number: NCT06381440.

The Effectiveness of Paired Associative Stimulation on Motor Recovery after Stroke: A Scoping Review.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.

A "test in-train out" program versus a "go home and walk" intervention for home-based exercise therapy in patients with peripheral artery disease: A randomized controlled trial.

OBJECTIVE: In this single-blinded randomized controlled trial, we compared the "Test in-Train Out" structured home-based exercise program (TiTo-SHB) with the traditional "go home and walk" exercise intervention in people with peripheral artery disease (PAD). METHODS: Peripheral artery disease patients at Leriche-Fontaine's stage II were randomized to receive TiTo-SHB or walking advice (C-WA). The TiTo-SHB group performed two daily 8-min sessions of pain-free interval walking at progressive low-to-moderate speed maintained with a metronome. The C-WA group was recommended to walk for 30 min at least three times per week and to endure claudication pain. Outcomes collected at baseline and at the end of the program (6 months) included: 6-min and pain-free walking distance (6MWD, PFWD), ankle-brachial index (ABI), 5-time sit-to-stand test (5STS), and health-related quality of life (HRQoL) by the VascuQoL-6 questionnaire. RESULTS: A total of 68 patients were randomized (males n = 50; aged 73 ± 9; TiTo-SHB n = 34). At the end of the program, patients in the TiTo-SHB group compared with the C-WA group had significantly improved 6MWD (Δ + 60 ± 32 m vs. Δ - 5 ± 37 m; p < 0.001) and PFWD (Δ + 140 ± 92 m vs. Δ - 7 ± 87 m; p < 0.001). A significant between-group difference in favor of the TiTo-SHB group was also recorded for all the secondary outcomes, including 5STS (Δ - 2.6 ± 1.8 s vs. Δ + 0.8 ± 2.6 s; p < 0.001), ABI of the more impaired limb (Δ + 0.10 ± 0.11 vs. Δ + 0.02 ± 0.08; p = 0.003), and VascuQoL-6 score (Δ +2 ± 2 vs. -1 ± 4; p < 0.001). CONCLUSION: In PAD patients with claudication, the pain-free in-home TiTo-SHB program was more effective in improving exercise capacity and HRQoL than the traditional walking advice recommendation.

Head-Mounted Displays for Upper Limb Stroke Rehabilitation: A Scoping Review.

Upper extremity (UE) paresis is one of the most frequent and disabling clinical consequences after stroke. Head-Mounted Displays (HMDs) are wearable virtual reality devices that seem effective in promoting the recovery of functional abilities by increasing adherence levels in this population. This scoping review is aimed at collecting available evidence on the use of HMD-based immersive virtual reality systems for UE rehabilitation treatment in stroke survivors. Four electronic bibliographic databases were consulted from inception until 18 January 2023. A total of 19 clinical trials in which HMDs were used as a clinical tool for increasing UE functioning, as a single intervention or in adjunct to other rehab treatments, were included; no restrictions were applied for UE paresis severity or stroke onset. The large majority of the clinical trials involved chronic stroke patients (15 out of 19), with a wide range of UE impairments. Overall, HMD use seemed to be well-tolerated and promising for increasing UE motor function in adult chronic stroke survivors, with benefits in subjects' arm use and independence. The possibility of executing highly realistic and task-oriented movements appears to be promising in enhancing gesture relevance, thus promoting new motor strategies in a "virtual ecological way". Across studies, we found a high heterogeneity in protocol design and a lack of reporting that prevents us drawing conclusions regarding potential subgroups of patients that could benefit more from HMD-based interventions or suggested treatment modalities.

Variations in Health-Related Quality of Life After Stroke: Insights From a Clinical Trial on Arm Rehabilitation With a Long-Term Follow-Up.

Despite rehabilitation, stroke patients continue to have impaired function and reduced health-related quality of life (HRQoL) even in a chronic stage. However, no clear information is available on long-term variations in HRQoL. In this study, we aimed to report the short- and long-term changes in HRQoL in a subacute stroke sample that was enrolled in a clinical trial on arm rehabilitation. Thirty-nine stroke survivors (62% male, mean age 68 years) were assessed using the Stroke Impact Scale Version 2.0 (SIS 2.0) pre and post rehabilitation and at 6 months and 6 years follow-up. Long-term changes in physical function were explored through clinically meaningful changes in the Stroke Impact Scale-16 (SIS-16). After rehabilitation (P < .001), an overall improvement was found in all SIS domains except the memory and thinking, emotions, and communication domains. The baseline SIS-16 score (P < .001), the presence of a sensory deficit, and rehabilitation setting (P < .05) were factors related to the SIS-16 domain scores at the end of rehabilitation and at 6 months follow-up. Patients showed the most deterioration in the mobility (P < .001), strength (P < .003), and hand function (P < .05) domains 6 years after stroke. Stroke severity, male gender, and age ⩾65 years are related with a long-term HRQoL reduction after stroke.

Poor Sleep Quality May Independently Predict Suicidal Risk in Covid-19 Survivors: A 2-Year Longitudinal Study.

Objective: Multiple symptoms of psychiatric, neurological, and physical illnesses may be part of Post-COVID conditions and may pose COVID-19 survivors a high suicidal risk. Accordingly, we aimed to study factors contributing to suicidal risk in Post COVID-19 patients. Method: Consecutive patients with post COVID-19 conditions were followed for 2 years at the University Hospital of Ferrara at baseline (T0), 6 (T1), 12 (T2), and 24 (T3) months. Demographics, and clinical data for all patients included: disease severity, hospital length of stay, comorbidity, clinical complications, sleep quality, cognitive complaints, anxiety and stress-related symptoms, depressive symptoms, and suicidal ideation. Results: The final sample included 81 patients with post COVID survivors. The mean age was 64 + 10,6 years, 35,8% were females, 65,4% had medical comorbidities, and 69,1% had WHO severe form of COVID forms. At T0 more than 90% of patients showed poor sleep quality, 59.3% reported moderate/severe depressive symptoms, and 51.% experienced anxiety, 25.9% experienced post-traumatic stress symptoms. At T0 suicidal ideation, interested 6.1% and at T3 it increased to 7.4%. In the regression analysis, suicidal ideation at baseline was best predicted by poor sleep quality (O.R. 1.71, p=0.044) and, after 2 years, suicidal ideation was best predicted by poor sleep quality experienced at baseline (OR 67.3, p=0.001). Conclusions: Poor sleep quality may play as an independent predictor of suicidal risk in post-COVID survivors. Evaluating and targeting sleep disturbances in COVID survivors is important to prevent the consequences of disrupted sleep in mental health.

A Multimodal Analysis to Explore Upper Limb Motor Recovery at 4 Weeks After Stroke: Insights From EEG and Kinematics Measures.

Background. Stroke is a leading cause of death and disability worldwide and there is a very short period of increased synaptic plasticity, fundamental in motor recovery. Thus, it is crucial to acquire data to guide the rehabilitation treatment. Promising results have been achieved with kinematics and neurophysiological data, but currently, few studies integrate these different modalities. Objectives. We explored the correlations between standardized clinical scales, kinematic data, and EEG measures 4 weeks after stroke. Methods. 26 patients were considered. Among them, 20 patients also performed the EEG study, beyond the kinematic analysis, at 4 weeks. Results. We found correlations between the Fugl-Meyer Assessment-Upper Extremity, movement duration, smoothness measures, and velocity peaks. Moreover, EEG measures showed a tendency for the healthy hemisphere to vicariate the affected one in patients characterized by better clinical conditions. Conclusions. These results suggest the relevance of kinematic (in particular movement duration and smoothness) and EEG biomarkers to evaluate post-stroke recovery. We emphasize the importance of integrating clinical data with kinematic and EEG analyses from the early stroke stages, in order to guide rehabilitation strategies to best leverage the short period of increased synaptic plasticity.

Effects of Exercise, Rehabilitation, and Nutritional Approaches on Body Composition and Bone Density in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

People with multiple sclerosis (pwMS) are affected by a wide range of disabilities, including a decrease in bone mineral density (BMD) and a worsening of body composition (BC), which negatively impact their quality of life quality. This study aims to analyze the effects of nonpharmacological interventions-in particular, physical activity, nutritional approaches, and rehabilitation-on BC and BMD in pwMS. This systematic review and meta-analysis was performed following the updated version of the PRISMA guidelines. In July 2022, five databases (MEDLINE, Embase, The Cochrane Library, Google Scholar, Web of Science) and gray literature were screened. Relevant articles published between 1 January 1990 and 1 September 2022 in any language were included. Outcomes of interest were anthropometric, BC measures, and BMD. The RoB 2.0 tool was used to assess the risk of bias. After duplicates elimination, 1120 records were screened, and 36 studies were included. A total of 25 articles were focused on physical activity and rehabilitation, 10 on nutrition, and 1 on multimodal intervention. One-third of the studies were judged to be at high risk of bias. The meta-analysis showed a high degree of heterogeneity due to the high variability in disease severity and intervention duration, intensity, frequency, and type. In general, no intervention showed consistent positive effects on BC. However, the most promising interventions seemed to be high-intensity training and ketogenic diets. Only a few studies considered BMD, and the results are inconsistent. Nevertheless, more studies are needed in order to confirm these results.

Quantitative Comparison of Hand Kinematics Measured with a Markerless Commercial Head-Mounted Display and a Marker-Based Motion Capture System in Stroke Survivors.

Upper-limb paresis is common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients' movements in ecological scenarios. These systems are, however, very expensive and not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. A total of 14 stroke patients executed ecologically relevant upper-limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest's and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1 (maximum distance: mean slope = 0.94 ± 0.1; peak velocity: mean slope = 1.06 ± 0.12). Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper-limb kinematic parameters in stroke patients.

Neurophysiological and Clinical Effects of Upper Limb Robot-Assisted Rehabilitation on Motor Recovery in Patients with Subacute Stroke: A Multicenter Randomized Controlled Trial Study Protocol.

BACKGROUND: The efficacy of upper limb (UL) robot-assisted therapy (RAT) on functional improvement after stroke remains unclear. However, recently published randomized controlled trials have supported its potential benefits in enhancing the activities of daily living, arm and hand function, and muscle strength. Task-specific and high-intensity exercises are key points in facilitating motor re-learning in neurorehabilitation since RAT can provide an assisted-as-needed approach. This study aims to investigate the clinical effects of an exoskeleton robotic system for UL rehabilitation compared with conventional therapy (CT) in people with subacute stroke. As a secondary aim, we seek to identify patients' characteristics, which can predict better recovery after UL-RAT and detects whether it could elicit greater brain stimulation. METHODS: A total of 84 subacute stroke patients will be recruited from 7 Italian rehabilitation centers over 3 years. The patients will be randomly allocated to either CT (control group, CG) or CT plus UL-RT through an Armeo®Power (Hocoma AG, CH, Volketswil, Switzerland) exoskeleton (experimental group, EG). A sample stratification based on distance since onset, DSO (DSO ≤ 30; DSO > 30), and Fugl-Meyer Assessment (FM)-UL (FM-UL ≤ 22; 22 < FM-UL ≤ 44) will be considered for the randomization. The outcomes will be recorded at baseline (T0), after 25 + 3 sessions of intervention (T1), and at 6 months post-stroke (T2). The motor functioning assessed by the FM-UL (0-66) will be considered the primary outcome. The clinical assessments will be set based on the International Classification of Function, Disability and Health (ICF). A patient satisfaction questionnaire will be evaluated in the EG at T1. A subgroup of patients will be evaluated at T0 and T1 via electroencephalography. Their brain electrical activity will be recorded during rest conditions with their eyes closed and open (5 min each). CONCLUSION: The results of this trial will provide an in-depth understanding of the efficacy of early UL-RAT through a whole arm exoskeleton and how it may relate to the neural plasticity process. The trial was registered at ClinicalTrial.gov with the registration identifier NCT04697368.

Non-invasive Brain Stimulation Techniques for the Improvement of Upper Limb Motor Function and Performance in Activities of Daily Living After Stroke: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the efficacy of non-invasive brain stimulation (NiBS) such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcutaneous vagus nerve stimulation (taVNS) in upper limb stroke rehabilitation. DATA SOURCES: PubMed, Web of Science, and Cochrane databases were searched from January 2010 to June 2022. DATA SELECTION: Randomized controlled trials (RCTs) assessing the effects of "tDCS", "rTMS", "TBS", or "taVNS" on upper limb motor function and performance in activities of daily livings (ADLs) after stroke. DATA EXTRACTION: Data were extracted by 2 independent reviewers. Risk of bias was evaluated with the Cochrane Risk of Bias tool. DATA SYNTHESIS: 87 RCTs with 3750 participants were included. Pairwise meta-analysis showed that all NiBS except continuous TBS (cTBS) and cathodal tDCS were significantly more efficacious than sham stimulation for motor function (standardized mean difference [SMD] range 0.42-1.20), whereas taVNS, anodal tDCS, and both low and high frequency rTMS were significantly more efficacious than sham stimulation for ADLs (SMD range 0.54-0.99). NMA showed that taVNS was more effective than cTBS (SMD:1.00; 95% CI (0.02-2.02)), cathodal tDCS (SMD:1.07; 95% CI (0.21-1.92)), and Physical rehabilitation alone (SMD:1.46; 95% CI (0.59-2.33)) for improving motor function. P-score found that taVNS is best ranked treatment in improving motor function (SMD: 1.20; 95% CI (0.46-1.95)) and ADLs (SMD:1.20; 95% CI (0.45-1.94)) after stroke. After taVNS, excitatory stimulation protocols (intermittent TBS, anodal tDCS, and HF-rTMS) are most effective in improving motor function and ADLs after acute/sub-acute (SMD range 0.53-1.63) and chronic stroke (SMD range 0.39-1.16). CONCLUSIONS: Evidence suggests that excitatory stimulation protocols are the most promising intervention in improving upper limb motor function and performance in ADLs. taVNS appeared to be a promising intervention for stroke patients, but further large RCTs are required to confirm its relative superiority.

Physiotherapy management of nociplastic pain: A Delphi study of Italian specialists.

BACKGROUND AND PURPOSE: Nociplastic pain due to central sensitization (CS) is common in people suffering from chronic pain, but no clinical practice guideline is available in rehabilitative settings for patients' management. The aim of this study is to achieve expert consensus on physiotherapy competencies in the management of people with nociplastic pain and suspected CS mechanisms. METHODS: A web-based Delphi process was employed. Experts in the rehabilitation field were recruited following pre-defined eligibility criteria. Following completion of three Delphi rounds, the final list of competencies was generated. RESULTS: In all, 23 participants were recruited. They all completed Round 1 (23/23, 100%), twenty Round 2 and Round 3 (20/23, 87%). Following Round 1, seven areas were identified by the panel as crucial for CS physiotherapy management; 19 competencies out of 40 reached the consensus between experts, and nine additional competencies were added to Round 2 following literary review. Round 2 identified the agreement for all the 29 competencies. During Round 3, all the experts confirmed the final list generated through the consensus process. DISCUSSION: An agreement between experts was found for the final list of competencies that a physiotherapist should implement every time it approaches people with suspected CS mechanisms. Further research is needed to support the clinical utility of our findings and their applicability in daily practice.

Lower All-Cause Mortality Risk in Females and Males with Peripheral Artery Disease following Pain-Free Home-Based Exercise: A 7-Year Observational Study.

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEXn = 138; FEXn = 62; MCOn = 149; FCOn = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331-0.885), FCO (45%, HR: 0.164 95% CI 0.088-0.305), and MCO (44%; HR: 0.157 95% CI 0.096-0.256). A significantly lower rate of hospitalization (p < 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women.

Clinical Application of Physical Therapy in Neurorehabilitation.

The knowledge from basic neuroscience studies on mechanisms of motor recovery and the development of theoretical models of learning and recovery has favoured the development and implementation of neurophysiologically sounded rehabilitative interventions [...].

Mobile Applications for Resting Tremor Assessment in Parkinson's Disease: A Systematic Review.

(1) Background: Resting tremor is a motor manifestation present in most Parkinson's disease (PD) patients. For its assessment, several scales have been created, but mobile applications could help in objectively assessing resting tremor in PD patients in person and/or remotely in a more ecological scenario. (2) Methods: a systematic review following the PRISMA recommendations was conducted in scientific databases (PubMed, Medline, Science Direct, Academic Search Premier, and Web of Science) and in the main mobile application markets (Google Play, iOS App Store, and Windows Store) to determine the applications available for the assessment of resting tremor in patients with PD using only the measurement components of the phone itself (accelerometers and gyroscopes). (3) Results: 14 articles that used mobile apps to assess resting tremor in PD were included, and 13 apps were identified in the mobile application markets for the same purpose. The risk of bias and of applicability concerns of the articles analyzed was low. Mobile applications found in the app markets met an average of 85.09% of the recommendations for the development of medical mobile applications. (4) Conclusions: the use of mobile applications for the evaluation of resting tremor in PD patients has great potential, but validation studies for this purpose are scarce.

TeleNEwCARe: An Italian case-control telegenetics study in patients with Hereditary NEuromuscular and CARdiac diseases.

Telemedicine provides healthcare services remotely and represents a fundamental resource for the management of rare and fragile patients. Tele-health implementation is a main objective of the European Reference Networks (ERNs) mission to accelerate diagnosis for rare diseases. TeleNewCARe is a pilot case-control project which evaluates the efficacy and satisfaction of telegenetics for neuromuscular and cardiac adult patients, compared to face-to-face genetic counselling. The virtual sessions were co-hosted by a medical geneticist and a neurologist/cardiologist. Specific questionnaires (Clinical Genetics Satisfaction Questionnaire (CGS), Telemedicine Satisfaction Questionnaire (TSQ) and a Satisfaction Questionnaire for medical geneticists) were used to assess the effectiveness and fulfilment of telecounselling, both for patients and health care providers. Satisfaction expressed for telegenetics did not significantly differ from face-to-face counselling. The virtually enrolled patients declared they had the possibility to relate confidentially with the specialists, to share information and to be informed in an exhaustive way about their disease. Almost all patients declared themselves willing to reuse the telecounselling in the future. The multidisciplinary care was perceived as a significant added value. No overt technical problems were reported although the need for digital skills and tools can limit patients' compliance. Our experience supports telegenetics as a valid alternative to traditional genetic counselling in cardiac and neuromuscular patients. This innovative approach facilitates multidisciplinary care, grants a periodical follow up, without forcing patients to discomfortable travelling, and allows to maintain expert care. This result meets the ERNs needs to reduce patients' burden to access and monitor their healthcare.

Action Observation Therapy for Arm Recovery after Stroke: A Preliminary Investigation on a Novel Protocol with EEG Monitoring.

This preliminary study introduces a novel action observation therapy (AOT) protocol associated with electroencephalographic (EEG) monitoring to be used in the future as a rehabilitation strategy for the upper limb in patients with subacute stroke. To provide initial evidence on the usefulness of this method, we compared the outcome of 11 patients who received daily AOT for three weeks with that of patients who undertook two other approaches recently investigated by our group, namely intensive conventional therapy (ICT), and robot-assisted therapy combined with functional electrical stimulation (RAT-FES). The three rehabilitative interventions showed similar arm motor recovery as indexed by Fugl-Meyer's assessment of the upper extremity (FMA_UE) and box and block test (BBT). The improvement in the FMA_UE was yet more favourable in patients with mild/moderate motor impairments who received AOT, in contrast with patients carrying similar disabilities who received the other two treatments. This suggests that AOT might be more effective in this subgroup of patients, perhaps because the integrity of their mirror neurons system (MNS) was more preserved, as indexed by EEG recording from central electrodes during action observation. In conclusion, AOT may reveal an effective rehabilitative tool in patients with subacute stroke; the EEG evaluation of MNS integrity may help to select patients who could maximally benefit from this intervention.