End-effector lower limb robot-assisted gait training effects in subacute stroke patients: A randomized controlled pilot trial.

BACKGROUND: This pilot study investigated end-effector lower limb rehabilitation robot training effects in subacute stroke patients. METHODS: Forty-nine stroke patients were randomly assigned to 2 treatment groups: a 30-minute end-effector lower limb rehabilitation robot training plus 1.5-hour conventional physiotherapy (robot group; n = 26), or a 2-hour conventional physiotherapy (control group; n = 23). All patients received 5 treatments weekly for 4 weeks. The functional ambulatory category was the primary outcome and the motricity index, Fugl Meyer assessment-lower extremity, rivermead mobility index, 10 meter walk test, Berg balance scale, and modified Barthel index were secondary outcomes. RESULTS: All outcome measures significantly improved in both groups after training (P > .05). The robot group improved more in FAC than the control group (P = .005). CONCLUSIONS: Compared with conventional physiotherapy alone, end-effector lower limb robot-assisted gait training with conventional physiotherapy improved subacute stroke patients walking ability.

The effect of a gait and balance training program on an unstable mudflats surface in older adults: A randomized controlled pilot study.

BACKGROUND: Balance training on an unstable support surface has been known to improve postural control. The aim of this study was to investigate the effect of a gait and balance training program on an unstable mudflats surface in older adults. METHODS: A total of 28 older people were assigned to participate in a gait and balance training program on an unstable mudflats surface (experimental group) or on firm ground (control group). All participants received the training program for 55 minutes per session, 2 sessions per day for 5 days. The primary outcomes were the Berg Balance Scale (BBS) and single-leg stance (SLS) test. Secondary outcomes were Timed Up and Go (TUG), 10-meter walk test (10MWT), Modified Falls Efficacy Scale (MFES), Motricity Index (MI) of the lower extremities, and medical research council (MRC) scale of lower extremities. RESULTS: SLS with eyes open and the MRC of the left and right ankles showed a large effect size whereas the MI of the left and right lower extremities and MRC of the left and right knees showed a medium effect size in the experimental group. Intergroup differences in changes from baseline to after the exercise program included a large effect size of the SLS with eye open and MI of the right lower extremity and a medium effect size of the MI of the left lower extremity and MRC of the right ankle and left hip. CONCLUSIONS: Muscle strength and balance of older people could be improved with gait and balance training on an unstable mudflat surface.

The Effect of Gait Training on a Sandy Beach in Patients with Chronic Stroke: A Randomized Controlled Pilot Study.

Background: A sandy beach provides an unstable support surface and may influence walking ability in patients with stroke. Primary Study Objective: To investigate the effect of gait training on a sandy beach in patients with chronic stroke. Methods/Design: This was a randomized controlled trial. Setting: Patients were recruited from a community center. Participants: A total of 28 patients with chronic stroke participated in the study. Intervention: Patients were randomly assigned to receive gait training either on a sandy beach (sand group) or firm ground (control group). All patients received gait training for 30 minutes per session, 2 sessions every day for 5 days. Context: Primary Outcome Measures • Primary outcomes were 10-minute walk test (10MWT) and Berg Balance Scale (BBS) scores. Secondary outcomes were Functional Ambulatory Category (FAC), Timed Up and Go (TUG) and spatiotemporal parameters of gait evaluated with a wearable inertial sensor. Psychological parameters, including the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI), were also measured. Outcome measurements were evaluated at baseline and after the intervention. Results: The 10MWT and BBS scores were significantly improved in the sand group (P < .05). Compared with the changes from pre- to post-treatment between the groups, 10MWT showed a large effect size and BBS score showed a medium effect size. Regarding spatiotemporal parameters, cadence and gait velocity were significantly higher after training than before training in the sand group (P < .05). Compared with the changes from pre- to post-treatment between groups, cadence and gait velocity showed large effect sizes and affected-side stride length showed a medium effect size. There was no difference in the changes from pre- to post-treatment in BDI and STAI between the 2 groups (P > .05). No adverse events occurred during the study. Conclusion: Gait training on a sandy beach may be beneficial for improving walking ability and balance in patients with stroke.

Safety and Efficacy of HU-014 in the Treatment of Post-Stroke Upper Limb Spasticity: A Phase I Pilot Study.

Botulinum toxin type A (BTX-A) is widely used for treating post-stroke upper limb spasticity. We evaluated the safety and efficacy of HU-014 in treating post-stroke upper limb spasticity. Thirteen patients were administered with HU-014. The primary outcome was safety, including adverse events, vital signs, physical examination, laboratory tests, and antibody formation test. The secondary outcomes were changes in the Modified Ashworth Scale (MAS) score for wrist, elbow, and finger flexor; Disability Assessment Scale (DAS); Investigator's Global Assessment (IGA) and Subject's Global Assessment (SGA); Caregiver Burden Scale (CBS); and Columbia Suicide Severity Rating Scale (C-SSRS) at weeks 4, 8, and 12 from baseline. No notable safety-related issues were reported. MAS and DAS scores were significantly decreased from those at baseline at 4, 8, and 12 weeks (p < 0.05). At weeks 4, 8, and 12, the IGA and SGA scores were 5.85 ± 0.55, 5.69 ± 0.48, and 5.62 ± 0.65 and 5.46 ± 1.20, 5.85 ± 0.38, and 5.77 ± 0.73, respectively. CBS scores decreased at all timepoints and those for cutting fingernails significantly decreased at 8 and 12 weeks compared with baseline (p < 0.05). C-SSRS scores showed that suicidal ideation in all patients was "low" at all timepoints. HU-014 is a safe treatment that can improve post-stroke upper limb spasticity.

Safety and efficacy of MT10107 in post-stroke upper limb spasticity treatment: A phase I randomized controlled trial.

BACKGROUND: Botulinum toxin type A injection is widely used treatment option for the treatment of upper limb spasticity in stroke patients. The purpose of this study was to explore the safety and efficacy of MT10107, a new botulinum toxin type A, in patients with post-stroke upper limb spasticity. METHODS: A prospective, randomized, double-blind, active drug-controlled, multi-center, phase I clinical trial. Thirty patients with post-stroke upper limb spasticity were received either MT10107 or onabotulinumtoxinA. Primary endpoint was change of modified Ashworth scale (MAS) score for wrist flexor from baseline to week 4. The secondary endpoints were changes of MAS scores for elbow and finger flexors, response rate, Disability Assessment Scale (DAS), and global assessment of treatment. The safety endpoints such as adverse events, vital signs, physical examination, and laboratory test were evaluated. The outcome measures were evaluated from baseline to week 4. RESULTS: The primary endpoints were -1.07 ± 0.70 and -1.23 ± 0.56 for the MT10107 and onabotulinumtoxinA groups, respectively. The intergroup difference of change between the 2 groups was 0.17 (95% confidence interval -0.31 to 0.64, P = .5769). In secondary endpoints, both groups showed a significant improvement in both MAS and DAS. There was no significant between-group difference in all secondary endpoints and safety measures. CONCLUSION: The safety and efficacy of MT10107 showed no significant difference compared to onabotulinumtoxinA in post-stroke upper limb spasticity treatment.

Effects of a lower limb rehabilitation robot with various training modes in patients with stroke: A randomized controlled trial.

BACKGROUND: The effect of robot-assisted gait training has been demonstrated to improve gait recovery in patients with stroke. The aim of this study was to determine effects of robot-assisted gait training with various training modes in patients post stroke. METHODS: Forty-seven patients post stroke were randomly assigned to one of 4 groups: Healbot T with pelvic off mode (pelvic off group; n = 11); Healbot T with pelvic control mode (pelvic on group; n = 12); Healbot T with constraint-induced movement therapy (CIMT) mode (CIMT group; n = 10); and conventional physiotherapy (control group; n = 10). All patients received a 30-minute session 10 times for 4 weeks. The primary outcomes were the 10-meter walk test (10MWT) and Berg Balance Scale (BBS). The secondary outcomes were functional ambulation category, timed up and go (TUG), and motricity index of the lower extremities (MI-Lower). RESULTS: The pelvic off group showed significant improvements in BBS, TUG, and MI-Lower (P < .05). The pelvic on and CIMT groups showed significant improvement in 10MWT, BBS, TUG, and MI-Lower (P < .05). Compared with control group, the pelvic on group showed greater improvement in the TUG and BBS scores; the CIMT group showed greater improvement in 10MWT and MI-Lower (P < .05). CONCLUSION: This study suggested that Healbot T-assisted gait training benefited patients with stroke. The Healbot T with pelvic motion and CIMT modes were more helpful in improving balance and walking ability and lower limb strength, respectively, compared with conventional physiotherapy.

Compliance and effect of thickener use in dysphagia patients with brain lesions: An observational pilot study.

The study aimed to investigate the status of thickener use in dysphagia patients with brain lesions and incidence of adverse events based on fluid viscosity. Twenty dysphagia patients with brain lesions who were recommended to use thickeners following a videofluoroscopic swallowing study were enrolled in this observational pilot study. Patients were educated to use thickener as level 2 or 3 based on the International Dysphagia Diet Standardization Initiative flow test. We evaluated the viscosity of the fluid that patients drank once a week for 2 weeks, and reviewed medical records regarding adverse events. Patients were divided into 2 groups based on the average value obtained from the viscosity evaluations as thin (Levels 0-2) and thick fluid groups (Levels 3-4). Adverse events were compared between the groups. The number of patients who did not follow the recommendations increased from 35.0 to 45.0% during the 1-week follow-up period. No patient developed pneumonia or urinary tract infection. Constipation (P = 0.338) and dehydration status (P = 0.202) were not significantly different between the 2 groups. In 2 evaluations for 20 patients, 40.0% of the cases did not follow the educated viscosity, and the number gradually increased in the follow-up evaluation. Considering that there were no significant differences in the incidence of adverse effects including pneumonia according to the fluid viscosity, a further study is necessary to establish detailed criteria for thickener use in dysphagia patients with brain lesions.

Intensity control of robot-assisted gait training based on biometric data: Preliminary study.

OBJECTIVE: This study is aimed to compare the effect of robot-assisted gait training when the intensity is controlled using patients' biometric data to when controlled by therapist's subjective judgment. DESIGN: This is non-blinded, prospective, randomized controlled study. Patients were randomly assigned to one of two groups. In biometric data control group, exercise intensity was controlled through the patient's heart rate or rating of perceived exertion (RPE). The intensity was raised to the next level when the patient's heart rate reserve was less than 40 percent or the RPE was less than 12 points. The exercise intensity of the therapist control group was adjusted according to the judgement of a therapist. All patients were instructed to perform robot (Morning Walk®)-assisted 20-minute gait training session five times a week during 3 weeks. The primary outcome was functional ambulation category (FAC). The secondary outcomes were modified Barthel index (MBI), Berg balance scale (BBS), timed up and go test (TUG) and 10-meter walk test (10MWT) The outcomes were evaluated at baseline and after 3-week gait training. RESULTS: A total of 55 patients with stroke were enrolled. After robotic rehabilitation, the primary outcome, FAC improved significantly (P < .05) in both groups. Also, secondary outcomes, including MBI, BBS, TUG, 10MWT, showed significant improvement (P < .05) in all groups. In addition, when comparing the functional change from baseline to week 3 between the two groups, there was no statistically significant difference in FAC (P > .05). The difference of baseline and week 3 of secondary outcome measure, MBI, BBS, TUG, 10MWT, showed no significant difference (P > .05). CONCLUSION: In conclusion, when the robot intensity was adjusted using the patient's heart rate or RPE, the treatment effect has no significant difference to when adjusting the intensity according to the know-how of the therapist.

The effect of robot-assisted gait training on cortical activation in stroke patients: A functional near-infrared spectroscopy study.

OBJECTIVE: To investigate the effects of the robot-assisted gait training on cortical activation and functional outcomes in stroke patients. METHODS: The patients were randomly assigned: training with Morning Walk® (Morning Walk group; n = 30); conventional physiotherapy (control group; n = 30). Rehabilitation was performed five times a week for 3 weeks. The primary outcome was the cortical activation in the Morning Walk group. The secondary outcomes included gait speed, 10-Meter Walk Test (10MWT), FAC, Motricity Index-Lower (MI-Lower), Modified Barthel Index (MBI), Rivermead Mobility Index (RMI), and Berg Balance Scale (BBS). RESULTS: Thirty-six subjects were analyzed, 18 in the Morning Walk group and 18 in the control group. The cortical activation was lower in affected hemisphere than unaffected hemisphere at the beginning of robot rehabilitation. After training, the affected hemisphere achieved a higher increase in cortical activation than the unaffected hemisphere. Consequently, the cortical activation in affected hemisphere was significantly higher than that in unaffected hemisphere (P = 0.036). FAC, MBI, BBS, and RMI scores significantly improved in both groups. The Morning Walk group had significantly greater improvements than the control group in 10MWT (P = 0.017), gait speed (P = 0.043), BBS (P = 0.010), and MI-Lower (P = 0.047) scores. CONCLUSION: Robot-assisted gait training not only improved functional outcomes but also increased cortical activation in stroke patients.

The neuroprotective effects of pregabalin after cerebral ischemia by occlusion of the middle cerebral artery in rats.

Activation of presynaptic voltage-gated calcium channels and glutamate release serves a central role in neuronal necrosis after cerebral ischemia. Pregabalin binds to the α2-δ subunit of voltage-gated calcium channels and results in reduced glutamate release. The aim of the current study was to evaluate the effect of pregabalin on cerebral outcome following cerebral ischemia using an established rat model. Male Sprague-Dawley rats were randomized to receive oral administration of 5 mg/kg pregabalin for 1 day (PD1 group) or 5 days (PD5 group), or an equal amount of normal saline for 1 day (SD1 group) or 5 days (SD5 group) after 1 day of middle cerebral artery occlusion (MCAO) and reperfusion. Behavioral tests were assessed at postoperative days 1 and 7. Cerebral infarct volume was measured using a brain MRI scan on days 1 and 7 following surgery. Using immunohistochemistry to detect brain-derived neurotrophic factor (BDNF), histologic examinations of perilesional cortex and ipsilateral hippocampus were performed at postoperative day 7. BDNF-positive immunostaining was more abundant in the perilesional cortex of mice of the PD1 group compared with mice of the SD1 group (P=0.001). In the ipsilateral hippocampus, greater BDNF-positive staining was present in the PD5 group compared with the SD5 group (P=0.04). No statistically significant differences were indicated for behavioral tests or cerebral infarct volume between the PD1 and SD1 groups or the PD5 and SD5 groups. In conclusion, treatment with pregabalin beneficially impacts BDNF expression and histologic cerebral outcome in rats after cerebral ischemia.

Effects of robot (SUBAR)-assisted gait training in patients with chronic stroke: Randomized controlled trial.

BACKGROUND: SUBAR is a new ground walking exoskeletal robot. The objective of this study is to investigate SUBAR-assisted gait training's effects in patients with chronic stroke. METHODS: This preliminary study is a prospective randomized controlled trial. Thirty adults were enrolled 6 months after the onset of stroke with functional ambulation category scores ≥ 3. Patients were randomly assigned to receive robot-assisted gait training (SUBAR group, n = 15) or conventional physiotherapy (control group, n = 15). All patients received a total of 10 treatment sessions of 30 minutes each for 3 weeks. Before and after the 10-treatment sessions, patients were evaluated. The primary outcome is the 10 meter walk test and the secondary outcomes were the functional ambulation category scale, the Motricity Index-Lower, Modified Ashworth Scale (MAS), timed up and go, Rivermead Mobility Index, Berg Balance Scale (BBS), and gait analysis. RESULTS: In the SUBAR group, MAS and step length were significantly improved between pre- and posttreatment measurements (Δmean ±â€ŠSD: -1.1 ±â€Š1.6 and 5.5 ±â€Š7.6, P = .019 and .016, respectively). The SUBAR group improved the stride length and step length of the affected limb but not significantly. The control group had significant improvements in the BBS, MAS, and stride length between pre- and posttreatment measurements (Δmean ±â€ŠSD: 3.5 ±â€Š4.6, -0.8 ±â€Š1.5, and 6.5 ±â€Š9.5; P = .004, .031, and .035, respectively). The BBS improved more in the control group than in the SUBAR group. There were no other differences between the SUBAR group and the control group. CONCLUSION: Our results suggest that SUBAR-assisted gait training improved gait parameters in patients with chronic stroke. However, there was no significant difference in most outcome measures compared to conventional physiotherapy. Further research is warranted to measure the effects of SUBAR-assisted gait training.

Efficacy and Safety of MT10107 (Coretox) in Poststroke Upper Limb Spasticity Treatment: A Randomized, Double-Blind, Active Drug-Controlled, Multicenter, Phase III Clinical Trial.

OBJECTIVE: To compare the efficacy and safety of MT10107 (Coretox) with those of onabotulinum toxin A (Botox) in patients with poststroke upper limb spasticity DESIGN: Prospective, randomized, double-blind, active drug-controlled, multicenter, phase III clinical trial. SETTING: Seven university hospitals in the Republic of Korea. PARTICIPANTS: Patients (N=220) with poststroke upper limb spasticity. INTERVENTIONS: All participants received a single injection of either MT10107 (Coretox group) or onabotulinum toxin A (Botox group). MAIN OUTCOME MEASURES: The primary outcome was change in wrist flexor spasticity from baseline to week 4, which was assessed using the modified Ashworth scale (MAS). The secondary outcomes were MAS scores for wrist, elbow, and finger flexors; percentage of treatment responders (response rate); Disability Assessment Scale (DAS) score, and global assessment of treatment. Safety was evaluated based on adverse events, vital signs, physical examination findings, and laboratory test results. The efficacy and safety were evaluated at 4, 8, and 12 weeks postintervention. RESULTS: The primary outcome was found to be -1.32±0.69 and -1.40±0.69 for the Coretox and Botox groups, respectively. MT10107 showed a non-inferior efficacy compared with onabotulinum toxin A, as the 95% confidence interval for between-group differences was -0.10 to 0.27 and the upper limit was less than the non-inferiority margin of 0.45. Regarding the secondary outcomes, MAS scores for all muscles and DAS scores showed a significant improvement at all time points in both groups, with no significant between-group difference. No significant between-group differences were observed regarding response rate, global assessment of treatment, and safety measures. CONCLUSIONS: MT10107 showed no significant difference in efficacy and safety compared with onabotulinum toxin A in poststroke upper limb spasticity treatment.

Effect of Extracorporeal Shockwave Therapy Versus Intra-articular Injections of Hyaluronic Acid for the Treatment of Knee Osteoarthritis.

OBJECTIVE: To evaluate and compare the effects and outcomes of extracorporeal shock wave therapy (ESWT) and intra-articular injections of hyaluronic acid (HA) in patients with knee osteoarthritis (OA). METHODS: Of the 78 patients recruited for the study, 61 patients met the inclusion criteria. The enrolled patients were randomly divided into two groups: the ESWT group and the HA group. The ESWT group underwent 3 sessions of 1,000 shockwave pulses performed on the affected knee with the dosage adjusted to 0.05 mJ/mm2 energy. The HA group was administered intra-articular HA once a week for 3 weeks with a 1-week interval between each treatment. The results were measured with the visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index, 40-m fast-paced walk test, and stair-climb test (SCT). A baseline for each test was measured before treatment and then the effects of the treatments were measured by each test at 1 and 3 months after treatment. RESULTS: In both groups, the scores of the VAS, WOMAC, Lequesne index, 40-m fast-paced walk test, and SCT were significantly improved in a time-dependent manner (p<0.01). There were no statistically significant differences measured at 1 and 3 months after treatment between the two groups (p>0.05). CONCLUSION: The ESWT can be an alternative treatment to reduce pain and improve physical functions in patients with knee OA.

Correction: Effectiveness of Lower Energy Density Extracorporeal Shock Wave Therapy in the Early Stage of Avascular Necrosis of the Femoral Head.

[This corrects the article on p. 871 in vol. 40, PMID: 27847717.].

Effects of Repetitive Transcranial Magnetic Stimulation Over Trunk Motor Spot on Balance Function in Stroke Patients.

OBJECTIVE: To assess the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) on balance function in patients with chronic stroke. METHODS: Thirty participants with chronic stroke were enrolled in this study. High frequency (10 Hz) rTMS was delivered with butterfly-coil on trunk motor spot. Each patient received both real and sham rTMS in a random sequence. The rTMS cycles (real or sham) were composed of 10 sessions each, administered over two weeks, and separated by a 4-week washout period. Balance function was measured by Berg Balance Scale and computerized dynamic posturography to determine the effect of rTMS before and one day after the end of each treatment period, as well as at a 1-month follow-up. RESULTS: The balance function was significantly improved after high frequency rTMS as compared with that after sham rTMS (p<0.05). There was no serious adverse effect in patients during the treatment period. CONCLUSION: In the chronic stroke patients, high frequency rTMS to the trunk motor area seems to be a helpful way to improve balance function without any specific adverse effects. Further studies are needed to identify the underlying mechanism and generate a detailed protocol.

Effectiveness of Lower Energy Density Extracorporeal Shock Wave Therapy in the Early Stage of Avascular Necrosis of the Femoral Head.

OBJECTIVE: To evaluate the effectiveness of lower energy flux density (EFD) extracorporeal shock wave therapy (ESWT) in the early stage of avascular necrosis (AVN) of the femoral head. METHODS: Nineteen patients and 30 hips were enrolled. All subjects received 4 weekly sessions of ESWT, at different energy levels; group A (n=15; 1,000 shocks/session, EFD per shock 0.12 mJ/mm2) and group B (n=15; 1,000 shocks/session, EFD per shock 0.32 mJ/mm2). We measured pain by using the visual analog scale (VAS), and disability by using the Harris hip score, Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). To determine the effect of the lower EFD ESWT, we assessed the VAS, Harris hip score, HOOS, WOMAC of the subjects before and at 1, 3, and 6 months. RESULTS: In both groups, the VAS, Harris hip score, HOOS, and WOMAC scores improved over time (p<0.05). CONCLUSION: Lower EFD ESWT may be an effective method to improve the function and to relieve pain in the early stage of AVN.

The Dose-Related Effects of Extracorporeal Shock Wave Therapy for Knee Osteoarthritis.

OBJECTIVE: To investigate the dose-related effects of extracorporeal shock wave therapy (ESWT) for knee osteoarthritis. METHODS: Seventy-five subjects were recruited, 60 of which met the inclusion criteria. The patients were randomly classified into two groups: group L, which was a low-energy group (n=30; 1,000 shocks/session; energy flux density [EFD], 0.040 mJ/mm(2)) and group M, which was a medium-energy group (n=30; 1,000 shocks/session; EFD, 0.093 mJ/mm(2)). For each group, 1,000 shock waves were delivered to the medial tibial plateau area, once a week, for 3 weeks. The main outcome measures were the visual analogue scale (VAS), the Roles and Maudsley (RM) score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and the Lequesne index. Each assessment was performed at the baseline and at 1, 4, and 12 weeks after ESWT. RESULTS: In both groups, the VAS, the RM and WOMAC scores, and the Lequesne index were significantly improved over time (p<0.001), and group M showed greater improvement over group L at the 1, 4 and 12 weeks assessments. CONCLUSION: In this study, medium-energy group (group M) showed greater improvement in regard to relieving pain and restoring functional outcome than the low-energy group (group L). Therefore, EFD can be considered to have significant influence when treating with ESWT for knee osteoarthritis.