A robotic exoskeleton device is an intelligent system designed to improve gait performance and quality of life for the wearer. Robotic technology has developed rapidly in recent years, and several robot-assisted gait devices were developed to enhance gait function and activities of daily living in elderly adults and patients with gait disorders. In this study, we investigated the effects of the Gait-enhancing Mechatronic System (GEMS), a new wearable robotic hip-assist device developed by Samsung Electronics Co, Ltd., Korea, on gait performance and foot pressure distribution in elderly adults. Thirty elderly adults who had no neurological or musculoskeletal abnormalities affecting gait participated in this study. A three-dimensional (3D) motion capture system, surface electromyography and the F-Scan system were used to collect data on spatiotemporal gait parameters, muscle activity and foot pressure distribution under three conditions: free gait without robot assistance (FG), robot-assisted gait with zero torque (RAG-Z) and robot-assisted gait (RAG). We found increased gait speed, cadence, stride length and single support time in the RAG condition. Reduced rectus femoris and medial gastrocnemius muscle activity throughout the terminal stance phase and reduced effort of the medial gastrocnemius muscle throughout the pre-swing phase were also observed in the RAG condition. In addition, walking with the assistance of GEMS resulted in a significant increase in foot pressure distribution, specifically in maximum force and peak pressure of the total foot, medial masks, anterior masks and posterior masks. The results of the present study reveal that GEMS may present an alternative way of restoring age-related changes in gait such as gait instability with muscle weakness, reduced step force and lower foot pressure in elderly adults. In addition, GEMS improved gait performance by improving push-off power and walking speed and reducing muscle activity in the lower extremities. NCT02843828 .

Background: Mesenchymal stem cells (MSCs) secrete trophic factors and extracellular vesicles (EVs). However, the level and role of EVs after MSC therapy in patients with stroke are unknown. We investigated whether circulating EVs and trophic factors are increased after MSCs and are related to the therapeutic benefits in the STARTING-2 trial (Stem Cell Application Researches and Trials in Neurology-2) participants. Methods: In this prospective randomized controlled trial, patients with chronic major stroke were assigned, in a 2:1 ratio, to receive autologous MSC intravenous injection (MSC group, n=39) or standard treatment (control group, n=15) and followed for 3 months. Detailed clinical assessment and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging were evaluated. Serial samples were collected, before/after MSCs therapy. The primary outcome measure was circulating factors that are associated with the clinical improvement in the Fugl-Meyer Assessment (secondary end point of the trial) and neuroplasticity on diffusion tensor image and resting-state functional magnetic resonance imaging. Additional outcome measures were microRNAs and trophic factors enriched in the plasma EVs, obtained using quantitative polymerase chain reaction and ELISA, respectively. Results: Circulating EV levels were increased ≈5-fold (mean±SD, from 2.7×10 ⁹ ±2.2×10 ⁹ to 1.3×10 ¹⁰ ±1.7×10 ¹⁰ EVs/mL) within 24 hours after injection of MSCs ( P =0.001). After adjustment of age, sex, baseline stroke severity, and the time interval from stroke onset to treatment, only the EV number was independently associated with improvement in motor function (odds ratio, 5.718 for EV number ^Log [95% CI, 1.144–28.589]; P =0.034). Diffusion tensor image and resting-state functional magnetic resonance imaging showed that integrity of the ipsilesional corticospinal tract and intrahemispheric motor network were significantly correlated with circulating EV levels, respectively ( P <0.05). MicroRNAs related to neurogenesis/neuroplasticity (eg, microRNA-18a-5p) were significantly increased in circulating EVs after MSC therapy ( P =0.0479). In contrast, trophic factor levels were not changed after MSC therapy. Conclusions: This trial is the first to show that treatment of ischemic stroke patients with MSCs significantly increases circulating EVs, which were significantly correlated with improvement in motor function and magnetic resonance imaging indices of plasticity. Registration: URL: https://www.clinical trials.gov ; Unique identifier: NCT01716481.

Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke. This study aims to evaluate whether Cerebrolysin provides additional motor recovery on top of rehabilitation therapy in the subacute stroke patients with moderate to severe motor impairment. This phase IV trial was designed as a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 70 patients (Cerebrolysin n = 35, placebo n = 35) with moderate to severe motor function impairment were included within 7 days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo, given in addition to standardized rehabilitation therapy. Assessments were performed at baseline, immediately after treatment as well as 2 and 3 months after stroke onset. The plasticity of motor system was assessed by diffusion tensor imaging and with resting state functional magnetic resonance imaging. Both groups demonstrated significant improvement in motor function (p < 0.05); however, no significant difference was found between the two groups. In the stroke patients with severe motor impairment, the Cerebrolysin group exhibited significantly more improvement in motor function compared with the placebo group (p < 0.05). Effects of Cerebrolysin were demonstrated as restricted increments of corticospinal diffusivity and as recovery of the sensorimotor connectivity. The combination of standard rehabilitation therapy with Cerebrolysin treatment in the subacute stroke has shown additional benefit on motor recovery and plastic changes of the corticospinal tract in patients with severe motor impairment. NCT01996761 (November 5, 2013)

Background: Recovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging. Several recent clinical trials have investigated mesenchymal stem cell (MSC) therapy for patients with ischemic stroke. We previously reported the results of a controlled trial on the application of autologous MSCs in patients with ischemic stroke with a long-term follow-up of up to 5 years (the 'STem cell Application Researches and Trials In NeuroloGy’ (STARTING) study). The results from this pilot trial are challenging, but also raise important issues. In addition, there have been recent efforts to improve the safety and efficacy of MSC therapy for stroke.Methods and design: The clinical and preclinical background and the STARTING-2 study protocol are provided. The trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial. Both acute and chronic stroke patients will be selected based on clinical and radiological features and followed for 3 months after MSC treatment. The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be intravenously administered afterex vivoculture expansion with autologous ischemic serum obtained as early as possible, to enhance the therapeutic efficacy (ischemic preconditioning). Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers.Discussion: This trial is the first to evaluate the efficacy of MSCs in patients with ischemic stroke. The results may provide better evidence for the effectiveness of MSC therapy in patients with ischemic stroke.Trial registration: This trial was registered with ClinicalTrials.gov, numberNCT01716481.

Background and purpose: Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. Methods: Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. Results: Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p < 0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. Conclusion: According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits.

Muscle co-activation plays an important role in enhancing joint stability for movement regulation during motor learning activities. In normal aging, greater muscle co-activation is induced during gait in elderly adults. This study investigated age-related changes in muscle co-activation and spatio-temporal parameters during gait and identified the relationship between muscle co-activation and gait speed. A total of 46 adult volunteers participated in this study in three age groups (15 young adults [8 males, 7 females; age, 24.27 ± 2.71], 15 middle-aged adults [8 males, 7 females; age, 53.71 ± 2.52], and 16 elderly adults [7 males, 9 females; age, 76.88 ± 3.48]). All participants underwent locomotion analysis using a Three-dimensional motion analysis system and 12-channel dynamic electromyography. The elderly adults showed significantly higher co-activation than the young and middle-aged adults during gait (p < 0.05). In contrast, elderly adults showed significantly lower trunk co-activation than the young and middle-aged adults (p < 0.05). Muscle co-activation was significantly correlated with gait speed by aging. Muscle co-activation of the trunk showed a significant positive correlation with gait speed based on age. However, muscle co-activation of the lower extremity showed a significant negative correlation with gait speed based on age. This finding demonstrated that less muscle co-activation of the trunk was related to locomotive instability in elderly adults. Therefore, clarification of the relationship between trunk co-activation and locomotor instability will be helpful for developing optimal rehabilitation of elderly people to prevent fall.