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.

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.

Anti-Inflammatory and Cortical Responses after Transcranial Direct Current Stimulation in Disorders of Consciousness: An Exploratory Study.

Disorders of consciousness (DoC) due to severe traumatic brain injury (TBI) are associated with severe disability and an alteration of cortical activation, angiogenesis, and inflammation, which are crucial elements for behavioural recovery. This exploratory study aimed to evaluate anti-inflammatory and cortical responses after transcranial direct current stimulation (tDCS) in traumatic prolonged disorders of consciousness. Ten minimally conscious state (MCS) patients underwent ten sessions of anodal tDCS (five sessions/week, two weeks, 40 min/session) on the primary motor cortex bilaterally. Clinical evaluations were performed using the Coma Recovery Scale-Revised (CRS-R) pre- and post-treatment. In contrast, after single and multiple tDCS sessions, the haemodynamic cortical response was obtained with functional near-infrared spectroscopy (fNIRS). Moreover, angiogenesis (angiopoietin-2, BMP9, endoglin, HbEFG, HGF, IL8, Leptin, PLGF, VEGF-A, and VEGF-C) and inflammation (GM-CSF, IFNg, IP10, MCP1, and TNFα) circulating biomarkers were collected. A significant haemodynamic response was observed after a single tDCS session, with an increased activation from 4.4 (3.1-6.1) to 7.6 (2.9-15.7) a.u. (p = 0.035). After ten tDCS sessions, a significant reduction of angiopoietin-2, VEGF-C, and IP-10 was detected. Moreover, a correlation between behavioural (CRS-R), TNFα (r = 0.89; p = 0.007), and IP10 (r = 0.81; p = 0.014) variation was found. In conclusion, a single tDCS session can increase the cortical activation in MCS patients. Moreover, multiple tDCS sessions showed an anti-inflammatory effect related to behavioural improvement.

The Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment for patients following acquired brain injury: Translation and reliability study.

OBJECTIVE: To develop the Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment and to investigate its internal consistency, intra- and inter-rater reliability. DESIGN: Prospective cohort study. SETTING: Rehabilitation department. SUBJECTS: A total of 34 patients with acquired brain injury. MAIN MEASURE: The translation and cultural adaptation process was completed, and the testing procedures of the Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment were standardized. Internal consistency was evaluated using Cronbach's alpha index; assessment of intra- and inter-rater reliability was carried out using weighted kappa coefficient. RESULTS: The internal consistency of the tactile sensations and the proprioception items of the Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment were generally acceptable to excellent with a range of Cronbach's alpha between 0.73 and 0.97. The intra-rater reliability of the tactile sensations and the proprioception items of the Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment were generally good to excellent with a range of weighted kappa coefficients between 0.47 and 1.00. Likewise, the inter-rater reliabilities of these items were predominantly good to excellent with a range of weighted kappa coefficients between 0.42 and 0.92. CONCLUSION: The Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment is a reliable screening tool to evaluate primary somatosensory impairments in patients with acquired brain injury. Further research is necessary to consolidate these results and establish the validity and responsiveness of the Italian version of the Erasmus MC modifications to the Nottingham Sensory Assessment.

Combined effects of cerebellar tDCS and task-oriented circuit training in people with multiple sclerosis: A pilot randomized control trial.

BACKGROUND: Balance and mobility impairments are frequent in people with multiple sclerosis, partly due to cerebellar dysfunctions. Task-oriented behavioural approaches were previously shown to promote physical function. The possibility exists that cerebellar transcranial direct current stimulation (ctDCS) applied during training, known to increase the excitability of the brain, can boost rehabilitation effects through modulation of cerebellum-brain inhibition. OBJECTIVE: To test the efficacy of cerebellar ctDCS stimulation combined with motor training on mobility and balance in people with multiple sclerosis. METHODS: 16 subjects were randomly assigned to receive real- or sham-ctDCS and task-oriented training daily over two weeks in a double-blind, randomised clinical pilot trial. Functional mobility, balance, walking performance and quality of life were tested before and after treatment and at two-week follow-up. Effects of cerebellar stimulation on psychological and executive functions were also recorded. RESULTS: Walking performance, balance and quality of life improved for both groups at post-treatment assessment which was maintained at 2-weeks follow up. A two-way ANOVA revealed a significant time effect for balance and walking performance. A significant interaction effect of time-treatment (F = 3.12, df = 2,26; p = 0.03) was found for motor aspects of quality of life assessment in patients who received real-ctDCS. CONCLUSIONS: Task-oriented training improves balance and mobility in people with multiple sclerosis, but ctDCS does not boost motor training effects.

Cortical Oxygenation during a Motor Task to Evaluate Recovery in Subacute Stroke Patients: A Study with Near-Infrared Spectroscopy.

In subacute stroke patients we studied cortical oxygenation changes by near-infrared spectroscopy (NIRS) during a motor task performed with the hemiparetic arm (15 s of reaching and grasping, 45 s of rest, repeated 6 times). Twenty-three subjects were included at baseline, compared with six healthy subjects, and restudied after 6 weeks of rehabilitation. Motor/premotor cortical changes in oxyhemoglobin detected by NIRS were quantified as the area under the curve (AUC) for the total cortex (TOT-AUC) and for both affected (AFF-AUC) and unaffected hemispheres (UN-AUC). The ratio between AUC and the number of task repetitions performed identified the cortical metabolic cost (CMC) or the oxygenation increase for a single movement. Fugl−Meyer assessment of the upper extremity (FMA-UE) was also performed. At baseline, both total and hemispheric CMC were significantly higher in stroke patients than in healthy subjects and inversely correlated with FMA-UE. After rehabilitation, changes in total-CMC and unaffected-CMC, but not Affected-CMC, were inversely correlated with variations in the FMA-UE score. A value > 5000 a.u. for the ratio baseline TOT-CMC/days since stroke was associated with not reaching the clinically important difference for FMA-UE after rehabilitation. In subacute stroke the CMC, a biomarker assessed by NIRS during a motor task with the hemiparetic arm, may describe cortical time/treatment reorganization and favor patient selection for rehabilitation.

Combining a supervised and home-based task-oriented circuit training improves walking endurance in patients with multiple sclerosis. The MS_TOCT randomized-controlled trial.

BACKGROUND: Balance and mobility impairments are widespread in patients with Multiple Sclerosis (PwMS), even at an early stage. They can contribute to disability, physical deconditioning and reduced quality of life. Task-oriented is a training modality that may promote walking abilities and conditioning. However, the effects usually are short-lasting and exercising at home can have several barriers. This randomized controlled trial aimed to test the effectiveness of the combination of a 2-weeks in-person, supervised task-oriented circuit training (TOCT), followed by a 12-weeks home-based task-oriented program with monthly in-person visits. METHODS: 36 PwMS with EDSS 4-5.5 and unassisted walking have been randomly assigned to 10 supervised TOCT sessions over two weeks (Phase 1) followed by a 12-weeks home-based task-oriented program (Phase 2) or a delayed-treatment group. At the end of Phase 2, the delayed-treatment group (usual care) received the same TOCT protocol. Phase 1 was composed of six gait-based workstations and treadmill training, whereas Phase 2 was based on progressive task-oriented tasks practice at home with monthly visits to adjust activities levels. Six Minute Walk Test (6MWT), Timed 25-foot walk test (T25FW), Timed Up and Go test (TUG), Dynamic Gait Index (DGI), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Walking Scale - 12 (MSWS-12), Multiple Sclerosis Impact Scale-29 (MSIS-29) and resting muscle oxygen consumption (rmVO2) were assessed as outcome measures at baseline, after Phase 1 and after Phase 2. Retention was tested on the whole sample at a 12-weeks follow-up. RESULTS: The entire sample completed the 2-weeks TOCT, whereas adherence was good for the 12-weeks home-based task-oriented program (6.2/10). The mean repetitions and level of difficulty of each task significantly increased after every timepoint. A superiority of task-oriented program was verified for 6MWT (F, 2,88 = 7.80; p<0.001) on usual care after the 12-weeks home-based program. Moreover, between-group differences were highlighted at the same point, even for T25FW, TUG and MSWS-12. RmVO2 and fatigue were significantly improved only in the experimental group. Positive effects on 6MWT were retained 12 weeks after the end of the protocol (p<0.001) in the whole sample. CONCLUSIONS: The combination of a supervised and self-managed task-oriented program enhances walking endurance with positive effects on walking ability, fatigue and resting muscle oxygen consumption in PwMS with unassisted walking. These preliminary results reflected how this intervention was effective for impairment and activity improvements; moreover, it was cardiorespiratory stressful and possibly reduced deconditioning.

Is robot-assisted gait training intensity a determinant of functional recovery early after stroke? A pragmatic observational study of clinical care.

Gait rehabilitation is a critical factor in functional recovery after a stroke. The aim of this pragmatic observational study was to identify the optimal dose and timing of robot-assisted gait training (RAGT) that can lead to a favourable outcome in a sample of subacute stroke survivors. Subacute patients with stroke who underwent a RAGT within a multidisciplinary rehabilitation program were enrolled. A set of clinical (i.e. age, type of stroke and time since stroke) and rehabilitation stay outcomes (length of stay and RAGT number of sessions) were recorded to evaluate their impact on functional outcome measures by functional independence measure (FIM) or functional ambulation category (FAC). We included 236 patients (62.73 ± 11.82 year old); 38.44% were females, and 59.32% were ischaemic stroke patients. Patients that received at least 14 RAGT sessions, had 15.83% more chance to be responders compared to those that receive less sessions (P = 0.006). Similarly, younger patients (≤60 years) were more prone to be responders (+15.1%). Lastly, an early rehabilitation (<6 weeks) was found to be more efficient (+21.09%) in determining responsiveness (P < 0.001). Becoming newly independent for gait, that refers to a FAC score ≥4, was related with age and RAGT sessions (P = 0.001). In conclusion, a younger age (≤60 years), an early rehabilitation (<6 weeks since stroke) and a higher RAGT dose (at least 14 sessions) were related to a favourable outcome in patients with subacute stroke.

Beneficial Effects of Robot-Assisted Gait Training on Functional Recovery in Women after Stroke: A Cohort Study.

Background and Objectives: Robot-assisted gait training (RAGT) could be a rehabilitation option for patients after experiencing a stroke. This study aims to determine the sex-related response to robot-assisted gait training in a cohort of subacute stroke patients considering mixed results previously reported. Materials and Methods: In this study, 236 participants (145 males, 91 females) were admitted to a rehabilitation facility after experiencing a stroke and performed RAGT within a multidisciplinary rehabilitation program. Functional Independence Measure (FIM) and Functional Ambulatory Category (FAC) were assessed at admission and discharge to determine sex-related outcomes. Results: At the baseline, no significant difference among sexes was observed. At the end of rehabilitation, both males and females exhibited significant improvements in FIM (71% of males and 80% of females reaching the MCID cut-off value) and FAC (∆score: men 1.9 ± 1.0; women 2.1 ± 1.1). A more remarkable improvement was observed in women of the whole population during the study, but statistical significance was not reached. When analysing the FAC variations with respect to the total number of RAGT sessions, a more significant improvement was observed in women than men (p = 0.025). Conclusion: In conclusion, among subacute stroke patients, benefits were observed following RAGT during a multidisciplinary rehabilitation program in both sexes. A greater significant recovery for women with an ischemic stroke or concerning the number of sessions attended was also highlighted. The use of gait robotics for female patients may favour a selective functional recovery after stroke.

Video game therapy on mobility and dual tasking in multiple sclerosis: study protocol for a randomised controlled trial.

INTRODUCTION: Multiple sclerosis (MS) is one of the major causes of disability in young adults and affects mobility, compromising daily living activities and participation in social life. Cognitive domain is also frequently impaired in people with MS (PwMS), particularly the capacity to perform dual-task activities. Impaired cognitive processing abilities need to be treated, and motor and cognitive aspects need to be considered together. Recently, video game therapy (VGT) has been used in rehabilitation to improve motor outcomes and cognitive processing speed. The aim of this study is to test the efficacy of commercially available VGT on mobility and dual tasking in PwMS compared with standardised balance platform training (BPT). METHODS AND ANALYSIS: This will be a parallel-assignment, double-blinded, randomised control trial. Forty-eight (24 per arm) PwMS with Expanded Disability Status Scale 4-5.5 will be randomly assigned to receive 1 hour training session over 4 weeks (three sessions/week) of either: (1) VGT on commercial video game console to train balance and mobility-related activities or (2) BPT to perform balance, postural stability and weight-shifting exercises with and without visual feedback. The same assessor will evaluate outcome measures at points: before and after the 12 training sessions and at 3 months of follow-up. The primary outcome will be functional mobility, assessed by the Timed Up and Go test. We will also evaluate gait, risk of fall, fatigue and health-related quality of life as well as cognitive and psychological aspects (depression, anxiety and attentional performance) and stability through posturographic evaluation. Dual-tasking assessment will be performed combining posturographic and neuropsychological tests. Data analysis will be performed to compare the efficacy of the two treatments. ETHICS AND DISSEMINATION: Ethical approval have been granted from the local Ethics Committee. Study results will be communicated through high-quality journals and national and international conferences. TRIAL REGISTRATION NUMBER: NCT03353974.

Telerehabilitation in Italy During the COVID-19 Lockdown: A Feasibility and Acceptability Study.

This study examined the feasibility and acceptability of a telerehabilitation program during the COVID-19 pandemic in a sample of adult patients with physical disabilities. Of the twenty-three patients enrolled, 11 agreed to participate in a video-based telerehabilitation program. Barriers and facilitators to the adoption of telerehabilitation were identified and clinical, demographic, and psychological variables were analysed as predictors of success. Age, cognitive reserve, and resilience were significant predictors of satisfaction with telerehabilitation (p<0.05). The telerehabilitation program was perceived as feasible and was well accepted by patients, despite some technology challenges. However, patients who took advantage of telerehabilitation perceived differences in the quality of service and preferred traditional in-person treatment to service delivery via telerehabilitation.

Motor Cortical Activation Assessment in Progressive Multiple Sclerosis Patients Enrolled in Gait Rehabilitation: A Secondary Analysis of the RAGTIME Trial Assisted by Functional Near-Infrared Spectroscopy.

This study aimed to determine cortical activation responses to two different rehabilitative programs, as measured through functional near-infrared spectroscopy (fNIRS). As a secondary analysis of the RAGTIME trial, we studied 24 patients with progressive multiple sclerosis (MS) and severe disability who were randomized to a regimen of robot-assisted gait training (RAGT) or overground walking (OW). Cortical activation during a treadmill walking task, assessed through fNIRS recordings from the motor and premotor cortexes (M1/PM), was calculated as the area under the curve (AUC) of oxyhemoglobin for each hemisphere and the total area (Tot-OxyAUC). Gait speed, endurance, and balance were also measured, along with five healthy control subjects. At baseline, Tot-OxyAUC during walking was significantly increased in MS patients compared to healthy people and was significantly higher for those with more severe disabilities; it was also inversely correlated with physical performance. After rehabilitation, significant opposite variations in Tot-OxyAUC were observed, with activity levels being increased after OW and decreased after RAGT (+242,080 ± 361,902 and -157,031 ± 172,496 arbitrary units, respectively; p = 0.002), particularly in patients who were trained at a lower speed. Greater reductions in the cortical activation of the more affected hemisphere were significantly related to improvements in gait speed (r = -0.42) and endurance (r = -0.44). Cortical activation, assessed through fNIRS, highlighted the brain activity in response to the type and intensity of rehabilitation.

Baseline and overtime variations of soluble adhesion molecule plasma concentrations are associated with mobility recovery after rehabilitation in multiple sclerosis patients.

Rehabilitative exercise outcomes and plasma concentrations of soluble adhesion molecules (sEndoglin, sE-Selectin, sL-Selectin, sICAM-1, sNCAM, sNCAM-1, sVCAM-1, sPECAM-1, sVAP-1) were evaluated in 60 severely disabled progressive multiple sclerosis (MS) patients at 4-time points. Changes of sE-Selectin, sL-Selectin, and sPECAM-1 concentrations were observed over time, and their variations were significantly correlated with rehabilitative outcome variations. Baseline sVAP-1 concentrations were able to predict functional mobility recovery. Our data suggest that the evaluation of adhesion molecules in plasma provides useful information to interpret rehabilitative exercise processes and to identify potential predictors of the rehabilitation-induced changes in mobility outcomes in MS patients.

Hyperalgesia and Central Sensitization in Subjects With Chronic Orofacial Pain: Analysis of Pain Thresholds and EEG Biomarkers.

Introduction: The presence of a temporomandibular disorder is one of the most frequent causes of orofacial pain (OFP). When pain continues beyond tissue healing time, it becomes chronic and may be caused, among other factors, by the sensitization of higher-order neurons. The aim of this study is to describe psychological characteristics of patients with chronic OFP, their peripheral pain threshold, and electroencephalography (EEG) recording, looking for possible signs of central sensitization (CS). Materials and methods: Twenty-four subjects with chronic OFP caused by temporomandibular disorder were evaluated using the Research Diagnostic Criteria for Temporomandibular Disorders Axis I and Axis II. Pain intensity, catastrophizing, and presence of CS were assessed through self-reported questionnaires. Pressure pain threshold (PPT) was recorded in facial and peripheral sites; EEG activity was recorded during open and closed eyes resting state and also during the pain threshold assessment. Pain thresholds and EEG recordings were compared with a cohort of pain-free age- and sex-matched healthy subjects. Results: Patients with chronic OFP showed a significant reduction in their pain threshold compared to healthy subjects in all sites assessed. Greater reduction in pain threshold was recorded in patients with more severe psychological symptoms. Decreased alpha and increased gamma activity was recorded in central and frontal regions of all subjects, although no significant differences were observed between groups. Discussion: A general reduction in PPT was recorded in people who suffer from chronic OFP. This result may be explained by sensitization of the central nervous system due to chronic pain conditions. Abnormal EEG activity was recorded during painful stimulation compared to the relaxed condition in both chronic OFP subjects and healthy controls.

Rehabilitation Improves Mitochondrial Energetics in Progressive Multiple Sclerosis: The Significant Role of Robot-Assisted Gait Training and of the Personalized Intensity.

Abnormal levels of pyruvate and lactate were reported in multiple sclerosis (MS). We studied the response of markers of mitochondrial function to rehabilitation in relation to type, intensity and endurance performance in severely disabled MS patients. Forty-six progressive MS patients were randomized to receive 12 walking sessions of robot-assisted gait training (RAGT, n = 23) or conventional overground therapy (CT, n = 23). Ten healthy subjects were also studied. Blood samples were collected to determine lactate, pyruvate, and glutathione levels and lactate/pyruvate ratio pre-post rehabilitation. In vivo muscle metabolism and endurance walking capacity were assessed by resting muscle oxygen consumption (rmVO2) using near-infrared spectroscopy and by six-minute walking distance (6MWD), respectively. The levels of mitochondrial biomarkers and rmVO2, altered at baseline with respect to healthy subjects, improved after rehabilitation in the whole population. In the two groups, an enhanced response was observed after RAGT compared to CT for lactate (p = 0.012), glutathione (<0.001), lactate/pyruvate ratio (p = 0.08) and rmVO2 (p = 0.07). Metabolic biomarkers and 6MWD improvements were exclusively correlated with a training speed markedly below individual gait speed. In severely disabled MS patients, rehabilitation rebalanced altered serum metabolic and muscle parameters, with RAGT being more effective than CT. A determinable slow training speed was associated with better metabolic and functional recovery. Trial Registration: ClinicalTrials.gov NCT02421731.

Effectiveness of blood flow-restricted slow walking on mobility in severe multiple sclerosis: A pilot randomized trial.

OBJECTIVE: We tested the safety, feasibility, and effectiveness of blood flow restriction-empowered low-intensity interval walking exercise (BFR-W) compared with conventional intensive overground walking (CON-W) at improving gait speed and functional capacity in patients with multiple sclerosis (MS) and severe gait disabilities. METHODS: 24 patients (58 ± 5 years; 7 males) with progressive MS (Expanded Disability Status Scale 5.5 - 6.5) were randomized to receive 12 rehabilitation sessions over 6 weeks. The BFR-W group (n = 12) performed interval walking (speed paced by a metronome that increased weekly) with BFR bands at the thighs. The CON-W group (n = 12) received physiotherapist-assisted overground walking therapy. The primary outcome was gait speed, measured by the timed 25-foot walk test. Secondary outcomes included walking endurance, balance, strength, fatigue, and quality of life. The measurements were collected at baseline, at the end of training, and a 6-week follow-up. RESULTS: The two groups did not present any baseline difference. BFR-W group safely walked without limitations due to sleeve compression, with lower increase in perceived exertion (RPE) (P < .001) and heart rate (P = .031) compared with the CON-W. Gait speed improved significantly in both groups (BFR-W + 13%; CON-W + 5%) with greater increases in the BFR-W group at end of the training (P = .001) and at the follow-up (P = .041). Most of the secondary outcomes significantly improved in the two groups, without between-group differences. CONCLUSIONS: Slow interval walking with moderate BFR to the lower limbs was superior to overground walking in improving gait speed in patients with MS with a lower training load and a more durable clinical benefit.

Functional recovery in multiple sclerosis patients undergoing rehabilitation programs is associated with plasma levels of hemostasis inhibitors.

BACKGROUND: Increasing evidence for contribution of hemostasis components in multiple sclerosis (MS) has been reported. Hemostasis protein inhibitors display key regulatory roles, extending to regulation of innate immune response and inflammation, and promotion of blood-brain barrier integrity. Whereas the effects on hemostasis of exercise and rehabilitation strategies have been extensively investigated, relationships between MS rehabilitation strategies and hemostasis have not been previously reported. OBJECTIVES: To investigate in MS patients the association between outcomes of rehabilitative exercise and plasma levels of selected hemostasis inhibitors. METHODS: Sixty-one severely disabled progressive-MS (P-MS) patients were randomized in the RAGTIME trial to receive 12 walking session of robot-assisted gait training (RAGT) or conventional overground therapy (CT). Outcome parameters were: timed 25-foot walk test (T25FWT) speed, 6-minute walking test (6MWT), Berg Balance Scale (BBS), and MS impact scale-29 (MSIS-29). Plasma levels of coagulation inhibitors protein S (PS), soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) were assayed by multiplex assay and ELISA at 4-time points: baseline (T0), intermediate (T1), end of rehabilitation (T2), 3-month follow-up (T3). Descriptive analysis, trend analysis, Spearman's rank and Pearson's correlations, and multiple regression models were used. RESULTS: Rehabilitative exercises moderately modified plasma protein concentrations. A significant trend to increase was observed for PS (p=0.015) and TFPI (p=0.047) in the whole population, and for PS (p=0.011) in the CT group. Correlation between TFPI and sTM levels was detectable at all time points in the whole P-MS patients and in RAGT group. The correlation between TFPI and PS, present at T0, was lost during the rehabilitation, and recovered at T3 in the whole population and CT group. During rehabilitation, positive variations of TFPI were inversely related with changes in 6MWT in the whole population (r=-0.309, p=0.021), and in the RAGT group (r=-0.51, p=0.004). In all P-MS, PS T0 levels were associated (r=0.379, p=0.004) with increased gait speed, which in the RAGT group was associated both with PS T0 (r=0.378, p=0.040), and sTM T0 (r=0.453, p=0.012). Accordingly, in the regression model including age, sex and EDSS and the stepwise enter of PS T0, higher PS T0 levels predicted increased gait speed in all P-MS (F=3.4, p=0.016) The regression model in the RAGT group indicated that higher PS and sTM T0 levels were both predictors of increased gait speed (F=5.7, p=0.001). CONCLUSIONS: Plasma levels of coagulation inhibitors were related to variations of outcome measurements after high-intensity walking rehabilitation programs. Patients with decreased TFPI levels from T0 to T2 displayed the most significant functional recovery following rehabilitation, and particularly after RAGT. Higher baseline total PS levels were associated with favorable outcomes of rehabilitation therapies in MS. These novel findings, which suggest that plasma levels of hemostasis inhibitors might have implication for rehabilitative therapy options in MS, warrant further investigation.

Biomarkers of Muscle Metabolism in Peripheral Artery Disease: A Dynamic NIRS-Assisted Study to Detect Adaptations Following Revascularization and Exercise Training.

We assessed whether muscle metabolism biomarkers (MMb) identified by near-infrared spectroscopy (NIRS) are valid for determining adaptations following revascularization or exercise training in peripheral artery disease (PAD). Eighteen patients (males n = 13; 69 ± 7 years) were randomized to receive revascularization (Rev = 6) or pain-free home-based exercise (Ex = 12). MMb were safely collected via a NIRS-assisted treadmill test as area-under-curve for the spectra of oxygenated (-oxy), deoxygenated (-deoxy), differential (-diff) and total (-tot) hemoglobin traces. MMb, ankle-brachial index (ABI), pain-free (PFWD) and 6-minute (6MWD) walking distances were assessed at baseline and after four months. MMb were correlated at baseline with ABI (MMb-oxy r = 0.46) and 6MWD (MMb-tot r = 0.51). After treatments, MMb-oxy showed an expected increase, which was more relevant for Rev group than the Ex (56% vs. 20%), with trends towards normalization for the other MMb. These changes were significantly correlated with variations in ABI (MMb-oxy r = 0.71; p = 0.002) and 6MWD (MMb-tot r = 0.58; p = 0.003). The MMb-diff in Rev group and MMb-deoxy in Ex group at baseline predicted clinical outcomes being correlated with PFWD improvements after 4-month (r=-0.94; p = 0.005 and r = -0.57; p = 0.05, respectively). A noninvasive NIRS-based test, feasible in a clinical setting, identified muscle metabolism biomarkers in PAD. The novel MMb were associated with validated outcome measures, selectively modified after different interventions and able to predict long-term functional improvements after surgery or exercise training.

The dose of robot-assisted gait therapy may influence functional recovery in a multidisciplinary rehabilitation program: an exploratory retrospective study.

Robot-assisted gait training (RAGT) has been introduced in clinical practice to increase training intensity in patients with neurological disorders. In this observational study, we investigated the effect of the number of RAGT sessions on functional recovery in a heterogeneous cohort of patients. We included patients with a diagnosis of gait impairment due to a neurological disease. A set of demographic, clinical, functional and training parameters was collected for each participant. Each patient received RAGT with an exoskeleton (Lokomat; Hocoma, Volketswil, Switzerland) as part of a multidisciplinary rehabilitation program. We stratified the patients as good responders and poor responders and investigated the effect of varying the number of RAGT sessions with a series of logistic regression models. A total of 143 patients were included in this analysis (good responders = 65, poor responders = 78). Good responder patients spent more days in the hospital (P < 0.01) and underwent a higher number of RAGT sessions (P = 0.04) compared to poor responder patients. Logistic regression models estimated that adding six RAGT sessions mildly increased (by approximately 4%) the probability of a patient becoming a good responder. The rehabilitation phase (subacute/chronic) appeared to be the main determinant of the probability of being a good responder, and stroke patients appeared to be more sensitive to changes in the number of RAGT sessions. Our results seem to confirm previous observations that robotic therapy increases the intensity of rehabilitation, possibly leading to a greater functional recovery in subacute patients with greater impairment.