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Abstract This study investigated whether machine learning (ML) has better predictive accuracy than logistic regression analysis (LR) for gait independence at discharge in subacute stroke patients (n = 843) who could not walk independently at admission. We developed prediction models using LR and five ML algorithms—specifically, the decision tree (DT), support vector machine, artificial neural network, ensemble learning, and k-nearest neighbor methods. Functional Independence Measure sub-items were used to evaluate the ability to walk independently. Model predictive accuracies were evaluated using areas under receiver operating characteristic curves (AUCs) as well as accuracy, precision, recall, F1 score, and specificity. The AUC for DT (0.812) was significantly lower than those for the other algorithms (p

Abstract Background Restoring shoulder function is critical for upper-extremity rehabilitation following a stroke. The complex musculoskeletal anatomy of the shoulder presents a challenge for safely assisting elevation movements through robotic interventions. The level of shoulder elevation assistance in rehabilitation is often based on clinical judgment. There is no standardized method for deriving an optimal level of assistance, underscoring the importance of addressing abnormal movements during shoulder elevation, such as abnormal synergies and compensatory actions. This study aimed to investigate the effectiveness and safety of a newly developed shoulder elevation exoskeleton robot by applying a novel optimization technique derived from the muscle synergy index. Methods Twelve chronic stroke participants underwent an intervention consisting of 100 robot-assisted shoulder elevation exercises (10 × 10 times, approximately 40 min) for 10 days (4–5 times/week). The optimal robot assist rate was derived by detecting the change points using the co-contraction index, calculated from electromyogram (EMG) data obtained from the anterior deltoid and biceps brachii muscles during shoulder elevation at the initial evaluation. The primary outcomes were the Fugl–Meyer assessment-upper extremity (FMA-UE) shoulder/elbow/forearm score, kinematic outcomes (maximum angle of voluntary shoulder flexion and elbow flexion ratio during shoulder elevation), and shoulder pain outcomes (pain-free passive shoulder flexion range of motion [ROM] and visual analogue scale for pain severity during shoulder flexion). The effectiveness and safety of robotic therapy were examined using the Wilcoxon signed-rank sum test. Results All 12 patients completed the procedure without any adverse events. Two participants were excluded from the analysis because the EMG of the biceps brachii was not obtained. Ten participants (five men and five women; mean age: 57.0 [5.5] years; mean FMA-UE total score: 18.7 [10.5] points) showed significant improvement in the FMA-UE shoulder/elbow/forearm score, kinematic outcomes, and pain-free passive shoulder flexion ROM (P

Abstract Post-stroke disability affects patients’ lifestyles after discharge, and it is essential to predict functional recovery early in hospitalization to allow time for appropriate decisions. Previous studies reported important clinical indicators, but only a few clinical indicators were analyzed due to insufficient numbers of cases. Although review articles can exhaustively identify many prognostic factors, it remains impossible to compare the contribution of each predictor. This study aimed to determine which clinical indicators contribute more to predicting the functional independence measure (FIM) at discharge by comparing standardized coefficients. In this study, 980 participants were enrolled to build predictive models with 32 clinical indicators, including the stroke impairment assessment set (SIAS). Trunk function had the most significant standardized coefficient of 0.221. The predictive models also identified easy FIM sub-items, SIAS, and grip strength on the unaffected side as having positive standardized coefficients. As for the predictive accuracy of this model, R2 was 0.741. This is the first report that included FIM sub-items separately in post-stroke predictive models with other clinical indicators. Trunk function and easy FIM sub-items were included in the predictive model with larger positive standardized coefficients. This predictive model may predict prognosis with high accuracy, fewer clinical indicators, and less effort to predict.

Study Design This is a single-center retrospective cohort study with a university hospital setting. Purpose This study aims to evaluate the short-term course of physical function and walking ability after intramedullary spinal cord tumor (ISCT) resection and predict walking independence 1 year after surgery. Overview of Literature Although several reports have shown the postoperative functional prognosis of spinal intramedullary tumors with long-term follow-up, no reports have identified the predictors associated with the functional outcome at an early stage. Methods A total of 79 individuals who underwent ISCT resection at our institute between 2014 and 2019 were enrolled in the study, whose preoperative walking state was independent ambulator regardless of cane support with the Functional Independence Measure Locomotor Scale (FIM-L) score of ≥6. The FIM-L, the American Spinal Injury Association (ASIA) motor and sensory scores in the lower extremities, and the Walking Index for Spinal Cord Injury II (WISCI II) were assessed for walking independence, lower-limb function, and walking ability, respectively. These evaluations were performed at 4 time points: preoperatively, 1 week (1W), 2 weeks (2W), and 1 year after surgery. Results In the early phase after surgery, 71% and 43% of the participants were nonindependent ambulators at 1W and 2W, respectively. Histopathology indicated that patients with solid tumors (ependymoma, astrocytoma, or lipoma) showed significantly lower indices at 1W and 2W than those with vascular tumors (hemangioblastoma or cavernous hemangioma). Regarding tumor location, thoracic cases exhibited poorer lower-limb function at 1W and 2W and poorer walking ability at 2W than cervical cases. According to the receiver operating characteristic (ROC) analysis, 2 WISCI II points at 2W had the highest sensitivity (100%) and specificity (92.2%) in predicting the level of walking independence at 1 year postoperatively (the area under the ROC curve was 0.99 (95% confidence interval, 0.93–1.00). Conclusions The higher the lower-limb function scores in the early phase, the better the improvement in walking ability is predicted 1 year after ISCT resection.

ObjectiveThis study aimed to classify and calculate the minimal detectable changes (MDC) in gait time and gait speed in a 10-meter walking test (10MWT) in patients with stroke classified according to their gait speed.MethodsThe participants were 84 patients with stroke. Their gait times were measured twice each at their comfortable gait speed (CGS) and maximum gait speed (MGS) on a 10-meter straight track, and gait speed was calculated using gait time. Participants were assigned to three speed groups based on their CGS: low-speed (0.8 m/s; n = 36). For each group, first and second retest reliability and MDC of CGS and MGS were calculated using gait time and gait speed in the 10MWT.ResultsMDCs in the 10MWT at CGS were: low-speed group, gait time 5.25 s, gait speed 0.05 m/s; moderate-speed group, gait time 2.83 s, gait speed 0.11 m/s; and high-speed group, gait time 1.58 s, gait speed 0.21 m/s. MDCs in the 10MWT at MGS were: low-speed group, gait time 7.26 s, gait speed 0.04 m/s; moderate-speed group, gait time 2.48 s, gait speed 0.12 m/s; and high-speed group, gait time 1.28 s, gait speed 0.19 m/s.ConclusionSince the MDC of gait speed and gait time differ depending on the participant’s gait speed, it is necessary to interpret the results according to the participant’s gait speed when judging the effectiveness of therapeutic interventions.

Abstract Background Therapeutic exercise for gait function using an exoskeleton-assisted Body Weight Supported Treadmill Training (BWSTT) has been identified as a potential intervention that allows for task-based repetitive training with appropriate kinematics while adjusting the amount of body weight support (BWS). Nonetheless, its effect on gait in patients with stroke in the chronic phase are yet to be clarified. The primary aim of this scoping review was to present the status of effectiveness of exoskeleton-assisted BWSTT in patients with chronic stroke. The secondary aims were to summarise intervention protocols, types and functions of BWSTT exoskeletal robotic devices currently used clinically. Method and results Articles were accessed and collected from PubMed, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases, which were completed in October 2020. Articles were included if the subjects were adults with stroke in the chronic phase (onset ≥ 6 months) and if they utilised a robotic exoskeleton with treadmill and body weight support and investigated the efficacy of gait exercise. A total of 721 studies were identified, of which 11 randomised controlled trials were selected. All included studies were published from 2008 to 2020. Overall, 309 subjects were enrolled; of these, 241 (156 males, 85 females) participated. Walking outcome measures were used more often to evaluate the functional aspects of gait than to evaluate gait independence. In 10 of 11 studies, showed the effectiveness of exoskeleton robot-assisted BWSTT in terms of outcomes contributing to improved gait function. Two studies reported that exoskeleton-assisted BWSTT with combination therapy was significantly more effective in improving than exoskeleton-assisted BWSTT alone. However, no significant difference was identified between the groups; compared with therapist-assisted BWSTT groups, exoskeleton-assisted BWSTT groups did not exhibit significant change. Conclusion This review suggests that exoskeleton-assisted BWSTT for patients with chronic stroke may be effective in improving walking function. However, the potential may be “to assist” and not because of using the robot. Further studies are required to verify its efficacy and strengthen evidence on intervention protocols.

Abstract The present study aimed to determine the magnitude of and risk factors for the effects of the COVID-19 pandemic on the international classification of functioning, disability and health (ICF) in patients with multiple system atrophy (PwMSA). The study was part of a cross-sectional, nationwide, multipurpose mail survey for Japanese PwMSA from October to December, 2020. The primary outcome was the impact of the early COVID-19 pandemic on ICF functioning, consisting of body function, activity, and participation. Age, sex, disease type, disease duration, and dwelling place were asked as participants’ characteristics, and the multiple system impairment questionnaire (MSIQ), patient health questionnaire-2, modified rankin scale, barthel index, life-space assessment (LSA), and EuroQoL were examined. Multivariate logistic regression analyses were performed to identify independent risk factors for a worse function score due to the COVID-19 pandemic for each ICF functioning domain. A total of 155 patients (mean age 65.6 [SD 8.1] years; 43.9% women; mean disease duration 8.0 [SD 6.2] years; 65% MSA with cerebellar ataxia, 13% MSA with parkinsonism, 9% MSA with predominant autonomic features) were analyzed. Of the ICF functioning domains, the respondents reported that the early COVID-19 pandemic affected body function in 17.4%, activity in 17.6%, and participation in 46.0%. The adjusted multivariate model identified MSIQ and LSA as the two variables that independently contributed to all domains. The COVID-19 pandemic affected ICF functioning of PwMSA in Japan, and the severity of disease-related impairments and a large daily living space were common risk factors. These results help support the focus on patient characteristics for medical and social welfare support.

Asymmetrically impaired standing control is a prevalent disability among stroke patients; however, most of the neuromuscular characteristics are unclear. Therefore, the main purpose of this study was to investigate between-limb differences in intermuscular coherence during quiet standing. Consequently, 15 patients who had sub-acute stroke performed a quiet standing task without assistive devices, and electromyography was measured on the bilateral tibialis anterior (TA), soleus (SL), and medial gastrocnemius (MG). The intermuscular coherence of the unilateral synergistic (SL–MG) pair and unilateral antagonist (TA–SL and TA–MG) pairs in the delta (0–5 Hz) and beta (15–35 Hz) bands were calculated and compared between the paretic and non-paretic limbs. The unilateral synergistic SL–MG coherence in the beta band was significantly greater in the non-paretic limb than in the paretic limb (p = 0.017), while unilateral antagonist TA–MG coherence in the delta band was significantly greater in the paretic limb than in the non-paretic limb (p < 0.01). During quiet standing, stroke patients showed asymmetry in the cortical control of the plantar flexor muscles, and synchronous control between the antagonistic muscles was characteristic of the paretic limb. This study identified abnormal muscle activity patterns and asymmetrical cortical control underlying impaired standing balance in patients with sub-acute stroke using an intermuscular coherence analysis.

Abstract Aim To investigate the cognitive function and its relation to the home discharge of patients following subacute stroke. Methods This retrospective cohort study included 1,229 convalescent patients experiencing their first subacute stroke. We determined discharge destination and demographic and clinical information. We recorded the following measurement scores: Mini-Mental State Examination (MMSE) score, Stroke Impairment Assessment Set score, grip strength, and Functional Independence Measure (FIM). We performed a multivariable logistic regression analysis with the forced-entry method to identify factors related to home discharge. Results Of the 1,229 participants (mean age: 68.7 ± 13.5 years), 501 (40.8%), 735 (59.8%), and 1,011 (82.3%) were female, had cerebral infarction, and were home discharged, respectively. Multivariable logistic regression analysis revealed that age (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.91 – 0.96; P

ObjectivesStepwise linear regression (SLR) is the most common approach to predicting activities of daily living at discharge with the Functional Independence Measure (FIM) in stroke patients, but noisy nonlinear clinical data decrease the predictive accuracies of SLR. Machine learning is gaining attention in the medical field for such nonlinear data. Previous studies reported that machine learning models, regression tree (RT), ensemble learning (EL), artificial neural networks (ANNs), support vector regression (SVR), and Gaussian process regression (GPR), are robust to such data and increase predictive accuracies. This study aimed to compare the predictive accuracies of SLR and these machine learning models for FIM scores in stroke patients.MethodsSubacute stroke patients (N = 1,046) who underwent inpatient rehabilitation participated in this study. Only patients' background characteristics and FIM scores at admission were used to build each predictive model of SLR, RT, EL, ANN, SVR, and GPR with 10-fold cross-validation. The coefficient of determination (R2) and root mean square error (RMSE) values were compared between the actual and predicted discharge FIM scores and FIM gain.ResultsMachine learning models (R2 of RT = 0.75, EL = 0.78, ANN = 0.81, SVR = 0.80, GPR = 0.81) outperformed SLR (0.70) to predict discharge FIM motor scores. The predictive accuracies of machine learning methods for FIM total gain (R2 of RT = 0.48, EL = 0.51, ANN = 0.50, SVR = 0.51, GPR = 0.54) were also better than of SLR (0.22).ConclusionsThis study suggested that the machine learning models outperformed SLR for predicting FIM prognosis. The machine learning models used only patients' background characteristics and FIM scores at admission and more accurately predicted FIM gain than previous studies. ANN, SVR, and GPR outperformed RT and EL. GPR could have the best predictive accuracy for FIM prognosis.

Body weight-supported treadmill training with the voluntary driven exoskeleton (VDE-BWSTT) has been shown to improve the gait function of patients with chronic spinal cord injury. However, little is known whether VDE-BWSTT can effectively improve the trunk function of patients with chronic spinal cord injury. In this open-label, single-arm study, nine patients with chronic spinal cord injury at the cervical or thoracic level (six males and three females, aged 37.8 ± 15.6 years, and time since injury 51.1 ± 31.8 months) who underwent outpatient VDE-BWSTT training program at Keio University Hospital, Japan from September 2017 to March 2019 were included. All patients underwent twenty 60-minute gait training sessions using VDE. Trunk muscular strength, i.e., the maximum force against which patient could maintain a sitting posture without any support, was evaluated in four directions: anterior, posterior, and lateral (right and left) after 10 and 20 training sessions. After intervention, lateral muscular strength significantly improved. In addition, a significant positive correlation was detected between the change in lateral trunk muscular strength after 20 training sessions relative to baseline and gait speed. The change in trunk muscular strength after 20 training sessions relative to baseline was greatly correlated with patient age. This suggests that older adult patients with chronic spinal cord injury achieved a greater improvement in trunk muscle strength following VDE-BWSTT. All these findings suggest that VDE-BWSTT can improve the trunk function of patients with chronic spinal cord injury and the effect might be greater in older adult patients. The study was approved by the Keio University of Medicine Ethics Committee (IRB No. 20150355-3) on September 26, 2017.

The risk of pneumonia and death is higher in acute stroke patients with signs of pulmonary infection on chest computed tomography (CT) at admission. However, few reports have examined the incidence of pneumonia and its predictors in subacute stroke patients. The aim of this study was to examine factors related to post-stroke pneumonia in subacute stroke patients. A total of 340 subacute stroke patients were included. Univariable logistic regression analysis was performed using variables that may contribute to pneumonia, with the development of pneumonia as the dependent variable. Multivariable logistic regression analysis using the three independent variables with the lowest p-values on the univariable logistic regression analysis was also performed to calculate adjusted odds ratios. Twenty-two patients developed pneumonia during hospitalization. The univariable logistic regression analysis showed that the top three items were serum albumin (Alb), functional Oral Intake Scale (FOIS) score, and signs of pulmonary infection on chest CT at admission. Multivariable logistic regression analysis adjusted for these three items showed that the presence of signs of pulmonary infection on chest CT at admission was the independent variable (OR: 4.45; 95% CI: 1.54–12.9). When signs of pulmonary infection are seen on admission chest CT, careful follow-up is necessary because pneumonia is significantly more likely to occur during hospitalization.

Abstract Stem cell-based regenerative therapy has opened an avenue for functional recovery of patients with spinal cord injury (SCI). Regenerative rehabilitation is attracting wide attention owing to its synergistic effects, feasibility, non-invasiveness, and diverse and systemic properties. In this review article, we summarize the features of rehabilitation, describe the mechanism of combinatorial treatment, and discuss regenerative rehabilitation in the context of SCI. Although conventional rehabilitative methods have commonly been implemented alone, especially in studies of acute-to-subacute SCI, the combinatorial effects of intensive and advanced methods, including various neurorehabilitative approaches, have also been reported. Separating the concept of combined rehabilitation from regenerative rehabilitation, we suggest that the main roles of regenerative rehabilitation can be categorized as conditioning/reconditioning, functional training, and physical exercise, all of which are indispensable for enhancing functional recovery achieved using stem cell therapies.

Objective:This study aimed to investigate the effect of robot-assisted gait training (RAGT) therapy combined with non-invasive brain stimulation (NIBS) on lower limb function in patients with stroke and spinal cord injury (SCI).Data sourcesPubMed, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Web of Science were searched.Study selectionRandomized controlled trials (RCTs) published as of 3 March 2021. RCTs evaluating RAGT combined with NIBS, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), for lower limb function (e.g., Fugl-Meyer assessment for patients with stroke) and activities (i.e., gait velocity) in patients with stroke and SCI were included.Data extractionTwo reviewers independently screened the records, extracted the data, and assessed the risk of bias.Data synthesisA meta-analysis of five studies (104 participants) and risk of bias were conducted. Pooled estimates demonstrated that RAGT combined with NIBS significantly improved lower limb function [standardized mean difference (SMD) = 0.52; 95% confidence interval (CI) = 0.06–0.99] but not lower limb activities (SMD = −0.13; 95% CI = −0.63–0.38). Subgroup analyses also failed to find a greater improvement in lower limb function of RAGT with tDCS compared to sham stimulation. No significant differences between participant characteristics or types of NIBS were observed.ConclusionThis meta-analysis demonstrated that RAGT therapy in combination with NIBS was effective in patients with stroke and SCI. However, a greater improvement in lower limb function and activities were not observed using RAGT with tDCS compared to sham stimulation.

IntroductionDysphagia is one of the most clinically significant disabilities in patients with multiple system atrophy (MSA), because it can cause aspiration pneumonia, which is potentially fatal. In this study, the Neuromuscular disease Swallowing Status Scale (NdSSS), which was developed to evaluate dysphagia in patients with neuromuscular diseases, was used to evaluate patients with MSA. In addition, correlation between a history of pneumonia and swallowing function was evaluated.MethodsStudy 1: Reliability, concurrent validity, and responsiveness of the NdSSS in patients with MSA. In 81 patients for whom evaluation items could be collected, the NdSSS was tested for its interrater and intrarater reliability using weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with existing scales (Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scale (FILS), and the unified MSA rating scale (UMSARS)) using Spearman's rank correlation coefficients. Sixty-three patients were evaluated by videofluorographic (VF) swallowing examination. To evaluate concurrent validity, Spearman's rank correlation coefficients were calculated between the NdSSS and VF swallowing assessments. Additionally, scale responsiveness was determined using the standardized response mean (SRM) in 23 patients who could be followed up to assess their long-term course. Study 2: Cross-sectional survey of swallowing function and history of pneumonia. Data regarding history of pneumonia, UMSARS, NdSSS, age, sex, MSA subtype, and disease duration were retrospectively obtained from the medical records of 113 patients with MSA. Differences in these parameters and NdSSS stage between those with and without a history of pneumonia were examined using the Mann-Whitney test or chi-squared test. Furthermore, clinical factors related to a history of pneumonia were examined by binomial logistic regression analysis.ResultsThe NdSSS showed satisfactory reliability, concurrent validity, and responsiveness. A history of pneumonia was related to the severity of MSA, age, MSA subtype, and NdSSS stage. Binomial logistic regression analysis showed that NdSSS stage (odds ratio (OR), 0.490; 95% confidence interval (CI), 0.301–0.797, p = 0.001) and MSA subtype (OR, 4.031; 95% CI, 1.225–13.269, p = 0.021) were significantly associated with a history of pneumonia.ConclusionsIn patients with MSA, the NdSSS has sufficient reliability, concurrent validity, and responsiveness for assessing dysphagia. Patients with a history of pneumonia have more severe dysphagia. We found that the pneumonia risk was related to NdSSS stage and MSA-p (predominantly parkinsonism). Meticulous care to prevent aspiration is needed from early stages of the disease.

Human behavior requires inter-regional crosstalk to employ the sensorimotor processes in the brain. Although external neuromodulation techniques have been used to manipulate interhemispheric sensorimotor activity, a central controversy concerns whether this activity can be volitionally controlled. Experimental tools lack the power to up- or down-regulate the state of the targeted hemisphere over a large dynamic range and, therefore, cannot evaluate the possible volitional control of the activity. We addressed this difficulty by using the recently developed method of spatially bivariate electroencephalography (EEG)-neurofeedback to systematically enable the participants to modulate their bilateral sensorimotor activities. Here, we report that participants learn to up- and down-regulate the ipsilateral excitability to the imagined hand while maintaining constant contralateral excitability; this modulates the magnitude of interhemispheric inhibition (IHI) assessed by the paired-pulse transcranial magnetic stimulation (TMS) paradigm. Further physiological analyses revealed that the manipulation capability of IHI magnitude reflected interhemispheric connectivity in EEG and TMS, which was accompanied by intrinsic bilateral cortical oscillatory activities. Our results show an interesting approach for neuromodulation, which might identify new treatment opportunities, e.g., in patients suffering from a stroke.

Genu recurvatum (knee hyperextension) is a common problem after stroke. It is important to promote the coordination between knee and ankle movements during gait; however, no study has investigated how multi-joint assistance affects genu recurvatum. We are developing a gait training technique that uses robotized knee-ankle-foot orthosis (KAFO) to assists the knee and ankle joints simultaneously. This report aimed to investigate the safety of robotized KAFO-assisted gait training (Experiment 1) and a clinical trial to treat genu recurvatum in a patient with stroke (Experiment 2). Six healthy participants and eight patients with chronic stroke participated in Experiment 1. They received robotized KAFO-assisted gait training for one or 10 sessions. One patient with chronic stroke participated in Experiment 2 to investigate the effect of robotized KAFO-assisted gait training on genu recurvatum. The patient received the training for 30 min/day for nine days. The robot consisted of KAFO and an attached actuator of four pneumatic artificial muscles. The assistance parameters were adjusted by therapists to prevent genu recurvatum during gait. In Experiment 2, we evaluated the knee joint angle during overground gait, Fugl-Meyer Assessment of lower extremity (FMA-LE), modified Ashworth scale (MAS), Gait Assessment and Intervention Tool (G.A.I.T.), 10-m gait speed test, and 6-min walk test (6MWT) before and after the intervention without the robot. All participants completed the training in both experiments safely. In Experiment 2, genu recurvatum, FMA-LE, MAS, G.A.I.T., and 6MWT improved after robotized KAFO-assisted gait training. The results indicated that the multi-joint assistance robot may be effective for genu recurvatum after stroke.

Aims: Therapy with kinesthetic illusion of segmental body part induced by visual stimulation (KINVIS) may allow the treatment of severe upper limb motor deficits in post-stroke patients. Herein, we investigated: (1) whether the effects of KINVIS therapy with therapeutic exercise (TherEx) on motor functions were induced through improved spasticity, (2) the relationship between resting-state functional connectivity (rs-FC) and motor functions before therapy, and (3) the baseline characteristics of rs-FC in patients with the possibility of improving their motor functions.Methods: Using data from a previous clinical trial, three path analyses in structural equation modeling were performed: (1) a mediation model in which the indirect effects of the KINVIS therapy with TherEx on motor functions through spasticity were drawn, (2) a multiple regression model with pre-test data in which spurious correlations between rs-FC and motor functions were controlled, and (3) a multiple regression model with motor function score improvements between pre- and post-test in which the pre-test rs-FC associated with motor function improvements was explored.Results: The mediation model illustrated that although KINVIS therapy with TherEx did not directly improve motor function, it improved spasticity, which led to ameliorated motor functions. The multiple regression model with pre-test data suggested that rs-FC of bilateral parietal regions is associated with finger motor functions, and that rs-FC of unaffected parietal and premotor areas is involved in shoulder/elbow motor functions. Moreover, the multiple regression model with motor function score improvements suggested that the weaker the rs-FC of bilateral parietal regions or that of the supramarginal gyrus in an affected hemisphere and the cerebellar vermis, the greater the improvement in finger motor function.Conclusion: The effects of KINVIS therapy with TherEx on upper limb motor function may be mediated by spasticity. The rs-FC, especially that of bilateral parietal regions, might reflect potentials to improve post-stroke impairments in using KINVIS therapy with TherEx.

The effective therapy for pulmonary arterial hypertension (PAH) with inadequate clinical response is scarce except for lung transplantation when prostacyclin infusion is ineffective. The purpose of this study is to investigate the efficacy and safety of selexipag in addition to the infusion of prostacyclin. Nine patients [median 38 (36–49) years of age; 78% female] with PAH whose clinical response was inadequate despite the use of prostacyclin infusion analogs, were evaluated. Addition of selexipag significantly improved hemodynamics and no serious adverse events were observed. Selexipag with prostacyclin infusion analogs can be an effective therapeutic strategy for the PAH patients with inadequate clinical response.

Background. The biopsychosocial mechanism by which exercise leads to improvement in chronic low back pain (CLBP) remains unstudied. This prospective cohort study was performed to examine the effectiveness of exercise on pain, disability, and psychological status for CLBP. We also tested path analytic models in which changes in these variables were included. Methods. CLBP patients who visited the Interdisciplinary Pain Center of Keio University Hospital from July 2018 to April 2020 were included. The propensity score matching was performed between patients who underwent exercise (the exercise group) and those who did not (the control group). At the first visit and at the 3-month follow-up, pain (Numerical Rating Scale (NRS)), disability (Pain Disability Assessment Scale (PDAS)), and psychological status (Pain Self-Efficacy Questionnaire (PSEQ), and Pain Catastrophizing Scale (PCS)) were assessed. Changes in pain and disability at the follow-up were compared between the groups. The relationships between changes in pain, disability, and psychological variables were examined using Pearson’s correlation and mediation analysis. Results. A significantly larger decrease in the PDAS was observed in the exercise group (N = 49) than in the control (N = 49) (p

Objectives: To investigate the physical, cognitive, and psychological factors related to daily step count in patients with subacute stroke. Design: Prospective cohort study. Setting: A subacute rehabilitation ward with 160 beds. Participants: Patients with subacute stroke who could walk independently (N=101). Among the 101 participants enrolled in this study (mean age, 64.5±13.5y), 64.4% (n=65) were men and 69.3% (n=70) were patients with cerebral infarction. Interventions: We assessed ambulatory activity using a pedometer placed in the pants pocket on the nonparalyzed side continuously for 7 consecutive days. We also obtained demographic and clinical information and recorded the following measurement scores: Stroke Impairment Assessment Set, FIM, Mini-Mental State Examination (MMSE), Self-Rating Depression Scale, and Apathy Scale. All measurements were collected at admission and discharge. Main Outcome Measures: The outcomes assessed were ambulatory activity, motor and sensory functions, functional disability, cognitive function, depressive symptoms, and motivation. Results: The median daily steps ambulated at admission and discharge were 5584 steps (interquartile range, 3763-7096 steps) and 5991 steps (interquartile range, 4329-8204 steps), respectively. In the univariate regression analysis, age, sex, serum albumin level, affected side of the brain, and MMSE score at admission were significantly associated with the daily step count at discharge. Multiple regression analysis using these 5 items as independent variables revealed that the MMSE score at admission (reference, 28-30 points; B, −2.07; 95% confidence interval, −3.89 to −0.35; β, −0.22; P=.027) was significantly associated with the daily step count at discharge. Conclusions: Cognitive function at admission had a significant association with the daily step count at discharge in patients with subacute stroke who could walk independently.

Objective: There are a lack of disaster preparedness measures that target populations with dysphagia. In particular, disaster response plans frequently overlook differences in textures between emergency foods and regularly consumed foods. The aim of this study was to estimate the number of community-dwelling elderly care recipients requiring specific food preparations, including the population at risk of aspiration when solely consuming common emergency foods. Design: A cross-sectional study. Patients: Community-dwelling elderly care recipients who were certified by the public long-term care insurance system in Japan and registered at one of 77 care managing offices in Shinjuku city. Methods: Special needs regarding food intake and risks associated with receiving emergency foods were assessed by government-certified care managers. Results: Data were acquired from 1,271 care recipients. Notably, 23.1% of the sampled population had special needs regarding food intake at all times (e.g. non-oral intake or need for texture-modified foods). An additional 11.5% were estimated to experience difficulty when ingesting common emergency foods, despite the ability to consume regular foods. Conclusion: A relatively large portion of community-dwelling elderly people will be at risk of aspiration due to the intake of commonly distributed emergency foods following a disaster. Appropriate preparation based on an assessment of special needs regarding food intake is therefore required when planning for future disasters.

Background: The evidence regarding triple oral combination therapy for patients with pulmonary arterial hypertension (PAH) is scarce. This study was performed to investigate the effectiveness and safety of triple oral combination therapy with macitentan, riociguat, and selexipag. Methods: Among consecutive patients with PAH who were referred to our hospital from 2009 to 2020, those who underwent triple oral combination therapy using macitentan, riociguat, and selexipag were retrospectively analyzed. Hemodynamic and echocardiographic assessments and Kaplan–Meier analyses of all-cause death and initiation of prostacyclin infusion were conducted. Results: Twenty-six patients underwent this combination therapy. These patients were predominantly female (73.1%) with a median age of 38 years at baseline and nine patients were taking some PAH medications at baseline. The median time from initiation of the first PAH drug to the third PAH drug in treatment naïve patients was 24 days (interquartile range, 12–47 days). Four patients (15.0%) discontinued taking any of the three vasodilators because of adverse events, and 17 patients (65.4%) reached the maximum dose of all three drugs. The mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output improved by 29%, 65%, and 82%, respectively (median observation period: 441 days) and similar improvements were observed in treatment-naïve patients at baseline. The survival rate and prostacyclin infusion-free rate since administration of all three vasodilators was 93.3% and 74.6% at 3 years, respectively. When patients were divided by risk stratification, the prostacyclin-free rate at 3 years was 92.9% in low-/intermediate-risk patients and 55.0% in high-risk patients. Conclusion: Triple oral combination therapy with macitentan, riociguat, and selexipag sufficiently improved clinical parameters and was well tolerated in patients with PAH. This combination could be a particularly promising strategy in patients with low/intermediate risk and possibly even in half of patients with high risk. Further studies are needed to validate these findings. The reviews of this paper are available via the supplemental material section.

Background: Somatosensory impairment is common in patients who have had a stroke and can affect their motor function and activities of daily living (ADL). Therefore, detecting and treating somatosensory impairments properly is considered to be very important, and various examinations have been developed. However, the reliability and validity of few of them have been verified due to differences in the procedure of each examiner or poor quantification by the examination itself.Objective: We hypothesized that, with fixed procedures two convenient clinical examinations, the Semmes-Weinstein Monofilament Test (SWMT) and the Thumb Localizing Test (TLT), could provide reliable assessments of light touch sensation and proprioception. The purpose of this study was to verify the reliability and validity of these two examinations as indices of somatosensory impairment of the upper extremity (UE) in patients with chronic post-stroke hemiparesis.Methods: Fifty patients with chronic stroke (median time after onset of stroke, 848 [474–1708] days, mean age 57 [standard deviation 14] years) were enrolled at Keio University Hospital from 2017 to 2018. Examiners learned the original method of the SWMT and the TLT rigorously and shared it with each other. The TLT procedure was partially modified by dividing the location of the patient's thumb into four spaces. Two examiners evaluated the SWMT and the TLT for 2 days, and intra-rater and inter-rater reliabilities were calculated using weighted kappa statistics. In addition to this, the evaluator size score of the SWMT was assessed with Bland-Altman analysis to evaluate systematic bias. The Stroke Impairment Assessment Set (SIAS) sensory items were used to assess validity, and Spearman's rank correlation coefficients were calculated.Results: Intra/inter-rater agreements of the SWMT grade score were 0.89 (thumb, 95%CI: 0.83–0.95)/ 0.75 (0.60–0.91) and 0.80 (index finger, 0.67–0.93)/0.79 (0.66–0.92), and of the TLT they were 0.83 (navel level proximal space, 0.71–0.95)/ 0.83 (0.73–0.92), 0.90 (navel level distal space, 0.85–0.96)/ 0.80 (0.69–0.90), 0.80 (shoulder level proximal space, 0.68–0.92)/ 0.77 (0.65–0.89), and 0.87 (shoulder level distal space, 0.80–0.93)/ 0.80 (0.68–0.92) (P < 0.001, each item). All of them showed substantial agreement, but the MDC of the SWMT evaluator size was 1.28 to 1.79 in the inter-rater test and 1.94–2.06 in the intra-rater test. The SWMT grade score showed a strong correlation with the SIAS light touch sensation item (r = 0.65, p < 0.001), as did the TLT with the SIAS position sense item (r = −0.70–0.62, p < 0.001 each space).Conclusions: The reliability and validity of the SWMT and the TLT were verified. These tests can be used as reliable sensory examinations of the UE in patients with chronic stroke, and especially for the SWMT, it is more reliable for screening.

AimsThe present study aimed to determine factors associated with the frequency of paralyzed upper extremity (UE) use in chronic stroke patients with severe UE functional deficiency.MethodsWe retrospectively reviewed the medical records of 138 consecutive patients, and 117 was analyzed (median age, 55 [range, 18-85] years; median stroke duration, 24.5 [range, 7-302] months) with chronic hemiparetic stroke who were admitted to our hospital for intensive upper extremity rehabilitation. The mean Fugl-Meyer Assessment (FMA) UE score was 28.6. All of them are independent in their activity of daily living (ADL) and without remarkable cognitive deficits. Amount-of-use score of Motor Activity Log-14 (MAL-AOU) was applied as the index of daily use of affected UE. The following parameters were examined as the explanatory variables: demographics, proximal and distal sub-scores of FMA UE, Modified Ashworth Scale (MAS), and sensory function scores in the Stroke Impairment Assessment Set (SIAS).ResultsThe median MAL-AOU score was 0.57 [range, 0.28-0.80]. Ordinal regression analysis revealed that FMA proximal, FMA distal, and SIAS sensory function (touch) were associated with AOU score of MAL-14 (Pseudo R-square = 0.460).ConclusionNot only motor but also sensory function, especially tactile sensation, play a crucial role in the daily use of affected UE in chronic stroke patients with severe UE hemiparesis.

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to

Background and Purpose: Limited research has been conducted with the aim of understanding which upper extremity movements are difficult for persons with severe chronic stroke. The purpose of this study was to test the structure of the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) using Rasch analysis in persons with chronic stroke with moderate to severe deficits and to determine the item difficulty hierarchy.Methods: This was a secondary analysis of data from previous randomized, controlled trials, or clinical trials. The participants were 101 persons with chronic stroke with moderate to severe hemiparesis (time after onset of stroke, 1375.3 ± 1157.9 days; the 33-item FMA-UE, 31.1 ± 12.8). Principal component analysis and infit statistics were used to evaluate dimensionality. Rasch analysis using a rating scale model was performed, and item difficulty was determined.Results: Six misfit items were removed. The results showed that the 27-item FMA-UE was unidimensional. Rasch analysis showed that the movements performed within synergies were among the easiest items. Shoulder and elbow movements were among the easiest items, whereas forearm and wrist movements were among the moderately to most difficult items. Hand items spanned various difficulty levels.Discussion and Conclusions: The FMA-UE is a valid assessment tool of upper extremity motor function in persons with chronic stroke with moderate to severe deficits. The results showed that item difficulty was consistent with the stepwise recovery course proposed by Fugl-Meyer. The movements that are difficult for patients with moderate to severe chronic paresis were determined, which would enable comparison of each movement using a measure of motion difficulty in future studies.

In post-stroke hemiparesis patients, the skeletal muscle mass decrease rapidly with the histological degradation. We investigated the effect of nutritional supplementation with whey protein and vitamin D on the muscle mass and muscle quality, in post-stroke convalescent rehabilitation patients in a randomized, single-blinded, placebo-controlled trial. Fifty patients were randomly assigned to two groups; HP group received supplemental jelly (100 kcal; whey protein 10 g; vitamin D 20 μg) twice a day throughout up to 16-week period, the control group received placebo jelly. Cross-sectional area (CSA) of thigh muscle, skeletal muscle index (SMI), muscle strength, activity of daily living (ADL), and some nutritional indicators in blood were measured. Although no significant difference was observed in CSA and SMI between the groups, fat infiltration into the thighs muscle was singnificantly lower in the HP group. There were no significant difference in muscle strength and ADL between the groups. Blood urea nitrogen and serum 25(OH)D at endpoint were significantly higher in the HP group but physiological normal ranges. Supplementation with whey protein and vitamin D in post-stroke patients led to suppression of fat infiltration into the muscle. Long-term follow-up studies are needed to verify whether this nutritional intervention provides substantial benefits for the prognosis of stroke survivors.

Objective: To propose alternative learning strategies for glossopharyngeal breathing in patients with Duchenne muscular dystrophy (DMD) and healthy men. Design: A feasibility study with small case series. Subjects: Five boys with DMD and 7 male physical therapists as healthy controls who had not learned glossopharyngeal breathing. Methods: Participants were instructed in a glossopharyngeal breathing protocol, including induction methods comprising sucking motions and phonation with inhalation. The protocol consisted of 1–6 sessions (10–15 min each; total 60 min). Criteria for glossopharyngeal breathing mastery were vital capacity with glossopharyngeal insufflation (VCGI)/VC ratio > 1.10 for the DMD group and > 1.05 for the Healthy group. Feasibility outcomes were time required for mastering glossopharyngeal breathing, self-reported outcomes, adverse events and drop-outs. Results: All participants learned glossopharyngeal breathing within the allocated 60 min. Mean VCGI/VC ratio was 1.31 for the DMD group and 1.09 for the Healthy group. No adverse events or drop-outs were encountered during the protocol. In most cases, self-reported outcomes showed that motivation increased and difficulty decreased. Conclusion: Induction methods for sucking motions and phonation with inhalation for glossopharyngeal breathing learning are feasible. This paper proposes alternative strategies for glossopharyngeal breathing learning in boys with DMD and their instructors.

ObjectivesTo examine the inter-rater reliability of the thumb localizing test (TLT) and its validity against quantitative measures of proprioception.MethodsThe TLT was assessed by two raters in a standardized manner in 40 individuals with hemiparetic stroke. Inter-rater reliability was examined with weighted Kappa. For the quantitative measures, a bimanual matching task in a planar robotic device was performed. Without vision, each participant moved the unaffected hand to the perceived mirrored location of the affected hand, which was passively moved by the robot. Three measures were taken after 54 trials: Variability, trial-to-trial variability of the mirrored-matched locations; Area, the ratio of the area enclosed by the active hand relative to the passive hand; and Shift, systematic shifts between the passive and active hands. The correlation between the TLT and each robotic measure was examined with Spearman's rank correlation coefficient.ResultsThe overall weighted kappa of the TLT was 0.84 (PConclusionsThe TLT had a high inter-rater reliability, and was validated against quantitative measures of proprioception reflecting the perceived area of movement and variability of the limb location.

Objective: To clarify the activities of daily living (ADL) structure of persons with spinal cord injury (SCI) by analyzing the associations between the Spinal Cord Independence Measure III (SCIM III) total score and individual SCIM III item scores. Design: A retrospective survey. Setting: A national hospital with 2 SCI units in Japan. Participants: Inpatients (N=81) within 60 days of SCI onset were included (men, 84%). The mean age was 62 years. Of these, 63 persons had incomplete SCI (47 persons had tetraplegia). Interventions: Not applicable. Main Outcome Measure: SCIM III was used to assess the ADL independence level on a monthly basis during hospitalization. SCIM III data were analyzed with ordinal logistic analyses. Results: The analyses revealed that SCIM III total scores accounted for the probabilities of individual SCIM III item scores. Goodness-of-fit of each logistic model by Wald test was significant (P10 attained modified independence level. Conclusions: The SCIM III total score can provide information on the probability and degree of difficulty of attaining independence for each item. Therefore, the present total SCIM III scores could be the indication for ADL attainment. In addition, the higher total SCIM III score and the probability of individual items score are useful for planning efficient rehabilitative approaches, considering the degree of difficulty of attaining independence for each item. Moreover, our results show good generalizability across patients with complete and incomplete SCI. Keywords: Paraplegia, Probability, Prognosis, Rehabilitation, Tetraplegia

Background: Somatosensory function has been frequently overlooked in clinics and research in the field of chronic stroke. The effects of neurorehabilitation interventions on sensory processing have still to be investigated using electrophysiological means. This study investigated the effect of hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy utilizing closed-loop electromyography-controlled neuromuscular electrical stimulation (NMES), on sensory changes and cortical plasticity among patients with chronic stroke. Methods: This study was a prespecified analysis of 23 participants involved in an ongoing large interventional study. Patients with severe upper limb hemiplegia dues to chronic stroke underwent 3 weeks of inpatient HANDS therapy, where daily treatment consisted of 8 h of NMES combined with wrist splinting, 90 min of comprehensive occupational therapy, and the practice of bimanual activities of daily living. Somatosensory evoked potentials (SEPs) and functional sensory assessments, including the Semmes–Weinstein monofilament test (SWMT) and thumb localizing test (TLT), were compared pre and post-treatment. Results: While no significant recovery of tactile sensation was observed, significant improvements in proprioception and motor function were induced. The number of cortical peaks significantly increased in the median nerve, but not in the tibial nerve. A total of 9 out of 11 participants who initially lacked certain peaks responded to treatment. Further analysis revealed a significant improvement in latency and amplitude of SEP peaks. Conclusions: Our results suggest that NMES-based neurorehabilitation induces certain plastic changes in the primary sensory cortex and in cortices associated with sensorimotor processing in people with chronic stroke sequelae, which may explain the observed improvements in proprioception.

We aimed to investigate whether a newly defined distance in the lower limb can capture the characteristics of hemiplegic gait compared to healthy controls. Three-dimensional gait analyses were performed on 42 patients with chronic stroke and 10 age-matched controls. Pelvis-toe distance (PTD) was calculated as the absolute distance between an anterior superior iliac spine marker and a toe marker during gait normalized by PTD in the bipedal stance. The shortening peak during the swing phase was then quantified as PTDmin. The sagittal clearance angle, the frontal compensatory angle, gait speed, and the observational gait scale were also collected. PTDmin in the stroke group showed less shortening on the affected side and excessive shortening on the non-affected side compared to controls. PTDmin on the affected side correlated negatively with the sagittal clearance peak angle and positively with the frontal compensatory peak angle in the stroke group. PTDmin in stroke patients showed moderate to high correlations with gait speed and observational gait scale. PTDmin adequately reflected gait quality without being affected by apparent improvements due to frontal compensatory patterns. Our results showed that various impairments and compensations were included in the inability to shorten PTD, which can provide new perspectives on gait rehabilitation in stroke patients.

Objective: Brain-machine interface training was developed for upper-extremity rehabilitation for patients with severe hemiparesis. Its clinical application, however, has been limited because of its lack of feasibility in real-world rehabilitation settings. We developed a new compact task-specific brain-machine interface system that enables task-specific training, including reach-and-grasp tasks, and studied its clinical feasibility and effectiveness for upper-extremity motor paralysis in patients with stroke. Design: Prospective before–after study. Subjects: Twenty-six patients with severe chronic hemiparetic stroke. Methods: Participants were trained with the brain-machine interface system to pick up and release pegs during 40-min sessions and 40 min of standard occupational therapy per day for 10 days. Fugl-Meyer upper-extremity motor (FMA) and Motor Activity Log-14 amount of use (MAL-AOU) scores were assessed before and after the intervention. To test its feasibility, 4 occupational therapists who operated the system for the first time assessed it with the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST) 2.0. Results: FMA and MAL-AOU scores improved significantly after brain-machine interface training, with the effect sizes being medium and large, respectively (p

Motor imagery (MI) combined with electrical stimulation (ES) enhances upper-limb corticospinal excitability. However, its after-effects on both lower limb corticospinal excitability and spinal reciprocal inhibition remain unknown. We aimed to investigate the effects of MI combined with peripheral nerve ES (MI + ES) on the plasticity of lower limb corticospinal excitability and spinal reciprocal inhibition. Seventeen healthy individuals performed the following three tasks on different days, in a random order: (1) MI alone; (2) ES alone; and (3) MI + ES. The MI task consisted of repetitive right ankle dorsiflexion for 20 min. ES was percutaneously applied to the common peroneal nerve at a frequency of 100 Hz and intensity of 120% of the sensory threshold of the tibialis anterior (TA) muscle. We examined changes in motor-evoked potential (MEP) of the TA (task-related muscle) and soleus muscle (SOL; task-unrelated muscle). We also examined disynaptic reciprocal inhibition before, immediately after, and 10, 20, and 30 min after the task. MI + ES significantly increased TA MEPs immediately and 10 min after the task compared with baseline, but did not change the task-unrelated muscle (SOL) MEPs. MI + ES resulted in a significant increase in the magnitude of reciprocal inhibition immediately and 10 min after the task compared with baseline. MI and ES alone did not affect TA MEPs or reciprocal inhibition. MI combined with ES is effective in inducing plastic changes in lower limb corticospinal excitability and reciprocal Ia inhibition.

Background: The combination of motor imagery (MI) and afferent input with electrical stimulation (ES) enhances the excitability of the corticospinal tract compared with motor imagery alone or electrical stimulation alone. However, its therapeutic effect is unknown in patients with hemiparetic stroke. We performed a preliminary examination of the therapeutic effects of MI + ES on upper extremity (UE) motor function in patients with chronic stroke. Methods: A total of 10 patients with chronic stroke demonstrating severe hemiparesis participated. The imagined task was extension of the affected finger. Peripheral nerve electrical stimulation was applied to the radial nerve at the spiral groove. MI + ES intervention was conducted for 10 days. UE motor function as assessed with the Fugl–Meyer assessment UE motor score (FMA-UE), the amount of the affected UE use in daily life as assessed with a Motor Activity Log (MAL-AOU), and the degree of hypertonia in flexor muscles as assessed with the Modified Ashworth Scale (MAS) were evaluated before and after intervention. To assess the change in spinal neural circuits, reciprocal inhibition between forearm extensor and flexor muscles with the H reflex conditioning-test paradigm at interstimulus intervals (ISIs) of 0, 20, and 100 ms were measured before and after intervention. Results: UE motor function, the amount of the affected UE use, and muscle hypertonia in flexor muscles were significantly improved after MI + ES intervention (FMA-UE: p < 0.01, MAL-AOU: p < 0.01, MAS: p = 0.02). Neurophysiologically, the intervention induced restoration of reciprocal inhibition from the forearm extensor to the flexor muscles (ISI at 0 ms: p = 0.03, ISI at 20 ms: p = 0.03, ISI at 100 ms: p = 0.01). Conclusion: MI + ES intervention was effective for improving UE motor function in patients with severe paralysis.

We investigated cortically mediated changes in reciprocal inhibition (RI) following motor imagery (MI) in short- and long(er)-term periods. The goals of this study were (1) to describe RI during MI in patients with chronic stroke and (2) to examine the change in RI after MI-based brain-machine interface (BMI) training. Twenty-four chronic stroke patients participated in study 1. All patients imagined wrist extension on the affected side. RI from the extensor carpi radialis to the flexor carpi radialis (FCR) was assessed using a FCR H reflex conditioning-test paradigm. We calculated the “MI effect score on RI” (RI value during MI divided by that at rest) and compared that score according to lesion location. RI during MI showed a significant enhancement compared with RI at rest. The MI effect score on RI in the subcortical lesion group was significantly greater than that in the cortical lesion group. Eleven stroke patients participated in study 2. All patients performed BMI training for 10 days. The MI effect score on RI at a 20 ms interstimulus interval was significantly increased after BMI compared with baseline. In conclusion, mental practice with MI may induce plastic change in spinal reciprocal inhibitory circuits in patients with stroke.

Hybrid Assistive Neuromuscular Dynamic Stimulation (HANDS) therapy is one of the neurorehabilitation therapeutic approaches that facilitates the use of the paretic upper extremity (UE) in daily life by combining closed-loop electromyography- (EMG-) controlled neuromuscular electrical stimulation (NMES) with a wrist-hand splint. This closed-loop EMG-controlled NMES can change its stimulation intensity in direct proportion to the changes in voluntary generated EMG amplitudes recorded with surface electrodes placed on the target muscle. The stimulation was applied to the paretic finger extensors. Patients wore a wrist-hand splint and carried a portable stimulator in an arm holder for 8 hours during the daytime. The system was active for 8 hours, and patients were instructed to use their paretic hand as much as possible. HANDS therapy was conducted for 3 weeks. The patients were also instructed to practice bimanual activities in their daily lives. Paretic upper extremity motor function improved after 3 weeks of HANDS therapy. Functional improvement of upper extremity motor function and spasticity with HANDS therapy is based on the disinhibition of the affected hemisphere and modulation of reciprocal inhibition. HANDS therapy may offer a promising option for the management of the paretic UE in patients with stroke.