Paving the way for a better management of pain in patients with spinal cord injury: An exploratory study on the use of Functional Electric Stimulation(FES)-cycling.

CONTEXT/OBJECTIVE: Chronic pain is common in patients with spinal cord injury (SCI), for whom it negatively affects quality of life, and its treatment requires an integrated approach. To this end, lower limb functional electrical stimulation (FES) cycling holds promise. OBJECTIVE: To investigate pain reduction in a sample of patients with SCI by means of lower limb rehabilitation using FES cycling. DESIGN, SETTING AND PARTICIPANTS: Sixteen patients with incomplete and complete SCIs, attending the Neurorobotic Unit of our research institute and reporting pain at or below the level of their SCI were recruited to this exploratory study. INTERVENTIONS: Patients undertook two daily sessions of FES cycling, six times weekly, for 6 weeks. OUTCOME MEASURES: Pain outcomes were measured using the 0-10 numerical rating scale (NRS), the Multidimensional Pain Inventory for SCI (MPI-SCI), and the 36-Item Short Form Survey (SF-36). Finally, we assessed the features of dorsal laser-evoked potentials (LEPs) to objectively evaluate Aδ fiber pathways. RESULTS: All participants tolerated the intervention well, and completed the training without side effects. Statistically significant changes were found in pain-NRS, MPI-SCI, and SF-36 scores, and LEP amplitudes. Following treatment, we found that three patients experienced high pain relief (an NRS decrease of at least 80%), six individuals achieved moderate pain relief (an NRS decrease of about 30-70%), and five participants had mild pain relief (an NRS decrease of less than 30%). CONCLUSION: Our preliminary results suggest that FES cycling training is capable of reducing the pain reported by patients with SCI, regardless of American Spinal Injury Association scoring, pain level, or the neurological level of injury. The neurophysiological mechanisms underlying such effects are likely to be both spinal and supraspinal.

Body Representation in Patients with Severe Spinal Cord Injury: A Pilot Study on the Promising Role of Powered Exoskeleton for Gait Training.

Patients with spinal cord injury (SCI) complain of changes in body representation, potentially leading to negative physical and psychological consequences. The purpose of our study is to evaluate the effects of robotic training with the Ekso-GT on body representation (BR) and on the quality of life in patients with SCI. The trial was designed as a pilot, assessor-blinded study. Forty-two inpatients with a diagnosis of SCI, classified as either American Spinal Cord Injury Association Impairment Scale (AIS), were enrolled in this study and randomized into either a control (CG: n = 21) or an experimental (EG: n = 21) group. Patients in the EG received rehabilitation training with the Ekso-GT device, whereas the CG patients were trained with conventional physical therapy (CPT), which consisted of physical and occupational therapy and psychological support. We considered as a primary outcome the modified Body Uneasiness Test (MBUT), focusing on three specific subscales on the patient's perception of BR, i.e., the Global Severity Index (MBUT-GSI), which is an indicator of body suffering; the Positive Symptom Distress Index (MBUT-PSDI) that expresses an individual's psychological distress; and the Lower Limb MBUT (MBUT-LL), which indicates the subject's perception of their thighs/legs. The Short-Form-12 Health Status Questionnaire (SF12) and the Beck's Depression Inventory (BDI) were used as secondary outcomes to evaluate the effect of the training on the quality of life and the psychological status. Non-parametric statistical analysis showed that the effect of the two treatments was significantly different on MBUT (BR), SF-12 (quality of life), and, partially, BDI (mood). Particularly, patients belonging to the EG achieved a major improvement in nearly all test scores compared to those in the CG. Our data suggest that the Ekso-GT training could be helpful in achieving positive changes in BR in patients with chronic SCI, especially in reducing psychological distress (PSDI) and thigh/leg perception (MBUT-LL) with an overall improvement in quality of life (SF-12).

Finding the Way to Improve Motor Recovery of Patients with Spinal Cord Lesions: A Case-Control Pilot Study on a Novel Neuromodulation Approach.

Robot-assisted rehabilitation (RAR) and non-invasive brain stimulation (NIBS) are interventions that, both individually and combined, can significantly enhance motor performance after spinal cord injury (SCI). We sought to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with active transvertebral direct current stimulation (tvDCS) (namely, NIBS) in association with RAR (RAR + NIBS) improves lower extremity motor function more than RAR alone in subjects with motor incomplete SCI (iSCI). Fifteen adults with iSCI received one daily session of RAR+NIBS in the early afternoon, six sessions weekly, for eight consecutive weeks. Outcome measures included the 6 min walk test (6MWT), the 10 m walk test (10MWT), the timed up and go (TUG) to test mobility and balance, the Walking Index for Spinal Cord Injury (WISCI II), the Functional Independence Measure-Locomotion (FIM-L), the manual muscle testing for lower extremity motor score (LEMS), the modified Ashworth scale for lower limbs (MAS), and the visual analog scale (VAS) for pain. The data of these subjects were compared with those of 20 individuals matched for clinical and demographic features who previously received the same amount or RAR without NIBS (RAR - NIBS). All patients completed the trial, and none reported any side effects either during or following the training. The 10MWT improved in both groups, but the increase was significantly greater following RAR + NIBS than RAR - NIBS. The same occurred for the FIM-L, LEMS, and WISCI II. No significant differences were appreciable concerning the 6MWT and TUG. Conversely, RAR - NIBS outperformed RAR + NIBS regarding the MAS and VAS. Pairing tvDCS with rTMS during RAR can improve lower extremity motor function more than RAR alone can do. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living.

Toward improving functional recovery in spinal cord injury using robotics: a pilot study focusing on ankle rehabilitation.

BACKGROUND: Conventional physical therapy interventions are strongly recommended to improve ambulation potential and upright mobility in persons with incomplete spinal cord injury (iSCI). Ankle rehabilitation plays a significant role, as it aims to stem drop foot consequences. RESEARCH QUESTION: This pilot study aimed to assess the neurophysiological underpinnings of robot-aided ankle rehabilitation (using a platform robot) compared to conventional physiotherapy and its efficacy in improving gait performance and balance in persons with iSCI. METHODS: Ten individuals with subacute/chronic iSCI (six males and four females, 39 ± 13 years, time since injury 8 ± 4 months, ASIA impairment scale grade C-D) were provided with one-month intensive training for robot-aided ankle rehabilitation (24 sessions, 1 h daily, six times a week). Clinical (10-Meter Walk Test (10MWT), 6-Minute Walk Test (6MWT), and Timed Up and Go test (TUG)), and electrophysiological aftereffects (surface-EMG from tibialis anterior and medial gastrocnemius muscles to estimate muscle activation patterns; and corticomuscular coherence-CMC-to assess functional synchronization between sensorimotor cortex and muscles, i.e. the functional integrity of corticospinal output) were assessed at baseline (PRE) and after the trial completion (POST). The experimental group (EG) data were compared with those coming from a retrospective control group (CG; n = 10) matched for clinical-demographic characteristics, who previously underwent conventional ankle rehabilitation. RESULTS: the EG achieved a greater improvement in balance and gait as compared to the CG (TUG EG from 70 ± 18 to 45 ± 15 s, p = 0.002; CG from 68 ± 21 to 48 ± 18 s, p = 0.01; group-comparison p = 0.001; 10MWT EG from 0.43 ± 0.11 to 0.51 ± 0.09 m/s, p = 0.006; CG from 0.4 ± 0.13 to 0.45 ± 0.12, p = 0.01; group-comparison p = 0.006; 6 MWT EG from 231 ± 13 to 274 ± 15 m, p < 0.001; CG from 236 ± 13 to 262 ± 15 m, p = 0.003; group-comparison p = 0.01). Furthermore, the EG showed a retraining of muscle activation (an increase within proper movements, with a reduction of co-contractions) and CMC (beta frequency increase within proper movements, i.e. in a framework of preserved motor coordination). The improvements in CMC, gait, balance, and muscle activation were not correlated with each other. CONCLUSIONS: Robot-aided ankle rehabilitation improved gait performance by selectively ameliorating CMC, muscle activation patterns, and, lastly, gait balance and speed. Despite CMC, gait, balance, and muscle activation were not correlated, this pilot study suggests that robot-aided ankle rehabilitation may favor a better communication between above-SCI and below-SCI structures. This communication improvement may depend on a more synchronized corticospinal output (as per CMC increase) and a better responsiveness of below-SCI motorneurons to corticospinal output (as per specific and ankle movement focused muscle activation increases at the surface EMG), thus favoring greater recruitment of spinal motor units and, ultimately, improving muscle activation pattern and strength. SIGNIFICANCE: Adopting robot-aided ankle rehabilitation protocols for persons with iSCI in the subacute/chronic phase may allow achieving a clinically significant improvement in gait performance.

Effects of Robotic Neurorehabilitation on Body Representation in Individuals with Stroke: A Preliminary Study Focusing on an EEG-Based Approach.

Patients with stroke can experience a drastic change in their body representation (BR), beyond the physical and psychological consequences of stroke itself. Noteworthy, the misperception of BR could affect patients' motor performance even more. Our study aimed at evaluating the usefulness of a robot-aided gait training (RAGT) equipped with augmented visuomotor feedback, expected to target BR (RAGT + VR) in improving lower limb sensorimotor function, gait performance (using Fugl-Meyer Assessment scale for lower extremities, FMA-LE), and BR (using the Body Esteem Scale-BES- and the Body Uneasiness Test-BUT), as compared to RAGT - VR. We also assessed the neurophysiologic basis putatively subtending the BR-based motor function recovery, using EEG recording during RAGT. Forty-five patients with stroke were enrolled in this study and randomized with a 1:2 ratio into either the RAGT + VR (n = 30) or the RAGT - VR (n = 15) group. The former group carried out rehabilitation training with the Lokomat©Pro; whereas, the latter used the Lokomat©Nanos. The rehabilitation protocol consisted of 40 one-hour training sessions. At the end of the training, the RAGT + VR improved in FMA-LE (p < 0.001) and BR (as per BES, (p < 0.001), and BUT, (p < 0.001)) more than the RAGT- did (p < 0.001). These differences in clinical outcomes were paralleled by a greater strengthening of visuomotor connectivity and corticomotor excitability (as detected at the EEG analyses) in the RAGT + VR than in the RAGT - VR (all comparisons p < 0.001), corresponding to an improved motor programming and execution in the former group.We may argue that BR recovery was important concerning functional motor improvement by its integration with the motor control system. This likely occurred through the activation of the Mirror Neuron System secondary to the visuomotor feedback provision, resembling virtual reality. Last, our data further confirm the important role of visuomotor feedback in post-stroke rehabilitation, which can achieve better patient-tailored improvement in functional gait by means of RAGT + VR targeting BR.

Can powered exoskeletons improve gait and balance in multiple sclerosis? A retrospective study.

Multiple sclerosis (MS) is a progressive neurologic disorder that can profoundly influence mobility, independence and quality of life. Gait dysfunction in MS is common, resulting in an increased risk of losing walking ability. Robotic exoskeletons have been developed to offer a new form of locomotor training. The aim of our study was to investigate the effectiveness of the powered exoskeleton (Ekso) in improving gait and balance in patients affected by MS. Twenty patients with MS (mean ± SD: age = 43.7 ± 10.3 years; 66.7% male) were enrolled in this retrospective study. They were divided into two groups, matched for demographic data (age and sex) and medical characteristics (disease duration and Expanded Disability Status Scale), but differing for the type of rehabilitation training performed. Group 1 [experimental group (EG)] received gait training with the Ekso device, whereas group 2 (control group) performed traditional gait training. Although both trainings led to a significant improvement in the ability to walk and balance, only in the EG a significant improvement in walking speed (10 Meter Walk test; P = 0.002), in person's mobility (Timed Up and Go test; P = 0.002), and in the perception of mental well-being (MSQoL-M; P = 0.004), with a good usability and acceptance of the device, was found. Powered exoskeletons could be considered a valuable tool to improve functional outcomes and get the therapeutic goal in patients with MS.

Robotic Rehabilitation in Spinal Cord Injury: A Pilot Study on End-Effectors and Neurophysiological Outcomes.

Robot-aided gait training (RAGT) has been implemented to provide patients with spinal cord injury (SCI) with a physiological limb activation during gait, cognitive engagement, and an appropriate stimulation of peripheral receptors, which are essential to entrain neuroplasticity mechanisms supporting functional recovery. We aimed at assessing whether RAGT by means of an end-effector device equipped with body weight support could improve functional ambulation in patients with subacute, motor incomplete SCI. In this pilot study, 15 patients were provided with six RAGT sessions per week for eight consecutive weeks. The outcome measures were muscle strength, ambulation, going upstairs, and disease burden. Furthermore, we estimated the activation patterns of lower limb muscles during RAGT by means of surface electromyography and the resting state networks' functional connectivity (RSN-FC) before and after RAGT. Patients achieved a clinically significant improvement in the clinical outcome measures substantially up to six months post-treatment. These data were paralleled by an improvement in the stair-climbing cycle and a potentiating of frequency-specific and area-specific RSN-FC patterns. Therefore, RAGT, by means of an end-effector device equipped with body weight support, is promising in improving gait in patients with subacute, motor incomplete SCI, and it could produce additive benefit for the neuromuscular reeducation to gait in SCI when combined with conventional physiotherapy.

Breaking the ice to improve motor outcomes in patients with chronic stroke: a retrospective clinical study on neuromodulation plus robotics.

BACKGROUND: Stroke is one of the main causes of impairment affecting daily activities and quality of life. There is a growing effort to potentiate the recovery of functional gait and to enable stroke patients to walk independently. AIM: To estimate the effects of dual-site transcranial direct current stimulation (dstDCS) on gait recovery in chronic stroke patients provided with robot-aided gait training (RAGT). METHODS: Thirty-seven patients were included in this retrospective clinical study. Nine patients were provided with dstDCS during the first 10 min of RAGT by using Lokomat®Pro (on-RAGT), 15 patients immediately after RAGT (post-RAGT), and 13 patients immediately before RAGT (pre-RAGT). RESULTS: Each group improved over time concerning disability burden and lower limb strength. on-RAGT and post-RAGT experienced better improvement in balance (p < 0.001) and, moderately, gait endurance (p = 0.04) as compared to pre-RAGT. Furthermore, all treatments decreased the facilitation of the unaffected hemisphere (p < 0.001) and the inhibition of the affected hemisphere (p < 0.001). The duration of such aftereffects was found to be greater for post-RAGT. DISCUSSION AND CONCLUSION: This is the first trial with dstDCS coupled with RAGT in chronic stroke patients with gait impairment. When timely coupled with RAGT, dstDCS may be considered an effective tool for the recovery of lower limb function in patients with first unilateral stroke in the chronic phase. Moreover, our data suggest the ductility of dstDCS concerning RAGT timing, thus making this intervention suitable in a neurorehabilitation setting and well adaptable to patients' needs.

Does overground robotic gait training improve non-motor outcomes in patients with chronic stroke? Findings from a pilot study.

Stroke is the leading cause of disability among the elderly in the industrialized world. No more than 40% of stroke survivors walk independently, and only after receiving appropriate rehabilitation treatment; many stroke patients have also non-motor symptoms. The aim of this pilot study is to evaluate the effects of Ekso-training on non-motor outcomes, including gastrointestinal function and psychological well-being, in post stroke patients. We enrolled 30 post-stroke subjects, which were randomized into two groups in order of recruitment: 15 patients were trained with the overground exoskeleton Ekso-GT (experimental group, EG), whereas 15 patients were submitted to a standard gait training (control group, CG). Both the groups underwent the same amount of physiotherapy. At the end of the training, only in the EG we observed a significant improvement in constipation, mood, and coping strategies, with regard to social support, as well as in the perception of quality of life (as per SF-12). According to these preliminary data, overground robotic gait training can be considered a valuable tool in improving non-motor symptoms, including constipation and behavioral disorders in patients with chronic stroke.

Can robotic gait rehabilitation plus Virtual Reality affect cognitive and behavioural outcomes in patients with chronic stroke? A randomized controlled trial involving three different protocols.

BACKGROUND: The rehabilitation of cognitive and behavioral abnormalities in individuals with stroke is essential for promoting patient's recovery and autonomy. The aim of our study is to evaluate the effects of robotic neurorehabilitation using Lokomat with and without VR on cognitive functioning and psychological well-being in stroke patients, as compared to traditional therapy. METHODS: Ninety stroke patients were included in this randomized controlled clinical trial. The patients were assigned to one of the three treatment groups, i.e. the Robotic Rehabilitation group undergoing robotic rehab with VR (RRG+VR), the Robotic Rehabilitation Group (RRG-VR) using robotics without VR, and the Conventional Rehabilitation group (CRG) submitted to conventional physiotherapy and cognitive treatment. RESULTS: The analysis showed that either the robotic training (with and without VR) or the conventional rehabilitation led to significant improvements in the global cognitive functioning, mood, and executive functions, as well as in activities of daily living. However, only in the RRG+VR we observed a significant improvement in cognitive flexibility and shifting skills, selective attention/visual research, and quality of life, with regard to the perception of the mental and physical state. CONCLUSION: Our study shows that robotic treatment, especially if associated with VR, may positively affect cognitive recovery and psychological well-being in patients with chronic stroke, thanks to the complex interation between movement and cognition.

Nabiximols plus robotic assisted gait training in improving motor performances in people with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, affecting ambulation even in people with only mild neurological signs. Patients with MS frequently experience spasticity, which contributes significantly to impair their motor functions, including ambulation, owing to muscle stiffness, spasms, and pain. OBJECTIVES: To clarify the role of delta-9-tetrahydrocannabinol(THC):cannabidiol(CBD) oromucosal spray, coupled to robot-aided gait training (RAGT) using the Lokomat©Pro to improve functional ambulation in patients with MS. METHODS: We compared 20 patients with MS, who were treated with THC:CBD oromucosal spray in add-on to the ongoing oral antispastic therapy (OAT) (group A), with 20 individuals with MS (matched for clinical-demographic characteristics) who were treated only with OAT (group B). Both the groups underwent RAGT using the Lokomat-Pro (three 45-minute sessions per week). Our primary outcome measures were the Functional Independence Measure (FIM) and the 10 meters walking test (10MWT). As secondary outcome measures we evaluated the brain cortical excitability by using Transcranial Magnetic Stimulation. Both parameters were taken before and after the end of the RAGT. RESULTS: FIM improved in group A more than in group B (p<0.001). Moreover, 10MWT decreased in group A more than in group B (p<0.001). These clinical findings were paralleled by a more evident reshape of intracortical excitability in both upper and lower limbs, as suggested by motor evoked potential amplitude increase (p<0.001), intracortical inhibition strengthening (p<0.001), and intracortical facilitation decrease (p=0.01) in group A as compared to group B. CONCLUSIONS: Our results suggest that the combined THC:CBD-RAGT approach could be useful in improving gait performance in patients with MS.

Do patients with PD benefit from music assisted therapy plus treadmill-based gait training? An exploratory study focused on behavioral outcomes.

Purpose: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, presenting not only with motor symptoms (resting tremor, bradykinesia, and muscular rigidity), but also with cognitive and behavioral problems that need to be addressed in a rehabilitation setting. Aim of the study was to evaluate the effects of a combined rehabilitative approach, using gait training coupled to music-based therapy, on cognitive and behavioral function in a sample of patients with PD.Materials and Methods: Forty patients, meeting the inclusion criteria, were enrolled in this study and were randomly divided into two groups. The control group (CG) underwent traditional over ground gait training, whilst the experimental group (EG) underwent gait training with the Biodex Gait Trainer 3 (a treadmill integrated with music therapy). Each subject was evaluated at baseline (T0) and after the training (T1), using specific neuropsychological and motor function tests.Results: The EG presented higher outcomes scores concerning mood and quality of life in all subscales of Psychological General Well-Being Index (i.e. anxiety, depression, health, vitality and positivity) and subscales of Brief-COPE, with regard to behavioral disengagement, positive reframing, planning, acceptance and use of emotional support, as compared to the CG. Moreover, a significant improvement in motor functioning, with regard to static and dynamic balance, was found in the EG.Conclusion: Music-based gait training rehabilitation may be considered an effective strategy to improve behavioral performances, coping strategies and rehabilitation outcomes in patients with PD.

Overground exoskeletons may boost neuroplasticity in myotonic dystrophy type 1 rehabilitation: A case report.

RATIONALE: Myotonic dystrophy type 1 (DM1) is a slowly progressive multisystem neuromuscular disease characterized by myotonia and muscle weakness and wasting of distal and axial muscles. People with DM1, due to the disease progression, are often concerned about their ability to carry out and participate in the activities of daily living. Rehabilitation approaches in DM1, including moderate-to-intense strength training, have shown not univocal efficacy to face such difficulties. Aim of this case-study was to demonstrate the effects of a combined approach by using conventional plus robotic training in rare neuromuscular diseases, such as DM1. PATIENT CONCERNS: A 46-year-old woman came to our observation complaining of difficulty in opening fist after strong voluntary muscle contraction for about 20 years. Over the years, she referred swallowing difficulties for solid foods, balance impairment complicated by tendency to stumble and falls, fatigability, hand muscle weakness with difficulty to open bottles and lifting weights, and daytime sleepiness DIAGNOSIS:: Paraparesis in DM1. INTERVENTIONS: The patient underwent 2 different trainings. The first period of treatment was carried out by using conventional physiotherapy, 6 times a week (twice a day) for 4 weeks. Then, she underwent a two-month specific task-oriented robotic rehabilitation training for the gait impairment using an overground exoskeleton, namely Ekso-GT, combined to the conventional therapy. OUTCOMES: The patient, after the EKSO training, gained a significant improvement in walking, balance and lower limbs muscle strength, as per 10-meter walking test and Left Lower Limb Motricity Index. Neurophysiological data (electroencephalography and surface electromyography) were also collected to more objectively assess the functional outcomes. LESSONS: Rehabilitation approaches in DM1, including moderate-to-intense strength training, have shown not univocal efficacy. Emerging and advancing robotic technologies can enhance clinical therapeutic outcomes by allowing therapists to activate and/or modulate neural networks to maximize motor and functional recovery.

Beyond the muscular involvement in non-dystrophic myotonias: The emerging role of neuromodulation.

BACKGROUND: The central nervous system involvement, in terms of a maladaptive sensory-motor plasticity, is well known in patients with dystrophic myotonias (DMs). To date, there are no data suggesting a central nervous system involvement in non-dystrophic myotonias (NDMs). OBJECTIVE: To investigate sensory-motor plasticity in patients with Myotonia Congenita (MC) and Paramyotonia Congenita (PMC) with or without mexiletine. METHODS: Twelve patients with a clinical, genetic, and electromyographic evidence of MC, fifteen with PMC, and 25 healthy controls (HC) were included in the study. TMS on both primary motor cortices (M1) and a rapid paired associative stimulation (rPAS) paradigm were carried out to assess M1 excitability and sensory-motor plasticity. RESULTS: patients showed a higher cortical excitability and a deterioration of the topographic specificity of rPAS aftereffects, as compared to HCs. There was no correlation among neurophysiological and clinical-demographic characteristics. Noteworthy, the patients who were under mexiletine showed a minor impairment of the topographic specificity of rPAS aftereffects as compared to those who did not take the drug. CONCLUSION: our findings could suggest the deterioration of cortical sensory-motor plasticity in patients with NDMs as a trait of the disease.

Shaping neuroplasticity by using powered exoskeletons in patients with stroke: a randomized clinical trial.

BACKGROUND: The use of neurorobotic devices may improve gait recovery by entraining specific brain plasticity mechanisms, which may be a key issue for successful rehabilitation using such approach. We assessed whether the wearable exoskeleton, Ekso™, could get higher gait performance than conventional overground gait training (OGT) in patients with hemiparesis due to stroke in a chronic phase, and foster the recovery of specific brain plasticity mechanisms. METHODS: We enrolled forty patients in a prospective, pre-post, randomized clinical study. Twenty patients underwent Ekso™ gait training (EGT) (45-min/session, five times/week), in addition to overground gait therapy, whilst 20 patients practiced an OGT of the same duration. All individuals were evaluated about gait performance (10 m walking test), gait cycle, muscle activation pattern (by recording surface electromyography from lower limb muscles), frontoparietal effective connectivity (FPEC) by using EEG, cortico-spinal excitability (CSE), and sensory-motor integration (SMI) from both primary motor areas by using Transcranial Magnetic Stimulation paradigm before and after the gait training. RESULTS: A significant effect size was found in the EGT-induced improvement in the 10 m walking test (d = 0.9, p < 0.001), CSE in the affected side (d = 0.7, p = 0.001), SMI in the affected side (d = 0.5, p = 0.03), overall gait quality (d = 0.8, p = 0.001), hip and knee muscle activation (d = 0.8, p = 0.001), and FPEC (d = 0.8, p = 0.001). The strengthening of FPEC (r = 0.601, p < 0.001), the increase of SMI in the affected side (r = 0.554, p < 0.001), and the decrease of SMI in the unaffected side (r = - 0.540, p < 0.001) were the most important factors correlated with the clinical improvement. CONCLUSIONS: Ekso™ gait training seems promising in gait rehabilitation for post-stroke patients, besides OGT. Our study proposes a putative neurophysiological basis supporting Ekso™ after-effects. This knowledge may be useful to plan highly patient-tailored gait rehabilitation protocols. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03162263 .

The role of virtual reality in improving motor performance as revealed by EEG: a randomized clinical trial.

BACKGROUND: Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training (RAGT) devices, including Lokomat, for the treatment of lower limb paresis. Virtual reality (VR) has proved to be a valuable tool to improve neurorehabilitation training. The aim of our pilot randomized clinical trial was to understand the neurophysiological basis of motor function recovery induced by the association between RAGT (by using Lokomat device) and VR (an animated avatar in a 2D VR) by studying electroencephalographic (EEG) oscillations. METHODS: Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were randomized into two groups. One group performed 40 sessions of Lokomat with VR (RAGT + VR), whereas the other group underwent Lokomat without VR (RAGT-VR). The outcomes (clinical, kinematic, and EEG) were measured before and after the robotic intervention. RESULTS: As compared to the RAGT-VR group, all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment. Moreover, they showed stronger event-related spectral perturbations in the high-γ and ß bands and larger fronto-central cortical activations in the affected hemisphere. CONCLUSIONS: The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance. EEG data suggest that the use of VR may entrain several brain areas (probably encompassing the mirror neuron system) involved in motor planning and learning, thus leading to an enhanced motor performance. TRIAL REGISTRATION: Retrospectively registered in Clinical Trials on 21-11-2016, n. NCT02971371 .

Who May Benefit From Armeo Power Treatment? A Neurophysiological Approach to Predict Neurorehabilitation Outcomes.

BACKGROUND: The Armeo Power, a rehabilitation exoskeleton that allows early treatment of motor disabilities, provides intelligent arm support in a large 3-dimensional work space, thus enabling patients to perform intensive, repetitive, and goal-oriented exercises. This device could efficiently induce new connections and facilitate plasticity phenomena potentiation. Knowledge of the potential brain plasticity reservoir after brain damage constitutes a prerequisite for an optimal rehabilitation strategy. OBJECTIVE: To identify potential neurophysiologic markers predicting the responsiveness of stroke patients to upper limb robotic treatment. DESIGN: Prospective cohort study. SETTING: Behavioral and Robotic Neurorehabilitation Laboratory of IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy. PATIENTS: We enrolled 35 patients who had sustained a first-ever ischemic supratentorial stroke at least 2 months before enrollment and had unilateral hemiplegia. METHODS: All patients underwent 40 Armeo Power training sessions that lasted 1 hour each (ie, 5 times a week for 8 weeks). MAIN OUTCOME MEASUREMENTS: We assessed the spasticity and motor function of the upper limb by means of the Modified Ashworth scale and Fugl-Meyer assessment, respectively. Moreover, we evaluated the cortical excitability and plasticity potential of the bilateral primary motor areas in response to the repetitive paired associative stimulation paradigm using transcranial magnetic stimulation and Armeo Power kinematic parameters. RESULTS: The patients who showed significant repetitive paired associative stimulation aftereffects at baseline exhibited an evident increase of cortical plasticity in the affected hemisphere (motor evoked potential amplitude increase, P = .03), a decrease of interhemispheric inhibition (affected hemisphere cortical silent period duration decrease, P = .01; unaffected hemisphere cortical silent period duration increase, P = .004; repetitive paired associative stimulation aftereffect increase, P = .008). Such findings were paralleled by clinical improvements (Fugl-Meyer, P = .04) and Armeo Power kinematic improvements (elbow flexion/extension, P = .02; shoulder range of movement, P = .002). CONCLUSIONS: Our data suggest that use of Armeo Power may improve upper limb motor function recovery as predicted by reshaping of cortical and transcallosal plasticity, according to the baseline cortical excitability. LEVEL OF EVIDENCE: IV.

Do post-stroke patients benefit from robotic verticalization? A pilot-study focusing on a novel neurophysiological approach.

BACKGROUND: Tilt-table equipped with the dynamic foot-support (ERIGO) and the functional electric stimulation could be a safe and suitable device for stabilization of vital signs, increasing patient's motivation for further recovery, decreasing the duration of hospitalization, and accelerating the adaptation to vertical posture in bedridden patients with brain-injury. Moreover, it is conceivable that verticalization may improve cognitive functions, and induce plastic changes at sensory motor and vestibular system level that may in turn facilitate motor functional recovery. OBJECTIVE: To test the safety and effectiveness of ERIGO treatment on motor and cognitive functions, cortical plasticity within vestibular and sensory-motor systems in a bedridden post-stroke sample. METHODS: 20 patients were randomly divided in two groups that performed ERIGO training (30 sessions) (G1) or physiotherapist-assisted verticalization training (same duration) (G2), beyond conventional neurorehabilitation treatment. Motor and cognitive functions as well as sensory-motor and vestibular system plasticity were investigated either before (T0) or after (T1) the rehabilitative protocols. RESULTS: Both the verticalization treatments were well-tolerated. Notably, the G1 patients had a significant improvement in cognitive function (p = 0.03), global motor function (p = 0.006), sensory-motor (p < 0.001) and vestibular system plasticity (p = 0.02) as compared to G2. CONCLUSIONS: ERIGO training could be a valuable tool for the adaptation to the vertical position with a better global function improvement, as also suggested by the sensory-motor and vestibular system plasticity induction.

Robotic neurorehabilitation in patients with chronic stroke: psychological well-being beyond motor improvement.

Although gait abnormality is one of the most disabling events following stroke, cognitive, and psychological impairments can be devastating. The Lokomat is a robotic that has been used widely for gait rehabilitation in several movement disorders, especially in the acute and subacute phases. The aim of this study was to evaluate the effectiveness of gait robotic rehabilitation in patients affected by chronic stroke. Psychological impact was also taken into consideration. Thirty patients (13 women and 17 men) affected by chronic stroke entered the study. All participants underwent neurological examination with respect to ambulation, Ashworth, Functional Independence Measure, and Tinetti scales to assess their physical status, and Hamilton Rating Scale for Depression, Psychological General Well-being Index, and Coping Orientation to Problem Experienced to evaluate the Lokomat-related psychological impact before and after either a conventional treatment or the robotic training. During each rehabilitation period (separated by a no-treatment period), patients underwent a total of 40 1 h training sessions (i.e. five times a week for 8 weeks). After the conventional treatment, the patients did not achieve a significant improvement in the functional status, except balance (P<0.001) and walking ability (P<0.01), as per the Tinetti scale. Indeed, after the robotic rehabilitation, significant improvements were detected in almost all the motor and psychological scales that we investigated, particularly for Psychological General Well-being Index and Coping Orientation to Problem Experienced. Manual and robotic-assisted body weight-supported treadmill training optimizes the sensory inputs relevant to step training, repeated practice, as well as neuroplasticity. Several controlled trials have shown a superior effect of Lokomat treatment in stroke patients' walking ability and velocity in particular. Therefore, our preliminary results proved that active robotic training not only facilitates gait and physical function but also the psychological status, even in patients affected by chronic stroke.

Lokomat training in vascular dementia: motor improvement and beyond!

Vascular dementia (VaD) is a general term describing problems with reasoning, planning, judgment, memory, and other thought processes caused by brain damage from impaired blood flow to the brain. Cognitive rehabilitation and physical therapy are the mainstays of dementia treatment, although often ineffective because of the scarce collaboration of the patients. However, emerging data suggest that physical activity may reduce the risk of cognitive impairment, mainly VaD, in older people living independently. Herein, we describe a 72-year-old male affected by VaD, in which traditional cognitive training in addition to intensive gait robotic rehabilitation (by using Lokomat device) led to a significant improvement in the motor and cognitive function. This promising finding may be related either to the intensive and repetitive aerobic exercises or to the task-oriented training with computerized visual feedback, which can be considered as a relevant tool to increase patients' motor output, involvement, and motivation during robotic training.